Emerging evidence has demonstrated that N6 -methyladenosine (m6 A) and long noncoding RNAs (lncRNAs) are both crucial regulators in gastric cancer (GC) tumorigenesis. However, the interaction of m6 A and lncRNAs in GC progression are still unclear. Here, our team discovered that lncRNA LINC00958 expression up-regulated in GC tissue and cells. Clinically, high-expression of LINC00958 was clinically correlated to lower survival of GC patients. Functionally, in vitro assays demonstrated that LINC00958 promoted the GC cells' aerobic glycolysis. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) found that there were m6 A-modificated sites in LINC00958, and moreover m6 A methyltransferase KIAA1429 catalyzed the m6 A modification on LINC00958 loci. Moreover, LINC00958 interacted with GLUT1 mRNA via the m6 A-dependent manner to enhance GLUT1 mRNA transcript stability, thereby positively regulating the aerobic glycolysis of GC. In conclusion, our findings reveal the function and mechanism of KIAA1429-induced LINC00958 in GC, delineating novel understanding of m6 A-lncRNA in cancer biology.
目的 研究微管相关蛋白样激酶1(doublecortin-like kinase 1,DCLK1)在胃癌组织中的表达及其临床意义.方法 回顾性分析2006年5月至2011年7月在河南省人民医院住院治疗的267例胃癌病人临床病理资料,免疫组化染色法检测267例胃癌组织和138例癌旁正常组织中DCLK1的表达,分析DCLK1表达与胃癌病人临床病理特征之问的关系,Cox风险回归模型回归分析影响胃癌病人预后生存的影响因素,Kaplan-Meier法绘制不同DCLK1表达水平病人的5年总体生存和无复发生存曲线,Log-rank法比较5年总体生存和无复发生存的差异.结果 DCLK1在胃癌组织中的高表达率71.9%(192/267)高于癌旁正常组织26.1%(36/138).单因素分析显示DCLK1高表达与病人性别、年龄,肿瘤大小,位置等临床病理因素之问无显著关联(P>0.05),与肿瘤分化程度、浸润深度、神经侵犯、脉管侵犯、淋巴转移及临床分期等临床病理因素之问有关(P<0.05).Cox回归分析显示DCLK1高表达、临床分期和肿瘤分化程度是胃癌病人总生存率和无复发生存率的独立影响因素(P<0.05).Kaplan-Meier生存分析显示,DCLK1高表达的胃癌病人的总生存率和无复发生存率较低(P<0.05).结论 DCLK1在胃癌组织中高表达是胃癌病人预后生存的独立影响因素.
Objective To investigate the expression and clinical significance of epithelial cell adhesion molecule(EpCAM) and Claudin-18 in gastric cancer.Methods Surgical specimens of gastric cancer were taken from 64 patients.The histological diagnostic criteria were based on WHO standards.Immunohistochemical staining was used to detect expression levels of EpCAM and Claudin-18 in all samples.The relationship between the expression of EpCAM and Claudin-18 and clinicopathological parameters of gastric cancer was analyzed.Correlations of the prognosis of gastric cancer patients with EpCAM and Claudin-18 expression were analyzed using the Cox proportional hazards regression model.Results The positive expression rate of EpCAM was elevated with the increase in tumor size and the occurrence of distant metastasis(x2 =4.526 and 36.090,P=0.033 and 0.000).There were significant differences in Claudin-18 protein expression among different age,TNM stage,growth pattern,depth of invasion and distant metastasis patients(all P<0.05).Cox regression model analysis showed that tumor size and distant metastasis were the main risk factors affecting the survival of patients with gastric cancer (RR =50.076 and 1.617,P =0.016 and 0.032),while levels of EpCAM and Claudin-18 were not independent risk factors (both P > 0.05).Conclusions EpCAM and Claudin-18 are closely related to the invasiveness of gastric cancer,but abnormally high levels of EpCAM and Claudin-18 are not independent risk factors for the prognosis of gastric cancer patients.
Background: The role of miR-200a-3p in gastric cancer (GC) remain unclear. Materials and methods: miR-200a-3p expression in 65 paired GC and adjacent tissues (AT) were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation, cell cycle, and cell migration were assessed by cell growth counting assay, cell cycle analysis, and transwell assay, respectively. The target of miR-200a-3p was analyzed by dual-luciferase reporter assay. Results: miR-200a-3p in GC tissues was significantly reduced compared with AT. miR-200a-3p expression was closely associated with clinicopathological features (P < .05). SGC-7901 cell line demonstrated the lowest level of miR-200a-3p. Cell proliferation and colony formation was significantly inhibited by miR-200a-3p overexpression, but increased by miR-200a-3p knockdown (P < .05). miR-200a-3p upregulation increased the G1/S cell ratio. The 3'-UTR of KLF12 directly interacted with miR-200a-3p. Furthermore, increased levels of KLF12 expression was detected in GC tissues. A correlation analysis suggested a negatively correlation between miR-200a-3p and KLF12 mRNA expressions. Conclusion: miR-200a-3p was down-regulated in GC tissues and was correlated with clinicopathological features. miR-200a-3p overexpression inhibits GC cell proliferation, cell cycle, and cell migration. Furthermore, miR-200a-3p might act as a tumor suppressor in GC by targeting KLF12.
面对医学科学的迅速发展和临床技能培养模式的改变,如何训练和加强临床医师主动学习的能力是医学教育的关键问题.如何分析学生临床学习过程中的难点、启迪其临床思维、提升诊断与鉴别诊断的分析能力,提高教学查房的效果,是当前消化内科临床教学面临的难点.我们探索和总结多种教学方法,根据不同的学员群体特点因人施教,遵循强调临床思维能力培养的理念,在消化亚专业发展和提升过程中,采取入科教育、临床路径、循证医学、病例讨论、教学查房、PBL、模拟教学等多种个体化的教学方法,同时注重创新思维能力培养,实现了消化病学教学质量的优化,有效提高了临床教学效果.
目的 探讨内镜黏膜下剥离术(ESD)治疗食管和胃早癌及癌前病变的临床疗效,并分析手术前后标本病理特点的差异.方法 337例研究对象术前经胃镜活检标本检查确诊为早期食管癌、早期胃癌或癌前病变,均经ESD治疗,观察其临床表现特征、术前及术后病理特点的差异等.结果 共切除病灶372处,其中多发病变30例.术前钳取活检总正确率为55.91%(208/372),漏诊率6.72%(25/372),对高级别上皮内瘤变(HGIN)和早癌的低估率为19.86%(29/146).边缘/基底阳性率4.57%(17/372).结论 ESD是治疗食管及胃早癌及癌前病变的有效方法,并且可以提高病理的诊断正确率.ESD术前的病理活检正确率需进一步提高.ESD病理标本阳性与术前判断病变、ESD操作有关.
AIM To observe the curative effects of Boerning capsules plus the XELOX (oxaliplatin,capecitabine) regimen in the treatment of colorectal cancer after operation.METHODS Sixty-four colorectal cancer patients were randomly divided into either a treatment group or a control group.Both groups were treated with the XELOX regimen,and Boerning capsules were additionally used in the treatment group.Therapeutic effects and adverse reactions were observed.RESULTS The response rate was 53.1% in the treatment group and 40.6% in the control group,and there was no significant difference between the two groups (P > 0.05).Boerning capsules markedly reduced the adverse reactions associated with chemotherapy and improved the quality of life in colorectal cancer patients (P < 0.05).There was a significant change in T-cell count/function,a parameter of the patients' immune function (P < 0.05).CONCLUSION Boerning capsules can improve the quality of life of colorectal cancer patients by ameliorating the adverse symptoms caused by chemotherapy.
Objective To investigate the expressions and significances of integrin α3 and β-catenin proteins in gastric cancer.Methods The expressions of integrin α3 and β-catenin proteins were detected by immunohistochemical method in primary gastric cancer tissues (gastric cancer group) and adjacent normal tissues (control group) from 48 patients with gastric cancer to compare the positive rates of integrin α3 and β-catenin proteins between those with and without lymph node metastasis,with and without serous infiltration,and between differently differentiated types in gastric cancer group.The correlation between integrin α3 and β catenin proteins was analyzed in gastric cancer group.Results The positive rates of integrin α3 and β-catenin were significantly higher in gastric cancer group (43.75%,52.08%) than those in control group (6.25%,0) (P<0.05),in those with lymph node metastasis (60%,64%) than those without lymph node metastasis (26.08%,39.13%%) (P<0.05),and in those with serous infiltration (61.54%,65.38%) than those without serous infiltration (22.73%,36.36%) (P< 0.05),and there were no significant differences between poorly differentiated type (47.83%,56.52%) and moderately and highly differentiated type (40.00%,48.00%) (P>0.05).The expression of integrin α3 was positively correlated with β-catenin (r=0.360,P=0.016) in gastric cancer group.Conclusion Both integrin α3 and β-catenin are highly expressed in gastric cancer tissue,playing a synergic role in the development,invasion and metastasis.
Objective To evaluate the effect and pathological characters for patients with early esophageal carcinoma and intraepithelial neoplasia after endoscopic submucosal dissection (ESD). Methods 69 patients from January 2013 to January 2016 were treated with ESD at the early stage of esophageal carcinoma and intraepithelial neoplasia. The clinical features and the size of the lesions of all the patients were collected. Then analyzed postoperative complications and pathological characteristics. Results Among 69 cases, 16 were early esophageal cancer, 38 were high-grade esophageal neoplasia and 35 were low-grade esophageal neoplasia. The whole piece resection rate was 100.00 % (69/69), complete resection rate and curative resection rate was 95.65 % (66/69), respectively. The largest removal diameter is 7.0 cm. Biopsy accuracy was 69.57 % (48/69). Compared with biopsy, diagnostic accuracy with ESD specimens is higher. Conclusion The early esophageal carcinoma and intraepithelial neoplasia can be treated with ESD. ESD can resect lesions primarily, provide complete specimen for further pathological assessment and improve diagnostic accuracy.
Objective To discuss the clinical efficacy of endoscopic submucosal dissection (ESD) for early esophageal cancer and precancerous lesions.Methods Selected 69 patients were diagnosed with early esophageal cancer or esophageal precancerous lesions by endoscopy, whom were confirmed by ESD treatment, observed the clinical features, complications, tumor size, preoperative and postoperative pathologic features.Results Surgical en bloc resection rate was 100%, complete resection rate was 95.7%, curative resection rate was 95.7%.Conclusion ESD is an effective treatment method of early esophageal cancer and precancerous lesions, which can provide a complete pathologic specimens for further assessment.
Ovarian cancer, primarily the epithelia-origin high-grade serous (HGS) type, is one of the most lethal gynecological malignancies. Clinically, over 75% of newly diagnosed HGS ovarian cancer patients carry stage III-IV diseases, and have less than 33% survival rate over a 5-year span. Current treatment of such aggressive disease remains largely dependent on two types of chemotherapeutic drugs: Taxane- and platinum-based agents. Thus, there is an imminent need for the improvement in the detection, diagnostic modalities and target-based therapies against this malignant disease. The majorities of HGS ovarian tumors exhibit mutational inactivation or loss of p53 and/or BRCA1/BRCA2 genes, thereby conferring strong genomic instabilities. As such, currently available target–based therapies, such as inhibitors targeting ErbB receptors or Raf/Ras/MAPK- or PI3k/Akt-dependent oncogenic pathways, display limited efficacy against HGS ovarian cancer. Our recent study suggests that the malignancy of this aggressive disease, at least in part, is regulated by CD151 and its associated laminin-binding (LB) integrins. Our clinical, functional and xenograft analyses consistently indicate that in contrast to prior reports on the RGD-based integrins, CD151-LB integrin complexes play a strong suppressive role in ovarian tumorigenesis and metastatic progression. In this short review/commentary, we will briefly summarize our current understanding of integrin function and signaling in ovarian cancer. We will discuss the emerging clinical significance and functional roles of CD151-LB integrin complexes in this disease. Finally, we will provide an outlook of how studies of CD151-integrin complexes may shape our understanding of ovarian cancer aggressiveness and facilitate the development of effective biomarkers and therapeutic targets.
Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumorsuppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated. Knocking down Slug partially restores CD151-α3β1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of β-catenin and Axin-2 as well as resistance to the inhibition in β-catenin-dependent transcriptional complexes. Together, our study demonstrates that CD151-α3β1 integrin complexes regulate ovarian tumor growth by repressing Slug-mediated EMT and Wnt signaling.
AIM:To investigate whether there were symptom-based tendencies in the Helicobacter pylori (H. pylori) eradication in functional dyspepsia (FD) patients. METHODS:A randomized, single-blind, placebo-controlled study of H. pylori eradication for FD was conducted. A total of 195 FD patients with H. pylori infection were divided into two groups: 98 patients in the treatment group were treated with rabeprazole 10 mg twice daily for 2 wk, amoxicillin 1.0 g and clarithromycin 0.5 g twice daily for 1 wk; 97 patients in the placebo group were given placebos as control. Symptoms of FD, such as postprandial fullness, early satiety, nausea, belching, epigastric pain and epigastric burning, were assessed 3 mo after H. pylori eradication. RESULTS:By per-protocol analysis in patients with successful H. pylori eradication, higher effective rates of 77.2% and 82% were achieved in the patients with epigastric pain and epigastric burning than those in the placebo group (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 46%, 36%, 52.5% and 33.3%, respectively, and there was no significant difference from the placebo group (39.3%, 27.1%, 39.1% and 31.4%) (P > 0.05). In 84 patients who received H. pylori eradication therapy, the effective rates for epigastric pain (73.8%) and epigastric burning (80.7%) were higher than those in the placebo group (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 41.4%, 33.3%, 50% and 31.4%, respectively, and did not differ from those in the placebo group (P > 0.05). By intention-to-treat analysis, patients with epigastric pain and epigastric burning in the treatment group achieved higher effective rates of 60.8% and 65.7% than the placebo group (33.3% and 31.8%) (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 34.8%, 27.9%, 41.1% and 26.7% respectively in the treatment group, with no significant difference from those in the placebo group (34.8%, 23.9%, 35.3% and 27.1%) (P > 0.05). CONCLUSION:The efficacy of H. pylori eradication has symptom-based tendencies in FD patients. It may be effective in the subgroup of FD patients with epigastric pain syndrome.
目的探讨小剂量奥沙利铂联合卡培他滨在老年晚期胃癌化疗中的近期疗效。方法对39例老年晚期胃癌患者采用小剂量奥沙利铂联合卡培他滨化疗,观察近期疗效及不良反应。结果化疗后,完全缓解1例、部分缓解24例、无变化9例、进展5例,总有效率为64.10%;平均生存期10.6个月;KPS≥80分者增加(P<0.01);毒副反应可耐受,经对症治疗后均好转。结论小剂量奥沙利铂联合卡培他滨治疗老年晚期胃癌的效果较好,毒副反应轻,可作为老年晚期胃癌的一线治疗方案。
目的观察含左氧氟沙星的三联疗法根除幽门螺杆菌(Hp)的疗效。方法选择98例有消化道症状的Hp阳性患者,随机分为3组,A组采用埃索美拉唑、阿莫西林、克拉霉素;B组采用埃索美拉唑、阿莫西林、左氧氟沙星;C组采用埃索美拉唑、克拉霉素、左氧氟沙星,疗程均为7 d。疗程结束后4周复查Hp。结果A、B、C组Hp根除率分别为59.38%、96.97%、78.79%,B组优于A、C组,后两组间无明显差异;症状缓解率分别为90.62%、93.94%、90.91%,组间无统计学差异。结论采用左氧氟沙星作为一线根除Hp方案根除率高,患者易于接受,是一种较为理想的治疗方案。
目的探讨溃疡性结肠炎(UC)患者的临床特征,提高对本病的认识及诊治水平。方法回顾性分析我院2000年-2008年收治的经消化内镜中心确诊的135例UC患者的临床特征。结果135例患者中,临床表现以腹泻发生率最高(82%),其次为脓血便(65.2%)和腹痛(58.5%);7.4%伴有肠外表现;9.6%出现并发症;大部分病例(76.3%)病变范围限于左半结肠炎;临床分型以初发型(36.3%)和慢性复发型(43%)为主;病情以轻度(32%)和中度(44%)为主;中度、重度患者腹痛发生率均显著高于轻度;轻度患者有16.3%为便秘型;重度患者76%为急性起病,肠外表现及严重并发症发生率均显著高于轻、中度患者。治疗药物主要为单纯5-氨基水杨酸类药物或5-氨基水杨酸类药物联用糖皮质激素,少数难治病例需要联用免疫抑制剂。单纯内科治疗的有效率为95.6%。结论UC有较明显的临床特征,认识这些特征有助于提高对本病的诊治水平。
Objective To study the relationship of serum contents of IL-8,IL-10 and TNF-α to ulcerative colitis.Methods Serum contents of IL-8,IL-10 and TNF-α in 40 patients with ulcerative colitis during different periods were determined with RIA,and were compared with 30 controls.Results Serum contents of IL-8 and TNF-α during acute period were higher than those during catabatic period in patients with ulcerative colitis significantly,and higher than those of controls too,but the contents of IL-10 were reverse.Serum contents of IL-8,IL-10 and TNF-α in patients with ulcerative colitis during catabatic period were not different from those of controls significantly.Serum contents of IL-8 and TNF-α during acute period in severe patients were higher than those of mild and moderate patients significantly,and IL-10 was adverse.Serum contents of IL-8 were positively correlated to TNF-α,negatively correlated to IL-10 during acute period significantly.Conclusion The immunity unbalance that IL-10 decreases and IL-8 and TNF-α increase during acute period induces ulcerative colitis.Serum contents of IL-8,IL-10 and TNF-α are correlated to the grade of inflammation.
Objective To evaluate the influence of compound glycyrrhizin combined with interferon to the immunologic function and anti - HBV effect in the treatment of chronic hepatitis B. Methods Sixty HBeAg positive HBV patients were divided into study group(30 cases) and control group(30 cases) according to partnership method, two group patients were all injected with interferonα -2b as basal remedy, besides the medicament,the study group received compound glycyrrhizin tablets in initial 12 weeks. T- lymphocyte- subsetes,liver funtion,blood routine,6 HBV markers, HBV -DNA and side effects were determined and inspected be-fore and after the treament. Results The study group' s immunologic function enhanced from the fourth week-end(8W >4W >0W, P <0.01 ),was approximate on the eighth weekend and the twelfth weekend ( P >0. 05) ;the control group's immunologic function enhanced from the eighth weekend (12W >8W >0W, P <0. 01 ) ;the study group's immunologic function excelleded the control group's on the fourth and eighth week-end ( P < 0.05), but no different on the twelvth weekend ( P > 0.05). The ALT value descended obviously from the second weekend in study group,but from the 8th weekend in control group, and the recovery rate of ALT exceeded the control group' s on 4th ,8th and 12th weekend ( P < 0.05 ). The rate of symptoms improverobviously or completely exceeded the control group' s on 4th, 8th and 12th weekend ( P < 0. 05 ). The rate of negative conversion of HBV - DNA and E - antigen conversion were not significantly different between two groups on 24th weekend ( P > 0.05). Conclusion Compound glyeyrrhizin combined interferon don' t debase body immunologic function, even enhance immunologic function in certain time, furthermore, could improve symptom and make ALT recovery rapidly,have no influence on interferon' s anti -HBV sequel.
Objective To test the expressions of multiple drug resistance(MDR) gene of human gastric carcinoma,and investigate its significance in guiding gastric carcinoma clinical chemotherapy by choosing appropriate remedy according to examination result.Methods Eighty gastric cancer patients diagnosed by endoscopy and pathology were random divided into two groups(fit group and non-fit group),each included 40 patients.The expression of P-gp、GST-π、Topo-Ⅱ was tested in 80 gastric cancer specimen using immunohistochemistry.The fit group patients were treated by choosing sensitive chemical remedy fitting for gene examination result.The non-fit group patients were treated with the experiential chemotherapeutic scheme of FOLFOX4.Results Positive expression rates of P-gp、GST-π、Topo-Ⅱ in 80 cases of gastric cancer were 51.5%、57.5%、46.3%,respectively.There were some correlations between the positive expression of P-gp、Topo-Ⅱ and the degree of tumor differentiation,which was higher in well differentiated tumor than that in poor differentiated one for P-gp,but it was reverse for Topo-Ⅱ. There were no correlations between the positive expression of GST-π and the degree of tumor differentiation.The response rate was 57.5% in the fit group,which was 35% in the non-fit group.There were significant different between the two groups(P0.05).Conclusion The mechanisms of drug resistance of P-gp、GST-π、Topo-Ⅱ in gastric cancer are different.It is of significance for guiding gastric cancer clinical therapy by applying the different,sensitive,scientific individual chemotherapy according to the detection results of drug resistance gene,and is helpful to achieve better chemotherapy efficacy for gastric cancer patients.