Efficacy and Safety of Sorafenib for Advanced Non-Small Cell Lung Cancer: a Meta-analysis of Randomized Controlled Trials

Wang, Wei-Lan,Tang, Zhi-Hui,Xie, Ting-Ting,Xiao, Bing-Kun,Zhang, Xin-Yu,Guo, Dai-Hong,Wang, Dong-Xiao,Pei, Fei,Si, Hai-Yan,Zhu, Man Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

Role of Nucleation-Promoting Factors in Mouse Early Embryo Development

Wang, Qiao-Chu,Liu, Jun,Wang, Fei,Duan, Xing,Dai, Xiao-Xin,Wang, Teng,Liu, Hong-Lin,Cui, Xiang-Shun,Sun, Shao-Chen,Kim, Nam-Hyung Cambridge University Press 2013 Microscopy and microanalysis Vol.19 No.3

<B>Abstract</B><P>During mitosis nucleation-promoting factors (NPFs) bind to the Arp2/3 complex and activate actin assembly. JMY and WAVE2 are two critical members of the NPFs. Previous studies have demonstrated that NPFs promote multiple processes such as cell migration and cytokinesis. However, the role of NPFs in development of mammalian embryos is still unknown. Results of the present study show that the NPFs JMY and WAVE2 are critical for cytokinesis during development of mouse embryos. Both JMY and WAVE2 are expressed in mouse embryos. After injection of JMY or WAVE2 siRNA, all embryos failed to develop to the morula or blastocyst stages. Moreover, using fluorescence intensity analysis, we found that the expression of actin decreased, and multiple nuclei were observed within a single cell indicating that NPFs-induced actin reduction caused the failure of cell division. In addition, injection of JMY and WAVE2 siRNA also caused ARP2 degradation, indicating that involvement of NPFs in development of mouse embryos is mainly through regulation of ARP2/3-induced actin assembly. Taken together, these data suggested that WAVE2 and JMY are involved in development of mouse embryos, and their regulation may be through a NPFs-Arp2/3-actin pathway.</P>

A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis

Fei-yu Wang,Yu-qing Zhang,Xin-min Wang,Chan Wang,Xiao-fang Wang,Jiang-dong Wu,Fang Wu,Wan-jiang Zhang,Le Zhang 한국미생물학회 2016 The journal of microbiology Vol.54 No.4

Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival pathways. Some studies indicated that the expression of Mcl-1 was upregulated in host cells during infection with the virulent Mycobacterium tuberculosis strain, H37Rv. The present study was designed to investigate the effect of inhibiting Mcl-1 expression both in vivo and in vitro on apoptosis of host macrophages infected with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected by the real time-polymerase chain reaction, western blotting, and immunohistochemistry. Flow cytometry and transmission electron microscopy were used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was downregulated efficiently in H37Rv-infected host macrophages using shRNA. Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host macrophages significantly. The increased apoptosis correlated with a decrease in M. tuberculosis colony forming units recovered from H37Rv-infected cells that were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed that specific knockdown of Mcl-1 expression increased apoptosis of host macrophages significantly and decreased the intracellular survival of a virulent strain of M. tuberculosis. These data indicate that interference with Mcl-1 expression may provide a new avenue for tuberculosis therapy.

Analysis of Death Causes of In-patients with Malignant Tumors in Sichuan Cancer Hospital of China from 2002 to 2012

Wang, Xiao,Song, Zheng-Fang,Xie, Rui-Meng,Pei, Jiao,Xiang, Ming-Fei,Wang, Huan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Objectives: To analyze underlying disease, fatality rate and the major causes of death of in-patients with malignant tumors in Sichuan Cancer Hospital. Methods: Clinical data of in-patients from 2002 to 2012 were retrospectively analyzed. Results: The top 10 tumors (82.0%of the total) of the malignant tumors of the in-patients were lung, cervical, esophagus, breast, colorectal, nasopharynx, liver and gastric cancers, lymphomas and ovarian cancers. The overall fatality rate was 2.7% during these eleven years, 3.4% and 2.0% for male and females, respectively with statistical significance for the difference (${\chi}^2$=164.737, P<0.001). The top 10 death causes were lung cancer, liver cancer, colorectal cancer, esophagus cancer, gastric cancer, lymphoma, breast cancer, pancreatic cancer, ovarian cancer and nasopharynx cancer. In-patients with pancreatic cancer had the highest fatality rate (9.6%). There were different ranks of death causes in different sex groups and age groups. Conclusion: Prevention and control work of cancer should be enhanced not only for cancers with high incidence such as lung cancer, esophageal cancer but also for the cancers which have low incidence but high fatality rate, such as pancreatic cancer and gallbladder cancer, which would help to improve the survival rate and quality of life of cancer patients in the future.

Regulation of ANKRD9 expression by Lipid metabolic perturbations

( Xiao Fei Wang ),( Robert F. Newkirk ),( Wilfrid Carre ),( Purnima Ghose ),( Barry Igobudia ),( James G. Townsel ),( Larry A. Cogburn ) 생화학분자생물학회 2009 BMB Reports Vol.42 No.9

Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-modulated Radiation Therapy: A Retrospective Study with 15-year Follow-up

Lin Wang,Jingjing Miao,Huageng Huang,Boyu Chen,Xiao Xiao,Manyi Zhu,Yingshan Liang,Weiwei Xiao,Shaomin Huang,Yinglin Peng,Xiaowu Deng,Xing Lv,Weixiong Xia,Yanqun Xiang,Xiang Guo,Fei Han,Chong Zhao 대한암학회 2022 Cancer Research and Treatment Vol.54 No.1

Purpose This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

CircularRNA_104670 plays a critical role in intervertebral disc degeneration by functioning as a ceRNA

Jian Son,Hong-Li Wang,Ke-Han Song,Zhi-Wen Ding,Hai-Lian Wang,Xiao-Sheng Ma,Fei-Zhou Lu,Xin-Lei Xia,Ying-Wei Wang,Fei-Zou,Jian-Yuan Jiang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

This study was carried out to explore the roles of circular RNAs (circRNAs) in nucleus pulposus (NP) tissues in intervertebral disc degeneration (IDD). Differentially expressed circRNAs in IDD and normal NP tissues were identified based on the results of microarray analysis. Bioinformatics techniques were employed to predict the direct interactions of selected circRNAs, microRNAs (miR), and mRNAs. CircRNA_104670 was selected as the target circRNA due to its large multiplier expression in IDD tissues. After luciferase reporter and EGFP/RFP reporter assays, we confirmed that circRNA_104670 directly bound to miR-17-3p, while MMP-2 was the direct target of miR-17-3p. The receiver-operating characteristic (ROC) curve showed that circRNA_104670 and miR-17-3p had good diagnostic significance for IDD (AUC circRNA_104670 = 0.96; AUC miRNA-17-3p = 0.91). A significant correlation was detected between the Pfirrmann grade and expression of circRNA_104670 (r = 0.63; p = 0.00) and miR-17-3p (r = −0.62; p = 0.00). Flow-cytometric analysis and the MTT assay showed that interfering with circRNA_104670 using small interfering RNA (siRNA) inhibited NP cell apoptosis (p < 0.01), and this inhibition was reduced by interfering with miR-17-3p. Interfering with circRNA_104670 suppressed MMP-2 expression and increased extracellular matrix (ECM) formation, which were also reduced by interfering with miR-17-3p. Finally, an MRI evaluation showed that circRNA_104670 inhibition mice had a lower IDD grade compared with control mice (p < 0.01), whereas circRNA_104670 and miRNA-17-3p inhibition mice had a higher IDD grade compared with circRNA_104670 inhibition mice (p < 0.05). CircRNA_104670 is highly expressed in the NP tissues of IDD and acts as a ceRNA during NP degradation.

Mini-Array of Multiple Tumor-associated Antigens (TAAs) in the Immunodiagnosis of Esophageal Cancer

Qin, Jie-Jie,Wang, Xiao-Rui,Wang, Peng,Ren, Peng-Fei,Shi, Jian-Xiang,Zhang, Hong-Fei,Xia, Jun-Fen,Wang, Kai-Juan,Song, Chun-Hua,Dai, Li-Ping,Zhang, Jian-Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.

Enantioselective Esterification of Ibuprofen by a Novel Thermophilic Biocatalyst: APE1547

Zhao Dan-tong,Xun Er-na,Wang Jia-xin,Wang Ren,Wei Xiao-fei,Wang Lei,Wang Zhi 한국생물공학회 2011 Biotechnology and Bioprocess Engineering Vol.16 No.4

The enantioselective esterification of ibuprofen catalyzed by a novel thermophilic esterase (APE1547)from the archaeon Aeropyrum pernix K1 was successfully conducted in organic solvents. The effects of acyl acceptor,substrate ratio, organic solvent, temperature, and water activity were investigated. Under optimum conditions, the highest enantioselectivity (E = 38.1) was obtained with a higher enzyme activity (216.5 μmol/g/h). Celites were added into the reaction mixture to remove the water produced in the esterification. The reaction achieved its equilibrium in approximately 96 h with a conversion of 57 and 99%(ee) of the un-reacted (S)-ibuprofen obtained.

rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

Zhang, Lin-Lin,Sun, Liang,Zhu, Xiao-Quan,Xu, Yong,Yang, Kuo,Yang, Fan,Yang, Yi-Ge,Chen, Guo-Qiang,Fu, Ji-Cheng,Zheng, Chen-Guang,Li, Ying,Mu, Xiao-Qiu,Shi, Xiao-Hong,Zhao, Fan,Wang, Fei,Yang, Ze,Wang, Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results: Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa ($OR_{recessive}=1.56$, p=0.006); and rs7837328 (A) was associated with PCa ($OR_{dominant}=1.38$, p=0.042/$OR_{recessive}=1.99$, p=0.003). Moreover, we observed a cumulative effects between them ($p_{trend}=2.58{\times}10^{-5}$). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) ($p_{age}=0.046$, $P_{tumorstage}=0.048$). Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.