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https://www.readbyqxmd.com/read/28445541/iqgap1-is-an-oncogenic-target-in-canine-melanoma
#1
Becky H Lee, Poornima H Neela, Michael S Kent, Ashley M Zehnder
Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%), human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28445515/correlation-of-histopathologic-characteristics-to-protein-expression-and-function-in-malignant-melanoma
#2
Charlotte Welinder, Krzysztof Pawłowski, A Marcell Szasz, Maria Yakovleva, Yutaka Sugihara, Johan Malm, Göran Jönsson, Christian Ingvar, Lotta Lundgren, Bo Baldetorp, Håkan Olsson, Melinda Rezeli, Thomas Laurell, Elisabet Wieslander, György Marko-Varga
BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information...
2017: PloS One
https://www.readbyqxmd.com/read/28445254/the-clinical-features-treatment-and-prognosis-of-primary-mediastinal-malignant-melanoma-a-case-report
#3
ZiHai Li, Hui Jia, Baijiang Zhang, Yongming Zhang, Hui Li, Pingping Song
RATIONALE: Primary malignant melanoma (MM) of the mediastinum is exceedingly rare; a review of the English-language literature reveals only a small number of case reports. In this paper, we discuss a case of primary mediastinal MM and present a review of the relevant literature on its clinical features and treatment. PATIENT CONCERNS: A 52-year-old male presenting with back pain was admitted to our hospital for treatment. Imaging examination revealed an anterior mediastinal mass and no evidence of other metastatic or primary lesions...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28444874/prognostic-impact-of-chromosomal-aberrations-and-gnaq-gna11-and-bap1-mutations-in-uveal-melanoma
#4
Kjersti M Staby, Karsten Gravdal, Sverre J Mørk, Steffen Heegaard, Olav K Vintermyr, Jørgen Krohn
PURPOSE: To evaluate clinico-pathological and molecular prognostic factors in a well-defined series of posterior uveal melanoma (UM) with focus on chromosomal aberrations and mutations in the GNAQ, GNA11 and BRCA1-associated protein 1 (BAP1) genes. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue samples were obtained from 50 consecutive eyes enucleated for UM between 1993 and 2005. The material was tested for loss of chromosome 3 and gain of chromosome 8q gene signatures by selective molecular gene markers using multiplex ligation-dependent probe amplification (MLPA), and for DNA mutations in the GNAQ, GNA11 and BAP1 genes...
April 26, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28444424/the-experience-of-immune-checkpoint-inhibitors-in-chinese-patients-with-metastatic-melanoma-a-retrospective-case-series
#5
Xizhi Wen, Ya Ding, Jingjing Li, Jingjing Zhao, Ruiqing Peng, Dandan Li, Baoyan Zhu, Yao Wang, Xing Zhang, Xiaoshi Zhang
Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively...
April 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28444227/incidence-and-prognosis-of-patients-with-brain-metastases-at-diagnosis-of-systemic-malignancy-a-population-based-study
#6
Daniel N Cagney, Allison M Martin, Paul J Catalano, Amanda J Redig, Nancy U Lin, Eudocia Q Lee, Patrick Y Wen, Ian F Dunn, Wenya Linda Bi, Stephanie E Weiss, Daphne A Haas-Kogan, Brian M Alexander, Ayal A Aizer
Background: Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program. Methods: We identified 1,302,166 patients diagnosed with non-hematologic malignancies originating outside of the central nervous system between 2010-2013 and described the incidence proportion and survival of patients with brain metastases...
April 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28442585/next-gen-sequencing-analysis-and-algorithms-for-pdx-and-cdx-models
#7
Garima Khandelwal, Maria Romina Girotti, Christopher Smowton, Sam Taylor, Chris Wirth, Marek Dynowski, Kristopher K Frese, Ged Brady, Caroline Dive, Richard Marais, Crispin Miller
Patient-derived xenograft (PDX) and CTC-derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these methods have been applied to multiple questions including the study of metastatic progression, genetic evolution and therapeutic drug responses. Since PDX and CDX models can recapitulate the highly heterogeneous characteristics of a patient tumor, as well as their response to chemotherapy, there is considerable interest in combining them with next-generation sequencing (NGS) in order to monitor the genomic, transcriptional, and epigenetic changes that accompany oncogenesis...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28442409/sinonasal-mucosal-melanoma-a-44-case-study-and-literature-analysis
#8
M Dréno, M Georges, F Espitalier, C Ferron, A Charnolé, B Dréno, O Malard
OBJECTIVES: Sinonasal mucosal melanoma is a rare disease, representing 4% of nasal cavity and paranasal sinus malignancies. The aim of this study was to assess the clinical characteristics, progression and treatment of this disease and to identify prognostic factors. MATERIAL AND METHODS: This retrospective review presents a cohort of 44 patients treated for a melanoma arising from the nasal cavity and paranasal sinuses, in the ENT Head and Neck Surgery Department of the University Hospital of Nantes (France) between 1988 and 2015...
April 22, 2017: European Annals of Otorhinolaryngology, Head and Neck Diseases
https://www.readbyqxmd.com/read/28441072/pro-tumor-activities-of-macrohpages-in-the-progression-of-melanoma
#9
Huafeng Wang, Luhong Yang, Dong Wang, Qi Zhang, Lijuan Zhang
Macrophages are located in essentially all tissues due to their "janitor" function. Macrophages can exert either anti- or pro-tumor activities depending upon the specific tumor microenvironment they inhabit. Substantial evidence indicates that macrophages, owing to their plasticity, can be reeducated to adopt a protumoral phenotype within a tumor microenvironment through the help of growth factors in the microenvironment and intercellular interactions. As the lethality of malignant melanoma is due to its aggressive capacity for metastasis and resistance to therapy, considerable effort has gone toward treatment of metastatic melanoma...
April 25, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28440609/clinical-significance-of-circulating-serum-cellular-heat-shock-protein-90-hsp90-level-in-patients-with-cutaneous-malignant-melanoma
#10
Faruk Tas, Elif Bilgin, Kayhan Erturk, Derya Duranyildiz
Background: Cellular heat shock proteins (HSPs) play significant roles in sustaining normal cellular conditions. The stimulated expressions of HSPs result in cellular stabilization at times of stress, such as cancer. The objective of this study was to determine the clinical significance of the serum levels of HSP90 in melanoma patients. Material and methods: A total number of 98 melanoma patients were enrolled into this study. Serum HSP90 concentrations were determined by the solid-phase sandwich ELISA method...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28439919/motor-polyradiculopathy-during-pembrolizumab-treatment-of-metastatic-melanoma
#11
Maria Sepúlveda, Eugenia Martinez-Hernandez, Lydia Gaba, Ivan Victoria, Nuria Sola-Valls, Neus Falgàs, Jordi Casanova-Molla, Francesc Graus
INTRODUCTION: Pembrolizumab, a monoclonal antibody directed against the immune checkpoint PD-1 (programmed cell death-1 receptor), has improved survival in patients with advanced melanoma. Neuromuscular immune-mediated side effects have been rarely reported. METHODS: We describe a 44-year-old man with metastatic melanoma who presented with progressive muscle weakness after 23 doses of pembrolizumab. RESULTS: The patient developed asymmetric, proximal muscle weakness and atrophy in all four limbs...
April 25, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#12
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28433794/detection-of-melanoma-metastases-with-pet-comparison-of-18-f-5-fpn-with-18-f-fdg
#13
Yichun Wang, Mengting Li, Yingying Zhang, Fengzhen Zhang, Chunbao Liu, Yiling Song, Yongxue Zhang, Xiaoli Lan
INTRODUCTION: (18)F-5-fluoro-N-(2-(Diethylamino)ethyl)picolinamide ((18)F-5-FPN) is a new positron-emission tomography (PET) radiopharmaceutical with potential for the detection of lymph node (LN) and pulmonary metastatic lesions of melanoma. We compared its performance with that of (18)F-deoxyglucose ((18)F-FDG). METHODS: Cervical LN and lung melanoma metastasis models were established in C57BL/6 mice. Primary tumors were created by injection of melanoma cells into the pinna, and the resulting cervical LN metastases were evaluated...
April 7, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28433199/glycoprotein-non-metastatic-melanoma-protein-b-gpnmb-is-highly-expressed-in-macrophages-of-acute-injured-kidney-and-promotes-m2-macrophages-polarization
#14
Letian Zhou, Hui Zhuo, Huiyu Ouyang, Yexin Liu, Fang Yuan, Lin Sun, Fuyou Liu, Hong Liu
Acute kidney injury (AKI) is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. During AKI process, macrophages, one of the important immune response cells, can polarize into M1 and M2 subtype from M0 subtype. It is well-known that M1 macrophages play a pro inflammatory role while M2 macrophages play an anti-inflammatory role. Glycoprotein non-metastatic melanoma protein b (Gpnmb) is a glycosylated transmembrane protein highly expressed in numerous cells, including osteoblasts, dendritic cells and macrophages...
March 31, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#15
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28432067/adoptive-t-cell-therapy-has-antitumor-activity-in-uveal-melanoma
#16
(no author information available yet)
Adoptive T-cell therapy achieved responses in 35% of patients with metastatic uveal melanoma.
April 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28430284/o-2-6-oxocyclohex-1-en-1-yl-methyl-diazen-1-ium-1-2-diolates-a-new-class-of-nitric-oxide-donors-activatable-by-gsh-gst%C3%AF-with-both-anti-proliferative-and-anti-metastatic-activities-against-melanoma
#17
Chengfeng Bai, Rongfang Xue, Jianbing Wu, Tian Lv, Xiaojun Luo, Yun Huang, Yan Gong, Honghua Zhang, Yihua Zhang, Zhangjian Huang
The new nitric oxide (NO) donor O(2)-(6-oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolate 3c could simultaneously liberate NO as well as an active 3-glutathionyl-2-exomethylene-cyclohexanone 2 in the presence of GSH/GSTπ; exhibit potent antiproliferative activity; repress migration, invasion, and lateral migration of metastatic B16-BL6 cells; and significantly decrease hetero-adhesion of B16-BL6 cells to human umbilical vein endothelial cells.
April 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28430133/nuclear-molecular-imaging-strategies-in-immune-checkpoint-inhibitor-therapy
#18
REVIEW
Kasper F Guldbrandsen, Helle W Hendel, Seppo W Langer, Barbara M Fischer
Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses...
April 21, 2017: Diagnostics
https://www.readbyqxmd.com/read/28430130/timp1-promotes-cell-survival-by-activating-the-pdk1-signaling-pathway-in-melanoma
#19
Mariana Toricelli, Fabiana H M Melo, Aline Hunger, Daniela Zanatta, Bryan E Strauss, Miriam G Jasiulionis
High TIMP1 expression is associated with poor prognosis in melanoma, where it can bind to CD63 and β1 integrin, inducing PI3-kinase pathway and cell survival. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), generated under phosphatidylinositol-3-kinase (PI3K) activation, enables the recruitment and activation of protein kinase B (PKB/AKT) and phosphoinositide-dependent kinase 1 (PDK1) at the membrane, resulting in the phosphorylation of a host of other proteins. Using a melanoma progression model, we evaluated the impact of Timp1 and AKT silencing, as well as PI3K, PDK1, and protein kinase C (PKC) inhibitors on aggressiveness characteristics...
April 21, 2017: Cancers
https://www.readbyqxmd.com/read/28429064/simple-and-cost-effective-liquid-chromatography-mass-spectrometry-method-to-measure-dabrafenib-quantitatively-and-six-metabolites-semi-quantitatively-in-human-plasma
#20
Svante Vikingsson, Jan-Olof Dahlberg, Johan Hansson, Veronica Höiom, Henrik Gréen
Dabrafenib is an inhibitor of BRAF V600E used for treating metastatic melanoma but a majority of patients experience adverse effects. Methods to measure the levels of dabrafenib and major metabolites during treatment are needed to allow development of individualized dosing strategies to reduce the burden of such adverse events. In this study, an LC-MS/MS method capable of measuring dabrafenib quantitatively and six metabolites semi-quantitatively is presented. The method is fully validated with regard to dabrafenib in human plasma in the range 5-5000 ng/mL...
April 20, 2017: Analytical and Bioanalytical Chemistry
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