Rare Cancer News & Clinical Trials

Hepatoblastoma (236 unread)

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Agnostic Therapy in Rare Solid Tumors

Posted: October 14th, 2024, 11:00pm UTC

Conditions: Urachal Cancer; Parathyroid Carcinoma; Fibrolamellar Carcinoma; Angiosarcoma; Secretory Carcinoma of Breast; Anal Neoplasms; Metaplastic Breast Carcinoma; Translocation Renal Cell Carcinoma; Carcinosarcoma; Small Intestine Neoplasms; Cholangiocarcinoma; Sertoli-Leydig Cell Tumor; Adenoid Cystic Carcinoma; Mesothelioma; Neuroblastoma; Adrenal Gland Neoplasms; Penile Neoplasms; Apocrine Carcinoma; Fibrosarcoma; Cancer of Unknown Primary; Hemangioblastoma; Thyroid Neoplasms; Hepatoblastoma; Fallopian Tube Neoplasms; Leiomyosarcoma; Vaginal Neoplasms; Neurofibrosarcoma; Gallbladder Neoplasms; Osteosarcoma; Biliary Tract Neoplasms; Clear Cell Endometrial Cancer; Yolk Sac Tumor; Vulvar Neoplasms; Kaposi Sarcoma; Ovarian Epithelial Cancer; Soft Tissue Sarcoma; Urethral Neoplasms; Granulosa Cell Tumor; Primitive Neuroectodermal Tumor; Neuroendocrine Tumors; Trophoblastic Tumor
Interventions: Drug: Nivolumab
Sponsors: Instituto do Cancer do Estado de SÃ£o Paulo; Financiadora de Estudos e Projetos
Recruiting

Phase 4 Paediatric Study to Evaluate Sonazoid Safety and Efficacy for Contrast-Enhanced Ultrasound Liver Imaging

Posted: October 14th, 2024, 11:00pm UTC

Conditions: Focal Liver Lesions
Interventions: Diagnostic Test: Contrast-Enhanced Ultrasound
Sponsors: GE Healthcare; PPD DEVELOPMENT, LP; Medidata Solutions
Recruiting

A French Multicenter Observational Retrospective Study of Rare Primary Liver Cancers

Posted: August 7th, 2024, 11:00pm UTC

Conditions: Hepatocholangiocarcinoma; Fibrolamellar Carcinoma; Hepatic Epithelioid Hemangioendothelioma; Hepatoblastoma; Hepatic Neuroendocrine Carcinoma; Hepatic Carcinosarcomas; Hepatic Cystadenoma; Hepatic Leiomyosarcomas; Hepatic Angiosarcomas; Cholangiocarcinoma
Sponsors: Federation Francophone de Cancerologie Digestive; SociÃ©tÃ© Nationale FranÃ§aise de GastroentÃ©rologie
Recruiting

Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells

Posted: January 10th, 2024, 1:00am UTC

Conditions: Hepatoblastoma; Hepatocellular Carcinoma; Wilms Tumor; Malignant Rhabdoid Tumor; Yolk Sac Tumor; Rhabdomyosarcoma; Liposarcoma; Embryonal Sarcoma of Liver
Interventions: Genetic: 21.15.GPC3-CAR T cells
Sponsors: Baylor College of Medicine; Center for Cell and Gene Therapy, Baylor College of Medicine
Not yet recruiting

Characteristics and Prognostic Value of 18F-FDG PET/CT (MR) in Blastoma

Posted: January 4th, 2024, 1:00am UTC

Conditions: 18F-FDG; Neuroblastoma; Hepatoblastoma; Wilms Tumor
Interventions: Other: Telephone follow-up
Sponsors: Wuhan Union Hospital, China
Completed

Evaluation of Lung Metastases Based on Ultrashort Echo Time MRI

Posted: March 10th, 2023, 1:00am UTC

Conditions: Hepatoblastoma; Radiology
Sponsors: RenJi Hospital
Completed

Sodium Thiosulfate Otoprotection During Salvage Cisplatin Therapy

Posted: March 6th, 2023, 1:00am UTC

Conditions: Ototoxicity, Drug-Induced
Interventions: Drug: Sodium Thiosulfate
Sponsors: Children's Hospital Medical Center, Cincinnati
Recruiting

Psychosocial Situation of Children With Rare Solid Abdominal Tumors and Their Families

Posted: February 17th, 2022, 1:00am UTC

Conditions: Neuroblastoma; Nephroblastoma; Hepatoblastoma
Sponsors: UniversitÃ¤tsklinikum Hamburg-Eppendorf
Completed

131I-omburtamab for the Treatment of Central Nervous System/Leptomeningeal Neoplasms in Children and Young Adults

Posted: October 1st, 2021, 11:00pm UTC

Conditions: Central Nervous System/Leptomeningeal Neoplasms
Interventions: Drug: 131I-omburtamab
Sponsors: Memorial Sloan Kettering Cancer Center; Y-mAbs Therapeutics
Available

Permalink for 'A Study of Codrituzumab in Children and Young Adults With Solid Tumors and Have Not Responded to Treatment or Have Come Back After Treatment'

A Study of Codrituzumab in Children and Young Adults With Solid Tumors and Have Not Responded to Treatment or Have Come Back After Treatment

Posted: June 16th, 2021, 11:00pm UTC

Conditions: Primary Extra-cranial Solid Tumor; Recurrent or Refractory Glypican 3 (GPC3)
Interventions: Drug: Codrituzumab
Sponsors: Memorial Sloan Kettering Cancer Center; Chugai Pharma USA
Recruiting

Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma

Posted: May 25th, 2021, 11:00pm UTC

Conditions: Recurrent Solid Tumor; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Wilms Tumor; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma
Interventions: Drug: Onivyde; Drug: Talazoparib; Drug: Temozolomide
Sponsors: St. Jude Children's Research Hospital; Pfizer; Ipsen
Active, not recruiting

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 11:00pm UTC

Conditions: Pediatric Solid Tumor; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Ewing Sarcoma; Wilms Tumor; Adrenocortical Cancer; Desmoplastic Small Round Cell Tumor; Germ Cell Cancer; Rhabdoid Tumor; Clear Cell Sarcoma; Hepatoblastoma; Melanoma; Carcinoma; Malignant Peripheral Nerve Sheath Tumors; Soft Tissue Sarcoma
Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MESNA; Drug: B7-H3 CAR T cells
Sponsors: St. Jude Children's Research Hospital
Recruiting

$Permalink for 'Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors'$

Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors

Posted: April 20th, 2021, 11:00pm UTC

Conditions: Colorectal Carcinoma; Endometrial Carcinoma; Melanoma; Neuroblastoma; Ovarian Carcinoma; Pancreatic Ductal Adenocarcinoma; Recurrent Desmoid Fibromatosis; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Hepatocellular Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Refractory Desmoid Fibromatosis; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Hepatocellular Carcinoma; Refractory Malignant Solid Neoplasm; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Solid Pseudopapillary Neoplasm of the Pancreas; Wilms Tumor
Interventions: Procedure: Biospecimen Collection; Procedure: Dual X-ray Absorptiometry; Drug: Tegavivint; Procedure: X-Ray Imaging
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Recruiting

ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma

Posted: November 18th, 2020, 1:00am UTC

Conditions: Hepatoblastoma; Hepatocellular Carcinoma (HCC); Liver Neoplasms; Metastatic Liver Cancer; Liver Cancer; HEMNOS
Interventions: Drug: ET140203 T Cells
Sponsors: Eureka Therapeutics Inc.
Recruiting

$Permalink for 'B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$

B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

Posted: July 23rd, 2020, 11:00pm UTC

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma; Melanoma
Interventions: Biological: second generation 4-1BBÎ¶ B7H3-EGFRt-DHFR; Biological: second generation 4-1BBÎ¶ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBÎ¶ CD19-Her2tG; Drug: Pembrolizumab
Sponsors: Seattle Children's Hospital
Active, not recruiting

Flavored, Oral Irinotecan VAL-413 (OrotecanÂ®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors

Posted: April 7th, 2020, 11:00pm UTC

Conditions: Solid Tumors; Neuroblastoma; Rhabdomyosarcoma; Ewing Sarcoma; Hepatoblastoma; Medulloblastoma
Interventions: Drug: VAL-413; Drug: Temozolomide
Sponsors: Valent Technologies, LLC
Recruiting

Permalink for 'Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial'

Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: March 25th, 2020, 11:00pm UTC

Conditions: Hematopoietic and Lymphatic System Neoplasm; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Histiocytic and Dendritic Cell Neoplasm; Recurrent Langerhans Cell Histiocytosis; Recurrent Lymphoma; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent WHO Grade 2 Glioma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Histiocytic and Dendritic Cell Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Lymphoma; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory WHO Grade 2 Glioma; Wilms Tumor
Interventions: Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Radionuclide Imaging; Drug: Selpercatinib; Procedure: X-Ray Imaging
Sponsors: National Cancer Institute (NCI); Children's Oncology Group
Active, not recruiting

Yttrium-90 (TARE-Y90) in Children, Adolescents, and Young Adults With Liver Tumors

Posted: March 20th, 2020, 11:00pm UTC

Conditions: Hepatoblastoma; Hepatocellular Carcinoma; Rhabdoid Tumor of Liver; Undifferentiated (Embryonal) Sarcoma of the Liver; Pediatric Liver Cancer; Liver Tumors
Interventions: Behavioral: Quality of Life Assessment; Radiation: Transarterial Radioembolization
Sponsors: Nemours Children's Clinic; Alfred I. duPont Hospital for Children
Terminated

Permalink for 'Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial'

Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: February 26th, 2020, 1:00am UTC

Conditions: Malignant Solid Neoplasm; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Ectomesenchymoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdoid Tumor of the Kidney; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Carcinoma; Recurrent WHO Grade 2 Glioma; Refractory Adrenal Gland Pheochromocytoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdoid Tumor of the Kidney; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Carcinoma; Refractory WHO Grade 2 Glioma
Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Radionuclide Imaging; Drug: Tipifarnib
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Permalink for 'Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)'

Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)

Posted: December 12th, 2019, 1:00am UTC

Conditions: Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent WHO Grade 2 Glioma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory WHO Grade 2 Glioma; Wilms Tumor
Interventions: Drug: Ivosidenib
Sponsors: National Cancer Institute (NCI); Children's Oncology Group
Active, not recruiting

Molecular Basis of Pediatric Liver Cancer

Posted: May 22nd, 2019, 11:00pm UTC

Conditions: Childhood Liver Cancer; Liver Malignant Tumors; Embryonal Sarcoma of Liver (Disorder); Hepatoblastoma; Hepatocellular Carcinoma; Rhabdoid Tumor of Liver
Sponsors: University of Pittsburgh
Recruiting

Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors

Posted: November 14th, 2018, 1:00am UTC

Conditions: Malignant Solid Tumors; Other Neoplasms Solid Tumors; Pediatric Solid Tumor; Refractory Solid Tumors; Solid Tumor
Sponsors: National Cancer Institute (NCI)
Recruiting

Permalink for 'Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)'

Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

Posted: October 9th, 2018, 11:00pm UTC

Conditions: Advanced Malignant Solid Neoplasm; Recurrent Ependymal Tumor; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Histiocytic and Dendritic Cell Neoplasm; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Primary Malignant Central Nervous System Neoplasm; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Histiocytic and Dendritic Cell Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Primary Malignant Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Wilms Tumor
Interventions: Other: Pharmacokinetic Study; Drug: Ulixertinib
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

$Permalink for 'EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$

EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

Posted: August 7th, 2018, 11:00pm UTC

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma
Interventions: Biological: second generation 4-1BBÎ¶ EGFR806-EGFRt; Biological: second generation 4-1BBÎ¶ EGFR806-EGFRt and a second generation 4 1BBÎ¶ CD19-Her2tG
Sponsors: Seattle Children's Hospital
Recruiting

Permalink for 'Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery'

Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery

Posted: May 23rd, 2018, 11:00pm UTC

Conditions: Childhood Hepatocellular Carcinoma; Childhood Malignant Liver Neoplasm; Fibrolamellar Carcinoma; Hepatoblastoma; Hepatocellular Malignant Neoplasm, Not Otherwise Specified
Interventions: Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Cisplatin; Drug: Doxorubicin; Drug: Etoposide; Drug: Fluorouracil; Drug: Gemcitabine; Drug: Irinotecan; Drug: Oxaliplatin; Other: Patient Observation; Procedure: Resection; Drug: Sorafenib; Drug: Vincristine Sulfate
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Active, not recruiting

$Permalink for 'Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)'$

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Posted: May 16th, 2018, 11:00pm UTC

Conditions: Advanced Malignant Solid Neoplasm; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma
Interventions: Other: Laboratory Biomarker Analysis; Drug: Palbociclib; Other: Pharmacological Study
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

$Permalink for 'Nab-paclitaxel in Combination With Gemcitabine for Pediatric Relapsed and Refractory Solid Tumors'$

Nab-paclitaxel in Combination With Gemcitabine for Pediatric Relapsed and Refractory Solid Tumors

Posted: April 25th, 2018, 11:00pm UTC

Conditions: Cancer
Interventions: Drug: Gemcitabine; Drug: Nab-paclitaxel
Sponsors: Emory University; Celgene Corporation
Completed

$Permalink for 'Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)'$

Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

Posted: July 28th, 2017, 11:00pm UTC

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Low Grade Glioma; Malignant Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Childhood Malignant Germ Cell Tumor; Refractory Ependymoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; Wilms Tumor
Interventions: Drug: Olaparib
Sponsors: National Cancer Institute (NCI)
Completed

$Permalink for 'Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)'$

Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

Posted: July 11th, 2017, 11:00pm UTC

Conditions: Advanced Malignant Solid Neoplasm; Recurrent Ependymoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma
Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Larotrectinib Sulfate; Procedure: Magnetic Resonance Imaging; Procedure: Radionuclide Imaging; Procedure: X-Ray Imaging
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

$Permalink for 'Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)'$

Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)

Posted: July 11th, 2017, 11:00pm UTC

Conditions: Advanced Malignant Solid Neoplasm; Malignant Solid Neoplasm; Recurrent Ependymoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Primary Central Nervous System Neoplasm; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Wilms Tumor
Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Ensartinib; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Other: Pharmacological Study; Procedure: Positron Emission Tomography; Procedure: Radionuclide Imaging; Procedure: X-Ray Imaging
Sponsors: National Cancer Institute (NCI); Children's Oncology Group
Recruiting

$Permalink for 'Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)'$

Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)

Posted: July 11th, 2017, 11:00pm UTC

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Malignant Glioma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Primary Central Nervous System Neoplasm; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Central Nervous System Neoplasm; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor
Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: FDG-Positron Emission Tomography; Procedure: Magnetic Resonance Imaging; Drug: Samotolisib; Procedure: X-Ray Imaging
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

$Permalink for 'Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)'$

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

Posted: May 16th, 2017, 11:00pm UTC

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Histiocytic Sarcoma; Juvenile Xanthogranuloma; Langerhans Cell Histiocytosis; Malignant Glioma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Primary Central Nervous System Neoplasm; Recurrent Rhabdoid Tumor; Recurrent Soft Tissue Sarcoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Primary Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Ensartinib; Drug: Erdafitinib; Other: Laboratory Biomarker Analysis; Drug: Larotrectinib Sulfate; Procedure: Magnetic Resonance Imaging; Procedure: Mutation Carrier Screening; Drug: Olaparib; Drug: Palbociclib; Other: Pharmacological Study; Procedure: Positron Emission Tomography; Procedure: Radionuclide Imaging; Drug: Samotolisib; Drug: Selpercatinib; Drug: Selumetinib Sulfate; Drug: Tazemetostat; Drug: Tipifarnib; Drug: Ulixertinib; Drug: Vemurafenib; Procedure: X-Ray Imaging
Sponsors: National Cancer Institute (NCI)
Recruiting

Paediatric Hepatic International Tumour Trial

Posted: January 11th, 2017, 1:00am UTC

Conditions: Hepatoblastoma; Carcinoma, Hepatocellular
Interventions: Drug: Cisplatin; Drug: Doxorubicin; Drug: Carboplatin; Drug: 5Fluorouracil; Drug: Vincristine; Drug: Etoposide; Drug: Irinotecan; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Sorafenib
Sponsors: University of Birmingham; FundaciÃ³ Institut Germans Trias i Pujol; University Hospital Munich; University Hospital, Bonn; University of Kiel; University Hospital Tuebingen; University of Padova; Ludwig-Maximilians - University of Munich; Medical University of Gdansk; Cliniques universitaires Saint-Luc- UniversitÃ© Catholique de Louvain; Motol University Hospital, Prague; Rennes University Hospital; Children's University Hospital, Ireland; University of Oslo; Princess Maxima Center for Pediatric Oncology; Andaluz Health Service; Swiss Pediatric Oncology Group; Gothia Forum - Center for Clinical Trial; The Leeds Teaching Hospitals NHS Trust; Bambino GesÃ¹ Hospital and Research Institute; Newcastle University Centre for Cancer, Newcastle; Experimental Cancer Medicine Centres; XenTech, Evry
Active, not recruiting

$Permalink for 'Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors'$

Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

Posted: August 16th, 2016, 11:00pm UTC

Conditions: Adrenal Cortical Carcinoma; Alveolar Soft Part Sarcoma; Central Nervous System Neoplasm; Childhood Clear Cell Sarcoma of Soft Tissue; Clear Cell Sarcoma of Soft Tissue; Ewing Sarcoma; Hepatoblastoma; Hepatocellular Carcinoma; Osteosarcoma; Recurrent Adrenal Cortical Carcinoma; Recurrent Alveolar Soft Part Sarcoma; Recurrent Clear Cell Sarcoma of Soft Tissue; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Hepatocellular Carcinoma; Recurrent Kidney Wilms Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Osteosarcoma; Recurrent Primary Malignant Central Nervous System Neoplasm; Recurrent Renal Cell Carcinoma; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Medullary Carcinoma; Refractory Adrenal Cortical Carcinoma; Refractory Alveolar Soft Part Sarcoma; Refractory Clear Cell Sarcoma of Soft Tissue; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Hepatocellular Carcinoma; Refractory Malignant Solid Neoplasm; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Primary Malignant Central Nervous System Neoplasm; Refractory Renal Cell Carcinoma; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Medullary Carcinoma; Refractory Wilms Tumor; Renal Cell Carcinoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Solid Neoplasm; Thyroid Gland Medullary Carcinoma; Wilms Tumor
Interventions: Drug: Cabozantinib; Drug: Cabozantinib S-malate; Other: Pharmacological Study
Sponsors: National Cancer Institute (NCI)
Active, not recruiting

Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

Posted: March 5th, 2013, 1:00am UTC

Conditions: Refractory and/or Relapsed Metastatic Solid Tumors
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: low dose total body irradiation; Drug: Melphalan; Drug: Tacrolimus
Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; National Cancer Institute (NCI)
Recruiting

Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

Posted: January 6th, 2012, 1:00am UTC

Conditions: Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors
Interventions: Drug: Ifosfamide; Drug: Etoposide; Drug: Mesna; Biological: G-CSF; Drug: Busulfan; Drug: Melphalan; Drug: Thiotepa; Biological: Autologous stem cell infusion; Radiation: Radiation; Drug: Carboplatin; Drug: Paclitaxel; Procedure: Leukapheresis; Drug: Anti-seizure prophylaxis; Drug: Ursodiol
Sponsors: Masonic Cancer Center, University of Minnesota
Completed

Central Liver Segments Resections vs Extended Hepatectomies in Children: Single-center Experience

Fetched: October 16th, 2024, 2:01am UTC by Dmitry G Akhaladze

J Pediatr Surg. 2024 Sep 14:161927. doi: 10.1016/j.jpedsurg.2024.161927. Online ahead of print.

ABSTRACT

BACKGROUND: Central liver segments resection (CLSR) still is not widely used in pediatric surgery due to its technical difficulty, whereas this procedure is widely spread as a parenchyma sparing approach of centrally located liver tumors in adults. The aim of this study is to analyze the outcomes of CLSR in comparison with extended hepatectomy (EH) in children with different liver tumors.

METHODS: A single-center retrospective analysis of patients who received CLSR (n = 14) and EH (n = 44) from June 2017 to December 2023 was applied. Patient's characteristics, preoperative, intra- and postoperative data were compared between 2 groups.

RESULTS: Preoperative CT-volumetry showed that future liver remnant volume was higher in CLSR group compared to EH (FLR-V; (54 Â± 29 (40-91) % vs 40 Â± 12 (17-73) %, p = 0.016). The intraoperative blood loss (200 [90-1150] (20-3000) ml vs 100 [30-275] (10-9000) ml, p = 0.088) and transfusion volume (310 [85-590] (0-1860) ml vs 150 [0-310] (0-4770) ml, p = 0.484) were similar in both groups, while operation time was longer in CLSR group (420 [320-595] (145-785) min vs 280 [203-390] (125-710) min), p = 0.011). There was no difference in biliary leakage (3 (21.4 %) vs 12 (27.3 %); p = 0.479), other complications (4 (28.6 %) vs 5 (11.4 %), p = 0.198) and complications â‰¥ IIIb by Clavien-Dindo (2 (14.3 %) vs 8 (18.2 %), p = 0.385) postoperatively.

CONCLUSION: CLSRs allow to preserve more healthy liver parenchyma compared to EH with similar intraoperative and postoperative outcomes. Â«Extended mesohepatectomyÂ» allows to achieve R0 resection when central liver tumor extends on the left lateral and/or right posterior section.

TYPE OF STUDY: Retrospective Comparative Study (Level of Evidence III).

PMID:39368854 | DOI:10.1016/j.jpedsurg.2024.161927

Permalink for 'Reappraisal of liver resection as an alternative to transplantation in locally advanced hepatoblastoma: A systematic review and analysis of pooled individual patient data'

Reappraisal of liver resection as an alternative to transplantation in locally advanced hepatoblastoma: A systematic review and analysis of pooled individual patient data

Fetched: October 16th, 2024, 2:01am UTC by Juri Fuchs

Pediatr Blood Cancer. 2024 Sep 27:e31339. doi: 10.1002/pbc.31339. Online ahead of print.

ABSTRACT

BACKGROUND: There is ongoing debate regarding liver transplantation (LT) versus liver resection (LR) for locally advanced hepatoblastoma. However, comparative studies are lacking. Consequently, a significant evidence gap persists, hindering the establishment of consensus guidelines. This study aimed to compare LT and LR for locally advanced hepatoblastoma, using predefined inclusion criteria to ensure comparable intervention groups.

METHODS: According to current Children's Oncology Group (COG) and SIOPEL (European Childhood Liver Tumour Study Group) recommendations, hepatoblastoma that requires LT evaluation was defined as either PRETEXT (PRE-Treatment EXTent of tumor) IV F+, POST-TEXT (POST-Treatment EXTent of tumor) IV, POST-TEXT P+, and/or POST-TEXT V+. A systematic literature search (Medline/Web-of-Science/Embase) was performed. Only patients who met the aforementioned criteria were included. Patient data were extracted individually and pooled.

RESULTS: A total of 189 patients with locally advanced hepatoblastoma from 55 studies met the specified criteria, with 111 undergoing LT and 78 LR. There were no significant differences between the two groups in age, alpha-fetoprotein (AFP), and PRETEXT stages. Local recurrence was more common after LR (14% vs. 3% in LT, p = .008), while distant recurrence was more often observed after LT (16% vs. 5% in LR, p = .035). Overall survival (OS) and event-free survival (EFS) did not differ significantly between LT and LR (5-year OS: LT = 75.3% [95% confidence interval: 66.5-85.2], LR = 87.6% [80.4-95.6], p = .140; 5-year EFS: LT = 68.5% [59.3-79.1], LR = 71.1% [60.7-83.3], p = .700).

CONCLUSION: Real-life data revealed that a considerable number of patients with locally advanced hepatoblastoma underwent LR. This analysis suggests that outcomes are similar and favorable for both approaches. LR can therefore be considered an effective alternative to LT in selected cases even in locally advanced hepatoblastoma.

PMID:39334537 | DOI:10.1002/pbc.31339

Modulating the unfolded protein response with ISRIB mitigates cisplatin ototoxicity

Fetched: October 16th, 2024, 2:01am UTC by Jiang Li

Sci Rep. 2024 Sep 27;14(1):22382. doi: 10.1038/s41598-024-70561-w.

ABSTRACT

Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin, and UPR marker gene expression and cell death measured. Treatment with ISRIB (Integrated Stress Response InhIBitor), a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested for its ability to reduce apoptosis in HEK cells, hair-cell death in cochlear cultures, and hearing loss using an in vivo mouse model of cisplatin ototoxicity. Finally, to evaluate whether ISRIB might interfere with cisplatin chemoeffectiveness, we tested it in head and neck squamous cell carcinoma (HNSCC) cell-based assays of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose-response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatin's cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.

PMID:39333235 | PMC:PMC11437005 | DOI:10.1038/s41598-024-70561-w

Gamma-butyrobetaine hydroxylase (BBOX1) exerts suppressive effects on HepG2 hepatoblastoma cells

Fetched: October 16th, 2024, 2:01am UTC by Yuling Zhan

Med Oncol. 2024 Sep 27;41(11):253. doi: 10.1007/s12032-024-02496-1.

ABSTRACT

Gamma-butyrobetaine hydroxylase (BBOX1) plays a pivotal role in catalyzing the final stage of L-carnitine biosynthesis. Recently, increasing number of studies have reported that BBOX1 is weakly expressed in tumor cells and exhibits antitumor activity. The role of BBOX1 in Hepatoblastoma (HB) has yet to be determined. To substantiate this, we have investigated BBOX1 expression and its clinical relevance in HB, and explored how BBOX1 might inhibit the occurrence and development of HB. The GSE104766 and GSE131329 datasets were used to screen for the core gene BBOX1 in HB and to analyze differences in expression between hepatoblastoma and normal tissues. Based on the clinicopathological features of the GSE131329 dataset, the connections between the expression of BBOX1 and the clinicopathological feature of HB patients were determined. After BBOX1 was overexpressed, CCK-8 and colony formation assays were employed to assess cell proliferation and wound healing experiments were utilized to assess cell migration. The presence of cell apoptosis, cell cycle changes, and reactive oxygen species (ROS) was assayed using flow cytometry. Compared with normal tissues, the expression of BBOX1 in hepatoblastoma tissues was notably decreased. Dysregulated expression of BBOX1 was indicated as a prognostic risk factor closely linked to clinical stag of patients with HB. Furthermore, following BBOX1 overexpression, cell proliferation and migration are decreased, the cell cycle is arrested, and ROS are attenuated. BBOX1 has suppressive effects on HepG2 cells, potentially through its ability to hinder cancer cell proliferation, arrest cell cycle progression, and decrease ROS levels, suggesting its potential as a novel prognostic biomarker and therapeutic candidate for hepatoblastoma.

PMID:39331195 | DOI:10.1007/s12032-024-02496-1

Update on surveillance for Wilms tumor and hepatoblastoma in Beckwith-Wiedemann Syndrome and other predisposition syndromes

Fetched: October 16th, 2024, 2:01am UTC by Jennifer M Kalish

Clin Cancer Res. 2024 Sep 25. doi: 10.1158/1078-0432.CCR-24-2100. Online ahead of print.

ABSTRACT

Wilms tumors are commonly associated with predisposition syndromes many, but not all, of which include overgrowth. Several of these syndromes also include a risk of other embryonal malignancies - particularly hepatoblastoma. Guidelines for surveillance in this population were published in 2017 and recently members of the AACR Pediatric Cancer Working Group met to update those guidelines with a review of more recently published evidence and risk estimates. This perspective serves to update pediatric oncologists, geneticists, radiologists, counselors and other healthcare professionals on revised diagnostic criteria, review previously published surveillance guidelines and harmonize updated surveillance recommendations in the North American and Australian context for patients with overgrowth syndromes and other syndromes associated with Wilms tumor predisposition.

PMID:39320341 | DOI:10.1158/1078-0432.CCR-24-2100

Can Dynamic Contrast-Enhanced MRI Be Used to Differentiate Hepatic Hemangioma from Other Lesions in Early Infancy?

Fetched: October 16th, 2024, 2:01am UTC by Dan Halevy

Indian J Radiol Imaging. 2024 Apr 21;34(4):612-619. doi: 10.1055/s-0044-1785208. eCollection 2024 Oct.

ABSTRACT

Background Confident diagnosis of hepatic hemangioma on imaging can avoid biopsy in early infancy and helps guide conservative management. Purpose This article aims to determine if dynamic contrast-enhanced magnetic resonance imaging (MRI) can be used to differentiate liver hemangioma from other lesions in infants â‰¤ 100 days and to determine association of MRI features with hepatic lesions. Methods MRI performed for liver lesions were retrospectively reviewed to note imaging characteristics and the MRI diagnosis. Final diagnosis was assigned based on pathology in available cases and by corroborative standard of reference including overall clinical features, lab findings, and follow-up. Results Of 30 infants (18 boys, 12 girls; average age 42.2 days) included, 18 had solitary and 12 had multifocal lesions. Diagnoses in total 33 lesions included hemangiomas (23), hepatoblastoma (6), arteriovenous malformation (2), neuroblastoma metastases (1), and infarction (1). MRI and final diagnosis matched in 94% lesions with almost perfect agreement (kappa 0.86) for reader 1, and matched in 88% lesions with substantial agreement (kappa 0.71) for reader 2. Interobserver agreement for MRI diagnosis was substantial (kappa 0.62). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI in differentiating hemangioma from other lesions were 100, 90, 96, 100, and 97%, respectively. Centripetal (16/23) or flash (5/23) filling were only seen with hemangioma. There was no significant difference in alpha-fetoprotein elevation ( p 0.08), average size ( p 0.35), multifocality ( p 0.38), and intralesional hemorrhage ( p 1) between hemangioma and hepatoblastoma. Conclusion Centripetal filling on dynamic imaging and absence of washout are characteristic MRI features of hepatic hemangioma that can help to differentiate it from other lesions in early infancy.

PMID:39318559 | PMC:PMC11419760 | DOI:10.1055/s-0044-1785208

A case report of congenital hepatoblastoma

Fetched: October 16th, 2024, 2:01am UTC by Hang Li

Int J Surg Case Rep. 2024 Sep 21;124:110337. doi: 10.1016/j.ijscr.2024.110337. Online ahead of print.

ABSTRACT

INTRODUCTION: Reports of congenital hepatoblastoma are rare, and there is limited experience in its management.

CASE PRESENTATION: We present a challenging case of congenital hepatoblastoma that was large at the time of presentation, occupying the first and second hepatic portals and deemed inoperable. Although liver tumors was detected in the child during the mother's pregnancy, the initial diagnosis was hepatic hemangioma. The diagnosis of hepatoblastoma was ultimately confirmed after a biopsy. Neoadjuvant chemotherapy, guided by 3D visual analysis based on enhanced CT, enabled successful block resection of the tumor. Despite a transient cholestatic parcel effusion post-operation, the child achieved good therapeutic outcomes with subsequent drainage and chemotherapy.

DISCUSSION: Regular monitoring of alpha-fetoprotein (AFP) levels and performing abdominal ultrasounds are useful for the differential diagnosis of liver tumors; however, pathology remains the gold standard for confirming malignancy. Chemotherapy is safe and effective for treating congenital hepatoblastoma in the perinatal period. 3D visual analysis is valuable tools in performing surgeries on children with large, strategically positioned tumors. Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) has been assessed for its adjuvant therapeutic efficacy in adult hepatocellular carcinoma, and we have preliminarily investigated its potential role in evaluating the treatment efficacy of congenital hepatoblastoma.

CONCLUSION: Puncture biopsy is a definitive and safe diagnostic method for congenital hepatoblastoma, while neoadjuvant chemotherapy is effective and facilitates subsequent complete tumor resection. Additionally, 3D visual analysis shows significant potential in the surgical treatment of pediatric liver masses.

PMID:39317020 | PMC:PMC11456881 | DOI:10.1016/j.ijscr.2024.110337

Permalink for 'Upfront or delayed surgery in resectable hepatoblastoma: analysis from the children's hepatic tumors international collaboration database'

Upfront or delayed surgery in resectable hepatoblastoma: analysis from the children's hepatic tumors international collaboration database

Fetched: October 16th, 2024, 2:01am UTC by Eiso Hiyama

EClinicalMedicine. 2024 Sep 9;76:102811. doi: 10.1016/j.eclinm.2024.102811. eCollection 2024 Oct.

ABSTRACT

BACKGROUND: In the treatment of resectable hepatoblastoma (HB), it has not been established whether upfront surgery (UF) at diagnosis or neoadjuvant chemotherapy and delayed surgery (DL) is preferred. We compared patients with localized HB who underwent either UF, or DL after neoadjuvant chemotherapy in the Children's Hepatic tumors International Collaboration (CHIC) database of 1605 cases enrolled in eight multicenter hepatoblastoma trials between 1988 and 2010.

METHODS: Among the 512 resectable HB patients who had PRETEXT (PRETreament EXTent of disease) I or II unruptured tumors at diagnosis without extrahepatic invasion, distant metastases, or massive vascular invasion, 172 underwent UF and 340 underwent DL. The primary outcomes were event-free and overall survivals after start of treatment in these two groups. Survival analysis was performed using the Kaplan-Maier analysis with long-rank tests and multivariable Cox regression models.

FINDINGS: Complete resection rates were comparable (93.6% in UF and 89.7% in DL). The total cycles of chemotherapy of DL (median:6) were significantly more than those of UF (median:4) (P < 0.01). The 5-year event-free survival (EFS) was 90.6% and 86.6% (P = 0.89) in the UF and DL cohorts, respectively. The surgical complications, recurrence rates, and late complications were not significantly different between the cohorts but the EFS rates of DL patients with a low alpha-fetoprotein (AFP) level (100-999 ng/mL) or older age at diagnosis (â‰¥3 years old) were significantly worse than others.

INTERPRETATION: The outcomes, surgical resectability, and complications were not significantly different between the UF and DL groups. Eligible patients with a low AFP level (<1000 ng/mL) or older age (â‰¥3 years old) showed better outcomes in the UF group and might be considered for initial resection.

FUNDING: European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission; Children's Oncology Group Cure Search grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research and Development; Japan Society for the Promotion of Science; and Swiss Cancer Research grant.

PMID:39309724 | PMC:PMC11414700 | DOI:10.1016/j.eclinm.2024.102811

Abdominal pain and distension in a 4-years-old child revealing an hepatoblastoma

Fetched: October 16th, 2024, 2:01am UTC by Kenza Berrada

Radiol Case Rep. 2024 Sep 12;19(12):5804-5808. doi: 10.1016/j.radcr.2024.07.185. eCollection 2024 Dec.

ABSTRACT

Hepatoblastoma (HBL) stands as the primary liver tumor most frequently encountered in children, typically identified within the initial 5 years of life. Cases involving patients older than 5 years are very rare. We report the case of a 4-year-old male child who presented to the emergency department with acute onset abdominal pain and fever. Clinical examination revealed significant abdominal distension, correlated with an abdominal mass later confirmed.

PMID:39308612 | PMC:PMC11416352 | DOI:10.1016/j.radcr.2024.07.185

Mechanism of ganoderic acid X in treating hepatoblastoma based on proteomics

Fetched: October 16th, 2024, 2:01am UTC by Ting Ye

Zhongguo Zhong Yao Za Zhi. 2024 Aug;49(15):4158-4166. doi: 10.19540/j.cnki.cjcmm.20240412.702.

ABSTRACT

This research explored the mechanism of ganoderic acid X(GAX) on human hepatocellular carcinoma cell models(HepG2, HuH6) and nonobese diabetic-severe combined immune deficient(NOD-SCID) mouse subcutaneous tumor models using proteomics, aiming to provide a basis for the clinical application of GAX. CCK-8 assay was employed to evaluate the effect of GAX on the viability of HepG2 and HuH6 cells. EdU assay was used to assess the effect of GAX on cell proliferation. Scratch assay was used to examine the effect of GAX on cell migration ability. Hoechst 33258 staining was used to investigate the effect of GAX on cell apoptosis. Moreover, a NOD-SCID mouse subcutaneous tumor model was established to analyze the tumor volume and weight in control group and GAX low-, medium-, and high-dose groups(5, 10, and 20 mgÂ·kg~(-1)). HE staining was conducted to evaluate the drug toxicity of GAX. Additionally, HepG2 cells in the control group and the GAX high-dose group were subjected to label-free proteomics analysis to identify differential proteins and enrich relevant signaling pathways. CYTO-IDÂ® staining was performed to detect autophagy, and Western blot was conducted to measure the expression levels of relevant proteins. In vitro results demonstrated that GAX dose-depen-dently inhibited proliferation, migration, and induced apoptosis in HepG2 and HuH6 cells. In vivo studies showed that GAX significantly inhibited tumor volume and weight without causing significant damage to major organs(heart, liver, spleen, lung, and kidney) in mice. Label-free proteomics analysis revealed that GAX participated in multiple signaling pathways during the treatment of hepatocellular carcinoma, with a high enrichment in the autophagy pathway. CYTO-IDÂ® staining and Western blot results showed that GAX induced autophagy, upregulated the expression of Beclin-1, ATG5, and LC3-â…¡ proteins, and downregulated the expression of p62 protein. This study suggests that GAX inhibits the proliferation, migration, and induces apoptosis of hepatocellular carcinoma cells by inducing autophagy, thereby significantly inhibiting tumor growth. GAX represents a promising adjuvant therapy for cancer treatment.

PMID:39307748 | DOI:10.19540/j.cnki.cjcmm.20240412.702

HAND2-AS1 plays a tumor-suppressive role in hepatoblastoma through the negative regulation of CDK1

Fetched: October 16th, 2024, 2:01am UTC by Keke Chen

Heliyon. 2024 Aug 8;10(17):e35930. doi: 10.1016/j.heliyon.2024.e35930. eCollection 2024 Sep 15.

ABSTRACT

OBJECTIVE: Hepatoblastoma (HB) is the most commonly seen pediatric liver malignancy. The preliminary experiment of our research group found that cyclin dependent kinase 1 (CDK1) was upregulated in HB. By in silico analysis, long noncoding RNA (lncRNA) HAND2 antisense RNA 1 (HAND2-AS1) was determined as the research object. Herein, HAND2-AS1 expression in HB and its effect and mechanism on HB were extensively investigated.

METHODS: CDK1-related lncRNAs were searched using the microarray data from the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA) online database. qRT-PCR, Western blot, and immunohistochemistry were performed to determine the mRNA expression and protein levels of target genes. MTT, flow cytometry and DAPI staining assays were conducted to measure proliferation activity, cell cycle progression, and apoptosis of HB cells. The interaction between lncRNA and protein was determined by RNA pull-down and FISH assays. Luciferase assay was applied to identify whether HAND2-AS1 stimulates the transcription of CDK1. CDK1 mRNA stability was detected through actinomycin D assay. Aycloheximide assay was used to detect the CDK1 protein stability.

RESULTS: HAND2-AS1 was downregulated in HB tissues and cells. HAND2-AS1 overexpression impeded HB cells proliferation activity and cycle progression while inducing cell apoptosis of HB cells, while knockdown of HAND2-AS1 emerged the opposite effect. HAND2-AS1 negatively correlated with CDK1. HAND2-AS1 downregulated CDK1 expression by affecting the transcriptional activity, mRNA and protein stability of CDK1. Furthermore, HAND2-AS1 impeded HB cell proliferation and cycle progression while inducing cell apoptosis by downregulating CDK1.

CONCLUSION: Our research highlights that HAND2-AS1 can exert a tumor-suppressive effect on HB through the negative regulation of CDK1, and the HAND2-AS1/CDK1 is expected to be a diagnostic molecular marker and therapeutic target for HB in clinical practice.

PMID:39286228 | PMC:PMC11402935 | DOI:10.1016/j.heliyon.2024.e35930

DICER1 syndrome with hepatoblastoma and pleuropulmonary blastoma

Fetched: October 16th, 2024, 2:01am UTC by Melda Berber Hamamci

Pediatr Blood Cancer. 2024 Sep 17:e31285. doi: 10.1002/pbc.31285. Online ahead of print.

NO ABSTRACT

PMID:39285752 | DOI:10.1002/pbc.31285

Permalink for 'Pylorus-preserving pancreaticoduodenectomy with superior mesenteric vein resection and reconstruction in a child with recurrent hepatoblastoma after liver transplantation'

Pylorus-preserving pancreaticoduodenectomy with superior mesenteric vein resection and reconstruction in a child with recurrent hepatoblastoma after liver transplantation

Fetched: October 16th, 2024, 2:01am UTC by Ioannis A Ziogas

Pediatr Blood Cancer. 2024 Sep 12:e31330. doi: 10.1002/pbc.31330. Online ahead of print.

ABSTRACT

Pancreaticoduodenectomy with vascular reconstruction is rarely performed in children. We present a 3-year-old male with stage IV hepatoblastoma and pre-treatment extent of disease (PRETEXT) stage III with tumor into the portal vein and superior mesenteric vein (SMV), and with brain and lung metastases status post chemotherapy and stereotactic radiosurgery to left frontal brain lesion. He then underwent deceased donor liver transplant with Roux-en-Y hepaticojejunostomy complicated by two recurrences to bilateral lungs treated with wedge resections. His course lastly involved a third hepatoblastoma recurrence to the SMV that was managed with pylorus-preserving pancreaticoduodenectomy with SMV resection and reconstruction.

PMID:39267234 | DOI:10.1002/pbc.31330

Development of Novel Indole-Based Covalent Inhibitors of TEAD as Potential Antiliver Cancer Agents

Fetched: October 16th, 2024, 2:01am UTC by Chen Zhou

J Med Chem. 2024 Sep 26;67(18):16270-16295. doi: 10.1021/acs.jmedchem.4c00925. Epub 2024 Sep 13.

ABSTRACT

Abnormal activation of the YAP transcriptional signaling pathway drives proliferation in many hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cases. Current treatment options often face resistance and toxicity, highlighting the need for alternative therapies. This article reports the discovery of a hit compound C-3 from docking-based virtual screening targeting TEAD lipid binding pocket, which inhibited TEAD-mediated transcription. Optimization led to the identification of a potent and covalent inhibitor CV-4-26 that exhibited great antitumor activity in HCC and HB cell lines in vitro, xenografted human HCC, and murine HB in vivo. These outcomes signify the potential of a highly promising therapeutic candidate for addressing a subset of HCC and HB cancers. In the cases of current treatment challenges due to high upregulation of YAP-TEAD activity, these findings offer a targeted alternative for more effective interventions against liver cancer.

PMID:39270302 | DOI:10.1021/acs.jmedchem.4c00925

Permalink for '[68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging-A First-in-Human Case Series'

[68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging-A First-in-Human Case Series

Fetched: October 16th, 2024, 2:01am UTC by Alex J Poot

J Nucl Med. 2024 Oct 1;65(10):1597-1603. doi: 10.2967/jnumed.124.268147.

ABSTRACT

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [⁶⁸Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [⁶⁸Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with ⁶⁸Ga from a ⁶⁸Ge/⁶⁸Ga generator and heating at 90Â°C for 10 min followed by sterile filtration. After administration of [⁶⁸Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non-tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor-to-healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUVmax of these lesions was 19.6 (range, 2.7-95.3), and the mean SUVmean was 10.1 (range, 1.0-49.2) at approximately 60 min after administration. Uptake in non-tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUVmean, <1.6), with a continuous decline to 4 h after administration (mean SUVmean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUVmax of 31.3) and decreased gradually afterward. Conclusion: [⁶⁸Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [⁶⁸Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

PMID:39266293 | DOI:10.2967/jnumed.124.268147

Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review

Fetched: October 16th, 2024, 2:01am UTC by Marjan Moghadamnia

Paediatr Drugs. 2024 Sep 9. doi: 10.1007/s40272-024-00648-4. Online ahead of print.

ABSTRACT

BACKGROUND: Immunosuppressive medications play a crucial role in determining both organ and patient survival following liver transplantation (LT). Typically, immunosuppressive protocols for pediatric LT patients rely on calcineurin inhibitors (CNIs). While inhibitors of mammalian target of rapamycin (mTOR) have demonstrated beneficial outcomes in adult recipients of liver allografts, such as improved renal function post-LT, their application in pediatric liver transplant recipients is a subject of debate due to uncertain efficacy and potential adverse effects.

OBJECTIVES: This review evaluates the potential roles of mTOR inhibitors in the context of pediatric LT patients.

METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for conduct and reporting. Databases until 31 August 2023 were searched using specific terms and keywords. All clinical studies focusing on mTOR inhibitors in pediatric LT were included.

RESULTS: Out of 888 identified articles, 30 studies, involving 386 children who had undergone liver transplantation and received mTOR-inhibitor-based immunosuppressive regimens, met the inclusion criteria. The beneficial impacts of switching from a CNI to an mTOR inhibitor or adding an mTOR inhibitor to CNI-reduced immunosuppression in LT pediatric patients with impaired kidney function are controversial, and high-powered clinical studies are need. It appears that enhancing immunosuppression by adding an mTOR inhibitor to CNI is helpful for pediatric LT recipients who are experiencing refractory acute rejection or chronic rejection. mTOR-inhibitor-containing regimens failed to reduce the occurrence of post-transplant lymphoproliferative disorders (PTLD) among children with LT that may be due to concomitant high CNI concentration among studied patients. The effectiveness of mTOR inhibitors in treating PTLD remains uncertain; however, in patients with PTLD who are at high risk of rejection, mTOR inhibitors may be administered. Conversion to or the addition of mTOR inhibitors to maintenance immunosuppression seems to be suitable for pediatric patients who received a transplant due to hepatic malignancies such as hepatoblastoma or hepatocellular carcinoma or for those with post-transplant primary or recurrent malignancies. Switching to an mTOR inhibitor may improve some CNI-related adverse effects such as gingival hyperplasia, neurotoxicity, nephropathy, hypertrophic cardiomyopathy, or thrombotic microangiopathy.

CONCLUSION: Although the exact role of mTOR inhibitors among pediatric patients who have received a liver transplant needs further study, two algorithms are presented in this review to guide conversion from CNIs to mTOR inhibitors or the addition of mTOR inhibitor to a CNI-minimization immunosuppressive regimen for pediatric patients who may benefit from this class of drugs. This review mainly consisted of retrospective studies with inadequate sample sizes and lacked a control group, which represents the main limitation of this study.

PMID:39251556 | DOI:10.1007/s40272-024-00648-4

Permalink for 'N6-methyladenosine modification of LATS2 promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis'

N6-methyladenosine modification of LATS2 promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis

Fetched: October 16th, 2024, 2:01am UTC by Guoqing Zhu

Int J Biol Sci. 2024 Aug 1;20(11):4146-4161. doi: 10.7150/ijbs.92413. eCollection 2024.

ABSTRACT

Ferroptosis has attracted extensive interest from cancer researchers due to its substantial potential as a therapeutic target. The role of LATS2, a core component of the Hippo pathway cascade, in ferroptosis initiation in hepatoblastoma (HB) has not yet been investigated. Furthermore, the underlying mechanism of decreased LATS2 expression remains largely unknown. In the present study, we demonstrated decreased LATS2 expression in HB and that LATS2 overexpression inhibits HB cell proliferation by inducing ferroptosis. Increased LATS2 expression reduced glycine and cysteine concentrations via the ATF4/PSAT1 axis. Physical binding between YAP1/ATF4 and the PSAT1 promoter was confirmed through ChIPâ€’qPCR. Moreover, METTL3 was identified as the writer of the LATS2 mRNA m6A modification at a specific site in the 5' UTR. Subsequently, YTHDF2 recognizes the m6A modification site and recruits the CCR4-NOT complex, leading to its degradation by mRNA deadenylation. In summary, N6-methyladenosine modification of LATS2 facilitates its degradation. Reduced LATS2 expression promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis. Targeting LATS2 is a potential strategy for HB therapy.

PMID:39247829 | PMC:PMC11379071 | DOI:10.7150/ijbs.92413

TRMT10C gene polymorphisms confer hepatoblastoma susceptibility: evidence from a seven-center case-control study

Fetched: October 16th, 2024, 2:01am UTC by Yanfei Liu

J Cancer. 2024 Aug 19;15(16):5396-5402. doi: 10.7150/jca.98555. eCollection 2024.

ABSTRACT

N1-methyladenosine (m¹A) is a reversible epigenetic modification of RNAs. Aberrant m¹A modification levels due to dysregulation of m¹A regulators have been observed in multiple cancers. tRNA methyltransferase 10C (TRMT10C) can install m¹A in RNAs; however, its role in hepatoblastoma remains unknown. We conducted this study to identify causal polymorphisms in the TRMT10C gene for hepatoblastoma susceptibility in a cohort of Chinese children (313 cases vs. 1446 controls). The genotypes of four potential functional polymorphisms (rs7641261 C>T, rs2303476 T>C, rs4257518 A>G, and rs3762735 C>G) were determined in participants using TaqMan real-time PCR. The associations of these polymorphisms with hepatoblastoma susceptibility were estimated by logistic regression analysis adjusted for age and sex. All four polymorphisms were significantly associated with hepatoblastoma risk. In particular, under the recessive genetic model, these polymorphisms conferred an increased risk of hepatoblastoma: rs7641261 C>T [adjusted odds ratio (OR)=1.64, 95% confidence interval (CI)=1.04-2.58, P=0.033], rs2303476 T>C (adjusted OR=1.87, 95% CI=1.16-3.02, P=0.010), rs4257518 A>G (adjusted OR=1.45, 95% CI=1.09-1.94, P=0.012), and rs3762735 C>G (adjusted OR=3.83, 95% CI=2.15-6.82, P<0.0001). Combined analysis revealed that kids had an increased risk of developing hepatoblastoma if they harbored at least one risk genotype (adjusted OR=1.94, 95% CI=1.48-2.54, P<0.0001). In addition, the combined risk effects of the four SNPs persisted across all the subgroups. We identified four hepatoblastoma susceptibility loci in the TRMT10C gene. Identifying more disease-causing loci may facilitate the development of genetic marker panels to predict individuals' hepatoblastoma predisposition.

PMID:39247598 | PMC:PMC11375554 | DOI:10.7150/jca.98555

Regulation of Hepatitis B Virus Replication by Modulating Endoplasmic Reticulum Stress (ER-Stress)

Fetched: October 16th, 2024, 2:01am UTC by Md Golzar Hossain

Int J Microbiol. 2024 Aug 30;2024:9117453. doi: 10.1155/2024/9117453. eCollection 2024.

ABSTRACT

Hepatitis B virus (HBV), resistant to several antiviral drugs due to viral genomic mutations, has been reported, which aggravates chronic infection and leads to hepatocellular carcinoma. Therefore, host cellular factors/signaling modulation might be an alternative way of treatment for drug-resistant HBV. Here, we investigated the viral protein expression, replication, and virion production using endoplasmic reticulum (ER) stress-modulating chemicals, tunicamycin (an ER-stress inducer), and salubrinal (an ER-stress inhibitor). We found that ER-stress could be induced by HBV replication in transfected HepG2 cells as well as by tunicamycin as demonstrated by dual luciferase assay. HBV intracellular core-associated DNA quantified by qPCR has been significantly increased by tunicamycin in transfected HepG2 cells. Inversely, intracellular core associated and extracellular particle DNA has been significantly decreased in a dose-dependent manner in salubrinal-treated HepG2 cells transfected with HBV-replicating plasmid pHBI. Similar results were found in stably HBV-expressing hepatoblastoma (HB611) cells treated with salubrinal. However, increased or decreased ER-stress by tunicamycin or salubrinal treatment, respectively, has been confirmed by expression analysis of grp78 using Western blot. In addition, Western blot results demonstrated that the expression of HBV core protein and large HBsAg is increased and decreased by tunicamycin and salubrinal, respectively. In conclusion, the sal-mediated inhibition of the HBV replication and virion production might be due to the simultaneous reduction of core and large HBsAg expression and maintaining the ER homeostasis. These results of HBV replication regulation by modulation of ER-stress dynamics would be useful for designing/identifying anti-HBV drugs targeting cellular signaling pathways.

PMID:39246409 | PMC:PMC11379510 | DOI:10.1155/2024/9117453

Adult Hepatoblastoma and Concomitant Hepatitis B Infection

Fetched: October 16th, 2024, 2:01am UTC by Alejandro Nieto Dominguez

ACG Case Rep J. 2024 Sep 5;11(9):e01491. doi: 10.14309/crj.0000000000001491. eCollection 2024 Sep.

ABSTRACT

We report a case of hepatoblastoma in a 26-year-old man with a background of type 2 diabetes mellitus and untreated hepatitis B, initially presenting with hematemesis and a recent diagnosis of hepatocellular carcinoma on computed tomography scan from a different hospital and recent referral to hospice. On presentation to our hospital, given atypical presentation for hepatocellular carcinoma, histological examination was made, revealing hepatoblastoma. Treatment included chemotherapy and management of hepatitis B, although complicated by chemotherapy-induced cytopenias and tumor progression, ultimately losing the patient to follow-up after 2 years.

PMID:39238883 | PMC:PMC11377089 | DOI:10.14309/crj.0000000000001491

Permalink for 'Liver Mitochondrial Morphology and Gene Expression as Markers of Liver Reserve: Prognostic Implications for Native Liver Survival in Biliary Atresia'

Liver Mitochondrial Morphology and Gene Expression as Markers of Liver Reserve: Prognostic Implications for Native Liver Survival in Biliary Atresia

Fetched: August 28th, 2024, 2:02am UTC by Takashi Fujimoto

J Pediatr Surg. 2024 Jul 26:161648. doi: 10.1016/j.jpedsurg.2024.07.033. Online ahead of print.

ABSTRACT

PURPOSE: Hepatocyte mitochondrial morphology and gene expression were compared between biliary atresia (BA), infantile cholestasis (IC), and normal liver (NL) as prognostic indicators.

METHODS: Specimens of liver at portoenterostomy (PE) for BA, from intrahepatic bile duct paucity patients for IC, and from choledochal cyst or hepatoblastoma patients for NL were collected prospectively (P) beginning in 2021 (P-BA = 11, P-IC = 9, P-NL = 7) and retrospectively (R) from paraffin-embedded tissue going back to 1981 (R-BA = 25, R-IC = 9, R-NL = 4). The P-cohort had transmission electron microscopy (TEM) to image mitochondria, immunoblotting for heat shock protein 60 (HSP60), and quantitative PCR (qPCR) for HSP60 and mitochondrial functional genes. Both cohorts had immunofluorescence for HSP60 quantified as a ratio to albumin-positive hepatocytes (ALB) with HSP60/ALB<1.0 as a cutoff limit using ImageJ.

RESULTS: HSP60 was significantly lower in BA/IC than NL on qPCR (BA: p < 0.01, IC: p < 0.05) and lower in BA than IC/NL on immunoblotting (p < 0.05). HSP60/ALB was significantly lower in BA than NL/IC (p < 0.001). Despite BA subjects being matched for types of BA and ages at PE, HSP60/ALB did not correlate with jaundice clearance (JC; T-Bil<1.2 mg/dL) but was significantly higher in native liver survivors (NLS) after PE compared with liver transplant (LTx) cases (p < 0.05) and significantly lower in LTx cases achieving JC than NLS achieving JC (p < 0.05). TEM showed BA had significantly more mitochondrial inclusion bodies (p < 0.05) and significantly larger cristae (p < 0.01) than IC/NL. qPCR in BA showed significant repression of mitochondrial functional genes for mRNA stabilization and energy facilitation.

CONCLUSION: HSP60/ALB correlates with NLS after PE for BA.

LEVEL OF EVIDENCE: II.

PMID:39187420 | DOI:10.1016/j.jpedsurg.2024.07.033

Clinical Characteristics and Outcomes of Neonatal Hepatoblastoma: A Single Center Study

Fetched: August 23rd, 2024, 2:02am UTC by Jiquan Zhou

J Pediatr Surg. 2024 Jul 23:161640. doi: 10.1016/j.jpedsurg.2024.07.025. Online ahead of print.

ABSTRACT

OBJECTIVE: Hepatoblastoma (HB) diagnosed within one month following birth qualifies for a diagnosis of neonatal HB, whose prognosis is reportedly controversial, and its treatment is challenging. This study discussed the diagnosis, treatment, and outcomes of neonatal HB at a single center so as to enhance its overall management in the future.

METHODS: The clinical information of babies diagnosed with neonatal HB at our center from August 2009 to September 2023 were retrospectively analyzed for demographics, clinical features, therapy, and outcomes. The outcomes were estimated by the Kaplan-Meier analysis method.

RESULTS: The study comprised 79 patients aged less than one year old, among which 14 had neonatal HB whereas 65 were non-neonatal HB patients. No differences were found between groups regarding gender, birth weight, delivery details, parental age, clinical signs, or treatment strategies. Neonatal HB patients were more likely to have PRETEXT I-II, smaller tumor size, congenital diseases, and lower risk tumor grade (p < 0.05). Additionally, the AFP levels of all neonatal HB patients were greater than 10,000 ng/ml (p = 0.009) and they had higher levels of ferritin (p = 0.003) and hemoglobin (p = 0.021), but lower levels of serum total proteins (p = 0.001). The three-year survival rate (100% vs 90.8%) and three-year event-free survival rate (100% vs 86.2%) in the neonatal HB group were higher than the non-neonatal HB group.

CONCLUSION: Neonatal HB patients have unique clinical features and can achieve an excellent prognosis following combined treatment with surgery and chemotherapy. Tumor resection, when carefully performed, was safe even in babies younger than one months old. Further and long-term studies are needed from a larger neonatal HB population.

LEVEL OF EVIDENCE: Level III.

PMID:39174446 | DOI:10.1016/j.jpedsurg.2024.07.025

Permalink for 'Suppressive effect of isofraxidin on the overexpression of IL-6 and its molecular mechanism in a TPA-treated human hepatocellular carcinoma cell line, HuH-7'

Suppressive effect of isofraxidin on the overexpression of IL-6 and its molecular mechanism in a TPA-treated human hepatocellular carcinoma cell line, HuH-7

Fetched: August 23rd, 2024, 2:02am UTC by Taisuke Yamazaki

Naunyn Schmiedebergs Arch Pharmacol. 2024 Aug 22. doi: 10.1007/s00210-024-03394-z. Online ahead of print.

ABSTRACT

Interleukin-6 (IL-6) is a pleiotropic cytokine that has many biological activities, including inflammation, hematopoiesis, bone metabolism, embryonic development, and other fundamental processes. Recently, IL-6 has been widely recognized as an important pro-inflammatory cytokine involved in cytokine storm pathogenesis during severe inflammatory diseases, such as coronavirus disease 2019 (COVID-19). Therefore, IL-6 is considered to be a therapeutic target for inhibiting cytokine storm. In the present study, we investigated the suppressive effect of isofraxidin, a major coumarin compound of Acanthopanax senticosus, on the overexpression of IL-6 and its molecular mechanism. The expression of IL-6 mRNA was measured using quantitative real-time PCR, and intracellular signaling molecules were detected using western blotting. When the HuH-7 human hepatocellular carcinoma cell line and HepG2 human hepatoblastoma cell line were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA), a marked induction of IL-6 mRNA expression was observed in HuH-7 cells compared with HepG2 cells. Isofraxidin significantly suppressed TPA-induced IL-6 mRNA expression in HuH-7 cells in a dose-dependent manner. Furthermore, isofraxidin inhibited TPA-induced phosphorylation of ERK1/2 in a dose-dependent manner. Similarly, the MAPK/ERK inhibitor U0126 suppressed TPA-induced IL-6 mRNA expression. However, isofraxidin had no effects on TPA-induced phosphorylation of SAPK/JNK, Akt (Ser473), and STAT3 (Tyr705), nuclear translocation of NF-ÎºB p65, and degradation of IÎºB. Taken together, isofraxidin suppresses TPA-induced overexpression of IL-6 mRNA by selectively inhibiting the activation of the MAPK/ERK pathway in HuH-7 cells, indicating that isofraxidin may be an effective anti-inflammatory agent for treating cytokine storm.

PMID:39172147 | DOI:10.1007/s00210-024-03394-z

Liver transplantation for pediatric liver malignancies

Fetched: August 23rd, 2024, 2:02am UTC by Seisuke Sakamoto

Liver Transpl. 2024 Aug 23. doi: 10.1097/LVT.0000000000000470. Online ahead of print.

ABSTRACT

In the last few decades, collaboration between international pediatric oncology groups has resulted in significant improvement in survival after liver transplantation (LT) for pediatric liver tumors, and LT has become the accepted standard of care for unresectable pediatric liver tumors-either living donor liver transplantation or deceased donor liver transplantation. Hepatoblastoma and HCC are the common pediatric liver malignancies treated by LT, and LT is now the accepted treatment modality for unresectable nonmetastatic cases. The long-term survival rate is more than 80% in hepatoblastoma transplants. Furthermore, with the advent of living donor liver transplantation, the waitlist mortality, availability of a better graft quality with shorter ischemic times, and performance of LT with the appropriate timing between chemotherapy have all improved. Up to 80% of pediatric HCCs are unresectable, and studies have shown that LT for pediatric HCC has better outcomes than liver resection. Furthermore, LT has also shown better results than liver resection for cases of HCC not meeting Milan criteria. Given the rarity of pediatric liver malignancies and challenges in optimal management, a multidisciplinary treatment approach, research models building on what is already known, and consideration of newer treatment modalities are required for further improving the treatment of pediatric liver malignancies.

PMID:39172014 | DOI:10.1097/LVT.0000000000000470

Permalink for 'Worldwide burden of liver cancer across childhood and adolescence, 2000-2021: a systematic analysis of the Global Burden of Disease Study 2021'

Worldwide burden of liver cancer across childhood and adolescence, 2000-2021: a systematic analysis of the Global Burden of Disease Study 2021

Fetched: August 23rd, 2024, 2:02am UTC by Zenghong Wu

EClinicalMedicine. 2024 Jul 26;75:102765. doi: 10.1016/j.eclinm.2024.102765. eCollection 2024 Sep.

ABSTRACT

BACKGROUND: Liver cancer is a significant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the first 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we first provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence.

METHODS: Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs.

FINDINGS: Globally, from 2000 to 2021 in the age 5-19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9-2689.8) to 1692.9 (95% UI: 1482.0-1992.5) and 2248.5 (95% UI: 2053.7-2474.9) to 1516.6 (95% UI: 1322.1-1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20-24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8-1609.4) to 1285.1 (95% UI: 1159.2-1447.2) and 1432.3 (95% UI: 1307.6-1585.7) to 1195.5 (95% UI: 1066.1-1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%-64.7%) to 26.4% (95% UI: 14.2%-39.1%) in the age 5-19 years group, and 46.6% (95% UI: 42.8%-51.5%) to 36.5% (95% UI: 33.1%-40.9%) in the age 20-24 years. From 2000 to 2021, in the age group of 5-19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8-6961.9) to 4045.6 (95% UI: 3250-4995.8) and 4059.2 (95% UI: 3494.5-4621.2) to 2416 (95% UI: 1940.2-3022.5), respectively. There was some variation in age-related sex-specific patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month.

INTERPRETATION: The results of the present study are significant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old.

FUNDING: This study was supported by the National Key R&D Program of China (grant numbers 2023YFC2307000), National Natural Science Foundation of China [grant numbers 82170571 and 81974068], China Postdoctoral Science Foundation (grant numbers 2023M741283).

PMID:39170941 | PMC:PMC11338123 | DOI:10.1016/j.eclinm.2024.102765

Permalink for 'Comparative study on three-dimensional versus two-dimensional imaging using a computer-assisted surgery system for preoperative planning in pediatric middle hepatic tumors'

Comparative study on three-dimensional versus two-dimensional imaging using a computer-assisted surgery system for preoperative planning in pediatric middle hepatic tumors

Fetched: August 22nd, 2024, 2:01am UTC by Nan Su

BMC Surg. 2024 Aug 21;24(1):236. doi: 10.1186/s12893-024-02531-y.

ABSTRACT

BACKGROUD: The study objective was to compare three-dimensional and two-dimensional imaging using computer-assisted systems (CASs) in clinical guidance for preoperative surgical planning for middle hepatic tumors in children.

METHODS: A retrospective analysis was performed on 23 children who underwent surgery for middle hepatic tumors in our hospital from January 2016 to June 2022. The surgical resection plan was formulated by the operator team using two-dimensional CT images before the operation. Then, the same qualified surgeons conducted an in-depth analysis and formulated the surgical resection scheme for the same pediatric patient using three-dimensional imaging of the middle hepatic tumor. The feasibility of the two schemes was compared and analyzed.

RESULT: All the tumors were successfully removed according to the preoperative method developed using three-dimensional imaging. The postoperative short-term follow-up revealed that all patients were doing well. Preoperative plans were revised in 9 cases after evaluating the three-dimensional images due to the disparity between the original plans and the three-dimensional relationship between the tumor and blood vessels, vascular variation, and the volume of remnant liver.

CONCLUSIONS: Three-dimensional imaging with a computer-assisted surgery system is superior to two-dimensional imaging in the preoperative planning of pediatric hepatoblastoma.

PMID:39169378 | PMC:PMC11337585 | DOI:10.1186/s12893-024-02531-y

Phenotypic spectrum and tumor risk in Simpson-Golabi-Behmel syndrome: Case series and comprehensive literature review

Fetched: August 20th, 2024, 2:02am UTC by Alex F Nisbet

Am J Med Genet A. 2024 Aug 19:e63840. doi: 10.1002/ajmg.a.63840. Online ahead of print.

ABSTRACT

Simpson-Golabi-Behmel syndrome (SGBS) is a rare congenital overgrowth condition characterized by macrosomia, macroglossia, coarse facial features, and development delays. It is caused by pathogenic variants in the GPC3 gene on chromosome Xq26.2. Here, we performed a comprehensive literature review and phenotyping of known patients with molecularly confirmed SGBS and reviewed a novel cohort of 22 patients. Using these data, we characterized the tumor risk for Wilms tumor and hepatoblastoma to suggest appropriate screening for this patient population. In addition, we discuss the phenotypic overlap between SGBS and Beckwith-Wiedemann Spectrum.

PMID:39158128 | DOI:10.1002/ajmg.a.63840

Permalink for 'Hepatic resections for pediatric hepatoblastoma: analysis of 30-day outcomes using the National Surgical Quality Improvement Program-Pediatric database'

Hepatic resections for pediatric hepatoblastoma: analysis of 30-day outcomes using the National Surgical Quality Improvement Program-Pediatric database

Fetched: August 19th, 2024, 2:02am UTC by Humza Thobani

Pediatr Surg Int. 2024 Aug 17;40(1):230. doi: 10.1007/s00383-024-05820-y.

ABSTRACT

BACKGROUND: Surgical resection remains the cornerstone of treatment for hepatoblastoma in children and offers the best chance of disease-free survival. We aimed to analyze the 30 day outcomes of hepatic resection for hepatoblastoma stratified by extent using the National Surgical Quality Improvement Program-Pediatric (NSQIP-P).

METHODS: We queried NSQIP-P for children undergoing resection of Hepatoblastoma from 2012 to 2021. Relevant clinical characteristics and outcomes were extracted for multivariate logistic regression to identify predictors of common adverse outcomes.

RESULTS: We included 458 children with a median age of 1.90 years. Overall complications were rare, and perioperative blood transfusion (64.2%) and postoperative ventilation > 48 h (10.0%) were the only adverse events prevalent in more than 5% of patients. Median transfusion volume was 15.7 ml/kg. On multivariate regression, only patients undergoing Trisectionectomy (aOR = 3.387, 95% C.I. = 1.348-8.510) had higher odds of receiving > 75th percentile blood transfusion. Furthermore, only perioperative transfusion and postoperative ventilation > 48 h were statistically more common in patients undergoing extended versus standard resections.

CONCLUSIONS: Outcomes following resection of hepatoblastoma are excellent, with low rates of postoperative adverse events. Although children undergoing trisectionectomy likely require greater transfusion volume, extended hepatic resections do not appear to have worse 30 day outcomes despite greater operative complexity and duration.

PMID:39154089 | DOI:10.1007/s00383-024-05820-y

Effect of surgical complications on outcomes of children with hepatoblastoma: a retrospective cohort study

Fetched: August 17th, 2024, 2:01am UTC by Masahiro Zenitani

Surg Today. 2024 Aug 16. doi: 10.1007/s00595-024-02906-x. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the incidence of severe surgical complications among children with hepatoblastoma, identify their risk factors, and evaluate the influence of surgical complications on long-term outcomes.

METHODS: Children with hepatoblastoma who underwent liver resection at our hospital between September 1992 and January 2023 were included in this study. Clinical data were retrospectively reviewed, and patients were categorized into complication and non-complication groups based on the need for radiological or surgical interventions or massive intraoperative blood loss (> 80 mL/kg).

RESULTS: Out of the 40 patients, 9 experienced severe complications (massive blood loss, n = 7; bile leakage, n = 3; and common bile duct stricture, n = 1). The participation of experienced liver surgeons was significantly greater in the non-complication group than in the complication group. The median duration from surgery to the start of postoperative chemotherapy was significantly shorter in the non-complication group than in the complication group. The overall 5-year survival rate was significantly higher in the non-complication group than in the complication group.

CONCLUSION: Severe surgical complications were associated with a worse prognosis. An experienced liver surgeon should participate in technically demanding liver resections.

PMID:39150537 | DOI:10.1007/s00595-024-02906-x

Synthesis and antiproliferative evaluation of new hybrids of piperine and acylhydrazone

Fetched: August 17th, 2024, 2:01am UTC by Shi-Kun Xu

Nat Prod Res. 2024 Aug 15:1-6. doi: 10.1080/14786419.2024.2391083. Online ahead of print.

ABSTRACT

Piperine, a natural amide isolated from the genus of Piper, serves as a pharmacophore in medicinal chemistry. In this study, we synthesised and evaluated 18 novel piperine-acylhydrazone hybrids (4a-4r) for their antiproliferative activities in vitro. The structures of these hybrids were validated using ¹H,¹³C NMR, and HR-ESI-MS data. Furthermore, we screened all synthesised compounds for their antiproliferative activities against three human cancer cell lines: FaDu (laryngeal carcinoma cells), HepG2 (hepatoblastoma carcinoma cells), and MGC803 (gastric carcinoma cells). Among them, compound 4o exhibited significantly inhibitory activities against FaDu, HepG2, and MGC803 with IC50 values of 13.85 Â± 0.19, 11.02 Â± 1.45, and 13.47 Â± 3.43 Î¼M, respectively, which was approximately two-fold lower than the positive control cisplatin. These findings suggest that compound 4o has the potential to be promising leads for the design of anti-cancer drugs.

PMID:39148321 | DOI:10.1080/14786419.2024.2391083

Persistently elevated liver enzymes and bile acids, icterus, and weight loss in a 1.5-year-old Thoroughbred colt

Fetched: August 16th, 2024, 2:01am UTC by Seongjue Ahn

J Am Vet Med Assoc. 2024 Aug 14:1-4. doi: 10.2460/javma.24.06.0422. Online ahead of print.

NO ABSTRACT

PMID:39142326 | DOI:10.2460/javma.24.06.0422

Surgery for hepatoblastoma in children with trisomy 18: a monocentric study

Fetched: August 16th, 2024, 2:01am UTC by Kazuki Hirohara

Pediatr Surg Int. 2024 Aug 14;40(1):223. doi: 10.1007/s00383-024-05813-x.

ABSTRACT

PURPOSE: Recently, children with trisomy 18 have been receiving more active treatment for malignancies. We report herein seven cases complete resection was achieved, and discuss multidisciplinary treatment for hepatoblastoma in patients with trisomy 18.

METHOD: The medical records of children with trisomy 18 who were treated at the study center between 2010 and 2023 were reviewed.

RESULT: Six of 69 patients had hepatoblastoma development, and three of these underwent multidisciplinary treatment. In addition, 6 patients had been referred by another hospital for treatment, and four of these underwent multidisciplinary treatment. Among the seven patients who underwent multidisciplinary treatment, three, two, and two were categorized in Pre-treatment Extent of Disease (PRETEXT) classification group I, II, and III, respectively. Neoadjuvant chemotherapy resulting in tumor reduction was performed in three cases. In all the cases, complete resection was achieved with pathologically safe margins. Perioperative complications included circulatory failure in one case and bile leakage in two cases. Adjuvant chemotherapy was administered in four cases. The postoperative observation period ranged from 3 months to 11 years, and all the patients are recurrence-free.

CONCLUSION: Children with trisomy 18 complicated with hepatoblastoma whose cardiopulmonary conditions are stable may be good candidates for chemotherapy and surgery.

PMID:39141149 | DOI:10.1007/s00383-024-05813-x

Permalink for 'Lactucopicrin promotes fatty acid beta-oxidation and attenuates lipid accumulation through adenosine monophosphate-activated protein kinase activation in free fatty acid-induced human hepatoblastoma cancer cells'

Lactucopicrin promotes fatty acid beta-oxidation and attenuates lipid accumulation through adenosine monophosphate-activated protein kinase activation in free fatty acid-induced human hepatoblastoma cancer cells

Fetched: August 16th, 2024, 2:01am UTC by Huiwen Tan

Food Sci Nutr. 2024 Apr 18;12(8):5357-5372. doi: 10.1002/fsn3.4176. eCollection 2024 Aug.

ABSTRACT

With its annually increasing prevalence, non-alcoholic fatty liver disease (NAFLD) has become a serious threat to people's life and health. After a preliminary research, we found that Lactucopicrin has pharmacological effects, such as lowering blood lipids and protecting the liver. Further research showed its significant activation for fatty acid Î²-oxidase hydroxyacyl-coenzyme A (CoA) dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), so we hypothesized that Lactucopicrin could ameliorate lipid accumulation in hepatocytes by promoting fatty acid Î²-oxidation. In this study, free fatty acid (FFA)-induced human hepatoblastoma cancer cells (HepG2) were used to establish an in vitro NAFLD model to investigate the molecular basis of Lactucopicrin in regulating lipid metabolism. Staining with Oil red O and measurements of triglyceride (TG) content, fatty acid Î²-oxidase (FaÎ²O) activity, reactive oxygen species (ROS) content, mitochondrial membrane potential, and adenosine triphosphate (ATP) content were used to assess the extent to which Lactucopicrin ameliorates lipid accumulation and promotes fatty acid Î²-oxidation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods were used to explore the regulatory effects of Lactucopicrin on factors related to fatty acid Î²-oxidation. Results showed that Lactucopicrin downregulated phosphorylated mammalian target of rapamycin (P-mTOR) by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and upregulated the messenger RNA (mRNA) and protein expression levels of coactivators (peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1Î±)), transcription factors (peroxisome proliferator-activated receptor Î± (PPARÎ±) and peroxisome proliferator-activated receptor Î³ (PPARÎ³)), and oxidative factors (carnitine palmitoyltransferase 1A (CPT1A) and HADHA). This phenomenon resulted in a significant increase in FaÎ²O activity, ATP content, and JC-1 and a significant decrease in ROS level, TG content, and intracellular lipid droplets. With the addition of Dorsomorphin, all the effects of Lactucopicrin intervention were suppressed. In summary, Lactucopicrin promotes fatty acid Î²-oxidation by activating the AMPK pathway, thereby ameliorating FFA-induced intracellular lipid accumulation in HepG2 cells.

PMID:39139977 | PMC:PMC11317671 | DOI:10.1002/fsn3.4176

Permalink for 'Synthesis of novel piperazine-based bis(thiazole)(1,3,4-thiadiazole) hybrids as anti-cancer agents through caspase-dependent apoptosis'

Synthesis of novel piperazine-based bis(thiazole)(1,3,4-thiadiazole) hybrids as anti-cancer agents through caspase-dependent apoptosis

Fetched: August 13th, 2024, 2:02am UTC by Doaa M Mohamed

RSC Adv. 2024 Aug 9;14(34):24992-25006. doi: 10.1039/d4ra05091f. eCollection 2024 Aug 5.

ABSTRACT

A series of novel piperazine-based bis(thiazoles) 13a-d were synthesized in moderate to good yields via reaction of the bis(thiosemicarbazones) 7a, b with an assortment of C-acetyl-N-aryl-hydrazonoyl chlorides 8a-f. Similar treatment of the bis(thiosemicarbazone) 7a, b with C-aryl-N-phenylhydrazonoyl chlorides 10a, b afforded the expected bis(thiadiazole) based piperazine products 13b-d in reasonable yields. Cyclization of 7a, b with two equivalents of Î±-haloketones 14a-d led to the production of the corresponding bis(4-arylthiazol)piperazine derivatives 15a-h in good yields. The structures of the synthesized compounds were confirmed from elemental and spectral data (FTIR, MALDI-TOF, ¹H, and ¹³C NMR). The cytotoxicity of the new compounds was screened against hepatoblastoma (HepG2), human colorectal carcinoma (HCT 116), breast cancer (MCF-7), and Human Dermal Fibroblasts (HDF). Interestingly, all compounds showed promising cytotoxicity against most of the cell lines. Interestingly, compounds 7b, 9a, and 9i exhibited IC50 values of 3.5, 12.1, and 1.2 nM, respectively, causing inhibition of 89.7%, 83.7%, and 97.5%, compared to Erlotinib (IC50 = 1.3 nM, 97.8% inhibition). Compound 9i dramatically induced apoptotic cell death by 4.16-fold and necrosis cell death by 4.79-fold. Compound 9i upregulated the apoptosis-related genes and downregulated the Bcl-2 as an anti-apoptotic gene. Accordingly, the most promising EGFR-targeted chemotherapeutic agent to treat colon cancer was found to be compound 9i.

PMID:39131497 | PMC:PMC11310838 | DOI:10.1039/d4ra05091f

LncRNA MEG9 Promotes Inflammation and Liver Fibrosis Through S100A9 in Biliary Atresia

Fetched: August 12th, 2024, 2:02am UTC by Lingdu Meng

J Pediatr Surg. 2024 Jul 18:161633. doi: 10.1016/j.jpedsurg.2024.07.018. Online ahead of print.

ABSTRACT

BACKGROUND: The pathogenesis of biliary atresia (BA) remains elusive. We aimed to investigate the role of long noncoding RNA (lncRNA) MEG9 in BA.

METHODS: LncRNA microarray was conducted to identify differentially expressed lncRNAs in three BA and three para-hepatoblastoma liver tissues. RT-qPCR validated the results. Human intrahepatic bile duct epithelial cells (HIBECs) were stably transfected with lncRNA MEG9 knockdown/overexpression to investigate its cellular localization and function. RNA sequencing (RNA-seq), differentially expressed genes (DEGs) analysis and gene set enrichment analysis were applied to MEG9-overexpresed HIBECs. RNA pull-down and mass spectrometry explored the interacting protein of MEG9, while clinical information was reviewed.

RESULTS: 436 differentially expressed lncRNAs were identified, with MEG9 highly upregulated in BA. RT-qPCR further confirmed MEG9's overexpression in BA and diagnostic potential (AUC = 0.9691). MEG9 was predominantly located in the nucleus and significantly promoted cell proliferation and migration. RNA-seq revealed inflammation- and extracellular matrix-related pathways enriched in MEG9-overexpressing HIBECs, with upregulated cytokine genes like CXCL6 and IL6. MMP-7 and collagen I were also overexpressed. Furthermore, 38 proteins were identified to specifically interact with MEG9, and S100A9 was highly expressed in cell models. S100A9 was also significantly upregulated in BA liver tissue and correlated with MEG9 expression (r = 0.313, p < 0.05), albumin level (r = -0.349, p < 0.05), and platelet level (r = -0.324, p < 0.05).

CONCLUSION: MEG9 influences cholangiocyte proliferation, migration, and cytokine production, potentially regulating BA inflammation and fibrosis via S100A9 interaction.

PMID:39127593 | DOI:10.1016/j.jpedsurg.2024.07.018

Permalink for 'Successful treatment of young childhood standard-risk hepatoblastoma with cisplatin monotherapy using a central review system'

Successful treatment of young childhood standard-risk hepatoblastoma with cisplatin monotherapy using a central review system

Fetched: August 11th, 2024, 2:02am UTC by Isamu Saeki

Pediatr Blood Cancer. 2024 Nov;71(11):e31255. doi: 10.1002/pbc.31255. Epub 2024 Aug 10.

ABSTRACT

BACKGROUND: The JPLT3-S (Japanese Study Group for Pediatric Liver Tumors-3) study, conducted cisplatin (CDDP) monotherapy for young children (<3 years old) with standard-risk hepatoblastoma (HB) using a central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT (PRETreatment EXTent of disease) classification (standard-risk HB) showed favorable outcomes with treatment consisting of CDDP and pirarubicin, but showed toxicities and late complications. In the JPLT3-S trial, a less intense regimen consisting of CDDP alone was evaluated.

METHODS: Patients who were less than 3 years of age and with PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, the central radiological and pathological features of all patients were reviewed. The primary outcome was the 3-year progression-free survival (PFS).

RESULTS: A total of 38 patients (23 female) were included. The median patient age was 12 months (range: 2-34). Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3-year PFS rate was 93.9% (95% confidence interval [CI]: 86.4%-100%). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (CI: 100). Eighteen of the 38 patients (47.4%) experienced ototoxicity as a late complication.

CONCLUSION: CDDP monotherapy regimen is feasible in young patients with localized HB, as classified by a central review.

PMID:39126361 | DOI:10.1002/pbc.31255

The impact of congenital heart disease on treatment and survival of patients with hepatoblastoma: A single-center experience

Fetched: August 10th, 2024, 2:01am UTC by Andres F Espinoza

Pediatr Blood Cancer. 2024 Nov;71(11):e31214. doi: 10.1002/pbc.31214. Epub 2024 Aug 8.

ABSTRACT

BACKGROUND: Patients with hepatoblastoma (HB) have a higher risk of congenital heart defects (CHD). There is limited literature on the management and outcomes of these patients. The purpose of this study was to identify demographics and outcomes of these patients in a single tertiary referral center.

METHODS: An Institutional Review Board (IRB)-approved retrospective chart review of patients with newly diagnosed HB from October 2004 to January 2021 was performed. CHD was defined as the presence of a septal defect, patent ductus arteriosus, pulmonary atresia, or bicuspid aortic valve. Chi-square and t-test were utilized for statistical analyses.

RESULTS: Of the 151 patients diagnosed with HB during the study timeframe, 29 patients were found to have CHD. Five-year overall survival (OS) for non-CHD HB patients was 81.9% compared to 68.9% in the CHD cohort (p = .12). The 5-year OS for patients without surgically intervened CHD was 63.6% compared to 70.5% for those with surgically repaired CHD (p = .88). Pre-treatment extent of tumor IV was present more often in patients with HB and CHD who passed away (6/9, 66.7%) compared to those who survived (3/16,18.8%, p = .01).

CONCLUSIONS: Patients with HB and CHD have similar survival compared to those without CHD. Our data support that patients with HB and CHD should be treated with curative intent including cardiac surgical intervention, medical oncology therapy, and oncological surgery for their HB.

PMID:39118259 | PMC:PMC11464190 | DOI:10.1002/pbc.31214

Impact of treatment on the prognosis of childhood in hepatoblastoma: A SEER based analysis

Fetched: August 9th, 2024, 2:02am UTC by Sihan Huang

Heliyon. 2024 Jul 11;10(14):e34510. doi: 10.1016/j.heliyon.2024.e34510. eCollection 2024 Jul 30.

ABSTRACT

BACKGROUND: The prognosis of patients with hepatoblastoma has been unsatisfactory. This study analyzed the effects of different treatment methods on cancer-specific survival (CSS) in children with hepatoblastoma.

METHOD: From 2000 to 2018, patients with hepatoblastoma were included in the Surveillance, Epidemiology, and End Results (SEER) database. CSS was estimated using the Kaplan-Meier method. Cox regression analysis assessed prognostic factors. The predictive models were validated using the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve.

RESULT: Of the 785 included patients, 730 (93.0 %) underwent chemotherapy, 516 (65.7 %) underwent liver tumour resection and 129 (16.4 %) underwent liver transplantation. Both chemotherapy and surgery could significantly improve the CSS rate (all p < 0.001). However, there was no difference in CSS rate between the two surgical methods (liver tumour resection and liver transplantation) (p = 0.613). Further subgroup analysis revealed that children who underwent liver tumour resection or liver transplantation based on chemotherapy (all p > 0.05) had a similar prognosis. Multivariate analysis revealed that age (p = 0.003), race (p = 0.001), operative method (p < 0.001), chemotherapy (p < 0.001), distant metastasis (p < 0.001) and tumour size (p < 0.001) were independent factors related to CSS. The C-index of the new nomogram was 0.759, and its consistency was good. The ROC curves verified that the nomogram had a better prediction ability for 1-, 3- and 5-year CSS rates.

CONCLUSION: In children with hepatoblastoma, there was no statistically significant difference in CSS between chemotherapy combined with liver transplantation and liver tumour resection. The nomogram we constructed demonstrated satisfactory CSS prediction ability.

PMID:39113986 | PMC:PMC11305182 | DOI:10.1016/j.heliyon.2024.e34510

Glypican-3 deficiency in liver cancer upregulates MAPK/ERK pathway but decreases cell proliferation

Fetched: August 9th, 2024, 2:02am UTC by Joon-Yong Chung

Am J Cancer Res. 2024 Jul 15;14(7):3348-3371. doi: 10.62347/TTNY4279. eCollection 2024.

ABSTRACT

Glypican-3 (GPC3) is overexpressed in hepatocellular carcinomas and hepatoblastomas and represents an important therapeutic target but the biologic importance of GPC3 in liver cancer is unclear. To date, there are limited data characterizing the biological implications of GPC3 knockout (KO) in liver cancers that intrinsically express this target. Here, we report on the development and characterization of GPC3-KO liver cancer cell lines and compare to them to parental lines. GPC3-KO variants were established in HepG2 and Hep3B liver cancer cell lines using a lentivirus-mediated CRISPR/Cas9 system. We assessed the effects of GPC3 deficiency on oncogenic properties in vitro and in murine xenograft models. Downstream cellular signaling pathway changes induced by GPC3 deficiency were examined by RNAseq and western blot. To confirm the usefulness of the models for GPC3-targeted drug development, we evaluated the target engagement of a GPC3-selective antibody, GC33, conjugated to the positron-emitting zirconium-89 (⁸⁹Zr) in subcutaneous murine xenografts of wild type (WT) and KO liver cancer cell lines. Deletion of GPC3 significantly reduced liver cancer cell proliferation, migration, and invasion compared to the parental cell lines. Additionally, the tumor growth of GPC3-KO liver cancer xenografts was significantly slower compared with control xenografts. RNA sequencing analysis also showed GPC3-KO resulted in a reduction in the expression of genes associated with cell cycle regulation, invasion, and migration. Specifically, we observed the downregulation of components in the AKT/NFÎºB/WNT signaling pathways and of molecules related to cell cycle regulation with GPC3-KO. In contrast, pMAPK/ERK1/2 was upregulated, suggesting an adaptive compensatory response. KO lines demonstrated increased sensitivity to ERK (GDC09994), while AKT (MK2206) inhibition was more effective in WT lines. Using antibody-based positron emission tomography (immunoPET) imaging, we confirmed that ⁸⁹Zr-GC33 accumulated exclusively in GPC3-expression xenografts but not in GPC3-KO xenografts with high tumor uptake and tumor-to-liver signal ratio. We show that GPC3-KO liver cancer cell lines exhibit decreased tumorigenicity and altered signaling pathways, including upregulated pMAPK/ERK1/2, compared to parental lines. Furthermore, we successfully distinguished between GPC3+ and GPC3- tumors using the GPC3-targeted immunoPET imaging agent, demonstrating the potential utility of these cell lines in facilitating GPC3-selective drug development.

PMID:39113871 | PMC:PMC11301284 | DOI:10.62347/TTNY4279

Permalink for 'IMPDH2 suppression impedes cell proliferation by instigating cell cycle arrest and stimulates apoptosis in pediatric hepatoblastoma'

IMPDH2 suppression impedes cell proliferation by instigating cell cycle arrest and stimulates apoptosis in pediatric hepatoblastoma

Fetched: August 1st, 2024, 2:03am UTC by Linman Li

J Cancer Res Clin Oncol. 2024 Aug 1;150(8):377. doi: 10.1007/s00432-024-05858-4.

ABSTRACT

BACKGROUND: Hepatoblastoma (HB) is the most common pediatric liver tumor, presenting significant therapeutic challenges due to its high rates of recurrence and metastasis. While Inosine Monophosphate Dehydrogenase 2(IMPDH2) has been associated with cancer progression, its specific role and clinical implications in HB have not been fully elucidated.

METHODS: This study utilized Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Tissue Microarray (TMA) for validation. Following this, IMPDH2 was suppressed, and a series of in vitro assays were conducted. Flow cytometry was employed to assess apoptosis and cell cycle arrest. Additionally, the study explored the synergistic therapeutic effects of mycophenolate mofetil (MMF) and doxorubicin (DOX) on HB cell lines.

RESULTS: The study identified a marked overexpression of IMPDH2 in HB tissues, which was strongly correlated with reduced Overall Survival (OS) and Event-Free Survival (EFS). IMPDH2 upregulation was also found to be associated with key clinical-pathological features, including pre-chemotherapy alpha-fetoprotein (AFP) levels, presence of preoperative metastasis, and the pre-treatment extent of tumor (PRETEXT) staging system. Knockdown of IMPDH2 significantly inhibited HB cell proliferation and tumorigenicity, inducing cell cycle arrest at the G0/G1 phase. Notably, the combination of MMF, identified as a specific IMPDH2 inhibitor, with DOX, substantially enhanced the therapeutic response.

CONCLUSION: The overexpression of IMPDH2 was closely linked to adverse outcomes in HB patients and appeared to accelerate cell cycle progression. These findings suggest that IMPDH2 may serve as a valuable prognostic indicator and a potential therapeutic target for HB.

IMPACT: The present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.

PMID:39085725 | PMC:PMC11291533 | DOI:10.1007/s00432-024-05858-4

Permalink for 'Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress'

Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress

Fetched: July 31st, 2024, 2:01am UTC by ClÃ©mence Jacquemin

Cell Mol Life Sci. 2024 Jul 30;81(1):320. doi: 10.1007/s00018-024-05361-6.

ABSTRACT

The hypoxia response pathway enables adaptation to oxygen deprivation. It is mediated by hypoxia-inducible factors (HIF), which promote metabolic reprogramming, erythropoiesis, angiogenesis and tissue remodeling. This led to the successful development of HIF-inducing drugs for treating anemia and some of these molecules are now in clinic. However, elevated levels of HIFs are frequently associated with tumor growth, poor prognosis, and drug resistance in various cancers, including hepatocellular carcinoma (HCC). Consequently, there are concerns regarding the recommendation of HIF-inducing drugs in certain clinical situations. Here, we analyzed the effects of two HIF-inducing drugs, Molidustat and Roxadustat, in the well-characterized HCC cell line Huh7. These drugs increased HIF-1Î± and HIF-2Î± protein levels which both participate in inducing hypoxia response genes such as BNIP3, SERPINE1, LDHA or EPO. Combined transcriptomics, proteomics and metabolomics showed that Molidustat increased the expression of glycolytic enzymes, while the mitochondrial network was fragmented and cellular respiration decreased. This metabolic remodeling was associated with a reduced proliferation and a lower demand for pyrimidine supply, but an increased ability of cells to convert pyruvate to lactate. This was accompanied by a higher resistance to the inhibition of mitochondrial respiration by antimycin A, a phenotype confirmed in Roxadustat-treated Huh7 cells and Molidustat-treated hepatoblastoma cells (Huh6 and HepG2). Overall, this study shows that HIF-inducing drugs increase the metabolic resilience of liver cancer cells to metabolic stressors, arguing for careful monitoring of patients treated with HIF-inducing drugs, especially when they are at risk of liver cancer.

PMID:39078527 | PMC:PMC11335246 | DOI:10.1007/s00018-024-05361-6

Survival disparities among racial groups with hepatic malignant tumors

Fetched: July 30th, 2024, 2:02am UTC by Deng Han

World J Gastrointest Oncol. 2024 Jul 15;16(7):2999-3010. doi: 10.4251/wjgo.v16.i7.2999.

ABSTRACT

BACKGROUND: Investigating the impact of race on the clinicopathologic characteristics and prognosis of hepatic malignant tumors represents a complex and significant area of research. Notably, distinct differences exist among various racial groups in terms of the clinical manifestations, pathologic features, and prognosis of hepatic malignant tumors.

AIM: To explore the effect of race on clinicopathologic features and prognosis of hepatic malignancies.

METHODS: Data from patients with hepatic malignancies diagnosed between 2000 and 2019 were collected from the Surveillance, Epidemiology, and End Results database and statistically analyzed.

RESULTS: This study included 123558 patients with hepatic malignant tumors, among whom 21078 (17.06%) were Asian, 14810 (11.99%) were Black, and 87670 (70.95%) were white. The median survival times for patients with hepatic malignant tumors of different races were 12.56, 7.70, and 9.35 months for Asian patients, Black patients, and white patients, respectively. The 3-year survival rates for Asian, Black, and white patients were 29%, 19%, and 21%, respectively, and the 5-year survival rates were 22%, 13%, and 15%, respectively. The Kruskal-Wallis test indicated a significant difference in the survival time of patients with hepatic malignant tumors between different races (P < 0.001). Univariate analysis revealed gender disparities in the prognosis among different ethnic groups (Asian: P > 0.05; Black: P < 0.001; White: P < 0.05). Among Black patients, the prognosis was less affected by the degree of hepatic fibrosis than among Asian patients and white patients (Black patients: P < 0.05; Asian patients: P < 0.001; White patients: P < 0.001). Significant differences were observed in the median survival time among patients with hepatic neuroendocrine tumors and hepatoblastomas during pathologic staging between races. Tumor number was inversely related to the prognosis. Cox regression analyses revealed that T stage, M stage, surgery, chemotherapy, alpha-fetoprotein, and tumor size independently influenced prognosis. Age was a specific independent prognostic factor for white patients. Among the tumor stages, N stage is a self-reliant prognostic element specific to white patients. Conversely, radiotherapy and liver fibrosis were not self-reliant prognostic factors for Black patients. Income alone did not independently influence the prognosis of Asian patients.

CONCLUSION: The prognosis of hepatic malignant tumors is better among Asian patients than among Black patients. The prognosis of hepatic malignant tumors among white patients is affected by multiple factors, including age and N stage.

PMID:39072178 | PMC:PMC11271794 | DOI:10.4251/wjgo.v16.i7.2999

Liver transplantation for primary liver tumors in pediatrics. A case series

Fetched: July 27th, 2024, 2:02am UTC by Erika M Selzer Soria

Arch Argent Pediatr. 2024 Aug 1:e202310222. doi: 10.5546/aap.2023-10222.eng. Online ahead of print.

ABSTRACT

Primary liver tumors are an increasing indication for pediatric liver transplantation. Here we report the cases of 10 patients who underwent liver transplantation for primary liver tumors in our hospital, from 2001 to date. Up to 2011, 1 transplant due to hepatoblastoma was done out of 117 liver transplants (0.8%). Since 2012, there were 9 patients out of 141 (6.4%) (5 due to hepatoblastoma, 2 due to hepatocellular carcinoma, 1 due to hepatic epithelioid hemangioendothelioma, and 1 due to hepatic mesenchymal hamartoma). Follow-up: 13.2 months (median); age at transplantation: living 4.7 years (median); weight: 17.6 kg (median). Eighty percent of patients received grafts from living donors. No tumor recurrence was observed. Survival was 100% in the follow-up period. In our series, patients with primary liver tumors requiring transplantation showed an adequate course, even in the case of hepatocellular carcinoma, Related living donors liver transplantation shortened the time between the indication and the surgery.

PMID:39058378 | DOI:10.5546/aap.2023-10222.eng

Mechanistic Association of Hepatoblastoma with Cerebral Palsy: A Narrative Review

Fetched: July 27th, 2024, 2:02am UTC by Noor Saeed Hasan

Saudi J Med Med Sci. 2024 Jul-Sep;12(3):203-209. doi: 10.4103/sjmms.sjmms_519_23. Epub 2024 Jun 20.

ABSTRACT

Hepatoblastoma is a rare liver cancer that occurs most often in children who present with lower birth weight. Cerebral palsy (CP) is a neurodevelopmental disorder distinguished by irregularities in muscle tone, movement, and motor skills. CP is caused by damage to the developing brain and is often associated with secondary complications such as severe constipation. Clinicians must be aware of sudden worsening constipation occurring in CP children because it can also be a sign of hepatoblastoma. The aim of this review is to summarize the current understanding of the risks for hepatoblastoma development in children with CP. Cancer risks likely include dysfunction of the immune system surveillance in CP children. Elevated C-reactive protein and tumor necrosis factor-alpha levels may be higher in children with CP, which weakens their innate immune system. Metabolic disruption increases the risk of some cancers, and poor nutrition and reduced growth that occur in CP patients may have an impact on cancer development through a loss in immune function. Increased mobility and physical activity can increase the T-cell, natural killer cell, and neutrophil population. Children with CP tend to engage poorly in physical activity, and consequently, their immune system is affected. There are multiple factors associated with CP that increase the risk of childhood cancers such as hepatoblastoma.

PMID:39055079 | PMC:PMC11268547 | DOI:10.4103/sjmms.sjmms_519_23

Permalink for 'Inhibition of Histone Deacetylase Activity Increases Cisplatin Efficacy to Eliminate Metastatic Cells in Pediatric Liver Cancers'

Inhibition of Histone Deacetylase Activity Increases Cisplatin Efficacy to Eliminate Metastatic Cells in Pediatric Liver Cancers

Fetched: July 14th, 2024, 2:02am UTC by Ruhi Gulati

Cancers (Basel). 2024 Jun 22;16(13):2300. doi: 10.3390/cancers16132300.

ABSTRACT

The pediatric liver cancers, hepatoblastoma and hepatocellular carcinoma, are dangerous cancers which often spread to the lungs. Although treatments with cisplatin significantly improve outcomes, cisplatin may not eliminate metastasis-initiating cells. Our group has recently shown that the metastatic microenvironments of hepatoblastoma contain Cancer Associated Fibroblasts (CAFs) and neuron-like cells, which initiate cancer spread from liver to lungs. In this study, we found that these cells express high levels of HDAC1; therefore, we examined if histone deacetylase inhibition improves cisplatin anti-proliferative effects and reduces the formation of tumor clusters in pediatric liver cancer metastatic microenvironments.

METHODS: New cell lines were generated from primary hepatoblastoma liver tumors (hbl) and lung metastases (LM) of HBL patients. In addition, cell lines were generated from hepatocellular neoplasm, not otherwise specified (HCN-NOS) tumor samples, and hcc cell lines. Hbl, LM and hcc cells were treated with cisplatin, SAHA or in combination. The effect of these drugs on the number of cells, formation of tumor clusters and HDAC1-Sp5-p21 axis were examined.

RESULTS: Both HBL and HCC tissue specimens have increased HDAC1-Sp5 pathway activation, recapitulated in cell lines generated from the tumors. HDAC inhibition with vorinostat (SAHA) increases cisplatin efficacy to eliminate CAFs in hbl and in hcc cell lines. Although the neuron-like cells survive the combined treatments, proliferation was inhibited. Notably, combining SAHA with cisplatin overcame cisplatin resistance in an LM cell line from an aggressive case with multiple metastases. Underlying mechanisms of this enhanced inhibition include suppression of the HDAC1-Sp5 pathway and elevation of an inhibitor of proliferation p21. Similar findings were found with gemcitabine treatments suggesting that elimination of proliferative CAFs cells is a key event in the inhibition of mitotic microenvironment.

CONCLUSIONS: Our studies demonstrate the synergistic benefits of HDAC inhibition and cisplatin to eliminate metastasis-initiating cells in pediatric liver cancers.

PMID:39001363 | PMC:PMC11240720 | DOI:10.3390/cancers16132300

A case of Abernethy malformation type I combined with hepatoblastoma

Fetched: July 12th, 2024, 2:02am UTC by Xuyan Liu

Rev Esp Enferm Dig. 2024 Jul 11. doi: 10.17235/reed.2024.10605/2024. Online ahead of print.

ABSTRACT

This article encountered an extremely rare case of a 2-year-old male with Abernethy malformation Type I combined with hepatoblastoma. Furthermore, the medical history was characterized by several other abnormalities: gross facial asymmetry and cardiac defectsï¼Œthus, diagnosis of Goldenhar syndrome in the setting of Abernethy type I was made. In this article, we exhibit the typical clinical presentation and Pathology imaging features of this disease.

PMID:38989888 | DOI:10.17235/reed.2024.10605/2024

Permalink for 'Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study'

Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study

Fetched: July 12th, 2024, 2:02am UTC by Huimin Yin

Chin J Cancer Res. 2024 Jun 30;36(3):298-305. doi: 10.21147/j.issn.1000-9604.2024.03.06.

ABSTRACT

OBJECTIVE: Nucleotide excision repair (NER) plays a vital role in maintaining genome stability, and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation. This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.

METHODS: In this five-center case-control study, we enrolled 966 subjects from East China (193 hepatoblastoma patients and 773 healthy controls). The TaqMan method was used to genotype 19 single nucleotide polymorphisms (SNPs) in NER pathway genes, including ERCC1, XPA, XPC, XPD, XPF, and XPG. Then, multivariate logistic regression analysis was performed, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to assess the strength of associations.

RESULTS: Three SNPs were related to hepatoblastoma risk. XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model (adjusted OR=1.49, 95% CI=1.07-2.08, P=0.019; adjusted OR=1.66, 95% CI=1.12-2.45, P=0.012, respectively). However, XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model (adjusted OR=0.68, 95% CI=0.49-0.95; P=0.024). Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups. Moreover, there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) analysis.

CONCLUSIONS: In summary, NER pathway gene polymorphisms (XPC rs2229090, XPD rs3810366, and XPD rs238406) are significantly associated with hepatoblastoma risk, and further research is required to verify these findings.

PMID:38988482 | PMC:PMC11230887 | DOI:10.21147/j.issn.1000-9604.2024.03.06

The effects of simvastatin-loaded nanoliposomes on human multilineage liver fibrosis microtissue

Fetched: July 11th, 2024, 2:02am UTC by Shima Parsa

J Cell Mol Med. 2024 Jul;28(13):e18529. doi: 10.1111/jcmm.18529.

ABSTRACT

In this in vitro study, for the first time, we evaluate the effects of simvastatin-loaded liposome nanoparticles (SIM-LipoNPs) treatment on fibrosis-induced liver microtissues, as simvastatin (SIM) has shown potential benefits in the non-alcoholic fatty liver disease process. We developed multicellular liver microtissues composed of hepatic stellate cells, hepatoblastoma cells and human umbilical vein endothelial cells. The microtissues were supplemented with a combination of palmitic acid and oleic acid to develop fibrosis models. Subsequently, various groups of microtissues were exposed to SIM and SIM-LipoNPs at doses of 5 and 10 mg/mL. The effectiveness of the treatments was evaluated by analysing cell viability, production of reactive oxygen species (ROS) and nitric oxide (NO), the expression of Kruppel-like factor (KLF) 2, and pro-inflammatory cytokines (interleukin(IL)-1 Î±, IL-1 Î², IL-6 and tumour necrosis factor-Î±), and the expression of collagen I. Our results indicated that SIM-LipoNPs application showed promising results. SIM-LipoNPs effectively amplified the SIM-klf2-NO pathway at a lower dosage compatible with a high dosage of free SIM, which also led to reduced oxidative stress by decreasing ROS levels. SIM-LipoNPs administration also resulted in a significant reduction in pro-inflammatory cytokines and Collagen I mRNA levels, as a marker of fibrosis. In conclusion, our study highlights the considerable therapeutic potential of using SIM-LipoNPs to prevent liver fibrosis progress, underscoring the remarkable properties of SIM-LipoNPs in activating the KLF2-NO pathway and anti-oxidative and anti-inflammatory response.

PMID:38984945 | PMC:PMC11234647 | DOI:10.1111/jcmm.18529

The Pattern of Anemia in Pediatric Solid Tumors Prior to and after Chemotherapy- A Retrospective Cohort Study

Fetched: July 11th, 2024, 2:02am UTC by Tomal Barman Aron

Curr Cancer Drug Targets. 2024 Jul 5. doi: 10.2174/0115680096292639240611050654. Online ahead of print.

ABSTRACT

BACKGROUND: Solid pediatric tumors refer to cancers that affect children and adoles-cents, and they present unique challenges due to their distinct biological characteristics and their vulnerability to young patients. This study aims to shed light on addressing anemia and the causes of anemia in patients with solid pediatric tumors.

MATERIALS AND METHODS: This retrospective cohort comprised 200 healthy children as controls and 235 patients with solid tumors. The study was conducted at first Affiliated Hospital of Zhengzhou University between January 2020 and June 2023. We evaluated different parameters of blood components in controls and patients with solid tumors such as medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and patients with only these tumors 3 weeks after the first cycle of chemotherapy. Further, we evaluated the relationship between serum ferritin and the weight of patients and assessed the relationship be-tween anemia and metastasis to the bone marrow in patients with neuroblastoma and hepatoblas-toma.

RESULTS: We observed various combinations of derangements in blood parameters such as hemo-globin, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscu-lar hemoglobin concentration, hematocrit, red cell distribution width, white blood cells, and plate-let in medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and 3 weeks after first cycle of chemotherapy. We found a significant correlation between serum ferritin levels and weight in neuroblastoma patients who are â‰¤ 2 years (p = 0.022). Involvement of tumor cells in bone marrow correlates with decreased Hb levels in both neuroblastoma (CI = 93.21-106.68, p = 0.001) and hepatoblastoma (CI = 113.36-121.00, p = 0.001).

CONCLUSION: Anemia may manifest as an early symptom in neuroblastoma, hepatoblastoma, and nephroblastoma. Also, anemia may be worse in patients with neuroblastoma and hepatoblastoma after chemotherapy and might warrant anemia therapy.

PMID:38982695 | DOI:10.2174/0115680096292639240611050654

Racial Disparities in Treatment and Outcomes of Pediatric Hepatoblastoma

Fetched: July 10th, 2024, 2:02am UTC by Taylor Billion

J Pediatr Hematol Oncol. 2024 Aug 1;46(6):e381-e386. doi: 10.1097/MPH.0000000000002918. Epub 2024 Jul 5.

ABSTRACT

Pediatric Hepatoblastoma is a rare malignancy of the liver. This study used the National Cancer Database (NCDB) to identify 1068 patients diagnosed with hepatoblastoma from 2004 to 2020. Ï‡ 2 and Analysis of Variance testing, as well as Kaplan-Meier, Cox Regression, and multinomial logistic regression models were used. Data was analyzed using SPSS version 27, and statistical significance was set at Î±=0.05. Our results found Black patients experienced a significantly lower median survival rate compared with White patients, a difference which persisted after controlling for covariates. Black patients were also less likely to receive surgery and chemotherapy and more likely to be from low-income households than White patients. White patients had a significantly shorter inpatient hospital stay compared to Black patients and were more likely to receive treatment at more than 1 CoC accredited facility. There was no significant difference in grade, size of tumor, metastasis, or time of diagnosis to surgery. This study showed Black patients experienced inferior overall survival when diagnosed and treated for hepatoblastoma compared to White patients.

PMID:38980918 | DOI:10.1097/MPH.0000000000002918

Cancer in 22q11.2 deletion syndrome: a case report and literature review

Fetched: July 7th, 2024, 2:02am UTC by Bingju Liu

Eur J Med Genet. 2024 Aug;70:104959. doi: 10.1016/j.ejmg.2024.104959. Epub 2024 Jul 3.

ABSTRACT

Clinically, the 22q11.2 deletion syndrome (22q11.2DS) is considered the most commonly detected microdeletion syndrome. Hepatoblastoma is the most prevalent malignant liver cancer in childhood. However, cases of hepatoblastoma in children with 22q11.2DS have only been reported in four patients. In this report, we present a-13-year-old male treated at our center due to growth retardation, and later diagnosed with hepatoblastoma. Whole genome sequencing (WGS) identified 22q11.2DS. Chromosomal microarray analysis (CMA) of peripheral blood sample showed a 2.9 Mb deletion of chromosome 22q11.2. While underlying mechanisms remain unclear, our literature review suggests that patients with 22q11.2DS may show an elevated risk of malignancy. After reviewing 21 previously reported cases, we identified 33 individuals with both cancer and 22q11.2 DS or DiGeorge syndrome. Of these cases, 7 out of 33 (21%) were hematologic tumors, while 26 out of 33 (78%) were solid tumors.

PMID:38969060 | DOI:10.1016/j.ejmg.2024.104959

Recurrent rejections after liver transplantation for hepatocellular carcinoma with stem cell features in an adult patient

Fetched: July 6th, 2024, 2:02am UTC by S Meganck

Acta Clin Belg. 2024 Jun;79(3):234-241. doi: 10.1080/17843286.2024.2376304. Epub 2024 Jul 3.

ABSTRACT

Patients with hepatoblastoma featuring carcinoma characteristics have better outcomes after liver transplantation, than after chemotherapy and resection. Possibly this should be extrapolated to aggressive subtypes of hepatocellular carcinomas in non-cirrhotic livers, where early liver transplantation might also be indicated. However, the risks associated with liver transplantation and immunosuppressive treatment after liver transplantation are once again demonstrated by this case of a 32-year-old women with a negative personal and familial history of liver diseases. She underwent transplantation (DBD) for a hepatocellular carcinoma with stem cell features (HCC-HS; an aggressive 'hepatoblast subtype' of hepatocellular carcinoma) after chemotherapeutical downstaging techniques failed to sufficiently downstage the tumor. Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels. Together, these episodes stress the importance of therapeutic drug monitoring of tacrolimus. Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.

PMID:38961614 | DOI:10.1080/17843286.2024.2376304

Management and Outcomes of Hepatoblastoma in Patients With Trisomy 18: A Systematic Review and Pooled Analysis of 70 Patients

Fetched: July 3rd, 2024, 2:01am UTC by Ioannis A Ziogas

J Pediatr Surg. 2024 Jun 11:S0022-3468(24)00363-4. doi: 10.1016/j.jpedsurg.2024.06.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Predicted 1-year survival of children with trisomy 18 (T18) has increased to 59.3%. We aimed to systematically review the characteristics, management, and outcomes of children with T18 and hepatoblastoma.

METHODS: A systematic literature review of the PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases was performed according to the PRISMA 2020 statement (end-of-search date: 03/03/2024).

RESULTS: Fifty studies reporting on 70 patients were included. The median age at diagnosis was 11.5 months, 85.9% were female (n = 55/64), and 15.0% had mosaic T18 (n = 6/40). Diagnosis was made during symptom evaluation (most commonly hepatomegaly or abdominal mass) in 45.5% (n = 15/33), incidentally in 24.2% (n = 8/33), during surveillance with abdominal ultrasound in 18.2% (n = 6/33), and at autopsy in 12.1% (n = 4/33). The median tumor size was 6.4 cm, 33.3% had multiple tumors (n = 14/42), and metastasis was present in one patient (3.8%; n = 1/26). Neoadjuvant chemotherapy was administered in 42.6% (n = 26/61) and adjuvant chemotherapy in 31.6% (n = 18/57). Surgical treatment was performed in 64.2% (n = 43/67). Of the patients not diagnosed on autopsy, overall mortality was 35.5% (n = 22/62) over a median follow-up of 11.0 months. Among the 26 deceased patients (including those diagnosed on autopsy), the most common causes of death were cardiopulmonary disease (38.5%, n = 10/26) and tumor progression (30.8%, n = 8/26).

CONCLUSIONS: T18 does not preclude resection with curative intent for hepatoblastoma. Combination of surgery and chemotherapy should be considered in children on an individualized basis depending on tumor characteristics and underlying cardiopulmonary comorbidities. Locoregional modalities may have a role in the setting of severe comorbidities.

LEVEL OF EVIDENCE: Level IV evidence.

PMID:38955626 | DOI:10.1016/j.jpedsurg.2024.06.005

Surgical management of liver tumors

Fetched: July 3rd, 2024, 2:01am UTC by Kimberly J Riehle

Pediatr Blood Cancer. 2024 Jul 2:e31155. doi: 10.1002/pbc.31155. Online ahead of print.

ABSTRACT

Two percent of pediatric malignancies arise primarily in the liver; roughly 60% of these cancers are hepatoblastoma (HB). Despite the rarity of these cases, international collaborative efforts have led to the consistent histological classification and staging systems, which facilitate ongoing clinical trials. Other primary liver malignancies seen in children include hepatocellular carcinoma (HCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), undifferentiated embryonal sarcoma of the liver (UESL), and hepatocellular neoplasm not otherwise specified (HCN-NOS). This review describes principles of surgical management of malignant pediatric primary liver tumors, within the context of comprehensive multidisciplinary care.

PMID:38953150 | DOI:10.1002/pbc.31155

When the Belly Looks Okay but Is Actually Not: A Case of Hepatoblastoma in a Well-Appearing Child

Fetched: July 3rd, 2024, 2:01am UTC by Margaret A Uchefuna

Cureus. 2024 Jun 1;16(6):e61480. doi: 10.7759/cureus.61480. eCollection 2024 Jun.

ABSTRACT

Hepatoblastoma is one of the pediatric tumors with genetic and intrauterine risk factors. It is typically asymptomatic at diagnosis, at which time most patients have metastasis to the lungs and are in an advanced stage of liver disease. We report an interesting case of a 13-month-old child who presented with a one-month history of abdominal distention. A review of the systems was unremarkable but a physical examination revealed a well-appearing child with abdominal distention, normal vital signs, and an abdominal mass. Abdominal imaging revealed a well-defined heterogeneously-enhancing mass arising from the right hepatic lobe and laboratory results were consistent with a diagnosis of hepatoblastoma. The mass was resected and the patient underwent chemotherapy with continued follow-up management. We shed light on pediatric hepatoblastoma and its clinical presentation, pathology, and laboratory and imaging findings, to aid clinicians in diagnosing the condition correctly.

PMID:38952613 | PMC:PMC11215703 | DOI:10.7759/cureus.61480

Congenital hepatoblastoma: Expanding knowledge, improving outcomes

Fetched: July 3rd, 2024, 2:01am UTC by Francesca Gigola

Pediatr Blood Cancer. 2024 Sep;71(9):e31132. doi: 10.1002/pbc.31132. Epub 2024 Jul 2.

ABSTRACT

Hepatoblastoma (HB) is a rare liver tumour, and its congenital counterpart (CHB) is even less frequent. CHB has a clinically challenging management and a generally perceived worse outcome. This study aims to review the literature on CHB to better define presentation, diagnosis, available treatments and management options. The analysis of outcomes suggests that a significant portion of mortality is unrelated to the malignant nature of the tumour. Key factors influencing overall outcomes were identified: mortality linked to the 'mass effect' during both the prenatal (22%) and perinatal (32%) stages, as well as 'oncological' mortality encompassing tumour and/or treatment-related factors (46%). Overall, after birth, CHB does not seem to confer a worse oncological prognosis per se, and should be managed similarly to older children, if patients are stable enough to undergo proper staging and treatment. A deeper knowledge and better outcomes would come from a large, homogeneous, collection of data possibly allowing a global protocol, focusing on a comprehensive management of CHB.

PMID:38952263 | DOI:10.1002/pbc.31132

Focal adhesion kinase and its epigenetic interactors as diagnostic and therapeutic hints for pediatric hepatoblastoma

Fetched: July 2nd, 2024, 2:01am UTC by Maria Rita Braghini

Front Oncol. 2024 Jun 14;14:1397647. doi: 10.3389/fonc.2024.1397647. eCollection 2024.

ABSTRACT

BACKGROUND: Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite the progress in HB treatment, investigating HB pathomechanisms to optimize stratification and therapies remains a focal point to improve the outcome for high-risk patients.

METHODS: Here, we pointed to explore the impact of these mechanisms in HB. An observational study was performed on liver samples from a cohort of 17 patients with a diagnosis of HB and two normal liver samples. The in vitro experiments were executed on the Huh6 human HB cell line treated with the FAK inhibitor TAE226.

RESULTS: Our results highlight a significant up-regulation of mRNA and protein expression of FAK in livers from HB with respect to normal livers. The increased protein expression of total and Tyr397 phosphorylated FAK (pTyr397FAK) was significantly correlated with the expression of some epigenetic regulators of histone H3 methylation and acetylation. Of note, the expression of pTyr397FAK, N-methyltransferase enzyme (EZH2) and tri-methylation of the H3K27 residue correlated with tumor size and alpha-fetoprotein (AFP) levels. Finally, TAE226 caused a significant reduction of pTyr397FAK, epigenetic regulators, AFP, EPCAM, OCT4, and SOX2, in association with anti-proliferative and pro-apoptotic effects on HB cells.

CONCLUSION: Our results suggest a role of FAK in HB that requires further investigations mainly focused on the exploration of its effective diagnostic and therapeutic translatability.

PMID:38947885 | PMC:PMC11211568 | DOI:10.3389/fonc.2024.1397647

Tumor-associated macrophages: The key player in hepatoblastoma microenvironment and the promising therapeutic target

Fetched: June 27th, 2024, 2:02am UTC by Ahmad Adawy

Microbiol Immunol. 2024 Aug;68(8):249-253. doi: 10.1111/1348-0421.13162. Epub 2024 Jun 25.

ABSTRACT

The tumor microenvironment of hepatoblastoma (HB), the most common pediatric liver tumor, predominantly exhibits a myeloid immune landscape. in which tumor-associated macrophages (TAMs) are considered the core component. The crosstalk between TAMs and HB cells markedly influences tumor behavior. TAM-derived factors are involved in tumor proliferation and vascular invasion. On the other hand, HB cell secretome attracts, stimulates, and reprograms TAMs to be immunosuppressive in favor of tumor invasion, rather than their innate role in combating tumor growth, such crosstalk sometimes forms bidirectional feedback loops, making the tumor more virulent and resistant to routine therapeutics. Consequently, TAMs are the common denominator of most suggested HB immunotherapeutic strategies. Macrophage immune checkpoint inhibitors, macrophage-mediated antibody-dependent cellular phagocytosis, and the novel chimeric antigen receptor macrophage therapy (CAR MÏ†) are currently under trial. In this review, we will summarize the significance of TAMs and their potential role as a therapeutic target in HB.

PMID:38923004 | DOI:10.1111/1348-0421.13162

Residential proximity to oil and gas developments and childhood cancer survival

Fetched: June 27th, 2024, 2:02am UTC by Thanh T Hoang

Cancer. 2024 Jun 25. doi: 10.1002/cncr.35449. Online ahead of print.

ABSTRACT

BACKGROUND: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers.

METHODS: The Texas Cancer Registry had 29,730 children (â‰¤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or gas development. Survival analyses were conducted using Cox regression, adjusting for potential confounders.

RESULTS: A total of 14.2% of cases lived within 1000 m of an oil or gas well or horizontal well. Living within 1000 m of an oil or gas well was associated with risk of mortality in cases with acute myeloid leukemia (AML) (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.01-1.84) and hepatoblastoma (aHR, 2.13; 95% CI, 1.03-4.39). An inverse association was observed with Ewing sarcoma (aHR, 0.35; 95% CI, 0.13-0.95). No associations were observed with horizontal well. There was evidence of a dose-response effect in children with AML or hepatoblastoma and residential proximity to oil or gas wells. In general, the magnitude of association increased with decreasing distance and with higher number of wells across the three distances.

CONCLUSIONS: Residential proximity to oil or gas wells at diagnosis is associated with the risk of mortality in children with AML or hepatoblastoma.

PMID:38922855 | DOI:10.1002/cncr.35449

Unusual Presentation of Beckwith-Wiedemann Syndrome in an Extremely Low Birth Weight Infant

Fetched: June 27th, 2024, 2:02am UTC by Abdulla A Alhamdan

Cureus. 2024 Jun 25;16(6):e63099. doi: 10.7759/cureus.63099. eCollection 2024 Jun.

ABSTRACT

Beckwith-Wiedemann syndrome (BWS) is a genetic disorder that affects fetal growth in which those afflicted present with features pertaining to that, such as macrosomia, macroglossia, hemihypertrophy, and abdominal wall defects. This case reports the presentation of an infant diagnosed with BWS who was born with an extremely low birth weight of 980 grams, in contrast to the typical presentation of overgrowth and macrosomia. As a result, reaching a diagnosis of BWS was delayed until the patient reached eight months of age, when other clinical features of BWS, such as hemihypertrophy, became apparent on follow-up visits. Although genetic testing can be used to diagnose this condition, a clinical scoring system consisting of a patient's clinical features is sufficient, allowing for a timely and precise diagnosis, which is of great significance to allow for early screening and detection of the associated embryonal tumors with such a syndrome.

PMID:38919860 | PMC:PMC11197392 | DOI:10.7759/cureus.63099

Transplanting Livers in Young Children - Looking Back at 100 Cases

Fetched: June 26th, 2024, 2:02am UTC by Reya Rachel Abraham

J Indian Assoc Pediatr Surg. 2024 May-Jun;29(3):192-198. doi: 10.4103/jiaps.jiaps_229_23. Epub 2024 May 8.

ABSTRACT

INTRODUCTION: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease (ESLD). However, its acceptance in India has been discouraging more due to financial and logistic reasons than the availability of expertise. This report outlines our journey and highlights issues pertinent to circumstances in an emerging economy like India.

AIM: The aim is to review a single center's 100 case experience with liver transplantation (LT).

MATERIALS AND METHODS: A prospective analysis of all children who underwent LT since 2005 at our institute was done. The data were collated from a maintained structured database.

RESULTS: Hundred children underwent LT. Sixty-four were boys. Age ranged from 5 to 144 months, with a median of 17 months. The mean weight of the cohort was 7.5 kg (ranging from 3.7 to 31.5 kg), with 60% of our children weighing between 5 and 10 kg. Biliary atresia is the most common indication (57%); others include metabolic disorders, progressive familial intrahepatic cholestasis, and hepatoblastoma. Two patients were for acute liver failure. Ninety-one children underwent live donor LT (mothers being the majority of the donors). None of the donors had any major postoperative complications. Major intraoperative complications include sepsis (39%), vascular complications (17%), biliary leak (11%), and intestinal complications (11%). Early postoperative deaths occurred in 18% of patients with sepsis being most common cause. The mean follow-up was 8.5 years and the overall survival is 70%. The mean survival is time (months) = 176.1. All surviving patients were followed up and had achieved good catch up growth by 3rd and 5th years posttransplant. The long-term sequalae include recurrent intercurrent infections, graft rejection (9%), posttransplant lymphoproliferative disease (5%), and portal vein stenosis (5%).

CONCLUSION: Our experience demonstrates the feasibility of LT in children with ESLD in India. With longer-living grafts, patients often struggle with other issues such as compliance with follow-up, financial issues, recurrent infections, and neurological problems. Close monitoring with regular follow-up of patients helps in early recognition and treatment of late-onset complications, thus helping the overall long-term outcomes.

PMID:38912017 | PMC:PMC11192256 | DOI:10.4103/jiaps.jiaps_229_23

From diagnosis to therapy: The critical role of lncRNAs in hepatoblastoma

Fetched: June 20th, 2024, 2:02am UTC by A Khuzaim Alzahrani

Pathol Res Pract. 2024 Aug;260:155412. doi: 10.1016/j.prp.2024.155412. Epub 2024 Jun 14.

ABSTRACT

According to findings, long non-coding RNAs (lncRNAs) serves an integral part in growth and development of a variety of human malignancies, including Hepatoblastoma (HB). HB is a rare kind of carcinoma of the liver that mostly affects kids and babies under the age of three. Its manifestations include digestive swelling, abdominal discomfort, and losing weight. This thorough investigation digs into the many roles that lncRNAs serve in HB, giving views into their varied activities as well as possible therapeutic consequences. The function of lncRNAs in HB cell proliferation, apoptosis, migratory and penetrating capacities, epithelial-mesenchymal transition, and therapy tolerance is discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell processes such as angiogenesis, apoptosis, immunity, and growth. Circulating lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. In addition to their diagnostic utility, lncRNAs provide curative opportunities as locations and actors, contributing to the expanding landscape of cancer research. Several HB-linked lncRNAs have been demonstrated to exhibit abnormal expression and are involved in tumor-like characteristics via DNA, RNA, or protein binding or encoding short peptides. As a result, a better knowledge of lncRNA instability might bring fresh perspectives into HB etiology as well as innovative strategies for HB early diagnosis and therapy. We describe the abnormalities of lncRNA expression in HB and their tumor-suppressive or carcinogenic activities during HB carcinogenesis in this study. Furthermore, we explore lncRNAs' diagnostic and therapeutic possibilities in HB.

PMID:38889493 | DOI:10.1016/j.prp.2024.155412

MicroRNA-141-regulated KLK10 and TNFSF-15 gene expression in hepatoblastoma cells as a novel mechanism in liver carcinogenesis

Fetched: June 13th, 2024, 2:02am UTC by Ahmed M Awad

Sci Rep. 2024 Jun 12;14(1):13492. doi: 10.1038/s41598-024-63223-4.

ABSTRACT

Liver cancer is one of the most pivotal global health problems, leading hepatocellular carcinoma (HCC) with a significant increase in cases worldwide. The role of non-coding-RNA in cancer proliferation and carcinogenesis has attracted much attention in the last decade; however, microRNAs (miRNAs), as non-coding RNA, are considered master mediators in various cancer progressions. Yet the role of miR-141 as a modulator for specific cellular processes in liver cancer cell proliferation is still unclear. This study identified the role of miR-141 and its potential functions in liver carcinogenesis. The level of miR-141 in HepG2 and HuH7 cells was assessed using quantitative real-time PCR (qRT-PCR) and compared with its expression in normal hepatocytes. A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HepG2 cells. The protein profile of the kallikrein-related peptidase 10 (KLK10) and tumor necrosis factor TNFSF-15 was investigated in HepG2 cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced inflammatory cytokines from transfected HepG2 cells. Our findings showed that the expression of miR-141 significantly increased in HepG2 and HuH7 cells compared to the normal hepatocytes. Transfection of HepG2 cells with an inhibitor, antagonist miR-141, showed a significant reduction of HepG2 cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HepG2 cells overexpressed miR-141 provided a hundred downregulated genes, including KLK10 and TNFSF-15. Furthermore, the expression profile of KLK10 and TNFSF-15 markedly depleted in HepG2 cells transfected with miR-141 overexpression accompanied by a decreasing level of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-Î±), indicating the role of miR-141 in HepG2 cell proliferation and programmed cell death. Interestingly, the experimental rats with liver cancer induced by Diethylnitrosamine injection further confirmed the upregulation of miR-141 level, IL-10, and TNF-Î± and the disturbance in KLK10 and TNFSF-15 gene expression compared with their expression in normal rats. The in-silico online tools, IntaRNA and miRWalk were used to confirm the direct interaction and potential binding sites between miR-141 and identified genes. Thus, the seeding regions of potential targeted sequences was cloned upstream of luciferase reporter gene in pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HepG2 cells pre-transfected with miR-141 overexpression vector, while increasing in cells pre-transfected with miR-141 specific inhibitor. In summary, these data suggest the crucial role of miR-141 in liver cancer development via targeting KLK10 and TNFSF-15 and provide miR-141 as an attractive candidate in liver cancer treatment and protection.

PMID:38866875 | PMC:PMC11169620 | DOI:10.1038/s41598-024-63223-4

New anti-adipogenic triterpenoid saponins from the aerial parts of Glinus oppositifolius

Fetched: June 6th, 2024, 2:02am UTC by Kim-Hoa Phi

Biomed Pharmacother. 2024 Jul;176:116851. doi: 10.1016/j.biopha.2024.116851. Epub 2024 Jun 4.

ABSTRACT

Glinus oppositifolius L., a member of the Molluginaceae family, has a long-standing history of utilization as both a vegetable and a medicinal agent across numerous countries. This plant possesses a diverse range of pharmacological activities and attracts scientific interest in studying its chemical profile. The present phytochemical investigation of the plant resulted in the isolation of eleven new triterpenoid saponins, accompanied by three known compounds. Their structures were elucidated by intensive spectroscopic analysis, DFT calculations, and comparison with previously reported data. The isolates were evaluated for their anti-adipogenic effect and cytotoxicity against human cancer cell lines, namely, colorectal carcinoma HCT116, hepatoblastoma cell HepG2, breast cancer cell MDA-MB-231, and human lung adenocarcinoma cell A549. Compounds 5, 7, and 13 exhibited a potent inhibitory effect against the differentiation of preadipocyte 3T3-L1. In addition, compound 13 displayed inhibitory effects against the growth of A549 cancer cells.

PMID:38838506 | DOI:10.1016/j.biopha.2024.116851

$Permalink for 'Successful Treatment of Refractory or Relapsed Hepatoblastoma With Autologous Hematopoietic Stem Cell Transplantation in Children'$

Successful Treatment of Refractory or Relapsed Hepatoblastoma With Autologous Hematopoietic Stem Cell Transplantation in Children

Fetched: June 4th, 2024, 2:02am UTC by Bo Kyung Kim

J Pediatr Hematol Oncol. 2024 Jul 1;46(5):e265-e271. doi: 10.1097/MPH.0000000000002888. Epub 2024 May 31.

ABSTRACT

BACKGROUND: The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate. This study aimed to demonstrate the efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) rescue in pediatric patients with R/R hepatoblastoma.

METHODS: We retrospectively analyzed 6 pediatric patients with R/R hepatoblastoma who underwent autologous HSCT. The MEC conditioning regimen was used for all patients, comprising melphalan 140 mg/m 2 /day intravenously (IV) on day 7 and 70 mg/m 2 on day 6, etoposide 200 mg/m 2 IV on days 5 to 8, and carboplatin 400 mg/m 2 IV on days 5 to 8. One patient received a TopoThioCarbo regimen, comprising topotecan 2 mg/m 2 /day IV on days 4 to 8, thiotepa 300 mg/m 2 /day IV on days 6 to 8, and carboplatin 500 mg/m 2 /day IV on days 3 to 5, as the conditioning regimen for the first transplantation. This was followed by salvage chemotherapy for relapse, and the second transplantation was performed using MEC as the conditioning regimen.

RESULTS: We report the retrospective results of 6 patients with a median age of 1.8 (range 0.4 to 10.2) years who had R/R hepatoblastoma and underwent autologous HSCT. The median follow-up period was 58 (range 28 to 113) months after diagnosis. The median stage at diagnosis was 2.0 (range 2 to 4). Two patients had lung metastases during diagnosis. The median initial alpha-fetoprotein level was 292,888 (range 28,831 to 2,406,942) ng/mL, and the median number of chemotherapy lines before autologous HSCT was 3.5 (range 2 to 7). The disease status before HSCT was complete remission (CR) for all patients. The engraftment rate was 100%. No treatment-related mortality was reported. The 3-year event-free survival and overall survival rates were 83.3% and 100%, respectively. One patient relapsed after the second HSCT and achieved CR after salvage chemotherapy.

CONCLUSION: This study suggests autologous HSCT as an effective treatment in pediatric patients with R/R hepatoblastoma. Nevertheless, future large-scale prospective studies are warranted.

PMID:38830616 | DOI:10.1097/MPH.0000000000002888

Accuracy of contrast-enhanced CT in liver neoplasms in children under 2Â years age

Fetched: June 4th, 2024, 2:02am UTC by Aishvarya Shri Rajasimman

Pediatr Radiol. 2024 Jun 3. doi: 10.1007/s00247-024-05958-w. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases.

OBJECTIVE: To evaluate the imaging features and diagnostic accuracy of computed tomography (CT) in liver tumors in children under 2 years.

METHODS: Eighty-eight children under 2 years with treatment naive liver neoplasms and baseline contrast-enhanced CT were included in this institutional review board approved retrospective study. Two blinded onco-radiologists assessed these tumors in consensus. Findings assessed included enhancement pattern, lobulated appearance, cystic change, calcifications, central scar-like appearance, and metastases. The radiologists classified the lesion as hepatoblastoma, infantile hemangioma, mesenchymal hamartoma, rhabdoid tumor, or indeterminate, first based purely on imaging and then after alpha-fetoprotein (AFP) correlation. Multivariate analysis and methods of comparing means and frequencies were used for statistical analysis wherever applicable. Diagnostic accuracy, sensitivity, and positive predictive values were analyzed.

RESULTS: The mean age of the sample was 11.4 months (95% CI, 10.9-11.8) with 50/88 (57%) boys. The study included 72 hepatoblastomas, 6 hemangiomas, 4 mesenchymal hamartomas, and 6 rhabdoid tumors. Presence of calcifications, multilobular pattern of arterial enhancement, lobulated morphology, and central scar-like appearance was significantly associated with hepatoblastomas (P-value < 0.05). Fourteen out of eighty-eight lesions were called indeterminate based on imaging alone; six lesions remained indeterminate after AFP correlation. Pure radiology-based diagnostic accuracy was 81.8% (95% CI, 72.2-89.2%), which increased to 92.1% (95% CI, 84.3-96.7%) (P-value > 0.05) after AFP correlation, with one hepatoblastoma misdiagnosed as a rhabdoid tumor. If indeterminate lesions were excluded for biopsy, the accuracy would be 98.8% (95% CI, 93.4-99.9%).

CONCLUSION: CT had high accuracy for diagnosing liver neoplasms in the under 2-year age population after AFP correlation. Certain imaging features were significantly associated with the diagnosis of hepatoblastoma. A policy of biopsying only indeterminate lesions after CT and AFP correlation would avoid sampling in the majority of patients.

PMID:38831055 | DOI:10.1007/s00247-024-05958-w

Multiple primary tumors in children: a clinicopathological analysis of four cases

Fetched: June 4th, 2024, 2:02am UTC by L X Li

Zhonghua Bing Li Xue Za Zhi. 2024 Jun 8;53(6):605-609. doi: 10.3760/cma.j.cn112151-20231024-00299.

ABSTRACT

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

PMID:38825907 | DOI:10.3760/cma.j.cn112151-20231024-00299

Permalink for 'Correction: First Transcriptome Analysis of Hepatoblastoma in Brazil: Unraveling the Pivotal Role of Noncoding RNAs and Metabolic Pathways'

Correction: First Transcriptome Analysis of Hepatoblastoma in Brazil: Unraveling the Pivotal Role of Noncoding RNAs and Metabolic Pathways

Fetched: June 2nd, 2024, 2:01am UTC by Talita Ferreira Marques Aguiar

Biochem Genet. 2024 Jun 1. doi: 10.1007/s10528-024-10848-9. Online ahead of print.

NO ABSTRACT

PMID:38822933 | DOI:10.1007/s10528-024-10848-9

Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants

Fetched: June 2nd, 2024, 2:01am UTC by Andrew M George

Am J Med Genet A. 2024 Jun 1:e63777. doi: 10.1002/ajmg.a.63777. Online ahead of print.

ABSTRACT

Beckwith-Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype. Notably, patients with CDKN1C variants appear to exhibit a different tumor risk than other BWSp molecular subtypes. We performed a comprehensive literature review using the search term "CDKN1C Beckwith" to identify 113 cases of patients with molecularly confirmed CDKN1C-BWSp. We then assessed the genotype and phenotype in a novel cohort of patients with CDKN1C-BWSp enrolled in the BWS Research Registry. Cardinal and suggestive features were evaluated for all patients reported, and tumor risk was established based on available reports. The most common phenotypes included macroglossia, omphalocele, and ear creases/pits. Tumor types reported from the literature included neuroblastoma, acute lymphocytic leukemia, superficial spreading melanoma, and intratubular germ cell neoplasia. Overall, this study identifies unique features associated with CDKN1C variants in BWSp, enabling more accurate clinical management. The absence of Wilms tumor and hepatoblastoma suggests that screening for these tumors may not be necessary, while the neuroblastoma risk warrants appropriate screening recommendations.

PMID:38822599 | DOI:10.1002/ajmg.a.63777

A rare case report: multiple intrahepatic masses in a pediatric patient with citrin deficiency

Fetched: June 1st, 2024, 2:01am UTC by Hui Lin

Discov Oncol. 2024 May 31;15(1):200. doi: 10.1007/s12672-024-01059-0.

ABSTRACT

Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions.

PMID:38819760 | PMC:PMC11143117 | DOI:10.1007/s12672-024-01059-0

Evaluation of surgical strategies and long-term outcomes in pediatric hepatocellular carcinoma

Fetched: June 1st, 2024, 2:01am UTC by Merve Karayazili

Pediatr Surg Int. 2024 May 31;40(1):144. doi: 10.1007/s00383-024-05721-0.

ABSTRACT

PURPOSE: Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors.

METHODS: A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed.

RESULTS: Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 Â± 4.1 years (0.8-16.4 years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9 ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%.

CONCLUSION: Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.

PMID:38819667 | DOI:10.1007/s00383-024-05721-0

Hepatoblastoma Presenting as Rapidly Progressive Abdominal Mass in a Toddler-A Case Report

Fetched: June 1st, 2024, 2:01am UTC by Padmapriya Balakrishnan

Indian J Surg Oncol. 2024 May;15(Suppl 2):355-358. doi: 10.1007/s13193-024-01887-0. Epub 2024 Feb 2.

ABSTRACT

Abdominal mass in a toddler is a common condition encountered in clinical practice. The nature of abdominal mass in toddlers can be a developmental cyst or benign and malignant tumours from various intraabdominal organs. Round blue cell tumours arising from the kidney, adrenals, pancreas, and liver in toddlers present as abdominal masses and are potentially fatal even with systematic treatment. Hepatoblastoma, a small round blue cell tumour of childhood, is a rare hepatic tumour. We report a case of hepatoblastoma in a toddler in view of its diagnostic challenge.

PMID:38818001 | PMC:PMC11133274 | DOI:10.1007/s13193-024-01887-0

Malignant melanoma in a 12-year-old boy 17 months after completing hepatoblastoma treatment

Fetched: May 28th, 2024, 2:01am UTC by Koji Kanezawa

Cancer Rep (Hoboken). 2024 May;7(5):e2118. doi: 10.1002/cnr2.2118.

ABSTRACT

BACKGROUND: Melanoma is rare as a secondary malignant neoplasm among childhood cancer survivors.

CASE: We report a case of a 12-year-old boy who developed malignant melanoma with systemic metastases 17 months after completing treatment for hepatoblastoma. The diagnosis was made unexpectedly based on a bone marrow examination. The patient did not respond to immune checkpoint inhibitor therapy and died 6 weeks after being diagnosed with melanoma. Whole-exome sequencing to examine 103 genes associated with cancer predisposition did not identify any germ-line variants.

CONCLUSION: This case study provides a unique example of melanoma in a childhood cancer survivor following hepatoblastoma treatment but does not identify any candidate variant to link hepatoblastoma and melanoma.

PMID:38801212 | PMC:PMC11129619 | DOI:10.1002/cnr2.2118

Permalink for 'Construction and validation of nomogram prognostic model for predicting survival in hepatoblastoma patients: a population-based study'

Construction and validation of nomogram prognostic model for predicting survival in hepatoblastoma patients: a population-based study

Fetched: May 26th, 2024, 2:02am UTC by Song Wang

Updates Surg. 2024 May 25. doi: 10.1007/s13304-024-01814-6. Online ahead of print.

ABSTRACT

For patients with hepatoblastoma (HB), current staging system is not accurate in predicting survival outcomes. The aim of this study was to develop two accurate survival prediction models to guide clinical decision making. A retrospective analysis of 424 HB patients was performed from 2004 to 2015 using the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis was used to screen for variables. The identified variables were used to build survival prediction model. The performance of the nomogram models was assessed based on the concordance index (C-index), calibration plot, and receiver operating characteristic (ROC) curve. The Cox regression analysis identified six variables affecting overall survival (OS) in HB patients, including race, tumor size, lymph node involvement, distant metastases, surgery and chemotherapy. And the Cox regression analysis identified five variables including race, lymph node involvement, distant metastases, surgery, and chemotherapy that affect cancer-specific survival (CCS) in HB patients. In the training cohort, the C-index of the nomogram in predicting the OS was 0.791 [95% confidence intervals (95% CI) 0.717-0.865], CSS was 0.805(95% CI 0.728-0.882). In the validation cohort, the C-index of the nomogram in predicting the OS was 0.712 (95% CI 0.511-0.913), the CSS was 0.751 (95% CI 0.566-0.936). In the training cohort, the area under the receiver operator characteristics curve (AUC) values of the nomogram in prediction of the 1-, 3-, and 5-year OS were 0.842 (95% CI 0.739-0.944), 0.759 (95% CI 0.670-0.849), and 0.770 (95% CI 0.686-0.852), respectively. In the validation cohort, the AUC values for prediction of the 1-, 3-, and 5-year OS were 0.920 (95% CI 0.806-1.034), 0.863 (95% CI 0.750-0.976), and 0.844 (95% CI 0.721-0.967), respectively. Two nomogram models were developed and validated in this study which provided accurate prediction of the OS and CSS in HB patients. The constructed models can be used for predicting survival outcomes and guide treatment for HB patients.

PMID:38795309 | DOI:10.1007/s13304-024-01814-6

Metastatic Hepatoblastoma in Adolescence: A Clinical Case Report and Literature Review

Fetched: May 21st, 2024, 2:02am UTC by Juan Manuel Millan-Alanis

Cureus. 2024 Apr 17;16(4):e58460. doi: 10.7759/cureus.58460. eCollection 2024 Apr.

ABSTRACT

Hepatoblastoma is the most common hepatic neoplasm in children. However, its incidence is infrequent beyond age five. We present the case of a 15-year-old female diagnosed with metastatic hepatoblastoma during hospitalization for liver function deterioration. The patient presented with abdominal distension, jaundice, and other symptoms indicative of advanced disease. Imaging and biopsy confirmed stage IV epithelial hepatoblastoma with pulmonary metastases. This case underscores the importance of considering hepatoblastoma in older pediatric patients or young adults presenting with hepatic masses despite lacking traditional risk factors for liver malignancies.

PMID:38765389 | PMC:PMC11100445 | DOI:10.7759/cureus.58460

Familial Adenomatous Polyposis

Fetched: May 20th, 2024, 2:02am UTC by Gopal Menon

2024 May 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Janâ€“.

ABSTRACT

Familial adenomatous polyposis (FAP) is an autosomal dominant polyposis syndrome characterized by varying degrees of penetrance. The primary genetic defect associated with this disorder is a germline mutation in the adenomatous polyposis coli (APC) gene. FAP presents with diverse phenotypic expressions, including Gardner and Turcot syndromes.

If left untreated, affected individuals develop hundreds to thousands of polyps throughout the colon and rectum, often manifesting in the early teenage years. This condition ultimately results in an almost 100% lifetime risk of colorectal cancer, typically occurring by age 40. Colectomy is recommended to significantly reduce the risk of developing colorectal cancer. Individuals with FAP face an elevated risk of other malignancies, such as gastric and duodenal adenocarcinoma, hepatoblastoma, and desmoid tumors. Screening for upper gastrointestinal and extraintestinal disease is crucial in managing affected individuals.

PMID:30855821 | Bookshelf:NBK538233

FOXM1 and CHD4 expression is associated with chemoresistance in hepatoblastoma

Fetched: May 19th, 2024, 2:01am UTC by Yuko Hino

Pathol Res Pract. 2024 Jun;258:155348. doi: 10.1016/j.prp.2024.155348. Epub 2024 May 13.

ABSTRACT

Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20ï¼… of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPathÂ®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p<0.0001 and p<0.0001, respectively). Regarding chemotherapy efficacy, the alpha-fetoprotein (AFP) level after chemotherapy was correlated with both the imaging shrinkage rate (R=-0.52) and histological residual rate (the percentage of the viable tumors of HB after chemotherapy)(R=0.62). High FOXM1 score was correlated with a high-postoperative AFP value (p<0.01) and a low AFP attenuation rate (p<0.05), but the FOXM1 score was not correlated with the imaging shrinkage rate (p=0.4418) or histological residual rate (p=0.4418). High CHD4 score showed a nonsignificant trend toward correlation with high postoperative AFP value (p=0.0849) and was not significantly correlated with the other parameters. Collectively, our results showed that FOXM1 expression may be useful in evaluating the response to CDDP-based chemotherapeutic regimens. Accurate measurement of FOXM1 expression by our scoring system using QuPathÂ® is important in cases with mixed HB components of various differentiation levels.

PMID:38761648 | DOI:10.1016/j.prp.2024.155348

An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer

Fetched: May 11th, 2024, 2:01am UTC by Andres F Espinoza

Hepatol Commun. 2024 May 10;8(6):e0435. doi: 10.1097/HC9.0000000000000435. eCollection 2024 Jun 1.

ABSTRACT

BACKGROUND: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

METHODS: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, and tested it with cell lines and noncancer control blood samples. We then used this panel to analyze whole-blood samples for CTC burden with a cohort of 15 patients with hepatoblastoma and HCC and correlated with patient characteristics and outcomes.

RESULTS: We showed that ICG accumulation is specific to liver cancer cells, compared to nonmalignant liver cells, non-liver solid tumor cells, and other nonmalignant cells, and can be used to identify liver tumor cells in a mixed population of cells. Experiments with the ICG/Glypican-3/DAPI panel showed that it specifically tagged malignant liver cells. Using patient samples, we found that CTC burden from sequential blood samples from the same patients mirrored the patients' responses to therapy.

CONCLUSIONS: Our novel ICG-based liquid biopsy test for CTCs can be used to specifically detect and quantify CTCs in the blood of pediatric patients with liver cancer.

PMID:38727682 | PMC:PMC11093570 | DOI:10.1097/HC9.0000000000000435

Staging and Restaging Pediatric Abdominal and Pelvic Tumors: A Practical Guide

Fetched: May 11th, 2024, 2:01am UTC by Luisa LeitÃ£o de Faria

Radiographics. 2024 Jun;44(6):e230175. doi: 10.1148/rg.230175.

ABSTRACT

The most common abdominal malignancies diagnosed in the pediatric population include neuroblastoma, Wilms tumor, hepatoblastoma, lymphoma, germ cell tumor, and rhabdomyosarcoma. There are distinctive imaging findings and patterns of spread for each of these tumors that radiologists must know for diagnosis and staging and for monitoring the patient's response to treatment. The multidisciplinary treatment group that includes oncologists, surgeons, and radiation oncologists relies heavily on imaging evaluation to identify the best treatment course and prognostication of imaging findings, such as the image-defined risk factors for neuroblastomas, the PRETreatment EXtent of Disease staging system for hepatoblastoma, and the Ann Arbor staging system for lymphomas. It is imperative for radiologists to be able to correctly indicate the best imaging methods for diagnosis, staging, and restaging of each of these most prevalent tumors to avoid inconclusive or unnecessary examinations. The authors review in a practical manner the most updated key points in diagnosing and staging disease and assessing response to treatment of the most common pediatric abdominal tumors. ^Â©RSNA, 2024 Supplemental material is available for this article.

PMID:38722785 | DOI:10.1148/rg.230175

Transcriptional repression of the oncofetal LIN28B gene by the transcription factor SOX6

Fetched: May 6th, 2024, 2:02am UTC by Valentina Pastori

Sci Rep. 2024 May 4;14(1):10287. doi: 10.1038/s41598-024-60438-3.

ABSTRACT

The identification of regulatory networks contributing to fetal/adult gene expression switches is a major challenge in developmental biology and key to understand the aberrant proliferation of cancer cells, which often reactivate fetal oncogenes. One key example is represented by the developmental gene LIN28B, whose aberrant reactivation in adult tissues promotes tumor initiation and progression. Despite the prominent role of LIN28B in development and cancer, the mechanisms of its transcriptional regulation are largely unknown. Here, by using quantitative RT-PCR and single cell RNA sequencing data, we show that in erythropoiesis the expression of the transcription factor SOX6 matched a sharp decline of LIN28B mRNA during human embryo/fetal to adult globin switching. SOX6 overexpression repressed LIN28B not only in a panel of fetal-like erythroid cells (K562, HEL and HUDEP1; â‰ˆ92% p < 0.0001, 54% p = 0.0009 and â‰ˆ60% p < 0.0001 reduction, respectively), but also in hepatoblastoma HepG2 and neuroblastoma SH-SY5H cells (â‰ˆ99% p < 0.0001 and â‰ˆ59% p < 0.0001 reduction, respectively). SOX6-mediated repression caused downregulation of the LIN28B/Let-7 targets, including MYC and IGF2BP1, and rapidly blocks cell proliferation. Mechanistically, Lin28B repression is accompanied by SOX6 physical binding within its locus, suggesting a direct mechanism of LIN28B downregulation that might contribute to the fetal/adult erythropoietic transition and restrict cancer proliferation.

PMID:38704454 | PMC:PMC11069503 | DOI:10.1038/s41598-024-60438-3

3D Bioprinting of Sugar Beet Pectin through Horseradish Peroxidase-Catalyzed Cross-Linking

Fetched: May 3rd, 2024, 2:01am UTC by Wildan Mubarok

ACS Appl Bio Mater. 2024 May 20;7(5):3506-3514. doi: 10.1021/acsabm.4c00418. Epub 2024 May 2.

ABSTRACT

Horseradish peroxidase (HRP)-mediated hydrogelation, caused by the cross-linking of phenolic groups in polymers in the presence of hydrogen peroxide (H2O2), is an effective route for bioink solidification in 3D bioprinting. Sugar beet pectin (SBP) naturally has cross-linkable phenols through the enzymatic reaction. Therefore, chemical modifications are not required, unlike the various polymers that have been used in the enzymatic cross-linking system. In this study, we report the application of SBP in extrusion-based bioprinting including HRP-mediated bioink solidification. In this system, H2O2 necessary for the solidification of inks is supplied in the gas phase. Cell-laden liver lobule-like constructs could be fabricated using bioinks consisting of 10 U/mL HRP, 4.0 and 6.0 w/v% SBP, and 6.0 Ã— 10⁶ cells/mL human hepatoblastoma (HepG2) cells exposed to air containing 16 ppm of H2O2 concurrently during printing and 10 min postprinting. The HepG2 cells enclosed in the printed constructs maintained their viability, metabolic activity, and hepatic functions from day 1 to day 7 of the culture, which indicates the cytocompatibility of this system. Taken together, this result demonstrates the potential of SBP and HRP cross-linking systems for 3D bioprinting, which can be applied in tissue engineering applications.

PMID:38696441 | DOI:10.1021/acsabm.4c00418

Permalink for 'Molecular docking, synthesis, characteristics and preliminary cytotoxic study of new coumarin-sulfonamide derivatives as histone deacetylase inhibitors'

Molecular docking, synthesis, characteristics and preliminary cytotoxic study of new coumarin-sulfonamide derivatives as histone deacetylase inhibitors

Fetched: May 2nd, 2024, 2:01am UTC by Ammar Abdul Aziz Alibeg

Wiad Lek. 2024;77(3):514-525. doi: 10.36740/WLek202403118.

ABSTRACT

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Coumarin as cap groups.

PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group and Coumarin as cap groups known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds.

RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. The synthesized compound assessed for their cytotoxic activity against hepatoblastoma HepG2 (IC50, I=0.094, II=0.040, III=0.032, IV=0.046, SAHA=0.141) and human colon adenocarcinoma MCF-7 (IC50, I=0.135, II=0.050, III= 0.065, IV=0.059, SAHA=0.107). The binding mode to the active site of [HDAC6] were determined by docking study which give results that they might be good inhibitors for [HDAC6].

CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed a comparable cytotoxic result with FDA approved drug (SAHA) toward HepG2 and MCF-7 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

PMID:38691794 | DOI:10.36740/WLek202403118

Permalink for 'Predicting response of hepatoblastoma primary lesions to neoadjuvant chemotherapy through contrast-enhanced computed tomography radiomics'

Predicting response of hepatoblastoma primary lesions to neoadjuvant chemotherapy through contrast-enhanced computed tomography radiomics

Fetched: May 2nd, 2024, 2:01am UTC by Yanlin Yang

J Cancer Res Clin Oncol. 2024 Apr 30;150(5):223. doi: 10.1007/s00432-024-05746-x.

ABSTRACT

OBJECTIVE: To investigate the clinical value of contrast-enhanced computed tomography (CECT) radiomics for predicting the response of primary lesions to neoadjuvant chemotherapy in hepatoblastoma.

METHODS: Clinical and CECT imaging data were retrospectively collected from 116 children with hepatoblastoma who received neoadjuvant chemotherapy. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, they were randomly stratified into a training cohort and a test cohort in a 7:3 ratio. The clinical model was constructed using univariate and multivariate logistic regression, while the radiomics model was developed based on selected radiomics features employing the support vector machine algorithm. The combined clinical-radiomics model incorporated both clinical and radiomics features.

RESULTS: The area under the curve (AUC) for the clinical, radiomics, and combined models was 0.704 (95% CI: 0.563-0.845), 0.830 (95% CI: 0.704-0.959), and 0.874 (95% CI: 0.768-0.981) in the training cohort, respectively. In the validation cohort, the combined model achieved the highest mean AUC of 0.830 (95% CI 0.616-0.999), with a sensitivity, specificity, accuracy, precision, and f1 score of 72.0%, 81.1%, 78.5%, 57.2%, and 63.5%, respectively.

CONCLUSION: CECT radiomics has the potential to predict primary lesion response to neoadjuvant chemotherapy in hepatoblastoma.

PMID:38691204 | PMC:PMC11063102 | DOI:10.1007/s00432-024-05746-x

Blastomas of the digestive system in adults: A review

Fetched: May 2nd, 2024, 2:01am UTC by Yu Liu

World J Gastrointest Surg. 2024 Apr 27;16(4):1030-1042. doi: 10.4240/wjgs.v16.i4.1030.

ABSTRACT

Blastomas, characterized by a mixture of mesenchymal, epithelial, and undifferentiated blastematous components, are rare malignant neoplasms originating from precursor blast cells. This review focuses on digestive system blastomas in adult patients, including gastroblastoma, hepatoblastoma, and pancreatoblastoma. Gastroblastoma is a biphasic, epitheliomesenchymal tumor, with only sixteen cases reported to date. In addition to the characteristic histology, metastasis-associated lung adenocarcinoma transcript 1 - glioma-associated oncogene homolog 1 gene fusion is typical, although recently novel ewing sarcoma breakpoint region 1 - c-terminal binding protein 1 and patched 1 - glioma-associated oncogene homolog 2 fusions have been described. Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty. Pancreatoblastoma, primarily a pediatric tumor, displays acinar differentiation and squamoid nests with other lines of differentiation also present, especially neuroendocrine. Diagnostic approaches for these blastomas include a combination of imaging modalities, histopathological examination, and molecular profiling. The treatment generally involves surgical resection, which may be supplemented by chemotherapy or radiotherapy in some cases. Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes, particularly in the setting of metastases. This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

PMID:38690053 | PMC:PMC11056657 | DOI:10.4240/wjgs.v16.i4.1030

Permalink for 'Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature'

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature

Fetched: May 2nd, 2024, 2:01am UTC by Wen-Li Xiu

World J Gastrointest Surg. 2024 Apr 27;16(4):1066-1077. doi: 10.4240/wjgs.v16.i4.1066.

ABSTRACT

BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option.

AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC.

METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC.

RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 Â± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases.

CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

PMID:38690040 | PMC:PMC11056661 | DOI:10.4240/wjgs.v16.i4.1066

IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway

Fetched: April 29th, 2024, 2:02am UTC by Li Yuan

Curr Mol Pharmacol. 2024 Feb 21. doi: 10.2174/0118761429257350231212093136. Online ahead of print.

ABSTRACT

BACKGROUND: Amplification of inosine monophosphate dehydrogenase II, EC 1,1,1,205 (IMPDH2) has been reported in various cancers, which results in transformation and tumorigenicity. In our current work, we have explored the oncogenic properties and the underlying pathophysiology of IMPDH2 in hepatoblastoma (HB).

METHODS: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB.

RESULTS: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB.

CONCLUSION: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.

PMID:38676510 | DOI:10.2174/0118761429257350231212093136

Permalink for 'l-Ornithine-l-Aspartate (LOLA) Normalizes Metabolic Parameters in Models of Steatosis, Insulin Resistance and Metabolic Syndrome'

l-Ornithine-l-Aspartate (LOLA) Normalizes Metabolic Parameters in Models of Steatosis, Insulin Resistance and Metabolic Syndrome

Fetched: April 28th, 2024, 2:01am UTC by Ali Canbay

Pharmaceutics. 2024 Apr 7;16(4):506. doi: 10.3390/pharmaceutics16040506.

ABSTRACT

l-Ornithine- l-aspartate (LOLA) reduces toxic ammonium (NH3) plasma levels in hepatic encephalopathy. NH3 detoxification/excretion is achieved by its incorporation into urea and glutamine via activation of carbamoyl phosphate synthetase 1 (CSP1) by l-ornithine and stimulation of arginase by l-aspartate. We aimed at identifying additional molecular targets of LOLA as a potential treatment option for non-alcoholic fatty liver disease (NAFLD). In primary hepatocytes from NAFLD patients, urea cycle enzymes CSP1 and ornithine transcarbamylase (OTC) increase, while the catabolism of branched-chain amino acids (BCAAs) decreases with disease severity. In contrast, LOLA increased the expression rates of the BCAA enzyme transcripts bcat2, bckdha, and bckdk. In untreated HepG2 hepatoblastoma cells and HepG2-based models of steatosis, insulin resistance, and metabolic syndrome (the latter for the first time established herein), LOLA reduced the release of NH3; beneficially modulated the expression of genes related to fatty acid import/transport (cd36, cpt1), synthesis (fasn, scd1, ACC1), and regulation (srbf1); reduced cellular ATP and acetyl-CoA; and favorably modulated the expression of master regulators/genes of energy balance/mitochondrial biogenesis (AMPK-Î±, pgc1Î±). Moreover, LOLA reconstituted the depolarized mitochondrial membrane potential, while retaining mitochondrial integrity and avoiding induction of superoxide production. Most effects were concentration-dependent at â‰¤40 mM LOLA. We demonstrate for l-ornithine-l-aspartate a broad range of reconstituting effects on metabolic carriers and targets of catabolism/energy metabolism impaired in NAFLD. These findings strongly advocate further investigations to establish LOLA as a safe, efficacious, and cost-effective basic medication for preventing and/or alleviating NAFLD.

PMID:38675168 | PMC:PMC11054838 | DOI:10.3390/pharmaceutics16040506

Therapeutic Management and Outcomes of Hepatoblastoma in a Pediatric Patient with Mosaic Edwards Syndrome

Fetched: April 28th, 2024, 2:01am UTC by Patrycja Sosnowska-Sienkiewicz

Genes (Basel). 2024 Apr 7;15(4):463. doi: 10.3390/genes15040463.

ABSTRACT

The mosaic form of Edwards syndrome affects 5% of all children with Edwards syndrome. The clinical phenotype is highly variable, ranging from the full spectrum of trisomy 18 to the normal phenotype. The purpose of this publication was to present the therapeutic process in an 18-month-old girl with the mosaic form of Edwards syndrome and hepatoblastoma, against the background of other cases of simultaneous occurrence of this syndrome and hepatoblastoma described so far. It appears that this particular group of patients with hepatoblastoma and Edwards syndrome can have good outcomes, provided they do not have life-threatening cardiac or other severe defects. Due to the prematurity of our patient and the defects associated with Edwards syndrome, the child required constant multidisciplinary care, but Edwards syndrome itself was not a reason to discontinue therapy for a malignant neoplasm of the liver. Regular abdominal ultrasound examination, along with AFP testing, may be helpful in the early detection of liver tumors in children with Edwards syndrome.

PMID:38674397 | PMC:PMC11049815 | DOI:10.3390/genes15040463

Functionalized Gelatin/Polysaccharide Hydrogels for Encapsulation of Hepatocytes

Fetched: April 27th, 2024, 2:01am UTC by Christian Willems

Gels. 2024 Mar 28;10(4):231. doi: 10.3390/gels10040231.

ABSTRACT

Liver diseases represent a considerable burden to patients and healthcare systems. Hydrogels play an important role in the engineering of soft tissues and may be useful for embedding hepatocytes for different therapeutic interventions or the development of in vitro models to study the pathogenesis of liver diseases or testing of drugs. Here, we developed two types of hydrogels by crosslinking hydrazide-functionalized gelatin with either oxidized dialdehyde hyaluronan or alginate through the formation of hydrazone bonds. Gel formulations were studied through texture analysis and rheometry, showing mechanical properties comparable to those of liver tissue while also demonstrating long-term stability. The biocompatibility of hydrogels and their ability to host hepatocytes was studied in vitro in comparison to pure gelatin hydrogels crosslinked by transglutaminase using the hepatocellular line HepG2. It was found that HepG2 cells could be successfully embedded in the hydrogels, showing no signs of gel toxicity and proliferating in a 3D environment comparable to pure transglutaminase cross-linked gelatin hydrogels used as control. Altogether, hydrazide gelatin in combination with oxidized polysaccharides makes stable in situ gelling systems for the incorporation of hepatocytes, which may pave the way for use in liver tissue engineering and drug testing.

PMID:38667650 | PMC:PMC11048940 | DOI:10.3390/gels10040231

Ameliorative effect of bofutsushosan (Fangfengtongshengsan) extract on the progression of aging-induced obesity

Fetched: April 26th, 2024, 2:01am UTC by Takafumi Saeki

J Nat Med. 2024 Jun;78(3):576-589. doi: 10.1007/s11418-024-01803-4. Epub 2024 Apr 25.

ABSTRACT

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.

PMID:38662301 | DOI:10.1007/s11418-024-01803-4

Commentary on the challenges of modeling hepatoblastoma in-vivo

Fetched: April 24th, 2024, 2:01am UTC by Edward H Hurley

Pediatr Res. 2024 Apr 22. doi: 10.1038/s41390-024-03215-2. Online ahead of print.

NO ABSTRACT

PMID:38649725 | DOI:10.1038/s41390-024-03215-2

Permalink for 'First Transcriptome Analysis of Hepatoblastoma in Brazil: Unraveling the Pivotal Role of Noncoding RNAs and Metabolic Pathways'

First Transcriptome Analysis of Hepatoblastoma in Brazil: Unraveling the Pivotal Role of Noncoding RNAs and Metabolic Pathways

Fetched: April 24th, 2024, 2:01am UTC by Talita Ferreira Marques Aguiar

Biochem Genet. 2024 Apr 22. doi: 10.1007/s10528-024-10764-y. Online ahead of print.

ABSTRACT

Hepatoblastoma stands as the most prevalent liver cancer in the pediatric population. Characterized by a low mutational burden, chromosomal and epigenetic alterations are key drivers of its tumorigenesis. Transcriptome analysis is a powerful tool for unraveling the molecular intricacies of hepatoblastoma, shedding light on the effects of genetic and epigenetic changes on gene expression. In this study conducted in Brazilian patients, an in-depth whole transcriptome analysis was performed on 14 primary hepatoblastomas, compared to control liver tissues. The analysis unveiled 1,492 differentially expressed genes (1,031 upregulated and 461 downregulated), including 920 protein-coding genes (62%). Upregulated biological processes were linked to cell differentiation, signaling, morphogenesis, and development, involving known hepatoblastoma-associated genes (DLK1, MEG3, HDAC2, TET1, HMGA2, DKK1, DKK4), alongside with novel findings (GYNG4, CDH3, and TNFRSF19). Downregulated processes predominantly centered around oxidation and metabolism, affecting amines, nicotinamides, and lipids, featuring novel discoveries like the repression of SYT7, TTC36, THRSP, CCND1, GCK and CAMK2B. Two genes, which displayed a concordant pattern of DNA methylation alteration in their promoter regions and dysregulation in the transcriptome, were further validated by RT-qPCR: the upregulated TNFRSF19, a key gene in the embryonic development, and the repressed THRSP, connected to lipid metabolism. Furthermore, based on protein-protein interaction analysis, we identified genes holding central positions in the network, such as HDAC2, CCND1, GCK, and CAMK2B, among others, that emerged as prime candidates warranting functional validation in future studies. Notably, a significant dysregulation of non-coding RNAs (ncRNAs), predominantly upregulated transcripts, was observed, with 42% of the top 50 highly expressed genes being ncRNAs. An integrative miRNA-mRNA analysis revealed crucial biological processes associated with metabolism, oxidation reactions of lipids and carbohydrates, and methylation-dependent chromatin silencing. In particular, four upregulated miRNAs (miR-186, miR-214, miR-377, and miR-494) played a pivotal role in the network, potentially targeting multiple protein-coding transcripts, including CCND1 and CAMK2B. In summary, our transcriptome analysis highlighted disrupted embryonic development as well as metabolic pathways, particularly those involving lipids, emphasizing the emerging role of ncRNAs as epigenetic regulators in hepatoblastomas. These findings provide insights into the complexity of the hepatoblastoma transcriptome and identify potential targets for future therapeutic interventions.

PMID:38649558 | DOI:10.1007/s10528-024-10764-y

Permalink for 'Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors'

Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors

Fetched: April 24th, 2024, 2:01am UTC by Ammar Abdul Aziz Alibeg

Pol Merkur Lekarski. 2024;52(2):178-188. doi: 10.36740/Merkur202402106.

ABSTRACT

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Isatin derivatives as cap group joined by mono amide linker as required to act as HDAC inhibitors.

PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group joined by N-alkylation reaction with ethyl-bromo hexanoate as linker group that joined by amide reaction with Isatin derivatives as cap groups which known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds.

RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. the compounds were synthesized and characterized by successfully by ART-FTIR, NMR and ESI- Ms. Assessed for their cytotoxic activity against human colon adenocarcinoma MCF-7 (IC50, I=105.15, II=60.00, III=54.11, IV=56.57, vorinostat=28.41) and hepatoblastoma HepG2 (IC50, I=63.91, II=135.18, III=118.85, IV=51.46, vorinostat=37.50). Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity.

CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

PMID:38642353 | DOI:10.36740/Merkur202402106

Two cases of hepatoblastoma in Bohring-Opitz syndrome: An emerging association

Fetched: April 19th, 2024, 2:02am UTC by Kritika Patel

Pediatr Blood Cancer. 2024 Jul;71(7):e31010. doi: 10.1002/pbc.31010. Epub 2024 Apr 18.

NO ABSTRACT

PMID:38637906 | DOI:10.1002/pbc.31010

Hepatoblastoma in the 21st century: An epidemiological survey and genetic mutation landscape review

Fetched: April 19th, 2024, 2:02am UTC by Yongqi Dong

Asian J Surg. 2024 Jul;47(7):3294-3296. doi: 10.1016/j.asjsur.2024.03.157. Epub 2024 Apr 17.

NO ABSTRACT

PMID:38637189 | DOI:10.1016/j.asjsur.2024.03.157

Permalink for 'PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study'

PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study

Fetched: April 17th, 2024, 2:01am UTC by Hongxiang Gao

Hepatol Int. 2024 Apr 16. doi: 10.1007/s12072-024-10668-4. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors.

METHODS: A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP.

RESULTS: The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone.

CONCLUSIONS: The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance.

TRIAL REGISTRATION: Clinical Trials, NCT03645655. Registered 20 August 2018, [https:]

CLINICALTRIALS: gov/ct2/show/NCT03645655 .

PMID:38622445 | DOI:10.1007/s12072-024-10668-4

Permalink for 'Extragonadal Germ Cell Tumor with Hepatic Infiltration in a Child: Aberrant Somatostatin Receptors and the Diagnostic Conundrum'

Extragonadal Germ Cell Tumor with Hepatic Infiltration in a Child: Aberrant Somatostatin Receptors and the Diagnostic Conundrum

Fetched: April 17th, 2024, 2:01am UTC by Nitin James Peters

J Indian Assoc Pediatr Surg. 2024 Mar-Apr;29(2):162-164. doi: 10.4103/jiaps.jiaps_167_23. Epub 2024 Mar 4.

ABSTRACT

Extragonadal germ cell tumors (GCTs) are challenging to diagnose. We present a case of suprarenal GCT, with hepatic infiltration where differential diagnosis included neuroblastoma and hepatoblastoma. The positive positron emission tomography scan further obfuscated the situation. The diagnosis was clinched by fine-needle aspiration cytology and cell block immunohistochemistry.

PMID:38616838 | PMC:PMC11014175 | DOI:10.4103/jiaps.jiaps_167_23

Permalink for 'Retraction: "H19 suppresses the growth of hepatoblastoma cells by promoting their apoptosis via the signaling pathways of miR-675/FADD and miR-138/PTK2"'

Retraction: "H19 suppresses the growth of hepatoblastoma cells by promoting their apoptosis via the signaling pathways of miR-675/FADD and miR-138/PTK2"

Fetched: April 10th, 2024, 2:02am UTC

J Cell Biochem. 2024 Apr 9. doi: 10.1002/jcb.30549. Online ahead of print.

ABSTRACT

Retraction: "H19 suppresses the growth of hepatoblastoma cells by promoting their apoptosis via the signaling pathways of miR-675/FADD and miR-138/PTK2" by Lili Ge, Xianwei Zhang, Shengnan Hu, Yinsen Song, Jinghui Kong, Bo Zhang, Xiaoang Yang, J Cell Biochem 2019, 120: 5218-5231. The above article, published online on 26 October 2018 in Wiley Online Library [https:] has been retracted by agreement between the authors, the journal's Editor in Chief, Christian Behl, and Wiley Periodicals LLC. The decision to retract the article was made following a request for retraction from the authors. An initial assessment uncovered the duplication of image elements between Figure 2A and 2C. The editors believe that these findings compromise the interpretation of the data and results presented.

PMID:38591423 | DOI:10.1002/jcb.30549

Permalink for 'Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study'

Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study

Fetched: April 10th, 2024, 2:02am UTC by Chiyi Jiang

Transl Pediatr. 2024 Mar 27;13(3):387-398. doi: 10.21037/tp-23-480. Epub 2024 Mar 14.

ABSTRACT

BACKGROUND: With the development of the novel coronavirus disease 2019 (COVID-19), China implemented measures in an attempt to control the infection rate. We conducted a single-center, cross-sectional study to ascertain the impact of the COVID-19 pandemic on the equitable availability of medical resources for children diagnosed with malignant solid tumors in China.

METHODS: Data on the demographics, clinical characteristics, and medical expenses of 876 patients diagnosed with neuroblastoma, rhabdomyosarcoma (RMS), Wilms tumor, hepatoblastoma (HB), Ewing sarcoma (ES), and central nervous system (CNS) tumors from 2019 to 2021, during the COVID-19 pandemic, were retrospectively collected from the National Center for Children's Health. The Pearson Ï‡² test and Mann-Whitney test were performed to analyze the differences among variables.

RESULTS: Except for the regional origin of children with tumors during the epidemic, no significant differences were found in the demographic or clinical characteristics of patients at initial diagnosis. The number of patients from northern China and northeastern China who attended Beijing Children's Hospital (BCH) increased after the outbreak of COVID-19 (P=0.001). There was no significant alteration observed in the frequency of hospitalizations per individual per annum (P=0.641) or the mean expense incurred per individual per hospitalization (P=0.361). In addition, the medical insurance coverage rate of real-time settlement increased year by year.

CONCLUSIONS: After the COVID-19 outbreak, the origin of patients with solid tumor who visited BCH was concentrated in the northern region of China. COVID-19 had no impact on the other demographic factors, clinical characteristics, or economic burden of patients with pediatric malignant solid tumors.

PMID:38590381 | PMC:PMC10998988 | DOI:10.21037/tp-23-480

TDF and TAF inhibit liver cancer cell migration, invasion via p7TP3

Fetched: April 9th, 2024, 2:02am UTC by Jing Zhao

Sci Rep. 2024 Apr 8;14(1):8161. doi: 10.1038/s41598-024-58807-z.

ABSTRACT

Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/Î²-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (p7TP3), a tumor suppressor in liver cancers, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of liver cancer cells, activity of Wnt/Î²-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for liver cancers, including HCC and hepatoblastoma, via Wnt/Î²-catenin signaling pathway, by up-regulating expression of the tumor suppressor, p7TP3.

PMID:38589540 | PMC:PMC11001947 | DOI:10.1038/s41598-024-58807-z

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