Predicting prognosis of rectal cancer patients with total mesorectal excision using molecular markers

AIM:To explore the prognostic variables in rectal cancer patients undergoing curative total mesorectal excision and the effect of postoperative chemotherapy in advanced rectal cancer. METHODS:A total of 259 consecutive rectal cancer patients treated with curative total mesorectal excision between 1999 and 2004 were collected. p53,p21,PCNA,and CD44v6 were examined using immunohistochemistry (IHC). The correlation between clinicopathological or molecular variables and clinical outcomes,including local recurrence,metastasis,disease-free survival and overall survival,was analyzed. RESULTS:The median follow-up was 44 mo. Five-year survival rates and 5-year disease free survival rates were 75.43% and 70.32%,respectively. Multi-analysis revealed TNM staging,preoperative CEA,and CD44v6 level were independent risk factors predicting overall survival or disease free survival. The hazard ratio of peroperative CEA was 2.65 (95% CI 1.4-5) and 3.10 (95% CI 1.37-6.54) for disease free survival and overall survival,respectively. The hazard ratio of CD44v6 was 1.93 (95% CI 1.04-3.61) and 2.21 (95% CI 1.01-4.88) for disease free survival and overall survival,respectively. TNM staging was the only risk factor predicting local recurrence. Postoperative chemotherapy without radiotherapy did not improve patients' outcome. CONCLUSION:TNM staging,preoperative CEA and CD44v6 were independent prognostic factors for rectal cancer patients with total mesorectal excision. Postoperative chemotherapy may be only used together with radiotherapy for rectal cancer patients.     

Association between interleukin-1 gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in a Chinese population

BACKGROUND AND AIM: Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. Interleukin-1 (IL-1) is a key cytokine involved in H. pylori-induced gastric inflammation. The present study aimed to determine polymorphisms of IL-1B and IL-1 receptor antagonist (IL-1RN) genes and their association with H. pylori infection and gastroduodenal diseases in Chinese patients. METHODS: Three hundred and ninety-nine patients with gastroduodenal diseases (129 chronic gastritis, 127 duodenal ulcer and 143 non-cardiac gastric cancer) and 264 healthy controls were genotyped for IL-1B-511 and IL-1RN gene polymorphisms by the PCR-RFLP method. H. pylori infection status was determined by a validated serological test. RESULTS: The frequency of IL-1B-511 T allele was significantly higher in H. pylori positive patients with non-cardiac gastric cancer than in both H. pylori negative patients with non-cardiac gastric cancer (60%vs 46%, P = 0.0342, OR = 1.666, 95% confidence interval [CI]: 1.045-2.656) and in healthy controls (60%vs 48%, P = 0.0071, OR = 1.665, 95%CI: 1.149-2.412). However, the polymorphism was not associated with chronic gastritis and duodenal ulcer. Multivariate logistic regression analyses identified that IL-1B-511 T/T carrier status was an independent risk factor for non-cardiac gastric cancer in the presence of H. pylori infection (adjusted OR = 3.01, 95%CI: 1.27-7.11, P = 0.01), and the frequency of IL-1B-511 T allele was an increased risk factor for developing gastric cancer (P = 0.03, adjusted OR = 2.29, 95%CI: 1.08-4.86). There was no association between IL-1RN gene polymorphisms and H. pylori infection and other gastroduodenal diseases. CONCLUSION: IL-1B-511 T allele is associated with H. pylori infection in non-cardiac gastric cancer in a Chinese population. The IL-1B-511 gene polymorphism appears to play an important role in gastric carcinogenesis in Chinese patients with H. pylori infection.     

Prevalence of metabolic syndrome, insulin resistance, impaired fasting blood glucose, and dyslipidemia in Uygur and Kazak populations

This study was designed to evaluate the prevalence of the metabolic syndrome (MetS), impaired fasting blood glucose (IFG), insulin resistance (IR), hypertriglyceridemia (HTG), and low high-density lipoprotein cholesterol (HDL-C) in adult Uygur and Kazak populations. Questionnaires, blood pressure, anthropometric measurement, and fasting glucose were evaluated. The age-adjusted prevalence of MetS and IFG was 3.43- and 1.47-fold higher, respectively, in Uygurs compared with Kazaks. The prevalence of IR and HTG was 1.33- and 2.22-fold higher, respectively, in Uygurs compared with Kazaks. In addition, the prevalence of low HDL-C was 4.05-fold higher in Uygurs compared with Kazaks. These data depicted greater risk for cardiometabolic syndrome in Uygurs compared with Kazaks. In addition, all prevalence with the exception of low HDL-C was greater in men compared with women in both ethnic groups. For body mass index (BMI)<24, 24 to 28, and ≥28 kg/m2, the prevalence of MetS, HTG, and low HDL-C was higher in Uygurs than Kazaks at the same BMI level. For individuals with a BMI between 24 and 28, the prevalence of IR but not IFG was significantly greater in Uygurs than Kazaks. At BMI≥28, neither IFG nor IR was overtly different between the two ethnic groups.     

支气管激发试验前后小气道功能测定对慢性咳嗽病因诊断的价值

目的 探讨慢性咳嗽患者支气管激发试验前后小气道功能、气道阻力及胸外气道反应的状况.方法 68例慢性咳嗽患者进行组胺支气管激发试验,观察FEV1、呼气中期流速(MEF50)及吸气中期流速(MIF50)的变化,并应用脉冲振荡技术测定激发前后患者气道阻力.结果 支气管激发试验阳性率52％,激发阳性患者激发前MEF50,R0与阴性组患者差异有统计学意义.MEF50激发后/激发前比值(MEF50％)与FEV1激发后/激发前比值(FEV1％)呈正相关,与R0激发前后差值(R0-d)呈负相关.13例患者呈现胸外气道高反应(占总例数20％),其中6例为单独存在胸外气道高反应,7例患者合并支气管气道高反应.结论 观察慢性咳嗽患者小气道功能变化,有利于对哮喘的及早诊治,有利于遏制小气道不可逆损害发展为COPD的危险.激发试验时联合观察支气管气道反应和胸外气道反应,可为临床诊断提供线索.     

反义IL-5载体构建及其对IL-5 mRNA和蛋白表达的影响

目的构建含反义IL-5的重组腺相关病毒(rAAV)asIL-5,观察rAAV asIL-5对哮喘大鼠CD+4T淋巴细胞IL-5mRNA和蛋白表达的影响。方法用基因重组方法构建反义IL5rAAV真核表达载体质粒pasIL-5/rAAV,磷酸钙沉淀法将真核表达载体质粒pasIL-5/rAAV、包装质粒pXX2、辅助质粒pXX6共转染入病毒包装细胞293细胞中,合成rAAV asIL5,Southernblot测重组病毒的滴度;将rAAV asIL5转染经密度梯度法和免疫磁珠法分离的哮喘大鼠CD+4T淋巴细胞,用半定量RT PCR、ELISA分别检测转染后细胞内IL5mRNA及细胞培养上清液中IL-5蛋白的表达水平。结果(1)成功构建并鉴定了rAAV asIL-5,滴度为1.3×1011病毒颗粒/ml;(2)病毒转染孔的相对吸光度值为1.0515±0.1477,低于对照孔(1.4271±0.1655,P<0.01);(3)细胞培养上清液中IL-5的含量病毒转染孔为(12.0840±1.4769)ng/L,低于对照组[(15.3590±1.2685)ng/L,P<0.01]。结论rAAV asIL-5能够抑制哮喘大鼠CD+4T淋巴细胞IL5mRNA和蛋白表达,为研究哮喘的基因治疗提供了实验依据。     

Phosphoinositol lipids bind to phosphatidylinositol 3 (PI3)-kinase enhancer GTPase and mediate its stimulatory effect on PI3-kinase and Akt signalings

Phosphatidylinositol 3 (PI3)-kinase enhancer (PIKE) is a nuclear GTPase that enhances PI3-kinase activity in a GTP-dependent manner. Both PIKE-L and -A isoforms contain GTPase, pleckstrin homology (PH), ADP ribosylation factor-GTPase-activating protein, and two ankyrin repeats domains, and C-terminal ADP ribosylation factor-GTPase-activating protein activates its internal GTPase activity. However, whether PH domain modulates the intramolecular action and subsequently influences its downstream signalings remains elusive. Here we show that PH domain from PIKE-L robustly binds PI(3,4,5)P(3) and exclusively resides in the nucleus. By contrast, the mutant (K679,687N), unable to bind phosphoinositol lipids, translocates to the cytoplasm. This mutation substantially compromises the stimulatory effects on PI3-kinase by PIKE-L. Surprisingly, PH domain from PIKE-A distributes in the cytoplasm. Similar mutation in PH domain of PIKE-A abolishes its binding to PI(3,4,5)P(3) and significantly decreases its activation of Akt. Moreover, amplified PIKE-A from human cancers contains mutations and highly stimulates Akt kinase activity, correlating with its GTPase activity. Thus, phosphatidylinositols regulate PIKE GTPase activity, mediating its downstream PI3-kinase/Akt signaling through a feedback mechanism by binding to its PH domain.     

健胃灵合剂防治胃癌癌前病变的临床研究

对经胃镜及病理学确诊的慢性萎缩性胃炎伴肠化和（或）异型增生的患者，随机分为治疗组（健胃灵合剂）61例，对照组（维酶素胶囊）31例。治疗6个月后复查，结果临床总有效率分别为91．8％、54．8％，胃镜疗效分别为86．9％、51．6％，病理疗效分别为77．0％、41．6％，两组比较均提示有非常显著性差异（均P＜0．01）。     

双膦酸盐相关性颌骨坏死1例报告及文献复习

双膦酸盐类药物被广泛用于治疗骨质疏松、恶性肿瘤骨转移等相关的骨骼疾病,引起颌骨骨坏死是其严重的并发症。这种并发症或自然发生,或发生于简单牙槽外科手术后。本文报告1例静脉使用双膦酸盐类药物唑来膦酸(zoledronic acid)致上颌骨骨坏死病例,并结合文献,对双膦酸盐相关性颌骨坏死的发病机制、临床表现、预防和治疗进行讨论。