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Background: Extensive-disease small-cell lung cancer (ED-SCLC) has been known to be rapid progression and relapse, despite highly sensitive to chemotherapy. Amrubicin (AMR), a third-generation synthetic anthracycline, was accepted as a feasible alternative compared with the standard first-line chemotherapy for previously untreated ED-SCLC. While, the efficacies of these amrubicin-based regimens are unsatisfactory. Aim: Our meta-analysis was performed to assess the efficacy and toxicity of first-line therapy comparing AMR and chemotherapy in patients with ED-SCLC. Methods: Electronic databases were searched for eligible trials updated on November 2018. Randomized-controlled trials assessing the efficacy and safety of AMR in ED-SCLC were included, of which the interested results were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: A total of 6 randomized controlled trials were included in this analysis. There are no significant differences in OS (OR=1.03, 95% CI=0.66–1.60, P=0.91), PFS (OR=1.2, 95% CI=10.77–1.88, P=0.41) or ORR (OR=1.31, 95% CI=0.90–1.92, P=0.16) with AMR (OR=0.90, 95% CI=0.76–1.05, P=0.17). The most common treatment-related AEs in the AMR group are leukopenia (OR=3.13, 95% CI=1.22–7.99, P=0.02) and neutropenia (OR=3.25, 95% CI=1.38–7.65, P=0.007). Fatigue, anemia, nausea, vomiting, diarrhea the difference between the two groups had no statistical significance. Conclusion: The results of our analysis indicated that AMR therapy demonstrated non-inferiority to the standard first-line chemotherapy for previously untreated ED-SCLC. Whether it can be accepted as an alternative regimen to the standard first-line chemotherapy is still warranted. [ABSTRACT FROM AUTHOR]

As our ongoing work on research of gelatinase inhibitors, an array of hydrazide-containing peptidomimetic derivatives bearing quinoxalinone as well as spiro-heterocyclic backbones were designed, synthesized, and assayed for their in vitro enzymatic inhibitory effects. The results demonstrated that both the quinoxalinone (series I and II) and 1,4-dithia-7-azaspiro[4,4]nonane-based hydrazide peptidomimetics (series III) displayed remarkably selectivity towards gelatinase A as compared to APN, with IC 50 values in the micromole range. Structure–activity relationships were herein briefly discussed. Given evidences have validated that gelatinase inhibition may be contributable to the therapy of HIV-1 infection, all the target compounds were also submitted to the preliminary in vitro anti-HIV-1 evaluation. It resulted that gelatinase inhibition really has positive correlation with anti-HIV-1 activity, especially compounds 4m and 7h , which gave enhanced gelatinase inhibition in comparison with the positive control LY52, and also decent anti-HIV-1 potencies. The FlexX docking results provided a straightforward insight into the binding pattern between inhibitors and gelatinase, as well as the selective inhibition towards gelatinase over APN. Collectively, our research encouraged potent gelatinase inhibitors might be used in the development of anti-HIV-1 agents. And else, compounds 4m and 7h might be promising candidates to be considered for further chemical optimization. [ABSTRACT FROM AUTHOR]

XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds ( e.g . 13a and 13b ) exhibited obvious cytotoxicity indicated by in vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert -butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in vivo mouse model study. The topo II-mediated kinetoplast DNA ( k DNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b , 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization. [ABSTRACT FROM AUTHOR]

Purpose: (1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor-cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer. Methods: We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC). Results: We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk ( P = 1.53 × 10, odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511-0.808 and P = 1.59 × 10, OR 0.642, 95 %CI 0.510-0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer ( P = 0.042, OR 1.279, 95 % CI 1.008-1.622 and P = 0.047, OR 1.334, 95 % CI 1.003-1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking ( P = 0.029, OR 0.343, 95 % CI 0.127-0.926 and P = 0.029, OR 0.343, 95 %CI 0.127-0.926) and OPN rs1126772 revealed associations with tumor-node-metastasis (TNM) stage ( P = 0.025, OR 1.765, 95 % CI 1.073-2.905) and tumor differentiation ( P = 0.031, OR 1.722, 95 % CI 1.049-2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion ( P = 0.013), TNM stage ( P = 0.003) and lymph node metastasis ( P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size ( P = 0.005) and lymph node metastasis ( P = 0.023), respectively. The OPN expression displayed a positive association with CD44 ( P = 0.01, r = 0.164). Conclusions: We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to investigate whether risk of gastric cancer (GC) was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We detected twenty-six SNPs in this gene cluster containing steroidogenic acute regulatory-related lipid transfer domain containing 3 (STARD3), protein phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1-like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2 (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls by Sequenom. We found no associations between genetic variations and GC risk. However, haplotype analysis implied that the haplotype CCCT of STARD3 (rs9972882, rs881844, rs11869286 and rs1877031) conferred a protective effect on the susceptibility to GC (P=0.043, odds ratio [OR]=0.805, 95% confidence intervals [95% CI]=0.643–0.992). The STARD3 rs1877031 TC genotype endued histogenesis of gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P=0.021, OR=2.882, 95% CI=1.173–7.084). We examined the expression of STARD3 in 243 tumor tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using immumohistochemical (IHC) analysis and tissue microarrays (TMA). The expression of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues and significantly correlated with gender (P=0.004), alcohol drinking (P<0.001), tumor location (P=0.007), histological type (P=0.005) and differentiation (P=0.023) in GC. We concluded that the combined effect of haplotype CCCT of STARD3 might affect GC susceptibility. STARD3 expression might be related to the tumorigenesis of GC in the Chinese population. [Copyright &y& Elsevier]

As a new and important technology in architecture, engineering, and construction (AEC), Building Information Modeling (BIM) has witnessed a decade of rapid development. It is highly necessary to analyze the research progress and development trend of BIM. Based on 1369 relevant literatures published and the core database "Web of Science", this study used co-citation analysis, co-word analysis, and cluster analysis to analyze the data and drew the mapping knowledge domains with Citespace software. The results show that BIM research is still in the rapid growth stage. And BIM research is mainly distributed in nine fields. In terms of time sequence, the development of BIM in the past decade developed from data collection to information integration and to knowledge management. The research hotspots are mainly concentrated in eleven directions, which can be further classified into three levels. This paper will provide valuable theoretical and practical reference for the future research of BIM. • Co-citation analysis, co-word analysis, and cluster analysis are used to draw the mapping knowledge domains. • BIM research is mainly distributed in nine fields that constitute the intellectual base of BIM research. • Research hotspots of BIM are mainly concentrated in the eleven directions. • The eleven directions of BIM research are classified into three levels. [ABSTRACT FROM AUTHOR]