Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.

Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion

AIM: To investigate the relation of expression transfor-mation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS: By using immunohistochemistry, expres-sion of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index (Ki-67) were detected and analyzed. RESULTS: In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas (including signet-ring cell carcinomas) was the highest. It was nega-tively related with the differentiation but positively related with the invasiveness and metastasis of gastric cancer. In invasive front, the claudin-1 over-expression rate was positively related with the differentiation, in-vasiveness and metastasis of gastric carcinoma. The expression transformation of claudin-1 was found in gastric carcinoma. The expression of claudin-1 in inva-sive front was transformed in 28/136 gastric carcinoma cases. The transformation rate in highly differentiated tubular adenocarcinomas was the highest (51.5%, 17/33). The deeper was the invasiveness, the higher was the transformation rate. The claudin-1 expression transformation rate in serosa and omenta was signifi -cantly higher (92.9%) than in tunica muscularis of in-vasive gastric cancer cases, as well as in patients withlymph node metastasis than in those without lymph node metastasis. CONCLUSION: Up-regulation of claudin-1 expres-sion and its transformation in invasive and metastatic gastric carcinoma suggest that claudin-1 participates in the transformation of biological behaviors in neo-plasms. Further study is needed to elucidate the pre-cise mechanism and the relation of claudin-1 expres-sion with the neoplasm progress.

Preliminary study correlating CX3CL1/CX3CR1 expression with gastric carcinoma and gastric carcinoma perineural invasion

AIM: To study the relationship between the CX3CL1 chemokine, its receptor CX3CR1, and gastric carcinoma/gastric carcinoma perineural invasion (PNI).

Expression of semaphorin 5A and its receptor plexin B3 contributes to invasion and metastasis of gastric carcinoma

AIM:To investigate the protein and mRNA expression of semaphorin 5A and its receptor plexin B3 in gastric carcinoma and explore its role in the invasion and metastasis of gastric carcinoma.METHODS:Expression of semaphorin 5A and its receptor plexin B3 in 48 samples of primary gastric carcinoma,its corresponding non-neoplastic mucosa,and matched regional lymph node metastasis was assayed by reverse transcription-polymerase chain reaction(RT-PCR),real-time RT-PCR and Western blotting.RESULTS:The protein and mRNA expression of semaphorin 5A and its receptor plexin B3 increased gradually in non-neoplastic mucosa,primary gastric carcinoma and lymph node metastasis(P<0.05).Moreover,the expression of semaphorin 5A was closely correlated with that of plexin B3.CONCLUSION:Semaphorin 5A and its receptor plexin B3 play an important role in the invasion and metastasis of gastric carcinoma.

Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude mice

AIM: To investigate the effects of class phosphatidy-linositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice. METHODS: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment, the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were observed.RESULTS: In this study, we showed that treatingthe tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% ± 3.11%, 43.20% ± 3.27% and 63.28% ± 2.10% at 5, 10 and 15 d, respectively) along with apoptosis. The expression of MMP-2 was also downregulated (from 71.4% ± 1.6% to 47.9% ± 0.7%, 31.9% ± 0.9% and 7.9% ± 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% ± 1.5% to 36.9% ± 0.4%, 23.5% ± 0.9% and 7.7% ± 0.6%), the mean MVD (from 51.2% ± 3.1% to 41.9% ± 1.5%, 30.9% ± 1.7% and 14.9% ± 0.8%), and the expression of VEGF (from 47.2% ± 3.1% to 25.9% ± 0.5%, 18.6% ± 1.2% and 5.1% ± 0.9%) by immunohistochemical staining.CONCLUSION: The classPI3K inhibitor LY294002could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

UROKINASE-TYPE PLASMINOGEN ACTIVATOR,ITS RECEPTOR AND INHIBITOR EXPRESSION IN HEPATOCELLULAR CARCINOMA RELATION TO CANCER INVASIVENESS AND PROGNOSIS

Objective: To study the relevance of uPA, uPAR and PAI 1 to hepatocellular carcinoma (HCC) Methods: The expression at protein level of uPA, uPAR and PAI 1 was determined in 48 cases of HCC and 12 cases of benign tumors of liver (as control) by immunohistochemistry Results: When compared to cancer adjacent liver tissue and the control, positive rate of immune staining for uPA, uPAR and PAI 1 on cell membrane were significantly higher in HCC cells ( P <0 05) Positive staining of uPA and uPAR was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively ( P <0 01 and P <0 001) In 8 of 8 cases with cancer embolus, and in 6 of 6 cases with lymph node metastasis was the expression of positive uPAR Compared with 2 of 17 cases without recurrence, uPAR was positive in 15 of 17 recurrent cases ( P <0 01) In 36 cases who survived, 17 was positive uPAR and 15 positive PAI 1, while in 12 cases who died 2 years after surgery, 12 were positive for uPAR and 9 positive PAI 1, respectively ( P <0 01 and P <0 05) In 15 positive cases for all three parameters, 11 had cancer invasion and 7 died within 2 years, while in negative cases, 2 had invasion and none died within 2 years ( P <0 05) Conclusion: Expression of uPA, uPAR and PAI 1 is increased in HCC, uPA and uPAR may contribute significantly to HCC invasion and metastasis uPAR and PAI 1 are associated with poor prognosis of HCC

Gastric submucosa-invasive carcinoma associated with EpsteinBarr virus and endoscopic submucosal dissection: A case report

BACKGROUND Epstein-Barr virus(EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma(GCLS).Clinicopathological studies have indicated a better prognosis for GCLS than for common gastric carcinomas.Some previous cases of early gastric cancer associated with EBV had been diagnosed by endoscopic resection.CASE SUMMARY We present two GCLS cases subjected to endoscopic submucosal dissection(ESD)for a definitive diagnosis.A protruded gastric lesion was identified by routine endoscopic examination,but forceps biopsy showed no atypical cells before ESD.The resected specimen showed a poorly differentiated adenocarcinoma with lymphoid cells involving the mucosa and submucosa.The final diagnosis was submucosa-invasive poorly differentiated gastric adenocarcinoma.Accordingly,additional gastrectomy was recommended to obtain a complete cure.One patient underwent additional distal gastrectomy with lymph node dissection,but the other was refused because of cardiovascular complications.Both patients remained in remission for more than half a year.EBV positivity was determined by EBV-encoded RNA in situ hybridization.We also conducted a literature review of cases of early gastric cancer associated with EBV that had been diagnosed by ESD.CONCLUSION Submucosa-invasive GCLS could be dissected using ESD,and EBV positivity should be subsequently assessed to determine whether or not any additional curative surgery is required.Further prospective investigations on the prevalence of lymph node metastasis in EBV-associated carcinoma should be performed to expand the indications for endoscopic resection.

Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

AIM To detect the expression of CD44v6 mRNA and nm23-H1 mRNA in hepatocellular carcinoma (HCC) by in situ hybridization, and to evaluate the relationship between their expression and also relationship between their expressions and tumor invasion and metastasis.METHODS CD44v6 cDNA probe was synthesized with PCR technique and the nm23-H1 cRNA probe by in vitro transcription. The expression of CD44v6 mRNA and nm23-H1 mRNA was detected by in situ hybridization.RESULTS In group with high invasion and metastasis potential, the positive rates of CD44v6 mRNA and nm23-H1 mRNA were 80% (8/10) and 40% (4/10), in group with poor invasion and metastasis potential, they were 21.7% (5/23) and 91.3% (21/23). There was a positive correlation between the expression of CD44v6 mRNA and tumor invasion and metastasis potential in HCC (P＜0.01), and a reverse correlation between the expression of nm23-H1 mRNA and tumor invasion and metastasis potential (P＜0.01) and a reverse correlation in the expression between CD44v6 mRNA and nm23-H1 mRNA in HCC (P＜0.01).CONCLUSION Detection of CD44v6 mRNA and nm23-H1 mRNA may be useful for tumor invasion and metastasis in HCC.INTRODUCTIONCD44 is a cell surface transmembrane glycoprotein. As a kind of adhesive molecule, it participates in cell-cell and cell-matrix adhesion and interactions. Many studies revealed a correlation between high-level expression of CD44, especially CD44v and tumor invasion, metastasis and prognosis. The exon 6v containing isoforms may be an independent diagnostic parameter[1,2]. Some other studies, however, had different results[3,4]. Some researches showed a reverse correlation between the expression of nm23-H1 mRNA and tumor metastasis[5,6]. In order to evaluate the relationship between the expression of CD44v6 mRNA and nm23-H1 mRNA and tumor invasive and metastatic potential in HCC and to evaluate the relationship in the expression between CD44v6 mRNA and nm23-H1 mRNA, we detected their expression in HCC by in situ hybridization.

Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis

Objective: To discuss the expression of long noncoding RNA TUG1 (IneRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Methods: Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of IncRNA-TUG I in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between IncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using IncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after IncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western -blot test. Results: The expression level of lneRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P<0.05) and the high expression level of IncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (/'<0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by IncRNA-TUG1 specific siRNA (P<0.05). The results of qRT-PCR and western -blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after IncRNA-TUG1 was silenced (P<0.05). Conclusions: IncRNA-TUG1 shows an up -regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. IncRNATUGI can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met.

Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa

AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated(pure D), pure undifferentiated(pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTS Of the 298 patients, 165(55.4%) had mucosa-confined EGC and 133(44.6%) had submucosa-invasive EGC. Only 13(7.9%) cases of mucosa-confined EGC and 30(22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion(OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type(OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixedtype(OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixedtype group(P = 0.012) and pure U group(P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group(P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixedtype(P = 0.012) and pure U group(P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group(P = 0.375). Multivariate logistic analysis showed that only female sex(OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion(OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC(P = 0.106).CONCLUSION for mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

Prognostic factors in patients with node-negative gastric carcinoma:A comparison with node-positive gastric carcinoma

AIM： To identify the clinicopathological characteristics of lymph node-negative gastric carcinoma, and also to evaluate outcome indicators in the lymph node-negative patients.METHODS： Of 2848 gastric carcinoma patients, 1524 （53.5%） were lymph nede-negative. A statistical analysis was performed using the Cox model to estimate outcome indicators. RESULTS： There was a significant difference in the recurrence rate between lymph nede-negative and lymph node-positive patients （14.4% vs 41.0%, P〈0.001）. The 5-year survival rate was significantly lower in lymph node-positive than in lymph node-negative patients （31.1% vs 77.4%, P〈0.001）. Univariate analysis revealed that the following factors influenced the 5-year survival rate： patient age, tumor size, depth of invasion, tumor location, operative type, and tumor stage at initial diagnosis. The Cox proportional hazard regression model revealed that tumor size, serosal invasion, and curability were independent, statistically significant, prognostic indicators of lymph node-negative gastric carcinoma. CONCLUSION： Lymph node-negative patients have a favorable outcome attributable to high curability, but the patients with relatively large tumors and serosal invasion have a poor prognosis. Curability is one of the most reliable predictors of long-term survival for lymph nodenegative gastric carcinoma patients.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Relationship between cell adhesion molecules expression and the biological behavior of gastric carcinoma

AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 non- tumor gastric mucosas. RESULTS: The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION: The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma.

Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice

AIM: To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2 and bax. METHODS: A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. Resveratrol (500 mg/kg, 1 000 mg/kg and 1 500 mg/kg) was directly injected beside tumor body 6 times at an interval of 2 d. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alterations by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis-regulated genes bcl-2 and baxby immunohistoch-emical staining and PT-PCR. RESULTS: Resveratrol could significantly inhibit carcinoma growth when it was injected near the carcinoma. An inhibitory effect was observed in all therapeutic groups and the inhibition rate of resveratrol at the dose of 500 mg/kg, 1 000 mg/kg and 1 500 mg/kg was 10.58%, 29.68% and 39.14%, respectively. Resveratrol induced implanted tumor cells to undergo apoptosis with apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation. The inhibition rate of 0.2 mL of normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol, and 1 500 mg/kg resveratrol was 13.68±0.37%, 13.8±0.43%, 48.7±1.07%, 56.44±1.39% and 67±0.96%, respectively. The positive rate of bd-2 protein of each group was 29.48±0.51%, 27.56±1.40%, 11.86±0.97%, 5.7±0.84% and 3.92±0.85%, respectively by immunohistochemical staining. The positive rate of bax protein of each group was 19.34±0.35%, 20.88±0.91%, 40.02±1.20%, 45.72±0.88% and 52.3±1.54%, respectively by immunohistochemical staining. The density of bcl-2 mRNA in 0.2 mL normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol, and 1 500 mg/kg resveratrol decreased progressively and the density of bax mRNA in 0.2 mL normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol, and 1 500 mg/kg increased progressively with elongation of time by RT-PCR. CONCLUSION: Resveratrol is able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated by down-regulating apoptosis-regulated gene bcl-2 and up-regulating the expression of apoptosis-regulated gene bax.

Lymph node metastasis in early gastric cancer with submucosal invasion:Feasibility of minimally invasive surgery

AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995.Besides investigating many clinicopathological features such as tumor size,gross appearance,and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS:The rate of lymph node metastasis in cases where the depth of invasion was<500 μm,500-2 000 μm,or >2 000 μm was 9%(2/23),19%(7136),and 33%(15/46), respectively(P<0.05).In univariate analysis,no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age,sex,tumor location,gross appearance,tumor differentiation,Lauren's classification,and lymphatic invasion.In multivariate analysis, tumor size(>4 cm vs≤2 cm,odds ratio=4.80, P=0.04)and depth of invasion(>2 000 μm vs ≤500 μm, odds ratio=6.81,P=0.02)were significantly correlated with lymph node metastasis.Combining the depth and size in cases where the depth of invasion was less than 500 μm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm.In cases where the tumor size was less than 2 cm,lymph node metastasis was found only where the depth of tumor invasion was more than 2 000 μm. CONCLUSION:MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 μm in depth.

Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

Reduction of CAII Expression in Gastric Cancer: Correlation withInvasion and Metastasis

Objective： Human carbonic anhydrases II （CAII） gene plays an important role in different cancer. However, its relevance to gastric cancer （GC） remains unclear. In the present study, we aimed to investigate the expression of CAII in GC and explore its correlation with some clinicopathologic characteristics of GC. Methods： The expression of CAII in 20 specimens of normal gastric mucosa, 38 specimens of intraepithelial neoplasia and 112 specimens of gastric carcinoma were detected by immunohistochemical techniques. Survival in GC with CAII expression was studied. Results： The positive rate of CAII protein in normal gastric mucosa was significantly higher than that in intraepithelial neoplasia and gastric carcinoma （100% vs. 63.16% and 28.57%, P0.001）. The positive rate of CAII protein was significantly higher in gastric carcinoma at early stages than that at advanced stages （70.0% vs. 19.57%, P0.001）. The positive rate of CAII protein was significantly lower in gastric carcinoma with lymph node metastases than that without lymph node metastases （10.81% vs. 37.33%, P0.05）. Furthermore, the positive rate of CAII protein was significantly lower in poorly-differentiated gastric carcinoma than in moderately- or well-differentiated gastric carcinoma （15.94% vs. 31.03% or 60.00%, P0.05）. Moreover, CAII expression was not related with sex, age and tumor size. The patients with CAII-positive tumors showed a better survival rate than those with CAII-negative tumors （P=0.024, log-rank test）. Conclusion： CAII expression was related with stages and lymph node metastases in gastric carcinoma. The reduction of CAII expression in GC might promote tumor cell motility and contribute to tumor growth and metastasis.

Prognostic factors of minimally invasive surgery for gastric cancer: Does robotic gastrectomy bring oncological benefit?

BACKGROUND Gastric cancer is the third leading cause of cancer-related death worldwide and surgical resection remains the sole curative treatment for gastric cancer.Minimally invasive gastrectomy including laparoscopic and robotic approaches has been increasingly used in a few decades.Thus far,only a few reports have investigated the oncological outcomes following minimally invasive gastrectomy.AIM To determine the 5-year survival following minimally invasive gastrectomy for gastric cancer and identify prognostic predictors.METHODS This retrospective cohort study identified 939 patients who underwent gastrectomy for gastric cancer during the study period.After excluding 125 patients with non-curative surgery(n=77),other synchronous cancer(n=2),remnant gastric cancer(n=25),insufficient physical function(n=13),and open gastrectomy(n=8),a total of 814 consecutive patients with primary gastric cancer who underwent minimally invasive R0 gastrectomy at our institution between 2009 and 2014 were retrospectively examined.Accordingly,5-year overall and recurrence-free survival were analyzed using the Kaplan–Meier method with the log-rank test and Cox regression analyses,while factors associated with survival were determined using multivariate analysis.RESULTS Our analysis showed that age>65 years,American Society of Anesthesiologists(ASA)physical status 3,total or proximal gastrectomy,and pathological T4 and N positive status were independent predictors of both 5-year overall and recurrencefree survival.Accordingly,the included patients had a 5-year overall and recurrence-free survival of 80.3%and 78.2%,respectively.Among the 814 patients,157(19.3%)underwent robotic gastrectomy,while 308(37.2%)were diagnosed with pathological stage II or III disease.Notably,our findings showed that robotic gastrectomy was an independent positive predictor for recurrence-free survival in patients with pathological stage II/III[hazard ratio:0.56(0.33-0.96),P=0.035].Comparison of recurrence-free survival between the robotic and laparoscopic approach using propensity score matching analysis verified that the robotic group had less morbidity(P=0.005).CONCLUSION Age,ASA status,gastrectomy type,and pathological T and N status were prognostic factors of minimally invasive gastrectomy,with the robot approach possibly improving long-term outcomes of advanced gastric cancer.

Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland(HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery(LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor(SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm intothe submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG.

Gastric neuroendocrine neoplasms: A review

Gastric neuroendocrine neoplasms(g-NENs)or neuroendocrine tumors are generally slow-growing tumors with increasing incidence.They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features.Type 1 and 2 are gastrin dependent,whereas type 3 and 4 are sporadic.The reason for hypergastrinemia is atrophic gastritis in type 1,and gastrin releasing tumor(gastrinoma)in type 2 g-NEN.The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy.g-NENs are positively stained with chomogranin A and synaptophysin.Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis.It is crucial to discriminate between types of g-NENs,because the management,treatment and prognosis differ significantly between subtypes.Treatment options for g-NENs include endoscopic resection,surgical resection with or without antrectomy,medical treatment with somatostatin analogues,netazepide or chemotherapy regimens.Follow-up without excision is another option in appropriate cases.The prognosis of type 1 and 2 g-NENs are good,whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.