Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The First International Symposium on Melanoma and Other Cutaneous Malignancies, held in New York City on 23-25 April 2004, brought together researchers and clinicians from all over the world to discuss recent advances in the prevention, treatment and diagnosis of melanoma and other cutaneous malignancies. Discussion topics included primary and secondary prevention; advances in surgical therapy, including sentinel and elective lymph node dissection; the biology and pathogenesis of melanoma, including pathways of drug resistance; genomic analysis of melanoma, serum and tumour cell markers; with point and counterpoint sessions debating therapeutic controversies. The role of vaccines in the management of melanoma was discussed, including cell vaccines, dendritic cell-based vaccination and present research to improve the generation of melanoma vaccine-specific immunity. Adjuvant immunotherapy with high-dose IFN-alpha and an ongoing trial with biochemotherapy were debated. In addition, the role of chemotherapy and novel targeted agents in metastatic melanoma were discussed. Among the emerging agents and therapeutic targets presented were Bcl-2 antisense therapy, RAF kinases, heat-shock proteins, thalidomide and newer immunomodulatory drugs, cytotoxic T lymphocyte antigen-4 antibody and topical imiquimod. The symposium also provided an overview of existing and emerging agents and modalities in the management of patients with cutaneous T cell lymphomas, ocular melanoma and melanoma involving brain metastases. Sessions also included case-based learning and devoted ample time to providing 'how to' information for practising physicians.
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PMID:First International Symposium on Melanoma and Other Cutaneous Malignancies. 1533 20

Deregulated expression of molecular of the Notch signaling pathway is observed in malignant tumor. Notch signaling pathway is activated by a series of catalytic cleavage of the Notch receptor by gamma secretase. Gamma secretase inhibitor (GSI) have demonstrated clinical activity in patients with solid tumor. Triple negative breast cancer (TNBC) is related to poor prognosis and a high probability of lung and brain metastases. As first line therapy for TNBC, doxorubicin is partially effective in TNBC control. An understanding of the mechanisms for enhancing sensitivity to doxorubicin would be significant for future drug development. We hypothesized that a combination of cytotoxic chemotherapy doxorubicin to inhibit cell proliferation, together with GSI, would result in more effective outcome than either monotherapy alone. We treated MDA-MB-231 cell lines with doxorubicin and evaluated the monotherapy efficacy and in combination with GSI in both vitro and vivo. GSI-induced proliferation inhibition and apoptosis was achieved with an induction of PTEN and pro-apoptotic protein Bax expression and suppression of Notch-1, HES-1, CyclinD1 and anti-apoptotic protein Bcl-2. These results indicate that MDA-MB-231 cells are susceptible to a GSI, whether alone or in combination with doxorubicin, are correlated with changing of some surrogate marker. This study demonstrates practicability of combined use of GSI and doxorubicin, and together these results encourage new therapeutic method in triple negative breast cancer.
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PMID:Gamma secretase inhibitor enhances sensitivity to doxorubicin in MDA-MB-231 cells. 2619 Nov 29