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Melanoma: HELP
Articles by Meijun Zhu
Based on 3 articles published since 2009
(Why 3 articles?)

Between 2009 and 2019, Meijun Zhu wrote the following 3 articles about Melanoma.
+ Citations + Abstracts
1 Clinical Trial Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. 2013

Hodi, F Stephen / Corless, Christopher L / Giobbie-Hurder, Anita / Fletcher, Jonathan A / Zhu, Meijun / Marino-Enriquez, Adrian / Friedlander, Philip / Gonzalez, Rene / Weber, Jeffrey S / Gajewski, Thomas F / O'Day, Steven J / Kim, Kevin B / Lawrence, Donald / Flaherty, Keith T / Luke, Jason J / Collichio, Frances A / Ernstoff, Marc S / Heinrich, Michael C / Beadling, Carol / Zukotynski, Katherine A / Yap, Jeffrey T / Van den Abbeele, Annick D / Demetri, George D / Fisher, David E. ·F. Stephen Hodi, Anita Giobbie-Hurder, Philip Friedlander, Jason J. Luke, Katherine A. Zukotynski, Jeffrey T. Yap, Annick D. Van den Abbeele, and George D. Demetri, Dana-Farber Cancer Institute · Jonathan A. Fletcher, Meijun Zhu, and Adrian Marino-Enriquez, Brigham and Women's Hospital · Donald Lawrence, Keith T. Flaherty, and David E. Fisher, Massachusetts General Hospital, Boston, MA · Christopher L. Corless, Michael C. Heinrich, and Carol Beadling, Portland Veterans Administration Medical Center and Oregon Health & Science University, Portland, OR · Philip Friedlander, Mount Sinai Medical Center, New York, NY · Rene Gonzalez, University of Colorado Cancer Center, Aurora, CO · Jeffrey S. Weber, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL · Thomas F. Gajewski, University of Chicago, Chicago, IL · Steven J. O'Day, Beverly Hills Cancer Center, Beverly Hills, CA · Kevin B. Kim, The University of Texas MD Anderson Cancer Center, Houston, TX · Frances A. Collichio, The University of North Carolina at Chapel Hill, Chapel Hill, NC · and Marc S. Ernstoff, Geisel School of Medicine and Norris Cotton Cancer Center, Hanover, NH. ·J Clin Oncol · Pubmed #23775962.

ABSTRACT: PURPOSE: Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities. PATIENTS AND METHODS: We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Patients received imatinib 400 mg once per day or 400 mg twice per day if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening was performed by mass spectroscopy. RESULTS: Twenty-five patients were enrolled (24 evaluable). Eight patients (33%) had tumors with KIT mutations, 11 (46%) with KIT amplifications, and five (21%) with both. Median follow-up was 10.6 months (range, 3.7 to 27.1 months). Best overall response rate (BORR) was 29% (21% excluding nonconfirmed responses) with a two-stage 95% CI of 13% to 51%. BORR was significantly greater than the hypothesized null of 5% and statistically significantly different by mutation status (7 of 13 or 54% KIT mutated v 0% KIT amplified only). There were no statistical differences in rates of progression or survival by mutation status or by melanoma site. The overall disease control rate was 50% but varied significantly by KIT mutation status (77% mutated v 18% amplified). Four patients harbored pretreatment NRAS mutations, and one patient acquired increased KIT amplification after treatment. CONCLUSION: Melanomas that arise on mucosal, acral, or CSD skin should be assessed for KIT mutations. Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib.

2 Article Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-κB pathways. 2012

Wu, Xinqi / Li, Jingjing / Zhu, Meijun / Fletcher, Jonathan A / Hodi, F Stephen. ·Department of Medical Oncology, Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02215, USA. ·Mol Cancer Ther · Pubmed #22653968.

ABSTRACT: Somatic GNAQ mutations at codon 209 have been identified in approximately 50% of uveal melanomas and have been reported to be oncogenic through activating PLCβ/PKC/Erk1/2 pathways. We hypothesized that protein kinase C (PKC) may provide new opportunities for therapeutic targeting of uveal melanoma carrying GNAQ mutations. To test this hypothesis, uveal melanoma cells harboring wild-type or mutant GNAQ were treated with the PKC inhibitor AEB071 (sotrastaurin) or infected with lentivirus-expressing short hairpin RNAs (shRNA) targeting PKC isoforms. Notably, AEB071 at low micromolar concentrations significantly inhibited the growth of uveal melanoma cells harboring GNAQ mutations through induction of G(1) arrest and apoptosis. However, AEB071 had little effect on uveal melanoma cells carrying wild-type GNAQ. AEB071-mediated cell inhibition in the GNAQ-mutated uveal melanoma was accompanied by inhibition of extracellular signal-regulated kinase (Erk)1/2 phosphorylation, NF-κB, decreased expression of cyclin D1, survivin, Bcl-xL, and XIAP, and increased expression of cyclin-dependent kinase inhibitor p27(Kip1). AEB071 suppressed the expression of PKC α, β, δ, ε, and θ in GNAQ-mutated uveal melanoma cells. Our findings from shRNA-mediated knockdown studies revealed that these PKC isoforms are functionally important for uveal melanoma cells harboring GNAQ mutations. Furthermore, inhibitors of Erk1/2 and NF-κB pathways reduced viability of uveal melanoma cells. Together, our findings show that AEB071 exerts antitumor action on uveal melanoma cells carrying GNAQ mutations via targeting PKC/Erk1/2 and PKC/NF-κB pathways. Targeted PKC inhibition with drugs such as AEB071 offers novel therapeutic potential for uveal melanoma harboring GNAQ mutations.

3 Article The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanoma. 2012

Wu, Xinqi / Zhu, Meijun / Fletcher, Jonathan A / Giobbie-Hurder, Anita / Hodi, F Stephen. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America. ·PLoS One · Pubmed #22253748.

ABSTRACT: GNAQ mutations at codon 209 have been recently identified in approximately 50% of uveal melanomas (UM) and are reported to be oncogenic through activating the MAPK/Erk1/2 pathway. Protein kinase C (PKC) is a component of signaling from GNAQ to Erk1/2. Inhibition of PKC might regulate GNAQ mutation-induced Erk1/2 activation, resulting in growth inhibition of UM cells carrying GNAQ mutations. UM cells carrying wild type or mutant GNAQ were treated with the PKC inhibitor enzastaurin. Effects on proliferation, apoptosis, and signaling events were evaluated. Enzastaurin downregulated the expression of several PKC isoforms including PKCβII PKCθ, PKCε and/or their phosphorylation in GNAQ mutated cells. Downregulation of these PKC isoforms in GNAQ mutated cells by shRNA resulted in reduced viability. Enzastaurin exhibited greater antiproliferative effect on GNAQ mutant cells than wild type cells through induction of G1 arrest and apoptosis. Enzastaurin-induced G1 arrest was associated with inhibition of Erk1/2 phosphorylation, downregulation of cyclin D1, and accumulation of cyclin dependent kinase inhibitor p27(Kip1). Furthermore, enzastaurin reduced the expression of antiapoptotic Bcl-2 and survivin in GNAQ mutant cells. Inhibition of Erk1/2 phosphorylation with a MEK specific inhibitor enhanced the sensitivity of GNAQ wild type cells to enzastaurin, accompanied by p27(Kip1) accumulation and/or inhibition of enzastaurin-induced survivin and Bcl-2 upregulation. PKC inhibitors such as enzastaurin have activity against UM cells carrying GNAQ mutations through inhibition of the PKC/Erk1/2 pathway and induction of G1 arrest and apoptosis. Inhibition of the PKC pathway provides a basis for clinical investigation in patients with UM.