Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The taxanes and Herceptin have been shown to possess significant clinical activity in metastatic breast cancer. Preclinical testing of taxane/Herceptin combinations demonstrated additive and synergistic interactions with paclitaxel and docetaxel, respectively. In a pivotal clinical trial, combination of paclitaxel (3-weekly) and Herceptin was associated with an increased response rate compared with paclitaxel monotherapy (41% vs. 17%; p = 0.001). The combination therapy also significantly improved time to disease progression (6.9 vs. 2.7 months; p < 0.05). In a phase II study of weekly paclitaxel plus Herceptin in patients with normal or increased tumor HER2 levels, a response was observed in 60% of patients and the regimen was well tolerated. Responses were more frequent in patients with HER2-overexpressing tumors (83% vs. 45%). Preliminary results from a phase II study of Herceptin plus docetaxel in patients with HER2-overexpressing tumors indicate significant activity, with a response observed in 7 (44%) of 16 evaluable patients. The preliminary results of a trial of weekly docetaxel and Herceptin demonstrate a response rate of 54% in 13 evaluable patients. Additional European trials of Hercep- tin/taxane combinations as first- and second-line and adjuvant therapy are ongoing. The results of the studies to date indicate that regimens combining Herceptin with 3-weekly and weekly taxane are effective and well tolerated.
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PMID:Interaction between Herceptin and taxanes. 1169 87

Metastasis is commonly seen in advanced stage of cancers, and matrix metalloproteinases (MMPs) are commonly up-regulated and have been identified as critical regulators. In this present study, a flavonoid, fisetin, which can be found in diverse foods, is investigated for its ability to inhibit cell motility, and the underlying mechanism is also studied in breast cancer cells (4T1 and JC cells). We have revealed that fisetin increased HO-1 mRNA and protein expressions. Besides, fisetin also elevated Nrf2 expression in nuclear fraction. By silencing Nrf2, fisetin-induced HO-1 expression was abrogated, suggested that HO-1 expression was mediated by up-regulation of the transcription factor Nrf2. In addition, we also found that fisetin decreased MMP-2 and MMP-9 enzyme activity and gene expression in both protein and mRNA levels. Moreover, by administration of HO-1 inhibitors, tin protoporphyrin and zinc protoporphyrin, fisetin-reduced MMP-2 and MMP-9 expressions were reversed. Furthermore, transfection of siRNA against HO-1 and Nrf2 also abolished MMP-2 and MMP-9 reduction exerted by fisetin. These findings suggest that fisetin-mediated MMP-2 and MMP-9 reduction is regulated by HO-1 through Nrf2. Therefore, fisetin may be useful as a potential therapeutic agent for the treatment of metastatic breast cancer.
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PMID:Fisetin inhibits cell migration via inducing HO-1 and reducing MMPs expression in breast cancer cell lines. 3007 13