Rash and diarrhea are common side effects of tyrosine kinase inhibitor (TKI) therapy administered to patients with non-small cell lung cancer (NSCLC). The polymorphisms of the epidermal growth factor receptor (EGFR) gene may be a potential predictor of these side effects. The aim of the present meta-analysis was to examine the association of EGFR polymorphisms and TKI-associated toxicities. Electronic databases (PubMed, Scopus and ISI Web of Science) were searched for relevant studies. According to the inclusion and exclusion criteria, a search of the databases identified 4,918 results, among which 6 clinical trials were obtained with 1,318 patients with NSCLC. A total of 9 EGFR single nucleotide polymorphisms (SNPs) associated with TKI toxicity were identified including, rs11568315, rs712829, rs712830, rs2227983, rs2075102, rs2293347, rs11977388, rs4947492 and rs884225. The data associated with skin toxicity from rs11568315, rs712829 and rs712830 were analyzed in the present meta-analysis. Data from rs11568315 were also analyzed in relation to diarrhea. Among all the examined SNPs, statistically significant results were obtained under the dominant genetic model for CA repeats in rs11568315 (SS vs. SL+LL) with skin toxicity. The long CA repeat (SL+LL) carriers were more likely to experience skin toxicity associated with TKIs (P=0.005). By contrast, there was no significant result for diarrhea (P=0.661) under dominant genetic model for CA repeats.
This study aimed to examine the biological activities of unique steroid hormone derivatives-steroidal imidazoheterocycles. The activity synthesized steroidal compounds were tested for the viability of JEG-3 trophoblast cells of choriocarcinoma. The results of the MTT cytotoxicity test showed that most of the examined steroidal imidazoheterocycles act proliferatively on the JEG-3 cell line, except (E, F, and J). Antiproliferative activity of these derivates is probably influenced by different substituents at position 17-C atom in the chemical structure of the hormone and by different substituents on the oxygen atom of acetamide group in the hormone molecule. In order to better confirm the antiproliferative activity of these derivatives, it is necessary to performed complex research on a large panel of cancer cell lines and by different assay.
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