LncRNA NEAT1 promotes proliferation, migration, and invasion of laryngeal squamous cell carcinoma cells through miR-411-3p/FZD3-mediated Wnt signaling pathway.

The lncRNA NEAT1 has been shown to promote the progression of several cancers, containing laryngeal squamous cell carcinoma (LSCC). However, the precise mechanism by which it promotes LSCC progression remains unclear. In this study, we verified the high expression of lncRNA NEAT1 in LSCC tissues and cells using RT-qPCR. Analysis of clinical data exhibited that high expression of lncRNA NEAT1 was associated with a history of smoking, worse T stage, lymph node metastasis, and later TNM stage in patients with LSCC. The promotion effect of lncRNA NEAT1 on LSCC cell proliferation, migration, invasion, and tumor growth in vivo was verified by CCK-8, plate clone formation, Transwell, and nude mouse tumorigenicity assays. Bioinformatics prediction and double luciferase reporter gene assay verified the binding of miR-411-3p to lncRNA NEAT1 and FZD3 mRNA, and inhibition of miR-411-3p reversed the inhibitory effect of lncRNA NEAT1 on FZD3 expression in LSCC cells. We also verified that lncRNA NEAT1-mediated FZD3 activation in the Wnt pathway affects LSCC development. In conclusion, we demonstrate that lncRNA NEAT1 promotes the progression of LSCC, and propose that the lncRNA NEAT1/miR-411-3p/FZD3 axis may be an effective target for LSCC therapy.

Overexpressed HGF promotes metastasis of squamous cell carcinoma of the head and neck through the PI3K/Akt and JNK signaling pathways.

Background: The role of HGF in squamous cell carcinoma of the head and neck (SCCHN) is not clear. Methods: Reverse transcription PCR, western blotting, gelatin zymography, immunohistochemistry, actin polymerization, chemotaxis and migration assays were used in the authors' study. Results: HGF expression level was upregulated in SCCHN cells, which was associated with clinical stage; tumor, node, metastasis classification; and lymphatic invasion. SCCHN cells with high Met expression were sensitive to cell invasion, which was blocked by inhibiting PI3K/Akt and JNK. HGF induced MMP9 expression and enhanced its activity. Akt induced the activation of JNK through the PI3K/Akt and JNK signaling pathways. Conclusion: HGF upregulates MMP9 through the activation of the PI3K/Akt and JNK signaling pathways in SCCHN cells.

Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature.

Human epidermal growth factor receptor 2 (HER2) plays an important role in the aggressiveness and progression of gastric cancer. With the publication of trial results, we conducted a meta-analysis to investigate its prognostic significance for patients with gastric cancer. PubMed, Ovid, Web of Science, and Cochrane databases were searched. Statistical analysis was carried out by STATA version 12.0 software. The Newcastle-Ottawa scale was used to assess the quality of evidence. Fifteen studies involving 5,290 patients met the inclusion criteria. The results showed that HER2 overexpression was significantly associated with patients' overall survival (HR = 1.56, 95% confidence interval (CI) 1.05-2.07; Z = 6.03; P = 0.000). The results also suggested that HER2 overexpression was associated with Bormann type (odds ratio (OR) = 1.76, 95% CI 1.19-2.59; Z = 2.85; P = 0.004), tumor differentiation (OR = 3.14, 95% CI 1.91-5.17; Z = 4.49; P = 0.000), Lauren's classification (OR = 6.25, 95% CI 4.29-9.10; Z = 9.54; P = 0.000), lymph node metastasis (OR = 1.43, 95% CI 1.15-1.77; Z = 3.23; P = 0.001), venous invasion (OR = 1.69, 95% CI 1.15-2.48; Z = 2.67; P = 0.008), and lymphovascular invasion (OR = 1.57, 95% CI 1.21-2.04; Z = 3.4; P = 0.001). However, it had no correlation with tumor size, depth of invasion, and tumor stage. This study showed that HER2 overexpression had an unfavorable prognostic role for patients with gastric cancer. HER2-positive expression was associated with Bormann type, Lauren's classification, tumor differentiation, lymph node status, venous invasion, and lymphovascular invasion.

Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials.

BACKGROUND: In this meta-analysis we aimed to determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPC) for patients with advanced gastric cancer who underwent gastrectomy. METHODS: In accordance with standard meta-analysis procedures, our study included patients who underwent resection for advanced gastric cancer and were randomly allocated to receive either hyperthermic intraperitoneal chemotherapy or control. We searched PubMed (up to November 2011), EMBASE (up to November 2011), Cochrane Database of Systematic Reviews (CDSR), and Cochrane Central Register of Controlled Trials (CCTR) (up to November 2011). Both published and unpublished trials were included in the analysis, and no search restrictions were imposed. There was no language restriction. The results were analyzed using RevMan 5.1 software, which was provided by Cochrane Collaboration. RESULTS: There were ten randomized controlled trials included in the analysis. A total of 1062 patients with gastric cancer in these studies were divided into the HIPC group (n = 518) and control group (n = 544). A significant improvement in survival was observed in the HIPC groups compared to the control group in the mitomycin C (MMC) subgroup (RR = 0.75, 95%CI 0.65-0.86; P < 0.00001) and the 5-FU group (RR = 0.69, 95%CI 0.52-0.90; P < 0.00001); the total RR was 0.73 (95%CI 0.64-0.83; P < 0.00001). Our findings indicated that HIPC potentially exhibited a lower peritoneal recurrence rate in the HIPC group compared to the control group (RR = 0.45, 95%CI 0.28-0.72; P = 0.001). CONCLUSIONS: Our meta-analysis demonstrated that HIPC may improve the overall survival rate for patients who receive resection for advance gastric cancer potentially, and help to prevent peritoneal local recurrence among patients with serosal invasion in gastric cancer.

Meta-analysis of TSH suppression therapy and the risk of cardiovascular events after thyroid cancer surgery.

Objective: To investigate the relationship between TSH suppression therapy and cardiovascular events in patients with thyroid cancer after surgery. Methods: Pub Med, Web of Science, and Embase databases were retrieved to collect studies related to the risk of cardiovascular events in patients treated with TSH suppression after thyroid cancer surgery. RevMan statistical software was used for meta-analysis. Results: A total of 14 studies were included. The mean heart rate of patients after thyroid cancer surgery was higher than that of the control group (SMD=2.59, 95% CI: -0.37,.54), and the risk of atrial fibrillation was increased compared with the control group (RR = 1.52, 95%CI, 1.28-1.81; I = 63%). Ejection fraction and left ventricular end-diastolic diameter were not significantly different between the two groups, ejection fraction SMD = -0.10, 95% CI: -3.73, 3.52, left ventricular end-diastolic diameter SMD = -0.09, 95% CI: - 1.29, 1.11. Patients with TSH suppression after thyroid cancer had higher mean systolic blood pressure than controls (SMD = 1.97, 95% CI: -1.09, 5.03) and mean diastolic blood pressure (SMD = 1.85, 95% CI: -0.15, 3.85). Conclusion: Meta-analysis concluded that TSH suppression therapy after thyroid cancer surgery increases the risk of atrial fibrillation in patients. In addition, the heart rate, systolic blood pressure and diastolic blood pressure are higher than those in the control group, and there is no significant difference in ejection fraction and left ventricular end-diastolic diameter.

Overexpression of microRNA-107 suppressed proliferation, migration, invasion, and the PI3K/Akt signaling pathway and induced apoptosis by targeting Nin one binding (NOB1) protein in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

Hypopharyngeal squamous cell carcinoma (HSCC) is one of the most common head and neck cancers, with a worst prognosis owing to its aggressivity. MicroRNA-107 (miR-107) is reported to regulate the progression of various cancers. Nevertheless, its implied function in HSCC remains unclear. This study is aimed to exploring the roles and potential mechanisms of miR-107 in HSCC. We found that miR-107 expression was significantly decreased in HSCC tissues compared with the para-cancer tissues. Moreover, miR-107 overexpression by miR-107 mimics decreased FaDu cell viability, led to cell cycle arrest in G1/S phase, accelerated apoptosis, and reduced cell migration and invasion. MiR-107 possibly resulted in deactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, evidenced by the decrease of phosphorylated (p-) PI3K and p-Akt. Besides, dual-luciferase reporter assay confirmed that miR-107 might bind to the 3'UTR of Nin one binding protein 1 (NOB1), and elevated NOB1 expression in HSCC tissues and a negative correlation between miR-107 and NOB1 were found. Rescue assays demonstrated the significant roles of miR-107 in FaDu cell behavior by modulating NOB1. In addition, the tumorigenic potential of miR-107 in vivo was conducted. It was found that miR-107 overexpression in FaDu cells significantly inhibited tumor growth and led to inactivation of the PI3K/Akt signaling. The above findings revealed that miR-107 could suppress FaDu cell proliferation, migration, invasion and induced apoptosis by targeting NOB1 through the PI3K/Akt pathway, suggesting that miR-107/NOB1 axis may exert a key role in FaDu HSCC development.

Beta-35 is a transferrin-derived inhibitor of angiogenesis and tumor growth.

An angiogenesis inhibitor named Beta-35 has been identified and purified from the conditioned medium of mouse pancreatic ß cells tumor cells. Beta-35 has a molecular weight of 35 kDa and inhibits DNA synthesis of bovine capillary endothelial cells at a half-maximal concentration of approximately 5 nM. It shows anti-angiogenic activity in the chick embryo chorioallantoic membrane at a dose of about 1 µg/embryo. Amino acid microsequencing and mass spectrometric analysis of the purified protein demonstrate that Beta-35 contains the first 314 residues of the N-terminal sequence of bovine transferrin. We have cloned and expressed this protein in Escherichia coli using the corresponding gene segment of Beta-35 contained in the cDNA of human transferrin. The recombinant protein of Beta-35 shows significant anti-tumor activity at a dose of 5mg/kg/day against human pancreatic cancer or melanoma implanted subcutaneously in SCID mice.

Which risk factors are associated with stomal recurrence after total laryngectomy for laryngeal cancer? A meta-analysis of the last 30 years.

INTRODUCTION: Stomal recurrence is a troublesome complication after total laryngectomy. Despite a large number of studies having been performed, there is still controversy about which risk factors are most significant for the development of stomal recurrence. OBJECTIVE: The objective of the present meta-analysis was to analyze the potential factors leading to stomal recurrence after total laryngectomy. METHODS: PubMed, Web of Science, Cochrane Library, and Ovid databases were systematically searched using multiple search terms. Eighteen studies with 6462 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. RESULTS: The results showed that, tumor subsite (supraglottic vs. subglottic, RR=0.292, 95% CI 0.142-0.600, p=0.001; glottic vs. subglottic, RR=0.344, 95% CI 0.175-0.676, p=0.002), T stage (RR=0.461, 95% CI 0.286-0.742, p=0.001), preoperative tracheotomy (RR=1.959, 95% CI 1.500-2.558, p<0.001) were the high-risk factors associated with the development of stomal recurrence. CONCLUSION: From the results of our study, tumor subsite, T stage and preoperative tracheotomy were the significant risk factors for stomal recurrence. Methodologically high-quality comparative investigations are needed for further evaluation.

Corrigendum: The Extracts of Morinda officinalis and Its Hairy Roots Attenuate Dextran Sodium Sulfate-Induced Chronic Ulcerative Colitis in Mice by Regulating Inflammation and Lymphocyte Apoptosis.

[This corrects the article DOI: 10.3389/fimmu.2017.00905.].

Free tissue flaps in head and neck reconstruction: clinical application and analysis of 93 patients of a single institution.

INTRODUCTION: Reconstruction with a free flap is routine in head and neck surgery because of better functional outcomes, improved esthetics, and generally higher success rates. OBJECTIVE: To evaluate the clinical outcomes in patients undergoing different microvascular free flap reconstructions. METHODS: This was a retrospective study of 93 patients undergoing reconstructions with free flaps from 2007 to 2015. Four types of free flap were performed: anterolateral thigh (76.3%), radial forearm (16.1%), fibula (4.3%) and jejunum (3.3%). Patients' demographic data were collected, and the outcomes measured included flap survival and complications. Postoperative functional and oncological outcome were also analyzed. RESULTS: The patients included 73 men and 20 women, with a mean age of 56.1 years. The most common tumor location was the tongue. Squamous cell carcinoma represented the vast majority of the diagnosed tumors (89.2%). The most common recipient vessels were the superior thyroid artery (77.4%) and the internal jugular vein (91.4%). Nine patients required emergency surgical re-exploration and the overall flap success rate was 90.3%. Venous thrombosis was the most common cause for re-exploration. Other complications included wound infection (5.4%), wound dehiscence (1.1%), partial flap necrosis (9.7%), fistula formation (10.8%), and 1 bleeding (1.1%). The majority of patients had satisfactory cosmetic and functional results of both donor site and recipient site after 46.7 months of mean follow-up. CONCLUSION: Microsurgical free flap is shown to be a valuable and reliable method in head and neck surgery. It can be used safely and effectively with minimal morbidity in selected patients. The reconstruction can be performed by appropriately skilled surgeons with acceptable outcomes. Success rate appears to increase as clinical experience is gained.

The Extracts of Morinda officinalis and Its Hairy Roots Attenuate Dextran Sodium Sulfate-Induced Chronic Ulcerative Colitis in Mice by Regulating Inflammation and Lymphocyte Apoptosis.

Morinda officinalis is beneficial for the treatment of inflammatory bowel disease (IBD). The hairy root with higher genetic and biochemical stability cultured from M. officinalis might have similar effects to treat IBD. In this study, the main chemical composition of the root extracts of M. officinalis (MORE) native plant and the hairy root extract of M. officinalis (MOHRE) was compared by quantitative HPLC. The difference of their therapeutic effects and potential mechanism was evaluated using 3% dextran sodium sulfate-induced chronic colitis in mice and T lymphocytes in vitro. The results found that MOHRE possesses many specific peaks unobserved in the chromatogram of native plant. The content of iridoids in the MORE (3.10%) and MOHRE (3.01%) is somewhat similar but quite different for their anthraquinones's content (0.14 and 0.66%, respectively). Despite all this, treatment with both MORE and MOHRE significantly attenuated the symptoms of colitis, including diarrhea, body weight loss, colon shortening, histological damage, and decreased inflammatory cytokine levels. In addition, they dose-dependently increased the apoptosis of T lymphocyte in vivo and in vitro. And, the differences for treatment effects on ulcerative colitis (UC) between them both in this study were mostly insignificant. The results demonstrated that the effects of MORE and MOHRE for the treatment of UC are similar, although there are a few difference on their chemical composition, indicating the hairy root cultured from M. officinalis might be able to replace its native plant on treatment of UC. The successful derivation of a sustainable hairy root culture provides a model system to study the synthetic pathways for bioactive metabolites, which will make the use of bioreactors to largely produce traditional medicine become reality.

[Clinicopathologic characteristics of familial versus sporadic papillary thyroid carcinoma].

OBJECTIVE: To investigated the clinicopathologic features of familial papillary thyroid carcinoma (PTC) compared to sporadic PTC. METHODS: Between January 2008 and August 2014, 20 patients who underwent surgery at Liaoning Cancer Hospital and Institute were diagnosed with familial PTC. We compared the clinicopathologic characteristics between familial PTC and sporadic PTC. RESULTS: The prevalence of familial PTC was 1.3% (20/1 587). The median age of patients at diagnosis was 37 years and there were 12 females and 8 males. Thirty percent of the familial PTC cases exhibited a parent-offspring relationship, and 70% exhibited a sibling relationship. There were significant differences between familial PTC and sporadic PTC in terms of concomitant chronic thyroiditis (P < 0.01), nodular goiter (P = 0.04), tumor multicentricity (P < 0.01), bilaterality (P < 0.01), histological subtype (P < 0.01), and central lymph node metastasis (P = 0.02). When familial PTC patients were classified based on parent-child and sibling relationship, there were significant differences in preoperative TSH level (P = 0.02) and concomitant chronic thyroiditis (P = 0.01) between the two categories. CONCLUSIONS: There are significant differences in clinicopathologic features between familial PTC and sporadic PTC and between familial PTC with parent-child and those with sibling relationship. Familial PTC appears more aggressive than sporadic carcinoma. Optimal treatment for familial PTC is not yet established, but improved awareness and screening will permit earlier detection, more timely intervention, and improved outcomes for patients and their families.

Which risk factors are associated with stomal recurrence after total laryngectomy for laryngeal cancer? A meta-analysis of the last 30 years / Quais fatores de risco estão associados à recorrência estomal após laringectomia total para câncer de laringe? Uma meta-análise dos últimos 30 anos

Abstract Introduction Stomal recurrence is a troublesome complication after total laryngectomy. Despite a large number of studies having been performed, there is still controversy about which risk factors are most significant for the development of stomal recurrence. Objective The objective of the present meta-analysis was to analyze the potential factors leading to stomal recurrence after total laryngectomy. Methods PubMed, Web of Science, Cochrane Library, and Ovid databases were systematically searched using multiple search terms. Eighteen studies with 6462 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. Results The results showed that, tumor subsite (supraglottic vs. subglottic, RR = 0.292, 95% CI 0.142-0.600, p = 0.001; glottic vs. subglottic, RR = 0.344, 95% CI 0.175-0.676, p = 0.002), T stage (RR = 0.461, 95% CI 0.286-0.742, p = 0.001), preoperative tracheotomy (RR = 1.959, 95% CI 1.500-2.558, p < 0.001) were the high-risk factors associated with the development of stomal recurrence. Conclusion From the results of our study, tumor subsite, T stage and preoperative tracheotomy were the significant risk factors for stomal recurrence. Methodologically high-quality comparative investigations are needed for further evaluation.

Resumo Introdução A recorrência estomal pós-laringectomia total e é uma complicação de difícil manejo. Apesar de um grande número de estudos ter sido feito, ainda há controvérsias sobre quais fatores de risco são mais significativos para o seu desenvolvimento. Objetivo O objetivo da presente meta-análise foi analisar os fatores potenciais para recorrência estomal após a laringectomia total. Método As bases de dados PubMed, Web of Science, Cochrane Library e Ovid foram sistematicamente pesquisadas com vários termos de busca. Dezoito estudos com 6.462 pacientes foram identificados. A qualidade da evidência foi avaliada pelo National Institute for Health and Clinical Excellence. Resultados Os resultados mostraram que o subsítio tumoral (supraglótico vs. subglótico, RR = 0,292, IC 95% 0,142 ± 0,600, p = 0,001; glótico vs. subglótico, RR = 0,344, IC 95% 0,175 ± 0,676, p = 0,002), estágio T (RR = 0,461, IC 95% 0,286 ± 0,742, p = 0,001), traqueotomia pré-operatória (RR = 1,959, IC 95% 1.500 ± 2.558, p < 0,001) foram os fatores de alto risco associados ao desenvolvimento de recorrência estomal. Conclusão Com base nos resultados de nosso estudo, o subsítio do tumor, o estágio T e a traqueotomia pré-operatória foram fatores de risco significativos para recorrência estomal. São necessárias investigações comparativas metodologicamente de alta qualidade para maior avaliação.

Pharyngocutaneous fistula after total laryngectomy: A systematic review and meta-analysis of risk factors.

OBJECTIVE: The pharyngocutaneous fistula (PCF) is the troublesome complication after total laryngectomy. Despite a large number of investigations having been performed, there is still controversy about which factors are most significant for PCF. The objective of the present meta-analysis was to analyze the potential risk factors for PCF after total laryngectomy. DATA SOURCES: Published English-language literature. REVIEW METHODS: PubMed, Ovid, Cochrane, and Web of Science databases were systematically searched using multiple search terms. Twenty-one studies with 3832 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. RESULTS: Sixteen studies involving 2598 patients were included for the meta-analysis. The results showed that, tumor subsite (RR=0.64, 95% CI 0.47-0.88, P<0.01), T stage (RR=0.70, 95% CI 0.51-0.96, P=0.03), previous radiotherapy (RR=0.62, 95% CI 0.46-0.84, P<0.01), postoperative hemoglobin <12.5g/L (RR=0.46, 95% CI 0.27-0.76, P<0.01), and surgical margin (RR=0.41, 95% CI 0.22-0.74, P<0.01) were the risk factors associated with the development of PCF. CONCLUSIONS: From the results of our study, several significant risk factors for PCF are identified. Methodologically high-quality comparative studies are needed for further evaluation.

Free tissue flaps in head and neck reconstruction: clinical application and analysis of 93 patients of a single institution / Retalhos livres de tecido para reconstrução em cirurgias de cabeça e pescoço: aplicação clínica e análise de 93 pacientes de uma única instituição

Abstract Introduction Reconstruction with a free flap is routine in head and neck surgery because of better functional outcomes, improved esthetics, and generally higher success rates. Objective To evaluate the clinical outcomes in patients undergoing different microvascular free flap reconstructions. Methods This was a retrospective study of 93 patients undergoing reconstructions with free flaps from 2007 to 2015. Four types of free flap were performed: anterolateral thigh (76.3%), radial forearm (16.1%), fibula (4.3%) and jejunum (3.3%). Patients' demographic data were collected, and the outcomes measured included flap survival and complications. Postoperative functional and oncological outcome were also analyzed. Results The patients included 73 men and 20 women, with a mean age of 56.1 years. The most common tumor location was the tongue. Squamous cell carcinoma represented the vast majority of the diagnosed tumors (89.2%). The most common recipient vessels were the superior thyroid artery (77.4%) and the internal jugular vein (91.4%). Nine patients required emergency surgical re-exploration and the overall flap success rate was 90.3%. Venous thrombosis was the most common cause for re-exploration. Other complications included wound infection (5.4%), wound dehiscence (1.1%), partial flap necrosis (9.7%), fistula formation (10.8%), and 1 bleeding (1.1%). The majority of patients had satisfactory cosmetic and functional results of both donor site and recipient site after 46.7 months of mean follow-up. Conclusion Microsurgical free flap is shown to be a valuable and reliable method in head and neck surgery. It can be used safely and effectively with minimal morbidity in selected patients. The reconstruction can be performed by appropriately skilled surgeons with acceptable outcomes. Success rate appears to increase as clinical experience is gained.

Resumo Introdução Reconstrução com retalhos livres é um procedimento de rotina nas cirurgias de cabeça e pescoço devido aos melhores resultados funcionais e estéticos e às taxas de sucesso geralmente maiores. Objetivo Avaliar os desfechos clínicos de pacientes submetidos a diferentes reconstruções microvasculares com retalhos livres. Método Estudo retrospectivo de 93 pacientes submetidos à reconstruções com retalhos livres, de 2007 a 2015. Foram utilizados quatro tipos de retalho livre: coxa anterolateral (76,3%), antebraço radial (16,1%), fíbula (4,3%) e jejuno (3,3%). Os dados demográficos dos pacientes foram coletados e os parâmetros avaliados incluíram sobrevida e complicações. Os resultados funcionais e oncológicos pós-operatórios também foram analisados. Resultados Os pacientes incluíram 73 homens e 20 mulheres, com idade média de 56,1 anos. O local mais comum para o tumor foi a língua. O carcinoma de células escamosas representou a maioria dos tumores diagnosticados (89,2%). As artérias receptoras mais comuns foram a artéria tireóidea superior (77,4%) e a veia jugular interna (91,4%). Nove pacientes necessitaram de reexploração cirúrgica de emergência e a taxa de sucesso global do retalho foi de 90,3%. A trombose venosa foi a causa mais comum da reexploração. Outras complicações incluíram infecção da ferida cirúrgica (5,4%), deiscência da ferida (1,1%), necrose parcial do retalho (9,7%), formação de fístula (10,8%) e sangramento (1,1%). A maioria dos pacientes apresentou resultados estéticos e funcionais satisfatórios, tanto no local doador quanto no receptor, após 46,7 meses de seguimento médio. Conclusão O retalho livre microcirúrgico mostrou ser um método valioso e confiável na cirurgia de cabeça e pescoço. Pode ser usado de forma segura e eficaz, com morbidade mínima em pacientes selecionados. A reconstrução pode ser feita por cirurgiões adequadamente qualificados com resultados aceitáveis. A taxa de sucesso parece aumentar à medida que a experiência clínica é adquirida.

Overexpression of methionine adenosyltransferase II alpha (MAT2A) in gastric cancer and induction of cell cycle arrest and apoptosis in SGC-7901 cells by shRNA-mediated silencing of MAT2A gene.

The aim of this study was to clarify the methionine adenosyltransferase II alpha (MAT2A) expression pattern and to explore its potential role in gastric cancer. Quantitative real-time PCR was performed to examine MAT2A mRNA expression in 20 cases of gastric cancer tissues and corresponding non-tumor tissue samples. Immunohistochemistry was conducted to detect MAT2A protein expression in 91 gastric cancer tissues. Moreover, the stable cell lines transfected with the small hairpin RNA (shRNA) targeting MAT2A mRNA plasmids were established and the biological characteristics of these cells were examined. The expression levels of MAT2A mRNA in gastric cancer tissues were significantly higher than those in corresponding non-tumor tissues. High-level MAT2A expression was observed in 40.7% (37 of 91 cases), and correlated with tumor classification (P=0.012), lymph node metastasis (P=0.001) and poor tumor differentiation (P=0.011) of gastric cancer patients. Additionally, the MAT2A expression level was significantly decreased in the transfected cells with MAT2A specific shRNA expression plasmid pGCsi-H1-792. The stable transfected cancer cells exhibited a decrease in growth ability and an increase in the incidence of spontaneous apoptosis and the percentage of the G1 phase. Our data suggest that MAT2A plays an important role in gastric cancer development and progression.

Laparoscopic versus open gastric resections for gastric gastrointestinal stromal tumors: a meta-analysis.

PURPOSE: We conducted a meta-analysis to compare surgical and oncologic outcomes of patients with gastric gastrointestinal stromal tumors (GISTs) undergoing laparoscopic resection surgery (LAP) and open resection surgery (OPEN). METHODS: PubMed, Ovid, Web of Science, Cochrane, CNKI, and Chinese Biomedical Database were searched. Statistical analysis was carried out by RevMan 5.0 software. The quality of evidence was assessed by the Newcastle-Ottawa scale. A decision tree analysis model was constructed to evaluate the treatment strategy. RESULTS: Seventeen studies involving 776 participants were included for the meta-analysis. The meta-analysis results showed that, compared with OPEN, LAP indicates potentially favorable outcomes in terms of intraoperative blood loss [weighted mean difference (WMD), -60.67; 95% confidence interval (95% CI), -116.66 to -4.69], time to first flatus (WMD, -1.19; 95% CI, -1.65 to -0.73), time to oral intake (WMD, -1.26; 95% CI, -1.89 to -0.63), and hospital stay (WMD, -2.62; 95% CI, -3.25 to -1.99). There were no differences in terms of the operative time, overall complication, and recurrence. Decision analysis showed that LAP was the strategy with a higher overall success (93%) compared with OPEN (88%). CONCLUSIONS: This meta-analysis showed that LAP for gastric GISTs was associated with less blood loss, earlier return of bowel function, earlier resumption of diet, and shorter length of hospital stay when compared with OPEN; however, LAP and OPEN had similar operative time, overall complication, and recurrence. The LAP might be superior to OPEN for the patients with GIST <5 cm. Methodologically, high-quality comparative studies are needed for further evaluation.

microRNA-192, -194 and -215 are frequently downregulated in colorectal cancer.

microRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. They have been increasingly shown to have aberrant expression in a number of tumor types. miR-192, -194 and -215 have not been comprehensively investigated using a large number of cases in colorectal cancer (CRC). We extracted total RNA from 107 CRC tissues and three CRC cell lines. Following polyadenylation and reverse transcription, the expression levels of miR-192, -194 and -215 were determined for evaluation of the association between expression levels and clinicopathological characteristics by a quantitative real-time polymerase chain reaction (real-time PCR) method. Finally, we studied the impact of miR-194 on cell proliferation in HCT-116 cells by MTT assay. miR-192, -194 and -215 were significantly downregulated in CRC tissues (all p<0.001, paired t-test) and cancer cell lines (all p<0.05) compared to non-tumor counterparts. Moreover, the expression levels of miR-192, -194 and -215 were demonstrated to be associated with increased tumor sizes (p=0.027, p=0.018, and p=0.027, respectively; Mann-Whitney U test). Also, there were marked correlations among these miRNAs in CRC tissues (all p<0.001, Pearson's regression analysis). Furthermore, we found that the overexpression of miR-194 could significantly inhibit cell proliferation in HTC-116 cells. miR-192, -194 and -215 may be important biological markers as tumor suppressors in the carcinogenesis of CRC.

The integration of macroscopic tumor invasion of adjacent organs into TNM staging system for colorectal cancer.

OBJECTIVE: In addition to pathological TNM (pTNM) staging, the macroscopic staging (surgical TNM, sTNM) is another method used to stage and assess tumors, and it also potentially influences patient treatment guidelines. However, for the same patient, surgeons and pathologists might assess tumor depth differently. We aimed to evaluate the prognosis of patients who exhibit unconformity of intraoperative and postoperative results and propose a revised pT category (r-pT category) to predict survival in colorectal cancer. METHODS AND RESULTS: In our study, 948 colorectal cancer patients were reviewed. We proposed a novel r-pT category in which surgical macroscopic T4b (sT4b) is incorporated into the pT category, namely, patients in the pT3 category with sT4b cancers are reclassified as being in the r-pT4a category; patients in the pT4a category with sT4b cancers are reclassified as being in the r-pT4b category. Cancer-specific survival according to the r-pT category was analyzed using Kaplan-Meier survival curves. A two-step multivariate analysis was used to determine correlations between the r-pT category and the prognosis. Harrell's C statistic was utilized to test the predictive capacity. There were significant prognostic differences among the r-pT subcategories. We substituted the r-pT category for the pT category in current TNM staging in a 2-step multivariate analysis. The Harrell's C statistical analysis results demonstrated that the r-pT category had superior predictive capacity compared to the pT category (Harrell' C: 0.668 vs. 0.636; P = 0.002). CONCLUSIONS: Patients in the pT3 category with sT4b cancers, and patients in the pT4a category with sT4b cancers, are potentially under-staged, reclassification into higher categories could potentially benefit these patients. The results indicate that the r-pT category we proposed is potentially superior to the pT category in the assessment of prognosis for colorectal cancer.

The association between individual SNPs or haplotypes of matrix metalloproteinase 1 and gastric cancer susceptibility, progression and prognosis.

BACKGROUND: The single nucleotide polymorphisms (SNPs) in matrix metalloproteinase 1(MMP-1) play important roles in some cancers. This study examined the associations between individual SNPs or haplotypes in MMP-1 and susceptibility, clinicopathological parameters and prognosis of gastric cancer in a large sample of the Han population in northern China. METHODS: In this case-controlled study, there were 404 patients with gastric cancer and 404 healthy controls. Seven SNPs were genotyped using the MALDI-TOF MS system. Then, SPSS software, Haploview 4.2 software, Haplo.states software and THEsias software were used to estimate the association between individual SNPs or haplotypes of MMP-1 and gastric cancer susceptibility, progression and prognosis. RESULTS: Among seven SNPs, there were no individual SNPs correlated to gastric cancer risk. Moreover, only the rs470206 genotype had a correlation with histologic grades, and the patients with GA/AA had well cell differentiation compared to the patients with genotype GG (OR=0.573; 95%CI: 0.353-0.929; P=0.023). Then, we constructed a four-marker haplotype block that contained 4 common haplotypes: TCCG, GCCG, TTCG and TTTA. However, all four common haplotypes had no correlation with gastric cancer risk and we did not find any relationship between these haplotypes and clinicopathological parameters in gastric cancer. Furthermore, neither individual SNPs nor haplotypes had an association with the survival of patients with gastric cancer. CONCLUSIONS: This study evaluated polymorphisms of the MMP-1 gene in gastric cancer with a MALDI-TOF MS method in a large northern Chinese case-controlled cohort. Our results indicated that these seven SNPs of MMP-1 might not be useful as significant markers to predict gastric cancer susceptibility, progression or prognosis, at least in the Han population in northern China.