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Oral melanoma

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https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#1
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28078671/melanoma-in-congenital-melanocytic-naevi
#2
REVIEW
V A Kinsler, P O'Hare, N Bulstrode, J E Calonje, W K Chong, D Hargrave, T Jacques, D Lomas, N J Sebire, O Slater
Congenital melanocytic naevi (CMN) are a known risk factor for melanoma, with the greatest risk currently thought to be in childhood. There has been controversy over the years about the incidence, and therefore over clinical management of CMN, due partly to the difficulties of histological diagnosis and partly to publishing bias towards cases of malignancy. Large cohort studies have demonstrated that risk in childhood is related to the severity of the congenital phenotype, not only cutaneous but neuroradiological...
January 12, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28058215/more-than-skin-deep-potential-nicotinamide-treatment-applications-in-chronic-kidney-transplant-recipients
#3
REVIEW
Andrew G Bostom, Basma Merhi, Joanna Walker, Leslie Robinson-Bostom
Non-melanoma cutaneous carcinomas, or skin cancers, predominantly squamous cell carcinomas (SCCs), are the most common malignancies occurring in kidney transplant recipients (KTRs). Squamous cell carcinoma risk is dramatically elevated in KTRs, occurring at rates of up 45-250 times those reported in general populations. New non-melanoma skin cancers in KTRs with a prior non-melanoma skin cancer also develop at 3-times the rate reported in non-KTRs with the same clinical history. The unique aggressiveness of SCCs in KTRs increases patient morbidity, due to the high rate of new lesions requiring treatment, frequently surgical excision...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28039178/the-natural-history-and-patterns-of-metastases-from-mucosal-melanoma-an-analysis-of-706-prospectively-followed-patients
#4
B Lian, C L Cui, L Zhou, X Song, X S Zhang, D Wu, L Si, Z H Chi, X N Sheng, L L Mao, X Wang, B X Tang, X Q Yan, Y Kong, J Dai, S M Li, X Bai, N Zheng, Charles M Balch, J Guo
BACKGROUND: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. PATIENTS AND METHODS: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites...
December 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28028129/long-term-outcomes-after-carbon-ion-radiotherapy-for-oral-mucosal-malignant-melanoma
#5
Kensuke Naganawa, Masashi Koto, Ryo Takagi, Azusa Hasegawa, Hiroaki Ikawa, Kazuo Shimozato, Tadashi Kamada, Yoshitaka Okamoto
Oral mucosal malignant melanoma (OMM) is extremely rare and has a poor prognosis. Owing to its rarity, it has not yet been possible to establish an optimal treatment modality. The objective of this study was to evaluate the long-term efficacy of carbon-ion radiotherapy (C-ion RT) for OMM. Between 1997 and 2013, 19 patients with OMM were treated with C-ion RT alone. Patient ages ranged from 44 to 84 years (median, 69 years). Nine men and 10 women were included. OMMs were restaged in accordance with the seventh edition of the tumour/node/metastasis (TNM) Staging System of the International Union Against Cancer...
December 26, 2016: Journal of Radiation Research
https://www.readbyqxmd.com/read/27974793/targeting-metastasis-initiating-cells-through-the-fatty-acid-receptor-cd36
#6
Gloria Pascual, Alexandra Avgustinova, Stefania Mejetta, Mercè Martín, Andrés Castellanos, Camille Stephan-Otto Attolini, Antoni Berenguer, Neus Prats, Agustí Toll, Juan Antonio Hueto, Coro Bescós, Luciano Di Croce, Salvador Aznar Benitah
The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44(bright) cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36(+) metastasis-initiating cells in a CD36-dependent manner...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926613/optimal-multidisciplinary-treatment-of-oral-cavity-mucosal-melanoma-outcome-analysis-in-a-case-series
#7
Francesco Perri, Salvatore Pisconti, Matteo Favia, Giuseppina Della Vittoria Scarpati, Manuel Conson, Mario Giuliano, Franco Ionna, Francesco Longo, Bonamonte Domenico, Eugenio Maiorano, Gianfranco Favia
Oral cavity mucosal melanomas (OCMM) represent only 3% of all malignant melanomas. Surgery is the mainstay of treatments and it is often followed by adjuvant radiotherapy. The role of adjuvant immunotherapy and/or chemotherapy is still debated and to date neither treatment is routinely used. From January 1990 to January 2010, we have collected from our database data of 20 patients with a histologically proven diagnosis of OCMM. Upfront surgery, followed by adjuvant radiotherapy was performed in 16/20 (80%) patients...
December 6, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27921276/relationship-between-physician-adjudicated-adverse-events-and-patient-reported-health-related-quality-of-life-in-a-phase-ii-clinical-trial-nct01143402-of-patients-with-metastatic-uveal-melanoma
#8
Thomas M Atkinson, Jennifer L Hay, Alexander Shoushtari, Yuelin Li, Daniel J Paucar, Sloane C Smith, Ragini R Kudchadkar, Austin Doyle, Jeffrey A Sosman, Jorge Fernando Quevedo, Mohammed M Milhem, Anthony M Joshua, Gerald P Linette, Thomas F Gajewski, Jose Lutzky, David H Lawson, Christopher D Lao, Patrick J Flynn, Mark R Albertini, Takami Sato, Karl Lewis, Brian Marr, David H Abramson, Mark Andrew Dickson, Gary K Schwartz, Richard D Carvajal
PURPOSE: Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the common terminology criteria for adverse events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data are becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied. METHODS: Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed...
December 5, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27920018/a-phase-ii-randomized-placebo-controlled-trial-of-oral-n-acetylcysteine-for-protection-of-melanocytic-nevi-against-uv-induced-oxidative-stress-in-vivo
#9
Pamela B Cassidy, Tong Liu, Scott R Florell, Matthew Honeggar, Sancy A Leachman, Kenneth M Boucher, Douglas Grossman
Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1,200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1-2 MED) using a solar simulator...
January 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/27919746/fhod1-formin-is-upregulated-in-melanomas-and-modifies-proliferation-and-tumor-growth
#10
Minna Peippo, Maria Gardberg, Tarja Lamminen, Katja Kaipio, Olli Carpén, Vanina D Heuser
The functional properties of actin-regulating formin proteins are diverse and in many cases cell-type specific. FHOD1, a formin expressed predominantly in cells of mesenchymal lineage, bundles actin filaments and participates in maintenance of cell shape, migration and cellular protrusions. FHOD1 participates in cancer-associated epithelial to mesenchymal transition (EMT) in oral squamous cell carcinoma and breast cancer. The role of FHOD1 in melanomas has not been characterized. Here, we show that FHOD1 expression is typically strong in cutaneous melanomas and cultured melanoma cells while the expression is low or absent in benign nevi...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27914687/braf-nras-kit-tert-gnaq-gna11-mutation-profile-analysis-of-head-and-neck-mucosal-melanomas-a-study-of-42-cases
#11
Şule Öztürk Sari, İsmaİl Yilmaz, Orhun Çiğ Taşkin, Gİzem Narli, Fatma Şen, Şenol Çomoğlu, Pinar Firat, Bİlge Bİlgİç, Dİlek Yilmazbayhan, Yasemİn Özlük, Nesİmİ Büyükbabanİ
Head and neck mucosal melanoma (HNMuM), which occurs mostly in the sinonasal and oral cavity, constitutes less than 1% of all malignant melanomas. Treatment options fail to improve the prognosis of this aggressive tumour that has low overall survival rates. Thus, development of new targeted therapies is essential. Unfortunately, limited data exist regarding their molecular profile. BRAF, NRAS, KIT, TERT and GNAQ/GNA11 oncogene mutations were investigated in 42 HNMuMs (28 sinonasal, 13 oral, 1 nasopharyngeal)...
January 2017: Pathology
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#12
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27864904/an-update-on-the-current-management-of-head-and-neck-mucosal-melanoma
#13
REVIEW
Ben Green, Ahmed Elhamshary, Ricardo Gomez, Siavash Rahimi, Peter A Brennan
Primary mucosal melanomas of the head and neck are rare and aggressive tumours that arise in the nasal cavity, paranasal sinuses and more rarely in the oral cavity. The current treatment options include radical surgical resection with adjuvant external beam radiotherapy being offered in high-risk patients. Although the latter can improve regional control, it does not reduce overall survival. Elective neck dissection is recommended for nodular oral mucosal melanoma, but its role in the clinically node negative neck is controversial...
November 19, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27836097/oral-melanoma-relevance-to-the-dental-team-members
#14
Yeshwant B Rawal, Thomas B Dodson, Harbinder S Bal
BACKGROUND AND OVERVIEW: Oral melanomas vary in color and morphology and resemble myriad other reactive, benign, or malignant conditions. The authors describe a case report of a patient with a primary oral melanoma that presented as a nonspecific ulcer, which showed nodal metastasis during resection. CASE DESCRIPTION: A 64-year-old man who was examined by his periodontist to assess implant healing had a reddish-purple ulcer of the maxillary mucosa of 3 to 4 weeks duration...
November 8, 2016: Journal of the American Dental Association
https://www.readbyqxmd.com/read/27835903/tumor-targeting-salmonella-typhimurium-a1-r-combined-with-temozolomide-regresses-malignant-melanoma-with-a-braf-v600e-mutation-in-a-patient-derived-orthotopic-xenograft-pdox-model
#15
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Bartosz Chmielowski, Tasuku Kiyuna, Ming Zhao, Yong Zhang, Arun Singh, Michiaki Unno, Scott D Nelson, Tara A Russell, Sarah M Dry, Yunfeng Li, Fritz C Eilber, Robert M Hoffman
Melanoma is a recalcitrant disease in need of transformative therapuetics. The present study used a patient-derived orthotopic xenograft (PDOX) nude-mouse model of melanoma with a BRAF-V600E mutation to determine the efficacy of temozolomide (TEM) combined with tumor-targeting Salmonella typhimurium A1-R. A melanoma obtained from the right chest wall of a patient was grown orthotopically in the right chest wall of nude mice to establish a PDOX model. Two weeks after implantation, 40 PDOX nude mice were divided into 4 groups: G1, control without treatment (n = 10); G2, TEM (25 mg/kg, administrated orally daily for 14 consecutive days, n = 10); G3, S...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27827301/validation-and-development-of-mth1-inhibitors-for-treatment-of-cancer
#16
U Warpman Berglund, K Sanjiv, H Gad, C Kalderén, T Koolmeister, T Pham, C Gokturk, R Jafari, G Maddalo, B Seashore-Ludlow, A Chernobrovkin, A Manoilov, I S Pateras, A Rasti, A-S Jemth, I Almlöf, O Loseva, T Visnes, B O Einarsdottir, F Z Gaugaz, A Saleh, B Platzack, O A Wallner, K S A Vallin, M Henriksson, P Wakchaure, S Borhade, P Herr, Y Kallberg, P Baranczewski, E J Homan, E Wiita, V Nagpal, T Meijer, N Schipper, S G Rudd, L Bräutigam, A Lindqvist, A Filppula, T-C Lee, P Artursson, J A Nilsson, V G Gorgoulis, J Lehtiö, R A Zubarev, M Scobie, T Helleday
BACKGROUND: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. MATERIAL AND METHODS: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA...
December 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27786591/suppression-of-b-raf-v600e-melanoma-cell-survival-by-targeting-mitochondria-using-triphenyl-phosphonium-conjugated-nitroxide-or-ubiquinone
#17
Seung-Keun Hong, Dmytro Starenki, Pui-Kei Wu, Jong-In Park
Most BRAF-mutated melanomas initially responsive to the FDA-approved inhibitors preferentially targeting B-Raf mutated in Val600 residue eventually relapse, requiring additional therapeutic modalities. Recent studies report the significance of metabolic reprograming in mitochondria for maintenance of BRAF-mutated melanomas and for development of their drug resistance to B-Raf inhibitors, providing a rationale for targeting mitochondria as a potential therapeutic strategy for melanoma. We therefore determined whether mitochondria-targeted metabolism-interfering agents can effectively suppress human B-Raf(V600E) melanoma cell lines and their dabrafenib/PLX4032-resistant progenies using mitochondria-targeted carboxy-proxyl (Mito-CP) and ubiquinone (Mito-Q)...
October 27, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27783987/the-combination-of-mln2238-ixazomib-with-interferon-alpha-results-in-enhanced-cell-death-in-melanoma
#18
Lorena P Suarez-Kelly, Gregory M Kemper, Megan C Duggan, Andrew Stiff, Tiffany C Nole, Joseph Markowitz, Eric A Luedke, Vedat O Yildiz, Lianbo Yu, Alena Cristina Jaime-Ramirez, Volodymyr Karpa, Xiaoli Zhang, William E Carson
The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27779366/immunohistochemical-expression-of-mdr1-pgp-170-in-canine-cutaneous-and-oral-melanomas-pattern-of-expression-and-association-with-tumour-location-and-phenotype
#19
R Finotello, J M Monné Rodriguez, M Vilafranca, J Altimira, G A Ramirez, A Haines, L Ressel
Canine melanoma (CMM) more commonly affects the oral mucosa and the cutis. CMM shares several features with human melanomas (HMM), included resistance to a broad variety of antineoplastic chemotherapy agents. P-glycoprotein 1 (Pgp) expression is a well-recognized feature of multi-drug resistance and the purpose of this study was to investigate its expression in treatment naïve CMM. We also investigated Pgp association with tumour location and histological features. Histology records of CMM were retrieved, including patients from 2012-2014...
October 25, 2016: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/27777130/atb-346-a-novel-hydrogen-sulfide-releasing-anti-inflammatory-drug-induces-apoptosis-of-human-melanoma-cells-and-inhibits-melanoma-development-in-vivo
#20
Paola De Cicco, Elisabetta Panza, Giuseppe Ercolano, Chiara Armogida, Giuseppe Sessa, Giuseppe Pirozzi, Giuseppe Cirino, John L Wallace, Angela Ianaro
Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H2S-NSAIDs). They consist of a traditional NSAID to which an H2S-releasing moiety is covalently attached. We have recently demonstrated that H2S donors inhibit melanoma cell proliferation. In the current study, we evaluated the potential beneficial effects of a new H2S-releasing derivative of naproxen, ATB-346 [2-(6-methoxynapthalen-2-yl)-propionic acid 4-thiocarbamoyl phenyl ester] which inhibits COX activity but also releases H2S...
December 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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