New plasma diagnostic markers for colorectal cancer: transporter fragments of glutamate tRNA origin.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Early diagnosis of the disease can greatly improve the clinical prognosis for patients with CRC. Unfortunately, there are no current simple and effective early diagnostic markers available. The transfer RNA (tRNA)-derived RNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs), which have been shown to play an important role in the development and prognosis of CRC. However, only a few studies on tRFs as early diagnostic markers in CRC have been conducted. In this study, previously ignored tRFs expression data were extracted from six paired small RNA sequencing data in the Sequence Read Archive (SRA) database using MINTmap. Three i-tRFs, derived from the tRNA that transports glutamate (i-tRF-Glu), were identified and used to construct a random forest diagnostic model. The model performance was evaluated using the receiver operating characteristic (ROC) curve and precision-recall (PR) curve. The area under the curves (AUC) for the ROC and PR was 0.941 and 0.944, respectively. We further verified the differences in expression of the these i-tRF-Glu in the tissue and plasma of both CRC patients and healthy subjects using quantitative real-time PCR (qRT-PCR). We found that the ROC-AUC of the three was greater than traditional plasma tumor markers such as CEA and CA199. Our bioinformatics analysis suggested that the these i-tRF-Glu are associated with cancer development and glutamate (Glu)-glutamine (Gln) metabolism. Overall, our study uncovered these i-tRF-Glu that have early diagnostic significance and therapeutic potential for CRC, this warrants further investigation into the diagnostic and therapeutic potential of these i-tRF-Glu in CRC.

Role of long non-coding RNAs in metabolic reprogramming of gastrointestinal cancer cells.

Metabolic reprogramming, which is recognized as a hallmark of cancer, refers to the phenomenon by which cancer cells change their metabolism to support their increased biosynthetic demands. Tumor cells undergo substantial alterations in metabolic pathways, such as glycolysis, oxidative phosphorylation, pentose phosphate pathway, tricarboxylic acid cycle, fatty acid metabolism, and amino acid metabolism. Latest studies have revealed that long non-coding RNAs (lncRNAs), a group of non-coding RNAs over 200 nucleotides long, mediate metabolic reprogramming in tumor cells by regulating the transcription, translation and post-translational modification of metabolic-related signaling pathways and metabolism-related enzymes through transcriptional, translational, and post-translational modifications of genes. In addition, lncRNAs are closely related to the tumor microenvironment, and they directly or indirectly affect the proliferation and migration of tumor cells, drug resistance and other processes. Here, we review the mechanisms of lncRNA-mediated regulation of glucose, lipid, amino acid metabolism and tumor immunity in gastrointestinal tumors, aiming to provide more information on effective therapeutic targets and drug molecules for gastrointestinal tumors.

TMUB1 expression is associated with the prognosis of colon cancer and immune cell infiltration.

Background: TMUB1 is a transmembrane protein involved in biological signaling and plays an important role in the stability and transcription of P53. However, its role in tumor remains unknown. Methods: Using R language, the expression level of 33 cancer spectrum TMUB1 was analyzed by the public database TCGA, GEO and HPA, the differential expressed gene (DEG) screening and protein interaction (PPI) network was constructed, and the differential genes of TMUB1 in colon cancer were identified. The relevant signaling pathways were identified by gene functional annotation and enrichment analysis. The ssGSEA algorithm in GSVA were used for immune infiltration analysis. The Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, nomogram and calibration map analysis were constructed to evaluate the correlation between TMUB1 expression and clinical prognosis. The expression levels of TMUB1 in intestinal cancer cell lines as well as in 10 intestinal cancer tissues were verified by qPCR experiments. Results: Through the bioinformatics analysis of multiple databases and preliminary experimental studies, we found that the expression of TMUB1 was significantly increased in colon cancer tumors, and was correlated with the clinical N stage, pathological grade, lymphatic metastasis and BMI of colon cancer. TMUB1 may be involved in the regulation of the malignant progression of colon cancer. Meanwhile, patients with high expression of TMUB1 mRNA had worse OS and DSS, and TMUB1 expression was an independent prognostic factor for OS and DSS. It was further found that highly expressed TMUB1 tissues showed low levels of immune infiltration and stromal infiltration. Conclusion: We reported the expression level of TMUB1 in colon cancer and analyzed its potential prognostic value in colon cancer through the bioinformatics analysis and preliminary experimental studies. The high expression of TMUB1 is a negative prognostic factor for colon cancer patients. TMUB1 may be a potential target for colon cancer.

"Caudal to cranial" versus "medial to lateral" approach in laparoscopic right hemicolectomy with complete mesocolic excision for the treatment of stage II and III colon cancer: perioperative outcomes and 5-year prognosis.

The purpose of this study was to compare the "caudal to cranial" (CC) versus "medial to lateral" (ML) approach for laparoscopic right hemicolectomy. Pertinent data from all patients with stage II and III between January 2015 and August 2017 were entered into a retrospective database. A total of 175 patients underwent the ML (N = 109) or CC approach (N = 66). Patient characteristics were equivalent between groups. The CC group showed a shorter surgical time 170.00 (145.00, 210.00) vs. (206.50 (178.75, 226.25) min) than the ML group (p < 0.001). The time to oral intake was shorter in the CC group than in the ML group ((3.00 (1.00, 4.00) vs. 3.00 (2.00, 5.00) days; p = 0.007). For the total harvested lymph nodes, there was no statistical significance between the CC group 16.50 (14.00, 21.25) and the ML group 18.00 (15.00, 22.00) (p = 0.327), and no difference was found in the positive harvested lymph nodes (0 (0, 2.00) vs. 0 (0, 1.50); p = 0.753). Meanwhile, no differences were found in other perioperative or pathological outcomes, including blood loss and complications. For 5-year prognosis, overall survival rates were 75.76% in the CC group and 82.57% in the ML group (HR 0.654, 95% CI 0.336-1.273, p = 0.207); disease-free survival rates were 80.30% in the CC group and 85.32% in the ML group (HR 0.683, 95% CI 0.328-1.422, p = 0.305). Both approaches were safe and feasible and resulted in excellent survival. The CC approach was beneficial in terms of the surgical time and time to oral intake.

Iron metabolism in colorectal cancer.

Iron, as one of the essential trace elements in the human body, is involved in a wide range of critical biochemical reactions and physiological processes, including the maintenance of the normal cell cycle, mitochondrial function, nucleotide metabolism, and immune response. In this context, iron is naturally associated with cancer occurrence. Cellular iron deficiency can induce apoptosis, however, iron can also engage in potentially harmful reactions that produce free radicals because of its capacity to gain and lose electrons. Studies suggest that dietary iron, particularly heme iron, may be one of the leading causes of colorectal cancer (CRC). Moreover, patients with CRC have abnormal iron absorption, storage, utilization, and exportation. Therefore, iron is crucial for the development and progression of CRC. Elaborating on the alterations in iron metabolism during the onset and advancement of CRC would help to further explain the role and mechanism of iron inside the body. Thus, we reviewed the alterations in numerous iron metabolism-related molecules and their roles in CRC, which may provide new clues between iron metabolism and CRC.

Relationship between copper and immunity: The potential role of copper in tumor immunity.

Copper is an essential trace element in an organism, and changes in copper levels in vivo often indicate a diseased state. Copper and immunity have been discussed since the last century, with copper deficiency significantly affecting the development and function of the immune system, such as increased host susceptibility to various pathogens, decreased number and impaired function of neutrophils, reduced antibacterial activity of macrophages, decreased proliferation of splenocytes, impaired B cell ability to produce antibodies and impaired function of cytotoxic T lymphocyte and helper T cells. In the past 20 years, some studies have shown that copper ions are related to the development of many tumors, including lung cancer, acute lymphoid leukaemia, multiple myeloma and other tumors, wherein copper ion levels were significantly elevated, and current studies reveal that copper ions are involved in the development, growth and metastasis of tumors through various pathways. Moreover, recent studies have shown that copper ions can regulate the expression of PD-L1, thus, attention should be paid to the important role of copper in tumor immunity. By exploring and studying copper ions and tumor immunity, new insights into tumor immunity could be generated and novel therapeutic approaches to improve the clinical prognosis of patients can be provided.

Construction and validation of a glycolysis-related lncRNA signature for prognosis prediction in Stomach Adenocarcinoma.

Background: Glycolysis is closely related to the occurrence and progression of gastric cancer (GC). Currently, there is no systematic study on using the glycolysis-related long non-coding RNA (lncRNA) as a model for predicting the survival time in patients with GC. Therefore, it was essential to develop a signature for predicting the survival based on glycolysis-related lncRNA in patients with GC. Materials and methods: LncRNA expression profiles, containing 375 stomach adenocarcinoma (STAD) samples, were obtained from The Cancer Genome Atlas (TCGA) database. The co-expression network of lncRNA and glycolysis-related genes was used to identify the glycolysis-related lncRNAs. The Kaplan-Meier survival analysis and univariate Cox regression analysis were used to detect the glycolysis-related lncRNA with prognostic significance. Then, Bayesian Lasso-logistic and multivariate Cox regression analyses were performed to screen the glycolysis-related lncRNA with independent prognostic significance and to develop the risk model. Patients were assigned into the low- and high-risk cohorts according to their risk scores. A nomogram model was constructed based on clinical information and risk scores. Gene Set Enrichment Analysis (GSEA) was performed to visualize the functional and pathway enrichment analyses of the glycolysis-related lncRNA. Finally, the robustness of the results obtained was verified in an internal validation data set. Results: Seven glycolysis-related lncRNAs (AL353804.1, AC010719.1, TNFRSF10A-AS1, AC005586.1, AL355574.1, AC009948.1, and AL161785.1) were obtained to construct a risk model for prognosis prediction in the STAD patients using Lasso regression and multivariate Cox regression analyses. The risk score was identified as an independent prognostic factor for the patients with STAD [HR = 1.315, 95% CI (1.056-1.130), p < 0.001] via multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves were drawn and the area under curve (AUC) values of 1-, 3-, and 5-year overall survival (OS) were calculated to be 0.691, 0.717, and 0.723 respectively. Similar results were obtained in the validation data set. In addition, seven glycolysis-related lncRNAs were significantly enriched in the classical tumor processes and pathways including cell adhesion, positive regulation of vascular endothelial growth factor, leukocyte transendothelial migration, and JAK_STAT signaling pathway. Conclusion: The prognostic prediction model constructed using seven glycolysis-related lncRNA could be used to predict the prognosis in patients with STAD, which might help clinicians in the clinical treatment for STAD.

The Regulatory Effects of MicroRNAs on Tumor Immunity.

MicroRNAs are endogenous noncoding small RNAs that posttranscriptionally regulate the expressions of their target genes. Accumulating research shows that miRNAs are crucial regulators of immune cell growth and antitumor immune response. Studies on miRNAs and tumors primarily focus on the tumor itself. At the same time, relatively few studies on the indirect regulatory effects of miRNAs in the development of tumors are achieved by affecting the immune system of tumor hosts and altering their immune responses. This review discusses the influence of miRNAs on the antitumor immune system.

The Regulatory Network of MicroRNA in the Metabolism of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common malignant tumor in the world. During the progression of CRC, the entire metabolic network undergoes reprogramming, including marked changes in the regulation of glucose, lipid and amino acid metabolism. Although microRNAs (miRNAs) account for only 1% of the entire human genome, they play an important role in almost all physiological and pathological processes in the body. MiRNAs can react directly with key enzymes in the metabolic processes. MiRNAs also interact with other ncRNAs, as a member of non-coding RNA (ncRNA), to form their own regulatory network in various oncogenic pathways of CRC metabolism. The progression of colorectal cancer is closely related to the intestinal flora, where miRNAs act as important mediators. Understanding how miRNAs act in the regulatory network of CRC metabolism is helpful to elucidate the characteristics of tumor occurrence, proliferation, metastasis and drug resistance. This review summarizes the role of miRNAs in the metabolism of CRC and how miRNAs interact with key enzymes, ncRNA and intestinal flora to further discuss how miRNAs affect CRC and realize some new strategies for the early diagnosis and treatment of CRC.

NOS1 inhibits the interferon response of cancer cells by S-nitrosylation of HDAC2.

BACKGROUND: The dysfunction of type I interferon (IFN) signaling is an important mechanism of immune escape and metastasis in tumors. Increased NOS1 expression has been detected in melanoma, which correlated with dysfunctional IFN signaling and poor response to immunotherapy, but the specific mechanism has not been determined. In this study, we investigated the regulation of NOS1 on the interferon response and clarified the relevant molecular mechanisms. METHODS: After stable transfection of A375 cells with NOS1 expression plasmids, the transcription and expression of IFNα-stimulated genes (ISGs) were assessed using pISRE luciferase reporter gene analysis, RT-PCR, and western blotting, respectively. The effect of NOS1 on lung metastasis was assessed in melanoma mouse models. A biotin-switch assay was performed to detect the S-nitrosylation of HDAC2 by NOS1. ChIP-qPCR was conducted to measure the binding of HDAC2, H4K16ac, H4K5ac, H3ac, and RNA polymerase II in the promoters of ISGs after IFNα stimulation. This effect was further evaluated by altering the expression level of HDAC2 or by transfecting the HDAC2-C262A/C274A site mutant plasmids into cells. The coimmunoprecipitation assay was performed to detect the interaction of HDAC2 with STAT1 and STAT2. Loss-of-function and gain-of-function approaches were used to examine the effect of HDAC2-C262A/C274A on lung metastasis. Tumor infiltrating lymphocytes were analyzed by flow cytometry. RESULTS: HDAC2 is recruited to the promoter of ISGs and deacetylates H4K16 for the optimal expression of ISGs in response to IFNα treatment. Overexpression of NOS1 in melanoma cells decreases IFNα-responsiveness and induces the S-nitrosylation of HDAC2-C262/C274. This modification decreases the binding of HDAC2 with STAT1, thereby reducing the recruitment of HDAC2 to the ISG promoter and the deacetylation of H4K16. Moreover, expression of a mutant form of HDAC2, which cannot be nitrosylated, reverses the inhibition of ISG expression by NOS1 in vitro and decreases NOS1-induced lung metastasis and inhibition of tumor infiltrating lymphocytes in a melanoma mouse model. CONCLUSIONS: This study provides evidence that NOS1 induces dysfunctional IFN signaling to promote lung metastasis in melanoma, highlighting NOS1-induced S-nitrosylation of HDAC2 in the regulation of IFN signaling via histone modification.

Comparison of outcomes of complete mesocolic excision with conventional radical resection performed by laparoscopic approach for right colon cancer.

BACKGROUND: This retrospective study compared the outcomes of laparoscopic complete mesocolic excision (CME) guided by superior mesenteric artery with laparoscopic conventional radical resection (CRR) performed for right-sided colon cancer. METHODS: Patients with right-sided colon cancer underwent CME (n=107; January 2011 to December 2015) or CRR (n=60; January 2008 to December 2010). RESULTS: The 2 groups were comparable regarding age, gender, body mass index, maximum tumor diameter, and tumor stage. In the CME group, the distances between the tumor and the high vascular tie (HVT; 12.6 cm), and between the closest bowel wall and HVT (10.4±0.9 cm) was significantly greater than that of the CRR group (11.5 cm and 9.3±1.0 cm, respectively; P<0.001). In the CME group, the number of retrieved lymph nodes (23.2) was significantly higher, and the volume of intraoperative bleeding (108.4 mL) was less than that of the CRR (14.0 and 128.7 mL; P<0.001). The length of resected bowel in the 2 groups was similar (25.8±0.7 cm and 25.5±2.1 cm; P=0.106), as was the operative time, postoperative hospitalization, time of first bowel movement, and complications. The 3-year recurrence rate of the CME group (8.4%) was significantly lower than that of the CRR (20.0%), the 3-year overall survival was significantly higher (93.5% cf. 85.0%), and the survival rates of T4 stage, N1 stage, pTNM stage II, pTNM stage III and lympho vascular invasion were significantly higher (P<0.05). The 2 groups were similar for survival rates of Tis, T1, T2, T3, N2 stage, pTNM stage I and perineural invasion (P>0.05). CONCLUSION: CME for right-sided colon cancer guided by superior mesenteric artery has similar short-term outcomes, higher lymph node yield, and higher 3-year overall survival compared with CRR.

Comparison of the safety and efficacy between linear stapler and circular stapler in totally laparoscopic total gastrectomy: protocol for a systematic review and meta-analysis.

INTRODUCTION: Total gastrectomy is often recommended for upper body gastric cancer, and totally laparoscopic total gastrectomy (TLTG) is deemed to be a promising surgical method with the well-known advantages such as less invasion and fast recovery. However, the anastomosis between oesophagus and jejunum is the difficulty of TLTG. Although staplers have promoted the development of TLTG, the choice of suitable staplers to complete oesophagojejunostomy is controversial and unclear. Therefore, a higher level of research evidence is needed to compare the two types of staplers in terms of safety and efficacy for oesophagojejunostomy in TLTG among patients with gastric cancer. METHODS AND ANALYSIS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Databases will be comprehensively searched from January 1990 to July 2019. All eligible randomised controlled trials (RCTs), non-RCTs or observational studies comparing the two types of staplers will be included. A meta-analysis will be performed using Review Manager V.5.3 software to compare the safety and efficacy of linear and circular staplers for oesophagojejunostomy in TLTG. The primary outcomes are anastomotic leakage, anastomotic stricture, anastomotic haemorrhage. The secondary outcomes include time to first instance of passing gas after surgery, first feeding time, total operation time, reconstruction time, estimated blood loss. The heterogeneity of this study will be assessed by p values and I2 statistic. Subgroup analyses and sensitivity analyses will be used to explore and explain the heterogeneity. The risk of bias will be assessed using the Cochrane tool or the Newcastle-Ottawa Quality Assessment Scale. ETHICS AND DISSEMINATION: Ethical approval will not be required because this proposed systematic review and meta-analysis is based on previously published data, which does not include intervention data on patients. The findings of this study will be submitted to a peer-reviewed journal and will be presented at a relevant congress. PROSPERO REGISTRATION NUMBER: CRD42018111680.

Protective effect of curcumin against irinotecan­induced intestinal mucosal injury via attenuation of NF­κB activation, oxidative stress and endoplasmic reticulum stress.

Irinotecan (CPT­11) is a DNA topoisomerase I inhibitor which is widely used in clinical chemotherapy, particularly for colorectal cancer treatment. However, late­onset diarrhea is one of the severe side­effects of this drug and this restricts its clinical application. The present study aimed to investigate the protective effects of curcumin treatment on CPT­11­induced intestinal mucosal injury both in vitro and in vivo and to elucidate the related mechanisms involved in these effects. For this purpose, mice were intraperitoneally injected with CPT­11 (75 mg/kg) for 4 days to establish a model of late­onset diarrhea. Curcumin (100 mg/kg) was intragastrically administered 8 days before the injection of CPT­11. Injury to small intestinal tissues was examined by H&E staining. The protein expression of prolyl 4­hydroxylase subunit beta (P4HB) and peroxiredoxin 4 (PRDX4) was detected by immunohistochemistry, as well as western blot analysis. IEC­6 cell viability was detected by MTT assay. Flow cytometry was performed to examine the cell apoptotic rate, mitochondrial membrane potential and reactive oxygen species (ROS) generation. Immunofluorescence was used to observe the localization of nuclear factor (NF)­κB. The levels of cleaved caspase­3, glucose­regulated protein, 78 kDa (GRP78), P4HB, PRDX4 and CHOP were detected by western blot analysis. The results revealed that in vivo, curcumin effectively attenuated the symptoms of diarrhea and abnormal intestinal mucosa structure induced by CPT­11 in nude mice. Treatment with curcumin also increased the expression of P4HB and PRDX4 in the tissue of the small intestine. In vitro, curcumin, exhibited little cytotoxicity when used at concentrations <2.5 µg/ml for 24 h in IEC­6 cells. At this concentration, curcumin also improved cell morphology, inhibited apoptosis, maintained mitochondrial membrane potential and reduced the elevated levels of ROS induced by CPT­11 (20 µg/ml). Furthermore, curcumin abolished NF­κB signal transduction and protected the cells from CPT­11­induced apoptosis by upregulating the expression of molecular chaperones, such as GRP78, P4HB and PRDX4, and suppressing the levels of the apoptosis­related proteins, CHOP and cleaved caspase­3. On the whole, our data indicate that curcumin exerted protective effects against CPT­11­induced intestinal mucosa injury. The protective effects of curcumin are mediated by inhibiting the activation of NF­κB, and suppressing oxidative stress and endoplasmic reticulum stress.

Laparoscopic versus Open Surgery in Lateral Lymph Node Dissection for Advanced Rectal Cancer: A Meta-Analysis.

AIM: To compare the clinical efficacies between laparoscopic and conventional open surgery in lateral lymph node dissection (LLND) for advanced rectal cancer. METHODS: We comprehensively searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang Data and performed a cumulative meta-analysis. According to inclusion criteria and exclusion criteria, all eligible randomized controlled trials (RCTs) or retrospective or prospective comparative studies assessing the two techniques were included, and then a meta-analysis was performed by using RevMan 5.3 software to assess the difference in clinical and oncological outcomes between the two treatment approaches. RESULTS: Eight studies involving a total of 892 patients were finally selected, with 394 cases in the laparoscopic surgery group and 498 cases in the traditional open surgery group. Compared with the traditional open group, the laparoscopic group had a longer operative time (WMD = 81.56, 95% CI (2.09, 142.03), P = 0.008), but less intraoperative blood loss (WMD = -452.18, 95% CI (-652.23, -252.13), P < 0.00001), shorter postoperative hospital stay (WMD = -5.30, 95% CI (-8.42, -2.18), P = 0.0009), and higher R0 resection rate (OR = 2.17, 95% CI (1.14, 4.15), P = 0.02). There was no significant difference in the incidence of surgical complications between the two groups (OR = 0.52, 95% CI (0.26, 1.07), P = 0.08). Lateral lymph node harvest, lateral lymph node metastasis, local recurrence, 3-year overall survival, and 3-year disease-free survival did not differ significantly between the two approaches (P > 0.05). CONCLUSION: Laparoscopic LLND has a similar efficacy in oncological outcomes and postoperative complications to the conventional open surgery, with the advantages of reduced intraoperative blood loss, shorter postoperative hospital stay, and higher R0 resection rate, and tumor radical cure is similar to traditional open surgery. Laparoscopic LLND is a safe and feasible surgical approach, and it may be used as a standard procedure in LLND for advanced rectal cancer.

Three surgical planes identified in laparoscopic complete mesocolic excision for right-sided colon cancer.

BACKGROUND: Complete mesocolic excision provides a correct anatomical plane for colon cancer surgery. However, manifestation of the surgical plane during laparoscopic complete mesocolic excision versus in computed tomography images remains to be examined. METHODS: Patients who underwent laparoscopic complete mesocolic excision for right-sided colon cancer underwent an abdominal computed tomography scan. The spatial relationship of the intraoperative surgical planes were examined, and then computed tomography reconstruction methods were applied. The resulting images were analyzed. RESULTS: In 44 right-sided colon cancer patients, the surgical plane for laparoscopic complete mesocolic excision was found to be composed of three surgical planes that were identified by computed tomography imaging with cross-sectional multiplanar reconstruction, maximum intensity projection, and volume reconstruction. For the operations performed, the mean bleeding volume was 73±32.3 ml and the mean number of harvested lymph nodes was 22±9.7. The follow-up period ranged from 6-40 months (mean 21.2), and only two patients had distant metastases. CONCLUSIONS: The laparoscopic complete mesocolic excision surgical plane for right-sided colon cancer is composed of three surgical planes. When these surgical planes were identified, laparoscopic complete mesocolic excision was a safe and effective procedure for the resection of colon cancer.

Perioperative Allogenenic Blood Transfusion is Associated With Worse Clinical Outcome for Patients Undergoing Gastric Carcinoma Surgery: A Meta-Analysis.

Whether perioperative allogenic blood transfusion (ABT) has adverse effect on patients with gastric carcinoma (GC) surgery or not, that is controversial. Our study evaluated the association between ABT and some clinical outcomes of GC surgery patients. Data of relevant studies were based on PubMed, EMBASE, and the Cochrane Library search. The relative risk (RR) of 5-year survival rates, tumor recurrence, and postoperative complications were performed; subgroup analyses included district, transfusion rates, age, participants, sex, and tumor stage. The study was approved by the ethics committee of the First People's Hospital of Shunde. In total, 9189 participants from 16 studies were included in the meta-analysis. The 5-year survival rate was decreased for the GC patients with ABT (RR = 0.74, 95% confidence interval [CI] = 0.69-0.79), the risk of tumor recurrence was significantly higher for ABT patients (RR = 1.82, 95% CI = 1.32-2.51), and postoperative complications increased in ABT patients (RR = 1.36, 95% CI = 1.02-1.81), respectively; in subgroup analyses, 5-year survival rates were not associated with the transfusion rates (χ2 = 0.37, P = 0.54). Transfusion for patients undergoing GC surgery, even low transfusion rates, would reduce the 5-year survival rates, and elevated the risk of tumor recurrence and postoperative complication.

Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance.

Twist1 is a highly conserved basic helix-loophelix transcription factor, and has been shown to play an important role in carcinogenesis of many tumors including colorectal cancer (CRC). Here we aimed to investigate the role of Twist1 in the clinical significance and chemoresistance in CRC. In this study, we examined the correlation between Twist1 expression and clinicopathological characteristics using immunohistochemistry in patients with CRC. The molecular mechanisms of Twist1 expression and its effects on chemosensitivity to 5-Fluorouracil and oxaliplatin were also explored by MTT assay, colony forming assay, flow cytometry assay. The results indicate that Twist1 is overexpressed in cancer tissue, and its positive expression are related to histological grade (P=0.004), T-stage (P=0.033), N-stage (P=0.000), M-stage (P=0.040), TNM stage (P=0.002) and recurrence (P=0.023). Moreover, positive Twist1 expression is correlated with poor overall survival in CRC patients (P<0.0001), and is a significant independent prognostic indicator. In addition, we show that knockdown of Twist1 inhibits proliferation, and increased the percentage of apoptotic cells of CRC cell lines. Our findings suggest that Twist1 promotes proliferation and chemoresistance of CRC cells. Twist1 may be a potential prognostic marker and a molecular target for therapies.

Biphasic Regulation of Lipid Metabolism: A Meta-Analysis of Icodextrin in Peritoneal Dialysis.

OBJECTIVES: The objective of this systematic meta-analysis was to study the impact of icodextrin (ICO) on lipid profiles. METHODS: MEDLINE, PubMed, Embase, Chinese Biomedical Literature, and the Cochrane Library and Reference lists were searched (last search September 2014) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Searches identified 13 eligible trials with a total of 850 patients. The differentials of total cholesterol (TC) and free fatty acid (FFA) in the ICO group were greater than those in the GLU group. Metaregression analysis showed that TC levels positively correlated with its baseline levels. In the subgroup of patients with dialysis duration more than 6 months, TC and TG in the ICO group were less. In pooled data from cross-sectional studies, differential of TG in the ICO group was less. In the subgroup of patients with diabetes (Martikainen et al., 2005, Sniderman et al., 2014, and Takatori et al., 2011), differential of high-density lipoprotein cholesterol (HDL-C) in the ICO group was less. There was no significant effect on low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), or lipoprotein(a). CONCLUSIONS: ICO may be beneficial to lipid metabolism, especially for its biphasic regulation of plasma TC levels.

Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.