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.

Autophagy-mediating microRNAs in cancer chemoresistance.

Chemoresistance is a complex phenomenon responsible for failure in response to chemotherapy agents and more than 90% of deaths in cancer patients. MicroRNAs (miRNAs), as a subgroup of non-coding RNAs with lengths between 21 and 25 nucleotides, are involved in various cancer processes like chemoresistance via interacting with their target mRNAs and suppressing their expression. Autophagy is a greatly conserved procedure involving the lysosomal degradation of cytoplasmic contents and organelles to deal with environmental stresses like hypoxia and starvation. Autophagy contributes to response to chemotherapy agents: autophagy can act as a protective mechanism for mediating the resistance in response to chemotherapy or can induce autophagic cell death and mediate the sensitivity to chemotherapy. On the other hand, one of the processes targeted by microRNAs in the regulation of chemoresistance is autophagy. Hence, we studied the literatures on chemoresistance mechanisms, the miRNAs' role in cancer, and the miRNAs' role in chemoresistance by modulating autophagy. Graphical Abstract.

[A comparative study of laparoscopic-assisted and open distal gastrectomy for advanced gastric cancer].

OBJECTIVE: To evaluate the safety, feasibility and the long-term outcomes of laparoscopy-assisted gastrectomy (LAG) for advanced gastric cancer (AGC). METHODS: The clinical and follow-up data of 46 cases after LAG from June 2008 to December 2009 were analyzed, and compared with 85 cases after conventional open gastrectomy (OG) for advanced gastric cancer at the same period at our hospital. The surgical safety, postoperative recovery, complications, radical degree, survival rate were compared. RESULT: As compared with OG group, operation time was longer in LATG group ((274 ± 78) min vs. ( 217 ± 41) min, t = 4.635, P = 0.000). Estimated blood loss in the LAG group ((254 ± 112) ml) was significantly less than in the OG group (t = 3.942, P = 0.000). Time to ambulation ((63 ± 16) hours), first flatus ((77 ± 20) hours), resumed liquid diet ((88 ± 15) hours), duration of analgesic medication ((53 ± 20) hours) and postoperative hospital stay ((11.1 ± 4.6) days) were significantly shorter in the LAG group (t = 5.549, 6.508, 9.436, 9.464 and 2.980 respectively, all P < 0.01). The distance of the proximal and distal resection margin were (5.7 ± 1.4) cm and (3.9 ± 1.5) cm in LAG group, (5.8 ± 1.1) cm and (4.7 ± 1.5) cm in OG group respectively, but the difference was not significant. The number of lymph node dissections was also similar, (30.5 ± 10.4) in LAG group and (32.6 ± 12.3) in OG group (t = 0.960, P = 0.339). The incidence of postoperative complications and mortality rate in LAG group (8.7% and 0 respectively) were also lower than in the OG group, with no statistically significant difference (P > 0.05). The mean follow-up was 31.0 months (range 6-48 months), and the cumulative survival of the 2 groups was similar (χ(2) = 1.594, P = 0.207). CONCLUSIONS: Laparoscopy-assisted gastrectomy for advanced gastric cancer is not significantly different with open surgery in surgical safety, radical degree, and survival rate. It is less traumatic and of fewer complications.

The Potential Value of Gastric Histopathology for Predicting Colorectal Adenomatous Polyps Among the Chinese Population: A Retrospective Cross-Sectional Study.

Background: It remains unknown whether gastric histopathology is associated with the occurrence of colonic neoplasms. We aimed to clarify the association between gastric histopathology and different types of colorectal polyps (CP) and colorectal cancer (CRC), and whether various gastric histopathologies are risk factors for different types of CP and CRC. Methods: A retrospective cross-sectional study was conducted on 5,986 patients who underwent gastroscopy and colonoscopy simultaneously at Shaoxing People's Hospital from August 1, 2019, to May 31, 2020. The Pearson χ2 test was used to analyze the occurrence of various gastric histopathologies in different types of CP and CRC, and logistic regression was used to determine whether various gastric histopathologies were risk factors for different types of CP and CRC. Results: For the Chinese population, male sex (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.41-1.97, P < 0.001) and old age (OR 1.03, 95% CI 1.02-1.04, P < 0.001) were risk factors for non-adenomatous polyps (NAP), but Helicobacter pylori (H. pylori) and various gastric histopathologies were not significant in the NAP compared with the normal group. Nevertheless, it is noteworthy that, similar to male sex and old age, H. pylori (OR 1.22, 95% CI 1.08-1.38, P = 0.002), low-grade intraepithelial neoplasia (LGIN) (OR 1.79, 95% CI 1.21-2.66, P = 0.004), gastric fundus gland polyps (FGPs) (OR 1.44, 95% CI 1.11-1.87, P = 0.007), hyperplastic/inflammatory gastric polyps (GHP or GIP) (OR 1.50, 95% CI 1.06-2.12, P = 0.022), and atrophy/intestinal metaplasia (AG or IM) (OR 1.27, 95% CI 1.13-1.43, P < 0.001) were all risk factors for colorectal adenomatous polyps (AP). However, the results of CRC showed that old age (OR 1.13, 95% CI 1.10-1.16, P < 0.001) and H. pylori (OR 1.67, 95% CI 0.99-2.75, P < 0.05) were risk factors for CRC (OR 1.67, 95% CI 0.99-2.75, P < 0.05), but not sex and various gastric histopathologies (P > 0.05). Conclusion: Gastric histopathology, such as AG or IM, LGIN, FGP, and GHP or GIP, were risk factors for AP, but not for NAP and CRC, indicating that gastric histopathology has potential predictive value for AP in the Chinese population.

The Role of Mesenchymal Stem Cells in the Induction of Cancer-Stem Cell Phenotype.

Cancer stem cells (CSCs) modify and form their microenvironment by recruiting and activating specific cell types such as mesenchymal stem cells (MSCs). Tumor-infiltrating MSCs help to establish a suitable tumor microenvironment for the restoration of CSCs and tumor progression. In addition, crosstalk between cancer cells and MSCs in the microenvironment induces a CSC phenotype in cancer cells. Many mechanisms are involved in crosstalk between CSCs/cancer cells and MSCs including cell-cell interaction, secretion of exosomes, and paracrine secretion of several molecules including inflammatory mediators, cytokines, and growth factors. Since this crosstalk may contribute to drug resistance, metastasis, and tumor growth, it is suggested that blockade of the crosstalk between MSCs and CSCs/cancer cells can provide a new avenue to improving the cancer therapeutic tools. In this review, we will discuss the role of MSCs in the induction of cancer stem cell phenotype and the restoration of CSCs. We also discuss targeting the crosstalk between MSCs and CSCs/cancer cells as a therapeutic strategy.

Role of regulatory B cells in gastric cancer: Latest evidence and therapeutics strategies.

Gastric cancer (GC) is the second most common cancer globally and kills about 700,000 people annually. Today's knowledge clearly shows a close and complicated relationship between the tumor microenvironment (TME) and the immune system. The immune system components can both stimulate tumor growth and inhibit tumor cells. However, numerous of these mechanisms are not yet fully understood. As an essential immune cell in humoral immunity, B lymphocytes can play a dual role during various pathologic states, including infections, autoimmune diseases, and cancer, depending on their phenotype and environmental signals. Inherently, B cells can inhibit tumor growth by producing antibodies as well as the presentation of tumor antigens. However, evidence suggests that a subset of these cells termed regulatory B cells (Bregs) with an inhibitory phenotype can suppress anti-tumor responses and support the tumor growth by producing anti-inflammatory cytokines and the expression of inhibitory molecules. Therefore, in this review, the role of Bregs in the microenvironment of GC and treatment strategies based on targeting this subset of B cells have been investigated.

Stress-induced phosphoprotein 1 promotes pancreatic cancer progression through activation of the FAK/AKT/MMP signaling axis.

BACKGROUND: Dependent on the extent of adenosine triphosphate (ATP) hydrolysis and/or ATP/ADP exchange, the stress-induced phosphoprotein 1 (STIP1) mediates molecular interaction and complex formation between the molecular chaperones heat shock protein (Hsp)70 and Hsp90. The overexpression of STIP1 is increasingly being documented in various human malignancies, including ovarian, cholangiocellular, renal and gastric cancers. However, the role of STIP1 in pancreatic cancer (PANC) and probable molecular mechanism remains largely unexplored. METHODS & RESULTS: In the present study, using clinical samples (n = 88) and human PANC cell lines PANC-1, Capan-2, SW1990, and BxPC-3, we demonstrated that STIP1 is aberrantly expressed in human PANC tissues or cell lines compared to adjacent non-tumor pancreas samples or human pancreatic duct epithelial cells (HPDEC), respectively. Clinicopathological correlation studies revealed significant positive correlation between high STIP1 expression and lymph node involvement (p = 0.001), cancer metastasis (p = 0.002), microvascular invasion (p = 0.002), advance TNM stage (p = 0.024), perineural invasion (PNI; p = 0.013), and cancer-related death (p = 0.002) among patients with PANC. Univariate and multivariate analyses indicate that STIP1overexpression is an independent prognostic factor of PANC. Furthermore, STIP1 knockdown significantly inhibit the migration and invasive ability of PANC-1 and SW1990 cells, while downregulating N-cadherin and Vimentin, but upregulating E-cadherin mRNA expression levels, concurrently. We also demonstrated that STIP1 knockdown suppressed p-FAK, p-AKT, MMP2, MMP9, and Slug protein and mRNA expression levels, thus, indicating, at least in part, a role for STIP1 in the activation of FAK/AKT/MMP signaling. CONCLUSION: Taken together, our results demonstrate a critical role for STIP1 in cancer metastasis, disease progression and poor prognosis, as well as, provide evidence suggestive of the therapeutic efficacy of STIP1-mediated targeting of the FAK/AKT/MMP signaling axis in patients with PANC.

Dual-targeting strategy using trastuzumab and lapatinib in a patient with HER2 gene amplification in recurrent metachronous metastatic gallbladder carcinoma.

Gallbladder carcinoma (GBC) is a rare and highly aggressive tumor. Early diagnosis is challenging, which results in a poor prognosis using systemic therapy. Recent studies have identified a subset of GBC patients with HER2 gene (ERBB2) amplification that could benefit from HER2-targeted therapy. Here, we report one patient with recurrent metachronous GBC with metastasis, who received the combination of trastuzumab and lapatinib. This approach achieved a partial response for both the brain and the lung metastases. This study demonstrated that HER2 inhibition is a promising therapeutic strategy for GBC with HER2 amplification and, combined with lapatinib, it can effectively target brain metastasis.

Impact of Abdominal Shape on Short-Term Surgical Outcome of Laparoscopy-Assisted Distal Gastrectomy for Gastric Cancer.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has been widely accepted for the treatment for gastric cancer. The aim of the present study was to explore the impact of abdominal shape parameters on gastric antrum cancer patients' short-term surgical outcomes of LADG with D2 lymph node dissection in both genders, including the number of lymph nodes retrieved and surgical safety index. METHODS: This was a retrospective analysis of 177 gastric antrum cancer patients, who underwent LADG between April 2009 and January 2016. The abdominal shape parameters, including abdominal anterior-posterior diameter (APD), transverse diameter (TD), xiphoid process of the sternum-navel distance (XND), and thickness of subcutaneous fat (SCF) at the umbilicus level, were calculated by preoperative abdominal computed tomography (CT) scans. The effects of abdominal shape parameters on the short-term surgical outcomes of LADG were analyzed. RESULTS: In male patients undergoing LADG and D2 lymph node dissection, the number of retrieved lymph nodes was significantly lower in patients with APD ≥17.3 cm (P = 0.005), TD ≥27.4 cm (P = 0.029), SCF ≥1.2 cm (P = 0.014), and BMI ≥22.2 (P = 0.008), whereas in female patients, these were statistically insignificant (P > 0.05). APD, TD, SCF, and BMI were negatively correlated with the number of retrieved lymph nodes in male patients. There was no significant difference in the number of lymph nodes retrieved between high-XND group and low-XND group in either gender. Operation time was significantly shorter in male patients with XND < 17.0 cm (P = 0.044) and in female patients with SCF < 2.15 cm (P = 0.013). Intraoperative blood loss and postoperative complication rate were not significantly different between high- and low-APD groups, high- and low-TD groups, high- and low-XND groups, and high- and low-SCF groups in either gender. Compared with male patients, SCF and TD were significantly higher in female patients. In addition, a higher incidence rate of hypertension was observed in patients of both genders with large APD and SCF, although statistically significant only in male patients. CONCLUSIONS: LADG with D2 lymph node dissection can effectively achieve the lymph node dissection requirement of radical distal gastrectomy for patients with various abdominal shapes. It is worth noting that APD, TD, and SCF can impact on lymph node dissection of LADG in male patients. Nevertheless, in female patients, abdominal shape do not impact on lymph node dissection of LADG. Moreover, LADG with D2 lymph node dissection is proved to be safe for various abdominal shape in both genders, even for abdominal obese patients.

Effects of small interfering RNA interference of connexin 37 on subcutaneous gastric tumours in mice.

The present study aimed to investigate the effects of small interfering (si)RNA interference of connexin 37 (Cx37) on subcutaneous gastric tumours in mice. Constructed lentiviruses carrying siRNA against Cx37 significantly knocked down Cx37 mRNA and protein expression in vitro. A total of 60 mice with gastric cancer were randomly divided into the Cx37 siRNA group, the mock­siRNA group and the control group. Cx37 siRNA, mock­siRNA and saline were separately injected (with the lentiviruses transfected into the gastric cancer cells). Following six weeks, the Cx37 mRNA expression, Cx37 protein expression and tumor apoptosis were detected using semiquantitative reverse transcription­polymerase chain reaction, western blot analysis and terminal deoxynucleotidyl transferase­mediated dUTP nick end labelling, respectively. Six weeks following lentiviral transfection, the Cx37 mRNA levels in the Cx37 siRNA group, mock­siRNA group and saline group decreased to 42, 63 and 67%, respectively (P<0.05). The mock­siRNA group demonstrated no significant change in Cx37 levels compared with the control group. Western blot analysis revealed lower Cx37 protein levels in the Cx37­RNAi group than in the other groups (0.21±0.07 vs. 0.65±0.06 vs. 0.54±0.07), and that the apoptotic index of the Cx37­RNAi group was higher than those of the mock­siRNA and control groups (19.7±5.1 vs. 9.8±6.4 vs. 10.5±7.2%, 11.1±6.9; P<0.05). In conclusion, it was demonstrated that Cx37 siRNA is correlated with gastric cancer. Interference of Cx37 effectively reduces Cx37 mRNA and protein expression and promotes tumour apoptosis.

Prognostic significance of nuclear hepatoma-derived growth factor expression in gallbladder cancer.

AIM: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance. METHODS: We studied 40 patients with gallbladder cancer (GBC) and a control group of 40 patients with cholelithiasis. All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery. None of the patients received chemotherapy or radiotherapy before surgery. All tissue samples were fixed in 4% formalin immediately after removal and embedded in paraffin for immunohistochemical staining. The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining. The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed. RESULTS: Nuclear HDGF expression was significantly higher (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear HDGF levels were associated with histopathological subtype (P < 0.05), clinical stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age, history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival (P < 0.01). Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival. CONCLUSION: The expression of nuclear HDGF might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

Association between C1019T polymorphism in the connexin 37 gene and Helicobacter pylori infection in patients with gastric cancer.

OBJECTIVE: To investigate the association between the connexin 37 C1019T polymorphism and Helicobacter pylori infection in patients with gastric cancer. METHODS: 388 patients with gastric cancer (GC), 204 with chronic superficial gastritis (CSG) were studied. H. pylori was detected by gastric mucosal biopsies biopsy dyeing method. Connexin 37 gene polymorphism 1019 site genotypes were determined by gene sequencing technology. Genotypes and alleles frequencies were compared. RESULTS: (1) Connexin37 gene 1019 site distribution frequency (CC type, TC type, TT type) in the CSG group was 18.1%, 45.1% and 36.8%; in the stomach cancer group it was 35.1%, 45.9% and 19.%, conforming to the Hardy-Weinberg euilibrium. (2) In comparison with CSG group, the frequency of Connexin37 C allele was higher in the gastric cancer group (58.0% vs 40.7%, OR=2.01, 95%CI=1.58-2.57, P<0.01). The prevalence of gastric cancer risk was significantly increased in the carriers of C allele (CC+TC) than in TT homozygote (OR=2.47, 5%CI=1.68-3.610. (3) Gastric cancer patients complicated with Hp infection 211 cases, gastric cancer group of the male patients with HP positive patients with 187 cases, 40 cases of female patients with negative patients, 24 cases were HP positive, negative in 137 cases, control group male patients, 28 cases were Hp positive, negative in 95 patients, female patients with Hp positive 6 cases, 75 cases were negative. On hierarchical analysis, the male group OR value was 15.9 (95%CI to 9.22-27.3), and the female OR was 2.19 (95%CI 0.88-5.59), indicating a greater contribution in males (P<0.01). After elimination of gender effects, positive HP and gastric cancer were closely related (OR 8.82, 95% CI: 5.45-14.3). (4) The distribution frequency of C allele in patients with Hp infection was much higher than that in Hp negative cases in the GC group (64.5% vs 47.0%, OR=2.05, 95%CI=1.54-2.74, P<0.01). Compared with TT homozygotes, (CC+TC) genotype prevalence of gastric cancer risk increased significantly (OR=2.96, 5%CI=1.76-2.99). CONCLUSION: The T allele in the connexin37 gene might not only be associated with gastric cancer but also with H. pylori infection.