Cancers, Vol. 11, Pages 1260: CRISPR/Cas9 Editing of the Polyomavirus Tumor Antigens Inhibits Merkel Cell Carcinoma Growth In Vitro

Cancers, Vol. 11, Pages 1260: CRISPR/Cas9 Editing of the Polyomavirus Tumor Antigens Inhibits Merkel Cell Carcinoma Growth In Vitro Cancers doi: 10.3390/cancers11091260 Authors: Arturo Temblador Dimitrios Topalis Graciela Andrei Robert Snoeck Merkel cell carcinoma (MCC) is an aggressive type of skin cancer whose main causative agent is Merkel cell polyomavirus (MCPyV). MCPyV is integrated into the genome of the tumor cells in most MCCs. Virus-positive tumor cells constitutively express two viral oncoproteins that promote cell growth: the small (sT) and the large (LT) tumor antigens (TAs). Despite the success of immunotherapies in patients with MCC, not all individuals respond to these treatments. Therefore, new therapeutic options continue to be investigated. Herein, we used CRISPR/Cas9 to target the viral oncogenes in two virus-positive MCC cell lines: MS-1 and WAGA. Frameshift mutations introduced in the target sequence upon repair of the Cas9-induced DNA break resulted in decreased LT protein levels, which subsequently impaired cell proliferation, caused cell cycle arrest, and led to increased apoptosis. Importantly, a virus-negative non-MCC cell line (HEK293T) remained unaffected, as well as those cells expressing a non-targeting single-guide RNA (sgRNA). Thus, we presumed that the noted effects were not due to the off-target activity of the TAs-targeting sgRNAs. Additionally, WAGA cells had altered levels of cellular proteins involved in cell cycle regulati...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

Related Links:

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
This article discusses the role of radiation in the treatment of cutaneous squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, and B-cell lymphomas.
Source: Hematology/Oncology Clinics of North America - Category: Cancer & Oncology Authors: Source Type: research
CONCLUSION: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor immune-mediated pathologic response criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes. PMID: 31672770 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Publication date: Available online 28 October 2019Source: Journal of Geriatric OncologyAuthor(s): Andrea Sbrana, Rachele Antognoli, Giuseppe Pasqualetti, Giuseppe Linsalata, Chukwma Okoye, Valeria Calsolaro, Federico Paolieri, Francesco Bloise, Sergio Ricci, Andrea Antonuzzo, Fabio MonzaniAbstractBackgroundOlder adults with cancer are less likely to be offered treatment for cost-benefit concern. The Multi-Prognostic Index (MPI) has been validated in various clinical settings for survival estimation. We aimed to evaluate MPI as a screening tool for older adults with cancer eligible to receive immunotherapy.Patients and Meth...
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
CONCLUSIONS: I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL-12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer. PMID: 31582519 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Abstract Skin cancers represent the most common type of malignancy. The incidence rate of melanoma and non-melanoma skin cancer depicts a continuous rise worldwide, which is attributed mainly (but not exclusively) to the growing incidence of non-melanoma skin cancer in the elderly population. Most skin cancer types are sensitive to immunotherapy. Melanoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma showed response rates of at least 40% for PD-1 inhibitor therapy as reported in recent articles. In this article we review the current and future immunotherapy agents and procedures for skin cancers. ...
Source: Magyar Onkologia - Category: Cancer & Oncology Authors: Tags: Magy Onkol Source Type: research
Contributors : Purnima Gupta ; Naveed Shahzad ; Alexis Robitaille ; Hector Hernandez-Vargas ; Geoffroy Durand ; Florence Le Calvez-Kelm ; Tarik Gheit ; Rosita Accardi ; Massimo TommasinoSeries Type : Expression profiling by arrayOrganism : Homo sapiensMerkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, a viral oncogene required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analysed the gene expression profile...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
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
More News: Cancer | Cancer & Oncology | Carcinoma | Gastroschisis Repair | Immunotherapy | Merkel Cell Carcinoma | Skin | Skin Cancer