Xianlu Zhuo

Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway

Previous reports have implicated epithelial-mesenchymal transition (EMT) as a major cause of cancer. TWIST, a novel zinc finger transcription factor, was suggested to be an important inducer of EMT and therefore be involved in different phases of tumorigenicity. However, whether TWIST suppression could increase chemosensitivity of cancer cells to chemotherapeutic agent remains unclear. In the present study, we utilized RNA interference to knockdown TWIST expression in A549 cells and further assessed the cell viability and apoptosis as well as possible MAPKs and mitochondrial pathways. The data showed that TWIST depletion significantly sensitized A549 cells to cisplatin by inducing activation of JNK/mitochondrial pathway but not ERK and p-38 pathways, suggesting critical roles of TWIST in A549 cell chemoresistance to cisplatin and raising the possibility of TWIST depletion as a promising approach to lung cancer therapy.

Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway

Previous reports have implicated epithelial-mesenchymal transition (EMT) as a major cause of cancer. Snail, a novel zinc finger transcription factor, was suggested to be an important inducer of EMT and therefore be involved in different phases of tumorigenicity. However, whether Snail could increase chemoresistance of cancer cells to chemotherapeutic agent remains unclear. To evaluate the roles and possible mechanisms of Snail in chemoresistance of lung cancer cells to cisplatin, we utilized RNA interference to knockdown Snail expression in A549 cells and further assessed the cell viability and apoptosis as well as possible signaling transduction pathways. The data showed that Snail depletion sensitized A549 cells to cisplatin possibly by inducing activation of JNK/mitochondrial pathway, suggesting critical roles of Snail in A549 cell chemoresistance to cisplatin and raising the possibility of Snail depletion as a promising approach to lung cancer therapy.

CYP1A1 and GSTM1 polymorphisms and oral cancer risk: association studies via evidence-based meta-analyses.

Previous studies have implicated CYP1A1 and GSTM1 polymorphisms as risk factors for various cancers. A number of studies have been devoted to the association of CYP1A1 or GSTM1 polymorphism with susceptibility to oral carcinoma and have yielded conflicting results. The aim of the present study was to assess the possible associations of oral cancer risk with CYP1A1 genetic variation and GSTM1 null genotype respectively via systematic meta-analyses. The data suggest that variant genotypes of CYP1A1 might not be risk factors for oral cancer, whereas GSTM1 null genotype significantly increases susceptibility to oral cancer in Asians but not Caucasians.

Association Studies of CYP1A1 and GSTM1 Polymorphisms with Esophageal Cancer Risk: Evidence-based Meta-analyses

BACKGROUND AND AIMS Previous studies have implicated cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) polymorphisms as risk factors for various cancers. A number of studies have been devoted to the association of CYP1A1 or GSTM1 polymorphism with susceptibility to esophageal carcinoma and have yielded conflicting results. We undertook this study to assess possible associations of esophageal cancer risk with CYP1A1 genetic variation and GSTM1 null genotype, respectively. METHODS We conducted a search in MEDLINE, EMBASE and Chinese National Knowledge Infrastructure (CNKI) without a language limitation, covering all papers published until May 2008. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. RESULTS Ultimately, 26 studies met the included criteria and thus were selected. Relevant data were extracted and further analyzed using systematic meta-analyses. Results showed that the overall OR for CYP1A1 Msp1 polymorphism was 1.24 (95% CI = 0.84-1.83). Restricting analyses to ethnic groups and histological groups, data failed to show a correlation between CYP1A1 Msp1 polymorphism and esophageal cancer risk. Overall OR for CYP1A1 exon7 polymorphism was 1.37 (95% CI = 1.06-1.77), and subgroup analyses showed that CYP1A1 exon7 polymorphism increases esophageal cancer risk in Asians but not in Caucasians. As for GSTM1 deficiency, the overall OR was 1.20 (95% CI = 0.96-1.49), and further subgroup analyses failed to show a marked association of GSTM1 deletion with esophageal cancer. CONCLUSIONS Results of the present study suggest that CYP1A1 exon7 polymorphisms may be a risk factor for esophageal cancer in Asians but not in Caucasians, whereas neither CYP1A1 Msp1 nor GSTM1 polymorphism was associated with increased susceptibility to esophageal cancer.

GSTM1 and GSTT1 polymorphisms and nasopharyngeal cancer risk: an evidence-based meta-analysis

BackgroundPrevious evidence implicates polymorphisms of GSTM1 and GSTT1, candidates of phase II enzymes, as risk factors for various cancers. A number of studies have conducted on the association of GSTM1 and GSTT1 polymorphism with susceptibility to nasopharyngeal carcinoma (NPC). However, inconsistent and inconclusive results have been obtained. In the present study, we aimed to assess the possible associations of NPC risk with GSTM1 and GSTM1 null genotype, respectively.MethodsThe associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications, then the extracted data were further analyzed using systematic meta-analyses.ResultsA total of 85 articles were identified, of which eight case-control studies concerning NPC were selected. The results showed that the overall OR was 1.42 (95%CI = 1.21–1.66) for GSTM1 polymorphism. While for GSTT1 polymorphism, the overall OR was 1.12 (95% CI = 0.93–1.34).ConclusionThe data were proven stable via sensitivity analyses. The results suggest GSTM1 deletion as a risk factor for NPC and failed to suggest a marked correlation of GSTT1 polymorphisms with NPC risk.

Possible Association of Helicobacter pylori Infection with Laryngeal Cancer Risk: An Evidence-based Meta-analysis

BACKGROUND Infection with Helicobacter pylori (H. pylori) is a major cause of various gastric diseases and has been reported to play a role in the process of tumorigenesis and progression of gastric carcinoma. However, whether H. pylori infection increases susceptibilities to other cancers is not fully understood. Several studies have been devoted to the relationship between H. pylori infection and laryngeal cancer risk and have yielded conflicting results. In this study, we aimed to evaluate the possible association of H. pylori infection with laryngeal cancer risk. METHODS The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. Extracted data were further analyzed by a systematic meta-analysis. RESULTS A total of 15 papers were identified. Of these, five case-control studies were selected. Laryngeal cancer risk for H. pylori infection was 2.03-fold (95% CI=1.28-3.23) (Z=3.00, p<0.01) compared with the controls. CONCLUSIONS The pooled data suggest infection with H. pylori as a possible risk factor for laryngeal cancer.

Assessment of the Relationship between Helicobacter pylori and Lung Cancer: A Meta-analysis

BACKGROUND AND AIMS Helicobacter pylori infection has been thought to play a critical role in gastric carcinoma tumorigenesis and progression. Several studies have been devoted to the relationship between H. pylori infection and lung cancer risk and have generated inconclusive results. In this study we aimed to evaluate the potential association of H. pylori infection with lung cancer risk. METHODS We conducted a search in Medline, OVID, EMBASE and CNKI, covering all published papers until October 2008. The relevant published papers were deliberately selected according to the established inclusion criteria for publications. Essential data were then extracted from the included studies and further analyzed by a systematic meta-analysis. RESULTS A total of 98 papers were identified. Of these, four case-control studies met the inclusion criteria and thus were finally selected. Lung cancer risk for H. pylori infection was 3.24-fold (95% CI=1.11-9.47) (Z=2.15, p<0.05) compared with the controls. CONCLUSIONS The pooled data suggest infection of H. pylori as a potential risk factor for lung cancer.

Helicobacter pylori Infection and Oesophageal Cancer Risk: Association Studies via Evidence-based Meta-analyses

AIMS Infection of Helicobacter pylori, a major cause of various gastric diseases, has been reported to play a role in the process of tumorigenesis and progression of gastric carcinoma. Some studies have been devoted to the relationship between H. pylori infection and oesophageal cancer and have yielded conflicting results. Whether infection of H. pylori is a risk factor for this cancer remains uncertain. In this study we aimed to evaluate the association of H. pylori infection with oesophageal cancer risk. MATERIALS AND METHODS The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications, then the extracted data were further analysed by systematic meta-analyses. RESULTS In total, 195 articles were identified, of which 12 case-control studies concerning oesophageal cancer were selected. Oesophageal adenocarcinoma risk for H. pylori infection was 0.58-fold (95% confidence interval 0.48-0.70) (Z=5.79, P<0.01) compared with the controls. Oesophageal squamous cell carcinoma risk was 0.80-fold (95% confidence interval 0.45-1.43) (Z=0.75, P>0.05) compared with the controls. Compared with CagA-negative H. pylori, CagA-positive H. pylori markedly decreased oesophageal cancer risk. CONCLUSION The pooled data suggest infection of H. pylori as a possible preventive factor for oesophageal adenocarcinoma and failed to suggest a significant association between H. pylori infection and oesophageal squamous cell carcinoma.

TP53 codon 72 polymorphism contributes to nasopharyngeal cancer susceptibility: a meta-analysis.

BACKGROUND AND AIMS Previously, TP53 codon 72 polymorphisms have been implicated as risk factors for various cancers. Several studies have been conducted on the association of TP53 codon 72 polymorphisms with susceptibility to nasopharyngeal carcinoma (NPC) and have yielded inconclusive results. The aim of the present study was to assess possible associations of NPC risk with TP53 codon 72 polymorphisms. METHODS We conducted a search in Medline, EMBASE, OVID, ScienceDirect, and Chinese National Knowledge Infrastructure (CNKI) without a language limitation, covering all papers published until November 2008. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. RESULTS Consequently, five studies including 394 cases and 606 controls met the included criteria and thus were selected. Ultimately, relevant data were extracted and further analyzed using systematic meta-analyses. The results showed that individuals carrying wild homozygote Arg/Arg genotype have a decreased risk of NPC compared with those carrying Pro/Pro genotype (OR: 0.46, 95% CI: 0.30-0.70). For Pro allele, no evidence indicated that individuals with a combined Pro genotype (Arg/Pro+Pro/Pro) have a significant risk of NPC compared with those with Arg/Arg genotype (OR: 0.81, 95% CI: 0.62-1.07). For Arg allele, individuals with a combined Arg genotype (Arg/Pro+Arg/Arg) have a marked decreased susceptibility to NPC relative to those with homozygote Pro/Pro genotype. CONCLUSIONS Results of the present study suggest that TP53 codon 72 polymorphisms may be a risk factor for NPC. Homozygote Pro/Pro genotype could significantly increase susceptibility to NPC, whereas Arg allele markedly decreases NPC risk.

Study on TP53 codon 72 polymorphisms with oral carcinoma susceptibility.

BACKGROUND AND AIMS Previous published data have implicated TP53 codon 72 polymorphisms as risk factors for various cancers. Growing bodies of studies have been conducted on the association of TP53 codon 72 polymorphisms with susceptibility to oral carcinoma and have yielded inconclusive results. The aim of the present study was to derive a more precise estimation of this relationship. METHODS We conducted a search in the relevant databases without a language limitation, covering all papers published until May 2009. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. RESULTS Nine studies including 1990 cases and 2074 controls were selected. Data were extracted and further analyzed using systematic meta-analyses. Results showed that no significant differences of oral cancer risk were found between individuals carrying homozygote Arg/Arg genotype and those carrying Pro/Pro genotype (OR: 0.96, 95% CI: 0.78-1.19). Likewise, no evidence indicated that individuals with Arg/Arg genotype have a significant risk of oral cancer compared with those with a combined Pro genotype (Arg/Pro+Pro/Pro) (OR: 0.98, 95% CI: 0.85-1.12). Similarly, individuals with a combined Arg genotype (Arg/Pro+Arg/Arg) do not have a marked increased or decreased susceptibility to oral cancer relative to those with homozygote Pro/Pro genotype (OR: 1.00, 95% CI: 0.83-1.21). Moreover, when stratifying for race, results were similar among Asians or Caucasians. In addition, TP53 codon 72 polymorphisms may not associate with oral cancer risks in smokers and HPV infection status. CONCLUSIONS No evidence suggests that TP53 codon 72 polymorphisms may be a risk factor for oral carcinoma.