Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 33-year-old woman presented with rare brain metastases from undifferentiated high-grade sarcoma manifesting as headache and vomiting. Magnetic resonance (MR) imaging demonstrated multiple tumors in the brain, subcutaneous soft tissue, and mediastinum. The patient underwent surgery, followed by chemotherapy and radiotherapy. The histological diagnosis was undifferentiated high-grade sarcoma. Radiotherapy was effective, but the brain tumors recurred 6 months later. The patient underwent high-dose methotrexate therapy, but showed no response. Promoter hypermethylation in the O(6)-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) genes was detected and MGMT protein expression was negative in the recurrent tumor, so temozolomide (TMZ) salvage chemotherapy was given, and follow-up MR imaging showed tumor reduction. This case suggests that TMZ may be effective for brain metastasis of undifferentiated sarcoma without MGMT protein expression.
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PMID:Brain metastasis of undifferentiated sarcoma and response to temozolomide treatment. Case report. 2080 57

Epigenetics has been defined as 'the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states.' Currently, several classes of anticancer drugs function at the epigenetic level, including inhibitors of DNA methyltransferase, histone deacetylase (HDAC), lysine-specific demethylase 1, zeste homolog 2, and bromodomain and extra-terminal motif (BET) proteins.BET proteins have multiple functions, including the initiation and elongation of transcription and cell cycle regulation. In recent years, inhibitors of BET proteins have been developed as anticancer agents. These inhibitors exhibit selectivity for tumor cells by preferentially binding to superenhancers, noncoding regions of DNA critical for the transcription of genes that determine a cell's identity. Preclinical research on BET inhibitors has identified them as a potential means of targeting MYC.Early clinical trials with BET inhibitors have had mixed results, with few responses in both hematologic and solid tumors that tend to be short-lived. Toxicities have included severe, thrombocytopenia, fatigue, nausea, vomiting, and diarrhea; GI side-effects, fatigue, and low-grade dysgeusia have limited compliance. However, preclinical data suggest that BET inhibitors may have a promising future in combination with other agents. They appear to be able to overcome resistance to targeted agents and have strong synergy with immune checkpoint inhibitors as well as with multiple epigenetic agents, particularly HDAC inhibitors. In many instances, BET and HDAC inhibitors were synergistic at reduced doses, suggesting a potential means of avoiding the overlapping toxicities of the two drug classes.BET inhibitors provide a novel approach to epigenetic anticancer therapy. However, to date they appear to have limited efficacy as single agents. A focus on BET inhibitors in combination with other drugs such as targeted and/or as other epigenetic agents is warranted, due to limited monotherapy activity, including pharmacodynamic correlatives differential activity amongst select drug combinations.
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PMID:BET inhibitors: a novel epigenetic approach. 2883 16