MBNL1­AS1 attenuates tumor cell proliferation by regulating the miR­29c­3p/BVES signal in colorectal cancer.

Dysregulation of long non­coding RNAs (lncRNAs) is involved in the development of colorectal cancer (CRC). In the present study, the identification of muscle blind like splicing regulator 1 antisense RNA 1 (MBNL1­AS1) lncRNA was reported. Firstly, Cell Counting Kit­8, EdU and colony formation assays were uesed to explore the role of MBNL1­AS1 in regulating the proliferation of CRC cells. According to TCGA database, it was found that MBNL1­AS1 was correlated with microRNA (miR)­29c­3p and blood vessel epicardial substance (BVES) expression in CRC cells. Then, the regulation among MBNL1­AS1, miR­29C­3P and BVES was detected by dual luciferase reporter assay and the function of MBNL1­AS1/miR­29C­3P/BVES axis was explored by rescue assay. The results demonstrated that MBNL1­AS1 expression was decreased in CRC and was associated with the size of tumors derived from patients with CRC. Functionally, the upregulation of MBNL1­AS1 suppressed CRC cell proliferation in vitro and inhibited tumor growth in vivo, while knockdown of MBNL1­AS1 expression caused the opposite effects. MBNL1­AS1 expression correlated with BVES expression in CRC tissues and MBNL1­AS1 enhanced the stability of BVES mRNA by functioning as a competing endogenous RNA to sponge miR­29c­3p; the latter directly targeted MBNL1­AS1 and BVES mRNA 3'UTR. Collectively, the results indicated that MBNL1­AS1 suppressed CRC cell proliferation by regulating miR­29c­3p/BVES signaling, suggesting that the MBNL1­AS1/miR­29c­3p/BVES axis may be a potential therapeutic target for CRC.

SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis.

Purpose: Silent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD). Materials and methods: Human immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism. Results: SGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD. Conclusion: The SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC.

Total versus inhaled intravenous anesthesia methods for prognosis of patients with lung, breast, or esophageal cancer: A cohort study.

Objective: To explore the influences of total intravenous anesthesia (TIVA) and inhaled-intravenous anesthesia on the prognosis of patients with lung, breast, or esophageal cancer. Methods: In this retrospective cohort study, patients with lung, breast, or esophageal cancer who underwent surgical treatments at Beijing Shijitan Hospital between January 2010 and December 2019 were included. The patients were categorized into the TIVA group and inhaled-intravenous anesthesia group, according to the anesthesia methods used for the patients for surgery of the primary cancer. The primary outcome of this study included overall survival (OS) and recurrence/metastasis. Results: Totally, 336 patients were included in this study, 119 in the TIVA group and 217 in the inhaled-intravenous anesthesia group. The OS of patients in the TIVA group was higher than in the inhaled-intravenous anesthesia group (P = 0.042). There were no significant differences in the recurrence/metastasis-free survival between the two groups (P = 0.296). Inhaled-intravenous anesthesia (HR = 1.88, 95%CI: 1.15-3.07, P = 0.012), stage III cancer (HR = 5.88, 95%CI: 2.57-13.43, P < 0.001), and stage IV cancer (HR = 22.60, 95%CI: 8.97-56.95, P < 0.001) were independently associated with recurrence/ metastasis. Comorbidities (HR = 1.75, 95%CI: 1.05-2.92, P = 0.033), the use of ephedrine, noradrenaline or phenylephrine during surgery (HR = 2.12, 95%CI: 1.11-4.06, P = 0.024), stage II cancer (HR = 3.24, 95%CI: 1.08-9.68, P = 0.035), stage III cancer (HR = 7.60, 95%CI: 2.64-21.86, P < 0.001), and stage IV cancer (HR = 26.61, 95%CI: 8.57-82.64, P < 0.001) were independently associated with OS. Conclusion: In patients with breast, lung, or esophageal cancer, TIVA is preferable than inhaled-intravenous anesthesia group for longer OS,, but TIVA was not associated with the recurrence/metastasis-free survival of patients.

CDX2 as a Predictive Biomarker Involved in Immunotherapy Response Suppresses Metastasis through EMT in Colorectal Cancer.

Background: Studies have confirmed that Caudal Type Homeobox 2 (CDX2) plays a tumor suppressor role in colorectal cancer (CRC) and as a prognostic and predictive marker for colorectal cancer. The epithelial to mesenchymal transition (EMT) is a transdifferentiation process, providing migratory and invasive properties to cancer cells during tumor progression. However, the role of CDX2 during the activation of EMT in CRC maintains controversial. Aim: To investigate whether CDX2 is associated with EMT in CRC. Methods: Forty-six CRC patients were included in the study. Expressions of CDX2, E-cadherin, and N-cadherin in all CRC patients were detected by IHC. ROC assays were applied to detect cut-off points for IHC scores to distinguish high and low expressions of CDX2 in 46 CRC samples. The prognostic value of CDX2 was statistically analyzed. MTT, Western blot, invasion, and migration assays in vitro were employed to explore the function of CDX2. Results: We observed that high expressions of CDX2 and E-cadherin as well as low expressions of N-cadherin were significantly correlated with favorable prognosis. The levels of CDX2 protein exhibited a positive associated with E-cadherin while negative correlation with N-cadherin. Then, the low expression of CDX2 and high expression of CA199 in combination are positively related with poor prognosis. Overexpression of CDX2 reduced expression of MMP-2 and diminished cell proliferation, invasion, and migration, while knockdown CDX2 enhanced MMP-2 expression and increased cell proliferation, invasion, and migration in HCT-116 cells. CDX2 was correlated with expression of EMT markers. Overexpression of CDX2 suppressed the EMT markers indicating that CDX2 suppresses CRC cell viability, invasion, and metastasis through inhibiting EMT. Finally, we found that the expression of CDX2 was negatively associated with Th1 cells, macrophages, Th2 cells, cytotoxic cells, T cells, and T helper cells. Conclusions: These results indicated CDX2 as prognostic biomarkers involved in immunotherapy response for CRC. CDX2 loss promotes metastasis in CRC through a CDX2-dependent mechanism.

Application of Intelligent Detection of Neural Signal in Depth Evaluation of Obstetrics and Gynecology Anesthesia.

In order to evaluate the application of EEG intelligent detection in gynecological anesthesia depth, the application of ANGEL-6000 EEG depth monitor in laparoscopic gynecological anesthesia was proposed. This method was applied to 60 patients who underwent elective laparoscopic gynecological surgery in our hospital from February to August 2016. Inclusion criteria were ASA i ∼ ii; the average age was (37.8 ± 6.6) years from 20 to 50 years old; the average body weight was (51.53 ± 3.87) kg; conscious and no communication barriers; and patients without instrument ventilation. The patients were divided into observation group and control group according to the random number table method, with 30 patients in each group. The two groups were anesthetized with the same anesthetic drugs, and their consciousness index was monitored. IoC values were recorded before induction of anesthesia (T0), 5 min after intubation (T1), 5 min after operation (T2), intraoperative exploration (T3), at the end of operation (T4), 1 min before extubation (T5), and 5 min after extubation (T6). The dosage of anesthetic drugs, operation time, extubation time, and operation time of the two groups were statistically analyzed. Compared with the operation time of patients in the two groups, the extubation time, awake time, and time out of the operating room of patients in the control group were longer than the observation group. The IoC values of patients in the control group at T0 and T6 time points were lower than those in the observation group at each time point from T1 to T5. Comparison of perioperative dose of remifentanil and atracurium between the two groups was performed. The control group used more propofol dose in perioperative period. The application of neuroelectric signal in laparoscopic gynecological surgery to detect changes in perioperative IoC value can well reflect the level of consciousness of patients and reflect the effect of perioperative stimulation at different time points on the EEG of patients in real time.

A Nomogram Model Involving Preoperative Fibrinogen and Prognostic Nutritional Index Score for Predicting Postoperative Outcome in Patients with Gastric Cancer.

BACKGROUND: Inflammation and nutrition play vital roles in the development of gastric cancer (GC). We combined the preoperative fibrinogen with prognostic nutritional index (PNI) to create a novel scoring system named as the fibrinogen and prognostic nutritional index (FPNI) score and establish a more effective model. PATIENTS AND METHODS: A total of 689 patients with gastric adenocarcinoma who underwent gastrectomy from January 2012 to December 2016 were reviewed. We measured correlations between FPNI score and clinicopathological variables and overall survival (OS). A nomogram predicting OS was constructed. Its predictive performance was verified using the concordance index, calibration curves, receiver operating characteristic curves, decision curve analysis and time-dependent receiver operating characteristic analysis. RESULTS: We observed that the FPNI score was an independent predictor of OS in patients with gastric cancer (P < 0.05). A high FPNI score was significantly related to older age at surgery, tumor size ≥4.6 cm, high ASA score, advanced TNM stage and poor outcome (both P < 0.05). And the FPNI score remained an independent indicator at various TNM stages (P < 0.05). Ultimately, the nomogram based on FPNI score, age, tumor size, histological grade and TNM stage showed a better predictive ability than TNM alone. CONCLUSION: The preoperative FPNI score is a novel, simple, and effective predictor of OS in patients with GC. Furthermore, the nomogram involving FPNI score will help clinicians to optimize individualized treatment plans.

A nomogram combining plasma fibrinogen and systemic immune­inflammation index predicts survival in patients with resectable gastric cancer.

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.

Intracellular Nampt impairs esophageal squamous cell carcinoma neo-adjuvant chemotherapy response independent of eNampt.

Nampt consists of iNampt and eNampt, might contribute to modulating obesity-related malignancies and impairing response to chemotherapy in a range of cancers. This study explored the role of Nampt and adiposity in the progression and response to neo-adjuvant chemotherapy of esophageal squamous cell carcinoma (ESCC). Patients with ESCC were treated with 2 cycles of neo-adjuvant chemotherapy, then evaluated for surgery. Tumor regression grading (TRG) and prognosis of these patients were collected. Anthropometry was well utilized. Serum eNampt was determined by enzyme-linked immunosorbent assay, iNampt expression in tissues were assessed by PCR, western blot and immunohistochemistry. eNampt in sera elevated significantly in these over-weight or obese patients, and was positively associated with body mass index (BMI), waist circumference, visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA) (P<0.05). iNampt expression in the mRNA and protein levels were up-regulated in ESCC compared to their adjacent non-tumor specimens (P<0.05). iNampt protein staining revealed mainly in the cytoplasm and nuclei, while it was not related to serum eNampt, BMI, waist circumference, VFA, SFA and TFA (P>0.05). Pre-treatment iNampt, BMI, SFA, TFA and age significantly correlated with neo-adjuvant chemotherapy response, and iNampt expression and age were independent predictors (P<0.05). Pre-treatment iNampt, ypT, ypN, ypTNM stage and TRG were associated with the survival of ESCCs, and ypN stage and TRG were independent prognostic factors (P<0.05). In conclusion, iNampt impaired ESCC response to neo-adjuvant chemotherapy independent of eNampt, targeting iNampt to increase ESCC response to neo-adjuvant chemotherapy would improve the prognosis of ESCCs.

Targeting ADAR1 suppresses progression and peritoneal metastasis of gastric cancer through Wnt / ß-catenin pathway.

Objective: Peritoneal metastasis frequently occurs in advanced gastric cancer, which is typically not eligible for radical surgery. Here, this study observed the function and regulatory mechanism of ADAR1 in peritoneal metastasis of gastric cancer. Methods: ADAR1, CALR and ß-catenin proteins were detected in normal mucosa, primary gastric cancer, metastatic lymph node and metastatic omentum tissues by immunohistochemistry, western blot, and immunofluorescence. After silencing ADAR1 by siADAR1, the effect and mechanism of ADAR1 on gastric cancer metastasis were observed in nude mouse models of gastric cancer with peritoneal metastasis as well as HGC-27 and AGS gastric cancer cells. Result: Our results showed that ADAR1 was significantly up-regulated in gastric cancer, metastatic lymph node and metastatic omentum tissues. Its up-regulation was significantly correlated to lymph node metastasis and peritoneal metastasis. Silencing ADAR1 significantly reduced the volume of peritoneal metastatic tumors and weakened oncogene CALR expression, Wnt / ß-catenin pathway and epithelial-mesenchymal transition (EMT) process in vivo. Furthermore, ADAR1 knockdown distinctly suppressed cell viability, colony formation and migration of HGC-27 and AGS cells and ameliorated the effects of Wnt pathway activator on tumor progression. The similar findings were investigated when treated with ADAR1 inhibitor 8-Azaadenosine. Conclusion: Collectively, this study identified a novel oncogenic function of ADAR1 in peritoneal metastasis of gastric cancer via Wnt / ß-catenin pathway. Hence, ADAR1 could be a novel marker and therapeutic target against gastric cancer metastasis.

Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway.

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly (P < 0.05); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly (P < 0.05) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly (P < 0.05); YAP and MMP9 mRNA expression increased significantly (P < 0.05) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

Intraoperative cell salvage for obstetrics: a prospective randomized controlled clinical trial.

BACKGROUND: The latest basic studies and clinical evidence have confirmed the safety and efficacy of intraoperative autologous blood cell transfusion in cardiac surgery and orthopaedics. However, in caesarean section, there are still concerns about the contamination of amniotic fluid and foetal components, and consequently the application of intraoperative autologous blood cell transfusion is not universal. Therefore, this study aimed to evaluate the clinical value of intraoperative autologous blood cell transfusion in obstetric surgery. METHODS: A prospective, randomized, controlled, feasibility study was performed in women undergoing caesarean section. One hundred sixteen participants were randomly assigned at a 1:1 ratio into either the intraoperative cell salvage group or the control group. Allogeneic blood cells were transfused into patients with haemoglobin concentrations < 80 g/dL in both the intraoperative cell salvage group and the control group. RESULTS: No significant differences were found between the two groups in age, weight, maternal parity, history of previous caesarean section, gestational weeks of delivery, etc. However, compared with the control group, patients in the intraoperative cell salvage group had a significantly lower amount of allogeneic blood cell transfusion, lower incidence of postoperative incision infection, delayed wound healing, perioperative allergy, adverse cardiovascular events, hypoproteinaemia and shorter hospital stay. CONCLUSION: The results of this study suggest that the use of autologous blood cell transfusion is safe and effective for patients with obstetric haemorrhage. TRIAL REGISTRATION: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (2016-XJS-003-01) as well as the 1964 Helsinki Declaration and its later amendments or other comparable ethical standards. The clinical trials were registered (ChiCTR-ICC-15,007,096) on September 28, 2015.

Muscular Tissue Oxygen Saturation and Posthysterectomy Nausea and Vomiting: The iMODIPONV Randomized Controlled Trial.

BACKGROUND: Suboptimal tissue perfusion and oxygenation during surgery may be responsible for postoperative nausea and vomiting in some patients. This trial tested the hypothesis that muscular tissue oxygen saturation-guided intraoperative care reduces postoperative nausea and vomiting. METHODS: This multicenter, pragmatic, patient- and assessor-blinded randomized controlled (1:1 ratio) trial was conducted from September 2018 to June 2019 at six teaching hospitals in four different cities in China. Nonsmoking women, 18 to 65 yr old, and having elective laparoscopic surgery involving hysterectomy (n = 800) were randomly assigned to receive either intraoperative muscular tissue oxygen saturation-guided care or usual care. The goal was to maintain muscular tissue oxygen saturation, measured at flank and on forearm, greater than baseline or 70%, whichever was higher. The primary outcome was 24-h postoperative nausea and vomiting. Secondary outcomes included nausea severity, quality of recovery, and 30-day morbidity and mortality. RESULTS: Of the 800 randomized patients (median age, 50 yr [range, 27 to 65]), 799 were assessed for the primary outcome. The below-goal muscular tissue oxygen saturation area under the curve was significantly smaller in patients receiving muscular tissue oxygen saturation-guided care (n = 400) than in those receiving usual care (n = 399; flank, 50 vs. 140% · min, P < 0.001; forearm, 53 vs. 245% · min, P < 0.001). The incidences of 24-h postoperative nausea and vomiting were 32% (127 of 400) in the muscular tissue oxygen saturation-guided care group and 36% (142 of 399) in the usual care group, which were not significantly different (risk ratio, 0.89; 95% CI, 0.73 to 1.08; P = 0.251). There were no significant between-group differences for secondary outcomes. No harm was observed throughout the study. CONCLUSIONS: In a relatively young and healthy female patient population, personalized, goal-directed, muscular tissue oxygen saturation-guided intraoperative care is effective in treating decreased muscular tissue oxygen saturation but does not reduce the incidence of 24-h posthysterectomy nausea and vomiting.

Perinatal changes in estradiol and Ang II concentrations in pregnant women with pulmonary arterial hypertension and their correlation.

Objective: This study aimed to analyze the perinatal changes of plasma estradiol (E2) and angiotensin II (Ang II) in pregnant women with pulmonary arterial hypertension before and after cesarean section. Methods: Depending on pulmonary arterial pressure, the subjects were divided into two groups, moderate group, and severe group. Plasma concentrations of E2 and Ang II were determined at different time points using electrochemiluminescence immunoassay and ELISA, respectively. The correlation between E2 and Ang II concentrations was analyzed. Results: Intragroup comparison indicated that E2 levels at different time points after surgery decreased in the two groups than before, with a greater reduction in the severe group. Besides, both groups showed a reduction in Ang II concentrations after surgery. As indicated by intragroup comparison, there was a significant difference at each time point in the two groups. The reduction in Ang II concentrations was more conspicuous at 48 h and 72 h after surgery (cesarean section) than before for the two groups. Moreover, E2 concentrations were correlated positively with AngII concentrations. Conclusion: Plasma concentrations of E2 and Ang II decreased after delivery. The plasma concentrations of E2 and Ang II were correlated with each other.

Effects of Sevoflurane Pretreatment on Myocardial Ischemia-Reperfusion Injury Through the Akt/Hypoxia-Inducible Factor 1-alpha (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway.

BACKGROUND The aim of this study was to investigate the effects of sevoflurane (SEV) on myocardial ischemia/reperfusion (I/R) injury in rats and its mechanism. MATERIAL AND METHODS Sixty male Sprague-Dawley rats were randomly divided into 3 groups: Sham group (n=20), I/R group (n=20) and I/R+SEV group (n=20). The I/R model was established by ligating and recanalizing the left anterior descending coronary artery (LAD). Triphenyl tetrazolium chloride (TTC) test and echocardiography (ECG) were used for analysis. Hematoxylin and eosin (H&E) staining was applied to detect the morphological changes. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was conducted to detect the apoptosis levels. The expression level of superoxide dismutase 2 (SOD2) was measured. Finally, the effect of SEV on the protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1alpha)/vascular endothelial growth factor (VEGF) signaling pathway was detected via western blotting. RESULTS SEV could significantly improve I/R-induced cardiac insufficiency, inhibit cardiac infarction, and as well as reduce the infarction area from 53.21±2.11% to 32.33±3.49% (P<0.05). Compared with rats in I/R group, the cardiac myofilament was better in alignment, degradation and necrosis were milder, and cell edema was notably reduced in the I/R+SEV group. Thus, SEV could significantly reverse the decreased expression of SOD2 caused by I/R and reduce oxidative stress in the heart (P<0.05). According to the western blotting results, SEV was capable of obviously activating the expressions of phosphorylated-Akt (p-Akt), HIF-1alpha, and VEGF. CONCLUSIONS SEV can significantly improve myocardial injury caused by I/R in rats, and its mechanism might be related to the activation of the Akt/HIF-1alpha/VEGF signaling pathway.

The role of propranolol as a radiosensitizer in gastric cancer treatment.

PURPOSE: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a ß-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. METHODS: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting. RESULTS: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups. CONCLUSION: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2.

Gastrointestinal stromal tumors: Fibrinogen levels are associated with prognosis of patients as blood-based biomarker.

Improved prediction of prognosis for primary gastrointestinal stromal tumors (GISTs) after curative resection is an important goal in clinical practice. Coagulation factor of fibrinogen may inform prognosis of tumor patients as blood-based biomarker. Here, we aimed to analyze the prognostic value of fibrinogen levels in patients with GIST and to explore potential threshold of fibrinogen on postoperative clinical outcome.A retrospective study was performed including data from 91 patients with newly diagnosed GISTs who underwent curative resection. Patients were followed-up for a median period of 2 years. Cox regression and competing risk analysis were applied to study the association between fibrinogen and risk of death or recurrence. Smoothing plot and threshold effect analysis were applied to learn the relationship further and explore potential threshold.High levels of fibrinogen are associated with decreased overall survival (OS) and recurrence free survival (RFS) in patients with GISTs. We discovered a nonlinear relationship between levels of fibrinogen and the risk of death or recurrence. Further, we detected a threshold for fibrinogen (3.7 g/L) on the prognosis of GISTs patients. When fibrinogen was above the inflection point, the increase in fibrinogen levels was strongly associated with increase in the risk of death or recurrence.Elevated fibrinogen can serve as an independent prognostic biomarker for a worse clinical outcome in GIST patients.

miR-135b-5p Promotes migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2.

The exact mechanisms of metastasis for pancreatic cancer remain to be uncovered. This study aimed to elucidate the potential functional mechanism of miR-135b-5p in migration, invasion and epithelial-to-mesenchymal transition (EMT) of pancreatic cancer cells. By real-time PCR and analysis of GEO database, we determined the up-regulated expression of miR-135b-5p in pancreatic cancer tissues and cell lines. Clinically, highly expressed miR-135b-5p was closely related to advanced TNM stage, more lymph node metastasis, more distant metastasis and worse overall survival (OS) and disease-free survival (DFS). Functionally, Transwell assays indicated that miR-135b-5p was a promoter for migration and invasion of pancreatic cancer cells. Additionally, immunohistochemistry staining and Western blot showed that highly expressed miR-135b-5p accelerated EMT process of pancreatic cancer cells. Furthermore, a series of experiments and rescue experiments revealed that Nuclear Receptor Subfamily 3 Group C Member 2 (NR3C2) was the target of miR-135b-5p in pancreatic cancer cells, mediating the promotion effects of miR-135b-5p on the tumor cells migration, invasion and EMT. In conclusion, miR-135b-5p, maybe a novel therapeutic target for pancreatic cancer, promoted migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2.