Neoadjuvant Chemotherapy Followed by Surgery versus Primary Surgery in Advanced Epithelial Ovarian Cancer: A Review of Outcomes at National Institute of Cancer Research Hospital in Bangladesh

Introduction: This study evaluated the difference in operative and clinical outcomes for patients with advanced ovarian cancer after primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in Bangladesh. Methods: Sixty patients with advanced epithelial ovarian cancer presenting to the department of Gynaecological Oncology at the National Institute of Cancer Research and Hospital were prospectively enrolled. Thirty patients underwent primary debulking surgery and thirty patients received NACT followed by IDS. Results: In the PDS and IDS groups respectively, 56.7% and 50% of patients presented with stage IIIC and 67.7% and 56.7% respectively had serious papillary type histopathology. Duration of surgery, amount of blood loss and total hospital stay were significantly lower (p < 0.001) in IDS group than in the PDS group. There was a statistically significant difference in postoperative tumor residuals between IDS and PDS patients. Complete tumor resection (R0) was obtained in 24 (80%) of IDS patients versus 13 (43.3%) PDS patients. In fifteen months of follow-up, 21 (70%) in the PDS group and 5 (16.7%) in the IDS group recurred (p = 0.021). Median progression free survival in PDS patients was twelve months while that of the IDS group was seventeen months. There was one death at 45 days in the PDS group. No other deaths were documented at fifteen months of follow-up. Conclusion: Interval debulking surgery has a more favorable outcome than primary debulking surgery on progression free survival in advanced ovarian cancer patients and permits a less aggressive surgery to be performed in Bangladesh.

Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer

BACKGROUND Lymph node(LN)staging in rectal cancer(RC)affects treatment decisions and patient prognosis.For radiologists,the traditional preoperative assessment of LN metastasis(LNM)using magnetic resonance imaging(MRI)poses a challenge.AIM To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs.METHODS In this retrospective study,270 LNs(158 nonmetastatic,112 metastatic)were randomly split into training(n=189)and validation sets(n=81).LNs were classified based on pathology-MRI matching.Conventional MRI features[size,shape,margin,T2-weighted imaging(T2WI)appearance,and CE-T1-weighted imaging(T1WI)enhancement]were evaluated.Three radiomics models used 3D features from T1WI and T2WI images.Additionally,a nomogram model combining conventional MRI and radiomics features was developed.The model used univariate analysis and multivariable logistic regression.Evaluation employed the receiver operating characteristic curve,with DeLong test for comparing diagnostic performance.Nomogram performance was assessed using calibration and decision curve analysis.RESULTS The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM.In the training set,the nomogram model achieved an area under the curve(AUC)of 0.92,which was significantly higher than the AUCs of 0.82(P<0.001)and 0.89(P<0.001)of the conventional MRI and radiomics models,respectively.In the validation set,the nomogram model achieved an AUC of 0.91,significantly surpassing 0.80(P<0.001)and 0.86(P<0.001),respectively.CONCLUSION The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer

BACKGROUND Radical surgery is the most commonly used treatment for hepatocellular carcinoma(HCC).However,the surgical effect remains not ideal,and prognostic evaluation is insufficient.Furthermore,clinical intervention is rife with uncertainty and not conducive to prolonging patient survival.AIM To explore correlations between the systemic immune inflammatory index(SII)and geriatric nutritional risk index(GNRI)and HCC operation prognosis.METHODS This retrospective study included and collected follow up data from 100 HCC.Kaplan–Meier survival curves were used to analyze the correlation between SII and GNRI scores and survival.SII and GNRI were calculated as follows:SII=neutrophil count×platelet count/lymphocyte count;GNRI=[1.489×albumin(g/L)+41.7×actual weight/ideal weight].We analyzed the predictive efficacy of the SII and GNRI in HCC patients using receiver operating characteristic(ROC)curves,and the relationships between the SII,GNRI,and survival rate using Kaplan–Meier survival curves.Cox regression analysis was utilized to analyze independent risk factors influencing prognosis.RESULTS After 1 year of follow-up,24 patients died and 76 survived.The area under the curve(AUC),sensitivity,specificity,and the optimal cutoff value of SII were 0.728(95%confidence interval:0.600-0.856),79.2%,63.2%,and 309.14,respectively.According to ROC curve analysis results for predicting postoperative death in HCC patients,the AUC of SII and GNRI combination was higher than that of SII or GNRI alone,and SII was higher than that of GNRI(P<0.05).The proportion of advanced differentiated tumors,tumor maximum diameter(5–10 cm,>10 cm),lymph node metastasis,and TNM stage III-IV in patients with SII>309.14 was higher than that in patients with SII≤309.14(P<0.05).The proportion of patients aged>70 years was higher in patients with GNRI≤98 than that in patients with GNRI>98(P<0.05).The 1-year survival rate of the SII>309.14 group(compared with the SII≤309.14 group)and GNRI≤98 group(compared with the GNRI>98 group)was lower(P<0.05).CONCLUSION The prognosis after radical resection of HCC is related to the SII and GNRI and poor in high SII or low GNRI patients.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Epithelial Ovarian Cancer Patients and Clinicopathological Features and Survival: A Comparison of Outcomes of Two Age Cohorts in Bangladesh

Objective: This study compared the clinicopathologic characteristics and overall survival of epithelial ovarian carcinoma in women younger versus older than 45 years in Bangladesh. Methods: A retrospective analysis identified 129 epithelial ovarian carcinoma patients who were admitted to the National Institute of Cancer Research and Hospital, in Dhaka, Bangladesh from 2016 through 2017 for surgery. These patients were grouped into two categories: the younger group (≤45 years) and the older group (>45 years). Clinicopathological features of epithelial ovarian carcinoma were analyzed in each age group. Cox proportional hazards model identified factors affecting survival and Kaplan-Meier survival curves with log rank test compared outcomes for each age group. Results: The median age of the 129 women was 46 years (IQR: 38, 56) and median time of follow-up was 9 months (inter-quartile range: 4, 26.5). We found a significant difference in the CA-125 level (p < 0.044), age of menopause (p < 0.001), follow-up duration (p < 0.016), disease outcome (p < 0.005) and histopathological type (p < 0.021) between the two groups. No significant differences were found in breakdown of Federation of Gynecology and Obstetrics (FIGO) stage of the disease. There was a significant difference in overall survival between the patients of two groups (p = 0.021) where there was a higher probability of death among the older cohort. The 5-year overall survival rates for the younger age versus older group were 34.0%, and 11.7% respectively. Independent prognostic factors by univariate analysis for the overall survival were age, FIGO stage, preoperative CA-125 and CEA level. However, when controlling for stage, survival was similar between age cohorts. Conclusions: Our data suggests that women in Bangladesh with epithelial ovarian cancer who are under the age of 45 years have a different clinical profile and better overall survival than women in the older age cohort.

Comparison of Propofol and Fentanyl for Preventing Emergence Agitation Following Sevoflurane Anesthesia in Pediatric Patients: A Single-Center Study in Bangladesh

Background: Emergence agitation (EA) is a common phenomenon observed in pediatric patients following general anesthesia. This study aimed to assess the efficacy of propofol and fentanyl in preventing EA and to compare their associated complications or side effects. Methods: This prospective randomized observational comparative study was conducted at Dhaka Medical College Hospital from July 2013 to June 2014. The study aimed to evaluate the effects of propofol and fentanyl on EA in children aged 18 to 72 months undergoing circumcision, herniotomy, and polypectomy operations. Ninety children were included in the study, with 45 in each group. Patients with psychological or neurological disorders were excluded. Various parameters including age, sex, weight, American Society of Anesthesiologists (ASA) class, duration of anesthesia, Saturation of Peripheral Oxygen (SPO2), heart rate (HR), respiratory rate (RR), Pediatric Anesthesia Emergence Delirium (PAED) score, duration of post-anesthesia care unit (PACU) stay, incidence of laryngospasm, nausea, vomiting, and rescue drug requirement were compared between the two groups. Results: Age, sex, weight, ASA class, and duration of anesthesia were comparable between the two groups. Perioperative SpO2 and HR were similar in both groups. However, the PAED score was significantly higher in the fentanyl group during all follow-ups except at 30 minutes postoperatively. The mean duration of PACU stay was significantly longer in the fentanyl group. Although the incidence of laryngospasm was higher in the fentanyl group, it was not statistically significant. Conversely, nausea or vomiting was significantly higher in the fentanyl group. The requirement for rescue drugs was significantly higher in the fentanyl group compared to the propofol group. Conclusion: Both propofol and fentanyl were effective in preventing emergence agitation in pediatric patients undergoing various surgical procedures under sevoflurane anesthesia. However, propofol demonstrated a better safety profile with fewer incidences of nausea, vomiting, and rescue drug requirements compared to fentanyl.

Post Thyroidectomy Assessment of Intact Parathyroid Hormone for Early Prediction of Hypocalcaemia

Background: As the half-life of intact parathyroid hormone (iPTH) is very low, it reflects parathyroid insufficiency within minutes to hours after total thyroidectomy. Therefore, iPTH level assessment in the postoperative period can be used to predict the development of hypocalcaemia. The optimal time point to measure serum iPTH is important for the accurate prediction of hypocalcaemia. Aim: This paper aims to evaluate the ability of iPTH as an early predictive marker of hypocalcaemia and determine which time iPTH is more able to predict postoperative hypocalcaemia. Method: This prospective observational study was conducted in the Department of Otolaryngology-Head & Neck Surgery, BSMMU, Dhaka, from July 2020 to December 2021, with 67 patients who underwent total thyroidectomy. iPTH levels were measured on the day before the operation and at 1 hour, 4 hours, and 24 hours after the operation. S.calcium levels were measured on the day before the operation and 1st postoperative day. All the data were compiled and sorted properly and were analyzed statistically. Results: Postoperative hypocalcaemia developed in 18 cases, with an incidence of 26.9%. Pearson correlation showed a significant correlation between postoperative iPTH at 1 hr, 4 h, and 24 hr with 1st postoperative calcium value. The Receiver operating characteristic (ROC) curve was processed for the postoperative iPTH at 1 hr, 4 h, and 24 hr. The sensitivity, specificity, cut-off value, and mean AUC found 93.9%, 94.4%, ≤14.0, 0.988;95.9%, 94.4%, ≤09.5, 0.993 and 91.8%, 94.4%, ≤11.0, 0.993 respectively. Conclusion: iPTH can be used as an early predictor of post-thy-roidectomy hypocalcaemia. 4 hr iPTH showed more sensitivity and specificity for a cut-off value near the laboratory reference range.

Polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 and esophageal cancer risk in Southeast Chinese males

AIM： To evaluate the impact of alcohol dehydrogenase-2 （ADH2） and aldehyde dehydrogenase-2 （ALDH2） polymorphisms on esophageal cancer susceptibility in Southeast Chinese males.METHODS： Two hundred and twenty-one esophageal cancer patients and 292 healthy controls from Taixing city in Jiangsu Province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase chain reaction and denaturing high-performance liquid chromatography. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （CI）.RESULTS： The ADH G allele carriers were more susceptible to esophageal cancer, but no association was found between ADH2 genotypes and risk of esophageal cancer when disregarding alcohol drinking status. Regardless of ADH2 genotype, ALDH2G/A or A/A carriers had significantly increased risk of developing esophageal cancer, with homozygous individuals showing higher esophageal cancer risk than those who were heterozygous. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk; the OR was 3.05 （95% CI： 2.49-6.25）. Compared with non-drinkers carrying both ALDH2 G/G and ADH2 A/A, drinkers carrying both ALDH2 A allele and ADH2 G allele showed a significantly higher risk of developing esophageal cancer （OR = 8.36, 95% CI： 2.98-23.46）.CONCLUSION： Both ADH2 G allele and ALDH2 A allele significantly increase the risk of esophageal cancer development in Southeast Chinese males. ALDH2 A allele significantly increases the risk of esophageal cancer development especially in alcohol drinkers. Alcohol drinkers carrying both ADH2 G allele and ALDH2 A allele have a higher risk of developing esophageal cancer.

The role of BRCA 1 and BRCA2 in prostate cancer

One of the strongest risk factors for prostate cancer is a family history of the disease. Germline mutations in the breast cancer predisposition gene 2 （BRCA2） are the genetic events known to date that confer the highest risk of prostate cancer （8.6-fold in men ≤ 65 years）. Although the role of BRCA2 and BRCA1 in prostate tumorigenesis remains unrevealed, deleterious mutations in both genes have been associated with more aggressive disease and poor clinical outcomes. The increasing incidence of prostate cancer worldwide supports the need for new methods to predict outcome and identify patients with potentially lethal forms of the disease. As we present here, BRCA germline mutations, mainly in the BRCA2gene, are one of those predictive factors. We will also discuss the implications of these mutations in the management of prostate cancer and hypothesize on the potential for the development of strategies for sooradic cases with similar characteristics.

Association of serum lipids and severity of epithelial ovarian cancer：an observational cohort study of 349 Chinese patients

While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We conducted a retrospective study of 349 epithelial ovarian cancer patients who received treatment at Jiangsu Cancer Hospital, China between 2011 and 2017. We analyzed age at diagnosis, blood pressure, plasma glucose content, body mass index（BMI）, lipid levels and clinical parameters. Severity of epithelial ovarian cancer was classified according to the International Federation of Gynecology and Obstetrics（FIGO） grading system. Univariate analysis of the clinical factors according to the severity of epithelial ovarian cancer was followed by logistic regression analysis to identify clinical factors significantly associated with epithelial ovarian cancer severity. Univariate analysis indicated that age,BMI, triglyceride（TG）, and high density lipoproteins（HDL） differed significantly among different stages of epithelial ovarian cancer（P〈0.05）. In the logistic regression model, elevated TG（OR： 1.883; 95% CI= 1.207-2.937）, and low HDL（OR： 0.497; 95% CI = 0.298-0.829） levels were significantly associated with the high severity epithelial ovarian cancer. Our data indicate that high TG and low HDL levels correlate with a high severity of epithelial ovarian cancer. These data provide important insight into the potential relationship between the lipid pathway and epithelial ovarian cancer phenotype and development.

Superior in vitro anticancer effect of biomimetic paclitaxel and triptolide co-delivery system in gastric cancer

As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.

Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B_(12) status

AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS:We examined the associations between MTHFR C677T genotype,and promoter methylation of P16,hMLH1,and hMSH2 tumor-related genes among151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit. RESULTS:We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison,we did not find a significant association between methylation in tumors and any single genotype. However,in comparison to controls with the CC genotype,an increased risk of tumor methylation was associated with the CT genotype(OR = 2.5;95% CI,1.1-5.6) . In case-case comparisons,folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high(above median) versus low(below median) serum folate/vitamin B12 levels were 4.9(95% CI,1.4-17.7) ,and 3.9(95% CI,1.1-13.9) ,respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group,especially in those with MTHFR CT(P = 0.01) ,and CT/TT(P = 0.002) genotypes,but not in those with the CC genotype(P = 1.0) . CONCLUSION:We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes,and this relationship is modified by MTHFR C677T genotypes.

Cost estimation and control of colorectal cancer screening

Objective:The aim of our study was to estimate the cost of colorectal cancer screening and to provide evidence for the cost control of colorectal cancer screening among general population in rural area of China.Methods:We determined the net cost for colorectal cancer mass-screening in Jiashan County,and evaluated the cost-benefit and cost effectiveness.Results:The compliance rate of primary screening and intensive screening were 84.6% and 78.7%,respectively.In primary screening,the average cost for each individual was 27.2 yuan,and the average cost for identifying one high-risk individual was 180.5 yuan.The mean cost to diagnose one colorectal cancer patient was 42963.3 yuan.As for identification of adenoma,the average cost for each case was 4384.0 yuan.Based on the calculation,the average cost of reducing one colorectal cancer patient was 12768 yuan by conducting the mass-screening protocol.Conclusion:It was beneficial to do the cost-benefit analysis of colorectal cancer screening in area of high incidence.Based on the results of cost-benefit analysis,more efforts should be made to reduce the cost and to improve the efficiency of the colorectal cancer screening.

Reduction of CAII Expression in Gastric Cancer: Correlation withInvasion and Metastasis

Objective： Human carbonic anhydrases II （CAII） gene plays an important role in different cancer. However, its relevance to gastric cancer （GC） remains unclear. In the present study, we aimed to investigate the expression of CAII in GC and explore its correlation with some clinicopathologic characteristics of GC. Methods： The expression of CAII in 20 specimens of normal gastric mucosa, 38 specimens of intraepithelial neoplasia and 112 specimens of gastric carcinoma were detected by immunohistochemical techniques. Survival in GC with CAII expression was studied. Results： The positive rate of CAII protein in normal gastric mucosa was significantly higher than that in intraepithelial neoplasia and gastric carcinoma （100% vs. 63.16% and 28.57%, P0.001）. The positive rate of CAII protein was significantly higher in gastric carcinoma at early stages than that at advanced stages （70.0% vs. 19.57%, P0.001）. The positive rate of CAII protein was significantly lower in gastric carcinoma with lymph node metastases than that without lymph node metastases （10.81% vs. 37.33%, P0.05）. Furthermore, the positive rate of CAII protein was significantly lower in poorly-differentiated gastric carcinoma than in moderately- or well-differentiated gastric carcinoma （15.94% vs. 31.03% or 60.00%, P0.05）. Moreover, CAII expression was not related with sex, age and tumor size. The patients with CAII-positive tumors showed a better survival rate than those with CAII-negative tumors （P=0.024, log-rank test）. Conclusion： CAII expression was related with stages and lymph node metastases in gastric carcinoma. The reduction of CAII expression in GC might promote tumor cell motility and contribute to tumor growth and metastasis.

Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2) and/or aldehyde dehydrogenase 2 (ALDH2) for risk of colorectal cancer (CRC) in Chinese males. METHODS: A case-control study was conducted in 190 cases and 223 population-based controls. ADH2 Arg47His (G-A) and ALDH2 Glu487Lys (G-A)genotypes were identified by PCR and denaturing high-performance liquid chromatography (DHPLC). Information on smoking and drinking was collected and odds ratio (OR) was estimated. RESULTS: The ADH2 A/A and ALDH2 G/G genotypes showed moderately increased CRC risk. The age- and smoking-adjusted OR for ADH2 A/A relative to G/A and G/G was 1.60 (95% CI=1.08-2.36), and the adjusted OR for ALDH2 G/G relative to G/A and A/A was 1.79 (95% CI=1.19-2.69). Signif icant interactions between ADH2, ALDH2 and drinking were observed. As compared to the subjects with ADH2 G and ALDH2 A alleles, those with ADH2 A/A and ALDH2 G/G genotypes had a signif icantly increased OR (3.05, 95% CI= 1.67-5.57). The OR for CRC among drinkers with the ADH2 A/A genotype was increased to 3.44 (95% CI= 1.84-6.42) compared with non-drinkers with the ADH2 G allele. The OR for CRC among drinkers with the ALDH2 G/G genotype was also increased to 2.70 (95% CI= 1.57-4.66) compared with non-drinkers with the ALDH2 A allele. CONCLUSION: Polymorphisms of the ADH2 and ALDH2 genes are significantly associated with CRC risk. There are also signifi cant gene-gene and gene- environment interactions between drinking and ADH2 and ALDH2 polymorphisms regarding CRC risk in Chinese males.

Arsenic trioxide inhibits the activity of SphK1 by decreasing the level of phosphatidylserine and phosphatidic acid in the human gastric cancer cell line MGC-803

Sphingosine kinase 1(SphK1)is an important synthetase during the synthesis of sphingosine-1-phosphate(S1P)from sphingosine(Sph).Previous studies demonstrated that arsenic trioxide(As_(2)O_(3))could reduce the level of S1P in human gastric cancer cell line MGC-803,indicating that As_(2)O_(3) may inhibit the activity of SphK1.In this study,the effect of As_(2)O_(3) on the SphK1 activation pathway was investigated.Western blot and quantitative real-time PCR analysis were used to evaluate the changes in protein and mRNA levels.The multi-dimensional mass spectrometry-based shotgun lipidomics method(MDMS-SL)was used for the quantitative detection of phosphatidylserine(PS)and phosphatidic acid(PA).The results revealed that As_(2)O_(3) did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells.However,As_(2)O_(3) increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS and PA in the MGC-803 cells.The outcomes suggested that As_(2)O_(3) may enhance the activity of SphK1 by increasing the levels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA.It was suggested that the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1.

The effect of Jinlong capsule on the immune function for intervened patients with primary liver cancer

Objective: The aim of this study was to evaluate the effect of Jinlong capsule on the immune function for intervened patients with primary liver cancer. Methods: Matched the inclusion criteria, 60 patients were selected and randomly divided into two groups. The treatment group had 30 cases treated with Jinlong capsule combined with the transcatheter arterial chemoembolization(TACE); the control group had 30 cases treated with TACE. Each group was treated 30 days as a cycle, which had completed at least two cycles. Indicators of cellular immune function about the activity of CD3, CD4, CD8, CD4/CD8 and natural killer(NK) cell were detected before and after treatment, then to compare and analysis with each other. Results: Before treatment, the activity of peripheral blood CD3, CD4, CD8, CD4/CD8 and NK cell in the two groups was no significant difference(P > 0.05); after treatment, the activity of CD3, CD4 and NK cell in the treatment group was significantly increased, the ratio of CD4/CD8 increased, and the value of CD8 decreased(P < 0.05), the activity of CD3, CD4 and NK cell in the control group was significantly decreased, the ratio of CD4/CD8 decreased(P < 0.05), and the value of CD8 slightly higher than before treatment(P > 0.05), the difference between the two groups indicated the statistical significance(P < 0.05). Incidence of gastrointestinal reactions, leucopenia, hemoglobin, platelet decline in the treatment group was lower than those in the control group, but without presenting the statistical significance(P > 0.05). Conclusion: Jinlong capsule with hepatic arterial infusion chemotherapy can improve the patients' immune function, and reduce the adverse reactions of interventional chemotherapy. Hence,it deserves to be promoted in clinically.

Prognostic significance of PD-L1 expression in patients with colorectal cancer: a meta-analysis

Background The association between the expression of programmed cell death 1(PD-1) or its ligand [programmed cell death ligand-1(PD-L1)] and colorectal cancer(CRC) survival rates remains unclear. Thus, we conducted a meta-analysis to investigate the prognostic value of PD-L1 expression in CRC patients.Methods All eligible studies related to evaluation of PD-L1 expression and survival of CRC patients were searched in PubMed, Medline, Cochrane library, and the EMBASE database. Hazard ratios(HRs) and 95% confidence intervals(CI) of overall survival(OS) were examined to assess the effect of PD-L1 expression on the survival of CRC patients. The outcomes of this meta-analysis were synthesized based on randomeffects model. Subgroup analyses were also performed. Results Seven studies, wherein OS data were stratified according to the expression status of PD-L1, were analyzed. CRC patients showing positive PD-L1 expression were associated with significantly poorer prognoses in terms of overall survival, compared with those displaying negative PD-L1 expression(HR = 1.43, 95% CI: 1.07–1.92; P = 0.02). In the subgroup analyses, H-scores as well as the percentage of stained cells indicated that PD-L1 expression was significantly associated with poor prognosis(HR = 1.90, 95% CI: 1.38–2.62, P < 0.01; HR = 1.81, 95% CI: 1.08–3.03, P = 0.02). Immunohistochemical staining, utilizing a rabbit anti-PD-L1 antibody, revealed significantly superior survival in the PD-L1 negative group compared with the PD-L1 positive expression group(HR = 1.92; 95% CI, 1.40-2.63; P < 0.01). Moreover, PD-L1 expression was significantly associated with poor prognosis when polyclonal antibodies were used(HR = 1.84; 95% CI, 1.30–2.61; P < 0.01). Conclusion Our meta-analysis indicated that PD-L1 expression status is a significant prognostic factor for CRC patients. Positive PD-L1 expression was associated with worse CRC survival. Evaluation via different immunohistochemistry based techniques may partly account for the contradictory results. Therefore, further investigative studies using larger sample sizes are felt to be needed to elucidate the prognostic value of PD-L1 expression in CRC patients.

Identification of new genetic risk factors for prostate cancer

There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.