The Effect of Next-Generation TKI in Non-Small Cell Lung Cancer after Failure of First-Line Treatment: a Meta-Analysis.

Resistance develops against first-generation tyrosine kinase inhibitors (TKIs), which target the epidermal growth factor receptor (EGFR), after a while for non-small-cell lung cancer (NSCLC). Recently, researchers have developed specific inhibitors against them. Among those inhibitors, next-generation EGFR-TKIs have gained prominence due to the greater efficacy and more favorable tolerability. Today, the efficacy of next-generation EGFR-TKIs in patients with advanced NSCLC after failure on first-generation EGFR-TKIs still remains under investigation. The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation EGFR-TKIs in advanced NSCLC after failure on first-generation EGFR-TKIs. We performed a comprehensive search of the several electronic databases to September, 2018 to identify clinical trials. The primary endpoint was overall survival (OS), progression-free survival (PFS), disease controlled rate (DCR), objective response rate (ORR), and adverse events (AEs). Severe adverse events (AEs) (grade ≥ 3) based on the EGFR-TKIs were analysed. Odds Ratio (OR) along with 95% confidence interval (95% CI) were utilized for the main outcome analysis. In total, we had 3 randomized controlled trials in this analysis. The group of next-generation EGFR-TKIs was significantly improved PFS (OR = 0.34,95%CI = 0.29-0.40, P < 0.00001), as well with the ORR (OR = 10.48,95%CI = 3.87-28.34, P < 0.00001) and DCR (OR = 6.03,95%CI = 4.41-8.25, P < 0.00001), respectively. However, there is no significant difference in overall survival with next-generation EGFR-TKIs (OR = 1.05,95%CI = 0.85-1.31, P = 0.66). While, the OR for the treatment-related AEs of grade 3 or 4 (diarrhoea, rash/acne, nausea, vomiting, anemia) between the patients who received next-generation EGFR-TKIs and chemotherapy did not show safety benefit (P>0.05). Next-generation EGFR-TKIs was shown to be the better agent to achieve higher response rate and the longer PFS in NSCLC patients as the later-line therapy for previously treated patients with first-generation EGFR-TKIs. While, the benefit of the OS and safety compared with the chemotherapy did not achieved. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.

[The study on correlativity between HLA-DQ gene polymorphism and primary Sjogren's syndrome of the Han nationality in Shanxi province].

AIM: To explore the correlativity between HLA-DQ allele and primary Sjogren's syndrome(pSS) of the Han nationality in Shanxi province and to understand the pathogenesis of pSS at the gene level. METHODS: Polymerase chain reaction sequence specific primers (PCR-SSP) technique was used to determine the alleles of HLA-DQA1 and HLA-DQB1 of pSS patients and healthy populations, and the difference in their HLA-DQA1 and HLA-DQB1 allelic frequencies were analyzed by using chi-square test and Fisher's exact test. RESULTS: (1) The gene frequency of HLA-DQA1*0501 in pSS patients was significantly higher than that in healthy controls(22.0% vs 12.0%, x(2);=7.087, P<0.05, RR=2.068). (2)The gene frequency of HLA-DQA1*0301/2 in pSS patients was significantly lower than that in controls(13.0% vs 24.5%, x(2);=8.681, P<0.05, RR=0.460). (3) The gene frequency of HLA-DQB1*0201 in pSS patients was significantly higher than that in controls(28.5% vs 18.5%, x(2);=5.563, P<0.05, RR=1.756). CONCLUSION: In Han nationality of Shanxi province, HLA-DQA1*0501 and HLA-DQB1*0201 alleles probably are susceptible genes of pSS, while HLA-DQA1*0301/2 allele probably is a protective gene of pSS.

Cytotoxicity and structure-activity relationships of four alpha-N-heterocyclic thiosemicarbazone derivatives crystal structure of 2-acetylpyrazine thiosemicarbazone.

A series of thiosemicarbazone ligands, HL(1) (2-acetylpyrazine thiosemicarbazone), HL(2) (2-acetylpyrazine N(4)-methylthiosemicarbazone), HL(3) (2-benzoylpyridine thiosemicarbazone) and HL(4) (2-benzoylpyridine N(4)-methylthiosemicarbazone), have been synthesized. The crystal structure of HL(1) has been determined by single-crystal X-ray diffraction. Hydrogen bonds link the different components to stabilize the crystal structure. The antitumor activity of the four ligands were tested against K562 leucocythemia and BEL7402 liver cancer cell lines. All the thiosemicarbazones showed significant antitumor activity. Different substituents on the ligands show different levels of antitumor activity. By comparison with the other thiosemicarbazone species studied, HL(4) with substitution at N(4) position in thiosemicarbazone along with 2-benzoylpyridine is the most active thiosemicarbazone ligand with IC(50)=0.002microm in the K562 leucocythemia cell line and 0.138microm in the BEL7402 liver cancer cell line, respectively.