Significance of regenerating islet-derived type Ⅳ gene expression in gastroenterological cancers

The regenerating islet-derived members (Reg ),a group of small secretory proteins,which are involved in cell proliferation or differentiation in digestive organs,are upregulated in several gastrointestinal cancers,functioning as trophic or antiapoptotic factors.Regenerating islet-derived type Ⅳ (RegⅣ ),a member of the Reg gene family,has been reported to be overexpressed in gastroenterological cancers.RegIV overexpression in tumor cells has been associated with carcinogenesis,cell growth,survival and resistance to apoptosis.Cancer tissue expressing RegⅣ is generally associated with more malignant characteristics than that without such expression,and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers.We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorectal cancer.The biologic functions of RegⅣ protein in cancer tissue,associated with carcinogenesis,antiapoptosis and invasiveness,are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegⅣ,and the feasibility of antibody therapy targeting RegⅣ is being assessed.These studies may lead to novel therapeutic strategies for gastroenterological cancers expressing RegⅣ .This review article summarizes the current information related to biological functions as well as clinical importance of RegⅣ gene to clarify the significance of RegⅣ expression in gastroenterological cancers.

Prognostic factors in stage IB gastric cancer

AIM:To identify the subset of patients with stage IB gastric cancer with an unfavorable prognosis.METHODS:Overall survival(OS)rates were examined in 103 patients with stage IB(T1N1M0 and T2N0M0)gastric cancer between January 2000 and December2011.Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model.RESULTS:The OS rates of patients with T1N1 and T2N0 cancer were 89.2%and 94.1%at 5-years,re-spectively.Both univariate and multivariate analyses demonstrated that tumor location was the only significant prognostic factor.The OS rate was 81.8%at5-years when the tumor was located in the upper third of the stomach and was 95.5%at 5-years when the tumor was located in the middle or lower third of the stomach(P=0.0093).CONCLUSION:These data may suggest that tumor location is associated with survival in patients with stage IB gastric cancer.

Feasibility of gastric endoscopic submucosal dissection in elderly patients aged≥80 years

BACKGROUND Endoscopic resection,especially endoscopic submucosal dissection(ESD),is increasingly performed in elderly patients with early gastric cancer,and lesions beyond the expanded indications are also resected endoscopically in some patients.It is essential to assess whether gastric ESD is safe and suitable for elderly patients and investigate what type of lesions carry an increased risk of ESD-related complications.AIM To assess the efficacy and feasibility of gastric ESD for elderly patients,and define high-risk lesions and prognostic indicators.METHODS Among a total of 1169 sessions of gastric ESD performed in Kanagawa Cancer Center Hospital from 2006 to 2014,179 sessions(15.3%)were performed in patients aged≥80 years,and 172 of these sessions were done in patients with a final diagnosis of gastric cancer.These patients were studied retrospectively to evaluate short-term outcomes and survival.The short-term outcomes included the rates of en bloc resection and curative resection,complications,and procedurerelated mortality.Curability was assessed according to the Japanese Gastric Cancer Treatment Guidelines 2010.Fisher’s exact test was used to statistically analyze risk factors.Clinical characteristics of each group were compared using Fisher’s exact test and Mann-Whitney U test.Survival rates at each time point were based on Kaplan-Meier estimation.Overall survival rates were compared between patients with gastric cancer in each group with use of the log-rank test.To identify prognostic factors that jointly predict the hazard of death while controlling for model overfitting,we used the least absolute shrinkage and selection operator(LASSO)Cox regression model including factors curative/noncurative,age,gender,body mass index,prognostic nutritional index,Charlson comorbidity index(CCI),Glasgow prognostic score,neutrophil-to-lymphocyte ratio,and antithrombotic agent use.We selected the LASSO Cox regression model that resulted in minimal prediction error in 10-fold cross-validation.P<0.05 was considered statistically significant.RESULTS The en bloc dissection rate was 97.1%,indicating that a high quality of treatment was achieved even in elderly patients.As for complications,the rates of bleeding,perforation and aspiration pneumonitis were 3.4%,1.1%and 0.6%,respectively.These complication rates indicated that ESD was not associated with a particularly higher risk in elderly patients than in nonelderly patients.A dissection incision>40 mm,lesions associated with depressions,and lesions with ulcers were risk factors for post-ESD bleeding,and location of the lesion in the upper third of the stomach was a risk factor for perforation in elderly patients(P<0.05).Location of the lesion in the lower third of the stomach tended to be associated with a higher risk of bleeding.The overall survival(OS)did not differ significantly between curative and noncurative ESD(P=0.69).In patients without additional surgery,OS rate was significantly lower in patients with a high CCI(≥2)than in those with a low CCI(≤1)(P<0.001).CONCLUSION Gastric ESD is feasible even in patients aged≥80 years.Observation without additional surgery after noncurative ESD is reasonable,especially in elderly patients with CCI≥2.

Growth inhibition of a human colon carcinoma cell, COLO 201, by a natural product, <i>Vitex agnus-castus</i>fruits extract, <i>in vivo</i>and <i>in vivo</i>

An extract from ripe fruit of Vitex agnus-castus (Vitex) has been used to treat patients with various obstetric and gynecological disorders in Europe. We have demonstrated that Vitex showed cytocidal effects on various types of cancer cell lines including a human colon carcinoma cell line, COLO 201. In this study, we extended our previous study to investigate the detailed mechanisms underlying cytocidal effects of Vi- tex on COLO 201. Furthermore, a possible clinical application of Vitex was also explored in vivo using nude mice xenografted with the cells. Treatment with Vitex induced apoptosis in COLO 201 in a time-dependent manner, accompanying with activa-tion of caspase-9 and -3, but not caspase-8. An inhibitor for c-Jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK), significantly suppressed the apoptosis induction along with caspase-3 activation. Endoplasmic reticulum (ER) stress-related genes were also upregulated by Vitex treatment. Most importantly, the in vivo efficacy of Vitex evaluated by assessing the tumor growth revealed that the administration of Vitex significantly suppressed tumor growth in COLO 201 xenografted mice. Collectively, current results suggest that apoptosis induction by Vitex in COLO 201 is mediated through the activation of JNK and caspase-9, -3 resulted from ER stress. Based on the current clinical application of Vitex, these results thus provide a new insight into the clinical use of Vitex and leave open a possibility of a new regimen as an alternative medicine approach for such devastating colon cancer treatment.

新辅助化疗后行腹腔镜辅助胃切除术治疗晚期胃癌

目前治疗晚期胃癌的方法为开腹胃切除及D2淋巴结清扫并在术后行S-1或卡倍他滨加奥沙利铂辅助化疗。然而III期胃癌患者的预后并不理想。为了提高生存率,需要加大化疗药物的剂量。鉴于患者接受二联或三联化疗的顺应性差,新辅助化疗将是一个充满前景的方法。目前在东亚国家,正进行多项III期临床试验用于评估新辅助化疗效果。另一方面,手术治疗方法已倾向于行腹腔镜手术。在日本和韩国已经进行了多项III期临床试验评估腹腔镜辅助远端胃切除(LADG)在早期和晚期患者中的疗效。因此,未来标准治疗肿瘤位于中、下1/3晚期胃癌的候选方案由综合治疗组成,包括新辅助化疗及随后的LADG。只要新辅助化疗是按标准实施,随后的腹腔镜胃切除术的可行性、安全性及长期生存率是有保障的。在这个背景下,我们实施了一项随机II期临床试验比较新辅助化疗后LADG和开腹远端胃切除术(ODG)治疗胃癌的疗效。