Knockdown of EIF3H inhibits the development and progression of pancreatic cancer by regulating cell proliferation and apoptosis in vitro.

Nowadays, pancreatic cancer has been recognized as one of the most fatal malignancies worldwide, the molecular mechanism of which is still not fully understood. In this study, we aimed to uncover the fundamental functions of the eukaryotic translation initiation factor 3H subunit (EIF3H) in the development and progression of pancreatic cancer. Firstly, the results of immunohistochemical (IHC) staining revealed that EIF3H was highly expressed in pancreatic cancer. Moreover, lentiviruses were used to deliver shRNAs into pancreatic cancer cells for silencing EIF3H. Furthermore, the loss-of-function assays demonstrated that knockdown of EIF3H could inhibit the progression of pancreatic cancer cells by reducing proliferation capacity, promoting apoptosis, arresting cell cycle in G2 and suppressing cell migration. In summary, EIF3H may play a critical role in the development and progression of pancreatic cancer, which possesses the potential to act as a therapeutic target for pancreatic cancer treatment.

Long noncoding RNA CCAL promotes gastric cancer cell proliferation and migration in a Myc dependent way.

AIMS: Long non-coding RNAs (lncRNAs) play key roles in cancers, yet their potential molecular mechanisms are not well understood. The objective of this study is to examine the expression, biological functions and mechanism of lncRNA CCAL in gastric cancer (GC). METHODS: MTT and Colony formation assay were used to detect cell proliferation and the colony formation ability of gastric cancer cells. Wound healing, Migration, and invasion assay were respectively used to explore the migration, and invasion in gastric cancer cell lines. Real-time polymerase chain reaction (RT-PCR) was performed to determine the expression level of CCAL. Western Blot was used to determine the expression of related proteins. RESULTS: In the present study, we found that CCAL was upregulated in gastric cancer cell lines. Patients whose tumors had high CCAL expression had a shorter overall survival than patients whose tumors had low CCAL expression. Overexpression CCAL promoted the proliferation, migration and invasion of GC by regulating the expression of myc. CONCLUSION: The present study reveals that CCAL is an oncogenic lncRNA that promotes the tumorigenesis and progression of GC.

Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer.

Long non-coding RNAs (lncRNAs) are widely transcribed in the genome, but their expression profile and roles in colorectal cancer are not well understood. The aim of this study was to investigate the long non-coding RNA expression profile in colorectal cancer and look for potential diagnostic biomarkers of colorectal cancer. Long non-coding RNA microarray was applied to investigate the global long non-coding RNA expression profile in colorectal cancer. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using standard enrichment computational methods. The expression levels of selected long non-coding RNAs were validated by quantitative reverse transcription polymerase chain reaction. The relationship between long non-coding RNA expression levels and clinicopathological characteristics of colorectal cancer patients was assessed. Coexpression analyses were carried out to find the coexpressed genes of differentially expressed long non-coding RNAs, followed by gene ontology analysis to predict the possible role of the selected long non-coding RNAs in colorectal carcinogenesis. In this study, a total of 1596 long non-coding RNA transcripts and 1866 messenger RNA transcripts were dysregulated in tumor tissues compared with paired normal tissues. The top upregulated long non-coding RNAs in tumor tissues were CCAT1, UCA1, RP5-881L22.5, NOS2P3, and BC005081 and the top downregulated long non-coding RNAs were AK055386, AC078941.1, RP4-800J21.3, RP11-628E19.3, and RP11-384P7.7. Long non-coding RNA UCA1 was significantly upregulated in colon cancer, and AK055386 was significantly downregulated in tumor with dimension <5 cm. Functional prediction analyses showed that both the long non-coding RNAs coexpress with cell cycle related messenger RNAs. The current long non-coding RNA study provided novel insights into expression profile in colorectal cancer and predicted the potential roles of long non-coding RNAs in colorectal carcinogenesis. Among the dysregulated long non-coding RNAs, UCA1 was found to be associated with anatomic site, and AK055386 was found associated with tumor size. Further functional investigations into the molecular mechanisms are warranted to clarify the role of long non-coding RNA in colorectal carcinogenesis.

A potential anatomic subtype of short bowel syndrome: a matched case-control study.

BACKGROUND: Fundamental researches suggest that ileum presents greater adaptive potential than the jejunum. However, few studies estimate the association between ileum and adaptive potential in human. To discover the association, we conducted this matched case-control study. METHODS: A 1:2 pair-matched, case-control study was conducted from January 1, 2001 to January 1, 2015 in Intestinal Rehabilition and Transplant Center. The case group was ileum predominated (IP) group and the control group was jejunum predominated (JP) group. Demographic data, medical history and progression of each patient were collected. RESULTS: There were 24 IP cases and 48 JP controls in this study. The cumulative probabilities of parenteral nutrition (PN) weaning in IP group were higher than that in JP group. The Bristol stool scale scores of IP group were lower than that of JP group at third month. The Cox proportional hazards regression model confirmed that IP had a higher odds of PN weaning (OR = 2.69; 95 % CI: 1.27, 5.70, p = 0.01) as compared with JP group. The conditional logistic regression with 1:2 matching also confirmed IP group had a higher odds (OR = 4.84; 95 % CI: 2.02, 11.56, p <0.01). CONCLUSIONS: Our results indicated that ileum presents greater adaptive potential than the jejunum in nutrition and fluid absorption. And a potential anatomic subtype of short bowel syndrome was proposed. Further research need to be conducted to more fully understand the adaptive potential of ileum besides nutrition and fluid absorption.

Tremella fuciformis polysaccharides induce ferroptosis in Epstein-Barr virus-associated gastric cancer by inactivating NRF2/HO-1 signaling.

Approximately 10% of gastric cancers are associated with Epstein-Barr virus (EBV). Tremella fuciformis polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory effects in different diseases. However, whether TFP improves EBV-associated gastric cancer (EBVaGC) has never been explored. The effects of TFP on EBV-infected GC cell viability were determined using a CCK-8 assay and flow cytometry. Western blotting and RT-qPCR were performed to explore the expression of ferroptosis-related proteins. The CCK-8 assay showed that TFP decreased EBV-infected GC cell viability in a dose- and time-dependent manner. Flow cytometry assays indicated that TFP significantly induced EBV-infected GC cell death. TFP also reduced the migratory capacity of EBV-infected GC cells. Furthermore, treatment with TFP significantly increased the mRNA levels of PTGS2 and Chac1 in EBV-infected GC cells. Western blot assays indicated that TFP suppressed the expression of NRF2, HO-1, GPX4 and xCT in EBV-infected GC cells. More importantly, overexpression of NRF2 could obviously rescue TFP-induced downregulation of GPX4 and xCT in EBV-infected GC cells. In summary, we showed novel data that TFP induced ferroptosis in EBV-infected GC cells by inhibiting NRF2/HO-1 signaling. The current findings may shed light on the potential clinical application of TFP in the treatment of EBVaGC.

Long noncoding RNA (lncRNA) HOTAIR: Pathogenic roles and therapeutic opportunities in gastric cancer.

Gastric cancer is one of the first malignant cancers in the world and a large number of people die every year due to this disease. Many genetic and epigenetic risk factors have been identified that play a major role in gastric cancer. HOTAIR is an effective epigenetic agent known as long noncoding RNA (lncRNA). HOTAIR has been described to have biological functions in biochemical and cellular processes through interactions with many factors, leading to genomic stability, proliferation, survival, invasion, migration, metastasis, and drug resistance. In the present article, we reviewed the prognostic value of the molecular mechanisms underlying the HOTAIR regulation and its function in the development of Gastric Cancer, whereas elucidation of HOTAIR-protein and HOTAIR-DNA interactions can be helpful in the identification of cancer processes, leading to the development of potential therapeutic strategies.

Overexpression of NAC1 confers drug resistance via HOXA9 in colorectal carcinoma cells.

Colorectal carcinoma (CRC) is one of the most common types of malignancy worldwide. Recently, neoadjuvant chemotherapy has become an important treatment strategy for CRC. However, treatment frequently fails due to the development of chemoresistance, which is a major obstacle for positive prognosis. However, the underlying mechanisms of chemoresistance remain unclear. The present study assessed the functions of nucleus accumbens­associated protein 1 (NAC1), an important transcriptional regulator, in CRC progression. Reverse transcription­quantitative polymerase chain reaction, western blot analysis and immunohistochemistry were performed to detect the expression levels of NAC1. It was identified that NAC1 was significantly overexpressed in CRC compared with non­tumorous tissues, indicating an oncogenic role. Following this, gain and loss of function analyses were performed in vitro to further investigate the function of NAC1. Cell viability and caspase­3/7 activity assays were used to assess chemotherapy­induced apoptosis. These results indicated that overexpression of NAC1 in CRC cells increased resistance to chemotherapy and inhibited apoptosis. Additionally, RNA interference­mediated knockdown of NAC1 restored the chemosensitivity of CRC cells. Furthermore, mechanistic investigation revealed that NAC1 increased drug resistance via inducing homeobox A9 (HOXA9) expression, and that knockdown of HOXA9 abrogated NAC1­induced drug resistance. In conclusion, the results of the present study demonstrated that NAC1 may be a critical factor in the develo-pment of chemoresistance, offering a potential novel target for the treatment of CRC.

LINC00052 Promotes Gastric Cancer Cell Proliferation and Metastasis via Activating the Wnt/ß-Catenin Signaling Pathway.

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. The etiology of GC is complex, and much more attention should be paid to genetic factors. In this study, we explored the role and function of LINC00052 in GC. We applied qRT-PCR and Northern blot to detect the expression of LINC00052 and found it was highly expressed during GC. We also investigated the effects of LINC00052 on tumor prognosis and progression and found that LINC00052 indicated poor prognosis and tumor progression. By performing MTT, colony formation, and Transwell assays, we found that LINC00052 promoted MGC-803 cell proliferation and metastasis. Pull-down and RIP assays showed that LINC00052 could interact with ß-catenin and methyltransferase SMYD2, and immunoprecipitation detection showed that LINC00052 promoted ß-catenin methylation to maintain its stability, so as to activate the Wnt/ß-catenin pathway. Furthermore, XAV939 (inhibitor of ß-catenin) was used to treat MGC-803 cells, and we found that LINC00052 promoted proliferation and metastasis, possibly by activation of the Wnt/ß-catenin pathway. In conclusion, our research demonstrated a carcinogenic role for LINC000052 in GC, which may represent a new approach for the prevention and therapy of this cancer.

Risk factors for central venous catheter-related bloodstream infections after gastrointestinal surgery.

We conducted this prospective study to evaluate the incidence of, major risk factors for, and causative pathogens of catheter-related bloodstream infection (CRBSI) related to central venous catheters (CVCs) in patients undergoing gastrointestinal surgery. The overall CRBSI rate was 8.0% (38/477), equaling 5.6 CRBSIs per 1,000 catheter days. CVC duration, emergency surgery, and male sex were risk factors for CRBSI. The most common organisms were coagulase-negative staphylococci, followed Enterobacteriaceae and Candida spp.

The roles of APOBEC3B in gastric cancer.

Gastric cancer was the third cause of death in China. In this study, we found that the APOBEC3 (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3) expression was higher in gastric cancer tissues than that in normal tissues and confirmed APOBEC3B expression was correlated with the unfavorable prognosis of the patients with gastric cancer. Furthermore, APOBEC3B expression was associated with gender, tumor size, histological grade, T stage, and TNM staging of the patients with gastric cancer. Down-regulation of APOBEC3B expression in MNK28 cells could enhance the cytotoxicity of PDCD2. No editing took place in PDCD2 positive MKN28 cells with APOBEC3B shRNA. These results indicated that loss of function of PDCD2 may be partly caused by APOBEC3B-induced extensive mutagenesis.

Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

Interventional therapy of malignant obstructive jaundice.

OBJECTIVE: To assess the short-term results of interventional therapy for malignant obstructive jaundice. METHODS: In 82 patients with malignant obstructive jaundice, hepatocellular carcinoma was detected in 10 patients, carcinoma of gallbladder in 14, hilar biliary carcinoma in 22, pancreatic carcinoma in 20, and hilar metastatic carcinoma in 16. Percutaneous transhepatic biliary internal and/or external drainage (PTBIED) was performed in 61 patients and percutaneous transhepatic insertion of biliary stent (PTIBS) in 21. RESULTS: The level of total serum bilirubin (TSB) was reduced in 71 patients and less markedly in others. The level of TSB of the 61 patients was reduced from 450.12+/-113.51 micromol/L before operation to 240.25+/-107.81 micromol/L and 90.91+/-101.72 micromol/L 1 and 2 weeks after operation respectively. The TSB level of the 21 patients was reduced from 410.53+/-98.13 micromol/L to 270.23+/-115.64 micromol/L and 105.43+/-97.85 micromol/L 1 and 2 weeks after operation, respectively. No significant difference was found in the effect between PTBIED and PTIBS. Short-term complications developed in 33 patients. Seven patients died 30 days after operation. CONCLUSION: Interventional therapy may be simple, safe and effective in the treatment of malignant obstructive jaundice.

Prognostic significance of plasma chemerin levels in patients with gastric cancer.

Chemerin is a novel adipokine, which is linked to adipogenesis and chemotaxis of the innate immune system. This study aimed to evaluate the relationship between preoperative plasma chemerin level and prognosis of gastric cancers. One hundred ninety-six patients and 196 age- and gender-matched healthy individuals were recruited. Fasting venous blood samples were collected 2 days prior to surgery for the gastric cancer patients and at the physical examination day for the healthy volunteers. Recorded clinicopathological information included invasion depth, lymph node metastasis, distant metastasis, peritoneal dissemination, tumor size and tumor-node metastasis stage. Plasma chemerin levels were determined using enzyme-linked immunosorbent assay. Plasma chemerin levels were statistically significantly in all patients than in healthy controls (53.1 ± 19.0 ng/mL vs. 31.3 ± 11.3 ng/mL; P < 0.001). And it was identified as an independent predictor for 5-year mortality [odds ratio (OR), 2.718; 95% confidence interval (CI), 1.201-4.229; P = 0.005) and adverse event (OR, 2.982; 95% CI, 1.223-4.879; P = 0.003) of gastric cancer, and had high area under receiver operating characteristic curve (AUC) for prediction of 5-year mortality (AUC, 0.808; 95% CI, 0.745-0.860) and adverse event (AUC, 0.787; 95% CI, 0.723-0.842). It also emerged as an independent predictor for overall survival (Hazard ratios, 1.788; 95% CI, 1.200-2.663; P = 0.002) and disease-free survival (Hazard ratios, 2.016; 95% CI, 1.312-3.125; P = 0.004). Thus, our results suggest that high plasma chemerin levels are associated with long-term poor prognosis and survival of gastric cancer as well as may play a role as prognostic biomarker in gastric cancer survival.