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Cancer: Melanoma

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Total 1255 results found since Jan 2013.

MLN4924 Genome-Wide RNAi Screen
MLN4924 is an investigational small-molecule inhibitor of the NEDD8-activating enzyme (NAE) in phase I clinical trials. NAE inhibition prevents the ubiquitination and proteasomal degradation of substrates for cullin-RING ubiquitin E3 ligases that support cancer pathophysiology, but the genetic determinants conferring sensitivity to NAE inhibition are unknown. To address this gap in knowledge, we conducted a genome-wide siRNA screen to identify genes and pathways that affect the lethality of MLN4924 in melanoma cells. Of the 154 genes identified, approximately one-half interfered with components of the cell cycle, apoptotic...
Source: Cancer Research - January 2, 2013 Category: Cancer & Oncology Authors: Blank, J. L., Liu, X. J., Cosmopoulos, K., Bouck, D. C., Garcia, K., Bernard, H., Tayber, O., Hather, G., Liu, R., Narayanan, U., Milhollen, M. A., Lightcap, E. S. Tags: Molecular and Cellular Pathobiology Source Type: research

Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents.
CONCLUSIONS: We demonstrate that activation of the PI3K/AKT pathway is a mechanism of both innate and acquired resistance to BRAF inhibitors in BRAFV600E CRC, and suggest combinatorial approaches to improve outcomes in this poor prognosis subset of patients. PMID: 23251002 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - December 18, 2012 Category: Cancer & Oncology Authors: Mao M, Tian F, Mariadason JM, Tsao L, Lemos R, Dayyani F, Yennu Nanda VG, Jiang ZQ, Wistuba I, Tang X, Bornmann WG, Bollag G, Mills GB, Powis G, Desai J, Gallick GE, Davies MA, Kopetz S Tags: Clin Cancer Res Source Type: research

The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.
Abstract Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox1...
Source: Developmental Biology - January 17, 2013 Category: Biology Authors: Silver DL, Leeds KE, Hwang HW, Miller EE, Pavan WJ Tags: Dev Biol Source Type: research

Novel splice variants of IL-33 expressed in normal human keratinocytes
In this study, we found 7 IL-33 splice variants including 5 newly determined variants in NHEKs. Some of these variants were cloned into mammalian expression vector fused with V5 and FLAG tags, and transfected into NHEKs. Most of them were expressed in the nucleus, however, some variants that lack specific exon were expressed in cytoplasmic fraction. When IL-33 was knocked down by siRNA, cell proliferation was down-regulated revealed by BrdU incorporation assay and cell cycle assay. IL-33 is not only a cytokine but also exerts important multiple roles in the nucleus and/or cytoplasm of keratinocytes.
Source: Journal of Dermatological Science - December 20, 2012 Category: Dermatology Authors: Hidetoshi Tsuda, Mayumi Komine, Tomoyuki Ohio, Satomi Hosoda, Shin-ichi Tominaga, Mamitaro Ohtsuki Tags: Abstracts from the 37th Annual Meeting of the Japanese Society for Investigative Dermatology Source Type: research

The expression and functional characterization of RIG-I-like receptors (RLRs) of mast cells in response to viral infection
Mast cells are well known to play important roles in innate immune responses. They express various receptors to recognize pathogen-derived molecular patterns (PAMP) and are activated to release inflammatory and anti-viral cytokines and chemokines. However, the precise mechanisms for recognition of virus by mast cells are not fully understood. To investigate the precise mechanisms of virus recognition by mast cells, we examined the expression of and functionally characterized virus recognition receptors that lead to mast cell activation. Our results suggest that mast cells are partly responsible for the early in vivo produc...
Source: Journal of Dermatological Science - December 20, 2012 Category: Dermatology Authors: Mizuho Takeuchi, Minoru Fukuda, Hiroko Ushio, Junko Kawasaki, Francois Niyonsaba, Ko Okumura, Shigaku Ikeda, Hideoki Ogawa Tags: Abstracts from the 37th Annual Meeting of the Japanese Society for Investigative Dermatology Source Type: research

Identification of Aurora Kinase B and WEE1 as Downstream Targets of (V600E)B-RAF in Melanoma.
Abstract B-RAF is the most mutated gene in melanoma, with approximately 50% of patients containing V600E mutant protein. (V600E)B-RAF can be targeted using pharmacological agents, but resistance develops in patients by activating other proteins in the signaling pathway. Identifying downstream members in this signaling cascade is important to design strategies to avoid the development of resistance. Unfortunately, downstream proteins remain to be identified and therapeutic potential requires validation. A kinase screen was undertaken to identify downstream targets in the (V600E)B-RAF signaling cascade. Involvement ...
Source: The American Journal of Pathology - February 12, 2013 Category: Pathology Authors: Sharma A, Madhunapantula SV, Gowda R, Berg A, Neves RI, Robertson GP Tags: Am J Pathol Source Type: research

Spliceosome as a Target for Anticancer Treatment
The spliceosome is a large ribonucleoprotein complex that guides pre-mRNA splicing in eukaryotic cells. Here, we determine whether the spliceosome could constitute an attractive therapeutic target in cancer. Analysis of gene expression arrays from lung, breast, and ovarian cancers datasets revealed that several genes encoding components of the core spliceosome composed of a heteroheptameric Sm complex were overexpressed in malignant disease as compared with benign lesions and could also define a subset of highly aggressive breast cancers. siRNA-mediated depletion of SmE (SNRPE) or SmD1 (SNRPD1) led to a marked reduction of...
Source: Cancer Research - April 2, 2013 Category: Cancer & Oncology Authors: Quidville, V., Alsafadi, S., Goubar, A., Commo, F., Scott, V., Pioche–Durieu, C., Girault, I., Baconnais, S., Le Cam, E., Lazar, V., Delaloge, S., Saghatchian, M., Pautier, P., Morice, P., Dessen, P., Vagner, S., Andre, F. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

MicroRNA-124a Is Epigenetically Regulated and Acts as a Tumor Suppressor by Controlling Multiple Targets in Uveal Melanoma Biochemistry and Molecular Biology
Conclusions. Our results demonstrated that miR-124a could function as a potent tumor suppressor by regulation of multiple targets, and was epigenetically silenced in the development of uveal melanoma.
Source: Investigative Ophthalmology - March 27, 2013 Category: Opthalmology Authors: Chen, X., He, D., Dong, X. D., Dong, F., Wang, J., Wang, L., Tang, J., Hu, D.-N., Yan, D., Tu, L. Tags: Biochemistry and Molecular Biology Source Type: research

The BH3-only protein BimL overrides Bcl-2-mediated apoptosis resistance in melanoma cells
Highlights: ► The BH3-only protein Bim(L) efficiently triggers apoptosis in melanoma cells. ► Bim(L) overcomes Bax and Bak single deficiency. ► Bim(L) overcomes apoptosis blockage by high Bcl-2 expression. ► Bim(L) interacts with all antiapoptotic Bcl-2 family members. ► Bim expression in melanoma cells is related to inhibition of BRAF.Abstract: Melanoma cells are characterized by apoptosis deficiency coinciding with reduced expression of the proapoptotic Bcl-2 protein Bim. An adenoviral vector was constructed with the BimL cDNA controlled by an inducible promoter. Highly efficient apoptosis induction and abrogat...
Source: Cancer Letters - March 4, 2013 Category: Cancer & Oncology Authors: Michael Plötz, Bernhard Gillissen, Sandra-Annika Quast, Anja Berger, Peter T. Daniel, Jürgen Eberle Tags: Research Articles Source Type: research

GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: Potential role for tissue engineering bone
Abstract Bone regeneration is a coordinated process involving the connection between blood vessels and bone cells. Glycoprotein non‐metastatic melanoma protein B (GPNMB) is known to be vital in bone formation. However, the effect of GPNMB on bone regeneration and the underlying molecular mechanism are still undefined. Fibroblast growth factor receptor (FGFR)‐mediating signaling is pivotal in bone formation and angiogenesis. Therefore, we assessed GPNMB function as a communicating molecule between osteoblasts and angiogenesis, and the possible correlation with FGFR‐1 signaling. Recombinant GPNMB dose‐dependently inc...
Source: Journal of Cellular Biochemistry - June 24, 2013 Category: Biochemistry Authors: Xuefeng Hu, Ping Zhang, Zhenjie Xu, Hongdong Chen, Xin Xie Tags: Article Source Type: research

Melanoma immunotherapy using mature DCs expressing the constitutive proteasome
Conclusion. These results suggest that the efficacy of melanoma DC–based immunotherapy is enhanced when tumor antigen–loaded DCs used for vaccination express cPs. Trial registration. Clinicaltrials.gov NCT00672542. Funding. Duke Clinical Research Institute/Duke Translational Medicine Institute, Duke Melanoma Consortium, and Duke University Department of Surgery.
Source: Journal of Clinical Investigation - July 1, 2013 Category: Biomedical Science Authors: Jens Dannull, N. Rebecca Haley, Gary Archer, Smita Nair, David Boczkowski, Mark Harper, Nicole De Rosa, Nancy Pickett, Paul J. Mosca, James Burchette, Maria A. Selim, Duane A. Mitchell, John Sampson, Douglas S. Tyler, Scott K. Pruitt Source Type: research

Impact of LIF (Leukemia Inhibitory Factor) Expression in Malignant Melanoma.
Abstract Leukemia inhibitory factor (LIF) signaling regulates cellular processes to maintain the self-renewal and pluripotency of embryonic stem (ES) cells. Independently of these capabilities, LIF was also identified to be responsible for cancer development and progression. However, its detailed cellular function in cancer remains unclear thus far. We found LIF to be expressed in melanoma cell lines of primary and metastatic origin and in melanoma tissue. We further elucidated stimuli that are responsible for the high expression levels of LIF. Interestingly, hypoxia, specifically through HIF-1α, is involved in r...
Source: Experimental and Molecular Pathology - July 4, 2013 Category: Pathology Authors: Kuphal S, Wallner S, Bosserhoff AK Tags: Exp Mol Pathol Source Type: research

A Kinome-Wide siRNA Screen Identifies Multiple Roles for Protein Kinases in Hypoxic Stress Adaptation, Including Roles for IRAK4 and GAK in Protection against Apoptosis in VHL-/- Renal Carcinoma Cells, Despite Activation of the NF-{kappa}B Pathway
Hypoxia induces changes to cancer cells that make them more resistant to treatment. We have looked at signaling pathways that facilitate these changes by screening the human kinome for effects on hypoxic responses in SW480 colon cancer cells. Hits identified in the screen were examined for effects on multiple molecular responses to hypoxia, including the endoplasmic reticulum stress and DNA damage responses in colon, melanoma, and renal cancer lines. To validate the hits from the small interfering RNA studies, we developed cell lines expressing stable short hairpin RNAs (shRNAs) in the A498 renal carcinoma cell line. Sever...
Source: Journal of Biomolecular Screening - July 23, 2013 Category: Molecular Biology Authors: Pan, J., Zhang, J., Hill, A., Lapan, P., Berasi, S., Bates, B., Miller, C., Haney, S. Tags: Original Research Source Type: research

Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway.
Abstract Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless, precise mechanism involved in ET-1-induced hyperpigmentation is still undefined. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key element in melanosome formation. Therefore, we speculated that GPNMB was correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin synthesis was significantly up-regulated, accompanying with increased expression of GPNMB and microphthalmia- associated transcription factor (...
Source: BMB Reports - July 1, 2013 Category: Biochemistry Authors: Zhang P, Liu W, Yuan X, Li D, Gu W, Gao T Tags: BMB Rep Source Type: research

A novel interaction between calcium-modulating cyclophilin ligand and Basigin regulates calcium signaling and matrix metalloproteinase activities in human melanoma cells
In this study, we demonstrate that the endoplasmic reticulum (ER)-associated protein calcium-modulating cyclophilin ligand (CAML) is bound to Basigin, a widely expressed integral plasma membrane glycoprotein and extracellular matrix metalloproteinase inducer (EMMPRIN, or CD147) implicated in melanoma proliferation, invasiveness, and metastasis. This interaction between CAML and Basigin was first identified using yeast two-hybrid screening and further confirmed by co-immunoprecipitation. In human A375 melanoma cells, CAML and Basigin were co-localized to the ER. Knockdown of Basigin in melanoma cells by siRNA significantly ...
Source: Cancer Letters - August 9, 2013 Category: Cancer & Oncology Authors: Tingting Long, Juan Su, Wen Tang, Zhongling Luo, Shuang Liu, Zhaoqian Liu, Honghao Zhou, Min Qi, Weiqi Zeng, Jianglin Zhang, Xiang Chen Tags: Research Articles Source Type: research