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metastatic melanoma

Karin Kfir-Elirachman, Rona Ortenberg, Bella Vizel, Michal J Besser, Iris Barshack, Jacob Schachter, Yael Nemlich, Gal Markel
BRAF becomes constitutively activated in 50% to 70% of melanoma cases. CEACAM1 has a dual role in melanoma, including facilitation of cell proliferation and suppression of infiltrating lymphocytes, which are consistent with its value as a marker for poor prognosis in melanoma patients. Here we show that BRAFV600E melanoma cells treated with BRAF and MEK inhibitors (MAPKi) downregulate CEACAM1 mRNA and protein expression in a dose- and exposure time-dependent manners. Indeed, there is a significant correlation between the presence of BRAFV600E and CEACAM1 expression in melanoma specimens obtained from 45 patients...
March 17, 2018: Neoplasia: An International Journal for Oncology Research
Honglin Jin, Chao Wan, Zhenwei Zou, Guifang Zhao, Lingling Zhang, Yuanyuan Geng, Tong Chen, Ai Huang, Fagang Jiang, Jue-Ping Feng, Jonathan F Lovell, Jing Chen, Gang Wu, Kunyu Yang
Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells...
March 20, 2018: ACS Nano
Erin E Burke, Jonathan S Zager
Introduction Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas Covered T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of TVEC is reviewed...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
Jiangchao Li, Xiaohan Zhang, Qing Liu, Mingming Yang, Zijun Zhou, Yuxiang Ye, Zeqi Zhou, Xiaodong He, Lijing Wang
Myeloid-derived suppressor cells (MDSCs) are found frequently in patients and mice bearing tumors, which derived from immature myeloid cells. In healthy individuals, immature myeloid cells formed in the bone marrow differentiating to dendritic cells, macrophages and neutrophils. However, it is unclear whether some gene deficiency will lead to MDSCs accumulation in mice without bearing tumor. Here, we observed that MDSCs accumulated in the bone marrow of matrix metalloproteinase 12 knockout mice (MMP12-/- mice) compared with wild type mice (MMP12+/+ mice)...
December 13, 2017: Cellular Immunology
Michael Saco, Jonathan Zager, Jane Messina
No abstract text is available yet for this article.
February 2018: Cutis; Cutaneous Medicine for the Practitioner
Shayan Sengupta, Angela C Weyand, Santhosh A Upadhyaya, Yi-Mi Wu, Dan R Robinson, Rajen J Mody
Germline mutation of BRCA-associated protein-1 has been implicated in the development of tumor predisposition syndrome and high risk for malignant mesothelioma, lung adenocarcinoma, uveal melanoma, and cutaneous melanoma. Here, we present the case of a patient with recurrent metastatic melanoma who was found to have germline BAP1 and somatic BRAF mutation by clinical genomic sequencing. Detection of a germline mutation prompted screening for other cancers and surveillance in family members. Prospective integrative sequencing for pediatric cancer patients may identify pathogenic germline mutations and may improve outcomes and treatment-related morbidity by early diagnosis of malignancy...
March 16, 2018: Journal of Pediatric Hematology/oncology
John E Mullinax, MacLean Hall, Sangeetha Prabhakaran, Jeffrey Weber, Nikhil Khushalani, Zeynep Eroglu, Andrew S Brohl, Joseph Markowitz, Erica Royster, Allison Richards, Valerie Stark, Jonathan S Zager, Linda Kelley, Cheryl Cox, Vernon K Sondak, James J Mulé, Shari Pilon-Thomas, Amod A Sarnaik
Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Experimental design: Thirteen patients with metastatic melanoma were enrolled...
2018: Frontiers in Oncology
Behdod Poushanchi, Hiren Vallabh, Gorman Joel Reynolds
Ipilimumab is a monoclonal antibody that works as an immunotherapeutic agent through selective targeting of T cells to strengthen the response to metastatic melanoma. It is well known that this pharmaceutical agent can cause the adverse effect of colitis. We report a rare presentation of ileocolitis refractory to both glucocorticosteroids and infliximab with a resultant pneumatosis and perforation requiring subtotal colectomy and end ileostomy.
2018: Case Reports in Gastrointestinal Medicine
Riccardo Marconcini, Francesco Spagnolo, Luigia Stefania Stucci, Simone Ribero, Elena Marra, Francesco De Rosa, Virginia Picasso, Lorenza Di Guardo, Carolina Cimminiello, Stefano Cavalieri, Laura Orgiano, Enrica Tanda, Laura Spano, Alfredo Falcone, Paola Queirolo
Metastatic melanoma was the first malignancy in which immune checkpoint inhibitors demonstrated their successful efficacy. Currently, the knowledge on the interaction between the immune system and malignant disease is steadily increasing and new drugs and therapeutic strategies are overlooking in the clinical scenario. To provide a comprehensive overview of immune modulating drugs currently available in the treatment of melanoma as well as to discuss of possible future strategies in the metastatic melanoma setting, the present review aims at analyzing controversial aspects about the optimal immunomodulating treatment sequences, the search for biomarkers of efficacy of immunocheckpoint inhibitors, and innovative combinations of drugs currently under investigation...
February 23, 2018: Oncotarget
Paola Queirolo, Francesco Spagnolo, Virginia Picasso, Laura Spano, Enrica Tanda, Valeria Fontana, Laura Giorello, Domenico Franco Merlo, Ester Simeone, Antonio Maria Grimaldi, Marcello Curvietto, Michele Del Vecchio, Paolo Bruzzi, Paolo Antonio Ascierto
Background: BRAF inhibitor vemurafenib achieves high response rate and an improvement in survival in patients with BRAF-mutated metastatic melanoma. However, median progression-free survival is only 6.9 months in the phase 3 study. Retrospective analyses suggest that treatment with BRAF inhibitors beyond initial progression might be associated with improved overall survival. We aimed to prospectively investigate the activity of prolonged treatment with vemurafenib and the addition of fotemustine in patients with systemic progression on prior single-agent BRAF inhibitor...
February 23, 2018: Oncotarget
Malgorzata Pieniazek, Rafal Matkowski, Piotr Donizy
Cutaneous melanoma is an aggressive cancer and its onset and growth are associated, through direct and indirect interactions, with the cancer microenvironment. The microenvironment comprises a dynamic complex of numerous types of cells (due to histogenesis) that constantly interact with each other through multiple cytokines and signaling proteins. Macrophages are one of the most thoroughly studied pleiotropic cells of the immune system. One of their major cytophysiological functions is their involvement in phagocytosis...
April 2018: Oncology Letters
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
Ibrahim Sayed-Ahmed, Juan Carlos Murillo, Pedro Monsalve, Jan Paul Ulloa, Maria P Fernandez, James Wong, George Elgart, Anat Galor, Sander R Dubovy, Carol L Karp
PURPOSE: Blue nevus is a melanocytic tumor that is commonly found in the skin. Extracutaneous presentations, including the ocular surface, are rare. As such, the purpose of this study was to characterize the clinical features and clinical course of congenital melanocytic tumor (blue nevus) of the conjunctiva. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-one patients with 23 blue nevi of the ocular surface that were excised surgically between 2000 and 2016...
March 15, 2018: Ophthalmology
Mitchell E Menezes, Sarmistha Talukdar, Stephen L Wechman, Swadesh K Das, Luni Emdad, Devanand Sarkar, Paul B Fisher
The incidence of melanoma has continued to increase over the past 30 years. Hence, developing effective therapies to treat both primary and metastatic melanoma are essential. While advances in targeted therapy and immunotherapy have provided novel therapeutic options to treat melanoma, gene therapy may provide additional strategies for the treatment of metastatic melanoma clinically. This review focuses upon the challenges and opportunities that gene therapy provides for targeting melanoma. We begin with a discussion of the various gene therapy targets which are relevant to melanoma...
2018: Advances in Cancer Research
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
Yao Li, Zhiqiang Yue, Hua Yu, Xiaojian Liu, Li Tao, Zhijie Zhu, Fangtian Fan, Cunsi Shen, Aiyun Wang, Wenxing Chen, Yin Lu
PURPOSE: A computational model based on clinical data from pancreatic cancer patients has been successfully created and used for predicting tumor sizes in primary and metastasis sites and survival time from kinetics of tumor cells, such as growth rate, metastasis rate and mutation rate, etc. Whether this computational model could be fitted or necessary modification of some parameters for fitting in mice is unknown. Here, we developed a computational model in mice for spontaneous metastasis to simulate the process of tumor metastasis based on the mathematical frameworks...
March 14, 2018: Journal of Pharmacological and Toxicological Methods
Emily Capone, Alessia Lamolinara, Daniela D'Agostino, Cosmo Rossi, Vincenzo De Laurenzi, Manuela Iezzi, Stefano Iacobelli, Gianluca Sala
Cutaneous melanoma is one of the cancers with the fastest rising incidence and in its advanced metastatic form is a highly lethal disease. Despite the recent approval of several new drugs, the 5-year overall survival rate for advanced cutaneous melanoma is still below 20% and therefore, the development of novel treatments remains a primary need. Antibody-Drug Conjugates are an emerging novel class of anticancer agents, whose preclinical and clinical development has recently seen a remarkable increase in different tumors, including melanoma...
March 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Matthew J Bott, Jonathan Cools-Lartigue, Kay See Tan, Joseph Dycoco, Manjit S Bains, Robert J Downey, James Huang, James M Isbell, Daniela Molena, Bernard J Park, Valerie W Rusch, Smita Sihag, David R Jones, Prasad S Adusumilli
BACKGROUND: Surgeons are increasingly asked to operate on patients with residual disease after immunotherapy. The safety and utility of lung resection in this setting are unknown. METHODS: We performed a retrospective review of patients who underwent lung resection within 6 months of treatment with checkpoint blockade agents for metastatic or unresectable cancer. Survival was estimated from first resection using the Kaplan-Meier approach. RESULTS: Database query identified 19 patients who underwent 22 resections for suspected residual disease with therapeutic intent following immunotherapy between 2012 and 2016...
March 14, 2018: Annals of Thoracic Surgery
G Marsavela, C A Aya-Bonilla, M E Warkiani, E S Gray, M Ziman
The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories...
March 13, 2018: Cancer Letters
Sara Valpione, Matteo S Carlino, Johanna Mangana, Meghan J Mooradian, Grant McArthur, Dirk Schadendorf, Axel Hauschild, Alexander M Menzies, Ana Arance, Paolo A Ascierto, AnnaMaria Di Giacomo, Francesco de Rosa, James Larkin, John J Park, Simone M Goldinger, Ryan J Sullivan, Wen Xu, Elisabeth Livingstone, Michael Weichenthal, Rajat Rai, Lydia Gaba, Georgina V Long, Paul Lorigan
No abstract text is available yet for this article.
March 13, 2018: European Journal of Cancer
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