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Oral melanoma cox

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...
October 21, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Sang Min Park, Tricia Li, Shaowei Wu, Wen-Qing Li, Abrar A Qureshi, Eunyoung Cho
Previous studies suggested a protective effect of vitamin D against skin cancer development. However, epidemiologic studies on orally taken vitamin D and risk of skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) are few. We prospectively evaluated whether total, dietary and supplemental vitamin D intake were associated with skin cancer risk based on 63,760 women in the Nurses' Health Study (1984-2010) and 41,530 men in the Health Professionals Follow-up Study (1986-2010)...
2016: PloS One
F Rodríguez, P Castro, G A Ramírez
A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies...
May 2016: Journal of Comparative Pathology
Donna S Cox, Alicia Allred, YanYan Zhou, Jeffrey R Infante, Michael S Gordon, Johanna Bendell, Suzanne Jones, Howard Burris, Keith Orford
Trametinib (Mekinist®) is a selective inhibitor of mitogen-activated protein kinase kinase (MEK) approved in the United States as a single agent and in combination with dabrafenib (Tafinlar®) for treatment of patients with unresectable or metastatic melanoma with a positive BRAF V600E/V600K mutation for which a pediatric oral solution formulation is being developed. This open-label, two-period, two-treatment, randomized, crossover study assessed the relative bioavailability of the trametinib pediatric oral solution compared to the tablet formulation after a single-dose administration to adult patients with solid tumors...
July 2015: Clinical Pharmacology in Drug Development
Daniele Ouellet, Nastya Kassir, Joannellyn Chiu, Mohamad-Samer Mouksassi, Cathrine Leonowens, Donna Cox, Douglas J DeMarini, Olivia Gardner, Wendy Crist, Kiran Patel
PURPOSE: To characterize the pharmacokinetics of oral trametinib, a first in class MEK inhibitor, identify covariates, and describe the relationship between exposure and clinical effects in patients with BRAF V600 metastatic melanoma. EXPERIMENTAL DESIGN: Trametinib concentrations obtained in three clinical studies were included in the population pharmacokinetic analysis. Trametinib 2 mg once daily was administered in the Phase 2 and 3 studies. The impact of exposure [trough (C min) or average concentration] on response rates and progression-free survival (PFS) was examined...
April 2016: Cancer Chemotherapy and Pharmacology
Juliana de Souza do Nascimento, Román Carlos, Wilson Delgado-Azañero, Adalberto Mosqueda Taylor, Oslei Paes de Almeida, Mário José Romañach, Bruno Augusto Benevenuto de Andrade
BACKGROUND: Cyclooxygenase-2 (COX-2) catalyses the conversion of arachidonic acid to prostaglandin, and its overexpression has been demonstrated in different malignant tumors, including cutaneous melanoma. However, no data about the expression of this protein in oral melanocytic lesions are available to date. The aim of this study was to evaluate the immunohistochemical expression of COX-2 in oral nevi and melanomas, comparing the results with correspondent cutaneous lesions. METHODS: COX-2 was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 36 intramucosal nevi and 13 primary oral melanomas, and in four cutaneous nevi and eight melanomas...
July 2016: Journal of Oral Pathology & Medicine
David S Hong, Razelle Kurzrock, Jennifer J Wheler, Aung Naing, Gerald S Falchook, Siqing Fu, Kevin B Kim, Michael A Davies, Ly M Nguyen, Goldy C George, Lucy Xu, Robert Shumaker, Min Ren, Jennifer Mink, Cynthia Bedell, Corina Andresen, Pallavi Sachdev, James P O'Brien, John Nemunaitis
PURPOSE: This "3+3" phase I study evaluated the safety, biologic, and clinical activity of lenvatinib, an oral multikinase inhibitor, in patients with solid tumors. EXPERIMENTAL DESIGN: Ascending doses of lenvatinib were administered per os twice daily in 28-day cycles. Safety and response were assessed for all patients. Angiogenic and apoptotic factors were tested as possible biomarkers in an expanded melanoma cohort. RESULTS: Seventy-seven patients were treated in 3 cohorts: 18 with intermittent twice-daily dosing (7 days on, 7 days off) of 0...
November 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
R C Dutra, M A Bicca, G C Segat, K A B S Silva, E M Motta, L F Pianowski, R Costa, J B Calixto
Evidences suggest protein kinase C epsilon (PKCε) activation is involved in both inflammatory and neuropathic pains. We have previously shown that tetracyclic triterpene euphol produces antinociception in different models of persistent pain, an action associated with its anti-inflammatory properties. Among these properties are the cannabinoid system activation and different PKC isozymes modulation. Herein, we sought to explore the potential role of PKCε modulation on euphol antinociceptive effect, in inflammatory and neuropathic pain models, in rodents...
September 10, 2015: Neuroscience
Mohammed I El-Gamal, Chang-Hyun Oh
A series of fused tricyclic coumarin sulfonate derivatives was synthesized. Their in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds 1e, 1f, 1h, 1i, and 1o showed the highest mean percentage of inhibition values over the 57 cell line panel at 10 μM, and they were further tested in 5-dose testing mode to determine their IC50 values. Compounds 1e, 1f, and 1o were more selective against leukemia and colon cancer subpanels, while compounds 1h and 1i showed broad-spectrum anticancer activities...
September 12, 2014: European Journal of Medicinal Chemistry
Kyoung-Won Seo, Ye-Rin Coh, Robert B Rebhun, Jin-Ok Ahn, Sei-Myung Han, Hee-Woo Lee, Hwa-Young Youn
Cyclooxygenase-2 (COX-2) is a potential target for chemoprevention and cancer therapy. Celecoxib, a selective COX-2 inhibitor, inhibits cell growth of various types of human cancer including malignant melanoma. In dogs, oral malignant melanoma represents the most common oral tumor and is often a fatal disease. Therefore, there is a desperate need to develop additional therapeutic strategies. The purpose of this study was to investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines that express varying levels of COX-2...
June 2014: Research in Veterinary Science
Deborah S Keller, Alan A Thomay, John Gaughan, Anthony Olszanski, Hong Wu, Adam C Berger, Jeffrey M Farma
BACKGROUND AND OBJECTIVE: Our goal was to evaluate the different subtypes of mucosal melanoma and describe specific variables that predict outcomes. METHODS: Prospective review of two tertiary care center databases identified 76 mucosal melanoma patients; 73 with complete records were included. Demographic and clinical data were analyzed. Cox regression determined variables impacting recurrence and survival. RESULTS: In the 73 patients, the mean age was 64 years, and 74% were female...
December 2013: Journal of Surgical Oncology
May Y K Ho, Michael J Morris, Jill L Pirhalla, John W Bauman, Carolyn B Pendry, Keith W Orford, Royce A Morrison, Donna S Cox
1. This study assessed the mass balance, metabolism and disposition of [(14)C]trametinib, a first-in-class mitogen-activated extracellular signal-related kinase (MEK) inhibitor, as an open-label, single solution dose (2 mg, 2.9 MBq [79 µCi]) in two male subjects with advanced cancer. 2. Trametinib absorption was rapid. Excretion was primarily via feces (∼81% of excreted dose); minor route was urinary (∼19% of excreted dose). The primary metabolic elimination route was deacetylation alone or in combination with hydroxylation...
April 2014: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Xin Wang, Weiwei Wen, Heming Wu, Yi Chen, Guoxin Ren, Wei Guo
Oral mucosal melanoma (OMM) is a lethal cancer with a poor prognosis. Despite the great interest in heparanase (HPSE) as a potential anticancer therapy target, the prognostic role of HPSE in oral mucosal melanoma has not been elucidated. In this study, we investigated HPSE expression in OMM tissues and examined its association with clinical outcome. A total of 81 patients with OMM were enrolled in this study. We examined the expression of HPSE in OMM, and its staining extent, intensity and cellular localization were analyzed for clinical significance...
2013: Medical Oncology
Jiawei Lin, Chuangwei Li, Guohao Wu, Zongyuan Zeng
OBJECTIVE: Primary mucosal melanoma of nasal and oral cavity is a rare tumor with a poor prognosis. This study aims to summarize the clinical features and survival status and then to evaluate the prognostic factors. METHOD: Clinical data of 66 patients with mucosal melanoma in nasal and oral cavity treated from Jan. 1980 to Jan. 2005, were retrospectively reviewed. All patients received the surgery. The following parameters: gender, age, primary location, tumor size, presence of ulcer, presence of pigment aggravation, lymph node metastasis, treatment mode and initially treatment outcome were investigated to evaluate their potential impact on survival...
January 2012: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
Chuan-Zheng Sun, Yan-Feng Chen, Yu-E Jiang, Ze-Dong Hu, An-Kui Yang, Ming Song
To evaluate the treatment and prognosis of oral mucosal melanoma (OMM) and provide basic data for clinical treatment. Retrospective analysis of clinicopathological data on OMM from January 1976 to December 2005. Survival analysis was performed and Kaplan-Meier analysis was used to compare the effects of clinicopathological factors on survival using SPSS 18.0 software. A Cox model was applied for multivariate analysis. The 3-year and 5-year overall survival (OS) rates of 51 cases of OMM were 35.0% and 20.7%, respectively...
July 2012: Oral Oncology
Fatima Birch-Johansen, Allan Jensen, Anne Braae Olesen, Jane Christensen, Anne Tjønneland, Susanne K Kjær
OBJECTIVE: We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women. METHODS: Using data from 29,875 women enrolled in the prospective "Diet, Cancer, and Health" study between 1993 and 1997, women with available information on HRT and OC use at baseline were identified. Statistical analyses were based on the Cox's proportional hazards model...
February 2012: Cancer Causes & Control: CCC
María Valcárcel, Lorea Mendoza, José-Julio Hernández, Teresa Carrascal, Clarisa Salado, Olatz Crende, Fernando Vidal-Vanaclocha
BACKGROUND: Human melanoma frequently colonizes bone marrow (BM) since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC) microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2) in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown...
2011: Journal of Translational Medicine
Daniel Jethanamest, Peter M Vila, Andrew G Sikora, Luc G T Morris
BACKGROUND: The head and neck is the most common site of mucosal melanoma, a cancer with poor prognosis. In contrast to cutaneous melanoma, mucosal melanoma of the head and neck (MMHN) is uncommon, with limited data regarding outcomes and prognostic factors drawn from small, single-institution case series. In order to identify factors predictive of survival, we analyzed MMHN outcomes in a large US cohort. METHODS: MMHN cases (n = 815) diagnosed in the USA between 1973 and 2007 were analyzed in the Surveillance, Epidemiology, and End Results registry, and cause of death was individually determined in 778 (95...
October 2011: Annals of Surgical Oncology
Chikara Muraki, Noritaka Ohga, Yasuhiro Hida, Hiroshi Nishihara, Yasutaka Kato, Kunihiko Tsuchiya, Kohei Matsuda, Yasunori Totsuka, Masanobu Shindoh, Kyoko Hida
Tumor angiogenesis is necessary for solid tumor progression and metastasis. Cyclooxygenase (COX)-2 is known to play an important role in cancer growth and invasion, and it activates the signaling pathways controlling cell proliferation, migration, apoptosis, and angiogenesis. COX-2 is reported to be expressed in many cancer cells. Several studies have reported successful treatment of cancer cells with COX-2 inhibitors (COX-2is). However, the effect of COX-2 inhibition on the tumor endothelium remains to be elucidated...
January 1, 2012: International Journal of Cancer. Journal International du Cancer
C M Martínez, C Peñafiel-Verdú, M Vilafranca, G Ramírez, M Méndez-Gallego, A J Buendía, J Sánchez
A direct relationship has been firmly established between cyclooxygenase-2 (COX-2) expression and malignant behavior in human melanoma. This report examines the relationship between COX-2 expression and tumor location, mitotic and proliferative indices, degree of T CD3(+) lymphocyte infiltration, overall survival, and frequency of recurrence and metastasis of 57 melanocytic tumors (25 oral and 32 cutaneous). COX-2 was highly or moderately expressed in 88% of oral neoplasms (22 of 25), whereas for their cutaneous counterparts, COX-2 expression was low or insignificant in 75% of cases (24 of 32)...
November 2011: Veterinary Pathology
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