Rare Cancer News & Clinical Trials

Rhabdomyosarcoma (145 unread)

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Google - Rhabdomyosarcoma

Overview of musculoskeletal cancers (Tumours) - Punch Newspapers

Posted: January 15th, 2022, 9:12pm GMT

Overview of musculoskeletal cancers (Tumours) Punch Newspapers
Cotgrave family 'living a nightmare' after girl, 7, diagnosed with cancer - Nottinghamshire Live

Posted: January 15th, 2022, 1:35pm GMT

Cotgrave family 'living a nightmare' after girl, 7, diagnosed with cancer Nottinghamshire Live
Father And Toddler Daughter Grapple With Cancer Together - TODAY

Posted: January 14th, 2022, 12:55pm GMT

Father And Toddler Daughter Grapple With Cancer Together TODAY
'The Brave Adventures of Triton Tough' graphic novel now available - County 10 News

Posted: January 13th, 2022, 6:41pm GMT

'The Brave Adventures of Triton Tough' graphic novel now available County 10 News
Other news to note for Jan. 12, 2022 - BioWorld Online

Posted: January 12th, 2022, 9:17pm GMT

Other news to note for Jan. 12, 2022 BioWorld Online
Bionano Genomics Hosts Day 3 o - GuruFocus.com

Posted: January 12th, 2022, 8:00pm GMT

Bionano Genomics Hosts Day 3 o GuruFocus.com
Bionano Genomics Hosts Day 3 of 2022 Symposium with New Research Demonstrating Applications of OGM in Solid Tumor Analysis - Yahoo Finance

Posted: January 12th, 2022, 7:30pm GMT

Bionano Genomics Hosts Day 3 of 2022 Symposium with New Research Demonstrating Applications of OGM in Solid Tumor Analysis Yahoo Finance
Necroptosis-related miRNAs signature for colon cancer | IJGM - Dove Medical Press

Posted: January 12th, 2022, 11:14am GMT

Necroptosis-related miRNAs signature for colon cancer | IJGM Dove Medical Press
Crafty, curious Oklahoma girl’s spirits high after tumor removed, chemotherapy completed - KFOR Oklahoma City

Posted: January 12th, 2022, 10:20pm GMT

Crafty, curious Oklahoma girl’s spirits high after tumor removed, chemotherapy completed KFOR Oklahoma City
Alpha DaRT Elicits Complete Responses in Malignant Skin and Soft Tissue Cancers - OncLive

Posted: January 11th, 2022, 4:20pm GMT

Alpha DaRT Elicits Complete Responses in Malignant Skin and Soft Tissue Cancers OncLive
Rochdale father to run 5k every day this year in memory of three-year-old son - In Your Area

Posted: January 10th, 2022, 12:04pm GMT

Rochdale father to run 5k every day this year in memory of three-year-old son In Your Area
Long-term urological complications after conservative local treatment (surgery and brachytherapy) in children with bladder–prostate rhabdomyosarcoma: A single-team experience - MD Linx

Posted: January 10th, 2022, 6:48am GMT

Long-term urological complications after conservative local treatment (surgery and brachytherapy) in children with bladder–prostate rhabdomyosarcoma: A single-team experience MD Linx
Norwich's Oscar, 2, battles rare childhood cancer - Norwich Evening News

Posted: January 10th, 2022, 5:00am GMT

Norwich's Oscar, 2, battles rare childhood cancer Norwich Evening News
Logan Gellert – Hamilton County Reporter - readthereporter.com

Posted: January 9th, 2022, 6:05pm GMT

Logan Gellert – Hamilton County Reporter readthereporter.com
Logan Gellert - The Times

Posted: January 9th, 2022, 6:03pm GMT

Logan Gellert The Times
Muscle-specific functional deficits and lifelong fibrosis in response to paediatric radiotherapy and tumour elimination - DocWire News

Posted: January 8th, 2022, 4:00am GMT

Muscle-specific functional deficits and lifelong fibrosis in response to paediatric radiotherapy and tumour elimination DocWire News
Chiropractor in Caversham Reading Sponsors Daughter of Patients for a Charitable Cause - Digital Journal

Posted: January 7th, 2022, 5:14pm GMT

Chiropractor in Caversham Reading Sponsors Daughter of Patients for a Charitable Cause Digital Journal
Kerry school community come together to support young pupil (7) with rare form of cancer - RSVP Live

Posted: January 6th, 2022, 12:51pm GMT

Kerry school community come together to support young pupil (7) with rare form of cancer RSVP Live
Rhabdomyosarcoma Drug Market Size 2021 Analysis by Top Key Players | Bellicum Pharmaceuticals Inc,Boehringer Ingelheim GmbH,Bristol-Myers Squibb Co,Celgene Corp – Industrial IT - Industrial IT

Posted: January 5th, 2022, 2:45pm GMT

Rhabdomyosarcoma Drug Market Size 2021 Analysis by Top Key Players | Bellicum Pharmaceuticals Inc,Boehringer Ingelheim GmbH,Bristol-Myers Squibb Co,Celgene Corp – Industrial IT Industrial IT
Kids Winter Clothes Market to Witness Rapid Growth by 2029 | Benetton Kids, Carrefour, H&M – Industrial IT - Industrial IT

Posted: January 5th, 2022, 2:45pm GMT

Kids Winter Clothes Market to Witness Rapid Growth by 2029 | Benetton Kids, Carrefour, H&M – Industrial IT Industrial IT
Octogenarian with pulmonary carcinosarcoma | CMAR - Dove Medical Press

Posted: January 5th, 2022, 12:57pm GMT

Octogenarian with pulmonary carcinosarcoma | CMAR Dove Medical Press
Safety an 'important differentiating factor' for novel CAR-T in B-cell malignancies - Healio

Posted: January 5th, 2022, 12:27pm GMT

Safety an 'important differentiating factor' for novel CAR-T in B-cell malignancies Healio
45 Biggest Movers From Yesterday - Benzinga - Benzinga

Posted: January 5th, 2022, 5:12am GMT

45 Biggest Movers From Yesterday - Benzinga Benzinga
34 Stocks Moving In Tuesday’s Mid-Day Session - News Nation USA

Posted: January 4th, 2022, 2:41pm GMT

34 Stocks Moving In Tuesday’s Mid-Day Session News Nation USA
Best Biotech Penny Stocks to Buy Now? 3 to Watch in January - Penny Stocks

Posted: January 4th, 2022, 12:43pm GMT

Best Biotech Penny Stocks to Buy Now? 3 to Watch in January Penny Stocks
Immix Biopharma shares are trading higher on continued momentum after the company announced the FDA granted Rare Pediatric Disease designation for IMX-110 for the treatment of a life-threatening form of pediatric cancer in children, rhabdomyosarcoma. - B

Posted: January 4th, 2022, 12:05pm GMT

Immix Biopharma shares are trading higher on continued momentum after the company announced the FDA granted Rare Pediatric Disease designation for IMX-110 for the treatment of a life-threatening form of pediatric cancer in children, rhabdomyosarcoma. Benzinga
34 Stocks Moving In Tuesday's Mid-Day Session - Benzinga - Benzinga

Posted: January 4th, 2022, 12:01pm GMT

34 Stocks Moving In Tuesday's Mid-Day Session - Benzinga Benzinga
Odhrán's fundraising walk for Mason Fletcher in Roscrea - Tipperary Live

Posted: January 4th, 2022, 10:46am GMT

Odhrán's fundraising walk for Mason Fletcher in Roscrea Tipperary Live
61 Biggest Movers From Yesterday - Benzinga - Benzinga

Posted: January 4th, 2022, 5:06am GMT

61 Biggest Movers From Yesterday - Benzinga Benzinga
Treaty 3 Police mourn the passing of Honourary Junior Chief of Police - KenoraOnline.com

Posted: January 4th, 2022, 10:33pm GMT

Treaty 3 Police mourn the passing of Honourary Junior Chief of Police KenoraOnline.com
FDA Grants Rare Pediatric Disease Designation to Novel Treatment for Rhabdomyosarcoma - Targeted Oncology

Posted: January 3rd, 2022, 9:51pm GMT
Mid-afternoon market update: Dow surges 150 points, Applied Therapeutics shares slide - FXStreet

Posted: January 3rd, 2022, 8:22pm GMT

Mid-afternoon market update: Dow surges 150 points, Applied Therapeutics shares slide FXStreet
Health Care Sector Update for 01/03/2022: APLT,IMMX,GNPX,MRK,AZN - Nasdaq

Posted: January 3rd, 2022, 4:48pm GMT

Health Care Sector Update for 01/03/2022: APLT,IMMX,GNPX,MRK,AZN Nasdaq
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Posted: January 3rd, 2022, 3:12pm GMT

831) 645-8650 Blinded By Sound
Dow Flat as Tesla Lifts Tech, Autos - Schaeffers Research

Posted: January 3rd, 2022, 2:47pm GMT

Dow Flat as Tesla Lifts Tech, Autos Schaeffers Research
Immix Biopharma (IMMX) Shares Halted on Upside Volatility, Up 116% - StreetInsider.com

Posted: January 3rd, 2022, 12:35pm GMT

Immix Biopharma (IMMX) Shares Halted on Upside Volatility, Up 116% StreetInsider.com
Health Care Sector Update for 01/03/2022: IMMX, ITOS, APLT, XLV, IBB - Nasdaq

Posted: January 3rd, 2022, 12:13pm GMT

Health Care Sector Update for 01/03/2022: IMMX, ITOS, APLT, XLV, IBB Nasdaq
35 Stocks Moving In Monday's Mid-Day Session - Benzinga - Benzinga

Posted: January 3rd, 2022, 12:06pm GMT

35 Stocks Moving In Monday's Mid-Day Session - Benzinga Benzinga
Immix Biopharma shares are trading higher after the company announced the FDA granted Rare Pediatric Disease designation for IMX-110 for the treatment of a life-threatening form of pediatric cancer in children, rhabdomyosarcoma. - Benzinga

Posted: January 3rd, 2022, 11:19am GMT

Immix Biopharma shares are trading higher after the company announced the FDA granted Rare Pediatric Disease designation for IMX-110 for the treatment of a life-threatening form of pediatric cancer in children, rhabdomyosarcoma. Benzinga
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Posted: January 3rd, 2022, 4:50am GMT

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Posted: January 3rd, 2022, 3:38am GMT

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Retired California state park ranger puts a lens on West Marin and its wildlife - Marin Independent Journal

Posted: January 1st, 2022, 6:02pm GMT

Retired California state park ranger puts a lens on West Marin and its wildlife Marin Independent Journal
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Posted: January 1st, 2022, 4:57pm GMT

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Alveolar Rhabdomyosarcoma Treatment Market Size 2021 Analysis by Top Companies, And Forecast to 2028 | Eli Lilly,GlaxoSmithKline,Boehringer Ingelheim,Bristol-Myers Squibb – Industrial IT - Industrial IT

Posted: December 30th, 2021, 3:55pm GMT

Alveolar Rhabdomyosarcoma Treatment Market Size 2021 Analysis by Top Companies, And Forecast to 2028 | Eli Lilly,GlaxoSmithKline,Boehringer Ingelheim,Bristol-Myers Squibb – Industrial IT Industrial IT
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Eye Cancer Market Reports Reviews The Eventual Trends With Top Key Players -Bristol-Myers Squibb Company (US), Eli Lilly and Company (US), AstraZeneca Plc. (UK) – Industrial IT - Industrial IT

Posted: December 30th, 2021, 11:08am GMT

Eye Cancer Market Reports Reviews The Eventual Trends With Top Key Players -Bristol-Myers Squibb Company (US), Eli Lilly and Company (US), AstraZeneca Plc. (UK) – Industrial IT Industrial IT
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Eastern junior has greater appreciation for life, basketball after battling cancer - NJ.com

Posted: December 30th, 2021, 11:30pm GMT

Eastern junior has greater appreciation for life, basketball after battling cancer NJ.com
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Body Composition May Be a Better Predictor of Chemotoxicities in Children With Lymphoma or a Type of Sarcoma Than BMI - Curetoday.com

Posted: December 29th, 2021, 8:00pm GMT

Body Composition May Be a Better Predictor of Chemotoxicities in Children With Lymphoma or a Type of Sarcoma Than BMI Curetoday.com
Putnam County girl known as 'Fighting Bean' dies after long battle with cancer - FOX 29

Posted: December 29th, 2021, 11:40am GMT

Putnam County girl known as 'Fighting Bean' dies after long battle with cancer FOX 29
Putnam County girl known as 'Fighting Bean' dies after long battle with cancer - WOAI

Posted: December 29th, 2021, 11:40am GMT

Putnam County girl known as 'Fighting Bean' dies after long battle with cancer WOAI
Putnam County girl known as 'Fighting Bean' dies after long battle with cancer - WCHS-TV8

Posted: December 29th, 2021, 11:40am GMT

Putnam County girl known as 'Fighting Bean' dies after long battle with cancer WCHS-TV8
Rossville community welcomes Braylie back home | Archive | wlfi.com - wlfi.com

Posted: December 29th, 2021, 6:00am GMT

Rossville community welcomes Braylie back home | Archive | wlfi.com wlfi.com
An attempted good deed in the first-degree - The Paintsville Herald

Posted: December 29th, 2021, 5:14am GMT

An attempted good deed in the first-degree The Paintsville Herald
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Ukrainian gymnast spoke about beatings in the national team by coaches - The Times Hub

Posted: December 24th, 2021, 2:08pm GMT

Ukrainian gymnast spoke about beatings in the national team by coaches The Times Hub
Five-year-old finishes chemo treatment just in time for Christmas after shock cancer diagnosis - Leicestershire Live

Posted: December 24th, 2021, 3:00am GMT

Five-year-old finishes chemo treatment just in time for Christmas after shock cancer diagnosis Leicestershire Live
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Dan Reynolds Opens Up About How A Teenager Battling Cancer Changed His Life - iHeartRadio

Posted: December 23rd, 2021, 9:23pm GMT

Dan Reynolds Opens Up About How A Teenager Battling Cancer Changed His Life iHeartRadio
Dan Reynolds Opens Up About How A Teenager Battling Cancer Changed His Life - On Air with Ryan Seacrest

Posted: December 23rd, 2021, 9:12pm GMT

Dan Reynolds Opens Up About How A Teenager Battling Cancer Changed His Life On Air with Ryan Seacrest

PubMed - Rhabdomyosarcoma

PET metabolic tumor volume as a new prognostic factor in childhood rhabdomyosarcoma

Fetched: January 15th, 2022, 5:02am GMT by Helio Fayolle

PLoS One. 2022 Jan 14;17(1):e0261565. doi: 10.1371/journal.pone.0261565. eCollection 2022.

ABSTRACT

PURPOSE: Childhood RMS is a rare malignant disease in which evaluation of tumour spread at diagnosis is essential for therapeutic management. F-18 FDG-PET imaging is currently used for initial RMS disease staging.

MATERIALS AND METHODS: This multicentre retrospective study in six French university hospitals was designed to analyse the prognostic accuracy of MTV at diagnosis for patients with RMS between 1 January 2007 and 31 October 2017, for overall (OS) and progression-free survival (PFS). MTV was defined as the sum of the primitive tumour and the largest metastasis, where relevant, with a 40% threshold of the primary tumour SUVmax. Additional aims were to define the prognostic value of SUVmax, SUVpeak, and bone lysis at diagnosis.

RESULTS: Participants were 101 patients with a median age of 7.4 years (IQR [4.0-12.5], 62 boys), with localized disease (35 cases), regional nodal spread (43 cases), or distant metastases (23). 44 patients had alveolar subtypes. In a univariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 3.47 [1.79;6.74], p<0.001) and PFS (HR = 3.03 [1.51;6.07], p = 0.002). SUVmax, SUVpeak, and bone lysis also influenced OS (respectively p = 0.005, p = 0.004 and p = 0.007) and PFS (p = 0.029, p = 0.019 and p = 0.015). In a multivariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 2.642 [1.272;5.486], p = 0.009) and PFS (HR = 2.707 [1.322;5.547], p = 0.006) after adjustment for confounding factors, including SUVmax, SUVpeak, and bone lysis.

CONCLUSION: A metabolic tumor volume greater than 200 cm3, SUVmax, SUVpeak, and bone lysis in the pre-treatment assessment were unfavourable for outcome.

PMID:35030176 | PMC:PMC8759649 | DOI:10.1371/journal.pone.0261565
Epidemiology and treatment of head and neck malignancies in the AYA generation

Fetched: January 15th, 2022, 5:02am GMT by Takahiro Asakage

Int J Clin Oncol. 2022 Jan 14. doi: 10.1007/s10147-021-02093-6. Online ahead of print.

ABSTRACT

The Adolescent and Young Adult (AYA) population refers to the population of young adults and adolescents in the 15-39 years age group. This population subgroup experiences various important life events. Head and neck malignancies are rare tumors, in general, but they are extremely rare in the AYA population. When analyzed by the primary site of the tumors, thyroid gland, soft tissue, and nasopharyngeal malignancies are the most commonly encountered head and neck malignancies in the AYA generation. The most common histopathologic subtypes are carcinomas (thyroid carcinoma, nasopharyngeal carcinoma) and rhabdomyosarcoma. Therefore, in this review, the author discusses these three diseases in the AYA population in detail. Especially, patients with parameningeal rhabdomyosarcoma are at a high risk of dysfunction and facial deformity. Infertility problems may also occur as long-term sequelae of chemotherapy in this population. Radiation therapy might be associated with considerable morbidity. Complications such as cataract, xerostomia, hearing loss, neck fibrosis, and trismus are also common. Head and neck surgeons and medical oncologists should choose the optimal treatment taking into account the curability of the tumors relative to the long-term adverse events of treatment use. Finally, little evidence has been accumulated on head and neck malignancies in the AYA population, and it is urgently necessary to build a high level of evidence for the future.

PMID:35028770 | DOI:10.1007/s10147-021-02093-6
Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study

Fetched: January 14th, 2022, 5:01am GMT by Zhichao Tian

BMC Cancer. 2022 Jan 12;22(1):56. doi: 10.1186/s12885-022-09176-1.

ABSTRACT

BACKGROUND: There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited.

METHODS: The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan-Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant.

RESULTS: A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8-3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018).

CONCLUSION: Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.

PMID:35022029 | DOI:10.1186/s12885-022-09176-1
Genitourinary Tract Tumors in Children: An Update

Fetched: January 14th, 2022, 5:01am GMT by Andrés Augusto González-Arboleda

Curr Pediatr Rev. 2022 Jan 11. doi: 10.2174/1573396318666220111143902. Online ahead of print.

ABSTRACT

BACKGROUND: Genitourinary tract tumors in children are less common than in adults. Most of these tumors have different genetic backgrounds, clinical presentation, and oncologic behavior than their adult counterpart. As a result of low prevalence in children, some of the treatment approaches and recommendations are based on treatment experience in adult patients. However, thanks to scientific and technological development, survival rates have risen considerably.

OBJECTIVE: This paper presents a review of the principal features of the tumors involving the genitourinary tract in children and an update in genetic background, diagnosis, and treatment.

METHODS: A narrative review was performed on published literature about genitourinary tract tumors in pediatric patients. Papers presented in English and Spanish literature were reviewed. PubMed, Science Direct, and SciELO databases were used to collect information and present this article.

RESULTS: Kidney tumors are the most common type of genitourinary tumors in children. Among those, Wilms tumor represents the majority of cases and shows the successful work of clinical trial groups studying this tumor type. Other tumors involving the genitourinary tract in children include Rhabdomyosarcoma, Transitional cell carcinoma, Testicular, and Adrenal tumors.

CONCLUSION: Genitourinary tract tumors in children represent significant morbidity and economic burden, so awareness in early diagnosis represents improvement in treatment, clinical and oncological outcomes.

PMID:35021978 | DOI:10.2174/1573396318666220111143902
Vincristine induced fever in a child with embryonal rhadbomyosarcoma

Fetched: January 13th, 2022, 5:02am GMT by Dr Arul Janani

J Oncol Pharm Pract. 2022 Jan 12:10781552221074015. doi: 10.1177/10781552221074015. Online ahead of print.

ABSTRACT

INTRODUCTION: Febrile episodes in oncology is common are mostly of infectious etiology requiring repeated investigations and escalation of antibiotics. But, drug induced fever occur more often than we think in oncological set-up.

CASE REPORT: A 5 year old male child with rhabdomyosarcoma, developed high grade fever spikes following Vincristine monotherapy. Infective etiology work up was negative and the fever responded to corticosteroids.

MANAGEMENT AND OUTCOME: He was treated with corticosteroids as premedication considering vincristine induced fever. The further courses of VCR- monotherapy were uneventful with steroids as premedication.

DISCUSSION: We present the case of vincristine induced fever in a child with embryonal rhabdomyosarcoma. Clinician's should consider drug induced fever at appropriate conditions, to avoid leading to antibiotic resistance.

PMID:35018851 | DOI:10.1177/10781552221074015
Splice-switching of the insulin receptor pre-mRNA alleviates tumorigenic hallmarks in rhabdomyosarcoma

Fetched: January 13th, 2022, 5:02am GMT by Safiya Khurshid

NPJ Precis Oncol. 2022 Jan 11;6(1):1. doi: 10.1038/s41698-021-00245-5.

ABSTRACT

Rhabdomyosarcoma (RMS) is an aggressive pediatric tumor with a poor prognosis for metastasis and recurrent disease. Large-scale sequencing endeavors demonstrate that Rhabdomyosarcomas have a dearth of precisely targetable driver mutations. However, IGF-2 signaling is known to be grossly altered in RMS. The insulin receptor (IR) exists in two alternatively spliced isoforms, IR-A and IR-B. The IGF-2 signaling molecule binds both its innate IGF-1 receptor as well as the insulin receptor variant A (IR-A) with high affinity. Mitogenic and proliferative signaling via the canonical IGF-2 pathway is, therefore, augmented by IR-A. This study shows that RMS patients express increased IR-A levels compared to control tissues that predominantly express the IR-B isoform. We also found that Hif-1α is significantly increased in RMS tumors, portraying their hypoxic phenotype. Concordantly, the alternative splicing of IR adapts to produce more IR-A in response to hypoxic stress. Upon examining the pre-mRNA structure of the gene, we identified a potential hypoxia-responsive element, which is also the binding site for the RNA-binding protein CUG-BP1 (CELF1). We designed Splice Switching Oligonucleotides (SSO) against this binding site to decrease IR-A levels in RMS cell lines and, consequently, rescue the IR-B expression levels. SSO treatment resulted in a significant reduction in cell proliferation, migration, and angiogenesis. Our data shows promising insight into how impeding the IGF-2 pathway by reducing IR-A expression mitigates tumor growth. It is evident that Rhabdomyosarcomas use IR alternative splicing as yet another survival strategy that can be exploited as a therapeutic intervention in conjunction with already established anti-IGF-1 receptor therapies.

PMID:35017650 | DOI:10.1038/s41698-021-00245-5
Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation

Fetched: January 12th, 2022, 5:01am GMT by Florence Choo

Cold Spring Harb Mol Case Stud. 2022 Jan 10;8(1):a006140. doi: 10.1101/mcs.a006140. Print 2022 Jan.

ABSTRACT

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma, commonly harboring a gain-of-function L122R mutation in the muscle-specific master transcription factor MYOD1. MYOD1-mutated ssRMS is almost invariably fatal, and development of novel therapeutic approaches based on the biology of the disease is urgently needed. MYOD1 L122R affects the DNA-binding domain and is believed to confer MYC-like properties to MYOD1, driving oncogenesis. Moreover, the majority of the MYOD1-mutated ssRMS harbor additional alterations activating the PI3K/AKT pathway. It is postulated that the PI3K/AKT pathway cooperates with MYOD1 L122R. To address this biological entity, we established and characterized a new patient-derived ssRMS cell line OHSU-SARC001, harboring MYOD1 L122R as well as alterations in PTEN, PIK3CA, and GNAS We explored the functional impact of these aberrations on oncogenic signaling with gain-of-function experiments in C2C12 murine muscle lineage cells. These data reveal that PIK3CA^I459_T462del, the novel PIK3CA variant discovered in this patient specimen, is a constitutively active kinase, albeit to a lesser extent than PI3KCA^E545K, a hotspot oncogenic mutation. Furthermore, we examined the effectiveness of molecularly targeted PI3K/AKT/mTOR and RAS/MAPK inhibitors to block oncogenic signaling and suppress the growth of OHSU-SARC001 cells. Dual PI3K/mTOR (LY3023414, bimiralisib) and AKT inhibitors (ipatasertib, afuresertib) induced dose-dependent reductions in cell growth. However, mTOR-selective inhibitors (everolimus, rapamycin) alone did not exert cytotoxic effects. The MEK1/2 inhibitor trametinib did not impact proliferation even at the highest doses tested. Our data suggest that molecularly targeted strategies may be effective in PI3K/AKT/mTOR-activated ssRMS. Taken together, these data highlight the importance of utilizing patient-derived models to assess molecularly targetable treatments and their potential as future treatment options.

PMID:35012940 | DOI:10.1101/mcs.a006140
The Effect of Direct and Indirect EZH2 Inhibition in Rhabdomyosarcoma Cell Lines

Fetched: January 12th, 2022, 5:01am GMT by Andreas Schmidt

Cancers (Basel). 2021 Dec 23;14(1):41. doi: 10.3390/cancers14010041.

ABSTRACT

Enhancer of Zeste homolog 2 (EZH2) is involved in epigenetic regulation of gene transcription by catalyzing trimethylation of histone 3 at lysine 27. In rhabdomyosarcoma (RMS), increased EZH2 protein levels are associated with poor prognosis and increased metastatic potential, suggesting EZH2 as a therapeutic target. The inhibition of EZH2 can be achieved by direct inhibition which targets only the enzyme activity or by indirect inhibition which also affects activities of other methyltransferases and reduces EZH2 protein abundance. We assessed the direct inhibition of EZH2 by EPZ005687 and the indirect inhibition by 3-deazaneplanocin (DZNep) and adenosine dialdehyde (AdOx) in the embryonal RD and the alveolar RH30 RMS cell line. EPZ005687 was more effective in reducing the cell viability and colony formation, in promoting apoptosis induction, and in arresting cells in the G1 phase of the cell cycle than the indirect inhibitors. DZNep was more effective in decreasing spheroid viability and size in both cell lines than EPZ005687 and AdOx. Both types of inhibitors reduced cell migration of RH30 cells but not of RD cells. The results show that direct and indirect inhibition of EZH2 affect cellular functions differently. The alveolar cell line RH30 is more sensitive to epigenetic intervention than the embryonal cell line RD.

PMID:35008205 | PMC:PMC8750739 | DOI:10.3390/cancers14010041
Mesenchymal Tumors Involving the Pancreas: A Clinicopathologic Analysis and Review of the Literature

Fetched: January 11th, 2022, 5:01am GMT by Gokce Askan

Turk Patoloji Derg. 2022;38(1):46-53. doi: 10.5146/tjpath.2022.01567.

ABSTRACT

OBJECTIVE: Most pancreatic tumors are epithelial, and, among these, more than 90% are of ductal origin. However, a variety of mesenchymal tumors may involve the pancreas and may manifest different clinicopathological characteristics. The literature on mesenchymal tumors in the pancreas is largely limited to individual case reports or analyses of small series, predominantly focusing on radiologic features.

MATERIAL AND METHOD: Authors' institutional and consultation databases were reviewed to identify the mesenchymal tumors involving the pancreas.

RESULTS: Forty cases were identified; twenty-five (63%) tumors were benign/borderline, and the remaining fifteen (37%) were malignant. Of the benign/borderline tumors; 9 were solitary fibrous tumors, 6 gastrointestinal stromal tumors (GISTs), 4 schwannomas, 2 desmoid type fibromatosis, 1 lymphangioma, 1 ganglioneuroma, 1 inflammatory myofibroblastic tumor, and 1 low grade mesenchymal neoplasm. Malignant tumors included 6 cases of leiomyosarcomas, 4 liposarcomas, 2 rhabdomyosarcomas, 1 epithelioid angiosarcoma, 1 malignant peripheral nerve sheet tumor, and 1 undifferentiated pleomorphic sarcoma. Four cases (multicystic schwannoma, desmoid fibromatosis, lymphangioma and inflammatory myofibroblastic tumor) were preoperatively misdiagnosed as a primary epithelial tumor of the pancreas.

CONCLUSION: Mesenchymal tumors rarely involve the pancreas. They are usually benign/borderline neoplasms but may be diagnostically challenging, especially clinically/radiologically, as they may form cystic and/or large lesions in the pancreas. Mesenchymal tumors should be considered in both the clinical/radiological and pathological differential diagnosis of pancreatic lesions.

PMID:35001360 | DOI:10.5146/tjpath.2022.01567
Pleuropulmonary Blastoma

Fetched: January 11th, 2022, 5:01am GMT by Mouna Mlika
2021 Dec 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.

ABSTRACT

Childhood tumors of the lung are rare malignant tumors accounting for 0.5% to 1% of all primary malignant lung tumors. These tumors are subdivided into 3 subtypes: pulmonary blastoma, fetal adenocarcinoma, and pleuropulmonary blastoma (PPB). An epithelial malignant and immature component characterizes fetal adenocarcinoma. A malignant immature mesenchymal proliferation characterizes the pleuropulmonary blastoma. Biphasic components define the blastoma; a mesenchymal and an epithelial malignant and immature component, that look like a 10- to 16-week gestational lung. In the 2015 World Health Organization Classification, fetal adenocarcinoma belongs to the group of adenocarcinomas, pulmonary blastoma belongs to the group of sarcomatoid carcinoma, and pleuropulmonary blastoma belongs to the group of mesenchymal tumors. Pleuropulmonary blastomas are rare tumors which present non-specific symptoms. Although the importance of the radiologic features to suspect the diagnosis, the positive diagnosis remains based on the microscopic features. Many synonyms of pleuropulmonary tumors exist in the literature including:
1. Cystic mesenchymal hamartoma
2. Mesenchymal cystic hamartoma
3. Pediatric pulmonary blastoma
4. Pneumoblastoma
5. Pulmonary rhabdomyosarcoma
6. Rhabdomyosarcoma in lung cyst
PMID:30480950 | Bookshelf:NBK534211
Muscle-specific functional deficits and lifelong fibrosis in response to paediatric radiotherapy and tumour elimination

Fetched: January 9th, 2022, 5:01am GMT by Jacob G Kallenbach

J Cachexia Sarcopenia Muscle. 2022 Jan 8. doi: 10.1002/jcsm.12902. Online ahead of print.

ABSTRACT

BACKGROUND: As paediatric cancer survivors are living into adulthood, they suffer from the age-related, accelerated decline of functional skeletal muscle tissue, termed sarcopenia. With ionizing radiation (radiotherapy) at the core of paediatric cancer therapies, its direct and indirect effects can have lifelong negative impacts on paediatric growth and maintenance of skeletal muscle. Utilizing our recently developed preclinical rhabdomyosarcoma mouse model, we investigated the late effects of paediatric radiation treatment on skeletal muscles from late adolescent (8 weeks old) and middle-aged (16 months old) mice.

METHODS: Paediatric C57BL/6J male mice (3 weeks old) were injected with rhabdomyosarcoma cells into their right hindlimbs, and then fractionated irradiation (3 × 8.2 Gy) was administered to those limbs at 4 weeks old to eliminate the tumours. Radiation-alone and tumour-irradiated mice were assessed at either 8 weeks (3 weeks post-irradiation) or 16 months (14 months post-irradiation) of age for muscle physiology, myofibre characteristics, cell loss, histopathology, fibrosis, inflammatory gene expression, and fibrotic gene expression.

RESULTS: Mice that received only paediatric radiation demonstrated reduced muscle mass (-17%, P < 0.001), muscle physiological function (-25%, P < 0.01), muscle contractile kinetics (-25%, P < 0.05), satellite cell number (-45%, P < 0.05), myofibre cross-sectional area (-30%, P < 0.0001), and myonuclear number (-17%, P < 0.001). Paediatric radiation increased inflammatory gene expression, increased fibrotic gene expression, and induced extracellular matrix protein deposition (fibrosis) with tumour elimination exacerbating some phenotypes. Paediatric tumour-eliminated mice demonstrated exacerbated deficits to function (-20%, P < 0.05) and myofibre size (-17%, P < 0.001) in some muscles as well as further increases to inflammatory and fibrotic gene expression. Examining the age-related effects of paediatric radiotherapy in middle-aged mice, we found persistent myofibre atrophy (-20%, P < 0.01), myonuclear loss (-18%, P < 0.001), up-regulated inflammatory and fibrotic signalling, and lifelong fibrosis.

CONCLUSIONS: The results from this paediatric radiotherapy model are consistent and recapitulate the clinical and molecular features of accelerated sarcopenia, musculoskeletal frailty, and radiation-induced fibrosis experienced by paediatric cancer survivors. We believe that this preclinical mouse model is well poised for future mechanistic insights and therapeutic interventions that improve the quality of life for paediatric cancer survivors.

PMID:34997696 | DOI:10.1002/jcsm.12902
Role of the Immunohistochemical ZEB1 Expression in Uterine Mesenchymal Neoplasms

Fetched: January 8th, 2022, 5:01am GMT by Murat Çelik

Int J Surg Pathol. 2022 Jan 7:10668969211070180. doi: 10.1177/10668969211070180. Online ahead of print.

ABSTRACT

The distinction of mesenchymal tumors of the uterus is a frequent diagnostic challenge in gynecologic pathology. Especially, distinguishing low-grade endometrial stromal sarcoma (ESS) from leiomyoma or distinguishing low-grade ESS from high-grade ESS can be difficult. Epithelial-mesenchymal transition (EMT) is a physiological and pathological process in which epithelial cells lose their morphological features, become elongated and acquire mesenchymal traits. The signaling pathway of Zinc finger E-box binding homeobox 1 (ZEB1) is one of the most significant pathways involved in the EMT process and it has a crucial role in cancer progression, metastasis, and therapy resistance. We studied a series of 69 uterine mesenchymal neoplasms including 18 endometrial stromal sarcomas (10 cases of low grade and 8 cases of high grade endometrial stromal sarcomas), 26 leiomyosarcomas (8 cases of grade 1 and 19 cases of grade 2-3 leiomyosarcomas), 15 leiomyomas, and 10 rhabdomyosarcomas, using an antibody ZEB1. We graded the leiomyosarcomas depending on the FNCLCC grading system. It was observed that leiomyosarcoma was more intensely stained with ZEB1 than leiomyoma (P < 0.001) and high-grade ESS was significantly more intensely stained with ZEB1 protein than low-grade ESS (P < 0.004). It also was observed that high-grade leiomyosarcoma was significantly more intensely stained with ZEB1 protein than low-grade leiomyosarcoma (P < 0.000). Our data suggest that Zeb1 can be used to differentiate high-grade sarcomas from their low-grade counterparts as well as benign and malignant smooth muscle tumors of the uterus.

PMID:34994578 | DOI:10.1177/10668969211070180
Primary cerebral rhabdomyosarcoma - an oncological headache

Fetched: January 8th, 2022, 5:01am GMT by Niranjan Vijayaraghavan

Rep Pract Oncol Radiother. 2021 Dec 30;26(6):1066-1067. doi: 10.5603/RPOR.a2021.0114. eCollection 2021.

NO ABSTRACT

PMID:34992883 | PMC:PMC8726457 | DOI:10.5603/RPOR.a2021.0114
Primary Cutaneous Alveolar Rhabdomyosarcoma in an Elderly Adult: A Rare Potential Mimic of Merkel Cell Carcinoma

Fetched: January 8th, 2022, 5:01am GMT by Miki S Lindsey

Am J Dermatopathol. 2022 Jan 5. doi: 10.1097/DAD.0000000000002124. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma (RMS) rarely arises as a primary skin tumor. It is also very rare in older adults, especially the alveolar type. We report an 80-year-old White woman who presented with a painful, erythematous, raised lesion (2 × 3.5 cm) above the left knee that was fixed within the skin, yet mobile about underlying soft tissue. A punch biopsy showed monotonous malignant round blue cells involving the dermis. Immunostains showed diffuse expression of CD56, focal chromogranin, focal dot-like pancytokeratin, CK7, and neurofilament, but negative for synaptophysin, CK20, SOX-10, MUM-1, CD43, TTF-1, and CD99. A CK20-negative variant of Merkel cell carcinoma was initially favored, but given the unusual immunophenotype and the presence of cellular dyscohesion, desmin and myogenin stains were performed, both of which were diffusely positive. Molecular testing revealed rearrangement of PAX3 and FOXO1 loci, confirming the diagnosis of alveolar RMS. PET/CT showed a probable 1.9-cm left inguinal lymph node metastasis; no internal or deep soft tissue primary tumor mass was identified, supporting a true primary cutaneous origin. Alveolar RMS may express keratins and neuroendocrine markers, making it easy to confuse with Merkel cell carcinoma on those exceptionally rare instances, when it arises in the skin of older adults.

PMID:34991098 | DOI:10.1097/DAD.0000000000002124
Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated Viral Translation

Fetched: January 6th, 2022, 5:01am GMT by Hui Li

Microbiol Spectr. 2022 Jan 5;10(1):e0138821. doi: 10.1128/spectrum.01388-21. Online ahead of print.

ABSTRACT

Enterovirus 71 (EV71) is the major pathogen of hand, foot, and mouth disease. In severe cases, it can cause life-threatening neurological complications, such as aseptic meningitis and polio-like paralysis. There are no specific antiviral treatments for EV71 infections. In a previous study, the host protein growth arrest and DNA damage-inducible protein 34 (GADD34) expression was upregulated during EV71 infection determined by ribosome profiling and RNA-sequencing. Here, we investigated the interactions of host protein GADD34 and EV71 during infections. Rhabdomyosarcoma (RD) cells were infected with EV71 resulting in a significant increase in expression of GADD34 mRNA and protein. Through screening of EV71 protein we determined that the non-structural precursor protein 3CD is responsible for upregulating GADD34. EV71 3CD increased the RNA and protein levels of GADD34, while the 3CD mutant Y441S could not. 3CD upregulated GADD34 translation via the upstream open reading frame (uORF) of GADD34 5'untranslated regions (UTR). EV71 replication was attenuated by the knockdown of GADD34. The function of GADD34 to dephosphorylate eIF2α was unrelated to the upregulation of EV71 replication, but the PEST 1, 2, and 3 regions of GADD34 were required. GADD34 promoted the EV71 internal ribosome entry site (IRES) activity through the PEST repeats and affected several other viruses. Finally, GADD34 amino acids 563 to 565 interacted with 3CD, assisting GADD34 to target the EV71 IRES. Our research reveals a new mechanism by which GADD34 promotes viral IRES and how the EV71 non-structural precursor protein 3CD regulates host protein expression to support viral replication. IMPORTANCE Identification of host factors involved in viral replication is an important approach in discovering viral pathogenic mechanisms and identifying potential therapeutic targets. Previously, we screened host proteins that were upregulated by EV71 infection. Here, we report the interaction between the upregulated host protein GADD34 and EV71. EV71 non-structural precursor protein 3CD activates the RNA and protein expression of GADD34. Our study reveals that 3CD regulates the uORF of the 5'-UTR to increase GADD34 translation, providing a new explanation for how viral proteins regulate host protein expression. GADD34 is important for EV71 replication, and the key functional domains of GADD34 that promote EV71 are PEST 1, 2, and 3 regions. We report that GADD34 promotes viral IRES for the first time and this process is independent of its eIF2α phosphatase activity.

PMID:34985336 | PMC:PMC8729766 | DOI:10.1128/spectrum.01388-21
Speech and swallowing function following microsurgical reconstruction of palatal defects in a series of six pediatric patients

Fetched: January 6th, 2022, 5:01am GMT by Abraham Zavala

Microsurgery. 2022 Jan 5. doi: 10.1002/micr.30860. Online ahead of print.

ABSTRACT

BACKGROUND: Reconstruction of extensive palatal defects in growing patients aims to restore speech intelligibility and swallowing function while avoiding excessive scarring formation that may cause growth disturbances in the palate and midface region. Free flaps transfer healthy, well-vascularized tissue to the defect area, and their combination with pharyngeal flaps allow for restoration of the velopharyngeal function. We examined speech and swallowing after microsurgical palate reconstruction in a series of six pediatric patients.

METHODS: Radial forearm free flaps were used in all cases, in combination with a superiorly based pharyngeal flap in five cases. Mean age at surgery was 10.7 years. Etiologies included recurrent oronasal fistula due to failed primary cleft palate repair (n = 4), embryonal rhabdomyosarcoma of the maxilla (n = 1), and inflammatory fibrous hyperplasia (n = 1). Speech evaluations (with the Hirose standard and listener ratings) and swallowing assessments (based on videofluoroscopy swallowing studies and patient-reported swallowing and diet) were performed in average 44 months postoperatively.

RESULTS: All flaps survived without major postoperative complications. Speech intelligibility was graded as "excellent" in four patients and "moderate" in two. Hypernasality and nasal obstruction were each judged as "none/minimal" in five cases and "moderate" in one case. All patients tolerated oral diet without significant nasal regurgitation. In five of six patients, the swallowing assessment showed good motion and velopharyngeal closure.

CONCLUSION: Microsurgical reconstruction of extensive palatal defects using radial forearm free flap, with or without a superiorly based pharyngeal flap, is a reliable technique that can deliver substantial improvement of speech and swallowing in pediatric patients.

PMID:34985140 | DOI:10.1002/micr.30860
$Permalink for 'High-dose Chemotherapy Response in Adults with Relapsed/Refractory Small Round Cell Tumours'$
High-dose Chemotherapy Response in Adults with Relapsed/Refractory Small Round Cell Tumours

Fetched: January 6th, 2022, 5:01am GMT by Musa Baris Aykan

J Coll Physicians Surg Pak. 2022 Jan;32(1):51-56. doi: 10.29271/jcpsp.2022.01.51.

ABSTRACT

OBJECTIVE: To demonstrate the treatment responses, survival analysis, and treatment-related mortality characteristics of high-dose chemotherapy (HDC) in patients with relapsed/refractory Ewing sarcoma (ES), osteosarcoma, rhabdomyosarcoma (RMS) and medulloblastoma (MB).

STUDY DESIGN: Observational study.

PLACE AND DURATION OF STUDY: Department of Medical Oncology, University of Health Sciences, Gulhane School of Medicine, from January 2016 and April 2020.

METHODOLOGY: Clinical features and follow-up data of relapsed/refractory ES, osteosarcoma, RMS and MB patients treated with HDC were recorded from the patients' registration database of the hospital. Patients <16 years and those whose medical records were not available were excluded. Progression-free survival (PFS), one-year overall survival (OS) rates and treatment-related mortality (TRM) after the HDC were determined. Ifosfamide, carboplatin and etoposide (HD-ICE) were used as the HDC protocol in all patients.

RESULTS: Thirty-seven adult patients were included. PFS was determined as 2.70 ± 0.97 months, 11.57 ± 3.63 months, 3.47 ± 0.44 months and 2.96 ± 0.91 months, for ES, MB, RMS and osteosarcoma, respectively. One-year OS rate was 44.8 ± 14.8% for ES; 75 ± 15.8% for MB. In ES, PFS was found to be better in males than females (p = 0.025). No patient died during HD-ICE. Mortality was observed most frequently in the RMS in the first 100 days (25%).

CONCLUSION: HD-ICE treatment may be an option in relapsed/refractory small round cell tumours (SRCT). Significant progression-free survival can be achieved in patients who received at least two lines of treatment, with acceptable treatment-related mortality. Key Words: Small round cell tumours, Ewing sarcoma, Osteosarcoma, Rhabdomyosarcoma, Medulloblastoma, High-dose chemotherapy, Autologous stem cell transplantation.

PMID:34983148 | DOI:10.29271/jcpsp.2022.01.51
Alveolar rhabdomyosarcoma: Two fusion-negative cases lacking PAX3-FOXO1 and PAX7-FOXO1

Fetched: January 5th, 2022, 5:01am GMT by Claudia Mestre-Alagarda

Rev Esp Patol. 2022 Jan-Mar;55(1):57-62. doi: 10.1016/j.patol.2019.03.006. Epub 2019 May 15.

ABSTRACT

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and adolescence. Morphologically, two major forms are described: alveolar and embryonal rhabdomyosarcoma. The former is generally associated with a poorer prognosis and it usually harbors a characteristic fusion gene, PAX3/7-FOXO1, that is used to confirm the diagnosis. We present two cases, both of which exhibited the classic alveolar histology with immunohistochemical myogenic differentiation (Desmin, MYOD-1 and Myogenin expression) and lacked the characteristic fusion gene PAX3/7-FOXO1. The aim of this report is to highlight the importance of the molecular status in the study and diagnosis of these cases, as it seems to be not only a useful diagnostic tool, but also an important prognostic factor.

PMID:34980443 | DOI:10.1016/j.patol.2019.03.006
ALK-positive anaplastic large T-cell lymphoma presenting primarily as a sinonasal mass with pseudoproptosis: A case report

Fetched: January 4th, 2022, 5:01am GMT by Siddhi G Sinai Khandeparkar

Indian J Cancer. 2021 Oct-Dec;58(4):592-597. doi: 10.4103/ijc.IJC_304_20.

ABSTRACT

We report a case of anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma (ALK+ALCL) presenting primarily as a sinonasal mass with pseudoproptosis in an 11-year-old boy. The diagnosis was based on histopathological and immunohistochemical (IHC) evaluation, which is indispensable for determining tumor type. On the basis of clinicoradiological findings, provisional differential diagnoses of angiofibroma and rhabdomyosarcoma were made. Upon histopathological examination of the biopsy sent, the diagnosis of lymphoma in the sinonasal region was considered. Upon IHC, the tumor cells showed immunoreactivity for vimentin, CD45, CD30, and ALK. The tumor cells showed focal immunoreactivity for CD3 and CD68. Ki-67 labeling index was 70%. They were nonimmunoreactive for PAN cytokeratin, epithelial membrane antigen, cluster of differentiation (CD) 20, CD15, CD56, S100, smooth muscle actin, and myogenin. The diagnosis of ALK+ALCL was rendered. The studied IHC markers confirmed the histopathological diagnosis and helped in further subtyping. To the best of our knowledge, this is the first case of ALCL presenting primarily as a sinonasal mass with pseudoproptosis.

PMID:34975099 | DOI:10.4103/ijc.IJC_304_20
SPARC-mediated long-term retention of nab-paclitaxel in pediatric sarcomas

Fetched: January 3rd, 2022, 5:01am GMT by Guillem Pascual-Pasto

J Control Release. 2021 Dec 30;342:81-92. doi: 10.1016/j.jconrel.2021.12.035. Online ahead of print.

ABSTRACT

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein overexpressed by several cancers. Because SPARC shows high binding affinity to albumin, we reasoned that pediatric sarcoma xenografts expressing SPARC would show enhanced uptake and accumulation of nanoparticle albumin-bound (nab)-paclitaxel, a potent anticancer drug formulation. We first evaluated the expression of SPARC in patient-derived xenografts (PDXs) of Ewing sarcoma, rhabdomyosarcoma and osteosarcoma, finding variable SPARC gene expression that correlated well with SPARC protein measured by immunoblotting. We revealed that the activity of the fusion gene chimera EWSR1-FLI1, the genetic driver of Ewing sarcoma, leads to lower expression of the gene SPARC in these tumors, likely due to enriched acetylation marks of the histone H3 lysine 27 at regions including the SPARC promoter and potential enhancers. Then, we used SPARC-edited Ewing sarcoma cells (A673 line) to demonstrate that SPARC knocked down (KD) cells accumulated significantly less amount of nab-paclitaxel in vitro than SPARC wild type (WT) cells. In vivo, SPARC KD and SPARC WT subcutaneous xenografts in mice achieved similar maximum intratumoral concentrations of nab-paclitaxel, though drug clearance from SPARC WT tumors was significantly slower. We confirmed such SPARC-mediated long-term intratumoral accumulation of nab-paclitaxel in Ewing sarcoma PDX with high expression of SPARC, which accumulated significantly more nab-paclitaxel than SPARC-low PDX. SPARC-high PDX responded better to nab-paclitaxel than SPARC-low tumors, although these results should be taken cautiously, given that the PDXs were established from different patients that could have specific determinants predisposing response to paclitaxel. In addition, SPARC KD Ewing sarcoma xenografts responded better to soluble docetaxel and paclitaxel than to nab-paclitaxel, while SPARC WT ones showed similar response to soluble and albumin-carried drugs. Overall, our results show that pediatric sarcomas expressing SPARC accumulate nab-paclitaxel for longer periods of time, which could have clinical implications for chemotherapy efficacy.

PMID:34974029 | DOI:10.1016/j.jconrel.2021.12.035
Systems Approaches in the Common Metabolomics in Acute Lymphoblastic Leukemia and Rhabdomyosarcoma Cells: A Computational Approach

Fetched: January 2nd, 2022, 5:01am GMT by Tselios C

Adv Exp Med Biol. 2021;1338:55-66. doi: 10.1007/978-3-030-78775-2_8.

ABSTRACT

Acute lymphoblastic leukemia is the most common childhood malignancy. Rhabdomyosarcoma, on the other hand, is a rare type of malignancy which belongs to the primitive neuroectodermal family of tumors. The aim of the present study was to use computational methods in order to examine the similarities and differences of the two different tumors using two cell lines as a model, the T-cell acute lymphoblastic leukemia CCRF-CEM and rhabdomyosarcoma TE-671, and, in particular, similarities of the metabolic pathways utilized by two different cell types in vitro. Both cell lines were studied using microarray technology. Differential expression profile has revealed genes with similar expression, suggesting that there are common mechanisms between the two cell types, where some of these mechanisms are preserved from their ancestor embryonic cells. Expression of identified species was modeled using known functions, in order to find common patterns in metabolism-related mechanisms. Species expression manifested very interesting dynamics, and we were able to model the system with elliptical/helical functions. We discuss the results of our analysis in the context of the commonly occurring genes between the two cell lines and the respective participating pathways as far as extracellular signaling and cell cycle regulation/proliferation are concerned. In the present study, we have developed a methodology, which was able to unravel some of the underlying dynamics of the metabolism-related species of two different cell types. Such approaches could prove useful in understanding the mechanisms of tumor ontogenesis, progression, and proliferation.

PMID:34973010 | DOI:10.1007/978-3-030-78775-2_8
Guide for paediatric radiotherapy procedures

Fetched: January 1st, 2022, 5:01am GMT by A Laprie

Cancer Radiother. 2021 Dec 27:S1278-3218(21)00308-5. doi: 10.1016/j.canrad.2021.11.018. Online ahead of print.

ABSTRACT

A third of children with cancer receive radiotherapy as part of their initial treatment, which represents 800 paediatric irradiations per year in France carried out in 15 specialized centres approved on the recommendations of the French national cancer institute in decreasing order of frequency, the types of cancer that require irradiation are: brain tumours, neuroblastomas, Ewing's sarcomas, Hodgkin's lymphomas, soft tissue sarcomas including rhabdomyosarcomas, and nephroblastomas. The treatment guidelines follow the recommendations of the French society for childhood cancers (SFCE) or the French and European prospective protocols. The therapeutic indications, the technical and/and ballistic choices of complex cases are frequently discussed during bimonthly paediatric radiotherapy technical web-conferences. All cancers combined, overall survival being 80%, long-term toxicity logically becomes an important concern, making the preparation of treatments complex. The irradiation methods include all the techniques currently available: 3D conformational irradiation, intensity modulation radiation therapy, irradiation under normal or hypofractionated stereotaxic conditions, brachytherapy and proton therapy. We present the update of the recommendations of the French society for radiation oncology on the indications, the technical methods of realization and the organisation and the specificities of paediatric radiation oncology.

PMID:34969622 | DOI:10.1016/j.canrad.2021.11.018
Surgical treatment for extremity rhabdomyosarcoma: longitudinal national questionnaire survey in Japan

Fetched: December 29th, 2021, 5:01am GMT by Yoshihiro Nishida

Jpn J Clin Oncol. 2021 Dec 29:hyab206. doi: 10.1093/jjco/hyab206. Online ahead of print.

ABSTRACT

BACKGROUND: Extremity rhabdomyosarcoma differs from other soft tissue sarcomas, being highly sensitive to chemotherapy and radiotherapy and having a high rate of metastasis to lymph nodes. Therefore, the treatment modality differs from that of other soft tissue sarcomas. The purpose of this study was to conduct a longitudinal questionnaire survey of orthopedic oncologists in charge of surgical treatment for extremity rhabdomyosarcoma in Japan to determine whether the treatment modality chosen here is in line with the international and national treatment ones.

METHODS: Questionnaire surveys were conducted in 2012 and 2019 to orthopedic oncologists of Japanese Orthopaedic Association and Japanese Musculoskeletal Oncology Group.

RESULTS: Responses were obtained from 80 facilities and 76 facilities, respectively. Fewer than 50% of the facilities treated one or more patients a year in both years. Many facilities first performed diagnostic biopsy, but most did not perform pretreatment re-excision. The number of facilities that provided radiotherapy in addition to surgery increased significantly from 2012 to 2019 (P = 0.028), but it was still 21% in 2019. The number of facilities performing excision and lymph node dissection was 19% in both 2012 and 2019, which was a very low result without improvement. The departments responsible for follow-up have been changed to pediatrics and orthopedic oncology in tandem (P = 0.0004).

CONCLUSIONS: Radiotherapy and pathological evaluation of lymph nodes are important for improving the prognosis of patients with extremity rhabdomyosarcoma. It is necessary to continue and develop more efficient educational activities on the appropriate medical treatment modalities for extremity RMS.

PMID:34963137 | DOI:10.1093/jjco/hyab206
Comment on: Patients with nonmetastatic embryonal rhabdomyosarcoma arising in the biliary tract should be treated on low-risk clinical trials

Fetched: December 29th, 2021, 5:01am GMT by Jamie M Aye

Pediatr Blood Cancer. 2021 Dec 28:e29554. doi: 10.1002/pbc.29554. Online ahead of print.

NO ABSTRACT

PMID:34962698 | DOI:10.1002/pbc.29554
Mechanism of Action of the Sesquiterpene Compound Helenalin in Rhabdomyosarcoma Cells

Fetched: December 29th, 2021, 5:01am GMT by Hakmin Mun

Pharmaceuticals (Basel). 2021 Dec 2;14(12):1258. doi: 10.3390/ph14121258.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in paediatric patients. Relapsed or refractory RMS shows very low 5-year survival rates, which urgently necessitates new chemotherapy agents. Herein, the sesquiterpene lactone, helenalin, was investigated as a new potential therapeutic agent against the embryonal RMS (eRMS) and alveolar RMS (aRMS) cells. We have evaluated in vitro antiproliferative efficacy of helenalin on RMS cells by the MTT and wound healing assay, and estimated several cell death pathways by flow cytometry, confocal microscopy and immunoblotting. It was shown that helenalin was able to increase reactive oxygen species levels, decrease mitochondrial membrane potential, trigger endoplasmic reticulum stress and deactivate the NF-κB pathway. Confirmation was obtained through the use of antagonistic compounds which alleviated the effects of helenalin in the corresponding pathways. Our findings demonstrate that oxidative stress is the pivotal mechanism of action of helenalin in promoting RMS cell death in vitro.

PMID:34959659 | PMC:PMC8703838 | DOI:10.3390/ph14121258
Selective BH3 mimetics synergize with BET inhibition to induce mitochondrial apoptosis in rhabdomyosarcoma cells

Fetched: December 29th, 2021, 5:01am GMT by Ufuk Erdogdu

Neoplasia. 2022 Feb;24(2):109-119. doi: 10.1016/j.neo.2021.11.012. Epub 2021 Dec 24.

ABSTRACT

BH3 mimetics are promising novel anticancer therapeutics. By selectively inhibiting BCL-2, BCL-xL, or MCL-1 (i.e. ABT-199, A-1331852, S63845) they shift the balance of pro- and anti-apoptotic proteins in favor of apoptosis. As Bromodomain and Extra Terminal (BET) protein inhibitors promote pro-apoptotic rebalancing, we evaluated the potential of the BET inhibitor JQ1 in combination with ABT-199, A-1331852 or S63845 in rhabdomyosarcoma (RMS) cells. The strongest synergistic interaction was identified for JQ1/A-1331852 and JQ1/S63845 co-treatment, which reduced cell viability and long-term clonogenic survival. Mechanistic studies revealed that JQ1 upregulated BIM and NOXA accompanied by downregulation of BCL-xL, promoting pro-apoptotic rebalancing of BCL-2 proteins. JQ1/A-1331852 and JQ1/S63845 co-treatment enhanced this pro-apoptotic rebalancing and triggered BAK- and BAX-dependent apoptosis since a) genetic silencing of BIM, BAK or BAX, b) inhibition of caspase activity with zVAD.fmk and c) overexpression of BCL-2 all rescued JQ1/A-1331852- and JQ1/S63845-induced cell death. Interestingly, NOXA played a different role in both treatments, as genetic silencing of NOXA significantly rescued from JQ1/A-1331852-mediated apoptosis but not from JQ1/S63845-mediated apoptosis. In summary, JQ1/A-1331852 and JQ1/S63845 co-treatment represent new promising therapeutic strategies to synergistically trigger mitochondrial apoptosis in RMS.

PMID:34959030 | PMC:PMC8718565 | DOI:10.1016/j.neo.2021.11.012
Evolving classification of rhabdomyosarcoma

Fetched: December 28th, 2021, 5:01am GMT by Narasimhan P Agaram

Histopathology. 2022 Jan;80(1):98-108. doi: 10.1111/his.14449.

ABSTRACT

Rhabdomyosarcomas comprise the single largest category of soft tissue sarcomas in children and adolescents in the United States, occurring in 4.5 million people aged below 20 years. Based on the clinicopathological features and genetic abnormalities identified, rhabdomyosarcomas are classified into embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. Each subtype shows distinctive morphology and has characteristic genetic abnormalities. This review discusses the evolution of the classification of rhabdomyosarcoma to the present day, together with a discussion of key histomorphological and genetic features of each subtype and the diagnostic approach to these tumours.

PMID:34958505 | DOI:10.1111/his.14449
Primary de-differentiated, trans-differentiated and undifferentiated melanomas: overview of the clinicopathological, immunohistochemical and molecular spectrum

Fetched: December 28th, 2021, 5:01am GMT by Ingrid Ferreira

Histopathology. 2022 Jan;80(1):135-149. doi: 10.1111/his.14545.

ABSTRACT

Primary cutaneous and mucosal melanoma shows a wide histological spectrum. The correct diagnosis depends upon the demonstration of melanocytic differentiation by recognition of an associated in-situ component or immunohistochemical evidence of a melanocytic phenotype using conventional melanocytic markers, such as S-100, SOX10, Melan-A and HMB-45. Exceptionally, melanomas lose their melanocytic phenotype, at least focally, and show differentiation towards other lineages. Review of the literature shows that de- and trans-differentiation in melanoma is rare but probably under-recognised and under-reported. These often large and frequently ulcerated tumours affect adults and show a wide anatomical distribution, including mucosal sites, although there is a predilection for sun-damaged skin of the head and neck. Histologically, the tumours are biphasic and contain a pre-existing conventional melanoma. The de-differentiated component closely resembles atypical fibroxanthoma, both morphologically and immunohistochemically. Trans-differentiated melanoma may show rhabdomyosarcomatous or spindle cell carcinomatous features. Undifferentiated melanomas are similar tumours in which the conventional melanoma component is absent. Their diagnosis depends entirely upon the clinical context and identification of a classical melanoma driver gene mutation, i.e. BRAF V600E. The diagnosis of these rare and unusual tumours is challenging, and requires thorough tumour sampling and recognition of the background of a pre-existing but often focal conventional melanoma together with molecular analysis.

PMID:34958502 | DOI:10.1111/his.14545
Abol-Enein pouch modification after radical cystectomy in bladder rhabdomyosarcoma in 5 years old child during COVID-19 pandemic: A case report

Fetched: December 28th, 2021, 5:01am GMT by Jeremy Thompson Ginting

Int J Surg Case Rep. 2022 Jan;90:106701. doi: 10.1016/j.ijscr.2021.106701. Epub 2021 Dec 20.

ABSTRACT

OBJECTIVE: To discuss the consideration of performing radical cystectomy for rhabdomyosarcoma in children during the COVID-19 pandemic in the urology department of Adam Malik Hospital, Medan.

INTRODUCTION: Rhabdomyosarcoma is a rare malignancy that develops from primitive mesenchymal stem cells. The gold standard for the treatment of rhabdomyosarcoma is radical cystectomy. However, during the COVID-19 pandemic, radical cystectomy becomes a concern due to the risk of virus transmission. This article reported a patient who underwent radical cystectomy during the COVID-19 pandemic.

CASE PRESENTATION: A five-year-old female child was admitted to the hospital with chief complaints of bloody urine 1 month before admission. A month before hospital admission, the patient had pain during urination and was treated with radical cystectomy with Abol-Enein pouch modification.

RESULT: After the surgery, the patient was able to urinate without any disturbance. Hematuria was not found. There was no complaint related to stricture of the ureter after the surgery.

CONCLUSION: In our center, radical cystectomy could be performed in child with bladder rhabdomyosarcoma during COVID-19 pandemic. The procedure is considered a high priority therapy in most regions during COVID-19 pandemic. Abol-Enein technique after radical cystectomy resulted in improvement of symptom with no reported complication in our case.

PMID:34956826 | PMC:PMC8686445 | DOI:10.1016/j.ijscr.2021.106701
Isolation and Identification of Andrographis paniculata (Chuanxinlian) and Its Biologically Active Constituents Inhibited Enterovirus 71-Induced Cell Apoptosis

Fetched: December 28th, 2021, 5:01am GMT by Wen-Wan Chao

Front Pharmacol. 2021 Dec 8;12:762285. doi: 10.3389/fphar.2021.762285. eCollection 2021.

ABSTRACT

Aim: Andrographis paniculata (Burm. f.) Nees (also known as Chuanxinlian in Chinese) of Acanthaceae family is one of the Chinese herbs reputed to be effective in the treatment of inflammation, infection, cold, and fever. Enterovirus 71 (EV71) is one of the most important enteroviruses that cause hand, foot, and mouth disease (HFMD) accompanied with neurological complication. Methods: To explore an anti-infective Chinese herb medicine, pure compounds isolated or synthesized analogues from A. paniculata (AP) ethyl acetate (EtOAc) extract are used to explore their anti-EV71-induced cytotoxicity. The antiviral activity was determined by cytopathic effect (CPE) reduction, and sub-G1 assays were used for measuring lysis and apoptosis of EV71-infected rhabdomyosarcoma (RD) cells. IFNγ-driven luciferase reporter assay was used to evaluate their potential roles in activation of immune responses. Results: Our data showed that EV71-induced sub-G1 phase of RD cells was dose dependently increased. Highly apoptotic EV71-infected RD cells were reduced by AP extract treatment. Ergosterol peroxide (4) has the most anti-apoptotic effect among these seven compounds. In addition, 3,19-O-acetyl-14-deoxy-11,12-didehydroandrographolide (8) synthesized from acetylation of compound 7 showed significantly better antiviral activity and the lowest sub-G1 phase of 6%-18%. Further investigation of IFNγ-inducer activity of these compounds showed that compounds 3, 6, 10, 11, and 12 had significantly higher IFNγ luciferase activities, suggesting their potential to promote IFNγ expression and thus activate immune responses for antivirus function. Conclusion: Our study demonstrated that bioactive compounds of AP and its derivatives either protecting EV71-infected RD cells from sub-G1 arrest or possessing IFNγ-inducer activity might be feasible for the development of anti-EV71 agents.

PMID:34955832 | PMC:PMC8692857 | DOI:10.3389/fphar.2021.762285
Oncogenic NRAS Accelerates Rhabdomyosarcoma Formation When Occurring within a Specific Time Frame during Tumor Development in Mice

Fetched: December 25th, 2021, 5:01am GMT by Nada Ragab

Int J Mol Sci. 2021 Dec 13;22(24):13377. doi: 10.3390/ijms222413377.

ABSTRACT

In the Ptch+/- mouse model for embryonal rhabdomyosarcoma (ERMS), we recently showed that oncogenic (onc) H-, K- or NRAS mutations do not influence tumor growth when induced at the advanced, full-blown tumor stage. However, when induced at the invisible ERMS precursor stage at 4 weeks of age, tumor development was enforced upon oncHRAS and oncKRAS but not by oncNRAS, which instead initiated tumor differentiation. These data indicate that oncRAS-associated processes differ from each other in dependency on the isoform and their occurrence during tumor development. Here, we investigated the outcome of oncNRAS induction at an earlier ERMS precursor stage at 2 weeks of age. In this setting, oncNRAS accelerates tumor growth because it significantly shortens the ERMS-free survival and increases the ERMS incidence. However, it does not seem to alter the differentiation of the tumors. It is also not involved in tumor initiation. Together, these data show that oncNRAS mutations can accelerate tumor growth when targeting immature ERMS precursors within a specific time window, in which the precursors are permissive to the mutation and show that oncNRAS-associated processes differ from each other in dependency on their occurrence during tumor development.

PMID:34948179 | PMC:PMC8703790 | DOI:10.3390/ijms222413377
WT1 and Cyclin D1 Immunohistochemistry: A Useful Adjunct for Diagnosis of Pediatric Small Round Blue Cell Tumors on Small Biopsies

Fetched: December 25th, 2021, 5:01am GMT by Lucia Salvatorelli

Diagnostics (Basel). 2021 Dec 2;11(12):2254. doi: 10.3390/diagnostics11122254.

ABSTRACT

Pediatric small round blue cell tumors (SRBCTs) are a heterogeneous group of neoplasms with overlapping morphological appearance. Accordingly, their diagnosis is one of the most difficult in the field of surgical pathology. The most common tumors include rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma, lymphoblastic lymphoma and Wilms' tumor (the blastemal component). Over time their diagnosis has become more difficult due to the increasing use of small biopsies. However, the advent of immunohistochemistry has improved the quality of diagnosis in most cases by the application of an adequate panel of immunomarkers. Recently, WT1 and Cyclin D1 have been shown to be useful in the differential diagnosis of SRBCTs on surgically-resected specimens, showing a diffuse cytoplasmic positivity of the former in all RMSs and a diffuse nuclear staining of the latter in both EWS and NB. The aim of the present study was to investigate the expression of WT1 and Cyclin D1 on small biopsies from a series of 105 pediatric SRBCTs to evaluate their diagnostic utility. Both immunomarkers were differentially expressed, with a diffuse and strong cytoplasmic staining for WT1 limited to all cases of RMS, and a diffuse nuclear staining for cyclin D1 restricted to all cases of EWS and NB. Notably, the expression of WT1 and cyclin D1 was also retained in those cases in which the conventional tumor markers (myogenin, desmin and MyoD1 for RMS; CD99 for EWS; NB84 for NB) were focally expressed or more rarely absent. The present study shows that WT1 and Cyclin D1 are helpful immunomarkers exploitable in the differential diagnosis of pediatric SRBCTs on small biopsies, suggesting their applicability in routine practice.

PMID:34943491 | PMC:PMC8700162 | DOI:10.3390/diagnostics11122254
Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity

Fetched: December 25th, 2021, 5:01am GMT by Francesca Rossi

Mol Cell. 2022 Jan 6;82(1):75-89.e9. doi: 10.1016/j.molcel.2021.11.032. Epub 2021 Dec 22.

ABSTRACT

Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response.

PMID:34942120 | PMC:PMC8751636 | DOI:10.1016/j.molcel.2021.11.032
Risk of Malignant Transformation Arising From Giant Congenital Melanocytic Nevi: A 20-year Single-center Study

Fetched: December 23rd, 2021, 5:01am GMT by Ji-Young Kim

Dermatol Surg. 2021 Dec 21. doi: 10.1097/DSS.0000000000003341. Online ahead of print.

ABSTRACT

BACKGROUND: Although giant congenital melanocytic nevus (GCMN) is regarded as premalignant, the incidence and risk factors of malignant transformation are controversial.

OBJECTIVE: This study aimed to share the authors' surgical experience with GCMNs and provide data on their demographics, malignant transformation, and prognosis.

METHODS: This single-center, consecutive study included 152 patients with GCMN who visited this center from March 2000 to February 2020. Their medical documentation was reviewed retrospectively, and the nevi were classified according to the size as follows: Group 1, 10 to 19.9 cm (n = 45); Group 2, 20 to 39.9 cm (n = 62); and Group 3, ≥40 cm (n = 45).

RESULTS: Seven malignancies were found (4.6%; 4 melanomas, 2 rhabdomyosarcomas [RMS], and 1 malignant peripheral nerve sheath tumor [MPNST]). The risk increased according to the nevus size (2.2% in Group 1, 3.2% in Group 2, and 8.9% in Group 3) but the difference was not statistically significant (p = .3305).

CONCLUSION: Malignant transformation from GCMN cannot be ignored. It can include transformation into melanoma, RMS, and MPNST. Early surgical resection and regular follow-up should be performed in patients with nevi ≥10 cm.

PMID:34935754 | DOI:10.1097/DSS.0000000000003341
Expression of Programmed Cell Death-L1 (PD-L1) Protein and Mismatch Repair Mutations in Orbital Tumours-a Pilot Study

Fetched: December 22nd, 2021, 5:01am GMT by Mohammad A AlSemari

Eur J Ophthalmol. 2021 Dec 21:11206721211066203. doi: 10.1177/11206721211066203. Online ahead of print.

ABSTRACT

PURPOSE: Programmed cell death protein 1 (PD-1) and DNA mismatch repair (MMR) deficiency play an important role in tumour progression and response to treatment.Both markers have been studied in some ocular tumours but little is known about these markers in orbital tumours. This pilot study reports on PD-L1 expression and MMR mutations using next generation sequencing (NGS) in specific orbital tumours.

METHODS: We reviewed surgical specimens from patients with rhabdomyosarcoma, adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA) and biopsy negative tissue from orbital tumours used as a control. immunohistochemistry (IHC) was performed on Formalin fixed paraffin embedded tissue using a PD-L1 antibody. DNA was extracted for targeted gene panel NGS of the MMR genes PMS2, MLH1, MSH6 and MSH2.

RESULTS: The study included 17 orbital specimens. Scattered membrane PD-L1 staining was noted in 3/6 rhabdomyosarcoma specimens without an accompanying lymphocytic infiltrate. PD-L1 immunostaining was absent in 3/3 ACC, and 5/6 PA specimens. PD-L1 immunostaining was not detected in 2/2 control specimens. 4/17 samples shared the same pathogenic mutation in the MLH1 gene, including 3/6 rhabdomyosarcoma and 1/3 ACC samples. 1/6 PA samples had a mutation in MSH6.

CONCLUSIONS: Our study demonstrated scattered, non-quantifiable or absent PD-L1 staining in a limited sample of orbital tumours suggesting that PD-1/PD-L1 inhibitor therapy may not be useful in treatment of malignant orbital tumours (rhabdomyosarcoma and ACC) when refractory to conventional therapy. Our pilot study suggest that PD-L1/MMR axis might not play a major role in the pathogenesis of primary orbital tumour.

PMID:34931541 | DOI:10.1177/11206721211066203
Clinical characteristics of perianal/perineal rhabdomyosarcoma-a report of 15 cases

Fetched: December 20th, 2021, 5:01am GMT by Y Y Guo

Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Dec 25;24(12):1100-1103. doi: 10.3760/cma.j.cn441530-20200407-00190.

NO ABSTRACT

PMID:34923795 | DOI:10.3760/cma.j.cn441530-20200407-00190
Primary Small Cell Malignancies of the Breast: Are They Rare Malignancies?

Fetched: December 20th, 2021, 5:01am GMT by Kemal Behzatoğlu

Acta Cytol. 2021 Dec 17:1-10. doi: 10.1159/000520875. Online ahead of print.

ABSTRACT

In contrast with the other organs such as the lung, small cell tumors have been less studied in the breast due to their relatively less frequency. Although rare, neuroendocrine neoplasms, some lymphomas, and some small cell sarcomas such as undifferentiated small round cell sarcoma and rhabdomyosarcoma can be seen in small cell morphology in the breast. Many cytological specimens such as fine-needle aspiration biopsies and touch imprint cytology are used for diagnosis and further prognostic/predictive marker determination in primary breast masses, sentinel and axillary lymph nodes, and metastatic masses. Lobular carcinoma deserves to be considered in the small cell tumor group because of its small, monomorphic, discohesive, scant cytoplasmic cytological features. Since so many different types of tumors in the breast can have small cell characteristics, they should be divided into small cell neuroendocrine tumors and small cell nonneuroendocrine tumors. When evaluating small cell breast tumors cytologically, wide tumor diversity should be kept in mind, and clinical, hematological, and radiological features should be taken into consideration.

PMID:34923492 | DOI:10.1159/000520875
Metastatic paratesticular rhabdomyosarcoma: A case report

Fetched: December 18th, 2021, 5:01am GMT by Mokhtari Mohamed

Urol Case Rep. 2021 Dec 6;41:101977. doi: 10.1016/j.eucr.2021.101977. eCollection 2022 Mar.

ABSTRACT

Paratesticular rhabdomyosarcoma (PRMS) is a rare and aggressive tumor in children and adolescents. Clinically, it is often revealed by the accidental discovery of a large painless bursa. The therapeutic strategy depends on the stage of the tumor and on the prognostic group according to the Intergroup Rhabdomyosarcoma Study (IRS) classification. We report the case of a patient treated in our institution for a paratesticular rhabdomyosarcoma of the embryonic type discovered at a late stage in an adolescent, with the aim of confirming the fatal evolution of this pathology with "awful" metastatic potential.

PMID:34917481 | PMC:PMC8666333 | DOI:10.1016/j.eucr.2021.101977
Clinical analysis of testicular rhabdomyosarcoma

Fetched: December 18th, 2021, 5:01am GMT by J F Ye

Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Dec 18;53(6):1178-1182. doi: 10.19723/j.issn.1671-167X.2021.06.028.

ABSTRACT

Testicular rhabdomyosarcoma is relatively rare in testicular tumors, but the age of patient is relatively young and the degree of malignancy is high. Therefore, this article introduces 4 cases of testicular rhabdomyosarcoma who were admitted to Peking University Third Hospital from May 1994 to February 2019, and reviews the literature to improve the diagnosis and treatment of this disease. The average age of the 4 patients was 17.5 years (14-21 years), the average hospital stay was 22.0 d (17-31 d), and the average body mass index was 19.6 kg/m² (14.7-25.8 kg/m²). All the patients underwent routine preoperative blood and urine routine, biochemical tests, as well as serum tumor markers. Preoperative examinations also included chest radiograph, electrocardiogram, ultrasound of the scrotum and groin, and abdominal enhanced CT. Lung CT or other examinations were performed if necessary. The median serum human chorionic gonadotropin (HCG) of the 4 patients was 0.20 IU/L (0.06-0.86 IU/L) (all normal), and the median serum alpha-fetoprotein (AFP) was 1.03 g/L (0.65-1.66 g/L) (all normal). The average maximum diameter of the tumor was 10.0 cm (4.5-15.0 cm). Testicular rhabdomyosarcoma was mainly diagnosed by pathology. The main treatment was radical orchiectomy combined with retroperitoneal lymph node dissection, with or without postoperative adjuvant chemotherapy. The clinical manifestations of the patients with testicular rhabdomyosarcoma had no specific characteristics, but most patients were young at onset with mainly painless masses in the testicles, which were already large when they were found. Patients with testicular rhabdomyosarcoma have a poor prognosis, most of whom recur within two years. Because of the small number of cases of testicular rhabdomyosarcoma, there is no standard treatment currently. It is recommended that patients with testicular rhabdomyosarcoma undergo radical testicular resection combined with retroperitoneal lymph node dissection. Retroperitoneal lymph node metastasis is an important prognostic factor, and patients with postoperative adjuvant chemotherapy can still survive for a longer time. If local recurrence or limited metastasis is found after operation, local resection and salvage radiotherapy are feasible.

PMID:34916701 | PMC:PMC8695152 | DOI:10.19723/j.issn.1671-167X.2021.06.028
An Analysis of 20 Cases of Radiation-Associated Sarcoma, Including 4 Cases Treated by Carbon Ion Radiotherapy

Fetched: December 17th, 2021, 5:01am GMT by Takahito Negishi

Oncology. 2021 Dec 16. doi: 10.1159/000521504. Online ahead of print.

ABSTRACT

Introduction Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. Methods We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). Results The primary diseases targeted by radiotherapy included malignant lymphoma (n=4), cervical cancer (n=3), pharyngeal cancer (n=3), breast cancer (n=2), lung cancer (n=1), rectal cancer (n=1), maxillary cancer (n=1), synovial sarcoma (n=1), and benign neoplasms (n=4). The histological diagnoses of RAS included osteosarcoma (n=8), leiomyosarcoma (n=3), undifferentiated pleomorphic sarcoma (n=3), rhabdomyosarcoma (n=1), angiosarcoma (n=1), malignant peripheral nerve sheath tumor (n=1), spindle cell sarcoma NOS (n=1), and sarcoma not further specified (n=2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a continuous disease free status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced Grade 3 toxicities that required surgical treatment. Conclusion RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.

PMID:34915507 | DOI:10.1159/000521504
Phenotypic similarities within the morphologic spectrum of DICER1-associated sarcomas and pleuropulmonary blastoma: Histopathologic features guide diagnosis in the LMIC setting

Fetched: December 17th, 2021, 5:01am GMT by Paromita Roy

Pediatr Blood Cancer. 2021 Dec 16:e29466. doi: 10.1002/pbc.29466. Online ahead of print.

ABSTRACT

Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracranial and genital tract sarcomas, suspected to have DS based on a heterogeneous yet defining combination of spindle-cell sarcomatous and blastemal morphology, with rhabdomyomatous differentiation. Foci of immature cartilage at diagnosis (n = 2/3) and increased neuroepithelial differentiation at recurrence (n = 1) were noted. Morphological suspicion prompted somatic testing at reference centers, confirming likely biallelic, loss-of-function, and "hotspot" missense DICER1 variants in all three tumors. This can serve as a model for this diagnosis in resource-limited settings and has implications for germline testing, surveillance, and tumor management.

PMID:34913555 | DOI:10.1002/pbc.29466
Incidental Discovery of Embryonal Rhabdomyosarcoma on CT Imaging

Fetched: December 17th, 2021, 5:01am GMT by Esha Jain

Eur J Case Rep Intern Med. 2021 Nov 24;8(11):002834. doi: 10.12890/2021_002834. eCollection 2021.

ABSTRACT

Rhabdomyosarcoma is an uncommon soft tissue sarcoma that rarely presents in adults. Clinical presentation is dependent on site and size. We present the case of a woman who presented with acute-onset dyspnoea and whose pathology report confirmed embryonal rhabdomyosarcoma (ERMS) seen as an incidental finding on chest computed tomography. We also describe the clinical, laboratory and radiological work-up conducted to diagnose and manage ERMS in the critical care setting.

LEARNING POINTS: Rhabdomyosarcoma is a rare malignancy with a poor prognosis in adults compared with children, especially if it presents in an unfavourable primary site and has an unfavourable histological diagnosis.Immunohistochemical diagnosis remains the gold standard for embryonal rhabdomyosarcoma diagnosis and differentiation from similar malignancies on initial imaging studies.Management of adult rhabdomyosarcoma is usually multimodal with surgical resection and a combination of chemo and radiotherapy.

PMID:34912733 | PMC:PMC8668012 | DOI:10.12890/2021_002834
DICER1-associated hepatic cystic neoplasm with pleuropulmonary blastoma-like features: a novel clinicopathologic diagnosis

Fetched: December 16th, 2021, 5:01am GMT by Sarah G Mitchell

Mod Pathol. 2021 Dec 14. doi: 10.1038/s41379-021-00947-y. Online ahead of print.

ABSTRACT

This report documents a unique multicystic neoplasm of the liver in an 8-month-old boy with a heterozygous germline pathogenic DICER1 variant. This neoplasm, initially considered most likely a mesenchymal hamartoma based on imaging, demonstrated the characteristic histologic pattern of embryonal rhabdomyosarcoma residing in the subepithelial or cambium layer-like zone of the epithelial-lined cysts. Thus, although the differential diagnosis includes mesenchymal hamartoma, a young child with a multicystic mass lesion in the liver, lung, or kidney should both raise the possibility of a germline pathogenic DICER1 variant and also not be mistaken for one of the other hepatic neoplasms of childhood.

PMID:34907324 | DOI:10.1038/s41379-021-00947-y
Co-targeting MCL-1 and ERK1/2 kinase induces mitochondrial apoptosis in rhabdomyosarcoma cells

Fetched: December 16th, 2021, 5:01am GMT by Marius Winkler

Transl Oncol. 2022 Feb;16:101313. doi: 10.1016/j.tranon.2021.101313. Epub 2021 Dec 11.

ABSTRACT

The RAS/MEK/ERK genetic axis is commonly altered in rhabdomyosarcoma (RMS), indicating high activity of downstream effector ERK1/2 kinase. Previously, we have demonstrated that inhibition of the RAS/MEK/ERK signaling pathway in RMS is insufficient to induce cell death due to residual pro-survival MCL-1 activity. Here, we show that the combination of ERK1/2 inhibitor Ulixertinib and MCL-1 inhibitor S63845 is highly synergistic and induces apoptotic cell death in RMS in vitro and in vivo. Importantly, Ulixertinib/S63845 co-treatment suppresses long-term survival of RMS cells, induces rapid caspase activation and caspase-dependent apoptosis. Mechanistically, Ulixertinib-mediated upregulation of BIM and BMF in combination with MCL-1 inhibition by S63845 shifts the balance of BCL-2 proteins towards a pro-apoptotic state resulting in apoptosis induction. A genetic silencing approach reveals that BIM, BMF, BAK and BAX are all required for Ulixertinib/S63845-induced apoptosis. Overexpression of BCL-2 rescues cell death triggered by Ulixertinib/S63845 co-treatment, confirming that combined inhibition of ERK1/2 and MCL-1 effectively induces cell death of RMS cells via the intrinsic mitochondrial apoptotic pathway. Thus, this study is the first to demonstrate the cytotoxic potency of co-inhibition of ERK1/2 and MCL-1 for RMS treatment.

PMID:34906889 | PMC:PMC8681038 | DOI:10.1016/j.tranon.2021.101313
Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth

Fetched: December 16th, 2021, 5:01am GMT by Rupesh Shrestha

J Exp Clin Cancer Res. 2021 Dec 14;40(1):392. doi: 10.1186/s13046-021-02199-9.

ABSTRACT

BACKGROUND: Flavonoids exhibit both chemopreventive and chemotherapeutic activity for multiple tumor types, however, their mechanisms of action are not well defined. Based on some of their functional and gene modifying activities as anticancer agents, we hypothesized that kaempferol and quercetin were nuclear receptor 4A1 (NR4A1, Nur77) ligands and confirmed that both compounds directly bound NR4A1 with KD values of 3.1 and 0.93 μM, respectively.

METHODS: The activities of kaempferol and quercetin were determined in direct binding to NR4A1 protein and in NR4A1-dependent transactivation assays in Rh30 and Rh41 rhabdomyosarcoma (RMS) cells. Flavonoid-dependent effects as inhibitors of cell growth, survival and invasion were determined in XTT and Boyden chamber assays respectively and changes in protein levels were determined by western blots. Tumor growth inhibition studies were carried out in athymic nude mice bearing Rh30 cells as xenografts.

RESULTS: Kaempferol and quercetin bind NR4A1 protein and inhibit NR4A1-dependent transactivation in RMS cells. NR4A1 also regulates RMS cell growth, survival, mTOR signaling and invasion. The pro-oncogenic PAX3-FOXO1 and G9a genes are also regulated by NR4A1 and, these pathways and genes are all inhibited by kaempferol and quercetin. Moreover, at a dose of 50 mg/kg/d kaempferol and quercetin inhibited tumor growth in an athymic nude mouse xenograft model bearing Rh30 cells.

CONCLUSION: These results demonstrate the clinical potential for repurposing kaempferol and quercetin for clinical applications as precision medicine for treating RMS patients that express NR4A1 in order to increase the efficacy and decrease dosages of currently used cytotoxic drugs.

PMID:34906197 | PMC:PMC8670039 | DOI:10.1186/s13046-021-02199-9

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