Therapeutic challenge for immunotherapy targeting cold colorectal cancer: A narrative review.

Cold colorectal tumors are not likely to trigger a robust immune response and tend to suppress the immune response. There may be three reasons. First, the complex tumor microenvironment of cold colorectal cancer (CRC) leads to tolerance and clearance of immunotherapy. Second, the modification and concealment of tumor-specific targets in cold CRC cause immune escape and immune response interruption. Finally, the difference in number and function of immune cell subsets in patients with cold CRC makes them respond poorly to immunotherapy. Therefore, we can only overcome the challenges in immunotherapy of cold CRC through in-depth research and understanding the changes and mechanisms in the above three aspects of cold CRC.

A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.

PURPOSE: To build a novel predictive model for hepatocellular carcinoma (HCC) patients based on DNA methylation data. METHODS: Four independent DNA methylation datasets for HCC were used to screen for common differentially methylated genes (CDMGs). Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the biological roles of CDMGs in HCC. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were performed to identify survival-related CDMGs (SR-CDMGs) and to build a predictive model. The importance of this model was assessed using Cox regression analysis, propensity score-matched (PSM) analysis and stratification analysis. A validation group from the Cancer Genome Atlas (TCGA) was constructed to further validate the model. RESULTS: Four SR-CDMGs were identified and used to build the predictive model. The risk score of this model was calculated as follows: risk score = (0.01489826 × methylation level of WDR69) + (0.15868618 × methylation level of HOXB4) + (0.16674959 × methylation level of CDKL2) + (0.16689301 × methylation level of HOXA10). Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer overall survival (OS; log-rank P-value =0.00071). The Cox model multivariate analysis and PSM analysis identified the risk score as an independent prognostic factor (P<0.05). Stratified analysis results further confirmed this model performed well. By analyzing the validation group, the results of receiver operating characteristic (ROC) curve analysis and survival analysis further validated this model. CONCLUSION: Our DNA methylation-based prognosis predictive model is effective and reliable in predicting prognosis for patients with HCC.

Ribosome assembly factor URB1 contributes to colorectal cancer proliferation through transcriptional activation of ATF4.

Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.

A scientometric study of the top 100 most-cited publications based on Web-of-Science regarding robotic versus laparoscopic surgery.

Minimally invasive surgery includes traditional laparoscopic and robot-assisted surgery. Although many studies related to robotic surgery and laparoscopic surgery have been published, when doing our search, scientometric studies that focus on related robotic surgery versus laparoscopic surgery were limited. In this study, we aimed to analyze and review the research hots and research status of robotic surgery versus laparoscopic surgery. We searched publications that involved robotic surgery versus laparoscopic surgery in the Web of Science database from 1980 to May 23, 2020. The top 100 publications were published in 2012 with the number of 17 and citations ranged from 618 to 64. Published across 34 different journals, namely European urology (n = 17) and others, the greatest contribution among 36 institutes was made by the Cleveland Clinic (n = 11). Of the top 100 publications, a total of 429 unique words were identified and the most frequently occurring keyword was laparoscopy (n = 33). The co-occurrence of keywords in the top 100 publications indicated that the study of diseases mainly focused on prostatectomy, complications, prostate cancer, retropubic prostatectomy, nephron-sparing surgery, lymph-node dissection, total mesenteric excision, sexual function, rectal cancer, and assisted distal gastrectomy. In recent years, comparative research on robot and laparoscopic surgery has decreased and most studies focus on cancer.

Comparison of total endoscopic thyroidectomy with conventional open thyroidectomy for treatment of papillary thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: Despite the fact that thyroid surgery has evolved towards minimal incisions and endoscopic approaches, the role of total endoscopic thyroidectomy (TET) in thyroid cancer has been highly disputed. We performed a systematic review and meta-analyses of peer reviewed studies in order to evaluate the safety and effectiveness of TET compared with conventional open thyroidectomy (COT) in papillary thyroid cancer (PTC). METHOD: Medical literature databases such as PubMed, Embase, the Cochrane Library, and Web of science were systematically searched for articles that compared TET and COT in PTC treatment from database inception until March 2019. The quality of the studies included in the review was evaluated using the Downs and Black scale using Review Manager software Stata V.13.0 for the meta-analysis. RESULTS: The systematic review and meta-analysis were based on 5664 cases selected from twenty publications. Criteria used to determine surgical completeness included postoperative thyroglobulin (TG) levels, recurrence of the tumor after long-term follow-up. Adverse event and complication rate scores included transient recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, transient hypocalcaemia, permanent hypocalcaemia, operative time, number of removed lymph nodes, length of hospital stay and patient cosmetic satisfaction. TET was found to be generally equivalent to COT in terms of surgical completeness and adverse event rate, although TET resulted in lower levels of transient hypocalcemia (OR 1.66; p < 0.05), a smaller number of the retrieved lymph nodes (WMD 0.46; p < 0.05), and better cosmetic satisfaction (WMD 1.73; p < 0.05). COT was associated with a shorter operation time (WMD - 50.28; p < 0.05) and lower rates of transient RLN palsy (OR 0.41; p < 0.05). CONCLUSIONS: The results show that in terms of safety and efficacy, TET was similar to COT for the treatment of thyroid cancer. Indeed, the tumor recurrence rates and the level of surgical completeness in TET are similar to those obtained for COT. TET was associated with significantly lower levels of transient hypocalcemia and better cosmetic satisfaction, and thus is the better option for patients with cosmetic concerns. Overall, randomized clinical trials and studies with larger patient cohorts and long-term follow-up data are required to further demonstrate the value of the TET.

RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1.

Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)-URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.

Evaluation of intra- and post-operative outcomes to compare robot-assisted surgery and conventional laparoscopy for gynecologic oncology.

OBJECTIVE: To compare robot-assisted surgery and conventional laparoscopy for gynecologic oncology regarding intra- and post-operative outcomes. METHODS: A retrospective study was performed on consecutive patients with gynecologic oncology from February 2014 to October 2017 at Gansu Provincial Hospital, China. Multivariable linear and logistic regression models were performed to explore the difference between two surgeries in the surgical outcomes after adjusting for potential confounders. RESULTS: 276 women were included in this study: 153 robot-assisted surgeries and 123 conventional laparoscopies. The multivariable linear regression model showed that robot-assisted surgery was longer operative time [coefficient (coef), 33.76; 95% CI, 12.47, 55.05; P = 0.002) ], higher lymph node yield (coef, 10.41; 95% CI, 7.47, 13.35; P < 0.001), shorter time to early post-operative feeding (coef, -1.09; 95% CI, -1.33, -0.84; P < 0.001) and less post-operative drainage volume (coef, -368.77; 95% CI, -542.46, -195.09; P < 0.001) than conventional laparoscopy. However, no difference was observed between the two surgeries regarding the estimated blood loss (P > 0.05). The multivariable logistic regression model showed that post-operative complications were similar between robot-assisted surgery and conventional laparoscopy (P > 0.05). CONCLUSION: Robot-assisted surgery was superior to conventional laparoscopy regarding intra- and post-operative outcomes for gynecologic oncology.

Short-Term Outcomes of Robotic versus Laparoscopic Total Mesorectal Excision for Rectal Cancer: A Cohort Study.

The aim of this study was to evaluate and compare the intestinal function recovery time and other short-term outcomes between robotic-assisted total mesorectal excision (R-TME) and laparoscopic total mesorectal excision (L-TME) for rectal cancer. This is a retrospective study using a prospectively collected database. Patients' records were obtained from Gansu Provincial Hospital between July 2015 and October 2017. Eighty patients underwent R-TME, and 116 with the same histopathological stage of the tumor underwent an L-TME. Both operations were performed by the same surgeon, comparing intra- and postoperative outcomes intergroups. The time to the first passage of flatus (P < 0.001), the time to the first postoperative oral fluid intake (P < 0.001), and the length of hospital stay (P < 0.01) of the R-TME group were about three days faster than those in the L-TME group. The rate of conversion to open laparotomy (P = 0.038) and postoperative urinary retention (P = 0.016) were significantly lower in the R-TME group than in the L-TME group. Intraoperative blood loss of the R-TME group was more than that of the L-TME group (P < 0.01).The operation time, number of lymph nodes harvested, and rate of positive circumferential resection margin were similar intergroup. The total cost of the R-TME group was higher than that of the L-TME group, but with a lack of statistical significance (85,623.91 ± 13,310.50 vs 67,356.79 ± 17,107.68 CNY, P = 0.084). The R-TME is safe and effective and has better postoperative short-term outcomes and faster intestinal function recovery time, contrasting with the L-TME. The large, multicenter, prospective studies were needed to validate the advantages of robotic surgery system used in rectal cancer.

Efficacy and safety of radiofrequency ablation versus minimally invasive liver surgery for small hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare radiofrequency ablation (RFA) with minimally invasive liver surgery (MIS) in the treatment of small hepatocellular carcinoma (SHCC) and to assess short-term and long-term clinical outcomes. METHODS: PubMed, Embase, Cochrane Library, Web of science, and CBM were systematically searched for articles from inception to July 2018, comparing RFA and MIS in SHCC treatment. We evaluated overall survival (OS), disease-free survival (DFS), local recurrence, and complication rates, as well as hospitalization duration and operation times. RESULTS: Six retrospective studies were analyzed, including a total of 597 patients, 313 treated with RFA and 284 treated with MIS. OS rates were significantly higher in patients treated with MIS at 3 years, when compared to RFA (OR 0.55; 95% CI 0.36 to 0.84). The 3-year DFS MIS rates were also superior to RFA (OR 0.63; 95% CI 0.41 to 0.98). In contrast, when compared to MIS, RFA demonstrated a significantly higher rate of local intrahepatic recurrences, (OR 2.24; 95% CI 1.47 to 3.42), and a lower incidence of postoperative complications (OR 0.34; 95% CI 0.22 to 0.53), as well as shorter operation times (OR - 145.31, 95% CI - 200.24 to - 90.38) and hospitalization duration (OR - 4.02,95% CI - 4.94 to - 3.10). CONCLUSIONS: We found that MIS led to higher OS, DFS, and lower local recurrences in SHCC patients. Meanwhile, RFA treatments led to significantly lower complication rates, shorter operation times, and hospitalization duration. Considering long-term outcomes, MIS was found to be superior to RFA. However, RFA may be an alternative treatment for patients presenting a single SHCC nodule (≤ 3 cm), given its minimally invasive nature and its comparable long-term efficacy with MIS. Nevertheless, our findings should be explained with caution due to the low level of evidence obtained.

Lymph node yield, survival benefit, and safety of high and low ligation of the inferior mesenteric artery in colorectal cancer surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was to compare high inferior mesenteric artery (IMA) ligation (HL) with low IMA ligation (LL) for the treatment of colorectal cancer and to evaluate the lymph node yield, survival benefit, and safety of these surgeries. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and China Biomedical Literature Database (CBM) were systematically searched for relevant articles that compared HL and LL for sigmoid or rectal cancer. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference (WMD) for continuous outcomes. RESULTS: In total, 30 studies were included in this analysis. There were significantly higher odds of anastomotic leakage and urethral dysfunction in patients treated with HL compared to those treated with LL (OR = 1.29; 95% CI = 1.08 to 1.55; OR = 2.45; 95% CI = 1.39 to 4.33, respectively). There were no significant differences between the groups in terms of the total number of harvested lymph nodes, the number of harvested lymph nodes around root of the IMA, local recurrence rate, and operation time. Further, no statistically significant group differences in 5-year overall survival rates and 5-year disease-free survival rates were detected among all patients nor among subgroups of stage II patients and stage III patients, respectively. CONCLUSIONS: LL can achieve equivalent lymph node yield to HL, and both procedures have similar survival benefits. However, LL is associated with a lower incidence of leakage and urethral dysfunction. Thus, LL is recommended for colorectal cancer surgery.

Suprapubic tube compared with urethral catheter drainage after robot-assisted radical prostatectomy: A systematic review and meta-analysis.

This meta-analysis aimed to compare the effectiveness of the suprapubic drainage and urethral catheterization after robot-assisted radical prostatectomy (RARP). PubMed, EMBASE, Cochrane Library and China Biology Medicine disc were systematically researched from their inception to December 2017. We selected randomized controlled trials, cohort studies comparing suprapubic tube with urethral catheter drainage in RARP patients. A meta-analysis was performed using R software, and a random-effects model was used to pool the effect size. Ten studies met eligibility criteria (N = 1248), including 3 RCTs, 3 prospective studies and 4 retrospective studies. Suprapubic drainage was associated with a reduction in the penile pain (39.64% [44 of 111]) compared with the UC group (62% [106 of 171]) (pooled RR 0.57, 95% CI 0.31 to 1.02, P = 0.05). However, two groups showed similarity in the overall pain (Postoperative days 1-3: pooled MD -0.26, 95% CI 1.34 to 0.83, P = 0.64; Postoperative days 6-7: pooled MD -0.50, 95% CI -1.54 to 0.54, P = 0.34), urinary incontinence (pooled RR 0.80, 95% CI 0.56 to 1.15, P = 0.23), bladder neck contracture (pooled RR 0.77, 95% CI 0.39 to 1.53, P = 0.45), urinary retention (pooled RR 0.88, 95% CI 0.29 to 2.70, P = 0.82), anastomotic stricture (P = 0.15), urethral stricture (P = 0.84) and bacteriuria (P = 0.40). The present meta-analysis showed that suprapubic drainage may be associated with less penile pain, but there was no conclusive evidence that suprapubic drainage was advantaged in other outcomes. Due to the low quality and small quantity of the available comparative studies, more high-quality randomized trials are needed to provide stronger evidence of the benefits of the two routes.

Comparison of Short-Term Outcomes Between Robotic-Assisted and Laparoscopic Surgery in Colorectal Cancer.

AIM: The robotic technique has been established as an alternative approach to laparoscopy in colorectal surgery. The aim of this study was to compare short-term outcomes of robot-assisted and laparoscopic surgery in colorectal cancer. METHODS: The cases of robot-assisted or laparoscopic colorectal resection were collected retrospectively between July 2015 and October 2017. We evaluated patient demographics, perioperative characteristics, and pathologic examination. A multivariable linear regression model was used to assess short-term outcomes between robot-assisted and laparoscopic surgery. Short-term outcomes included time to passage of flatus and postoperative hospital stay. RESULTS: A total of 284 patients were included in the study. There were 104 patients in the robotic colorectal surgery (RCS) group and 180 in the laparoscopic colorectal surgery (LCS) group. The mean age was 60.5 ± 10.8 years, and 62.0% of the patients were male. We controlled for confounding factors, and then the multiple linear model regression indicated that the time to passage of flatus in the RCS group was 3.45 days shorter than the LCS group (coefficient = -3.45, 95% confidence interval [CI] = -5.19 to -1.71; P < .001). Additionally, the drainage of tube duration (coefficient = 0.59, 95% CI = 0.3 to 0.87; P < .001) and transfers to the intensive care unit (coefficient = 7.34, 95% CI = 3.17 to 11.5; P = .001) influenced the postoperative hospital stay. The total costs increased by 15501.48 CNY in the RCS group compared with the LCS group ( P = .008). CONCLUSIONS: The present study suggests that colorectal cancer robotic surgery was more beneficial to patients because of shorter postoperative recovery time of bowel function and shorter hospital stays.

Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer.

AIM: To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS: Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/mTOR signaling by CXCL12 involved in the metastatic process of colon cancer. RESULTS: CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration (P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells (P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/mTOR pathway. CONCLUSION: Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells, and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/mTOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer.

Robotic versus Laparoscopic Gastrectomy for Gastric Carcinoma: a Meta-Analysis of Efficacy and Safety.

PURPOSE: To systematically review efficacyand safety of robotic gastrectomy (RG) compared with conventional laparoscopic gastrectomy (LG) for gastric carcinoma. MATERIALS AND METHODS: A systematic literature search was carried out using PubMed, Cochrane Library, CBM, CNKI, WanFang, VIP and other sources like relevant references to obtain comparative studies assessing the effectiveness and safety between RG and LG published between 2013 and 2016. Then the literature was screened and the data were extracted by 2 independent reviewers. The quality of the literature was assessed, and the data analyzed using Stata/SE 14 software. Fixed effects or random effects models wereapplied according to heterogeneity. RESULTS: A total of 12 non-randomized observational clinical studies involving 3,580 patients were included, of which 1,096 had undergone RG and 2,484 had received LG. The results of the meta-analysis showed in terms of effectiveness, RG was associated with less blood loss, less time to first flatus and greater number of harvested lymph nodes, but there were no significant differences in proximal and distal resection margins, compared with LG. In terms of efficiency, RG was associated with shorter hospital stay, but longer operative time. In terms of safety, there were no statistically significant differences in complications, mortality and conversions between RG and LG. CONCLUSIONS: RG can achieve comparable or better short-term and radical effects than LG, with respect to effectiveness, efficiency and safety in treatment of gastric carcinoma. Future studies involving RG should focus on decreasing operative time and reducing cost. Moreover, there is a need for randomized controlled trials comparing the two techniques with long-term follow-up.

Laparoscopy-assisted versus open distal gastrectomy for early gastric cancer: A meta-analysis based on seven randomized controlled trials.

OBJECTIVE: This study aims to answer the superiority of comparing laparoscopy-assisted distal gastrectomy (LADG) with open distal gastrectomy (ODG) in the treatment early gastric cancer (EGC). MATERIAL AND METHODS: A comprehensive search up to May 31, 2014 was conducted on PubMed, Web of science, and the Cochrane Library. All eligible studies comparing LADG versus ODG were included. Data synthesis and statistical analysis were performed using RevMan 5.2 software. RESULTS: Seven randomized controlled trials (RCTs) totaling 390 patients (195 LADG and 195 ODG) were analyzed. Compared to ODG, LADG showed longer operative time (WMD = 79.60; 95%CI = 59.86 to 99.35; P < 0.00001), but was associated with less blood loss (WMD = -108.11; 95%CI = -145.97 to -70.26; P < 0.00001), fewer administered analgesics (WMD = -1.70; 95%CI = -2.19 to -1.22; P < 0.00001), fewer number of harvested lymph node (WMD = -2.77; 95%CI = -4.38 to -1.16; P = 0.0007), lower incidence of postoperative complications (OR = 0.26; 95%CI = 0.13 to 0.54; P = 0.0003), shorter postoperative hospital stay (WMD = -1.0; 95% CI = -1.83 to -0.16; P = 0.02) and earlier passage of flatus (WMD = -0.62; 95% CI = -0.96 to -0.27; P = 0.0005). CONCLUSION: This meta-analysis demonstrated that LADG significantly reduced blood loss, decreased the frequency of analgesic administration, faster recovery, a shorter hospital stay and fewer postoperative complications compared with ODG, though at the price of longer operative times and the number of harvested lymph nodes lesser as compared to ODG.

Association of Romo1 gene genetic polymorphisms with risk of gastric cancer in northwestern Chinese population.

Increased expression of reactive oxygen species modulator 1 protein-triggered reactive oxygen species production was reported in the mitochondria of various cancer cell lines. To date there is no report on association between Romo1 gene polymorphisms and gastric cancer risk. To investigate the relationship between Romo1 gene polymorphisms and GC risk, we conducted a case-control study in a population from northwest China (358 GC patients and 412 healthy controls). The genotypes of two SNPs were determined with PCR-denaturing high-performance liquid chromatography and direct DNA sequencing. We found that the genotype and allele distributions of two polymorphisms were significantly different in GC patients compared with controls, When the wild type of two loci were served as the reference group, respectively, significantly increased risk for gastric cancer were associated with rs6060566 TC genotype (Adjusted OR = 1.525, 95 % CI =1.126-2.138), rs6060567 GC genotype (Adjusted OR = 1.641, 95 % CI =1.238-2.291) and CC genotype (Adjusted OR = 1.594, 95 % CI =1.102-2.973). This effect was more pronounced in patients with smoking, alcohol consumption, H.pylori infection,and male patients subgroups. Haplotypes analysis of two genetic variants showed that the most common haplotype TG displayed the strongest evidence of association with GC (corrected P = 9.30 × 10(-5)), and was associated with protection against GC (OR = 0.584). Whereas the CC haplotypes had significant correlation with GC risk (OR = 1.732). These findings suggested genetic polymorphisms of Romo1 gene were associated with significant risk of GC in Northwestern Chinese population, which is strengthened by alcohol use, smoking, H.pylori infection or male patients.

Liposome-mediated induction of apoptosis of human hepatoma cells by c-myc antisense phosphorothioate oligodeoxynucleotide and 5-fluorouracil.

BACKGROUND: The aim of this study was to investigate the effect of a c-myc antisense oligodeoxynucleotide and 5-fluorouracil on the expression of c-myc, invasion and proliferation of HEPG-2 liver cancer cells. MATERIALS AND METHODS: HEPG-2 cells were treated with lipiosome-mediated c-myc ADSON and 5-fluorouracil. The proliferation inhibition rate and invasion were measured by MTT and invasion assay, respectively. Cell apoptosis was detected by flow cytometry and expression of c-myc by RT-PCR and immunohistochemistry. RESULTS: The proliferation inhibition rate was significantly higher in the antisense oligodeoxynucleotide added-5-fluorouracil group than single antisense oligodeoxynucleotide or 5-fluorouracil group (p<0.05). G0/G1 cells in the antisense oligodeoxynucleotide group and S cells in the 5-fluorouracil groups were significantly increased than that in the control group, respectively (P<0.01). The amplification strips of PCR products in 5-FU, ASODN and combination groups were significantly weaker than that in the control group (P<0.01). The percentage of c-myc-protein- positive cells were significantly lower in antisense oligodeoxynucleotide, 5-fluorouracil and combination groups than that in the control group (P<0.01). CONCLUSIONS: A liposome-mediated c-myc antisense oligodeoxynucleotide and 5-fluorouracil can inhibit the proliferation and invasion of liver cancer cells by reducing the expression of c-myc. A c-myc antisense oligodeoxynucleotide can increase the sensitivity of liver cancer cells to 5-fluorouracil and decrease the dosage of the agent necessary for efficacy, providing an experimental basis for the clinical therapy of liver cancer.

Plasma microRNAs serve as novel potential biomarkers for early detection of gastric cancer.

Recent studies have shown that microRNAs can be stably detected in human plasma and have the potential as non-invasive biomarkers for the diagnosis of cancers. This study evaluates the potential application of plasma microRNAs for the early detection of gastric cancer (GC). We first measured the plasma expression levels of 15 selected microRNAs (miR-1, -106a, -106b, -17-5p, -20a, -21, -221, -27a, -34, -376c, -378, -423-5p, -451, -486, -744) in 30 GC patients and 30 age- and gender-matched healthy controls and then validated those microRNAs that differentiating GC and controls in another 60 GC patients and 60 matched controls using quantitative reverse transcription-polymerase chain reaction. The areas under the receiver operating characteristic (ROC) curves were used to test the sensitivity and specificity of GC diagnosis using these identified plasma microRNAs. Three plasma microRNAs, miR-106b, miR-20a, and miR-221, were significantly elevated in GC patients than in healthy controls (P < 0.05). Furthermore, the areas under the ROC curves using miR-106b, miR-20a, and miR-221 for GC diagnosis were 0.7733 (95 % CI, 0.7758-0.8409), 0.8593 (95 % CI, 0.8046-0.9139), and 0.7960 (95 % CI, 0.7256-0.8664), respectively. Furthermore, these three microRNAs had a statistically significant elevation in GC patients compared with healthy controls at each of the four stages. However, there were no significant differences in the plasma levels of the three microRNAs among the four TNM stages (P > 0.05). Plasma miR-106b, miR-20a, and miR-221 have the potential as novel, non-invasive biomarkers for the early detection of GC.

Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis.

In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic injection of TNBS, GRd (10, 20 and 40 mg/kg) was administered to experimental colitis rats for 7 days. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. The levels of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6 were determined by ELISA. Mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by western blotting method. The results showed that GRd markedly attenuates the inflammatory response to TNBS-induced relapsing colitis, as evidenced by improved signs, increased body weight, decreased colonic weight/length ratio, reduced colonic macroscopic and microscopic damage scores, inhibited the activity of MPO, lowered proinflammatory cytokine levels and suppressed phosphorylation of p38 and JNK. The possible mechanism of protection on experimental colitis after GRd administration was that it could reduce the accumulation of leukocytes and down-regulate multiple proinflammatory cytokines through modulation of JNK and p38 activation.

Association of mtDNA D-loop polymorphisms with risk of gastric cancer in Chinese population.

The aim of present study was to evaluate the association of common polymorphisms detected in mitochondrial DNA (mtDNA) D-loop region (mononucleotide repetitive D310, single nucleotide polymorphism (SNP) D16521) with susceptibility to gastric cancer (GC) in northwestern Chinese population. A total of 180 GC patients and 218 healthy controls were investigated by using PCR- denaturing high performance liquid chromatography (DHPLC) assay. Genotype and allele distributions and haplotype construction were analyzed in case-control study. We found D310 and D16521 heteroplasmy were significantly different between GC cases and controls (p < 0.05), and D16521 homoplasmy showed association with histological grade of GC (p < 0.05). Haplotype 7C/T, 8C/C and 9C/C had significant association with GC risk implied from analysis of D310 and D16521. Taken together, these findings suggested that mtDNA D-Loop polymorphisms and haplotypes may contribute to genetic susceptibility to GC in Chinese population.