人原发性肝癌中p16基因表达及CpG岛甲基化状态的研究

目的　进一步探讨人原发性肝癌中 p16基因 m RNA转录水平变化与其基因启动子区 Cp G岛甲基化的关系 ,及其在肝癌发生中的意义。方法　采用狭缝印迹杂交检测 2 0例人原发性肝癌及相应的癌旁、远癌组织及 2例正常人肝组织中 p16基因 m RNA表达水平 ,以甲基化特异性 PCR分析各组织中 p16基因启动子区 Cp G岛的甲基化状况 ,并进行统计分析。结果　 2 0例人原发性肝癌中 14例 (70 % ) p16 m RNA水平比远癌组织显著降低 ;13例 (6 5 % )显示 p16基因启动子区 Cp G岛甲基化 ,其中 84 .6 % (11例 )伴 p16 m RNA转录水平降低。结论　人原发性肝癌中存在高频率的 p16基因表达失活 ,其主要机制可能是启动子区 Cp G岛甲基化抑制了基因的转录 ,在人原发性肝癌的发生发展中有重要作用。其临床诊断和治疗意义有待进一步深入研究。     

胃癌组织中P16、Cyclin D1、Rb表达及其生物学行为的研究

目的研究P16、Cyclin、D1Rb基因在胃癌中的表达及其与胃癌生物学行为的关系.方法采用免疫组化方法检测10例正常胃黏膜、30例胃癌组织中P16、Cyclin D1、Rb蛋白的表达,并结合其临床资料进行分析.结果P16、Cyclin D1、Rb蛋白阳性表达,正常胃粘膜分别为90%、10%、90%;胃癌分别为36.67%、53.33%、50%,胃癌纽与正常对照组间差异均有显著性(P＜0.05),P16、Cyclin D1蛋白与胃癌分化程度、淋巴结转移与否、远处转移与否呈一定的相关性.结论P16、Cyclin D1、Rb基因与胃癌发生有关,P16、Cyclinp蛋白检测有助于胃癌预后的判断.     

p14ARF、E2F-1与肺癌

p14ARF基因和核转录因子E2F-1在细胞周期调控，细胞凋亡和肿瘤发生中具有重要作用。近年来，有研究表明p14ARF在肺癌中的表达率低于正常组织，E2F-1的表达率高于正常组织。本文将就p14ARF、E2F-1与肺癌的关系进行综述。     

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

Tityus perijanensis González-Sponga (Scorpiones, Buthidae): molecular assessment of its geographical distribution and venom lethality of Venezuelan populations.

An extensive field survey allowed us to expand the geographical distribution of the scorpion Tityus perijanensis in the Perijá range, western Zulia State, Venezuela, including areas where adult cases of severe scorpionism have been reported. 16S ribosomal RNA (rRNA) gene sequencing, DL(50) determination, and native PAGE suggest low genetic and venom proteomic divergence across the distribution range. The results also indicate phylogenetic divergence between T. perijanensis and T. discrepans, the species prevalent in northcentral Venezuela. T. perijanensis venom lethality (0.91-0.94 mg/kg) is comparable to that of the Brazilian T. serrulatus and ranks highest among toxic Venezuelan Tityus studied so far. The data indicate that the Perijá range should be included amongst the endemic areas of scorpionism of Venezuela and Colombia.     

Open, Double-Blind and Long-Term Study of Vigabatrin in Chronic Epilepsy

We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of mattress characteristics on house dust mite allergen concentration

BACKGROUND: Exposure to a high level of house dust mite allergens (HDMAs) is considered as a risk factor for HDM sensitization and development of asthma in genetically disposed people. Mattresses are one of the most important sources of HDMA in people's living environment. OBJECTIVE: The aim of this study was to evaluate the association between mattress characteristics and HDMA concentrations on mattresses. METHODS: Dust samples of mattress surfaces were taken to evaluate the level of Der p 1 allergen. All participants filled in a questionnaire about the type of mattress, the type of covering (upper layer) of the mattress, dwelling characteristics and cleaning habits. Humidity and temperature of the bedroom were measured at the time of dust sampling. RESULTS: One hundred and sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress was associated with a higher level of Der p 1 compared with cotton upper layer (2.6 vs. 0.8 microg/g Der p 1). Moreover, higher relative humidity (RH) was associated with significant higher concentrations and density of Der p 1. CONCLUSIONS: Two factors were associated with lower levels of Der p 1 found on mattresses, namely: a cotton upper layer of the mattress compared with a layer of synthetic material and lower RH at the time of sampling. As far as we know, the association between type of upper layer and concentration of Der p 1 has not been described before and could lead to the formulation of practical advices in order to reduce HDMA concentrations on mattresses.     

Expression of Anion Exchanger 1 Sequestrates p16 in the Cytoplasm in Gastric and Colonic Adenocarcinoma

p16^INK4A (p16) binds to cyclin-dependent kinase 4/6 and negatively regulates cell growth. Recent studies have led to an understanding of additional biologic functions for p16; however, the detailed mechanisms involved are still elusive. In this article, we show an unexpected expression of anion exchanger 1 (AE1) in the cytoplasm in poorly and moderately differentiated gastric and colonic adenocarcinoma cells and in its interaction with p16, thereby sequestrating the protein in the cytoplasm. Genetic alterations of p16 and AE1 were not detectable. Forced expression of AE1 in these cells sequestrated more p16 in the cytoplasm, whereas small interfering RNA-mediated silencing of AE1 in the cells induced the release of p16 from the cytoplasm to the nucleus, leading to cell death and growth inhibition of tumor cells. By analyzing tissue samples obtained from patients with gastric and colonic cancers, we found that 83.33% of gastric cancers and 56.52% of colonic cancers coexpressed AE1 and p16 in the cytoplasm. We conclude that AE1 plays a crucial role in the pathogenesis of gastric and colonic adenocarcinoma and that p16 dysfunction is a novel pathway of carcinogenesis.     

p53,p16,PCNA蛋白在食管癌中的表达及其临床意义

目的探讨p53,p16,PCNA蛋白在食管癌中的表达及临床意义。方法用免疫组织化学染色SP法对62例食管癌标本进行p53,p16,PCNA蛋白测定。结果62例食管癌中,p53,PCNA蛋白阳性表达均为71.0%(44/62),p16缺失率48.4%(30/62)。p16缺失与肿瘤浸润深度、淋巴结转移密切相关(P<0.05、P<0.01)。而p53,PCNA蛋白同时表达56.5%(35/62),亦与肿瘤浸润深度、淋巴结转移密切相关(P<0.05、P<0.01)。结论食管癌p53,PCNA蛋白同时表达及p16缺失可视为危险预后因素。     

P16INK4、PCNA在肺癌中表达的研究

目的 通过检测肺癌组织中p16、PCNA的表达，探讨其在肺癌发生发展中的作用及相互关系。方法 采用S—P免疫组化方法，检测83例肺癌标本及15例正常肺组织标本中P16^INK4和PCNA的表达。结果 P16^INK4和PCNA在正常肺组织和肺癌组织中表达的阳性率存在显著性差异。P16^INK4表达的阳性率在小细胞癌与非小细胞癌之间有显著性差异。PNTM分期高的肺癌标本P16^INK4及PCNA表达阳性率显著高于分期低的肺癌标本。不同分化程度的肺癌组织P16^INK4及PCNA表达阳性率有显著性差异。结论 肺癌的发生与P16^INK4的低表达和PCNA的高表达有关。而P16^INK4的表达与肺癌的组织学类型、分化程度、临床分期有关；PCNA的表达与肺癌的分化程度、临床分期有关。