转化生长因子β1/SMAD信号通路在六亚甲基二乙酰胺抑制K562细胞增殖中的作用

目的探讨转化生长因子β1(TGF-β1)/SMAD信号通路在六亚甲基二乙酰胺(HMBA)抑制K562细胞增殖中的作用.方法采用HMBA诱导K562细胞分化模型后,四甲基偶氮唑盐(MTT)实验和流式细胞术分别检测HMBA对K562细胞的增殖和细胞周期作用,逆转录.聚合酶链反应(RT-PCR)检测TGF-β1、SMAD3、SMAD4和亲嗜性病毒整合位点1(EV11)在基因水平上相对表达量的变化趋势.结果 HMBA能抑制K562细胞增殖并促进其分化,作用程度随时间延长或剂量加大而增大,作用72 h时半数抑制浓度(IC50)为2 mmot/L.K562细胞经2 mmol/L HMBA作用72 h内,G0-G1期细胞百分率逐渐增高;TGF-β1、SMAD3和SMAD4在mRNA水平的相对表达量逐渐增高,而EVI1在mRNA水平的相对表达量逐渐降低.结论HMBA通过TGF-β1/SMAD信号通路抑制K562细胞增殖.     

p27Kip1在As2O3诱导白血病细胞凋亡中的作用机制

目的:研究三氧化二砷(arsenic trioxide,As2O3)及转录生长因子(transforming growth factor-β1,TGF-β1)对人HL-60细胞增殖的影响,并探讨相关信号通路.方法:流式细胞术检测细胞周期及凋亡,RT-PCR检测p27Kip1、TGF-β1、Cyclin E和Bcl-2表达,免疫组织化学方法和Western blot方法检测p27Kip1、TGF-β1、Cyclin E和Bcl-2蛋白水平.结果:As2O3、TGF-β1单药或联合处理均可诱导细胞凋亡,以联合处理组凋亡最明显,并且As2O3单药组及联合处理组细胞周期阻滞于G1期.As2O3单药及联合处理组可见p27Kip1、内源性TGF-β1表达上调,Cyclin E和Bcl-2表达下调,外源性TGF-β1处理组可见p27Kip1 mRNA及蛋白表达上调,内源性TGF-β1 mRNA表达上调,内源性TGF-β1蛋白水平与对照组比较无明显变化,Cyclin E和Bcl-2表达下调,联合处理组p27Kip1及内源性TGF-β1表达上调及Cyclin E和Bcl-2表达下调程度强于单药处理组.结论:As2O3诱导细胞凋亡的机制可能是通过上调TGF-β1,从而上调p27Kip1,拮抗Cyclin E和Bcl-2的作用,抑制细胞增殖,使细胞周期阻滞于G1期,从而诱导细胞发生凋亡,外源性TGF-β1通过上调内源性TGF-β1,从而上调p27Kip1,增强As2O3诱导细胞凋亡的作用.     

六亚甲基二乙酰胺对K562细胞作用的实验研究

目的：研究六亚甲基二乙酰胺（HMBA）体外对K562细胞的抑制增殖、诱导凋亡和促进分化的作用。方法：MTT法检测不同浓度HMBA对于K562细胞的增殖抑制率；流式细胞仪（FCM）检测HMBA对于K562细胞周期分布的影响；Annexin V／PI染色方法检测HM—BA诱导K562细胞凋亡的作用；通过瑞氏染色、联苯胺染色和FCM检测分化抗原研究K562细胞分化情况。结果：HMBA可以抑制K562细胞增殖，1、2、3和4mmol／L对K562细胞增殖抑制率分别为21．97％、36．05％、41．56％和47．59％；HMBA可以阻滞K562细胞周期，主要表现为G0／G1期的阻滞；HMBA诱导K562细胞凋亡的作用不明显，4mmol／L的HMBA对K562细胞诱导凋亡率〈5％；HMBA处理后，瑞氏染色显示K562细胞有一定程度的成熟表现，联苯胺染色基本为阴性；K562细胞膜表面CD11b、CD14、CD68和胞质内溶茵酶抗原的表达在HMBA处理前后均为阴性。结论：HM—BA可以抑制K562细胞的增殖，提示具有一定的治疗作用；HMBA对K562的作用机制和阻滞细胞周期有关，诱导凋亡不是主要作用机制；HMBA有促进K562细胞分化的迹象，但分化方向和机制有待进一步研究。     

三氧化二砷诱导K562细胞凋亡过程中Par-4及WT1基因表达的变化

 目的　探讨三氧化二砷（As2O3）诱导K562细胞凋亡过程中前列腺凋亡反应因子-4（Par-4）和WT1基因表达的变化。方法　用不同浓度As2O3（2～10 μmol／L）处理K562细胞24～72 h,MTT法测定细胞增生活力,流式细胞术检测细胞凋亡,采用荧光定量RT-PCR检测Par-4和WT1基因 mRNA表达变化,Western blotting检测Par-4和WT1蛋白表达的变化。结果　不同浓度As2O3作用于K562细胞,随浓度增加能明显抑制细胞的生长,诱导细胞发生凋亡。同时Par-4基因mRNA和蛋白表达逐渐增加;而WT1基因mRNA及蛋白表达逐渐下降。结论　As2O3可抑制K562细胞生长,诱导细胞凋亡,Par-4与WT1基因可能参与As2O3诱导K562细胞凋亡的调控。     

三氧化二砷诱导K562细胞凋亡与其抑制Evi-1表达有关

背景与目的： 探讨三氧化二砷(As2O3)诱导K562细胞凋亡的分子机制。 材料与方法： 分别以1、2、4、8 μmol/L的As2O3诱导K562细胞凋亡,每隔24 h采用光镜和电镜观察细胞形态变化,MTT观察细胞增殖抑制率,流式细胞仪检测细胞凋亡率,RT-PCR检测Evi-1mRNA表达率,ELISA检测细胞内JNK蛋白。 结果： As2O3对K562细胞增殖具有明显的抑制作用,且呈剂量-时间关系;1、2、4、8 μmol/L的As2O3可使K562细胞发生凋亡,在本实验时间段内随着作用时间的延长细胞凋亡逐渐升高,诱导细胞凋亡的最佳浓度为4 μmol/L;在此过程中K562细胞的Evi-1基因表达下调,JNK蛋白表达增多,两者跟As2O3浓度存在剂量-时间关系。 结论： As2O3通过抑制K562细胞Evi-1表达,从而激活JNK信号传导途径,促进细胞凋亡,这可能是As2O3促进K562细胞凋亡的机制之一。     

转化生长因子-β1对人卵巢癌细胞增殖的抑制作用

目的:探讨转化生长因子(TGF)-β1对人卵巢癌细胞系HO-8910增殖的影响及其作用机制.方法:采用MTT及流式细胞术检测TGF-β1对HO-8910细胞增殖的抑制作用,同时采用半定量RT-PCR和Western blot方法分别检测TGF-β1作用不同时相细胞中Smad7、p15、p21和c-myc基因mRNA及蛋白表达水平的变化.结果:TGF-β1明显抑制HO-8910细胞的增殖;在TGF-β1(10ng/ml)刺激下,细胞中p15和Smad7的表达上调而c-myc的表达明显降低,p21的表达无明显变化.结论:TGF-β1可能通过上调p15、下调c-myc基因表达水平影响细胞周期调控,从而抑制卵巢癌细胞的增殖.     

PMA诱导K562细胞向单核细胞分化机制探讨

目的：探讨佛波酯（phorbol-12-myristate-13-ace-tate,PMA）诱导K562细胞向单核/巨噬细胞分化的作用机制。方法：采用CCK8法检测0、6.25、12.5、25、50、100和200nmol/L PMA对K562细胞增殖的影响,应用Wright-Gimesa染色观察细胞形态学变化,采用流式细胞术检测细胞表面分化抗原CD11b和CD14的表达变化,采用RT-PCR分析TGF-β1及其下游基因SMAD3和SMAD4在基因水平的表达趋势,并采用蛋白质印迹法检测TGF-β1在蛋白水平的表达变化。结果：K562细胞经6.25nmol/L PMA处理后72h增殖抑制率为（22.03±2.7）%,12.5nmol/L为（31.04±4.3）%,25nmol/L为（35.03±3.5）%,50nmol/L为（47.01±4.1）%,100nmol/L为（55.06±5.2）%,200nmol/L为（76.72±5.4）%,差异有统计学意义,F=2.24,P〈0.05。PMA能抑制K562细胞的增殖并能促进其分化,作用效果随剂量的加大逐渐增强;细胞形态学上趋向于成熟分化;细胞表面分子CD11b和CD14的表达量升高。在mRNA水平,TGF-β/SMAD信号通路因子TGF-β1的表达量随时间的延长逐渐升高其下游因子SMAD3和SMAD4的表达也呈上升趋势;在蛋白水平,TGF-β1的表达亦呈上升趋势。结论：PMA可通过促进TGF-β/SMAD信号的传导诱导白血病细胞株K562细胞向单核/巨噬细胞分化。     

三氧化二砷对人白血病细胞株NB4和K562及MOLt4的增殖、周期及凋亡的影响

目的：观察三氧化二砷(As2O3)对人白血病细胞株NB4、K562、MOLt4的增殖，周期及凋亡的影响。方法：采用台盼蓝拒染法计数活细胞数．并计算细胞生长率；细胞涂片经Wright-Giemsa染色，光镜下观察细胞的形态；流式细胞仪解析细胞周期。结果：1)As2O3能够抑制NB4、K562、MOLt4细胞的增殖。2)4μmol/L As2O3能够使K562细胞发生M期阻滞。但NB4、MOLt4细胞未见明显改变。3)2、4μmol/L的As2O3处理NB4、MOLt4和K562细胞48h．NB4、MOLt4细胞株的凋亡细胞明显增多。但是．K561细胞未见明显改变。结论：As2O3不但对NB4细胞具有抑制增殖．诱导细胞凋亡的作用．而且对非，t(15：17)的K562、MOLt4细胞也具有抑制增殖的作用．同时诱导MOLt4细胞凋亡．使K562细胞发生M期阻滞。     

NPM1 A型突变体对TGF-β1诱导K562细胞增殖及AKT磷酸化的影响

  目的  观察核仁磷酸蛋白（nucleophosmin 1,NPM1）A型突变体过表达对TGF-β1诱导的K562细胞增殖及AKT磷酸化的影响。  方法  腺病毒载体（Ad5－NPM1）转染髓系白血病K562细胞建立过表达NPM1蛋白细胞株;应用Western blot法及ELISA法分别检测细胞NPM1蛋白表达及上清液含量,Western blot法检测K562细胞NPM1、AKT和P-AKT蛋白表达,MTT法检测细胞增殖。  结果  K562细胞NPM1蛋白表达水平呈Ad5-NPM1转染复数[（multiplicity of infection,MOI）:30-200]依赖性增加,与空载组（Ad5-vector-100）相比,Ad5-NPM1-30、Ad5-NPM1-100组K562细胞及细胞上清液NPM1蛋白水平均显著增高（P < 0.01）。TGF-β1（10 ng/mL）能够诱导K562细胞AKT蛋白磷酸化,但对总AKT水平无明显影响。TGF-β1（10 ng/mL）+Ad5-NPM1-100组K562细胞P-AKT水平显著高于TGF-β1处理组（P < 0.05）,各组总AKT水平无显著差别（P>0.05）。与空白对照组（CT）相比,TGF-β1（10 ng/mL）处理可促进K562细胞增殖;但TGF-β1（10 ng/mL）+Ad5-NPM1-100组细胞的增殖水平明显高于TGF-β1处理组（P < 0.01）。  结论  NPM1可促进TGF-β1诱导的K562细胞增殖。NPM1促进TGF-β1诱导的K562细胞可能与AKT磷酸化有关。      

放射线诱导的K562细胞增殖抑制的初步研究

 目的　研究60Coγ射线诱导K562细胞增殖抑制的剂量效应关系以及受照过程中的K562细胞形态学变化和Egr-1基因表达的变化。方法　通过3H-TdR竞争性地掺入K562细胞的DNA合成,使用低本底液体闪烁计数器测定掺入细胞的放射性活度,分析K562细胞在受到60Coγ射线照射后的增殖抑制情况。采用吉姆萨染色法在显微镜下观察K562细胞的形态学改变。采用反转录PCR方法分析K562细胞在受照射后发生增殖抑制的过程中Egr-1基因的表达变化。结果 　细胞增殖抑制表现出明显的剂量依赖性;照射前后K562细胞的形态和染色特点发生了明显的变化,具备了某些较高分化程度的红细胞才有的特点;在接受照射后的早期,与细胞分化、凋亡密切相关的基因Egr-1有一过性的表达上调,表现为在照射后的0.5 h和 1 h ,早期生长反应基因Egr-1的转录水平迅速升至最高,此后迅速下降,到8 h下降到低于正常水平。结论　K562细胞的增殖抑制表现显著的剂量依赖性;受照后的K562细胞在形态学上向更成熟的阶段分化。Egr-1基因在受60Coγ射线照射后可被一过性激活表达。     

Cytologic classification of precancer and cancer of the endometrium and esophagus and of malignant lymphomas

The paper discusses cytological classifications of precancer and cancer of the endometrium, esophagus and malignant lymphomas presented by cytologists from five Soviet research institutes of oncology. The classifications were based on the data of 4400 cases in conformity with WHO histologic classifications.     

E-钙粘蛋白及PTEN基因编码蛋白与胃癌浸润转移

目的:观察抑癌基因PTEN蛋白和ECD在胃癌组织中的表达,探讨其与胃癌生物学行为及预后的关系。方法:以兔抗人PTEN多克隆抗体、鼠抗人ECD单克隆抗体,采用SABC免疫组化法,检测100例胃癌手术切除标本中拟测指标的表达。以χ2和Logrank检验对结果做统计学分析。结果:ECD、PTEN蛋白在非癌胃粘膜中均见表达;在胃癌组织中表达下调或缺失。ECD异常表达率为42.0%;弥漫型胃癌异常表达率(48.57%),明显高于肠型胃癌(26.67%),(P<0.05);ECD异常表达与浸润深度有关(P<0.05)。胃癌组织中PTEN蛋白缺失率为59%;弥漫型胃癌缺失率(65.71%)明显高于肠型胃癌(43.33%),(P<0.05);伴淋巴结转移的胃癌缺失率(64.47%)明显高于无淋巴结转移者(41.67%),(P<0.05);PTEN蛋白缺失的患者比阳性表达者预后差(P=0.0066)。65.85%PTEN阳性表达者同时伴ECD正常表达。结论:两种标志物与胃癌浸润转移有关,PTEN表达与胃癌患者预后密切相关。将两种指标联合检测,可作为正确判断胃癌患者预后,指导临床治疗的分子生物学指标。     

Schwannomas of Head and Neck and Review of Literature

Benign nerve cell tumours have been given various names like schwannoma, neurilemmoma, neurinoma, neurofibroma, spindle cell tumours etc. Extra cranial head and neck schwannomas usually present as solitary and well-demarcated lesions. The lesion can cause secondary symptoms, such as nasal obstruction, dysphasia, and hoarseness, depending upon the location of the lesion. Fine needle aspiration cytology, CT scans, and MRI may be of limited help in the diagnosis of schwannomas. The treatment is complete surgical excision of the benign tumour and postoperative histopathological examination establishes the final diagnosis.     

世界卫生组织骨质疏松症防治工作报告和防治建议

引 言 作为对第51号综合处理非传染性疾病预防与控制的世界卫生组织决议的反应,1998年7月WHO成立了致力于不断完善对骨质疏松预防和治疗策略的工作小组。小组成员来自世界各国致力于骨质疏松研究的知名专家。Harry K.Genant为本届主席。这一项世界范围内的骨质疏松教育计划旨在通过世界范围的研究,不断改善对骨质疏松的诊断水平和发展并完善对骨质疏松病人的合理治疗。其重点将以发展中国家为主。并为各国政府及其卫生部门和病人群体提供世界性有关骨质疏松症的总体的、完整的指导性资料。该项研究、教育计划的实施将由世界各国的骨质疏松症研究和治疗机构共同完成,并经权威学术机构、政府和非政府组织进行有针对性的回顾研究,最终由WHO审议通过。     

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers

BACKGROUND: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. METHODS: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. RESULTS: With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. CONCLUSIONS: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.     

A comparative study of knowledge and awareness of colorectal and breast cancerA comparative study of knowledge and awareness of colorectal and breast cancer

Aims: To assess and compare knowledge and awareness of colorectal cancer and breast cancer in a sample of the general population. Methods: Eleven hundred visitors to six different outpatient clinics, in a University Hospital, were given a study-specific questionnaire, based on educational material from the British Association of Cancer United Patients (CancerBACUP). The questionnaire consisted of 12 statements on the incidence, presentation, detection, treatment and prognosis of colorectal and breast cancer. Results: One thousand and sixty-eight individuals returned the questionnaire. One thousand and four completed questionnaires were analysed. The mean age (SD) of respondents was 50.1 (17.2) years, and the male to female ratio was 2:3. Respondents had read more about breast than about colorectal cancer (60.3%vs 32.4%,P <0.0001, McNemar's test). The proportion of correct answers for each statement on breast cancer was higher than for answers to corresponding items on colorectal cancer. Mean overall scores (95% CI) for breast and colorectal cancer were 88.1 (86.9, 89.2) and 64.4 (62.5, 66.3) respectively, the mean difference (95% CI) being 23.7 (22.0, 25.5). Scores were higher for breast cancer irrespective of age or gender. Conclusion: There is a low level of understanding of colorectal cancer in the general population when compared to breast cancer. This highlights the importance of public education in this common cancer.     

Quality of life and care in leukemia,myeloma and non-malignant disease. Opinions of patients and relatives,and effects of geography and time

In a questionnaire study 140 subjects answered 4200 questions in 1980 and 1986. They consisted of patients with myeloma, acute leukemia, lung carcinoma, and non-malignant disease and their relatives. In 22 additional cases the questionnaire was not answered. The results show that myeloma patients are less content with the general care than leukemia patients (P < 0.05). Similarly, relatives of deceased myeloma patients are less satisfied with the information given to them than relatives of deceased leukemia patients (P < 0.001). The information has improved with time, however, since the patients were more satisfied in 1986 than in 1980 (P < 0.001) and relatives of myeloma patients still alive were more satisfied than relatives of patients who had died earlier (P < 0.001).     

Quality of life and care in leukemia, myeloma and non-malignant disease. Opinions of patients and relatives, and effects of geography and time

In a questionnaire study 140 subjects answered 4200 questions in 1980 and 1986. They consisted of patients with myeloma, acute leukemia, lung carcinoma, and non-malignant disease and their relatives. In 22 additional cases the questionnaire was not answered. The results show that myeloma patients are less content with the general care than leukemia patients (P less than 0.05). Similarly, relatives of decreased myeloma patients are less satisfied with the information given to them than relatives of deceased leukemia patients (P less than 0.001). The information has improved with time, however, since the patients were more satisfied in 1986 than in 1980 (P less than 0.001) and relatives of myeloma patients still alive were more satisfied than relatives of patients who had died earlier (P less than 0.001). The opinions of patients were similar to those of their relatives. However, the relatives of leukemia patients were even more satisfied with the contact with the medical staff than the patients themselves (P less than 0.05). As many as 10-30% of the relatives never gave up hope for their relative's survival. Only two out of 27 deaths were considered not dignified. The lung carcinoma patients reported a less good quality of life (P less than 0.001), and less satisfaction with the information given (P less than 0.01), than the hematological patients from the same year. Similarly, their attitude to the medical care improved less (P less than 0.01), and they were less content with the general care than the leukemia group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)