Correlation Analysis between T790M Status and Clinical Characteristics of Patients with EGFR-sensitive Mutation Advanced NSCLC who Progressed after the First-line EGFR-TKIs Administration: A Real-world Exploratory Study.

AIM: The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) administration. METHODS: A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively. The clinical and demographic characteristics of these patients were collected, which were manifested as pathological type, metastasis location, initial biopsy method, initial genetic test specimens, and baseline gene mutations status. Correlation analysis between T790M status and these characteristics was performed and prognostic analysis regarding the different subgroups was carried out accordingly. RESULTS: The prevalence of secondary T790M after resistance to initial EGFR-TKIs among the 167 patients was 52.7%. Correlation analysis indicated that the median progression-free Survival (PFS) to initial EGFR-TKIs >12 months were more likely to develop secondary T790M in univariate analysis. However, the conclusion failed to show statistically significant in multivariate analysis. Additionally, patients with intracranial progression of initial EGFR-TKIs therapy were associated with secondary EGFR-T790M. However, it should be noted that those whose best overall response was partial response (PR) during the EGFR-TKI therapy were relevant to secondary T790M. Furthermore, The median PFS of the initial EGFR-TKIs administration was longer among patients with T790M positive mutation and patients with PR reaction than those without T790M mutation and patients with stable disease (SD), respectively (median PFS: 13.6 vs 10.9 months, P=0.023) and (median PFS: 14.0 vs 10.1 months, P=0.001). CONCLUSION: This retrospective study highlighted the real-world evidence that the best efficacy and intracranial progression with initial EGFR-TKIs therapy among patients with advanced NSCLC might be the promising indicators to predict the occurrence of EGFR-T790M. Patients with PR reaction and T790M positive mutation conferred longer PFS of the initial EGFR-TKIs administration. Also, the conclusion should be confirmed in more patients with advanced NSCLC subsequently.

Recombinant human endostatin combined with chemotherapy for advanced squamous cell lung cancer: a meta-analysis.

BACKGROUND: This paper aims to compare the efficacy and safety of recombinant human endostatin combined with chemotherapy in patients with squamous cell lung cancer (SqCLC). METHODS: We searched the Cochrane Library, PubMed, Embase, CNKI, Wanfang database, Metstr, VIP, and others and manually searched books and magazines until 2019 for articles about the efficacy and safety of recombinant human endostatin combined with chemotherapy in patients with SqCLC. A second search was conducted on the review literature. According to the criteria of the literature screen, the relevant randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) of recombinant human endostatin combined with chemotherapy and chemotherapy alone in the treatment of SqCLC were included. After the data were extracted and analyzed, RevMan 5.3 software was used for meta-analysis for the outcome indicators. Then, heterogeneity tests and sensitivity analyses were carried out, and the publication bias of this study was tested in Stata 13.0 software. Six RCTs and eight non-RCTs were included. In total, 821 patients with SqCLC were included. RESULTS: The response rate (RR) was 2.12 (95% CI: 1.57-2.85, p < 0.00001). The disease control rate (DCR) was 2.38 (95% CI: 1.70-3.32, p < 0.00001). The difference between the two groups was statistically significant. Regarding safety, the incidence rates of the adverse reactions cardiotoxicity, leukopenia, thrombocytopenia, and gastrointestinal reactions were not significantly different between the two groups (OR = 1.70, 95% CI: 0.79-3.68; OR = 0.93, 95% CI: 0.61-1.42; OR = 1.08, 95% CI: 0.71-1.64; OR = 0.86, 95% CI: 0.56-1.30, respectively). CONCLUSION: The combined treatment had a better therapeutic effect than chemotherapy alone. It did not increase the incidence of adverse reactions in the course of treatment.

TNNT2 as a potential biomarker for the progression and prognosis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. At present, there are limited effective biomarkers of CRC. The present study aimed to identify potential signatures associated with the tumorigenesis and prognosis of CRC using publicly available databases, and further validate the identified biomarkers in CRC cell lines. Identification of differentially expressed mRNAs between CRC and paracancerous samples was conducted based on data from The Cancer Genome Atlas (TCGA; 471 tumor samples and 41 normal samples). Survival analysis was performed to explore the prognostic value of troponin 2 (TNNT2) in the TCGA training set, which was further validated in an external dataset, GSE17531. Functional enrichment analysis was conducted to determine the possible biological functions using GSEA 3.0. Reverse transcription­quantitative PCR (RT­qPCR) and western blotting were utilized to detect the mRNA and protein expression levels of TNNT2 between CRC and normal colorectal cells. Immunohistochemistry was performed to detect the protein expression of TNNT2 in CRC and normal tissues. TNNT2 was significantly upregulated in CRC samples compared with adjacent normal samples in the TCGA dataset. Increased expression of TNNT2 was associated with inferior prognosis in the TCGA training dataset and GSE17531 validation dataset. Functional enrichment analysis revealed that the ErbB signaling pathway and glycerophospholipid metabolism pathway were significantly activated in the TNNT2 high expression group. Overexpression of TNNT2 mRNA and TNNT2 protein in CRC tumor cells was confirmed by RT­qPCR and western blotting, respectively. Immunohistochemistry indicated increased protein expression levels of TNNT2 in CRC tissues in comparison with normal tissues. TNNT2 was associated with the tumorigenesis and prognosis of CRC, which may be useful for novel biomarker identification and targeted therapeutic strategy development.

Limonoid compounds from Xylocarpus granatum and their anticancer activity against esophageal cancer cells.

BACKGROUND: To investigate the anticancer effects of limonoid compounds that were isolated and purified from Xylocarpus granatum fruits on human esophageal cancer (EC) cells. A structure-activity relationship experiment was designed to identify the functional moiety of limonoid compounds identified as being critical for its anticancer activity. METHODS: Eca109 cells were cultured in RPMI1640 medium and treated with limonoid compounds. Cell proliferation was determined by the MTT assay in vitro. Eca109 cells apoptosis was analyzed by by flow cytometry after being treated with xylogranatin C. The expression of p53, Bax, bcl-2, caspase-3 and GRP78 in Eca109 cells after xylogranatin C treatment was examined by western blot assay. RESULTS: Four linonoid compounds strongly inhibited the cellular proliferation of Eca109 cells. Xylogranatin C was the strongest inhibitor, whose inhibitory effect was comparable to that of the well-known chemotherapeutic agent, cisplatin. Furthermore, xylogranatin C might induce Eca109 cell apoptosis through joint effects on multiple pathways, including the death receptor and endoplasmic reticulum pathways. Additionally, xylogranatin C suppressed tumor cell proliferation by upregulating miR-203a expression in Eca109 cells. CONCLUSIONS: Xylogranatin C induced Eca109 cellular apoptosis and exerted antitumor activity. Xylogranatin C suppressed tumor cell proliferation by upregulating miR-203a expression in Eca109 cells.