Notch信号转导通路与肿瘤分子靶向治疗研究进展

Notch信号转导通路与细胞增生、分化、凋亡密切相关,与肿瘤的关系日益受到关注,以Notch通路为靶点的肿瘤治疗策略显示了其广阔的应用前景.本文将从肿瘤中Notch通路的调控、分子靶向治疗机制及应用进展方面做一综述.     

Telomerase Activity in Tumor and Remnant Liver as Predictor of Recurrence and Survival in Hepatocellular Carcinoma after Resection

Background and Aim Results after curative liver resection in hepatocellular carcinoma are unsatisfactory with regard to high postoperative intrahepatic recurrence and liver failure. This study evaluates telomerase activity in liver with and without tumor as a predictor of recurrence and survival. Materials and Methods Liver tissue with and without tumor from 53 hepatocellular carcinoma patients receiving curative resection during the period of 1998–2000 was used for detecting telomerase activity by PCR-ELISA. Clinicopathological data were compared to identify predictors of recurrence and survival. Results Telomerase activity was detected in 98% of liver tissue with tumor and 70% liver tissue without. Telomerase activity in cancerous liver correlated significantly with HCV infection (P = 0.012) and cirrhotic change in liver parenchyma (P = 0.006). Telomerase activity in non-cancerous liver correlated with high serum AFP level (P = 0.002). The telomerase activity of liver tissue with and without tumor is significant higher in patients with recurrence than in those without recurrence, 413.7 ± 100.5 versus 110.8 ± 32.7, P = 0.006, and 34.7 ± 14.2 versus 4.2 ± 1.4, P = 0.039. Recurrence could be predicted by abnormally high tumor telomerase activity (P = 0.026) or by advanced TNM stage (P = 0.001). TNM stage or high serum ALT level could predict multinodular intrahepatic recurrence (P = 0.028 and P = 0.030). High serum AFP combined with high telomerase activity in liver without tumor had a significant ability to predict poor survival (OR: 11.19, CI: 1.95–64.12, P = 0.007). Conclusion Tumor telomerase is an independent predictor of recurrence. Simultaneous high remnant liver telomerase and high serum AFP is a strong negative predictor of survival.     

胰腺囊肿的诊断与治疗体会

目的探讨胰腺囊肿的诊断与治疗方法，减少对胰腺囊性疾病的误诊和误治。方法对1998年-2006年我院收治的44例胰腺囊肿患者的临床资料进行回顾性分析。结果假性胰腺囊肿占36例，占81，8％（36／44）；囊性肿瘤6例，占13．6％（6／44）；潴留性囊肿2例。6例假性胰腺囊肿经保守治疗后消退，8例行经皮穿刺引流，其余均行手术引流或切除术。结论假性胰腺囊肿占全部囊肿大多数且多由急性胰腺炎所致。在诊断假性囊肿时应首先排除囊性肿瘤，术前ERCP检查和术中组织冰冻切片对胰腺囊肿的鉴别诊断和选择合理的治疗方案至关重要。对已诊断的囊性肿瘤，无论良、恶性应尽可能作根治性切除术。     

肿瘤坏死因子α对人肝癌多药耐药逆转作用的实验研究

目的研究肿瘤坏死因子α（TNF-α）对体外培养的人肝癌耐阿霉素细胞系（HepG2／ADM）多药耐药现象的逆转作用。方法不同浓度（100、500及2500U／ml）TNF-α作用于HepG2／ADM细胞72h后进行以下试验：用实时荧光定量聚合酶链反应技术检测各组多药耐药相关基因（MDR1）及脂质过氧化物酶体增殖物激活受体α（PPAR-α）基因的mRNA表达情况;用罗丹明外排法检测各组P-糖蛋白活性;用Annexin V检测0．5mg／L阿霉素诱导的各组细胞凋亡情况;利用MTF法检测各组耐药性的改变。结果TNF-α能诱导HepG2／ADM细胞的MDR1基因表达下调,PPAR-α基因表达上调,且能增加阿霉素诱导的凋亡细胞的比例及细胞毒作用。结论TNF-α可能分别通过抑制MDR1表达及促进PPAR-α表达而逆转HepG2／ADM细胞的耐药性。     

Significance of CD44 Expression in Gastrointestinal Stromal Tumors in Relation to Disease Progression and Survival

Background CD44 is a transmembrane glycoprotein belonging to the cell-adhesion molecule family. It has been identified as being involved in tumor progression and metastasis, and its expression has been found to be of prognostic significance in several human malignancies. The aim of this study was to assess CD44 expression in gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumor of the gastrointestinal tract. Methods Between January 1995 and March 2006, 92 patients undergoing surgical resection for GIST in National Cheng Kung University Hospital were evaluated. To study the significance of CD44 expression, immunohistochemical staining of CD44 in tumor specimens was performed, and the clinicopathological information of patients was reviewed. Results Fifty-nine of 81 patients (73%) showed positive CD44 expression. Loss of CD44 expression was associated with disease progression (p = 0.019). Kaplan-Meier analysis revealed better progression-free survival among patients with strong CD44 expression (++ and +++) (p = 0.034), absence of disease progression (p < 0.001), and lower risk, according to National Institutes of Health (NIH) Consensus Criteria for GIST risk stratification (p = 0.003). Multivariate analysis demonstrated that high-risk status was the only independent risk factor for disease progression and the only independent predictor for a poor progression-free survival (p = 0.023 and 0.045, respectively). Conclusions It is demonstrated that high-risk status by NIH criteria is significantly associated with disease progression and poor progression-free survival in GIST.     

Safety of bariatric surgery in patients older than 65 years

BackgroundThe increase in life expectancy along with the obesity epidemic has led to an increase in the number of older patients undergoing bariatric surgery. There is conflicting evidence regarding the safety of performing bariatric procedures on older patients.ObjectiveThe purpose of this study was to compare the safety of laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) for older patients (>65 yr).SettingNationwide analysis of accredited centers.MethodsThe Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program 2015 to 2017 database was used to identify nonrevisional laparoscopic RYGB and SG procedures. Comparisons were made based on patient age. Clinical outcomes included postoperative events and mortality.ResultsThere was a total 13,422 and 5395 matched pairs for SG and RYGB in comparing patients aged 18 years to those aged 65 and >65 years, respectively, and 5395 matched RYGB and SG procedures performed in patients >65 years. The complication rate was higher in older patients undergoing RYGB compared with SG (risk difference = 2.39%, 95% confidence interval: 1.57%–3.21%, P < .0001). When comparing older to younger patients, the older group had a higher complication rate for SG but not for RYGB (SG: risk difference = 1.01%, 95% confidence interval: .59%–1.43%, P < .0001, RYGB: risk difference = .59%, 95% confidence interval: ?.29% to 1.47%, P = .2003).ConclusionsOverall complication rates of bariatric surgery are low in patients >65 years. SG appears to have a favorable safety profile in this patient population compared with RYGB. The overall complication rate for RYGB is not significantly different between the older and younger groups.     

内皮细胞固有型一氧化氮合酶基因内含子4插入/缺失多态性与糖尿病肾病的关系

目的：对天津地区汉族人内皮细胞固有型一氧化氮合酶（ecNOS)基因内含子4的插入／缺失多态性（ecNOS4b/a)与2型糖尿病肾病（DN）的关联性进行研究。方法：应用PCR－小卫星DNA多态性分析技术对ecNOS4b/a基因型分布进行检测。包括正常对照组70例，2型糖尿病无DN组48例，2型糖尿病有DN无慢性肾功能不全（CRF）组35例，2型糖尿病DN有CRF组45例和非DN导致的CRF组58例。结果：（1）发现1例罕见基因型（女性DN无CRF患者），为447bp 420bp杂合子。（2）2型糖尿病无DN组a等位基因频率高于正常对照组，差异无显著性意义（χ^2=1.672,P=0.196).(3)2型糖尿病伴DN组a等位基因频率低于2型糖尿病无DN组，差异无显著性意义（χ^2=1.082,P=0.298)。（4）DN无CRF组与DN伴CRF组等位基因频率相近（校正χ^2=0.002,P=0.967)。（5）DN伴CRF组a等位基因频率低于其它原因导致的CRF组，差异有显著性意义（χ^2=0.002,P=0.967)。（5）DN伴CRF组a等位基因频率低于其它原因导致的CRF组，差异有显著性意义（χ^2=4.360,P=06037)。结论：a等位基因可能不是天津汉族人DN的危险因素；天津地区汉族健康人群a等位基因频率低于日本；ecNOS在DN导致的CRF中的作用可能与非DN CRF不同。     

125I放射性粒子植入治疗晚期胰腺癌26例临床分析

目的 探讨125I放射性粒子植入治疗晚期胰腺癌的临床效果.方法 选择无外科根治性手术适应证的胰腺癌患者26例,开腹行125I放射性粒子植入术,胆肠Rou-en-y吻合术.术后观察：（1）术后胆红素下降情况;（2）术后1周内每日患者疼痛的缓解情况;（3）术后并发症发生情况.随访观察肿瘤变化、疼痛缓解程度以及存活期.结果 （1）术后1周内胆红素值降至术前一半的占52.3％（11/21）,以后胆红素继续缓慢下降,所有患者均在3周内降至正常;（2）术后1周94.7％的患者疼痛缓解,平均缓解时间为（5.0±1.5）d.18例（69.2％）术后出现胃肠功能紊乱,6例出现胃瘫（23％）,平均治愈时间为（16±5.1）d.胰漏3例经保守治疗痊愈,24例患者进行术后随访,平均生存期（12±5.1）个月,肿瘤较术前有缩小9例（37.5％）,肿瘤无明显增大10例（41.6％）,肿瘤明显增大5例（20.8％）.结论 125I放射性粒子植入可有效改善晚期胰腺癌症状,一定程度上抑制肿瘤,是晚期胰腺癌有效治疗方法之一.     

整合医学在感染性疾病学科发展中的应用

感染性疾病学由传染病学演变而来,部分感染性疾病具有传染性;感染性疾病具有发病率高,致病微生物和寄生虫种类多,全身各个系统、器官、组织可单个或多个被感染侵犯并产生免疫反应以及病情复杂等特点;感染性疾病已成为全球性的医疗问题和影响社会稳定的公共卫生问题。要解决感染性疾病的临床防治问题,应用生物医学模式将思路局限于某一系统、器官、组织显然不利于感染性疾病的科学诊治;必须在生物-社会-心理医学模式指导下,应用整体整合医学(HIM)的方法开展临床诊疗。本文以中国感染性疾病科需要重点关注的4组疾病即感染性疾病、急性发热、长期不明原因发热(FUO)和肝硬化性心肌病(CCM)诊治为例,阐述HIM在感染性疾病科应用的必要性和科学性。