519 Paranuclear cytokeratin aggregates help Merkel cell carcinoma evade extrinsic apoptosis

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. Most MCC tumors are virus positive and express Merkel cell polyomavirus oncogenes, whereas virus negative MCC are associated with abundant UV signature mutations. The majority of MCC tumors express CK20. Staining for CK20 and other intermediate filaments in a paranuclear dot pattern is a histological feature used to diagnose MCC. The functional significances of these paranuclear protein aggregates is unknown. We immunostained native MCC tumors with a pan-CK antibody and found areas of paranuclear dot staining in 94% of tumors.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Melanoma and Other Skin Cancers Source Type: research

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Publication date: Available online 3 January 2020Source: Seminars in Cancer BiologyAuthor(s): Kelly Olino, Tristen Park, Ntia AhujaAbstractAdvances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1–4 merkel cell carcinoma5, urological cancers6–8, non-small cell lung cancer9–11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
We report the preclinical safety, antitumor efficacy, and immune-potentiating effects of pegzilarginase, a highly potent human arginine-degrading enzyme. Toxicology studies showed that pegzilarginase-mediated arginine depletion is well tolerated at therapeutic levels that elicit an antitumor growth effect. To determine which tumor types are best suited for clinical development, we profiled clinical tumor samples for ASS1 expression, which correlated with pegzilarginase sensitivity in vivo in patient-derived xenograft (PDx) models. Among the histologies tested, malignant melanoma, small cell lung cancer and Merkel cell carc...
Source: Translational Research : the journal of laboratory and clinical medicine - Category: Laboratory Medicine Authors: Tags: Transl Res Source Type: research
Publication date: Available online 11 December 2019Source: Best Practice &Research Clinical Endocrinology &MetabolismAuthor(s): Giusy Elia, Silvia Martina Ferrari, Maria Rosaria Galdiero, Francesca Ragusa, Sabrina Rosaria Paparo, Ilaria Ruffilli, Gilda Varricchi, Poupak Fallahi, Alessandro AntonelliAbstractAnticancer immunotherapy, in the form of immune checkpoint inhibition (ICI), is a paradigm shift that has transformed the care of patients with different types of solid and hematologic cancers. The most notable improvements have been seen in patients with melanoma, non-small-cell lung, bladder, renal, cervical, u...
Source: Best Practice and Research Clinical Endocrinology and Metabolism - Category: Endocrinology Source Type: research
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Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
Authors: KamiƄska-Winciorek G, Cybulska-Stopa B, Lugowska I, Ziobro M, Rutkowski P Abstract The introduction of immunotherapy into the treatment of cancer patients has revolutionised the oncological approach and significantly improved patient survival. The key drugs are immune checkpoint inhibitors (CPIs), whose mechanism of action is to elicit immune response against cancer cell antigens. Three types of CPIs are currently used and approved: an anti-CTLA-4 antibody, ipilimumab; anti-PD-1 antibodies, nivolumab and pembrolizumab; and anti-PD-L1 antibodies: atezolizumab, avelumab and durvalumab. CPIs have been widely...
Source: Advances in Dermatology and Allergology - Category: Dermatology Tags: Postepy Dermatol Alergol Source Type: research
This article reviews current evidence and recommendations for the diagnosis and treatment of MCC and discusses recent therapeutic advances and their implications for care in patients with advanced disease. This consensus statement is the result of a collaboration between the Spanish Cooperative Group for Neuroendocrine Tumors, the Spanish Group of Treatment on Head and Neck Tumors, and the Spanish Melanoma Group.Implications for Practice.Merkel cell carcinoma (MCC) is an uncommon aggressive skin cancer associated with advanced age, UV light exposure, and immunosuppression. Up to 80% are associated with Merkel cell polyomav...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Melanoma and Cutaneous Malignancies Source Type: research
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Source: Magyar Onkologia - Category: Cancer & Oncology Authors: Tags: Magy Onkol Source Type: research
The incidence of Merkel cell carcinoma (MCC), a rare and highly metastatic skin malignancy, has sharply increased in the last decade. Clinical biomarkers are urgently needed for MCC prognosis, treatment response monitoring, and early diagnosis of relapse. The clinical interest of circulating tumors cells (CTCs) has been validated in many solid cancers. The aim of this study was to compare CTC detection and characterization in blood samples of patients with MCC using the CellSearch ® System and the RosetteSep™ -DEPArray™ workflow, an innovative procedure to enrich, detect and isolate single CTCs.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Melanoma and Other Skin Cancers Source Type: research
Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer that is highly immunogenic. Approximately 80% of MCC tumors are virus positive (VP-MCC) and express Merkel cell polyomavirus (MCPyV) T antigens that drive oncogenesis. As VP-MCC have a low mutation burden with few predicted neoantigens, viral oncogenes are thought to be the primary target for anti-cancer immunity. Immune checkpoint inhibitors improve MCC survival, yet
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Melanoma and Other Skin Cancers Source Type: research
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