• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3607-3612
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• 2013

Introduction: Reported prognostic roles of hypoxic inducible factor (HIF) expression in non-small cell lung cancer (NSCLC) have varied. This meta-analysis aimed to examine the relationship between HIF expression and clinical outcome in NSCLC patients. Methods: PubMed were used to identify relevant literature with the last report up to December $20^{th}$, 2012. After careful review, survival data were collected from eligible studies. We completed the meta-analysis using Stata statistical software (Version 11) and combined hazard ratio (HR) for overall survival (OS). Subgroup specificity, heterogeneity and publication bias were also assessed. All of the results were verified by two persons to ensure accuracy. Results: Eight studies were finally stepped into this meta-analysis in which seven had available data for HIF-$1{\alpha}$ and three for HIF-$2{\alpha}$. Combined HRs suggested that higher expression of $HIF1{\alpha}$ had a negative impact on NSCLC patient survival (HR=1.50; 95%CI=1.07-2.10; p=0.019). The expression of HIF-$2{\alpha}$ was also relative to a poorer survival (HR=2.02; 95%CI=1.47-2.77; p=0.000). No bias existed in either of the two groups. Conclusion: This study suggests that elevations of HIF-$1{\alpha}$ and HIF-$2{\alpha}$ expression are both associated with poor outcome for patients with NSCLC. The data support further and high quality investigation of HIF expression for predicting poor outcome in patients with NSCLC.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.11
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• pp.1445-1454
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• 2010

Two separate animal trials were conducted to evaluate the coincidence of dry matter intake (DMI) and average daily gain (ADG) predicted by the Cornell Net Carbohydrate and Protein System (CNCPS) and observed actually in crossbred growing bulls kept in a traditionally confined feeding system in China. In Trial 1, 45 growing Simmental${\times}$Mongolia crossbred F1 bulls were assigned to three treatments (T1-3) with 15 animals in each treatment. Trial 2 was conducted with 60 Limousin${\times}$Fuzhou crossbred F2 bulls allocated to 4 treatments (t1-4). All of the animals were confined in individual stalls. DMI and ADG for each bull were measured as a mean of each treatment. All of the data about animals, environment, management and feeds required by the CNCPS model were collected, and model predictions were generated for animals on each treatment. Subsequently, model-predicted DMI and ADG were compared with the actually recorded results. In the three treatments in Trial 1, 93.3, 80.0 and 73.3% of points fell within the range from -0.4 to 0.4 kg/d for DMI mean bias; similarly, in the four treatments in Trial 2, about 86.7, 73.3, 73.3 and 80.0% of points fell within the same range. These results indicate that the CNCPS model can accurately predict DMI of crossbred bulls in the traditionally confined feeding system in China. There were no significant differences between predicted and observed ADG for T1 (p = 0.06) and T2 (p = 0.09) in Trial 1, and for t1 (p = 0.07), t2 (p = 0.14) and t4 (p = 0.83) in Trial 2. However, significant differences between predicted and observed ADG values were observed for T3 in Trial 1 (p<0.01) and for t3 in Trial 2 (p = 0.04). By regression analysis, a statistically different value of intercept from zero for the regression equation of DMI (p<0.01) or an identical value of ADG (p = 0.06) were obtained, whereas the slopes were significantly different (p<0.01) from unity for both DMI and ADG. Additionally, small root mean square error (RMSE) values were obtained for the unbiased estimator of the two variances (DMI and ADG). Thus, the present results indicated that the CNCPS model can give acceptable estimates of DMI and ADG of crossbred growing bulls kept in a traditionally confined feeding system in China.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10329-10334
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• 2015

Background: To systematically summarize the association between the X-ray repair cross complementing 3 (XRCC3) gene polymorphism and oral cancer susceptibility by meta-analysis. Materials and Methods: Databases including PubMed, EMbase, CNKI, VIP and WanFang Data were searched to identify case-control studies concerning the association between an XRCC3 gene polymorphism and the risk of oral cancer from the inception to June 2014. Two reviewers independently screened the literature according to the criteria, extracted the data and assessed the quality. Then meta-analysis was performed using Stata 11.0 software. Results: Seven published case-control studies including 775 patients with oral cancer and 1922 controls were selected. Associations between the rs861539 polymorphism and overall oral cancer risk were not statistically significant in all kinds of comparison models (CT vs CC: OR=0.94, 95%CI=0.74-1.18; TT vs CC: OR=0.94, 95%CI=0.64-1.38; dominant model: OR=0.95, 95%CI=0.76-1.18; recessive model: OR=0.94, 95%CI=0.69-1.29; allele T vs C: OR=0.97, 95%CI=0.84-1.11). In the stratified analysis by ethnicity, no significant associations were found among Asians and Caucasians. On stratification by tumor type, no significant associations were found for cancer and oral premalignant lesions. Conclusions: The XRCC3 gene polymorphism was not found to be associated with the risk of oral cancer. Considering the limited quality of the included case-control studies, more high quality studies with large sample size are needed to verify the above conclusion.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1321-1326
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• 2014

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7171-7177
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• 2013

Purpose: To compare the safety and efficacy of first-line chemotherapy regimen with or without doxorubicin in treating patients with advanced soft tissue sarcoma (STS). Patients and Methods: We retrospectively analyzed a cohort of 56 patients histologically confirmed with STS who were treated at Jiangsu Cancer Hospital and Research Institute from July 2011 to June 2012.The basic element of first line chemotherapy contained epirubicin in group B and lacked epirubicin in group A. Response was assessed using RECIST criteria. The Kaplan-Meier method was used to estimate progress free survival (PFS). Results: According to RECIST criteria, patients in group treated by chemotherapy without epirubicin, the objective response (OR) ratio was 6.5 % (CR0%+PR6.5%). Disease control rate (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2 patients achieving a partial response (PR 6.5%) and a stable response (SD 19.4%) in 6. In group B with epirubicin based regimens, no patient had complete response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observed in 13 patients (52%). By Fisher's exact test, the DCR difference between the two groups was statistically significant (p=0.046). In group A, median PFS was 3.0 months (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03-4.97) in group B (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance status 0-1 were identified as favorable factors for progression in our cohort of patients. Differences of nonhematologic and hematologic toxicities were not statistically significant between the two groups, and the addition of epirobicin was not associated with cardiac toxicity (p=0.446). Conclusion: Our study demonstrates that epirubicin-based chemotherapy is effective and well tolerated, and is superior to chemotherapy without epirubicin regarding efficacy. Therefore it is recommended that epirubicin-based chemotherapy should be considered as first line for patients with advanced STS.

• Journal of Microbiology and Biotechnology
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• v.26 no.4
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• pp.790-798
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• 2016

Chlamydiae, obligate intracellular bacteria, are associated with a variety of human diseases. The chlamydial life cycle undergoes a biphasic development: replicative reticulate bodies (RBs) phase and infectious elementary bodies (EBs) phase. At the end of the chlamydial intracellular life cycle, EBs have to be released to the surrounded cells. Therefore, the interactions between Chlamydiae and cell death pathways could greatly influence the outcomes of Chlamydia infection. However, the underlying molecular mechanisms remain elusive. Here, we investigated host cell death after Chlamydia infection in vitro, in L929 cells, and showed that Chlamydia infection induces cell necrosis, as detected by the propidium iodide (PI)-Annexin V double-staining flow-cytometric assay and Lactate dehydrogenase (LDH) release assay. The production of reactive oxygen species (ROS), an important factor in induction of necrosis, was increased after Chlamydia infection, and inhibition of ROS with specific pharmacological inhibitors, diphenylene iodonium (DPI) or butylated hydroxyanisole (BHA), led to significant suppression of necrosis. Interestingly, live-cell imaging revealed that Chlamydia infection induced lysosome membrane permeabilization (LMP). When an inhibitor upstream of LMP, CA-074-Me, was added to cells, the production of ROS was reduced with concomitant inhibition of necrosis. Taken together, our results indicate that Chlamydia infection elicits the production of ROS, which is dependent on LMP at least partially, followed by induction of host-cell necrosis. To our best knowledge, this is the first live-cell-imaging observation of LMP post Chlamydia infection and report on the link of LMP to ROS to necrosis during Chlamydia infection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.647-652
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• 2015

Background: Lung cancer was one of the most common cancers in both men and women all over the world. In this study, we aimed to clarify who could survive after long term chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: We enrolled 186 patients with stage IV NSCLC after long term chemotherapy from Jun 2006 to Nov 2014 diagnosed in Jiangsu Cancer Hospital. Multiple variables like age, gender, smoking, histology of adenocarcinoma and squamous-cell cancer, number of metastatic sites, metastatic sites (e.g. lung, brain, bone, liver and pleura), hemoglobin, lymphocyte rate (LYR), Change of LYR during multiple therapies, hypertension, diabetes, chronic bronchitis, treatments (e.g.radiotherapy and targeted therapy) were selected. For consideration of factors influencing survival and response for patients with advanced NSCLC, logistic regression analysis and Cox regression analysis were used in an attempt to develop a screening module for patients with elevated survival after long term chemotherapy become possible. Results: Of the total of 186 patients enrolled, 69 survived less than 1 year (short-term group), 45 one to two years, and 72 longer than 3 years (long-term group). For logistic regression analysis, the short-term group was taken as control group and the long-term group as the case group. We found that age, histology of adenocarcinoma, metastatic site (e.g. lung and liver), treatments (e.g. targeted therapy and radiotherapy), LYR, a decreasing tendency of LYR and chronic bronchitis were individually associated with overall survival by Cox regression analysis. A multivariable Cox regression model showed that metastatic site (e.g. lung and liver), histology of adenocarcinoma, treatments (e.g. targeted therapy and radiotherapy) and chronic bronchitis were associated with overall survival. Thus metastatic site (e.g. lung and liver) and chronic bronchitis may be important risk factors for patients with advanced NSCLC. Gender, metastatic site (e.g. lung and liver), LYR and the decreasing tendency of LYR were significantly associated with long-term survival in the individual-variable logistic regression model (P<0.05). On multivariate logistic regression analysis, gender, metastatic site (e.g. lung and liver) and the decreasing tendency of LYR associated with long-term survival. Conclusions: In conclusion, female patients with stage IV adenocarcinoma of NSCLC who had decreasing tendency of LYR during the course therapy and had accepted multiple therapies e.g. more than third-line chemotherapy, radiotherapy and/or targeted therapy might be expected to live longer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1925-1929
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• 2013

Background: As a negative regulator of P53, MDM2 plays an important role in carcinogenesis; a polymorphism in its promoter region. SNP309 T>G, is known to increase the expression of MDM2, thus being considered related to higher susceptibility to neoplasia. However, no agreement has been achieved regarding its effects on gastric cancer. Methods: The present systematic meta-analysis was performed based on comprehensive literature search from Pubmed, Web of science and CBM databases. Results: It was suggested from 6 independent studies that the GG genotype is associated with a significantly increased risk of gastric cancer (Recessive: OR = 1.43, 95% CI = 1.08-1.91, P = 0.013), and subgroup analysis also confirmed the relationship (English publications-recessive model: OR = 1.45, 95% CI = 1.10-1.91, P = 0.009; Studies in China-recessive model: OR = 1.58, 95% CI = 1.08-2.30, P = 0.017). No publication bias was detected. Conclusion: The meta-analysis indicated a significant inverse association between GG genotype carriage and elevated risk of gastric cancer. However, more studies and detailed information are needed to fully address the topic.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2019-2022
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• 2013

Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6257-6261
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• 2012

Objective: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Methods: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Results: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). Conclusions: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.