Many cases of breast cancer show loss of estrogen receptor (ER) a expression, which leads to unresponsiveness to antihormonal treatment even though there is no loss of the structurally and biochemically similar ER b. ER activity is positively and negatively regulated by transcriptional regulators such as histone deacetylase (HDAC), which is known to be a negative ER regulator. Here, we evaluated using ER b as an alternative target for tamoxifen therapy by treating ER a-negative, b-positive breast cancer cells with the HDAC inhibitor trichostatin A (TSA), and testing whether tamoxifen responsiveness increased following upregulation of ER b. TSA enhanced the overall ER transcriptional activity in these cells, as visualized by estrogen response element-regulated reporter and the expression of progesterone receptor, a known ER target, without ER a restoration. Additionally, TSA induced the expression and nuclear translocation of ER b but not a, suggesting that these actions leading to increase of ER transcriptional activity are mediated through ER b rather than a. Furthermore, following treatment with TSA, the formerly unresponsive MDA-MB-231 and Hs578T breast cancer cells became responsive to tamoxifen. However, reduction of ER b expression by short interfering RNA abrogated this TSA-induced sensitization effect in these cells. Together, these results show that the HDAC inhibitor TSA sensitized ER a-negative, antihormone-unresponsive breast cancer cells to tamoxifen treatment possibly by upregulating ER b activity.
This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m À2 at week 1 and 250 mg m À2 weekly thereafter until disease progression. Oxaliplatin (100 mg m À2 ) and leucovorin (100 mg m
À2) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m À2 ) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1 -65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5 -6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-a levels showed a 100% RR compared to 37.0% in the remaining 27 patients (Po0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.
Five prognostic factors were identified from patients receiving first-line cisplatin-based chemotherapy for advanced gastric cancer. A simple prognostic index was then developed that produced distinct survival rates among the different risk groups. Therefore, this prognostic model could help clinicians and patients in clinical decision-making and treatment tailoring based on the estimated prognosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.