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PubMed - Neuroendocrine Tumor (91 unread)

A rare case of life-threatening giant plexiform schwannoma.

Fetched: May 20th, 2012, 11:00pm MDT

A rare case of life-threatening giant plexiform schwannoma.

Spine J. 2012 Jan;12(1):83

Authors: Capone F, Pravatà E, Novello M, Moncelsi S, Pirronti T, Meglio M, Servidei S

PMID: 22209242 [PubMed - indexed for MEDLINE]

Off-resonance plasmonic enhanced femtosecond laser optoporation and transfection of cancer cells.

Fetched: May 20th, 2012, 11:00pm MDT

Off-resonance plasmonic enhanced femtosecond laser optoporation and transfection of cancer cells.

Biomaterials. 2012 Mar;33(7):2345-50

Authors: Baumgart J, Humbert L, Boulais É, Lachaine R, Lebrun JJ, Meunier M

Abstract
A femtosecond laser based transfection method using off-resonance plasmonic gold nanoparticles is described. For human cancer melanoma cells, the treatment leads to a very high perforation rate of 70%, transfection efficiency three times higher than for conventional lipofection, and very low toxicity (<1%). Off-resonance laser excitation inhibited the fracture of the nanoparticles into possibly toxic DNA intercalating particles. This efficient and low toxicity method is a promising alternative to viral transfection for skin cancer treatment.

PMID: 22177619 [PubMed - indexed for MEDLINE]

Face skin neoplasms--reasons for delayed treatment.

Fetched: May 20th, 2012, 11:00pm MDT

Face skin neoplasms--reasons for delayed treatment.

Pol Przegl Chir. 2011 Jul;83(7):361-6

Authors: Antoszewski B, Kasielska A, Fijałkowska M

Abstract
UNLABELLED: The most common skin neoplasms are carcinoma: basocellulare, spinocellulare, planoepitheliale and melanoma malignum. Early surgical treatment is crucial for recovery as well as for good aesthetic result, especially on exposed body parts. All those lesions are visible for observers and the time from their appearance to surgical treatment seems to be too long. The aim of the study was to answer the following questions: 1. After what time from the skin lesion appearance the patients report to a surgeon? 2. What is the underlying cause of delayed reporting for treatment of patients with skin lesions?
MATERIAL AND METHODS: Questionnaire studies and analysis of medical histories were performed in the group of patients referred to Plastic Surgery Out-Patient Clinic in Łódź because of facial skin tumor in the last 5 years. Finally we collected data for 123 patients.
RESULTS: The analyzed group consisted mostly of men (n=72). The age of respondents ranged from 45 to 92 years, mean 69.9 years ± 10.8 years. Mean time from observing lesion to the first medical consultation was 7.3 months and to visiting our Out-Patient Clinic was 2.7 years (ranged from 3 months to 16 years). All patients were qualified to surgical excision of tumor. Histopathological verification confirmed diagnosis of malignant neoplasms in 116 patients. In question concerning causes of delay in medical consultation or treatment, all respondents answered that fear of surgical procedure was one of the reasons.
CONCLUSIONS: Fear of surgical treatment is the most common cause of delay in patients' visiting doctor. In our society conviction of neoplasm spreading after surgical excision is common, especially among elderly.

PMID: 22166663 [PubMed - indexed for MEDLINE]

Permalink for 'Popliteal sentinel lymph node biopsy is important in malignant melanoma of the distal lower extremities: a case report of acral lentiginous melanoma with simultaneous inguinal and popliteal lymph node micrometastases.'

Popliteal sentinel lymph node biopsy is important in malignant melanoma of the distal lower extremities: a case report of acral lentiginous melanoma with simultaneous inguinal and popliteal lymph node micrometastases.

Fetched: May 20th, 2012, 11:00pm MDT

Popliteal sentinel lymph node biopsy is important in malignant melanoma of the distal lower extremities: a case report of acral lentiginous melanoma with simultaneous inguinal and popliteal lymph node micrometastases.

Eur J Dermatol. 2012 Jan-Feb;22(1):135-6

Authors: Kaku Y, Tanioka M, Tanizaki H, Miyachi Y

PMID: 22157852 [PubMed - indexed for MEDLINE]

Catecholamine-induced cardiomyopathy and paraganglioneuroma in a pediatric patient.

Fetched: May 20th, 2012, 11:00pm MDT

Catecholamine-induced cardiomyopathy and paraganglioneuroma in a pediatric patient.

Anadolu Kardiyol Derg. 2011 Dec;11(8):743-4

Authors: Narin N, Baykan A, Sezer S, Onan SH, Uzüm K, Küçükaydın M

PMID: 22137946 [PubMed - indexed for MEDLINE]

Intramuscular metastasis of malignant melanoma mimicking leg cellulitis.

Fetched: May 20th, 2012, 11:00pm MDT

Intramuscular metastasis of malignant melanoma mimicking leg cellulitis.

Eur J Dermatol. 2012 Jan-Feb;22(1):156-7

Authors: Ikawa T, Kasuya A, Ito T, Hirakawa S, Tokura Y

PMID: 22133451 [PubMed - indexed for MEDLINE]

Pigmented mammary Paget's disease mimicking melanoma: report of three cases.

Fetched: May 20th, 2012, 11:00pm MDT

Pigmented mammary Paget's disease mimicking melanoma: report of three cases.

Eur J Dermatol. 2012 Jan-Feb;22(1):121-4

Authors: Hida T, Yoneta A, Nishizaka T, Ohmura T, Suzuki Y, Kameshima H, Yamashita T

Abstract
Pigmented mammary Paget's disease (PMPD) is a rare subtype of mammary Paget's disease. The differential diagnosis of PMPD and melanoma is difficult clinically and sometimes histopathologically. Here we present three cases of PMPD with a variable-sized lesion. All cases showed an irregular-shaped black-brown macule, one of which was accompanied by nipple retraction. Dermoscopically, all cases showed reticular pigmentation with or without irregular black dots, regression structures and streaks, which were indistinguishable from those of melanoma. In all but one of the cases, preoperative examinations confirmed the presence of a subcutaneous mammary lesion. All patients underwent a total mastectomy with the histopathological results indicating invasive ductal carcinoma. These cases emphasize how difficult it is to distinguish PMPD from melanoma. Dermoscopic features also mimic those of melanoma, but the reticular pigmentation seen in all cases could be a feature specific to PMPD. For suspicious cases, histopathological assessment using immunohistochemistry is highly recommended.

PMID: 22064040 [PubMed - indexed for MEDLINE]

Overexpression of autophagy-related beclin-1 in advanced malignant melanoma and its low expression in melanoma-in-situ.

Fetched: May 20th, 2012, 11:00pm MDT

Overexpression of autophagy-related beclin-1 in advanced malignant melanoma and its low expression in melanoma-in-situ.

Eur J Dermatol. 2012 Jan-Feb;22(1):128-9

Authors: Hara Y, Nakamura M

PMID: 22062628 [PubMed - indexed for MEDLINE]

Filamin-A as a marker and target for DNA damage based cancer therapy.

Fetched: May 20th, 2012, 11:00pm MDT

Filamin-A as a marker and target for DNA damage based cancer therapy.

DNA Repair (Amst). 2012 Feb 1;11(2):192-200

Authors: Yue J, Lu H, Liu J, Berwick M, Shen Z

Abstract
Filamin-A, also called actin binding protein 280 (ABP-280), cross-links the actin filaments into dynamic orthogonal network to serve as scaffolds in multiple signaling pathways. It has been reported that filamin-A interacts with DNA damage response proteins BRCA1 and BRCA2. Defects of filamin-A impair the repair of DNA double strand breaks (DSBs), resulting in sensitization of cells to ionizing radiation. In this study, we sought to test the hypothesis that filamin-A can be used as a target for cancer chemotherapy and as a biomarker to predict cancer response to therapeutic DNA damage. We found that reduction of filamin-A sensitizes cancer cells to chemotherapy reagents bleomycin and cisplatin, delays the repair of not only DSBs but also single strand breaks (SSBs) and interstrand crosslinks (ICLs), and increases chromosome breaks after the drug treatment. By treating a panel of human melanoma cell lines with variable filamin-A expression, we observed a correlation between expression level of filamin-A protein and drug IC(50). We further inhibited the expression of filamin-A in melanoma cells, and found that this confers an increased sensitivity to bleomycin and cisplatin treatment in a mouse xenograft tumor model. These results suggest that filamin-A plays a role in repair of a variety of DNA damage, that lack of filamin-A is a prognostic marker for a better outcome after DNA damage based treatment, and filamin-A can be inhibited to sensitize filamin-A positive cancer cells to therapeutic DNA damage. Thus filamin-A can be used as a biomarker and a target for DNA damage based cancer therapy.

PMID: 22051193 [PubMed - indexed for MEDLINE]

Permalink for 'Assessment of tumor hypoxia and interstitial fluid pressure by gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging.'

Assessment of tumor hypoxia and interstitial fluid pressure by gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging.

Fetched: May 20th, 2012, 11:00pm MDT

Assessment of tumor hypoxia and interstitial fluid pressure by gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging.

Radiother Oncol. 2011 Oct;101(1):217-22

Authors: Gulliksrud K, Hompland T, Galappathi K, Rofstad EK

Abstract
BACKGROUND AND PURPOSE: Extensive hypoxia and high interstitial fluid pressure (IFP) in the primary tumor may cause resistance to radiation treatment and promote metastatic spread. The potential of gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the extent of hypoxia and the level of interstitial hypertension in tumors was investigated in this preclinical study.
MATERIALS AND METHODS: Twenty-three A-07 tumors were subjected to DCE-MRI and subsequent measurement of IFP and fraction of pimonidazole-positive hypoxic tissue (HF(Pim)). Parametric tumor images of K(trans), v(e), and V(b)(Tofts) (Tofts model) and of K(i) and V(b)(Patlak) (Patlak model) were produced by pharmacokinetic analyses of the DCE-MRI series.
RESULTS: There was no correlation between IFP and HF(Pim) in the tumors. K(trans) and K(i) decreased significantly with increasing HF(Pim), whereas V(b)(Tofts) and V(b)(Patlak) increased significantly with increasing IFP.
CONCLUSION: Information on both the extent of hypoxia and the level of interstitial hypertension in A-07 tumors can be derived from a single DCE-MRI series by using gadomelitol as contrast agent.

PMID: 21840612 [PubMed - indexed for MEDLINE]

Regression of paclitaxel-induced maculopathy with oral acetazolamide.

Fetched: May 20th, 2012, 11:00pm MDT

Regression of paclitaxel-induced maculopathy with oral acetazolamide.

Graefes Arch Clin Exp Ophthalmol. 2012 Mar;250(3):463-4

Authors: Meyer KM, Klink T, Ugurel S, Bröcker EB

PMID: 21431400 [PubMed - indexed for MEDLINE]

[Submental flap for auricule reconstruction].

Fetched: May 20th, 2012, 11:00pm MDT

[Submental flap for auricule reconstruction].

Rev Laryngol Otol Rhinol (Bord). 2011;132(3):163-6

Authors: Bakhos D, Kim S, Morinière S, Darsonval V

Abstract
OBJECTIVE: We present our experience in the use of submental flap in reconstruction of post-auricular excision defects.
MATERIAL AND METHODS: Three patients underwent reconstruction with submental flap.
RESULTS: The submental flap has been used in 3 patients for auricular defect reconstruction. All patients had a carcinoma involving the auricle. All the donor site defects were closed primarily. Outcomes were simple. In one case, we noticed a partial necrosis of the flap extremity.
CONCLUSION: The submental flap produces excellent skin color and contour. It leaves a very well-hidden donor site. The operative technique makes it easy to use. So, the submental flap has definite advantages over distant flaps and it is a useful addition to the reconstruction in head and neck surgery.

PMID: 22533071 [PubMed - indexed for MEDLINE]

PET/CT with 68Gallium-DOTA-peptides in NET: an overview.

Fetched: May 20th, 2012, 11:00pm MDT

PET/CT with 68Gallium-DOTA-peptides in NET: an overview.

Eur J Radiol. 2011 Nov;80(2):e116-9

Authors: Ambrosini V, Campana D, Tomassetti P, Grassetto G, Rubello D, Fanti S

Abstract
In the present review article we presented the major technical innovations regarding the diagnosis of NET with PET/CT 68Ga-DOTA-peptides compounds over conventional radiologic and scintigraphic imaging, discussing both the different types of radiopharmaceuticals commercially available, trying to making a comparison on the possible advantages and drawbacks of these radiopharmaceuticals, and providing also some technical recommendations to the radiologists and nuclear physicians for using these new methodology in an appropriate manner in the clinical setting.

PMID: 20800401 [PubMed - indexed for MEDLINE]

Permalink for 'PAX8 Mouse Monoclonal Antibody [BC12] Recognizes a Restricted Epitope and Is Highly Sensitive in Renal Cell and Ovarian Cancers But Does Not Cross-react With B Cells and Tumors of Pancreatic Origin.'

PAX8 Mouse Monoclonal Antibody [BC12] Recognizes a Restricted Epitope and Is Highly Sensitive in Renal Cell and Ovarian Cancers But Does Not Cross-react With B Cells and Tumors of Pancreatic Origin.

Fetched: May 20th, 2012, 11:00pm MDT

PAX8 Mouse Monoclonal Antibody [BC12] Recognizes a Restricted Epitope and Is Highly Sensitive in Renal Cell and Ovarian Cancers But Does Not Cross-react With B Cells and Tumors of Pancreatic Origin.

Appl Immunohistochem Mol Morphol. 2012 May 16;

Authors: Tacha D, Qi W, Zhou D, Bremer R, Cheng L

Abstract
PAX8 is expressed in a high percentage of renal cell and ovarian cancers; however, the current existing anti-PAX8 rabbit polyclonal (P) antibodies also recognize B cells, pancreatic cancers, carcinoids, and some soft tissue tumors. Cross-reactivity with B cells can be especially troublesome in lymph nodes when identifying tumors of unknown origin. A new mouse monoclonal (M) anti-PAX8 antibody (Clone BC12) has been developed that recognizes PAX8 expression in a high percentage of renal cell and ovarian carcinomas, whereas exhibiting no staining of B cells. PAX8 (M) was tested for specificity and sensitivity in over 1300 cases of both normal and neoplastic tissues. PAX8 (M) demonstrated superior staining sensitivity in clear cell and papillary renal cell carcinomas (88.8% vs. 84.4%) and in serous and endometrioid ovarian carcinomas (87% vs. 83%), when compared with PAX8 (P). PAX8 (M) also stained a high percentage of endometrial and thyroid cancers, 67.5% and 60.7%, respectively. PAX8 (M) demonstrated low sensitivity in cervical and bladder cancers, 2.5% and 1.4%, respectively. All other cancers including lung, breast, prostate, stomach, liver, soft tissue, pancreas, testis, brain, colon, melanoma, lymphoma, adrenal, pituitary, and rectal were negative. In normal tissue, PAX8 (P) stained lymph nodes, pancreas, and neuroendocrine cells of stomach and colon. In contrast, PAX8 (M) was negative in each of these tissues. These results demonstrate that mouse monoclonal PAX8 [BC12] stains nuclei exclusively and performs well in formalin-fixed paraffin-embedded tissues. PAX8 (M) is a highly sensitive marker for thyroid, renal, and ovarian cancers. Importantly, PAX8 (M) does not stain B cells and does not seem to recognize epitopes of pancreatic origin and neuroendocrine cells in stomach and colon; thus, providing superior specificity and making PAX8 [BC12] an excellent marker for confirming primary tumor site and for differential diagnosis.

PMID: 22595948 [PubMed - as supplied by publisher]

Reverse Takotsubo Cardiomyopathy in the Setting of Anaphylaxis Treated with High-dose Intravenous Epinephrine.

Fetched: May 20th, 2012, 11:00pm MDT

Reverse Takotsubo Cardiomyopathy in the Setting of Anaphylaxis Treated with High-dose Intravenous Epinephrine.

J Emerg Med. 2012 May 15;

Authors: Khoueiry G, Abi Rafeh N, Azab B, Markman E, Waked A, Abourjaili G, Shariff M, Costantino T

Abstract
BACKGROUND: Takotsubo cardiomyopathy is seen, though rarely, in anaphylaxis treated with epinephrine. Stress cardiomyopathy is most likely to occur in middle-aged women. The underlying etiology is believed to be related to catecholamine release in periods of intense stress. Catecholamines administered exogenously, and those secreted by neuroendocrine tumors (e.g., pheochromocytoma) or during anaphylaxis have been reported to cause apical ballooning syndrome, or takotsubo syndrome. However, reverse takotsubo stress cardiomyopathy is rarely seen or reported in anaphylaxis treated with epinephrine. OBJECTIVES: To report a case illustrating that high-dose intravenous epinephrine can trigger stress cardiomyopathy, and that the risk is heightened with inappropriate dosing in the treatment of anaphylaxis. CASE REPORT: We report a rare case of iatrogenic reverse takotsubo syndrome in a young woman who was inappropriately treated with high-dose intravenous epinephrine for mild anaphylaxis. CONCLUSION: Inappropriately high doses of intravenous epinephrine can trigger stress cardiomyopathy. Emergency physicians should be familiar with the diagnosis, grading, and appropriate treatments of anaphylaxis to avoid this unnecessary complication.

PMID: 22595633 [PubMed - as supplied by publisher]

Permalink for 'Non-THC cannabinoids counteract prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.'

Non-THC cannabinoids counteract prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.

Fetched: May 20th, 2012, 11:00pm MDT

Non-THC cannabinoids counteract prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.

Br J Pharmacol. 2012 May 18;

Authors: De Petrocellis L, Ligresti A, Schiano Moriello A, Iappelli M, Verde R, Stott CG, Cristino L, Orlando P, Di Marzo V

Abstract
Background. Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but plant cannabinoids other than Δ(9) -tetrahydrocannabinol (THC), which lack strong activity at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival. Experimental approach. We tested pure cannabinoids and extracts from Cannabis strains enriched in certain cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating: 1) cell viability with the MTT test, 2) cell-cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and 3) size of xenograft tumors induced by LNCaP and DU-145 cells. Key results. Cannabidiol (CBD) exerted a significant inhibition of cell viability. Other compounds became efficacious in cells deprived of serum for 24 hours. Several BDS were more potent than pure compounds in the presence of serum. Intra-peritoneal CBD-BDS potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumors, respectively, and per se reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and markers of intrinsic pathways thereof, i.e. PUMA and CHOP expression and intracellular Ca(2+) . In LNCaP cells, the pro-apoptotic effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down-regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP cells differentiated to androgen-insensitive neuroendocrine-like cells were more sensitive to CBD-induced apoptosis. Conclusions. These data support the clinical testing of CBD against prostate carcinoma. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

PMID: 22594963 [PubMed - as supplied by publisher]

Specifically targeting ERK1 or ERK2 kills melanoma cells.

Fetched: May 20th, 2012, 11:00pm MDT

Specifically targeting ERK1 or ERK2 kills melanoma cells.

J Transl Med. 2012;10:15

Authors: Qin J, Xin H, Nickoloff BJ

Abstract
BACKGROUND: Overcoming the notorious apoptotic resistance of melanoma cells remains a therapeutic challenge given dismal survival of patients with metastatic melanoma. However, recent clinical trials using a BRAF inhibitor revealed encouraging results for patients with advanced BRAF mutant bearing melanoma, but drug resistance accompanied by recovery of phospho-ERK (pERK) activity present challenges for this approach. While ERK1 and ERK2 are similar in amino acid composition and are frequently not distinguished in clinical reports, the possibility they regulate distinct biological functions in melanoma is largely unexplored.
METHODS: Rather than indirectly inhibiting pERK by targeting upstream kinases such as BRAF or MEK, we directly (and near completely) reduced ERK1 and ERK2 using short hairpin RNAs (shRNAs) to achieve sustained inhibition of pERK1 and/or pERK2.
RESULTS AND DISCUSSION: Using A375 melanoma cells containing activating BRAFV600E mutation, silencing ERK1 or ERK2 revealed some differences in their biological roles, but also shared roles by reduced cell proliferation, colony formation in soft agar and induced apoptosis. By contrast, chemical mediated inhibition of mutant BRAF (PLX4032) or MEK (PD0325901) triggered less killing of melanoma cells, although they did inhibit proliferation. Death of melanoma cells by silencing ERK1 and/or ERK2 was caspase dependent and accompanied by increased levels of Bak, Bad and Bim, with reduction in p-Bad and detection of activated Bax levels and loss of mitochondrial membrane permeability. Rare treatment resistant clones accompanied silencing of either ERK1 and/or ERK2. Unexpectedly, directly targeting ERK levels also led to reduction in upstream levels of BRAF, CRAF and pMEK, thereby reinforcing the importance of silencing ERK as regards killing and bypassing drug resistance.
CONCLUSIONS: Selectively knocking down ERK1 and/or ERK2 killed A375 melanoma cells and also increased the ability of PLX4032 to kill A375 cells. Thus, a new therapeutic window is open for future clinical trials in which agents targeting ERK1 and ERK2 should be considered in patients with melanoma.

PMID: 22277029 [PubMed - indexed for MEDLINE]

Multiple plexiform schwannoma of a finger.

Fetched: May 20th, 2012, 11:00pm MDT

Multiple plexiform schwannoma of a finger.

Eur J Dermatol. 2012 Jan-Feb;22(1):149-50

Authors: Zhou J, Man XY, Zheng M, Cai SQ

PMID: 22266205 [PubMed - indexed for MEDLINE]

Permalink for 'Glutathione and Bcl-2 targeting facilitates elimination by chemoradiotherapy of human A375 melanoma xenografts overexpressing bcl-xl, bcl-2, and mcl-1.'

Glutathione and Bcl-2 targeting facilitates elimination by chemoradiotherapy of human A375 melanoma xenografts overexpressing bcl-xl, bcl-2, and mcl-1.

Fetched: May 20th, 2012, 11:00pm MDT

Glutathione and Bcl-2 targeting facilitates elimination by chemoradiotherapy of human A375 melanoma xenografts overexpressing bcl-xl, bcl-2, and mcl-1.

J Transl Med. 2012;10:8

Authors: Mena S, Rodriguez ML, Ortega A, Priego S, Obrador E, Asensi M, Petschen I, Cerdá M, Brown BD, Estrela JM

Abstract
BACKGROUND: Bcl-2 is believed to contribute to melanoma chemoresistance. However, expression of Bcl-2 proteins may be different among melanomas. Thus correlations among expression of Bcl-2-related proteins and in vivo melanoma progression, and resistance to combination therapies, was investigated.
METHODS: Human A375 melanoma was injected s.c. into immunodeficient nude mice. Protein expression was studied in tumor samples obtained by laser microdisection. Transfection of siRNA or ectopic overexpression were applied to manipulate proteins which are up- or down-regulated, preferentially, during melanoma progression. Anti-bcl-2 antisense oligonucleotides and chemoradiotherapy (glutathione-depleting agents, paclitaxel protein-binding particles, daunorubicin, X rays) were administered in combination.
RESULTS: In vivo A375 cells down-regulated pro-apoptotic bax expression; and up-regulated anti-apoptotic bcl-2, bcl-xl, and mcl-1, however only Bcl-2 appeared critical for long-term tumor cell survival and progression in vivo. Reduction of Bcl-2, combined with partial therapies, decreased melanoma growth. But only Bcl-2 targeting plus the full combination of chemoradiotherapy eradicated A375 melanoma, and led to long-term survival (> 120 days) without recurrence in 80% of mice. Tumor regression was not due to immune stimulation. Hematology and clinical chemistry data were within accepted clinical toxicities.
CONCLUSION: Strategies to target Bcl-2, may increase the effectiveness of antitumor therapies against melanomas overexpressing Bcl-2 and likely other Bcl-2-related antiapoptotic proteins.

PMID: 22233801 [PubMed - indexed for MEDLINE]

Relevance of angiogenesis in neuroendocrine tumors.

Fetched: May 19th, 2012, 11:00pm MDT

Relevance of angiogenesis in neuroendocrine tumors.

Target Oncol. 2012 May 17;

Authors: Teulé A, Casanovas O

Abstract
While traditional cytotoxic drugs have shown limited efficacy in neuroendocrine tumors (NETs), their biological features have been characterized and can be exploited therapeutically. Their most prominent trait is an extraordinary vascularization in low-grade NETs and an hypoxia-dependent angiogenesis in high-grade NETs, which is associated to a significant expression of many proangiogenic molecules. Therefore, several antiangiogenic compounds have been tested in these malignancies, and among these, sunitinib has demonstrated activity in pancreatic NET patients by dually targeting the VEGFR and PDGFR pathways. In spite of these efficacious clinical results, apparent resistance to antiangiogenic therapies has been described in NET animal models and in clinical trials. Therefore, overcoming antiangiogenic resistance is a crucial step in the subsequent development of antiangiogenic therapies. Several strategies have been postulated to fight resistance, but preclinical studies and clinical trials will investigate and address these therapeutic approaches in the coming years in order to overcome resistance to antiangiogenic therapies in NETs.

PMID: 22592949 [PubMed - as supplied by publisher]

Permalink for 'Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan(R) in two cases.'

Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan(R) in two cases.

Fetched: May 19th, 2012, 11:00pm MDT

Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan(R) in two cases.

World J Surg Oncol. 2012 May 16;10(1):82

Authors: Cossetti RJ, Bezerra RO, Gumz B, Telles A, Costa FP

Abstract
ABSTRACT: Neuroendocrine tumor (NET) patients must be adequately staged in order to improve a multidisciplinary approach and optimal management for metastatic disease. Currently available imaging studies include somatostatin receptor scintigraphy, like OctreoScan(R), computed tomography (CT), scans and magnetic resonance imaging (MRI), which analyze vascular concentration and intravenous contrast enhancement for anatomic tumor localization. However, these techniques require high degree of expertise for interpretation and are limited by their availability, cost, reproducibility, and follow-up imaging comparisons. NETs significantly reduce water diffusion as compared to normal tissue. Diffusion-weighted imaging (DWI) in MRI has an advantageous contrast difference: the tumor is represented with high signal over a black normal surrounding background. The whole-body diffusion (WBD) technique has been suggested to be a useful test for detecting metastasis from various anatomic sites. In this article we report the use of DWI in MRI and WBD in two cases of metastatic pulmonary NET staging in comparison with OctreoScan(R) in order to illustrate the potential advantage of DWI and WBD in staging NETs.

PMID: 22591909 [PubMed - as supplied by publisher]

[Multiple endocrine neoplasia type 1].

Fetched: May 19th, 2012, 11:00pm MDT

[Multiple endocrine neoplasia type 1].

Pol Merkur Lekarski. 2012 Feb;32(188):116-22

Authors: Krysiak R, Okopień B

Abstract
Multiple endocrine neoplasia (MEN) type 1 exhibits an autosomal dominant pattern of inheritance and results from mutation of the MEN-1 gene that is a tumor suppressor gene acting on the transcriptional level. The disease is characterized by a variety of neuroendocrine neoplasias and hormone excess syndromes. The major components of MEN-I are hyperparathyroidism due to multiple parathyroid adenomas, pancreatic or duodenal neuroendocrine tumors, and pituitary adenomas, in addition to some less common neoplastic manifestations. The development of the tumors often follows a substantially similar pattern: the initial lesion is a diffuse hyperplastic proliferation of the affected endocrine tissue with bilateral involvement of pair organs, followed by development of multiple micro- and, eventually, macronodular lesions. Its unpredictable course causes that there is controversy regarding treatment of the different manifestations and screening modalities of this disorder. This article reviews our current approach to the diagnosis, surveillance and management of these patients.

PMID: 22590916 [PubMed - in process]

Atypical adenolymphoma and glomus caroticum tumour: a rare coincidence.

Fetched: May 19th, 2012, 11:00pm MDT

Atypical adenolymphoma and glomus caroticum tumour: a rare coincidence.

B-ENT. 2012;8(1):43-7

Authors: Broes K, Vanderveken OM, Salgado R, Verfaillie J, Pauwels P, Van de Heyning PH, Van Laer C

Abstract
We describe the rare simultaneous appearance of an atypical adenolymphoma with a glomus caroticum tumour on the same side of the neck in a middle-aged man. This case report is the first to describe this coexistence. Due to the atypical, cyst-like presentation of the Warthin's tumour, a final diagnosis was made only after surgical resection and histopathological examination. Both the adenolymphoma and glomus caroticum tumour were successfully removed surgically.

PMID: 22545390 [PubMed - indexed for MEDLINE]

Permalink for 'Clinicopathologic and molecular analysis of a choroidal pigmented schwannoma in the context of a PTEN hamartoma tumor syndrome.'

Clinicopathologic and molecular analysis of a choroidal pigmented schwannoma in the context of a PTEN hamartoma tumor syndrome.

Fetched: May 19th, 2012, 11:00pm MDT

Clinicopathologic and molecular analysis of a choroidal pigmented schwannoma in the context of a PTEN hamartoma tumor syndrome.

Ophthalmology. 2012 Apr;119(4):857-64

Authors: Venturini G, Moulin AP, Deprez M, Uffer S, Bottani A, Zografos L, Rivolta C

Abstract
PURPOSE: To report the first case of choroidal schwannoma in a patient affected by PTEN hamartoma tumor syndrome (PHTS) and investigate the molecular involvement of the phosphatase and tensin homolog (PTEN) and neurofibromin 2 (NF2) genes in this rare intraocular tumor.
DESIGN: Observational case report.
PARTICIPANT: A 10-year-old girl diagnosed with PHTS.
METHODS: The enucleated specimen underwent histologic, immunohistochemical, and transmission electronic microscopy. The expression of PTEN and NF2 and their protein products were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Somatic mutations of PTEN and NF2, as well as allelic loss, were investigated by direct sequencing of DNA extracted from the tumor. PTEN epigenetic silencing was investigated by pyrosequencing.
MAIN OUTCOME MEASURES: Histopathologic and molecular characterization of a choroidal pigmented schwannoma.
RESULTS: Histopathologic, immunohistochemical, and electron microscopic analysis demonstrated features consistent with a pigmented cellular schwannoma of the choroid. We found no loss of heterozygosity at the genomic level for the PTEN germline mutation and no promoter hypermethylation or other somatic intragenic mutations. However, we observed an approximate 40% reduction of PTEN expression at both the mRNA and the protein level, indicating that the tumor was nonetheless functionally deficient for PTEN. Although DNA sequencing of NF2 failed to identify any pathologic variants, its expression was abolished within the tumor.
CONCLUSIONS: We report the first description of a pigmented choroidal schwannoma in the context of a PHTS. This rare tumor showed a unique combination of reduction of PTEN and absence of NF2 expression.

PMID: 22281088 [PubMed - indexed for MEDLINE]

Cutaneous melanoma in Latin America: the need for more data.

Fetched: May 19th, 2012, 11:00pm MDT

Cutaneous melanoma in Latin America: the need for more data.

Rev Panam Salud Publica. 2011 Nov;30(5):431-8

Authors: Schmerling RA, Loria D, Cinat G, Ramos WE, Cardona AF, Sánchez JL, Martinez-Said H, Buzaid AC

Abstract
OBJECTIVE: To identify the scientific literature on cutaneous melanoma in Latin America and compile all available epidemiologic data to demonstrate the need for reliable regional and country-specific data on incidence and mortality estimates.
METHODS: Literature searches were conducted in PubMed, Embase, LILACS, and Google Scholar databases for epidemiologic studies from 1 January 2000 to 31 October 2010 related to melanoma in Argentina, Brazil, Colombia, Mexico, Puerto Rico, and Venezuela. A final search on melanoma cases was carried out using country-specific population-based cancer registries. No statistical analyses were conducted.
RESULTS: For all six countries, most epidemiological research on cutaneous melanoma consists of hospital-based or case-control studies. Very few studies report incidence and mortality rates. Attempts to estimate disease rates have relied on national incidence and mortality data and information extracted from cancer registries. While predominance of European ancestry is a known risk factor for developing melanoma, the association of melanoma and ethnicity is not well-documented in some of the populations reviewed. Latin Americans are frequently exposed to ultraviolet (UV) radiation due to the tropical weather, high altitude, and thinning ozone layer in some regions. Tanned skin is viewed as healthy and beautiful. While melanoma public health campaigns have been under way in Latin America for decades, increasing melanoma awareness remains imperative.
CONCLUSIONS: There is an urgent need to collect accurate epidemiologic melanoma data in Latin America. Future research in the region should include more comprehensive, country-specific, population-based studies to allow for comparative evaluation of incidence and mortality rates.

PMID: 22262269 [PubMed - indexed for MEDLINE]

Permalink for 'Investigating the role of melanin in UVA/UVB- and hydrogen peroxide-induced cellular and mitochondrial ROS production and mitochondrial DNA damage in human melanoma cells.'

Investigating the role of melanin in UVA/UVB- and hydrogen peroxide-induced cellular and mitochondrial ROS production and mitochondrial DNA damage in human melanoma cells.

Fetched: May 19th, 2012, 11:00pm MDT

Investigating the role of melanin in UVA/UVB- and hydrogen peroxide-induced cellular and mitochondrial ROS production and mitochondrial DNA damage in human melanoma cells.

Free Radic Biol Med. 2012 Feb 1;52(3):626-34

Authors: Swalwell H, Latimer J, Haywood RM, Birch-Machin MA

Abstract
Skin cancer incidence is dramatically increasing worldwide, with exposure to ultraviolet radiation (UVR) a predominant factor. The UVA component initiates oxidative stress in human skin, although its exact role in the initiation of skin cancer, particularly malignant melanoma, remains unclear and is controversial because there is evidence for a melanin-dependent mechanism in UVA-linked melanoma studies. Nonpigmented (CHL-1, A375), moderately pigmented (FM55, SKmel23), and highly pigmented (FM94, hyperpigmented FM55) human melanoma cell lines have been used to investigate UVA-induced production of reactive oxygen species using FACS analysis, at both the cellular (dihydrorhodamine-123) and the mitochondrial (MitoSOX) level, where most cellular stress is generated. For the first time, downstream mtDNA damage (utilizing a quantitative long-PCR assay) has been investigated. Using UVA, UVB, and H(2)O(2) as cellular stressors, we have explored the dual roles of melanin as a photoprotector and photosensitizer. The presence of melanin has no influence over cellular oxidative stress generation, whereas, in contrast, melanin protects against mitochondrial superoxide generation and mtDNA damage (one-way ANOVA with post hoc Tukey's analysis, P<0.001). We show that if melanin binds directly to DNA, it acts as a direct photosensitizer of mtDNA damage during UVA irradiation (P<0.001), providing evidence for the dual roles of melanin.

PMID: 22178978 [PubMed - indexed for MEDLINE]

Plaque radiotherapy for residual or recurrent iris melanoma after surgical resection in 32 cases.

Fetched: May 19th, 2012, 11:00pm MDT

Plaque radiotherapy for residual or recurrent iris melanoma after surgical resection in 32 cases.

Ophthalmology. 2012 Apr;119(4):838-842.e2

Authors: Shah SU, Shields CL, Bianciotto C, Emrich J, Komarnicky L, Shields JA

Abstract
PURPOSE: To evaluate plaque radiotherapy for management of residual or recurrent iris melanoma after surgical resection.
DESIGN: Retrospective, nonrandomized interventional case series.
PARTICIPANTS: We included 32 patients with residual or recurrent iris melanoma after surgical resection.
INTERVENTION: Custom designed iodine-125 plaque radiotherapy.
MAIN OUTCOME MEASURES: Tumor control, recurrence, poor visual acuity, enucleation, metastasis, and radiation complications.
RESULTS: There were 32 eyes with residual (n = 12) or recurrent (n = 20) iris melanoma after surgical resection that were treated with iodine-125 plaque radiotherapy. The residual melanoma was evident clinically in 3 cases and histopathologically in 9; plaque radiotherapy was delivered at a mean interval of 2 months after resection. For the recurrent cases, the mean interval from initial tumor resection to detection of recurrence was 58 months, at which time plaque radiotherapy was applied. For all cases, the mean tumor basal diameter was 6 mm (range, 1-13) and thickness was 2 mm (range, 0.8-4.0) at the time of radiotherapy. Anterior chamber seeding was present in 26 (81%) eyes and glaucoma in 11 (34%) eyes. Visual acuity at presentation was good (20/20-20/50) in 27 (84%), intermediate (20/60-20/150) in 3 (9%), and poor (≤20/200) in 2 eyes (6%). At 6 years after plaque radiotherapy, outcomes included complete tumor control in 87%, poor visual acuity in 9%, enucleation in 13% (for reasons of tumor recurrence [n = 3] and severe glaucoma [n = 1]), and metastasis in 3%. At 6 years, radiation complications included corneal epitheliopathy in 6%, scleral necrosis in 3%, cataract in 53%, elevated intraocular pressure (from tumor or radiotherapy) in 19%, and macular edema in 6%.
CONCLUSIONS: Iodine-125 plaque radiotherapy is effective in the management of residual or recurrent iris melanoma after surgical resection, providing tumor control in 87% of patients at 6 years and avoiding enucleation in most cases.

PMID: 22133794 [PubMed - indexed for MEDLINE]

P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.

Fetched: May 19th, 2012, 11:00pm MDT

P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.

Nat Commun. 2011;2:555

Authors: Lindsay CR, Lawn S, Campbell AD, Faller WJ, Rambow F, Mort RL, Timpson P, Li A, Cammareri P, Ridgway RA, Morton JP, Doyle B, Hegarty S, Rafferty M, Murphy IG, McDermott EW, Sheahan K, Pedone K, Finn AJ, Groben PA, Thomas NE, Hao H, Carson C, Norman JC, Machesky LM, Gallagher WM, Jackson IJ, Van Kempen L, Beermann F, Der C, Larue L, Welch HC, Ozanne BW, Sansom OJ

Abstract
Metastases are the major cause of death from melanoma, a skin cancer that has the fastest rising incidence of any malignancy in the Western world. Molecular pathways that drive melanoblast migration in development are believed to underpin the movement and ultimately the metastasis of melanoma. Here we show that mice lacking P-Rex1, a Rac-specific Rho GTPase guanine nucleotide exchange factor, have a melanoblast migration defect during development evidenced by a white belly. Moreover, these P-Rex1(-/-) mice are resistant to metastasis when crossed to a murine model of melanoma. Mechanistically, this is associated with P-Rex1 driving invasion in a Rac-dependent manner. P-Rex1 is elevated in the majority of human melanoma cell lines and tumour tissue. We conclude that P-Rex1 has an important role in melanoblast migration and cancer progression to metastasis in mice and humans.

PMID: 22109529 [PubMed - indexed for MEDLINE]

Immunotherapy of malignant melanoma with tumor lysate-pulsed autologous monocyte-derived dendritic cells.

Fetched: May 19th, 2012, 11:00pm MDT

Immunotherapy of malignant melanoma with tumor lysate-pulsed autologous monocyte-derived dendritic cells.

Yonsei Med J. 2011 Nov;52(6):990-8

Authors: Kim DS, Kim DH, Goo B, Cho YH, Park JM, Lee TH, Kim HO, Kim HS, Lee H, Lee JD, Byamba D, Je JH, Lee MG

Abstract
PURPOSE: Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea.
MATERIALS AND METHODS: Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4×10⁷ DC were injected each time.
RESULTS: Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-γ-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients.
CONCLUSION: In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.

PMID: 22028165 [PubMed - indexed for MEDLINE]

Persistent pain after surgery for cutaneous melanoma.

Fetched: May 19th, 2012, 11:00pm MDT

Persistent pain after surgery for cutaneous melanoma.

Clin J Pain. 2012 Feb;28(2):149-56

Authors: Høimyr H, von Sperling ML, Rokkones KA, Stubhaug A, Finnerup K, Jensen TS, Finnerup NB

Abstract
OBJECTIVES: Chronic pain is a well-known complication after surgery, but the prevalence of persistent pain after melanoma surgery is unknown. This study examined the prevalence and predictors of persistent pain after melanoma surgery.
METHODS: Between September 2005 and June 2009, 448 patients underwent surgery for cutaneous melanoma at the Department of Plastic Surgery, Aalborg Hospital. A questionnaire was sent to all 402 survivors, and 350 (87.1%) responded. In addition, all patients with pain and a control group of sex-matched and age-matched patients without pain were invited to a clinical examination.
RESULTS: Thirty-four patients (9.7%) reported pain in the scar area within the last month, and 8.6% reported chronic pain. The pain was mostly mild with little impact on daily life, but 1.7% reported moderate to severe pain, and 3.4% reported at least moderate impact of pain on daily life. Sensory changes were reported by 108 patients (31.5%); 25% of these had pain compared with 3% of patients with normal sensation [P<0.001, 10.8 (4.5 to 25.8)]. Young age was a predictor for persistent pain. A small group of patients (10 with and 22 without pain in the questionnaire) were clinically examined, suggesting that the areas of sensory disturbances were larger in patients reporting persistent pain or dysesthesia.
DISCUSSION: The results support previous findings that persistent postoperative pain is a complication of almost any surgical intervention. Persistent pain was related to abnormal sensation, and neuropathic pain should be considered in these patients.

PMID: 21904198 [PubMed - indexed for MEDLINE]

Bilateral primary adrenal lymphoma accompanying hypertension.

Fetched: May 19th, 2012, 11:00pm MDT

Bilateral primary adrenal lymphoma accompanying hypertension.

Urology. 2012 Feb;79(2):e27-8

Authors: Wang Q, Cao X, Jiang J, Wang T, Jin MS

Abstract
Primary adrenal lymphoma (PAL) accompanied by hypertension is extremely rare. We present a case of PAL with hypertension, whom was treated with bilateral adrenalectomy and a combination of the modified Appleby operation and chemotherapy. Computed tomography and biopsy is helpful to aid diagnosis.

PMID: 21862117 [PubMed - indexed for MEDLINE]

Incomplete sentinel node biopsy is not clearly related to survival or regional recurrence in cutaneous melanoma patients.

Fetched: May 19th, 2012, 11:00pm MDT

Incomplete sentinel node biopsy is not clearly related to survival or regional recurrence in cutaneous melanoma patients.

Ann Surg Oncol. 2012 Jan;19(1):280-6

Authors: Lee NC, Spillane AJ, Pang TC, Haydu LE, Uren RF

Abstract
BACKGROUND: In melanoma patients, we define incomplete sentinel node biopsy (I-SNB) as when fewer lymph nodes are removed during sentinel node biopsy (SNB) than identified on preoperative lymphoscintigraphy (LS). This study quantifies the frequency of I-SNB and evaluates any correlation with patient outcomes.
METHODS: Evaluation of a prospective database of consecutive patients having LS and negative SNB from 1996 to 2006. Additional LS information was obtained from a nuclear medicine database. All statistical analyses were performed using the IBM SPSS Statistic 19.0 software package.
RESULTS: I-SNB occurred in 20% of the cohort (n = 2007). For axillary (n = 895), groin (n = 569), and neck/axial patients (n = 334) I-SNB occurred in 12%, 26%, and 28% of cases, respectively (P < .001). On univariate analysis, there was a significant association between I-SNB and worse disease-free survival (DFS), P = .007 and trend toward worse melanoma-specific survival (MSS), P = .056. I-SNB was not associated with worse regional recurrence-free survival (RRFS), P = .144. There was no relationship between I-SNB and worse DFS, RRFS, or MSS on multivariate analysis. Sentinel node region (axilla better than groin and neck/axial) had a significant association with RRFS (P = .039) on univariate analysis and DFS on univariate (P = .009) and multivariate analysis. Significantly worse outcomes for MSS, DFS, and RRFS were seen with male gender, increasing age, high mitotic count, ulceration, and increasing Breslow thickness.
CONCLUSION: This study demonstrates no statistically significant relationship between I-SNB and patient outcomes when adjusting for known prognostic factors. These data do not exclude the possibility that I-SNB may have a weak association with worse outcomes.

PMID: 21833669 [PubMed - indexed for MEDLINE]

Validation of statistical predictive models meant to select melanoma patients for sentinel lymph node biopsy.

Fetched: May 19th, 2012, 11:00pm MDT

Validation of statistical predictive models meant to select melanoma patients for sentinel lymph node biopsy.

Ann Surg Oncol. 2012 Jan;19(1):287-93

Authors: Sabel MS, Rice JD, Griffith KA, Lowe L, Wong SL, Chang AE, Johnson TM, Taylor JM

Abstract
INTRODUCTION: To identify melanoma patients at sufficiently low risk of nodal metastases who could avoid sentinel lymph node biopsy (SLNB), several statistical models have been proposed based upon patient/tumor characteristics, including logistic regression, classification trees, random forests, and support vector machines. We sought to validate recently published models meant to predict sentinel node status.
METHODS: We queried our comprehensive, prospectively collected melanoma database for consecutive melanoma patients undergoing SLNB. Prediction values were estimated based upon four published models, calculating the same reported metrics: negative predictive value (NPV), rate of negative predictions (RNP), and false-negative rate (FNR).
RESULTS: Logistic regression performed comparably with our data when considering NPV (89.4 versus 93.6%); however, the model's specificity was not high enough to significantly reduce the rate of biopsies (SLN reduction rate of 2.9%). When applied to our data, the classification tree produced NPV and reduction in biopsy rates that were lower (87.7 versus 94.1 and 29.8 versus 14.3, respectively). Two published models could not be applied to our data due to model complexity and the use of proprietary software.
CONCLUSIONS: Published models meant to reduce the SLNB rate among patients with melanoma either underperformed when applied to our larger dataset, or could not be validated. Differences in selection criteria and histopathologic interpretation likely resulted in underperformance. Statistical predictive models must be developed in a clinically applicable manner to allow for both validation and ultimately clinical utility.

PMID: 21822550 [PubMed - indexed for MEDLINE]

How good are US dermatologists at discriminating skin cancers? A number-needed-to-treat analysis.

Fetched: May 19th, 2012, 11:00pm MDT

How good are US dermatologists at discriminating skin cancers? A number-needed-to-treat analysis.

J Dermatolog Treat. 2012 Feb;23(1):65-9

Authors: Wilson RL, Yentzer BA, Isom SP, Feldman SR, Fleischer AB

Abstract
BACKGROUND: Identification of skin cancer requires discrimination of malignant lesions from benign lesions. The number of biopsies performed to yield one cancer diagnosis can be presented as a number needed to treat (NNT), and provides an assessment of the efficiency of skin cancer detection.
OBJECTIVE: To assess the clinical accuracy of US dermatologists screening for skin cancer, the NNT for both melanoma and non-melanoma skin cancer was examined.
METHODS: Pathology reports from 2021 biopsies performed at the Wake Forest University Department of Dermatology were reviewed, including the physician's differential diagnosis and final pathological diagnosis. The NNT was calculated for melanoma, non-melanoma skin cancer, and all skin cancer diagnosed.
RESULTS: Of 1240 biopsies suspicious for skin cancer, 559 cancers were diagnosed, yielding a NNT of 2.22 for any cancer. The NNT specifically for non-melanoma skin cancer was 1.6, while the NNT for melanoma was 15. Patient age, anatomical location, sex and physician all significantly impacted on NNT values.
CONCLUSIONS: The NNT for melanoma in our study was lower compared to recently published values obtained from general practitioners in Australian skin cancer clinics (NNT of 30). Variability amongst institutions, practice settings and physicians supports the need to establish a benchmark NNT.

PMID: 21756146 [PubMed - indexed for MEDLINE]

Diagnostic accuracy of surgeon-performed ultrasound-guided fine-needle aspiration of thyroid nodules.

Fetched: May 19th, 2012, 11:00pm MDT

Diagnostic accuracy of surgeon-performed ultrasound-guided fine-needle aspiration of thyroid nodules.

Ann Surg Oncol. 2012 Jan;19(1):45-51

Authors: Bohacek L, Milas M, Mitchell J, Siperstein A, Berber E

Abstract
BACKGROUND: There is scant data concerning surgeon-performed thyroid fine-needle aspiration (FNA), and controversy regarding its accuracy in larger nodules. This study aimed to specifically assess accuracy of surgeon-performed ultrasound (US)-guided FNA on a per-nodule basis, with a subanalysis of nodule size.
METHODS: Data of 1,000 surgeon-performed US-guided thyroid FNAs at a single institution from 2000 to 2010 were prospectively collected. Standard clinical information, FNA results using the Bethesda criteria, and final histology were recorded.
RESULTS: Fine-needle aspiration results were reported as: cancer (7%), suspicious for cancer (2%), suspicious for follicular neoplasm (17%), atypia of unknown significance (AUS) (1%), benign (67%), and insufficient (6%). Of nodules with FNA results of cancer, suspicious for cancer, suspicious for follicular neoplasm, and atypia of unknown significance, 94% were operated on, with malignancy rates of 97%, 58%, 21%, and 12%, respectively. Of nodules with benign FNA, 26% underwent surgery for associated symptoms, concerning features, or other remote pathology. A total of 56% were followed, and 18% were lost to follow-up. Of nodules with insufficient FNA, 46% had repeat FNA (yielding a diagnosis in 81%), 23% underwent surgery, 21% with hypocellular features were followed, and 9% were lost to follow-up. In size subanalysis, there was no statistically significant difference in risk of malignancy or increased rate of falsely negative FNA with increasing nodule size.
CONCLUSIONS: The Bethesda system appropriately stratified lesions for risk of malignancy, and repeat FNA had high diagnostic yield in lesions with inadequate FNA. The results suggest no trend toward larger lesions harboring thyroid malignancy nor an increased likelihood of false-negative benign FNA.

PMID: 21633868 [PubMed - indexed for MEDLINE]

Simultaneous medullary and papillary thyroid cancer: a novel entity?

Fetched: May 19th, 2012, 11:00pm MDT

Simultaneous medullary and papillary thyroid cancer: a novel entity?

Ann Surg Oncol. 2012 Jan;19(1):37-44

Authors: Machens A, Dralle H

Abstract
BACKGROUND: The causes underlying the phenomenon of simultaneous medullary (MTC) and papillary thyroid cancer (PTC) are unclear.
METHODS: This study of 26 patients with simultaneous MTC and PTC aimed at clarifying clinical and histopathologic characteristics and trends of this unusual condition among MTC and PTC patients who were operated on at a tertiary referral center in Germany.
RESULTS: A total of 26 patients revealed simultaneous MTC and PTC, yielding the following rates: 2.6% (26 patients) among all 1019 PTC patients, 2.6% (6 patients) among all 235 hereditary MTC patients, 4.1% (20 patients) among all 492 sporadic MTC patients, and 3.6% (26 patients) among all 727 MTC patients. Simultaneous MTC and PTC were consistently smaller than nonsimultaneous MTC (6 vs. 13 mm for hereditary MTC, P = .16; 12 vs. 23 mm for sporadic MTC, P = .009; and 11 vs. 20 mm for any MTC, P = .008) and PTC (8 vs. 20 mm, P < .001). Simultaneous MTC and PTC increased among MTC and PTC patients over time: from 0% to 4.3% (PTC), from 0% to 4.6% (hereditary MTC), from 0% to 8.1% (sporadic MTC), and from 0% to 7.0% (any MTC). For sporadic MTC, these rates virtually doubled every 5 years. Of 6 patients with simultaneous hereditary MTC and PTC, 5 revealed late-onset REarranged during Transfection (RET) mutations (1 L790F carrier; 2 V804L and 2 S891A carriers).
CONCLUSIONS: Greater pathologic scrutiny, in addition to environmental changes, explains the surge of simultaneous MTC and PTC in Germany. More data are needed from additional geographic areas and populations to delineate individual contributions of these factors.

PMID: 21626080 [PubMed - indexed for MEDLINE]

Permalink for 'Usefulness of ultrafast dynamic 3D-T1w data acquisition in detection of hypervascular lesions of the middle ear: first experience.'

Usefulness of ultrafast dynamic 3D-T1w data acquisition in detection of hypervascular lesions of the middle ear: first experience.

Fetched: May 19th, 2012, 11:00pm MDT

Usefulness of ultrafast dynamic 3D-T1w data acquisition in detection of hypervascular lesions of the middle ear: first experience.

Eur J Radiol. 2012 Feb;81(2):257-61

Authors: Aschenbach R, Basche S, Esser D, Vogl TJ

Abstract
OBJECTIVE: To evaluate ultrafast dynamic 3D-T1w acquisition for improved detection of tympanic hypervascularized lesions.
METHODS: Retrospective evaluation of a total of 50 patients referred from ENT-Department for suspected tympanic lesion. All underwent magnetic resonance imaging including ultrafast dynamic 3D-T1w acquisition imaging. Quantitative and qualitative evaluation was performed as well as statistical analysis. Comparison with intra-operative results.
RESULTS: 12/50 patients showed a hypervascularized lesion proved intraoperative as 8 paragangliomas, 2 adenoms, 1 hemangioma and 1 neurinoma. 8/50 do not show hypervascularization though an enhancement was detected. Intra-operative granulation tissue was found. 30 patients did not show any lesions or enhancement. Sensitivity and specificity was 100%/100% for ultrafast dynamic imaging.
CONCLUSION: Additional ultrafast dynamic 3D-T1w imaging is superior to conventional imaging in detection of hypervascularized lesions.

PMID: 21123017 [PubMed - indexed for MEDLINE]

Transferred melanoma-specific CD8+ T cells persist, mediate tumor regression, and acquire central memory phenotype.

Fetched: May 11th, 2012, 11:00pm MDT

Transferred melanoma-specific CD8+ T cells persist, mediate tumor regression, and acquire central memory phenotype.

Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4592-7

Authors: Chapuis AG, Thompson JA, Margolin KA, Rodmyre R, Lai IP, Dowdy K, Farrar EA, Bhatia S, Sabath DE, Cao J, Li Y, Yee C

Abstract
Adoptively transferred tumor-specific T cells offer the potential for non-cross-resistant therapy and long-term immunoprotection. Strategies to enhance in vivo persistence of transferred T cells can lead to improved antitumor efficacy. However, the extrinsic (patient conditioning) and intrinsic (effector cell) factors contributing to long-term in vivo persistence are not well-defined. As a means to enhance persistence of infused T cells in vivo and limit toxicity, 11 patients with refractory, progressive metastatic melanoma received cyclophosphamide alone as conditioning before the infusion of peripheral blood mononuclear cell-derived, antigen-specific, CD8(+) cytotoxic T-lymphocyte (CTL) clones followed by low-dose or high-dose IL-2. No life-threatening toxicities occurred with low-dose IL-2. Five of 10 evaluable patients had stable disease at 8 wk, and 1 of 11 had a complete remission that continued for longer than 3 y. On-target autoimmune events with the early appearance of skin rashes were observed in patients with stable disease or complete remission at 4 wk or longer. In vivo tracking revealed that the conditioning regimen provided a favorable milieu that enabled CTL proliferation early after transfer and localization to nonvascular compartments, such as skin and lymph nodes. CTL clones, on infusion, were characterized by an effector memory phenotype, and CTL that persisted long term acquired phenotypic and/or functional qualities of central memory type CTLs in vivo. The use of a T-cell product composed of a clonal population of antigen-specific CTLs afforded the opportunity to demonstrate phenotypic and/or functional conversion to a central memory type with the potential for sustained clinical benefit.

PMID: 22393002 [PubMed - indexed for MEDLINE]

Whole-body 18F FDG positron emission tomography/computed tomography evaluation of patients with uveal metastasis.

Fetched: May 11th, 2012, 11:00pm MDT

Whole-body 18F FDG positron emission tomography/computed tomography evaluation of patients with uveal metastasis.

Am J Ophthalmol. 2012 Apr;153(4):661-8

Authors: Patel P, Finger PT

Abstract
PURPOSE: To investigate the value of whole-body positron emission tomography/computed tomography (PET/CT) as a screening tool for patients with uveal metastasis.
DESIGN: Retrospective observational case series.
METHODS: setting: Clinical practice. study population: Eighteen patients with uveal metastatic tumors were evaluated. Patients had no history of malignancy or a past medical history of malignancy without known active metastasis or known systemic cancer. intervention: Whole-body PET/CT was used as a screening tool to evaluate the intraocular tumor, to evaluate for multi-organ metastatic disease, and for cancer staging. main outcome measures: Detection and PET/CT uptake of primary tumors and metastatic disease.
RESULTS: PET/CT imaging uncovered previously occult primary nonocular cancers (11/18, 61%), revealed progression of known primary systemic cancer (7/18, 39%), and confirmed multi-organ metastases in all cases (18/18, 100%). PET/CT findings were used to direct nonocular, confirmatory biopsy in 67% of cases (12/18). No uveal biopsies were required. PET/CT revealed lymph nodes and bone as the most common metastatic sites. The intraocular tumor was detectable in 28% of cases. Small, non-avid tumors and those within the hypermetabolic, PET-avid brain were falsely negative.
CONCLUSION: This study suggests that whole-body PET/CT can be useful for clinical evaluation of patients with uveal metastases. It allowed for screening of the entire body and directed extraocular biopsy. Commonly used for tumor staging, PET/CT aided in the detection of the primary cancer in patients with metastatic uveal tumors.

PMID: 22264690 [PubMed - indexed for MEDLINE]

Intraoperative medialization of medial rectus muscle as a new endoscopic technique for approaching intraconal lesions.

Fetched: May 11th, 2012, 11:00pm MDT

Intraoperative medialization of medial rectus muscle as a new endoscopic technique for approaching intraconal lesions.

Am J Rhinol Allergy. 2011 Sep-Oct;25(5):363-7

Authors: Tomazic PV, Stammberger H, Habermann W, Gerstenberger C, Braun H, Gellner V, Mokry M, Klein A, Langmann G, Köele W

Abstract
BACKGROUND: Intraconal tumors of the orbit are rare entities and surgical treatment is challenging. Endoscopic transnasal approaches to the orbit offer a new perspective for surgery, although only few reports exist in literature. This study displays the Graz experience with endoscopic approaches to intraorbital tumors between 2006 and 2010 introducing a novel endoscopic technique for temporary medialization of the medial rectus muscle facilitating access to the orbital cone.
METHODS: A retrospective analysis of patients' charts was performed.
RESULTS: For approaches to intraconal lesions a special endoscopic temporary medialization technique of the medial rectus muscle through applying transseptal sutures was developed. Six patients (four male and two female patients) have been included in this study presenting with intraconal/intraorbital tumors. Three patients underwent endoscopic surgery for two hemangiomas and one Schwannoma, respectively, and three patients were successfully biopsied endoscopically revealing one malignant melanoma, one malignant lymphoma, and one optic glioma each. Both hemangiomas were completely resected without any deterioration of vision. The Schwannoma was partially resected with postoperative imaging showing no tumor progression within 3 months. No intraoperative complications occurred. Five cases were performed with computer assisted surgery using CT/MR fusion navigation.
CONCLUSION: Although technically challenging, the endoscopic approach to the orbit, even for intraconal lesions with medialization of the medial rectus muscle, can be safe and promising for well-selected cases. Good postoperative results and sufficient material acquisition for proper histological examination can be obtained. Advantages are good visualization of the surgical field and avoidance of external scars. Limitations to endoscopic techniques are tumors in the lateral superior and lateral inferior quadrant of the orbit.

PMID: 22186253 [PubMed - indexed for MEDLINE]

Permalink for 'In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma.'

In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma.

Fetched: May 11th, 2012, 11:00pm MDT

In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma.

Cancer Biother Radiopharm. 2011 Oct;26(5):547-56

Authors: Ballard B, Jiang Z, Soll CE, Revskaya E, Cutler CS, Dadachova E, Francesconi LC

Abstract
Melanoma is a malignancy with increasing incidence. Although primary tumors that are localized to the skin can be successfully treated by surgical removal, there is no satisfactory treatment for metastatic melanoma, a condition that has currently an estimated 5-year survival of just 6%. During the last decade, β- or α-emitter-radiolabeled peptides that bind to different receptors on a variety of tumors have been investigated as potential therapeutic agents in both the preclinical and clinical settings with encouraging results. A recent study demonstrated that 188-Rhenium ((188)Re)-labeled, via HYNIC ligand, fungal melanin-binding decapeptide 4B4 was effective against experimental MNT1 human melanoma and was safe to normal melanized tissues. The availability of radiolanthanides with diverse nuclear emission schemes and half-lives provides an opportunity to expand the repertoire of peptides for radionuclide therapy of melanoma. The melanin-binding decapeptide 4B4 was radiolabeled with (177)Lu, (166)Ho, and (153)Sm via a DO3A chelate. The stability studies of Ln*-DO3A-4B4 in phosphate-buffered saline, serum, and a hydroxyapatite assay demonstrated that (177)Lu-labeled peptide was more stable than (166)Ho- and (153)Sm-labeled peptides, most likely because of the smallest ionic radius of the former allowing for better complexation with DO3A. Binding of Ln*-DO3A-4B4 to the lysed highly melanized MNT1 melanoma cells demonstrated the specificity of peptides binding to melanin. In vivo biodistribution data for (177)Lu-DO3A-4B4 given by intraperitoneal administration to lightly pigmented human metastatic A2058 melanoma-bearing mice demonstrated very high uptake in the kidneys and low tumor uptake. Intravenous administration did not improve the tumor uptake. The plausible explanation of low tumor uptake of (177)Lu-DO3A-4B4 could be its decreased ability to bind to melanin during in vitro binding studies in comparison with (188)Re-HYNIC-4B4, exacerbated by the very fast clearance from the blood and the kidneys "sink" effect.

PMID: 21970319 [PubMed - indexed for MEDLINE]

Potent antitumor effect elicited by RGD-mda-7, an mda-7/IL-24 mutant, via targeting the integrin receptor of tumor cells.

Fetched: May 11th, 2012, 11:00pm MDT

Potent antitumor effect elicited by RGD-mda-7, an mda-7/IL-24 mutant, via targeting the integrin receptor of tumor cells.

Cancer Biother Radiopharm. 2011 Oct;26(5):647-55

Authors: Zhang BF, Liu JJ, Pei DS, Yang ZX, Di JH, Chen FF, Li HZ, Xu W, Wu YP, Zheng JN

Abstract
The melanoma differentiation-associated gene-7/interleukin-24 gene (mda-7/IL-24) is a novel tumor-suppressor/cytokine gene that exhibits potent tumor-suppressive activity without damaging normal cells. To enhance the antitumor effect, an mda-7/IL-24 mutant, RGD-mda-7, which includes the cell adhesive sequence 164Arg-165Gly-166Asp (RGD motif), was constructed and evaluated for bioactivity. RGD peptide binds to integrins α(V)β(3) and α(V)β(5), which are selectively expressed in tumor neovasculature and in the surface of some tumor cells. The wtmda-7/IL-24 and RGD-mda-7 were expressed in Escherichia coli and then purified and renatured. The immunostimulatory activity of RGD-mda-7 was assayed by stimulating peripheral blood mononuclear cells. The results suggested that the abilities of RGD-mda-7 to induce IL-6, TNF-α, and IFN-γ production were higher than wtmda-7/IL-24. Tumor targeting of RGD-mda-7 was assayed using cell adhesion experiments. The antitumor effect of the purified RGD-mda-7 on cell proliferation in vitro was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) uptake, cell apoptosis by staining with fluorescent probes of FITC-annexin V and DAPI, and caspase-3 expression and activity. The in vitro results showed that RGD-mda-7 inhibited the proliferation of multiple tumor cell lines (Hela, ACHN, HepG2, and A549). Staining with fluorescent probes of FITC-annexin V and DAPI indicated that RGD-mda-7 could induce apoptosis more effectively in four tumor cell lines than wtmda-7/IL-24, but has no effect on normal cell line NHLF. Western blotting showed that treatment of tumor cells with RGD-mda-7 could activate apoptotic pathway by cleavage of caspase-3 as same as wtmda-7/IL-24. Further, RGD-mda-7 group showed a higher cleaved level of caspase-3, but not in NHLF cells. These results demonstrate that RGD-MDA-7 possesses more potent antitumor effects than wtmda-7/IL-24 and therefore merits further investigation in preclinical and clinical studies.

PMID: 21902545 [PubMed - indexed for MEDLINE]

Expression of Cocaine- and Amphetamine-Regulated Transcript is Associated with Worse Survival in Small Bowel Carcinoid Tumors.

Fetched: May 5th, 2012, 11:00pm MDT

Expression of Cocaine- and Amphetamine-Regulated Transcript is Associated with Worse Survival in Small Bowel Carcinoid Tumors.

Clin Cancer Res. 2012 May 2;

Authors: Landerholm K, Shcherbina L, Falkmer S, Jarhult J, Wierup N

Abstract
PURPOSE: Cocaine- and amphetamine-regulated transcript (CART) peptide exerts several regulatory functions acting both as neurotransmitter and hormone. We recently showed that CART is expressed in various neuroendocrine tumors, including small bowel carcinoids. The main objective of the present study was to examine whether CART expression is associated with survival in small bowel carcinoid patients. Secondary aims were to assess if CART expression is associated with other tumor characteristics or clinical symptoms. EXPERIMENTAL DESIGN: Specimens from 97 patients with small bowel carcinoids were examined for CART expression using immunohistochemistry. A CART score was introduced based on the proportion of CART immunoreactive cells. On inclusion, specimens were examined by routine histopathological methods and detailed clinical patient data were retrieved. The effect of CART on cell viability was assessed in vitro using two intestinal tumor cell lines.RESULTS: Expression of CART (P = 0.011), and increasing CART score (P = 0.033) were associated with worse disease-specific survival. Adjusting for age, disease stage, and tumor grade in multivariable analysis, CART expression was still associated with worse survival (Low CART hazard ratio (HR) 5.47, 95% confidence interval (CI) 0.71 to 42.46; and High CART HR 9.44, 95% CI 1.14 to 78.14). CART expression was not associated with patient age, disease stage, tumor grade, or any presenting symptom. Supporting our clinical data, we found that CART promoted tumor cell viability in vitro in two different tumor cell lines. CONCLUSION: Expression of CART in small bowel carcinoid tumors is associated with worse survival.

PMID: 22553341 [PubMed - as supplied by publisher]

Multicentric neurofibromatosis with rectal prolapse in a California sea lion (Zalophus californianus).

Fetched: May 5th, 2012, 11:00pm MDT

Multicentric neurofibromatosis with rectal prolapse in a California sea lion (Zalophus californianus).

J Zoo Wildl Med. 2012 Mar;43(1):110-9

Authors: Rush EM, Ogburn AL, Garner MM

Abstract
An approximately 31-yr-old California sea lion (Zalophus californianus) with a history of chronic visual impairment and corneal disease presented with slow onset, progressive neurologic deficits. Treatment for rear flipper paresis was not effective and the animal was euthanatized. Histopathologic findings included hepatocellular and biliary neoplasia, ocular amyloidosis, adrenal adenoma and pheochromocytoma, and spinal cord changes consistent with multicentric neurofibromatosis. This is the first documentation of these conditions in a California sea lion.

PMID: 22448517 [PubMed - indexed for MEDLINE]

Effects of angiopoietin-2-blocking antibody on endothelial cell-cell junctions and lung metastasis.

Fetched: May 5th, 2012, 11:00pm MDT

Effects of angiopoietin-2-blocking antibody on endothelial cell-cell junctions and lung metastasis.

J Natl Cancer Inst. 2012 Mar 21;104(6):461-75

Authors: Holopainen T, Saharinen P, D'Amico G, Lampinen A, Eklund L, Sormunen R, Anisimov A, Zarkada G, Lohela M, Heloterä H, Tammela T, Benjamin LE, Ylä-Herttuala S, Leow CC, Koh GY, Alitalo K

Abstract
BACKGROUND: Angiopoietin-2 (Ang2), a ligand for endothelial TEK (Tie2) tyrosine kinase receptor, is induced in hypoxic endothelial cells of tumors, where it promotes tumor angiogenesis and growth. However, the effects of Ang2 on tumor lymphangiogenesis and metastasis are poorly characterized.
METHODS: We addressed the effect of Ang2 on tumor progression and metastasis using systemic Ang2 overexpression in mice carrying tumor xenografts, endothelium-specific overexpression of Ang2 in VEC-tTA/Tet-OS-Ang2 transgenic mice implanted with isogenic tumors, and administration of Ang2-blocking antibodies to tumor-bearing immunodeficient mice. Fisher's exact test was used for analysis of metastasis occurrence, and repeated measures one-way analysis of variance was used for the analysis of primary tumor growth curves. Unpaired t test was used for all other analyses. All statistical tests were two-sided.
RESULTS: Adenoviral expression of Ang2 increased lymph node and lung metastasis in tumor xenografts. The metastatic burden in the lungs was increased in transgenic mice in which Ang2 expression was induced specifically in the vascular endothelium (tumor burden per grid, VEC-tTA/Tet-OS-Ang2 mice [n = 5] vs control mice [n = 4]: 45.23 vs 12.26 mm(2), difference = 32.67 mm(2), 95% confidence interval = 31.87 to 34.07, P < .001). Ang2-blocking antibodies reduced lymph node and lung metastasis, as well as tumor lymphangiogenesis, and decreased tumor cell homing to the lungs after intravenous injection. In the lung metastases, Ang2 overexpression decreased endothelial integrity, whereas the Ang2-blocking antibodies improved endothelial cell-cell junctions and basement membrane contacts of metastasis-associated lung capillaries. At the cellular level, the Ang2-blocking antibodies induced the internalization of Ang2-Tie2 receptor complexes from endothelial cell-cell junctions in endothelial-tumor cell cocultures.
CONCLUSION: Our results indicate that blocking Ang2 inhibits metastatic dissemination in part by enhancing the integrity of endothelial cell-cell junctions.

PMID: 22343031 [PubMed - indexed for MEDLINE]

Permalink for 'Tumor-promoting versus tumor-antagonizing roles of γδ T cells in cancer immunotherapy: results from a prospective phase I/II trial.'

Tumor-promoting versus tumor-antagonizing roles of γδ T cells in cancer immunotherapy: results from a prospective phase I/II trial.

Fetched: May 5th, 2012, 11:00pm MDT

Tumor-promoting versus tumor-antagonizing roles of γδ T cells in cancer immunotherapy: results from a prospective phase I/II trial.

J Immunother. 2012 Feb-Mar;35(2):205-13

Authors: Kunzmann V, Smetak M, Kimmel B, Weigang-Koehler K, Goebeler M, Birkmann J, Becker J, Schmidt-Wolf IG, Einsele H, Wilhelm M

Abstract
Emerging evidence suggests that nitrogen-containing bisphosphonates have direct and indirect anticancer effects including immunomodulatory effects. Using in vivo targeting of bisphosphonate-reactive γδ T cells by adding low-dose interleukin-2 to zoledronic acid, we evaluated the safety, pharmacodynamics, and antitumor activity of this immunotherapy approach in 21 adults with advanced malignancies (renal cell carcinoma [RCC], malignant melanoma, and acute myeloid leukemia). A total of 58 treatment cycles were administered and the median number of treatment cycles was 2.7 (range, 1 to 6). The regimen was well tolerated, with no grade 3 to 4 drug-related adverse events, except for fever. No objective responses were observed in both cohorts of solid tumors (RCC and malignant melanoma), whereas 2 patients with acute myeloid leukemia (25%) achieved objective tumor responses (partial remission). Pharmacodynamic analyses showed significant in vivo activation (interferon-γ production) and expansion of γδ T cells in all evaluable patients. High pretreatment serum vascular endothelial growth factor (VEGF) levels and an unexpected increase in VEGF induced by zoledronic acid plus low-dose interleukin-2 were correlated with the lack of a clinical response. In conclusion, this study indicates that immunotherapy-induced VEGF can limit clinical innate tumor immune responses, especially for angiogenesis-dependent solid tumors. Our data challenge the current cellular immunotherapy paradigms in the treatment of cancer.

PMID: 22306909 [PubMed - indexed for MEDLINE]

Permalink for 'PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer.'

PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer.

Fetched: May 5th, 2012, 11:00pm MDT

PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer.

J Immunother. 2012 Feb-Mar;35(2):169-78

Authors: Dulos J, Carven GJ, van Boxtel SJ, Evers S, Driessen-Engels LJ, Hobo W, Gorecka MA, de Haan AF, Mulders P, Punt CJ, Jacobs JF, Schalken JA, Oosterwijk E, van Eenennaam H, Boots AM

Abstract
Negative costimulation on T cells is exploited by both prostate cancer and melanoma to evade antitumor immunity. Blocking such mechanisms restores antitumor immunity as was demonstrated by the improved survival of patients with metastatic melanoma after treatment with an antibody blocking the CTLA-4 inhibitory receptor (ipilimumab). Enhanced expression of another inhibitory immunoreceptor, programmed death-1 (PD-1), and its ligand, PD-L1, was found to correlate with a poor prognosis in prostate cancer and melanoma. PD-1-blocking antibodies are being developed to modulate antitumor immune responses. To support preclinical and clinical development of anti-PD-1 therapy, we sought to develop biomarker assays that can detect the effect of PD-1-blocking agents in whole blood and peripheral blood mononuclear cells. In this study, we assessed the effect of PD-1 blockade in modulating super antigen (staphylococcus enterotoxin B)-induced and recall antigen (tetanus toxoid)-induced T-cell reactivity in vitro using whole blood and peripheral blood mononuclear cells from patients with advanced melanoma, prostate cancer, and healthy controls. PD-1 blockade was found to shift antigen-induced cellular reactivity toward a proinflammatory Th1/Th17 response, as evidenced by enhanced production of interferon γ, interleukin (IL)-2, tumor necrosis factor α, IL-6, and IL-17 and reduced production of the Th2 cytokines IL-5 and IL-13. It is interesting to note that suppression of Th2 responsivity was seen with whole blood cells only from patients with cancer. Taken together, we identified novel biomarker assays that might be used to determine the functional consequences of PD-1 blockade in peripheral blood cells from patients with cancer. How these assays translate to the local antitumor response remains to be established in a clinical setting.

PMID: 22306905 [PubMed - indexed for MEDLINE]

Improving T-cell immunotherapy for melanoma through a mathematically motivated strategy: efficacy in numbers?

Fetched: May 5th, 2012, 11:00pm MDT

Improving T-cell immunotherapy for melanoma through a mathematically motivated strategy: efficacy in numbers?

J Immunother. 2012 Feb-Mar;35(2):116-24

Authors: Kronik N, Kogan Y, Schlegel PG, Wölfl M

Abstract
T-cell mediated immunotherapy for malignant diseases has become an effective treatment option, especially in malignant melanoma. Recent advances have enabled the transfer of high T-cell numbers with high functionality. However, with more T cells becoming technically available for transfer, questions about dose, treatment schedule, and safety become most relevant. Mathematical oncology can simulate tumor characteristics in silico and predict the tumor response to novel therapeutics. Using similar methods to classical pharmacokinetics/pharmacodynamics-type models, mathematical oncology translates the findings into a multiparameter model system and simulates T-cell therapy for malignant diseases. The tumor and immune system dynamics model can provide minimal requirements (in terms of T-cell dose and T-cell functionality) depending on the tumor characteristics (growth rate, residual tumor size) for a clinical study, and help select the best treatment schedule (repetitive doses, minimally required duration, etc.). Here, we present a new mathematical model developed for modeling cellular immunotherapy for melanoma. Computer simulations based on the new model offer an explanation for the observed finding from clinical trials that the patients with the smallest tumor load respond better. We simulate different parameters critical for improvement of cellular therapy for patients with high tumor load of fast-growing tumors. We show that tumor growth rate and tumor load are crucial in predicting the outcome of T-cell therapy. Rather than intuitively extrapolating from experimental data, we demonstrate how mathematical oncology can assist in rational planning of clinical trials.

PMID: 22306899 [PubMed - indexed for MEDLINE]

Ascorbate depletion increases growth and metastasis of melanoma cells in vitamin C deficient mice.

Fetched: May 5th, 2012, 11:00pm MDT

Ascorbate depletion increases growth and metastasis of melanoma cells in vitamin C deficient mice.

Exp Oncol. 2011 Dec;33(4):226-30

Authors: Cha J, Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M

Abstract
AIM: Our main objective was to determine the effect of ascorbate supplementation in mice unable to synthesize ascorbic acid (gulo KO) when challenged with murine B16FO cancer cells.
METHODS: Gulo KO female mice 36-40 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to subcutaneous injection of 2.5×10(6) B16FO murine melanoma cells in the right flank of mice. A control group of wild type mice were also injected with the melanoma cells and maintained on a regular murine diet. Mice were continued on their respective diets for another 2 weeks after injection. The mice were then sacrificed, blood was drawn and their tumors were measured, excised and processed for histology.
RESULTS: Mean weight of animals decreased significantly (30%, p < 0.0001) in the ascorbate-restricted group but increased slightly, but insignificantly, in the ascorbate-supplemented group. The mean tumor weight in ascorbate supplemented mice was significantly reduced (by 64%, p = 0.004) compared to tumor weight in ascorbate-deprived gulo mice. The mean tumor weight of wild type mice did not differ significantly from the ascorbate-supplemented mice. Gulo KO mice supplemented with ascorbate developed smaller tumors with more collagen encapsulation and fibrous capsule interdigitation, while gulo KO mice deprived of ascorbate hosted large tumors with poorly defined borders, showing more necrosis and mitosis. Ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine IL-6 (90% decrease, p = 0.04) and IL-1β (62% decrease) compared to the levels in gulo KO mice deprived of ascorbate.
CONCLUSION: Ascorbate supplementation modulated tumor growth and inflammatory cytokine secretion as well as enhanced encapsulation of tumors in scorbutic mice.

PMID: 22217712 [PubMed - indexed for MEDLINE]

[The molecular mechanism of extravasation in mouse melanoma lung metastasis model].

Fetched: May 5th, 2012, 11:00pm MDT

[The molecular mechanism of extravasation in mouse melanoma lung metastasis model].

Sichuan Da Xue Xue Bao Yi Xue Ban. 2011 Sep;42(5):594-8

Authors: Pang LM, Zhao CJ, Zhao YW, Li ZM, Yang HS, Wei YQ

Abstract
OBJECTIVE: To study molecular mechanisms underlying the extravasation of mice melanoma cells during lung metastasis.
METHODS: B16-RED melanoma cell line was established which stably express the red fluorescent protein. B16-RED cells were compared with B16 cells in ability of proliferation and lung metastasis. A mouse lung metastasis model was established with B16-RED melanoma cells. FITC-dextran was injected i.v. and CD31 indirect immunoflourescence (IIF) staining was made to identify the location of the tumor cells and the time of tumor cell extravasation. Finally, at 48 hours post cell injection, the lung and a normal lung were removed and used for 32K mice microarray analysis.
RESULTS: B16-RED was consistent with B16 in cell shape and ability of proliferation and lung metastasis. 52.7% of B16-RED melanoma cells completed the extravasation within 48 hours in mouse lung metastasis model. Many important signal pathways were involved during lung metastasis, including leukocyte transendothelial migration, MAPK signaling pathway, neuroactive ligand-receptor interaction, focal adhesion, cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, axon guidance, calcium signaling pathway, tight junction, etc.
CONCLUSION: The extravasation during metastasis is a complex and multiple-steps process, in which many important signal pathways in host tissues were involved.

PMID: 22007479 [PubMed - indexed for MEDLINE]

Permalink for 'Controlled release of octreotide and assessment of peptide acylation from poly(D,L-lactide-co-hydroxymethyl glycolide) compared to PLGA microspheres.'

Controlled release of octreotide and assessment of peptide acylation from poly(D,L-lactide-co-hydroxymethyl glycolide) compared to PLGA microspheres.

Fetched: May 5th, 2012, 11:00pm MDT

Controlled release of octreotide and assessment of peptide acylation from poly(D,L-lactide-co-hydroxymethyl glycolide) compared to PLGA microspheres.

Pharm Res. 2012 Jan;29(1):110-20

Authors: Ghassemi AH, van Steenbergen MJ, Barendregt A, Talsma H, Kok RJ, van Nostrum CF, Crommelin DJ, Hennink WE

Abstract
PURPOSE: To investigate the in vitro release of octreotide acetate, a somatostatin agonist, from microspheres based on a hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA).
METHODS: Spherical and non-porous octreotide-loaded PLHMGA microspheres (12 to 16 μm) and loading efficiency of 60-70% were prepared by a solvent evaporation. Octreotide release profiles were compared with commercial PLGA formulation (Sandostatin LAR(®)); possible peptide modification with lactic, glycolic and hydroxymethyl glycolic acid units was monitored.
RESULTS: PLHMGA microspheres showed burst release (~20%) followed by sustained release for 20-60 days, depending on the hydrophilicity of the polymer. Percentage of released loaded peptide was high (70-90%); > 60% of released peptide was native octreotide. PLGA microspheres did not show peptide release for the first 10 days, after which it was released in a sustained manner over the next 90 days; > 75% of released peptides were acylated adducts.
CONCLUSIONS: PLHMGA microspheres are promising controlled systems for peptides with excellent control over release kinetics. Moreover, substantially less peptide modification occurred in PLHMGA than in PLGA microspheres.

PMID: 21744173 [PubMed - indexed for MEDLINE]

Permalink for 'Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patients.'

Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patients.

Fetched: May 5th, 2012, 11:00pm MDT

Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patients.

Cell Oncol (Dordr). 2011 Oct;34(5):435-41

Authors: Muscarella LA, D'Alessandro V, la Torre A, Copetti M, De Cata A, Parrella P, Sperandeo M, Pellegrini F, Frusciante V, Maiello E, Merla G, Fazio VM, Vendemiale G

Abstract
BACKGROUND: Somatostatin (SS) acts as a universal endocrine off-switch, and also inhibits the growth of neuroendocrine tumours through its specific receptors (SSTRs). Somatostatin receptors are G-protein-coupled receptors, which are encoded by five separate genes (SSTR1-5). Short peptide analogues demonstrate specific binding only for the subgroup consisting of SSTR2a, SSTR3 and SSTR5. Moreover, previous studies reported that expression of mRNA for SSTR2a correlated with therapeutic outcome in patients with carcinoid tumours treated with somatostatin analogs.
PURPOSE: To develop and apply a Real Time Quantitative PCR technique (RT-qPCR) to compare and contrast the mRNA levels of SSTR2a, SSTR3 and SSTR5 in Neuroendocrine Lung Cancer affected patients.
METHODS: Peripheral blood samples from 21 neuroendocrine lung cancer affected patients (14 SCLC, 6 LC and 1 LCNEC) subjected to scintigraphy with (111)In-DTPA-D-Phe(1)-octreotide (OctreoScan) and 24 healthy blood donors were investigated by RT-qPCR. mRNA levels for SSTR2a, SSTR3 and SSTR5 were measured in peripheral blood samples with a relative quantification method using plasmid dilutions as calibration curves and GAPDH as reference gene.
RESULTS: A statistically significant increase in target genes/GAPDH copy number ratio was found for SSTR2a (median 38; IQR 22-141) and SSTR5 (median 51; IQR 19-499) in neuroendocrine lung cancer affected patients as compared with samples from healthy blood donors (P ≤ 0.0003 and P ≤ 0.0005). Since low levels of expression were detected in the control group for all three genes, optimal cut-off values were assessed using ROC curve analyses and were equal to 9.05 for SSTR2a and 16.97 for SSTR5. These cut off values resulted in a sensitivity of 86% (95%IC 65-95) for both markers and a specificity of 83% (95%IC 64-93%) and 79% (95%IC 60-91%) for SSTR2a and SSTR5 respectively. Comparison between OctreoScan results and RT-qPCR analysis demonstrated agreement in 76% of the cases.
CONCLUSIONS: Our results suggest that SSTR2a and SSTR5 mRNAs are detectable in peripheral blood of neuroendocrine lung cancer affected patients using real-time quantitative PCR, with a good agreement with OctreoScan. The high sensitivity of this non-invasive molecular technique suggests that this method could represent a useful tool in the clinical management of neuroendocrine lung cancers.

PMID: 21503779 [PubMed - indexed for MEDLINE]

[Surgery strategy about C1-2 dumbbell tumor].

Fetched: May 5th, 2012, 11:00pm MDT

[Surgery strategy about C1-2 dumbbell tumor].

Beijing Da Xue Xue Bao. 2011 Apr 18;43(2):301-3

Authors: Ma CC, Wang ZY, Yu T

Abstract
OBJECTIVE: To study the operation of C1-2 dumbbell-shaped tumor, and its effect on the cervical spine stability.
METHODS: Different surgical tumor resection was selected according to the tumor size and the invasion scope. Hemilaminectomy was the first choice for the resection of the tumor at intr-extraspinal canal in the conventional prone position. After the tumor was fully revealed, the epidural tumor was removed first with enough space to be vacated, then the subdural section was removed. If the tumor in the spinal canal was more than half of the spinal canal, to prevent spinal cord injury, the part of the C1-2 spinous process base should be removed to facilitate the exposure. Dural defect should be repaired and the muscle sutured to achieve anatomic reduction in order to facilitate the stability of the cervical spine. Lateral approach should be combined to resect the tumor if its total removal was impossible as the tumor had invaded the spinal canal outside over 4 cm or completely surrounded the vertebral artery.
RESULTS: C1-2 dumbbell-type tumors were treated in 16 cases, of which 12 were of schwannoma, 3 of meningioma and 1 of ganglion cell tumor. Total resection was in 14 cases, and subtotal resection in 2. After operation, the symptoms of pain in the neck and upper limb muscle weakness were relieved. All the patients were followed up. The follow-up period was 3-48 months. No cervical spine instability or tumor recurrence was found.
CONCLUSION: C1-2 dumbbell-shaped tumors could be well resected by poster-median hemilamiectomy approach or joint lateral approach , and the stability of cervical spine could be better maintained at the same time.

PMID: 21503131 [PubMed - indexed for MEDLINE]

[(131)I labeling and bioactivity evaluation of a novel RGD dimer targeted to integrin αvβ3 receptor].

Fetched: May 5th, 2012, 11:00pm MDT

[(131)I labeling and bioactivity evaluation of a novel RGD dimer targeted to integrin αvβ3 receptor].

Beijing Da Xue Xue Bao. 2011 Apr 18;43(2):295-300

Authors: Zhang CL, Wang RF, Zhang L, Guo FQ, Li L, Kang L, Yan P, Yang M

Abstract
OBJECTIVE: To study the (131)I labeling, tumor targeting property, biodistrubution and imaging of a novel disulfide bridged Arg-Gly-Asp (RGD) peptide dimer and investigate its possibility for tumor angiogenesis imaging.
METHODS: A disulfide bridged cRGD peptide dimer [c(RGD)2] was designed according to the published RESULTS of structure-activity relationship study of c(RGDfV) and modified with hydrophilic amino acid. The affinity of the peptide to αvβ3 receptor was determined by binding assay. The peptide was labeled with (131)I by ChT method. The stability and lg n-octanol-water partition coefficient of the labeled peptide were tested. The biodistribution, inhibition with unlabeled peptide and imaging were performed by injecting the labeled peptide into the mice bearing meloma B16.
RESULTS: The (131)I labeling efficiency and radiochemical purity were (76.35 ± 2.33)% and (95.20 ± 3.25)%, respectively. Ka was (0.137 ± 0.057) × 10(9) /mol/L, and lgPo(ctanol/water) was-1.628. The tumor uptake of the labeled peptide at 1 h, 3 h, 5 h and 24 h were (0.67 ± 0.13)%ID/g, (0.42 ± 0.08)%ID/g, (0.51± 0.11)%ID/g and (0.18 ± 0.02)%ID/g, respectively. The tumor clearance was low, so the T/NT increased with time. The T/M and T/B were 4.42 ± 1.70 and 2.27 ± 0.45, respectively, 24 h post-injection. The hepatic uptake of the labeled peptide was low. The tumor-to-liver ratio was 2.10 ± 0.60 at 1 h post-injection, coinjection of c(RGD)2 with (131)I-c(RGD)2 resulted in a significant decrease in tumor uptake. In total body images, only kidneys were distinctive whereas tumor was clear in chest images 3 h post-injection.
CONCLUSION: c(RGD)2 can be successfully labeled with (131)I by ChT method. The labeled peptide can be specifically combined with tumor, which suggests its possibility in tumor angiogenesis imaging. Its low liver uptake provides an advantage for tumor imaging.

PMID: 21503130 [PubMed - indexed for MEDLINE]

[Laboratory evaluation of TGFbeta1, IL-10, VEGF levels in vivo and in vitro in patients with solid tumors].

Fetched: May 5th, 2012, 11:00pm MDT

[Laboratory evaluation of TGFbeta1, IL-10, VEGF levels in vivo and in vitro in patients with solid tumors].

Vopr Onkol. 2011;57(6):759-66

Authors: Danilova AB, Danilov AO, Fakhrutdinova OL, Baldueva IA, Moiseenko VM

Abstract
Tumor cells can acquire the mechanisms of immune response evasion. One of these mechanisms is synthesis and secretion in the microenvironment of immunosuppressive factors able to block immune cells maturation and function. We investigated plasma levels of TGFbeta1 and IL0 in 10 healthy volunteers and 114 patients with solid tumors (breast cancer--24, gastrointestinal tumors--27, renal cell carcinoma--15, lung cancer--9, ovarian cancer--13, cutaneous melanoma--18, primary multiple tumors--2, prostate cancer--6). TGFbeta and IL10 concentration in supernatants of 37 primary cultures (cutaneous melanoma, renal cell carcinoma and prostate cancer) and 10 cultures of melanoma during cultivation were also studied. VEGF was determined by immunocytochemistry staining in 15 melanoma culture specimens. The lowest level of TGFbeta1 was documented in rectal cancer patients, 30.05 +/- 12.30 ng/ml (p < 0.05), the highest in renal cell cancer and pancreatic cancer patients, 145.61 +/- 11.32 and 146.15 +/- 30.56 ng/ml (p < 0.001), respectively. Primary cultures of tumor cells can synthesize traceable amounts of TGFbeta1 and IL10. Cultures of cutaneous melanoma, renal cell carcinoma and prostate cancer cells did not change expression level of IL-10 after several passages. VEGF was expressed in 20% of cutaneous melanoma cultures. We suppose that tests for TGFbeta1, IL10 and VEGF in culture supernatants from tumor cell lines, on the surface of the cells purposed for cancer vaccines and in serum of patients to be vaccinated are potentially useful.

PMID: 22416394 [PubMed - indexed for MEDLINE]

Ki-67 labeling: A more sensitive indicator of malignant phenotype than mitotic count or tumor size?

Fetched: May 4th, 2012, 11:00pm MDT

Ki-67 labeling: A more sensitive indicator of malignant phenotype than mitotic count or tumor size?

J Surg Oncol. 2012 May 1;

Authors: Lowe K, Khithani A, Liu E, Winston T, Christian D, Saad J, Jeyarajah DR

Abstract
BACKGROUND AND OBJECTIVES: The Ki-67 index has been incorporated into The World Health Organization's classification system of pancreatic neuroendocrine tumors. However, pathologists continue to question the utility of Ki-67 index over that of mitotic count as an indicator of proliferative activity. The intent of the current study is to compare K-i67 index with tumor size and mitotic rate for the association of each with lymph node metastasis and survival. METHODS: The current study is a review of 24 patients with pancreatic neuroendocrine tumors. RESULTS: Regional LNM were present in 100% of tumors with Ki-67 index >10%, while only 25% of tumors with <10% Ki-67 had LNM (P = 0.003). No tumors <2 cm had >10% Ki-67 labeling. Of patients with tumors showing ≥10% Ki-67 labeling, 80% died during the observation period of this study, while during the same time period, no patients with <10% Ki-67 labeling died. CONCLUSION: Ki-67 index of >10% is a sensitive indicator of malignant behavior and mortality. Future advances in management of pNETs will require development of staging guidelines with higher predictive value. Inclusion of Ki-67 labeling >10% as an indicator of aggressive disease may contribute to such improvements. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.

PMID: 22549809 [PubMed - as supplied by publisher]

The ghost carcinoid in a patient with 120-fold elevated 5-HIAA.

Fetched: May 4th, 2012, 11:00pm MDT

The ghost carcinoid in a patient with 120-fold elevated 5-HIAA.

Endocr Pract. 2012 May 1;:1-6

Authors: Yu R

PMID: 22548955 [PubMed - as supplied by publisher]

Feasibility of transanal minimally invasive surgery for mid-rectal lesions.

Fetched: May 2nd, 2012, 11:00pm MDT

Feasibility of transanal minimally invasive surgery for mid-rectal lesions.

Surg Endosc. 2012 Apr 28;

Authors: Lim SB, Seo SI, Lee JL, Kwak JY, Jang TY, Kim CW, Yoon YS, Yu CS, Kim JC

Abstract
BACKGROUND: Transanal minimally invasive surgery (TAMIS) has emerged as an alternative to transanal endoscopic microsurgery. We assessed the feasibility of TAMIS for lesions located in the mid rectum. METHODS: From July 2010 to October 2011, 16 consecutive patients with rectal pathology underwent TAMIS. After a single-incision laparoscopic surgery port was introduced into the anal canal, pneumorectum was established with a laparoscopic device, followed by transanal excision with conventional laparoscopic instruments, including graspers, monopolar electrocautery, and needle drivers. Clinicopathological findings, surgical procedure results, and perioperative outcomes were determined prospectively. RESULTS: Of the 16 patients, 11 had rectal cancers (3 T1 lesions and 8 after preoperative chemoradiotherapy), 4 had neuroendocrine tumors, and 1 had a mucocele. The median length of the lesions from anal verge was 7.5 cm (range 4-10 cm). All procedures were completed laparoscopically without conversion to conventional transanal approach. The median operating time was 86 min (range 33-160 min), and the median estimated blood loss was 15 ml (range 0-150 ml) with no patient requiring intraoperative transfusions. There was no surgical morbidity or mortality, but one patient died during follow-up due to synchronous advanced gastric cancer. The median postoperative hospital stay was 3 days (range 2-6 days). CONCLUSIONS: TAMIS seems to be a feasible and safe treatment option for lesions located in the mid rectum.

PMID: 22543995 [PubMed - as supplied by publisher]

MENX.

Fetched: May 2nd, 2012, 11:00pm MDT

MENX.

Ann Endocrinol (Paris). 2012 Apr 25;

Authors: Pellegata NS

Abstract
Multiple endocrine neoplasias (MEN) are a group of hereditary disorders characterized by tumors arising in more than one neuroendocrine tissue. There are two major forms which can occur in humans, MEN type 1 (MEN1) and MEN type 2 (MEN2). These syndromes are transmitted as autosomal dominant traits with high penetrance and have a different tumor spectrum. MEN1 and MEN2 are caused by germline mutations in the MEN1 and RET genes, respectively. Recently, a variant of the MEN syndromes was discovered in a rat colony and was named MENX since affected animals develop tumors with a spectrum that shares features with both MEN1 and MEN2 human syndromes. Extensive genetic studies identified a germline mutation in the Cdkn1b gene, encoding the p27 cell cycle inhibitor, as the causative mutation for MENX. Capitalizing on these findings, heterozygous germline mutations in the human homologue, CDKN1B, were searched for and identified in patients with multiple endocrine tumors. As a consequence of this discovery, a novel human MEN syndrome, named MEN4, was recognized which is caused by mutations in p27. Altogether these studies identified Cdkn1b/CDKN1B as a novel tumor susceptibility gene for multiple endocrine tumors in both rats and humans. Here I review the phenotypic features and the genetics of the MENX rat syndrome. I briefly address the main functions of p27 and how they are affected by the MENX-associated mutation. Finally, I present examples of how this animal model might be exploited as a translational platform for preclinical studies of pituitary adenomas.

PMID: 22542001 [PubMed - as supplied by publisher]

Permalink for 'Asymmetric intense bilateral adrenal uptake on [18F]fluorodeoxyglucose positron emission tomography/computed tomography in a patient with solitary pulmonary nodule.'

Asymmetric intense bilateral adrenal uptake on [18F]fluorodeoxyglucose positron emission tomography/computed tomography in a patient with solitary pulmonary nodule.

Fetched: May 2nd, 2012, 11:00pm MDT

Asymmetric intense bilateral adrenal uptake on [18F]fluorodeoxyglucose positron emission tomography/computed tomography in a patient with solitary pulmonary nodule.

J Clin Oncol. 2012 Feb 20;30(6):e83-5

Authors: Cheng MF, Lin MW, Wu CT, Shih SR, Wu YW, Tzen KY, Yen RF

PMID: 22215749 [PubMed - indexed for MEDLINE]

Posterior reversible encephalopathy syndrome during ipilimumab therapy for malignant melanoma.

Fetched: May 2nd, 2012, 11:00pm MDT

Posterior reversible encephalopathy syndrome during ipilimumab therapy for malignant melanoma.

J Clin Oncol. 2012 Feb 20;30(6):e76-8

Authors: Maur M, Tomasello C, Frassoldati A, Dieci MV, Barbieri E, Conte P

PMID: 22203769 [PubMed - indexed for MEDLINE]

[A case of a carcinoid tumour presenting as an "upper lobe syndrome"].

Fetched: May 2nd, 2012, 11:00pm MDT

[A case of a carcinoid tumour presenting as an "upper lobe syndrome"].

Rev Mal Respir. 2011 Nov;28(9):1172-5

Authors: Noël-Savina E, Tromeur C, Quere G, Choplain JN, Leroyer C, Descourt R

Abstract
A 53-year-old woman presented with progressive cough related to an endobronchial carcinoid tumour. The location of the tumour in the right upper lobe bronchus could be described as an "upper lobe syndrome" by analogy with the "middle lobe syndrome" or Brock's syndrome. Surgical management consisted of lobectomy and lymph node dissection. This established the diagnosis of typical carcinoid tumour. There was no mediastinal nodal invasion. Three months after surgery all symptoms had disappeared.

PMID: 22123146 [PubMed - indexed for MEDLINE]

Suppression of the maturation and activation of the dendritic cell line DC2.4 by melanoma-derived factors.

Fetched: May 2nd, 2012, 11:00pm MDT

Suppression of the maturation and activation of the dendritic cell line DC2.4 by melanoma-derived factors.

Cell Immunol. 2012;272(2):275-82

Authors: Hargadon KM, Forrest OA, Reddy PR

Abstract
Dendritic cells play critical roles in both innate and adaptive immunity, and their numerous functions are tightly linked to their maturation and activation status. Here, we characterize the murine dendritic cell line DC2.4 as a model for studying dendritic cell maturation and activation, and we evaluate the influence of melanoma tumor cells on these processes. Exposure of DC2.4 cells to the Toll-like receptor ligand lipopolysaccharide induces both maturation and activation of these cells, characterized by upregulation of costimulatory molecule expression and proinflammatory cytokine/chemokine production. This maturation and activation is suppressed by soluble factors derived from both the highly tumorigenic B16-F1 and the poorly tumorigenic D5.1G4 murine melanoma cell lines. Interestingly, the extent of DC2.4 immunosuppression by these melanomas correlates with their tumorigenicity, suggesting a potentially vital role for dendritic cell/tumor cell interactions in the regulation of anti-tumor immunity and tumor outgrowth.

PMID: 22051048 [PubMed - indexed for MEDLINE]

Permalink for '[Management of pregnant women with advanced cervical cancer: About five cases observed in Lille from 2002 till 2009. Evaluation of practices referring to the new French recommendations of 2008].'

[Management of pregnant women with advanced cervical cancer: About five cases observed in Lille from 2002 till 2009. Evaluation of practices referring to the new French recommendations of 2008].

Fetched: May 2nd, 2012, 11:00pm MDT

[Management of pregnant women with advanced cervical cancer: About five cases observed in Lille from 2002 till 2009. Evaluation of practices referring to the new French recommendations of 2008].

J Gynecol Obstet Biol Reprod (Paris). 2011 Oct;40(6):514-21

Authors: Carillon MA, Emmanuelli V, Castelain B, Taieb S, Collinet P, Vinatier D, Lesoin A, Chevalier-Evain V, Leblanc E, Narducci F

Abstract
PURPOSE: An update on the management of invasive cervical cancer (from stage IB) diagnosed during pregnancy with reference to the recent French guidelines.
PATIENTS AND METHODS: We retrospectively analyzed patients for whom invasive cervical cancer was diagnosed during pregnancy and managed jointly by Jeanne-de-Flandres and Roubaix maternity and by Oscar-Lambret cancer center between 2002 and 2009.
RESULTS: Five patients were included: four stage IB1, and one stage IB2. Five pregnancies resulted in the birth of six alive children. Three patients received neoadjuvant chemotherapy during pregnancy. One patient had a laparoscopic pelvic lymphadenectomy in first trimester. Two laparoscopic extraperitoneal paraortic lymphadenectomy have been made. The mean time of survey is 47.5 months (12-94 months). One patient died of her cancer.
CONCLUSION: The diagnosis of cervical cancer during pregnancy involves the same therapeutic guidelines in the absence of pregnancy. The laparoscopic pelvic lymphadenectomy (up to 20 to 24 weeks of gestation) is crucial in the therapeutic treatment for tumors less than 4cm. Neoadjuvant chemotherapy is used during pregnancy for patients refusing medical termination of pregnancy.

PMID: 21807469 [PubMed - indexed for MEDLINE]

Permalink for 'The clinical value of MRI using single-shot echoplanar DWI to identify liver involvement in patients with advanced gastroenteropancreatic-neuroendocrine tumors (GEP-NETs), compared to FSE T2 and FFE T1 weighted image after i.v. Gd-EOB-DTPA contrast enhan'

The clinical value of MRI using single-shot echoplanar DWI to identify liver involvement in patients with advanced gastroenteropancreatic-neuroendocrine tumors (GEP-NETs), compared to FSE T2 and FFE T1 weighted image after i.v. Gd-EOB-DTPA contrast enhan

Fetched: April 28th, 2012, 11:00pm MDT

The clinical value of MRI using single-shot echoplanar DWI to identify liver involvement in patients with advanced gastroenteropancreatic-neuroendocrine tumors (GEP-NETs), compared to FSE T2 and FFE T1 weighted image after i.v. Gd-EOB-DTPA contrast enhancement.

Med Sci Monit. 2012 Apr 23;18(5):MT33-40

Authors: Sankowski AJ, Cwikla JB, Nowicki ML, Chaberek S, Pech M, Lewczuk A, Walecki J

Abstract
Background: To assess the detection rate of liver lesions in patients with advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs) using echo planar (EP) DWI (diffusion weighted imaging) as compared to standard FSE T2 wi and FFE T1 wi with i.v. (Gd-EOB)-DTPA.<br /> Material/Methods: This prospective single-institution study included 55 patients with liver involvement confirmed by GEP-NETs 1.5T MRI system, using FSE T2, EP DWI and FFE T1 with i.v. (Gd-EOB)-DTPA. The potential differences between detection rates of liver deposits using 3 different MR approaches and between groups of patients were compared.<br /> Results: Mean number of liver deposits: FSE T2=20.7, FFE T1=25.7 and tested EP DWI=24.0. No significant difference was found in overall detection rate of liver deposits seen in 3 different techniques. A significant difference in detection rate of liver deposits was noted between male vs. female and secreting vs. non-secreting cancers. There was nearly perfect agreement between both observers, and each of the tested MRI approaches in regards to number of detected liver lesions (Cohen's kappa=0.848-1).<br /> Conclusions: There were no significant differences among the 3 different MRI approaches in detection rates of liver deposits. Perfect agreement with high detection rate of liver deposits provides a rationale for the use of EP DWI in follow-up studies in GEP-NET patients.<br />

PMID: 22534718 [PubMed - in process]

Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic features, terminology, immunohistochemical profile, and clinical outcomes in a series of 50 cases from a single institution in India.

Fetched: April 28th, 2012, 11:00pm MDT

Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic features, terminology, immunohistochemical profile, and clinical outcomes in a series of 50 cases from a single institution in India.

Ann Diagn Pathol. 2012 Apr 23;

Authors: Rekhi B, Patil B, Deodhar KK, Maheshwari A, A Kerkar R, Gupta S, Tongaonkar HB, Shrivastava SK

Abstract
Neuroendocrine carcinomas of the cervix are uncommon, characterized by a histomorphological spectrum and, mostly, an aggressive clinical course. There are only few substantial studies on such cases documented from our country, where cervical cancer is the second most common cancer affecting women. Herein, we present a spectrum of 50 cervical neuroendocrine carcinomas, including histopathologic features, terminology, immunohistochemical (IHC) profile, and clinical outcomes, wherever available. Fifty tumors occurred in women, with their age ranging from 23 to 69 years (mean, 48.6 years; median, 46.5 years). Stagewise, among 25 cases, most cases (6, or 24%) presented with stage IB. Average tumor size was 4.7 cm. On histopathologic review, 26 tumors (52%) were classified as small cell carcinoma (SMCA); 14 (28%), as large cell neuroendocrine carcinomas (LCNECs); 4 (8%), as SMCA+LCNECs; and 6, as mixed carcinomas, including 3 tumors (6%) with SMCA and squamous cell carcinoma (SCC), 2 tumors (4%) with LCNEC and adenocarcinoma, and a single tumor (2%) with LCNEC and squamous cell carcinoma. On IHC performed in 41 tumors (82%), 36 tumors (87.8%) were positive for at least a single neuroendocrine marker, and 22 (53.6%) expressed 2 neuroendocrine markers. Synaptophysin was positive in 22 (59.4%) of 37 tumors; chromogranin, in 27 (72.9%) of 37; CD56, in 8 (100%) of 8; and neuron-specific enolase in 7 (87.5%) of 8 tumors. Treatment wise, among 30 patients (60%), 6 (20%) underwent surgery, including Wertheim hysterectomy (5) and simple hysterectomy (1); 8 (26.6%) underwent surgery with adjuvant treatment, and 10 patients (33.3%) were offered chemotherapy and/or radiotherapy. On follow-up (27 patients, or 54%) over 1 to 144 months, 16 patients (59.2%) were alive with disease over median duration of 9 months, and 7 (25.9%) were free of disease over median duration of 26.5 months. There were 5 recorded deaths. Thirteen tumors (48.1%) metastasized, most commonly to liver. In cases with early stage disease and adjuvant treatment, including radiotherapy, LCNEC histology fared well. This study forms the largest documented series on cervical neuroendocrine carcinomas from our country, testifying the current histopathologic classification system. Although SMCAs can be recognized on morphology, LCNECs need to be correctly identified because these can be misdiagnosed in the absence of neuroendocrine markers. Synaptophysin, chromogranin, and CD56 are optimal IHC markers. Small cell carcinomas, pure or mixed, are relatively more aggressive. All these tumors are best treated with multimodal therapy. Early stage disease treated with radical surgery and adjuvant treatment seems to increase survival. Despite aggressive treatment, prognosis is dismal.

PMID: 22534245 [PubMed - as supplied by publisher]

[Choroidal melanoma and maculopathy].

Fetched: April 28th, 2012, 11:00pm MDT

[Choroidal melanoma and maculopathy].

Vestn Oftalmol. 2011 Nov-Dec;127(6):3-6

Authors: Brovkina AF, Zargarian AE, Tyrkina KI, Shut'ko EIu

Abstract
Distant macular changes were revealed in 21 of 28 patients with intraocular melanoma. In 13 eyes maculopathy was very distant from choroidal melanoma (CM), in 4 cases the tumor was located preequatorially and in 9 patients in the posterior fundus beyond the macular zone. In 8 patients bilateral AMD was found along with CM. Revealed changes are considered to be tumor-associated sign of progressing CM. Association of AMD and CM should be considered as a combination of two distinct conditions, when CM disturbs hematoretinal barrier and thus leads to AMD progression.

PMID: 22442984 [PubMed - indexed for MEDLINE]

[Laparoscopic pancreatic distal resection for vipoma].

Fetched: April 28th, 2012, 11:00pm MDT

[Laparoscopic pancreatic distal resection for vipoma].

Klin Khir. 2011 Dec;(12):71-2

Authors: Skums AV, Shkarban VP, Lips'ka OIe

PMID: 22432199 [PubMed - indexed for MEDLINE]

Pre- and posttransplant management of solid organ transplant recipients: risk-adjusted follow-up.

Fetched: April 28th, 2012, 11:00pm MDT

Pre- and posttransplant management of solid organ transplant recipients: risk-adjusted follow-up.

Curr Probl Dermatol. 2012;43:57-70

Authors: Schreve BS, Anliker M, Arnold AW, Kempf W, Laffitte E, Lapointe AK, Mainetti C, Pelloni F, Oberholzer P, Serra A, Streit M, Hofbauer GF,

Abstract
Solid organ transplant recipients (SOTR) have an increased risk of skin cancer due to their long-term immunosuppressive state. As the number of these patients is increasing, as well as their life expectancy, it is important to discuss the screening and management of skin cancer in this group of patients. The role of the dermatologist, in collaboration with the transplant team, is important both before transplantation, where patients are screened for skin lesions and the individual risk for skin cancer development is assessed, and after transplantation. Posttransplant management consists of regular dermatological consultations (the frequency depends on different factors discussed below), where early skin cancer screening and management, as well as patient education on sun protective behavior is taught and enforced. Indeed, SOTR are very sensitive to sun damage due to their immunosuppressive state, leading to cumulative sun damage which results in field cancerization with numerous lesions such as in situ squamous cell carcinoma, actinic keratosis and Bowen's disease. These lesions should be recognized and treated as early as possible. Therapeutic options discussed will involve topical therapy, surgical management, adjustment of the patient's immunosuppressive therapy (i.e. reduction of immunosuppression and/or switch to mammalian target of rapamycin inhibitors) and chemoprevention with the retinoid acitretin, which reduces the recurrence rate of squamous cell carcinoma. The dermatological follow-up of SOTR should be integrated into the comprehensive posttransplant care.

PMID: 22377920 [PubMed - indexed for MEDLINE]

Critical skin cancer in organ transplant recipients--a dermatopathological view.

Fetched: April 28th, 2012, 11:00pm MDT

Critical skin cancer in organ transplant recipients--a dermatopathological view.

Curr Probl Dermatol. 2012;43:18-35

Authors: Kempf W, Mertz KD, Kanitakis J, Hofbauer GF

Abstract
Organ transplant recipients (OTR) are at significantly increased risk to develop a wide variety of skin cancers, particularly epithelial skin cancer, Merkel cell carcinoma and Kaposi's sarcoma. In addition, melanoma, skin adnexal neoplasm and cutaneous lymphomas are more common in OTR and may differ in their clinicopathological presentation from tumors in immunocompetent patients. The accuracy of clinical diagnosis of suspected premalignant and malignant skin lesions in OTR is modest. Therefore, histopathological diagnosis is an essential element for the diagnostic workup of skin cancers, and additionally provides important information on prognosis. This review discusses the histopathological aspects of skin cancers in OTR, the impact of dermatopathological analysis on prognosis and understanding of the pathogenesis of these neoplasms.

PMID: 22377917 [PubMed - indexed for MEDLINE]

The current status of S-100B as a biomarker in melanoma.

Fetched: April 28th, 2012, 11:00pm MDT

The current status of S-100B as a biomarker in melanoma.

Eur J Surg Oncol. 2012 Apr;38(4):281-5

Authors: Kruijff S, Hoekstra HJ

Abstract
Melanoma is the most malignant type of all skin cancer types. It causes over 75% of all skin cancer related mortality. In the Netherlands, the total number of new diagnosed melanoma patients is expected to increase from 2400 patients in 2000 to 4800 patients in 2015. After surgical treatment, 20-28% of melanoma patients present with loco-regional recurrence, 26-60% with regional recurrences, and 15-50% with distant metastases. Early detection of lymph node (micro) metastases by means of a sentinel lymph node biopsy (SLNB) is therefore of crucial importance since early lymph node dissection decrease treatment morbidity and improve overall survival. However when patients present with palpable nodes, given the heterogeneity in survival, the suspicion rises that numerous patients have a form of subclinical dissemination, which can remain undetected by current modern imaging methods. Biomarkers could illuminate on this matter, although there is very little understanding of their biological significance. It can be expected that the strongest biological markers are surrogates of key biological events. The protein S-100B seems to be the best analyzed biomarker in melanoma. It has the potential to identify high-risk stage III melanoma patients who may benefit from adjuvant systematic treatment. In the stratification of new adjuvant therapeutic trials in patients with loco-regional recurrences, we therefore recommend the use of S-100B in the stratification. Since an effective (adjuvant) therapy for loco-regional metastatic and disseminated melanoma is recently introduced, the use of S-100B seems to alter dramatically in the near future.

PMID: 22240030 [PubMed - indexed for MEDLINE]

Long-term tumor control and cranial nerve outcomes following γ knife surgery for larger-volume vestibular schwannomas.

Fetched: April 28th, 2012, 11:00pm MDT

Long-term tumor control and cranial nerve outcomes following γ knife surgery for larger-volume vestibular schwannomas.

J Neurosurg. 2012 Mar;116(3):598-604

Authors: Milligan BD, Pollock BE, Foote RL, Link MJ

Abstract
OBJECT: γ knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors.
METHODS: Prospectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm(3) (range 5.3-19.1 cm(3)). The median maximum posterior fossa diameter was 2.8 cm (range 2.5-3.8 cm). The median tumor margin dose was 12 Gy (range 12-14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26-121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection.
RESULTS: Four patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction.
CONCLUSIONS: Single-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.

PMID: 22175724 [PubMed - indexed for MEDLINE]

Late diagnosis of type 2B multiple endocrine neoplasia (MEN 2B) in a 23 year-old patient.

Fetched: April 28th, 2012, 11:00pm MDT

Late diagnosis of type 2B multiple endocrine neoplasia (MEN 2B) in a 23 year-old patient.

Endokrynol Pol. 2011;62(6):548-53

Authors: Andrysiak-Mamos E, Sowińska-Przepiera E, Żochowska E, Kazimierczyk-Puchalska A, Syrenicz J, Lubikowski J, Birkenfeld B, Syrenicz A

Abstract
We present a case of MEN 2B diagnosed in a 23 year-old patient on the basis of bilateral pheochromocytoma and medullary thyroid carcinoma. This young male patient also had multiple paragangliomas located along the spine, marfanoid features of body habitus and numerous mucosal neuromas of the oral cavity and intestinal ganglioneuromatosis. The patient was hospitalised several times between the ages of 11 and 14 due to heart rhythm disorders (tachycardia, multiple supraventricular beats) and pain in the precardiac area. Elevated blood pressure was not observed at that time. In 2010, the patient was admitted to hospital due to abdominal pain, nausea, vomiting and hypertension; bilateral adrenal tumours were then detected. The patient was referred to the Department of Endocrinology in Szczecin, with suspected pheochromocytoma in order to continue the diagnostic process. This resulted in the diagnosis of bilateral pheochromocytoma and medullary thyroid carcinoma. On the basis of the whole clinical picture, the diagnosis of MEN 2B was established and subsequently confirmed with genetic test results. Following the removal of adrenal tumours and thyroidectomy, the patient was referred to the Cancer Centre and Institute of Oncology in Gliwice for further treatment (X-ray therapy and further surgery due to recurrence of medullary carcinoma). This article presents a case of late MEN 2B diagnosis despite the presence of clinical symptoms suggestive of Multiple Endocrine Neoplasia observed from early childhood.

PMID: 22144222 [PubMed - indexed for MEDLINE]

Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumours.

Fetched: April 28th, 2012, 11:00pm MDT

Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumours.

Endokrynol Pol. 2011;62(6):512-6

Authors: Lubikowski J, Kiedrowicz B, Szajko M, Andrysiak-Mamos E, Pynka S, Wójcicki M, Jarosz K, Koziołek M, Fuchs H, Post M, Safranow K, Syrenicz A

Abstract
BACKGROUND: The purpose of this study was a retrospective analysis of outcomes following laparoscopic adrenalectomy (LA) performed for benign adrenal tumours responsible for various endocrinological disorders. The patients were diagnosed with non-functioning (NFT) and functioning adrenal tumours (FT) including pheochromocytoma (PH), Conn's syndrome (CO) and Cushing's (CS) syndrome.
MATERIAL AND METHODS: A total of 165 LAs were carried out between August 1995 and September 2009 via either the transperitoneal (n = 38) or retroperitoneal (n = 127) approach. The analysed factors included demographic data of patients, the American Association of Anaesthesiology score (ASA), indication for surgery, tumour size and side, intraoperative and postoperative outcome of LA including duration of surgery, blood loss, time until ambulation, length of hospital stay, time until return to normal activity, the complication rate, as well as the conversion rate to open adrenalectomy.
RESULTS: There were 111 patients with NFT and 54 with FT. Patients with NFT were significantly older than those with CO (p < 0.05). The mean size of the lesion differed between CO and other adrenal tumours (p < 0.05) as well as between NFT and PH (p < 0.05). All the lesions except aldosteronomas were detected predominantly in the right adrenal gland (p < 0.05). However, despite the different characteristic and clinical disorders related to laparoscopically removed adrenal tumours, the intraoperative and postoperative outcomes did not significantly differ in most cases between the analysed groups of patients.
CONCLUSION: This study shows that LA is a safe, effective, and well-tolerated procedure despite the hormonal activity of the removed lesions. Minimal invasive surgery may be recommended as the 'gold standard' in the treatment of both functioning and non-functioning benign tumours of the adrenal gland.

PMID: 22144217 [PubMed - indexed for MEDLINE]

Evaluation of apoptotic effect of cyclic imide derivatives on murine B16F10 melanoma cells.

Fetched: April 28th, 2012, 11:00pm MDT

Evaluation of apoptotic effect of cyclic imide derivatives on murine B16F10 melanoma cells.

Bioorg Med Chem. 2011 Nov 1;19(21):6285-91

Authors: Machado KE, Oliveira KN, Santos-Bubniak L, Licínio MA, Nunes RJ, Santos-Silva MC

Abstract
Cyclic imides are a large class of compounds obtained by organic synthesis including several sub-classes (succinimides maleimide, glutarimide, phthalimides naphtalimides, and its derivatives). Recently, some cyclic imide derivatives have shown important results as potential antitumor agents, as a Mitonafide and Amonafide. Based on this fact, we have studied antitumoral properties of nine cyclic imide derivatives, four of which are unpublished compounds, against Murine Melanoma Cells (B16F10). Initially, the MTT assay was used to select the compound with the best cytotoxic potential. After this selection, the compound 2-benzyl-1H-benzo[de]isoquinoline-1,3(2H)-dione (4), which showed the best cytotoxic effects, was evaluated by flow cytometry, and a significant increase was observed in the proportion of cells in the subG0/G1, S and G2/M phases accompanied by a significant decrease in the G0/G1 phases. Then the mechanism involved on the death route (necrosis or apoptosis) was evaluated the by bromide and acridine orange method and by an Annexin V-FITC Apoptosis Detection kit. These results confirm that the percentage of B16F10 cells observed in the sub G0/G1 phase were undergoing apoptosis. The biological effects observed in the current study for the cyclic imide derivatives suggested promising applications, especially for the prototype compound 4.

PMID: 21964182 [PubMed - indexed for MEDLINE]

Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands.

Fetched: April 28th, 2012, 11:00pm MDT

Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands.

Bioorg Med Chem. 2011 Nov 1;19(21):6419-29

Authors: Peduto A, Pagano B, Petronzi C, Massa A, Esposito V, Virgilio A, Paduano F, Trapasso F, Fiorito F, Florio S, Giancola C, Galeone A, Filosa R

Abstract
A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)(3) binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UV-melting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment.

PMID: 21944546 [PubMed - indexed for MEDLINE]

Cardiac metastasis of malignant melanoma mimicking acute coronary syndrome.

Fetched: April 28th, 2012, 11:00pm MDT

Cardiac metastasis of malignant melanoma mimicking acute coronary syndrome.

Eur Heart J. 2012 Mar;33(5):676

Authors: Auer J, Schmid J, Berent R, Niedermair M

PMID: 21846676 [PubMed - indexed for MEDLINE]

Hydrodynamic cell delivery for simultaneous establishment of tumor growth in mouse lung, liver and kidney.

Fetched: April 28th, 2012, 11:00pm MDT

Hydrodynamic cell delivery for simultaneous establishment of tumor growth in mouse lung, liver and kidney.

Cancer Biol Ther. 2011 Oct 15;12(8):737-41

Authors: Li J, Yao Q, Liu D

Abstract
To mimic advanced stage of cancer development involving multi-organ metastasis, hydrodynamic delivery commonly used in gene transfer was explored for establishing concurrent tumors in the lung, liver and kidney using B16-F1 melanoma cells, 4T1 breast cells and Renca renal carcinoma cells, as a model. The procedure involves a rapid injection into a mouse tail-vein of serum-free medium, containing tumor cells in a volume equal to approximately 7-9% of body weight. Compared to the conventional tail vein injection of tumor cells resulting in tumor growth only in the lung, hydrodynamic injection is highly effective in establishing tumor growth in the liver, kidney and lung. All tumor cells examined including melanoma, breast metastatic, and renal carcinoma cells showed significant tumor growth in these organs. These results suggest that the hydrodynamic delivery can be a valuable tool for modeling cancer in laboratory animals, especially in experimental mice.

PMID: 21832881 [PubMed - indexed for MEDLINE]

Disseminated and circulating tumor cells in gastrointestinal oncology.

Fetched: April 27th, 2012, 11:00pm MDT

Disseminated and circulating tumor cells in gastrointestinal oncology.

Bull Cancer. 2012 Apr 25;

Authors: Vegas H, André T, Bidard FC, Ferrand FR, Huguet F, Mariani P, Pierga JY

Abstract
Circulating (CTC) and disseminated tumor cells (DTC) represent two different steps of the metastatic process. As with other types of cancer, the recent development of techniques for the detection of CTC and DTC respectively in the blood and bone marrow of patients generated many results in digestive cancers. However, the interpretation of these results and of the prognostic value of CTC/DTC is often limited by the small cohort size and the heterogeneity of detection methods. The aim of this article is to review the different results and their clinical impact, and discuss the possible use of CTC and DTC as new biomarkers. First of all, it is important to take into account the variability of epithelial markers used for the initial stage of immunoselection of CTC/DTC as well as that of molecular or cytological markers used for the second stage of detection. In esophageal, gastric, pancreatic and hepatocellular carcinomas, and in the ileal and pancreatic neuroendocrine tumors, some studies showed a correlation between the detection of CTC and/or DTC and a clinical pejorative course, whether these tumors were at localized or metastatic stages. On colorectal cancer in the adjuvant setting, a recent meta-analysis showed an association between the detection of CTC in peripheral blood and disease-free survival or overall survival. These results are consistent with those of a study that identified detection of CTC as a prognostic factor for relapse in stage II. This last study concluded that it was necessary to achieve long-term evaluation of CTC as a biomarker to guide the decisions of chemotherapy for stage II. In metastatic colorectal cancer, the FDA approved in 2007 the use of pretherapeutic levels of CTC and its variations per-treatment, determined by CellSearch(®) technology, as a tool in treatments management. However, the modalities of this monitoring have to be specified and clinical benefit or the cost-effectiveness of a treatment based on this new biomarker has to be evaluated. Finally, the qualitative and quantitative monitoring of CTC could be a non-invasive tool to monitor changes in tumor biology throughout the disease, and thereby improve the understanding of the processes of dissemination and therapeutic resistance.

PMID: 22531892 [PubMed - as supplied by publisher]

[Nevus or malignant melanoma?].

Fetched: April 27th, 2012, 11:00pm MDT

[Nevus or malignant melanoma?].

Tidsskr Nor Laegeforen. 2012 Mar 6;132(5):511

Authors: Schopf T, Funk J

PMID: 22398767 [PubMed - indexed for MEDLINE]

A single centre melanoma thickness trend (1985-2009) in relation to skin areas accessible and non-accessible to self-inspection.

Fetched: April 27th, 2012, 11:00pm MDT

A single centre melanoma thickness trend (1985-2009) in relation to skin areas accessible and non-accessible to self-inspection.

Australas J Dermatol. 2012 Feb;53(1):32-6

Authors: Rubegni P, Rossi S, Nami N, Risulo M, Biagioli M, Miracco C, Fimiani M

Abstract
BACKGROUND/OBJECTIVES: Melanoma has become a major public health problem worldwide and its incidence in individuals of Caucasian origin continues to rise. The objective was to determine historical changes in thickness, melanoma proportions and anatomical site of presentation over a 25-year period in our Department.
METHODS: This was a historical retrospective study (January 1985 to December 2009). Only patients born and living in Italy were considered. The following parameters were evaluated: age, gender, year of diagnosis, site of primitive lesion (head, back, chest, anterior and posterior upper limbs, anterior and posterior lower limb, and acral sites) and Breslow thickness of the lesion.
RESULTS: In the 25-year period, 993 cases of melanoma were diagnosed. The total number of cases per year tripled between 1985-1989 and 1995-1999 and more than doubled between 1995-1999 and 2005-2009. Our results also revealed that thicker melanomas were more frequent in elderly patients and on parts of the body that cannot be readily self-inspected.
CONCLUSION: The importance of observation of the posterior parts of the body is stressed, since not only did most melanomas arise in these sites but the diagnosis of lesions in these sites is often delayed.

PMID: 22309328 [PubMed - indexed for MEDLINE]

Sentinel lymph node biopsy in patients with Merkel cell carcinoma: an emerging role and the Westmead hospital experience.

Fetched: April 27th, 2012, 11:00pm MDT

Sentinel lymph node biopsy in patients with Merkel cell carcinoma: an emerging role and the Westmead hospital experience.

Australas J Dermatol. 2012 Feb;53(1):26-31

Authors: Howle J, Veness M

Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy which has a high rate of nodal metastasis. Sentinel lymph node biopsy (SLNB) enables the identification of occult nodal metastases. We sought to calculate the rates of positive and false negative SLNB and to evaluate the impact of SLNB on the staging and management of patients with MCC at our institution.
METHODS: A total of 16 patients with stage I or II MCC who had undergone SLNB were identified from a prospectively maintained database of 114 patients with MCC who presented to Westmead Hospital, Sydney, Australia between 2000 and 2010. Data on patient characteristics, tumour and treatment details and patient follow up were extracted from a computer database and patient medical records.
RESULTS: Eight patients (50%) had a positive SLNB and eight had a negative SLNB. The median follow up from diagnosis was 19.5 months (range 4-40) with most patients (69%) alive without evidence of disease at the time of last follow up. All eight patients with a positive SLNB subsequently underwent nodal treatment. This consisted of radiotherapy in five and completion lymphadenectomy and adjuvant radiotherapy in three. None of the eight patients who had a negative SLNB underwent any nodal treatment following SLNB. Two of these patients developed nodal relapse, giving a false negative rate of 20%.
CONCLUSION: Half of our patients were upstaged and underwent nodal treatment as a result of their SLNB. Given the high rate of SLNB positivity, we believe that SLNB has a role in the management of MCC. As there is a risk of a false negative SLNB, close observation of the regional nodal basins is warranted in patients who have had a negative SLNB. Further studies are required to investigate the impact of SLNB on survival.

PMID: 22309327 [PubMed - indexed for MEDLINE]

Is there an optimal scan time for 6-[F-18]fluoro-L-DOPA PET in pheochromocytomas and paragangliomas?

Fetched: April 27th, 2012, 11:00pm MDT

Is there an optimal scan time for 6-[F-18]fluoro-L-DOPA PET in pheochromocytomas and paragangliomas?

Clin Nucl Med. 2012 Feb;37(2):e24-9

Authors: Hentschel M, Rottenburger C, Boedeker CC, Neumann HP, Brink I

Abstract
PURPOSE: To define the appropriate scan time for fluorine-18-labeled dihydroxyphenylalanine (F-18 DOPA) PET in oncological imaging of pheochromocytomas and paragangliomas.
MATERIALS AND METHODS: F-18 DOPA PET examinations were performed in 9 patients with 7 pheochromocytomas and 4 head and neck paragangliomas using a dedicated PET scanner. The acquisition started with a dynamic single-bed scan in the tumor region over the first 60 minutes after tracer injection followed by a late time whole-body scan at approximately 130 minutes. Standard uptake values (SUVs) were calculated in tumors, surrounding background, and adjacent normal tissues of relevance. Furthermore, kinetic analysis was performed using a 2-compartment model with rate constants for uptake (K1'), release (k2'), metabolism (k3'), and reverse reaction (k4') for region of interest and pixel-wise analysis.
RESULTS: All tumors show a marked increased F-18 DOPA uptake, which was visually detectable and distinguishable from the surrounding tissue. The SUV is significantly lower in neck paraganglioma compared with abdominal pheochromocytomas. Mean time-activity curves of F-18 DOPA in tumors show a rapid uptake of the tracer. Already 2 minutes after the injection, the activity in the tumor is beyond that of the blood pool. The average maximum value (SUVmean = 8.2) has already been reached after 20 minutes. Afterward, a very slight decrease of the tumor SUV starts, which still amounts to 80% of the maximum value after 132 minutes. Due to the continuous decrease of activity in the background tissue, the tumor-to-background ratio of SUVs shows a constant increase within the entire period of examination. The mean values of apparent kinetic constants obtained by region of interest analysis averaged over all tumors are as follows: K1' = 2.89 ± 2.56 min(-1), k2' = 2.59 ± 2.81 min(-1), k3' = 0.301 ± 0.395 min(-1), and k4' = 0.044 ± 0.043 min(-1).
CONCLUSIONS: Pheochromocytoma and paraganglioma take up F-18 DOPA very quickly. At best, the acquisition for static clinical PET imaging of paraganglioma with F-18 DOPA can start at 20 minutes postinjection for maximum uptake in tumors. Separation of tumor, background, and adjacent normal tissues is feasible due to their differences in SUV values and kinetics. The kinetic analysis demonstrates an F-18 DOPA accumulation within the tumor due to considerable differences between the rate constants of uptake and metabolism. Second, in contradiction to healthy brain, paraganglionic tumors show a reversible F-18 DOPA metabolism.

PMID: 22228360 [PubMed - indexed for MEDLINE]

Retroperitoneal schwannoma mimicking an ovarian cyst.

Fetched: April 27th, 2012, 11:00pm MDT

Retroperitoneal schwannoma mimicking an ovarian cyst.

J Obstet Gynaecol. 2012 Jan;32(1):102-3

Authors: Gupta S, Tyagi M, Pandey S, Bansal R

PMID: 22185553 [PubMed - indexed for MEDLINE]

The remote assessment of melanocytic skin lesions: a viable alternative to face-to-face consultation.

Fetched: April 27th, 2012, 11:00pm MDT

The remote assessment of melanocytic skin lesions: a viable alternative to face-to-face consultation.

Dermatology. 2011;223(3):244-50

Authors: Boyce Z, Gilmore S, Xu C, Soyer HP

Abstract
BACKGROUND: The incidence of melanoma continues to rise in the Western world, prompting health care professionals to search for novel tools that may increase rates of early detection. Here we focus on one such tool: remote specialist diagnosis of melanocytic lesions utilising mobile-phone camera patient-generated clinical images.
OBJECTIVE: We aim to test the hypothesis that patient-generated clinical images utilising mobile phones are of acceptable quality, and that digital image diagnostic outcomes are comparable with face-to-face (FTF) diagnostic outcomes.
METHODS: Study participants were asked to photograph, using their mobile-phone camera any number of their own melanocytic naevi, and then upload these clinical images to a central server. Diagnostic accuracy of the management decision based on assessing these digital images was tested by comparing results from digital image assessment with results from FTF assessments.
RESULTS: We provide evidence that suggests potential patients are capable of uploading good quality clinical images of melanocytic lesions for diagnostic purposes, and we show that good concordance rates can be achieved with respect to digital image and FTF diagnostic outcomes. With respect to the latter, exact agreement was found in 116 of 167 assessable lesions (69%).
CONCLUSIONS: This work suggests that specialist remote diagnosis of patient-generated clinical images of melanocytic lesions utilising mobile-phone cameras may be a viable alternative to traditional FTF assessments.

PMID: 22095005 [PubMed - indexed for MEDLINE]

No association between Parkinson disease alleles and the risk of melanoma.

Fetched: April 27th, 2012, 11:00pm MDT

No association between Parkinson disease alleles and the risk of melanoma.

Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):243-5

Authors: Meng S, Song F, Chen H, Gao X, Amos CI, Lee JE, Wei Q, Qureshi AA, Han J

Abstract
BACKGROUND: Recent data showed that melanoma was more common among patients with Parkinson disease than individuals without Parkinson disease and vice versa. It has been hypothesized that these two diseases may share common genetic and environmental risk factors.
METHODS: We evaluated the association between single-nucleotide polymorphisms (SNP) selected on the basis of recent genome-wide association studies (GWAS) on Parkinson disease risk and the risk of melanoma using 2,297 melanoma cases and 6,651 controls.
RESULTS: The Parkinson disease SNP rs156429 in the chromosome 7p15 region was nominally associated with melanoma risk with P value of 0.04, which was not significant after the Bonferroni correction for multiple comparisons. No association was observed between the remaining 31 Parkinson disease SNPs and the risk of melanoma. The genetic score based on the number of Parkinson disease risk allele was not associated with melanoma risk [OR for the highest genetic score quartile (30-35) vs. the lowest (15-20), 1.13, 95% confidence interval (CI), 0.47-2.70].
CONCLUSION: The Parkinson disease SNPs identified in published GWAS do not seem to play an important role in melanoma development.
IMPACT: The Parkinson disease susceptibility loci discovered by GWAS contribute little to the observed epidemiologic association between the Parkinson disease and melanoma.

PMID: 22086882 [PubMed - indexed for MEDLINE]

Case-control study of Merkel cell polyomavirus infection and cutaneous squamous cell carcinoma.

Fetched: April 27th, 2012, 11:00pm MDT

Case-control study of Merkel cell polyomavirus infection and cutaneous squamous cell carcinoma.

Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):74-81

Authors: Rollison DE, Giuliano AR, Messina JL, Fenske NA, Cherpelis BS, Sondak VK, Roetzheim RG, Iannacone MR, Michael KM, Gheit T, Waterboer T, Tommasino M, Pawlita M

Abstract
BACKGROUND: Merkel cell polyomavirus (MCV) DNA has been reported in 0% to 25% of squamous cell carcinomas (SCC) occurring in immunocompetent individuals. We conducted the first serologic case-control study of MCV and SCC.
METHODS: Patients with histologically confirmed cutaneous SCC (n = 173) were recruited from a university dermatology clinic. Controls were individuals who screened negative for and had no history of skin or other cancers (n = 300). Levels of antibodies against capsid antigens for MCV and another polyomavirus, JC virus (JCV), were determined by fluorescent bead-based multiplex serology. Fresh-frozen tumor tissues were obtained from 145 SCC cases and tested for MCV DNA by multiplexed PCR. Associations between MCV seroreactivity and SCC were estimated by ORs and 95% CIs calculated using logistic regression with adjustment for age and sex.
RESULTS: MCV DNA was detected in SCC tumor tissues from 55 (38%) of 145 cases. A statistically significant association was observed between MCV seropositivity and MCV DNA-positive SCC (OR = 2.49, 95% CI = 1.03-6.04), with an almost four-fold association observed when comparing those with MCV antibodies in the fourth versus first quartiles (OR = 3.93, 95% CI = 1.43-10.76, P(trend) = 0.01). No significant associations were observed between MCV seropositivity and MCV DNA-negative SCC (OR = 1.38, 95% CI = 0.76-2.48) or between JCV seropositivity and MCV DNA-positive or DNA-negative SCC.
CONCLUSION: Past exposure to MCV may be a risk factor for SCC.
IMPACT: Understanding the role of viral infections in the development of nonmelanoma skin cancer could lead to novel prevention strategies.

PMID: 22016472 [PubMed - indexed for MEDLINE]

Unsuspected pheochromocytoma: is it time for a registry?

Fetched: April 27th, 2012, 11:00pm MDT

Unsuspected pheochromocytoma: is it time for a registry?

Can J Anaesth. 2012 Jan;59(1):112-3

Authors: Mackenzie-Feder J, Tsang J, Demyttenaere S

PMID: 21989552 [PubMed - indexed for MEDLINE]

In vitro anti-uveal melanoma activity of phenolic compounds from the Egyptian medicinal plant Acacia nilotica.

Fetched: April 27th, 2012, 11:00pm MDT

In vitro anti-uveal melanoma activity of phenolic compounds from the Egyptian medicinal plant Acacia nilotica.

Fitoterapia. 2011 Dec;82(8):1279-84

Authors: Salem MM, Davidorf FH, Abdel-Rahman MH

Abstract
Anti-uveal melanoma activity-guided fractionation of the MeOH extract of Acacia nilotica pods resulted in the isolation of the new compound gallocatechin 5-O-gallate in addition to methyl gallate, gallic acid, catechin, catechin 5-O-gallate, 1-O-galloyl-β-D-glucose, 1,6-di-O-galloyl-β-D-glucose and digallic acid. The structures of the isolated compounds were elucidated on the basis of HRESIMS, NMR spectroscopy and CD data. In addition to uveal melanoma, the antiproliferative activities of the isolated compounds and the related compound epigallocatechin 3-O-gallate (EGCG) were evaluated against cutaneous melanoma, ovarian cancer, glioblastoma and normal retinal pigmented cells.

PMID: 21903153 [PubMed - indexed for MEDLINE]

Hepatic hemangioma and hemochromatosis misdiagnosed by MRI as metastatic melanoma.

Fetched: April 27th, 2012, 11:00pm MDT

Hepatic hemangioma and hemochromatosis misdiagnosed by MRI as metastatic melanoma.

J Dtsch Dermatol Ges. 2011 Oct;9(10):842-3

Authors: Forschner A, Schmidt D, Garbe C

PMID: 21790994 [PubMed - indexed for MEDLINE]

The role of phytonutrients in skin health.

Fetched: April 27th, 2012, 11:00pm MDT

The role of phytonutrients in skin health.

Nutrients. 2010 Aug;2(8):903-28

Authors: Evans JA, Johnson EJ

Abstract
Photodamage is known to occur in skin with exposure to sunlight, specifically ultraviolet (UV) radiation. Such damage includes inflammation, oxidative stress, breakdown of the extracellular matrix, and development of cancer in the skin. Sun exposure is considered to be one of the most important risk factors for both nonmelanoma and melanoma skin cancers. Many phytonutrients have shown promise as photoprotectants in clinical, animal and cell culture studies. In part, the actions of these phytonutrients are thought to be through their actions as antioxidants. In regard to skin health, phytonutrients of interest include vitamin E, certain flavonoids, and the carotenoids, β-carotene, lycopene and lutein.

PMID: 22254062 [PubMed - indexed for MEDLINE]

Rare Cancer News & Clinical Trials » PubMed - Neuroendocrine Tumor

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PubMed - Neuroendocrine Tumor (91 unread)

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