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Melanoma treatment

Fang Miao, Ying Shi, Zhi-Feng Fan, Shan Jiang, Shi-Zheng Xu, Tie-Chi Lei
Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ). At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy...
2016: PloS One
Bella H V Nguyen, James Kuo, Anadian Budiman, Hayden Christie, Sayed Ali
Immune checkpoint inhibitors have changed the landscape of the treatment of multiple solid malignancies, and have been used increasingly in the recent years. Although usually well tolerated, given the relative inexperience of using immune checkpoint inhibitors, we are still learning of new side effects from the treatment. We report on two cases of ocular myasthenia gravis that occurred after treatment with pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody for advanced melanoma in responding patients...
October 21, 2016: Melanoma Research
F Bath-Hextall, S Nalubega, C Evans
BACKGROUND: Skin cancer incidence is increasing worldwide. This is an update of a previous review published in 2010 that identified only two studies and found that the needs and experiences of individuals with skin cancer were under-researched. OBJECTIVES: To undertake a qualitative systematic review of the needs and experiences of people with a diagnosis of skin cancer. METHODS: As an update of a previous review, the following databases were searched from 2010 to 30/11/15: CINAHL PsycINFO, MEDLINE and EMBASE...
October 24, 2016: British Journal of Dermatology
Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
Mary Jc Hendrix, Irawati Kandela, Andrew P Mazar, Elisabeth A Seftor, Richard Eb Seftor, Naira V Margaryan, Luigi Strizzi, George F Murphy, Georgina V Long, Richard A Scolyer
Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. It is the leading cause of skin cancer deaths with a median overall survival for advanced-stage metastatic disease of <6 months. Despite advances in the field with conventional and targeted therapies, the heterogeneity of melanoma poses the greatest ongoing challenge, ultimately leading to relapse and progression to a more drug-resistant tumor in most patients. Particularly noteworthy are recent findings, indicating that these therapies exert selective pressure on tumors resulting in the activation of pathways associated with cancer stem cells that are unresponsive to current therapy...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
M M F Aubuchon, L J J Bolt, M L G Janssen-Heijnen, S T H P Verleisdonk-Bolhaar, A van Marion, C L H van Berlo
BACKGROUND: Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. METHODS: Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed...
October 23, 2016: Acta Chirurgica Belgica
Neil M D'Souza, Penny Fang, Jennifer Logan, Jinzhong Yang, Wen Jiang, Jing Li
Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies...
2016: Frontiers in Oncology
Boris Pinchuk, Thorsten von Drathen, Viktoria Opel, Christian Peifer
Dabrafenib (Tafinlar) was approved in 2013 by the FDA as a selective single agent treatment for patients with BRAF(V600E) mutation-positive advanced melanoma. One year later, a combination of dabrafenib and trametinib was used for treatment of BRAF(V600E/K) mutant metastatic melanoma. In the present study, we report on hitherto not described photosensitivity of dabrafenib both in organic and aqueous media. The half-lives for dabrafenib degradation were determined. Moreover, we revealed photoinduced chemical conversion of dabrafenib to its planar fluorescent derivative dabrafenib_photo 2...
October 13, 2016: ACS Medicinal Chemistry Letters
Ibiayi Dagogo-Jack, Corey M Gill, Daniel P Cahill, Sandro Santagata, Priscilla K Brastianos
Development of brain metastasis (BM) portends a dismal prognosis for patients with cancer. Melanomas and carcinomas of the lung, breast, and kidney are the most common malignancies to metastasize to the brain. Recent advances in molecular genetics have enabled the identification of actionable, clinically relevant genetic alterations within primary tumors and their corresponding metastases. Adoption of genotype-guided treatment strategies in the management of systemic malignancy has resulted in dramatic and durable responses...
October 20, 2016: Pharmacology & Therapeutics
Pharkphoom Panichayupakaranant, Md Iftekhar Ahmad
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a plant-derived naphthoquinones obtained mainly from three families, including Plumbaginaceae, Droseraceae, and Ebenaceae. Plumbagin has exhibited its potential therapeutic benefits on numerous chronic diseases, i.e., breast cancer, non-small cell lung cancer, melanoma, ovarian, squamous cell carcinomas, pancreatic cancer, and prostate cancer. In addition, its anti-inflammatory and antimicrobial activities as well as control of diabetes and cardiovascular diseases have been reported...
2016: Advances in Experimental Medicine and Biology
Joachim Mikkelsen, Steen Henrik Matzen
INTRODUCTION: Cancer is a recognized risk factor of venous thromboembolism (VTE) as it induces a prothrombotic state through various mechanisms of activation of coagulation. Recognizing occult cancer as a risk factor is equally important. In patients with no known thromboembolic risk factors, utilizing PET/CT as a screening tool may be considered in order to reveal occult malignancy associated with otherwise unexplainable VTE. METHODS: This case report has been reported in line with the SCARE criteria...
October 14, 2016: International Journal of Surgery Case Reports
Raghavendra Gowda, Arati Sharma, Gavin P Robertson
Melanoma is a highly drug resistant cancer. To circumvent this problem, a class of synergistically acting drug combinations, which inhibit multiple key pathways in melanoma cells, could be used as one approach for long-term treatment of this deadly disease. A screen has been undertaken on cell lines to identify those that could be combined to synergistically kill melanoma cells. Plumbagin and Celecoxib are two agents that were identified to synergistically kill melanoma cells by inhibiting the COX-2 and STAT3 pathways, which are constitutively activated in up to 70% of melanomas...
October 18, 2016: Cancer Letters
C Franklin, E Livingstone, A Roesch, B Schilling, D Schadendorf
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma...
September 2, 2016: European Journal of Surgical Oncology
M J Aguado-Romeo, S Benot-López, A Romero-Tabares
Electrochemotherapy is a therapeutic option for the treatment of cutaneous and subcutaneous metastases from melanoma and other tumors. The procedure consists of the administration of anticancer drugs followed by locally applied electrical impulses to achieve an effect known as electroporation, which facilitates entry into the cytosol of drugs that cannot cross the cell membrane. The aim of this review is to evaluate the evidence that supports the use of electrochemotherapy as a therapeutic strategy in melanoma...
October 18, 2016: Actas Dermo-sifiliográficas
Nitin Chakravarti, Doina Ivan, Van A Trinh, Isabella C Glitza, Jonathan L Curry, Carlos Torres-Cabala, Michael T Tetzlaff, Roland L Bassett, Victor G Prieto, Wen-Jen Hwu
Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is the first immune checkpoint inhibitor approved for the treatment of unresectable melanoma on the basis of its overall survival (OS) benefit. However, ipilimumab is associated with significant immune-related adverse events. We hypothesized that biomarker exploration of pretreatment tumor samples and correlation with clinical outcome would enable patient selection with an increased benefit/risk ratio for ipilimumab therapy...
October 20, 2016: Melanoma Research
Boris Redko, Helena Tuchinsky, Tamar Segal, Dror Tobi, Galia Luboshits, Osnat Ashur-Fabian, Albert Pinhasov, Gabi Gerlitz, Gary Gellerman
The newly discovered short (9 amino acid) non-RGD S-S bridged cyclic peptide ALOS-4 (H-cycl(Cys-Ser-Ser-Ala-Gly-Ser-Leu-Phe-Cys)-OH), which binds to integrin αvβ3 is investigated as peptide carrier for targeted drug delivery against human metastatic melanoma. ALOS4 binds specifically the αvβ3 overexpressing human metastatic melanoma WM-266-4 cell line both in vitro and in ex vivo assays. Coupling ALOS4 to the topoisomerase I inhibitor Camptothecin (ALOS4-CPT) increases the cytotoxicity of CPT against human metastatic melanoma cells while reduces dramatically the cytotoxicity against non-cancerous cells as measured by the levels of γH2A...
October 19, 2016: Oncotarget
R C Gerring, C T Ott, J M Curry, Z B Sargi, S T Wester
PurposeTo describe prognostic factors and survival outcomes in patients who underwent orbital exenteration for periocular non-melanoma cutaneous malignancies.MethodsThe authors performed an institutional review board-approved retrospective review of all patients who underwent orbital exenteration for non-melanoma periocular cutaneous malignancies at a tertiary care hospital system over a 10-year period. Patient demographics, tumor, and treatment data were recorded. Survival outcomes included disease-free survival (DFS) and overall survival (OS)...
October 21, 2016: Eye
Yun-Wen Yang, Chun-Mei Zhang, Xian-Jie Huang, Xiao-Xin Zhang, Lin-Kai Zhang, Jia-Huang Li, Zi-Chun Hua
Fas-associated protein with death domain (FADD), a pivotal adaptor protein transmitting apoptotic signals, is indispensable for the induction of extrinsic apoptosis. However, overexpression of FADD can form large, filamentous aggregates, termed death effector filaments (DEFs) by self-association and initiate apoptosis independent of receptor cross-linking. A mutant of FADD, which is truncated of the C-terminal tail (m-FADD, 182-205 aa) named N-FADD (m-FADD, 1-181 aa), can dramatically up-regulate the strength of FADD self-association and increase apoptosis...
October 21, 2016: Scientific Reports
Marta Polkowska, Edyta Czepielewska, Małgorzata Kozłowska-Wojciechowska
Advanced melanoma is related to a very grim prognosis and fast progression. Until recently, there has been no indicated treatment that would affect the disease's outcome. However, the progress in immunotherapy and molecular therapy has significantly changed the unfavourable prognosis of melanoma progression and its short survival rate. Both approaches have improved patients' outcomes and provided renewed hope for successful treatment. Moreover, in order to further enhance patients' outcomes and to avoid mechanisms of tumour resistance, investigators attempted a combined approach...
December 2016: Current Treatment Options in Oncology
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