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Melanoma: HELP
Articles by James S. Blachly
Based on 3 articles published since 2008
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Between 2008 and 2019, James Blachly wrote the following 3 articles about Melanoma.
 
+ Citations + Abstracts
1 Article Identification of NRAS isoform 2 overexpression as a mechanism facilitating BRAF inhibitor resistance in malignant melanoma. 2017

Duggan, Megan C / Stiff, Andrew R / Bainazar, Maryam / Regan, Kelly / Olaverria Salavaggione, Gonzalo N / Maharry, Sophia / Blachly, James S / Krischak, Madison / Walker, Christopher J / Latchana, Nicholas / Tridandapani, Susheela / de la Chapelle, Albert / Eisfeld, Ann-Kathrin / Carson, William E. ·Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210. · Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210. · Division of Surgical Oncology, The Ohio State University, Columbus, OH 43210. · Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210; Albert.delaChapelle@osumc.edu ann-kathrin.eisfeld@osumc.edu william.carson@osumc.edu. · Division of Surgical Oncology, The Ohio State University, Columbus, OH 43210 Albert.delaChapelle@osumc.edu ann-kathrin.eisfeld@osumc.edu william.carson@osumc.edu. ·Proc Natl Acad Sci U S A · Pubmed #28827320.

ABSTRACT: Activating mutations in BRAF are found in 50% of melanomas and although treatment with BRAF inhibitors (BRAFi) is effective, resistance often develops. We now show that recently discovered NRAS isoform 2 is up-regulated in the setting of BRAF inhibitor resistance in melanoma, in both cell lines and patient tumor tissues. When isoform 2 was overexpressed in BRAF mutant melanoma cell lines, melanoma cell proliferation and in vivo tumor growth were significantly increased in the presence of BRAFi treatment. shRNA-mediated knockdown of isoform 2 in BRAFi resistant cells restored sensitivity to BRAFi compared with controls. Signaling analysis indicated decreased mitogen-activated protein kinase (MAPK) pathway signaling and increased phosphoinositol-3-kinase (PI3K) pathway signaling in isoform 2 overexpressing cells compared with isoform 1 overexpressing cells. Immunoprecipitation of isoform 2 validated a binding affinity of this isoform to both PI3K and BRAF/RAF1. The addition of an AKT inhibitor to BRAFi treatment resulted in a partial restoration of BRAFi sensitivity in cells expressing high levels of isoform 2. NRAS isoform 2 may contribute to resistance to BRAFi by facilitating PI3K pathway activation.

2 Article Structural characterization of NRAS isoform 5. 2016

Markowitz, Joseph / Mal, Tapas K / Yuan, Chunhua / Courtney, Nicholas B / Patel, Mitra / Stiff, Andrew R / Blachly, James / Walker, Christopher / Eisfeld, Ann-Kathrin / de la Chapelle, Albert / Carson, William E. ·Moffitt Cancer Center Department of Cutaneous Oncology, The Ohio State University, Columbus, Ohio. · The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. · The Ohio State University Campus Chemical Instrument Center-NMR, The Ohio State University, Columbus, Ohio. · The Ohio State University Wexner Medical Center Department of Surgery, The Ohio State University, Columbus, Ohio. ·Protein Sci · Pubmed #26947772.

ABSTRACT: It was recently discovered that the NRAS isoform 5 (20 amino acids) is expressed in melanoma and results in a more aggressive cell phenotype. This novel isoform is responsible for increased phosphorylation of downstream targets such as AKT, MEK, and ERK as well as increased cellular proliferation. This structure report describes the NMR solution structure of NRAS isoform 5 to be used as a starting point to understand its biophysical interactions. The isoform is highly flexible in aqueous solution, but forms a helix-turn-coil structure in the presence of trifluoroethanol as determined by NMR and CD spectroscopy.

3 Article Cotreatment of hairy cell leukemia and melanoma with the BRAF inhibitor dabrafenib. 2015

Blachly, James S / Lozanski, Gerard / Lucas, David M / Grever, Michael R / Kendra, Kari / Andritsos, Leslie A. ·From the Division of Hematology, Department of Internal Medicine, Department of Pathology, and Division of Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio. ·J Natl Compr Canc Netw · Pubmed #25583765.

ABSTRACT: The activating BRAF mutation p.V600E has been identified in many cancers, including colon and lung adenocarcinomas, papillary thyroid cancer, malignant melanoma, and hairy cell leukemia (HCL). Malignant melanoma and HCL are of particular interest because of both the high proportion of cases harboring the mutation and the dramatic responses to BRAF inhibitor therapy reported in the literature. This report presents a patient with HCL and malignant melanoma with the BRAF p.V600E mutation, and discusses the successful treatment of both cancers with the BRAF inhibitor dabrafenib.