TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer.

PURPOSE: This study aims to evaluate the value of tissue inhibitors of MMPs-2 (TIMP-2) to indicate 5-Fluorouracil (5-Fu) resistance status in colorectal cancer. METHODS: The 5-Fu resistance of colorectal cancer cell lines was detected using Cell-Counting Kit-8 (CCK-8) and calculated using IC50. Enzyme-linked immunosorbent assay (ELISA) and real time-quantitative polymerase chain reaction (RT-qPCR) were used to detect TIMP-2 expression level in the culture supernatant and serum. Twenty-two colorectal cancer patients' TIMP-2 levels and clinical characteristics were analyzed before and after chemotherapy. Additionally, the patient-derived xenograft (PDX) model of 5-Fu resistance was used to evaluate the feasibility of TIMP-2 as a predictive biomarker of 5-Fu resistance. RESULTS: Our experimental results display that TIMP-2 expression is elevated in colorectal cancer drug-resistant cell lines, and its expression level is closely related to 5-Fu resistance. Moreover, TIMP-2 in colorectal cancer patient serum undergoing 5-Fu-based chemotherapy could indicate their drug resistance status, and its efficacy is higher than CEA and CA19-9. Finally, PDX model animal experiments reveal that TIMP-2 can detect 5-Fu resistance in colorectal cancer earlier than tumor volume. CONCLUSION: TIMP-2 is a good indicator of 5-Fu resistance in colorectal cancer. Monitoring the serum TIMP-2 level can help the clinician identify 5-Fu resistance in colorectal cancer patients earlier during chemotherapy.

CircRNA_0043691 sponges miR-873-3p to promote metastasis of gastric cancer.

Circular RNAs (circRNAs) are a class of novel RNAs, and aberrant expression of circRNAs has been implicated in human diseases, including gastric cancer (GC). This study aimed to identify the mechanism of circRNA_0043691 in regulating the progression of GC. GSE141977 was downloaded from Gene Expression Omibus ( http://www.ncbi.nlm.nih.gov/geo/ ). Differentially expressed circRNAs were obtained by R software. The expression levels of circRNA_0043691 in GC tissue and normal tissue were identified by quantitative real-time polymerase chain reaction (qRT-PCR). Knockdown of circRNA_0043691 was then constructed and verified by qRT-PCR. Cell viability, migration, and invasion capacity were determined by Cell Counting Kit-8 assay, Transwell migration, and invasion, respectively. Next, knockdown of miR-873-3p was constructed and co-cultured with circRNA_0043691 knockdown to identify whether knockdown of miR-873-3p could attenuate the circRNA_0043691 knockdown on GC cells proliferation, migration, and invasion. The relationship between miR-873-3p and circRNA_0043691 or GART was predicted by bioinformatics tools and verified by dual-luciferase reporter. A total of 211 circRNAs were significantly differentially expressed, including 143 remarkably downregulated circRNAs and 68 significantly upregulated circRNAs. CircRNA_0043691 was upregulated in GC tissue. Knockdown of circRNA_0043691 decreased cell viability, migration, and invasion in GC cells. CircRNA_0043691 has potential putative binding sites with miR-873-3p. Moreover, CircRNA_0043691 positively regulated GART expression by sponging miR-873-3p. Furthermore, knockdown of miR-591 could partially attenuate the si-circRNA_0043691 on the GART expression. GART was upregulated in GC tissue and knockdown of GART could inhibit GC cells proliferation and invasion. Knockdown of circRNA_0043691 delayed the progression of GC via modulating the miR-873-3p-GART axis.

Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

A strangulated internal hernia beneath the left external iliac artery after radical hysterectomy with laparoscopic pelvic lymphadenectomy: a case report and literature review.

BACKGROUND: Ileum obstruction due to internal hernia beneath external iliac artery after pelvic lymph node dissection (PLND) is extremely rare. We reported a case of acute strangulated internal hernia between the left external iliac artery and psoas major as late complication of laparoscopic hysterectomy with pelvic lymphadenectomy. CASE PRESENTATION: A 46-year-old woman, who with histories of laparoscopic hysterectomy, bilateral salpingo-oophorectomy and PLND 9 years ago for the cervical malignant tumor, open appendectomy 18 years ago, visited our hospital complaining of aggravated left lower abdominal pain, bloating, nausea and vomiting from few hours ago. Left abdomen distention, tympanitic with rebound tenderness and muscular tension was detected during physical examinations. Accompanying with elevated inflammatory markers and mild intestinal dilatation showed in lab results and contrast-enhanced computed tomography (CT) respectively. After carefully reading the CT images, a small bowel was found between the left external iliac artery (EIA) and the psoas major, combined with the patient's surgical history, we suspected it might be internal hernia. Eventually, the emergency laparoscopic laparotomy confirmed our conjecture, the gap between the iliac vessels and the psoas major was closed with an absorbable suture, the patient was discharged on the fourth postoperative day. CONCLUSION: Primary closure of peritoneal fissue maybe an effective measure to potentially prevent internal hernia. The choice of surgical approach for pelvic tumors still needs further exploration but faster diagnosis and immediate laparotomy might promise a better prognosis.

Individualized treatment for gastric cancer with rib metastasis: A case report.

BACKGROUND: Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even less common. The clinical prognosis of GC with bone metastasis is poor given the lack of an effective treatment. CASE SUMMARY: A 70 year old man was referred to Shaoxing People's Hospital with left chest pain and slight dyspnea. Chest computed tomography (CT) revealed a metastatic lesion in the left 3rd rib. Esophagogastroduodenoscopy revealed several ulcers in the angle and antrum of the stomach, and tumor biomarkers including CEA and CA-199 were clearly increased. In addition, lymph node metastasis in the lesser curvature of the stomach was identified by positron emission tomography/CT scanning. Further pathological examination confirmed metastatic adenocarcinoma in the rib and medium-low differentiated adenocarcinoma in the gastric space. The patient had GC with rib metastasis, and was clinically staged as T3NxM1 (IVB). Based on multidisciplinary team opinions, the patient received five courses of chemotherapy (CAPOX plus aptinib), and then underwent rib resection and laparoscopic radical distal gastrectomy. The patient started four courses of chemotherapy after surgery, and then capecitabine and aptinib were administered orally for 3 mo. Follow-up was performed on an outpatient basis using abdominal/chest CT and tumor biomarkers. The patient exhibited an overall survival greater than 2 years, and the disease-free survival was approximately 18 mo. His adverse events were tolerable. CONCLUSION: The incidence of GC with rib metastases is extremely low, and patients can obtain more benefits from individualized treatment formulated by multidisciplinary team. Chemotherapy plus surgery might represent an alternative option for GC with rib metastasis.

Laparoscopic Versus Open Major Hepatectomy for Hepatocellular Carcinoma: A Meta-Analysis.

BACKGROUND: Although large series of laparoscopic resections for hepatocellular carcinoma (HCC) were published, reports of laparoscopic major hepatectomy (LMH) are still limited in expert centers because LMH for HCC remains a challenging procedure requiring extensive experience in both laparoscopic and hepatic surgery. We performed a meta-analysis to assess the safety and efficacy of LMH and open major hepatectomy (OMH) for HCC. METHODS: A literature search was performed to identify studies comparing LMH with OMH for HCC. Postoperative morbidity, mortality, operative time, intraoperative blood loss, length of hospital stay, R0 rate, and long-term survival outcomes were analyzed. RESULTS: Eight studies with a total of 780 HCC patients were included for meta-analysis. The pooled data showed that LMH was associated with longer operative time [weighted mean differences (WMD)=81.04 min; 95% confidence interval (CI), 37.95~124.13; P<0.01], less blood loss (WMD=-117.14 mL; 95% CI, -170.35~-63.93; P<0.01), and shorter hospital stay (WMD=-3.41 d; 95% CI, -4.90~-1.92; P<0.01). Overall morbidity was significantly lower in the LMH group (odds ratio=0.45; 95% CI, 0.23~0.86; P=0.02), as were major complications (odds ratio=0.36; 95% CI, 0.18~0.73; P<0.01). However, there was no difference in margin negativity and long-term survival outcomes. CONCLUSIONS: LMH can be performed as safely and efficiently as OMH for HCC regarding both surgical and oncological outcomes. LMH is associated with less intraoperative blood loss and postoperative morbidity and may serve as a promising alternative to OMH for HCC patients.

Comparison of Delta-Shape Anastomosis and Extracorporeal Billroth I Anastomosis after Laparoscopic Distal Gastrectomy for Gastric Cancer: A Systematic Review with Meta-Analysis of Short-Term Outcomes.

OBJECTIVE: The aim of this systematic review and meta-analysis is to evaluate the safety and relative benefits of delta-shape anastomosis (DA) by comparing to conventional laparoscopy-assisted distal gastrectomy with Billroth I gastroduodenostomy (LADG BI). METHODS: Studies and relevant literature regarding DA versus LADG BI were searched in the electronic databases. Operation time, postoperative complications, estimated blood loss, number of retrieved lymph nodes, time to first flatus, time to oral intake, length of postoperative hospitalization in DA and LADG BI were pooled and compared using meta-analysis. Weighted mean differences (WMDs) and odds ratios (ORs) were calculated with 95% confidence intervals (CIs) to evaluate the effect of DA. RESULTS: Eight studies of 1739 patients were included in the meta-analysis. Compared with LADG BI, DA had shorter postoperative hospitalization (WMD = -0.47, 95%CI: -0.69 to -0.25, P<0.01), less blood loss (WMD = - 25.90, 95%CI: -43.11 to -8.70, P<0.01), shorter time to oral intake (WMD = -0.25, 95%CI: -0.49 to -0.01, P = 0.04), and more retrieved lymph nodes (WMD = 1.36, 95%CI: 0.30 to 2.43, P = 0.01). Operation time (WMD = -0.07, 95%CI -15.58 to 15.43, P = 0.99), overall postoperative complication rate (OR = 1.05, 95%CI: 0.74 to 1.49, P = 0.63), surgical complication rate (OR = 1.02, 95%CI: 0.70 to 1.49, P = 0.90), nonsurgical complication rate (OR = 1.21, 95%CI: 0.54 to 2.72, P = 0.64), leakage rate (OR = 2.54, 95%CI: 0.92 to 7.01, P = 0.07), stricture rate (OR = 0.36, 95%CI: 0.09 to 1.44, P = 0.15), wound complication rate (OR = 0.71, 95%CI: 0.33 to 1.55, P = 0.39), time to first flatus (WMD = -0.10, 95%CI: -0.27 to 0.07, P = 0.26), and proximal surgical margin (WMD = -0.25, 95%CI: -1.14 to 0.65, P = 0.59) was not statistically different. CONCLUSION: Compared with LADG BI, DA is a safe and feasible procedure, with significantly reduced blood loss, time to oral intake, and postoperative hospitalization.

Prognostic value of microRNA-21 in pancreatic ductal adenocarcinoma: a meta-analysis.

BACKGROUND: Recently, microRNA-21 (miR-21) has been reported to be associated with prognosis of pancreatic ductal adenocarcinoma (PDAC). The present studies aimed to evaluate the prognostic value of miR-21 for PDAC with meta-analysis. METHODS: A systematic search in the PubMed and other databases was conducted to identify eligible studies. The pooled hazard ratios (HRs) with 95% confidence interval (CI) were calculated. The meta-analysis was conducted using the STATA 12.0 software. RESULTS: A total of 12 articles (13 studies) which included 963 cases were selected for the meta-analysis. Elevated miR-21 expression was significantly predictive of poor overall survival (HR = 2.05, 95% CI 1.71-2.46, P < 0.001). In the subgroup analyses, similar results were observed in Asian (HR = 2.09, 95% CI 1.62-2.71, P < 0.001) and Caucasian (HR = 2.36, 95% CI 1.53-3.65, P < 0.001); in tissue sample (HR = 2.14, 95% CI 1.73-2.65, P < 0.001) and serum sample (HR = 1.84, 95% CI 1.30-2.60, P = 0.001); with quantitative real-time polymerase chain reaction assay method (HR = 2.31, 95% CI 1.86-2.86, P < 0.001); and in patients receiving adjuvant chemotherapy (HR = 2.37, 95% CI 1.88-3.00, P < 0.001). The association between miR-21 expression level and lymph node metastasis was statistically significant (OR = 1.45, 95% CI 1.02-2.06, P = 0.038). However, no significant relationship between miR-21 expression level and sex or vascular invasion or neural infiltration was observed (P > 0.05). CONCLUSIONS: Our meta-analysis indicated that elevated miR-21 expression level can predict poor prognosis in patients with PDAC.

Gas chromatographic-mass spectrometric characterization of all acyclic C5-C7 alkenes from fluid catalytic cracked gasoline using polydimethylsiloxane and squalane stationary phases.

Published retention indices of acyclic alkenes C5-C7 on squalane and polydimethylsiloxane as stationary phases were investigated, and reliable retention indices of alkenes from various sources were converted to separation systems used in a laboratory. Retention indices measured on available authentic commercial alkenes and on alkenic fraction of gasoline, published retention indices as well as means of GC-MS were used for verification of calculated retention indices. Retention of some gas chromatographic unseparated isomer pairs was obtained by mass spectrometric deconvolution using a specific single-ion monitoring. On the basis of these retention data, C5-C7 alkenes were identified and analyzed in the gasoline from fluid catalytic cracking. In the gasoline all 59 acyclic C5-C7 isomeric alkenes were determined at significantly different concentration levels.