HIF - 1α 的表达与乳腺癌临床病理特征及预后的研究

目的：分析缺氧诱导因子1仪（HIF—1a）、缺氧相关蛋白血管上皮生长因子A（VEGF—a）和葡萄糖转运蛋白-1（GLUT-1）在非特殊浸润性乳腺癌中的表达情况。运用流行病学与统计学方法分析HIF-10t与乳腺癌临床病理学特征及预后的关系。方法：采用免疫组化法检测HIF～1a、VEGF—a及GLUT-1在163例非特殊浸滑l生乳腺癌中的表达晴况;分析HIF—1a．VEGF—a及GLUT—1的表达与乳腺癌临床病理特征的关系;对HIF—l仪表达不同的乳腺癌患者进行生存分析,检验其预后意义;分析HIF-1a与缺氧相关蛋白VEGF—a和GLUT-1的表达水平的相关性;多因素分析HIF-10t的表达与临床病理资料是否为独立危险因素。结果：HIF-1a在163例非特殊浸润性乳腺癌的表达情况：阴性表达94例（57．7％）,阳性表达69例（42．3％）。HIF-1a的表达情况与乳腺癌高TNM分期、分化差的分子分型、组织病理分型、复发情况密切相关。对HIF-1仪表达不同的病例进行生存分析,显示HIF-10t阴性表达的病例预后好于阳性表达病例（P〈0．05）。缺氧相关蛋白VEGF—a和GLUT-1的表达情况：VEGF—a表达阳性95例（58．3％）,阴性68例（41．7％）;GLUT-1表达阳性126例（77．3％）,阴性37例（22．7％）。HIF-1ot与VEGF—a表达呈显著正相关,相关系数为0．538和0．668,与GlUT-1表达情况为中等程度负相关,相关系数为-0．31和-0．40。Cox多因素分析显示,HIF-1饯阳性表达、高TNM分期、非腺管型分子分型是影响乳腺癌预后的独立危险因素,相对危险度分别为1．41、4．56、3．47。结论：HIF—1a广泛表达于乳腺癌组织中,其表达与乳腺癌的TNM分期、分子分型和病理类型密切相关。生存分析显示：HIF-1a高表达是影响乳腺癌预后的独立危险因素。HIF-1d与缺氧相关蛋白VEGF—a的表达呈正相关,证明其参与了缺氧调控的乳腺癌微环境改变。     

Correlations of bcl-2 and p53 expression with the clinicopathological features in tongue squamous cell carcinomas

bcl-2 oncogene prolongs cell survival by inhibition of apoptosis. p53 tumor suppressor gene participates not only in cell proliferation control but also in induction of apoptosis. The expression of both bcl-2 and p53 proteins in 52 primary tongue squamous cell carcinomas (SCCs) was immunohistochemically explored in correlations with clinico-pathological features, patient's prognosis and apoptosis index (AI) of this tumor type. bcl-2 and p53 expression were identified in 26/52 (50%) cases and 31/52 (60%) cases, respectively. The frequency of bcl-2 expression was associated with tumor histologic grade (P = 0.0128) and marginally with mode of tumor invasion (P = 0.0671) but not with lymph nodal involvement. The frequency of p53 expression was associated with mode of tumor invasion (P = 0.0458) and pN status (P = 0.0224) but not with tumor histologic grade. Moreover, the three combined bcl-2/p53 staining patterns of bcl-2-/p53-, bcl-2+/p53- and bcl-2-/p53+, and bcl-2+/p53+ were significantly correlated with tumor histologic grade (P = 0.0299), mode of tumor invasion (P = 0.0022) and pN status (P = 0.0024). In addition, the frequent appearance of bcl-2 protein expression was associated with a decrease in AI (P = 0.0290). Our results suggest that the combined investigation on the two biological markers may have value in assessment of tumor aggressiveness, and that the suppressing mechanism of bcl-2 oncogene in regulation of apoptosis preserves in tongue SCC.     

裸鼠动物模型中胰腺癌神经侵袭的研究

  目的   探讨在裸鼠动物模型中胰腺癌神经侵袭发生情况。   方法  人Mia PaCa-2和Capan-2胰腺癌细胞株培养,裸鼠皮下胰腺癌细胞注射成瘤后,将瘤块取出切碎后裸鼠胰腺原位移植建立裸鼠原位胰腺癌动物模型,于术后4、6、8周分批处死裸鼠,采用大体标本观察和病理切片HE染色的方法观察模型中肿瘤大小、转移情况和胰腺癌神经侵袭的情况。   结果  裸鼠胰腺原位植瘤术后成瘤率100%,术后4周Mia PaCa-2组3例（50.00%）发生腹膜后神经侵犯,Capan-2组2例（33.33%）发生腹膜后神经侵犯;原位植瘤术后6周,Mia PaCa-2组5例（83.33%）发生腹膜后神经侵犯,Capan-2组4例（66.67%）发生腹膜后神经侵犯;原位植瘤术后8周,Mia PaCa-2组8例（100.00%）发生腹膜后神经侵犯,Capan-2组7例（100.00%）发生腹膜后神经侵犯。腹膜后神经侵犯组与其他组比较差异均有统计学意义（P<0.01）。   结论  神经侵袭是胰腺癌发展过程中的一个早期、独立的事件,在胰腺癌发生的早期,无其他转移或很少时,已经发生了腹膜后神经侵犯。      

基于脑肠肽Ghrelin水平探讨远志散对AD大鼠学习记忆能力及进食量的影响

目的:通过制备阿尔茨海默病(AD)大鼠模型,观察远志散对模型大鼠胃促生长素(Ghrelin)表达水平的调控,探讨其防治AD的可能作用机制。方法:采用随机数字表法将120只SD大鼠分为6组,分别为假手术组,模型组,多奈哌齐组(1.02 mg·kg~(-1)),远志散高、中、低剂量组(12,6,3 g·kg~(-1)),每组20只,雌雄各半。除假手术组注射同等剂量生理盐水,其余各组大鼠双侧海马立体定向注射β淀粉样蛋白1-40(Aβ1-40)诱导AD大鼠模型。连续灌胃治疗10周,观察并记录各组大鼠进食量。灌胃结束后通过Morris水迷宫法检测大鼠学习记忆能力,留取全脑和胃体胃窦,苏木素-伊红(HE)染色观察海马CA1区病理改变,免疫组化法检测Ghrelin表达。结果:与假手术组比较,模型组大鼠逃避潜伏期显著延长(P0.01),穿越站台次数、有效区域停留时间及运动路程均显著减少(P0.01),海马CA1区细胞排列紊乱、数量减少、胞核固缩,雌雄大鼠进食量明显下降(P0.05,P0.01),海马CA1区、胃黏膜组织中Ghrelin蛋白表达显著降低(P0.01)。与模型组比较,远志散各剂量组大鼠逃避潜伏期均有不同程度的缩短(P0.05,P0.01),穿越站台次数、有效区域停留时间及运动路程均增加(P0.05,P0.01),海马CA1区细胞数目与形态有明显改善,远志散高、中剂量组雌雄大鼠每日进食量显著增加(P0.05,P0.01);远志散各剂量组大鼠海马CA1区、胃黏膜组织Ghrelin蛋白表达明显增加(P0.05,P0.01)。结论:远志散能够有效改善AD大鼠学习记忆能力,增加每日进食量,其机制可能与其上调海马CA1区及胃黏膜组织Ghrelin含量有关。     

CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity

Recently increasing reported data have suggested that only a small subset of cancer cells possess capability to initiate malignancies including leukemia and solid tumors, which was based on investigation in these cells displaying a distinct surface marker pattern within the primary cancers. CD133 is a putative hematopoietic and neuronal stem-cell marker, which was also considered as a tumorigenic marker in brain and prostate cancer. We hypothesized that CD133 was a marker closely correlated with tumorigenicity, since it was reported that CD133 expressed in human fetal liver and repairing liver tissues, which tightly associated with hepatocarcinogenesis. Our findings showed that a small population of CD133 positive cells indeed exists in human hepatocellular carcinoma (HCC) cell lines and primary HCC tissues. From SMMC-7721 cell line, CD133+ cells isolated by MACS manifested high tumorigenecity and clonogenicity as compared with CD133- HCC cells. The implication that CD133 might be one of the markers for HCC cancer stem-like cells needed further investigation.     

氯喹联合拓扑替康对结肠癌细胞增殖的抑制作用

目的:探讨靶向溶酶体药物氯喹(chloroquine,CQ)联合拓扑替康(topotecan,TPT)对结肠癌细胞的增殖抑制作用及其可能的机制.方法:应用MTT法检测TPT对结肠癌SW480、SW620、Colo205和LoVo细胞的抑制率,以及CQ和TPT联合应用对LoVo细胞的增殖抑制作用.CQ或TPT作用于LoVo细胞后,免疫印迹法检测自噬标志蛋白LC3、P62及自噬相关蛋白Beclin1的表达;共聚焦显微镜下观察细胞质内YFP-LC3的点状聚集;采用小干扰RNA(small interfering RNA,siRNA)沉默Beclin1基因表达后,应用TPT作用LoVo细胞,锥虫蓝染色法计数细胞死亡率.结果:低浓度的CQ能够增强TPT对LoVo细胞的增殖抑制作用;CQ通过干扰自噬溶酶体功能阻断TPT诱导的自噬;通过siRNA沉默自噬相关基因Beclin1,也可增强TPT对LoVo细胞的杀伤作用.结论:CQ能够增强TPT对结肠癌细胞的增殖抑制作用,其机制可能与其阻断自噬有关.预测CQ在结肠癌治疗方面有望成为一种新型的化疗药物增敏剂.     

经药盒导管系统化疗栓塞治疗肝癌及相关药物监测

目的探讨经药盒导管系统(PCS)化疗栓塞治疗肝癌的临床价值。方法100例患者分成两组,PCS组(56例)经药盒导管系统灌注抗癌药与碘油混合成的乳剂,TACE组(44例)按常规方法栓塞治疗,对每组患者的疗效及药物代谢特征分别进行观察。结果PCS组患者肿瘤内的阿霉素可维持相当持久的较高浓度,7周后平均值7.9ug/克并取得较好治疗效果,其1、3年生存率分别为36/56(64%)及13/56(23%)。TACE组结果则较差,其阿霉素值为4.4ug/克,1、3年生存率分别为19/44(43%)及5/44(11%)。结论经PCS给药方法简便,疗效确切,经药物监测符合药代动力学规律,是治疗肝癌的较好方法。     

蟾蜍灵对胃癌组织MGC-803细胞周期作用机制的研究

目的探讨蟾蜍灵对胃癌MGC803细胞周期及周期蛋白的影响。方法采用台盼蓝拒染法测定细胞增殖活力;瑞士姬姆萨染色观察细胞形态学的变化;流式细胞仪检测细胞周期;免疫组织化学方法检测细胞周期相关蛋白p16、p21、pRb的表达。结果1)蟾蜍灵抑制胃癌MGC803细胞的增殖,24、48、72h的IC50分别为0.086、0.048和0.036μmol/L。2)蟾蜍灵在0.01～0.1μmol/L时作用24～72h,形态学上可见细胞体积增大,出现双核、多核细胞。3)流式细胞仪显示蟾蜍灵浓度为0.01～0.1μmol/L时可明显诱导细胞周期G2/M期阻滞。4)蟾蜍灵作用于胃癌MGC803细胞,观察到p16、p21、pRb蛋白的表达明显上调。结论蟾蜍灵引起胃癌MGC803细胞的周期阻滞可能与p16、p21、pRb蛋白的上调有关。     

Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study

Kaposiform hemangioendothelioma (KHE) is an aggressive disease with high morbidity and mortality. The aim of this study was to retrospectively evaluate the efficacy and safety of sirolimus for the treatment of progressive KHE. A multicenter, retrospective cohort study was conducted in patients with progressive KHE treated with sirolimus. A total of 52 patients were analyzed. Thirty‐seven (71%) patients exhibited Kasabach‐Merritt phenomenon (KMP) and were significantly younger than the patients without KMP [95% confidence interval (CI), 14.39–41.61; p < 0.001]. Patients without KMP were all treated with sirolimus alone, whereas 21 KMP patients with severe symptoms received short‐term combination therapy with prednisolone. Overall, 96% and 98% of patients showed improved relief of notable symptoms and/or improved complications at 6 and 12 months after treatment, respectively. After sirolimus treatment, significant decreases in mean severity scores occurred at 6 months (95% CI, 2.23–2.54, p < 0.001) and 12 months (95% CI, 1.53–1.90, p < 0.001). Compared to KMP patients, patients without KMP showed a response that was similar to but less pronounced during the 12 months of treatment (95% CI, 40.87–53.80; p < 0.001). For subgroup analysis of KMP patients, there were no significant differences in tumor shrinkage between those treated with combination therapy and those receiving sirolimus alone (95% CI, 18.11–25.02; p > 0.05). No patients permanently discontinued treatment due to toxicity‐related events, and no drug‐related deaths occurred. Sirolimus was effective and safe for the treatment of progressive KHE. Sirolimus may be considered as a first‐line therapy or as part of a multidisciplinary approach for the treatment of KHE.     

从肺主治节探讨低氧性肺动脉高压的中医辨治思路

低氧性肺动脉高压（hypoxic pulmonary hypertension,HPH）是临床的常见症,也是急危重症之一,中医药在其治疗上具 有一定优势。通过分析中医理论中肺对气、血、水的治节作用,并结合低氧性肺动脉高压的发病基础、症状及病理生理特 征等,认为HPH的病程演变即是肺对气、血、水的治节逐步失职的过程。HPH患者发病以气虚为基础,气虚、血瘀、水停 为其重要病机。HPH早期以气虚为主,病位在肺,兼有瘀血痰浊内生,治疗重在益气,恢复肺对“气”的治节作用;晚期 以血瘀、水停为主,由肺及心,以水饮泛溢为急,亦兼有气虚,治疗以活血化瘀、利水逐饮为主,重在恢复肺对“血、水” 的治节作用。临证应重视肺对气、血、水的治节作用,把握患者病程演变中的气虚、血瘀、水停病机间的动态演变,分期、 辨证施治以恢复肺主治节之职,提高低氧性肺动脉高压的临床疗效。