用原位杂交对树鼩肝组织乙型肝炎病毒DNA定位及其与黄曲霉毒素B_1在肝癌发生中的作用

用生物素标记的HBV DNA探针对经83～158周实验的55只树鼩肝组织的福尔马林固定、石蜡包埋的切片进行原位分子杂交研究。在45只接种过人HBV的树鼩中,有30只在肝细胞检出HBV DNA。这55只树鼩,有41只摄入了AFB_1,其中肝细胞HBV DNA阳性的A组22只,有10只发生了HCC;19只HBVDNA阴性的B组,只发生2例HCC,两组差别显著(P<0.05)。未接触过AFB_1的14只树鼩中,肝细胞HBVDNA阳性的8只(C组),发生1例HCC;而HBV DNA阴性的6只(D组)无HCC发生。提示HBV和AFB_1在诱发树鼩HCC中起协同作用;并支持HBV感染与HCC存在病因学关系的观点。该实验HBV DNA阳性物质主要分布于癌外肝细胞胞浆内,少数位于肝细胞核。癌组织内HBV DNA阳性率低于癌外肝组织。与在人肝癌研究的结果一致。表明树鼩是研究HBV致癌分子机理的较好的模型。     

人肝癌细胞内HBV DNA和HBsAg的分布及意义

用原位分子杂交和免疫组化技术双标记方法,在31例人肝细胞癌(HCC)的石蜡切片中检测HBV DNA和HBsAg。在31例HCC中,20例(64.5％)HBV DNA阳性,14例(45.2％)HBsAg阳性,8例(25.8％)HBV DNA和HBsAg两者同时阳性。HBV DNA主要分布于癌细胞的胞浆内(20例),也见于胞核内(16例)及核浆内(16例)。此结果表明,HCC的发生与HBV感染有密切关系。     

HBV DNA阳性肝癌患者血清HBeAg检测与肝细胞癌复发转移的关系

目的:研究HBV DNA阳性肝癌(HCC)患者血清HBeAg检测与肝细胞癌复发转移的关系.方法: HBV DNA阳性HCC肝切除术患者60例,HBV DNA阴性HCC肝切除术患者60例.60例HBV DNA阳性HCC患者中依据肿瘤病灶局限、肉眼以及镜下均无肝内播散和门静脉浸润的低侵袭组,共28例;肿瘤组织伴有多发性肝内播散和(或)门静脉主肝癌栓者为高侵袭组,共32例.检测患者术前及术后1周血清HBV DNA水平,观察肝功能变化并检测血清HBeAg水平.结果:HBV DNA阳性组与HBV DNA阴性组比较,60例HBV DNA阳性HCC患者中HBeAg阳性患者为48例,阳性率为80%,60例HBV DNA阴性HCC患者中HBeAg阳性患者为12例,阳性率为20%,(P<0.05).不同侵袭组HBeAg表达比较: 32例高侵袭组中29例HBeAg检测阳性,阳性率为90.62% ,28例低侵袭组中19例HBeAg检测阳性, 阳性率为67.86%,(P<0.05).结论:早期肝癌患者血清HBV DNA和HBeAg可作为肝细胞癌复发转移监测指标.     

广西肝癌高发区原发性肝细胞癌 HBV X 基因的整合及影响因素分析

目的 了解广西肝癌高发区乙型肝炎病毒（hepatitis B virus,HBV）X区基因在肝细胞癌（hepatocellular carcinoma,HCC）染色体中的整合及影响因素。方法 以30例与HBV相关的原发性肝细胞癌患者为研究对象。提取HCC组织及癌旁组织标本DNA作为模板,以HBV X基因上游序列和人类基因组Alu重复序列为引物,应用重复序列-多聚酶链反应（Alu-PCR）扩增整合的HBV X片段及两侧的人类基因组DNA片段。扩增产物进行测序,计算目的片段整合率并分析相关的影响因素。结果 18例HCC组织检测到HBV X基因的整合片段,整合率为60.00%（18/30）;26例癌旁组织检测到HBV X基因的整合片段,整合率为86.67%（26/30）。癌旁组织HBV病毒整合率高于HCC组织,差异有统计学意义（χ²=5.445,P=0.020）。不同性别、年龄、HBeAg、HBV DNA、ALT、AST的HCC癌组织及其癌旁组织HBV X基因整合率比较差异均无统计学意义（P＞0.05）。结论 广西肝癌高发区癌旁组织比HCC组织HBV整合率高,说明HBV整合发生在感染早期。HBV X基因整合与HCC患者性别、年龄、HBeAg、HBV DNA、ALT、AST无明显关系。     

整合型HBVDNA前C区突变和p53基因突变与肝细胞癌发生的关系

背景与目的:乙型肝炎病毒 (hepatitis B virus, HBV)的慢性感染是肝细胞癌 (hepatocellular carcinoma, HCC)发生的主要危险因素,但其确切的作用机理还不清楚.本研究拟探讨整合型 HBV 前 C区突变、 p53基因突变与 HCC发生的关系,以期更好地了解 HCC发生的分子机理.方法 :应用聚合酶链反应技术( PCR)和聚合酶链反应-单链构象多态 (single strand conformation polymorphism analysis of polymerase chain reaction products, PCR SSCP) 技术对 28例肝癌组织、 25例癌旁肝硬化组织、 12例肝硬化组织和 15例正常肝组织标本内的整合型 HBV DNA及其前 C区基因突变和肝细胞 p53基因突变进行检测分析.结果:( 1)正常肝组织、肝硬化组织、癌旁肝硬变组织和肝癌组织中整合 HBV DNA 阳性率分别为 6.66%、 66.67%、 96.43% 和 96.43%,正常肝组织与其它三组间阳性率差异有非常显著性( P< 0.005); (2)4组整合型 HBV DNA前 C区突变率分别为 0%、 25.00% 、 48.15% 和 70.37%, 4组间的突变率差异有显著性( P< 0.05); ( 3)肝癌组织的 p53基因突变率( 57.14%)明显高于肝硬化组( 16.67%) (P< 0.05);( 4)不同肝组织中 p53基因突变率与整合 HBV DNA 阳性率、 HBV前 C区基因突变率呈正相关.结论:在肝细胞癌的发生、发展中整合 HBV DNA及其前 C区基因突变和 p53基因突变可能起协同作用.     

肝癌及癌旁肝组织内HBsAg和HBV—DNA定位研究

全国肝癌病理协作组研究表明肝细胞癌(HCC)和乙型肝炎病毒(HBV)感染的病理学相关性。Gowans首先应用原位分子杂交技术检测肝细胞内HBV-DNA,以及由Blum完臻这项技术以来,使HBV感染和HCC发生的相关性病理学研究提高到一个新水平。本文应用免疫组织化学ABC染色法和原位分子杂交技术检测经福马林溶液固定,石蜡包埋的肝癌及癌旁肝组织块内HBsAg和HBV-DNA。在免疫病理学和分子病理学水平上进一步研究HBV感染和HCC的相关性。     

组织相容抗原和肝细胞癌的研究

Sherlock等首先报告了肝癌与HBsAg的关系。而后很多国家报导了肝细胞癌(HCC)病人HBsAg的高发生率、其滴度存在差别,e抗体阳性率有增高的倾向。HCC的发生率虽有种族差异,但在HBsAg携带者中发生HCC的危险性是正常人的50倍至350倍,其死亡率相差28.3倍。 有人提出HBsAg和HCC之间的关系可能是互为因果关系的假说,其病程的发展模式为:幼年的HBV感染→HBV携带状态→慢性活动性感染→肝硬变→肝癌。 论证上述假说的根据有:(1)在培养的人肝癌细胞中产生HBsAg;(2)肝癌患者癌细胞染色体组中有HBV的DNA整合;(3)肝癌患者95％以上有乙型肝炎病毒感染;(4)肝癌患者血清中含有     

广西地区肝细胞癌患者组织中p53蛋白表达的研究

目的：探索广西肝癌高发区肝细胞癌（HCC）的组织中检测p53蛋白的表达情况。方法：用免疫组织化学方法对30例肝细胞癌（HCC）和癌旁组织进行检测。p53蛋白的免疫组化染色一抗用的是兔抗。连续切片染色乙型肝炎表面抗原和核心抗原。结果：30例肝细胞癌组织中有13例（13／30,43.3％）p53蛋白表达阳性;在≤5.0的肝细胞癌组织中有25％（1／4）的p53蛋白表达阳性;在＞10.0cm的肝细胞癌组织中有71.4%(5/7)的p53蛋白表达阳性。p53蛋白阳性在中、低分化肝细胞癌中的表达高于在高分化肝细胞癌组织中,而且大多数在年轻患者的肝细胞组织中。结论：本组资料表明,p53蛋白表达与肿瘤的大小、分级和患者的年龄有着密切的关系。30例中有27例（90.0％）证实为HBV感染,表明p53蛋白表达与性别和HBV感染、肝硬化及AFP水平无密切相关关系。     

肝癌中Fas相关死亡区蛋白与细胞凋亡相关性初探

目的：研究肝癌中Fas相关死亡区蛋白(FADD)与细胞凋亡间的相关性。方法：采用原位末端标记及免疫组化法分别检测肝癌中细胞凋亡及FADD蛋白表达。结果：78例肝癌中20例(25.6％)表达FADD蛋白，显著低于癌旁非癌肝组织(10／16，62.5％，P＜0.05)。12／36(33.3％)分化中等良好的HCC中FADD表达，略高于分化差的HCC(8／42，19％，P＞0.05)。Ⅰ／Ⅱ级HCC中，16例为FADD阳性(16／42，38.1％)，而Ⅲ／Ⅳ级HCC中阳性率仅为11.1％(P＜0.05)。所有标本中均能检测到细胞凋亡，在FADD蛋白中等阳性和强阳性的HCC中，细胞凋亡程度较高，与FADD表达弱阳性或阴性的HCC相比P＜0.05，癌旁组织中FADD表达与细胞凋亡无关(P＞0.05)。结论：FADD表达降低在肝癌发生中起作用，且与肝癌细胞凋亡相关。     

原发性肝细胞癌患者癌细胞及癌旁组织中HBV—DNA及HBV抗原的定位研究

应用原位核酸杂交技术和免疫金银染色法分别检测42名原发性肝癌(PHC)患者肝癌及癌旁组织中的HBV-DNA 和 HB 抗原。结果:28例(66.7%)癌旁组织中 HBV-DNA 阳性,其中17例癌组织中也阳性.免疫组化结果显示 HBsAg 阳性者24例、HBcAg 阳性者6例,均见于癌旁组织。提示本组病例 HBV 感染是 PHC 的主要病因之一。本文部分 PHC 患者癌旁组织中仍有活跃的病毒复制,但癌组织中却未见表达相应抗原,推测 HBV 与机体长期作用后,部分病毒通过某种机制从免疫反应中逃逸并整合进入肝细胞基因组中,诱发恶变,可能是 PHC 的主要发病机制之一。     

外泌体在肿瘤发展中的研究进展

外泌体是细胞经过"内吞-融合-外排"等一系列调控过程而形成的细胞外纳米级小囊泡。外泌体可以携带蛋白,运送RNA,在细胞间物质和信息转导中起重要作用。外泌体可能通过调控免疫功能,促进肿瘤血管新生和肿瘤转移,以及直接作用于肿瘤细胞等途径,影响肿瘤的进展。外泌体可应用于肿瘤的诊断。本文总结了近年来有关外泌体在肿瘤发展中作用的研究进展。     

Inhibitory effect of suramin in rat models of angiogenesis in vitro and in vivo

The aim of the present study was to test the ability of the chemotherapeutic agent suramin to inhibit angiogenesis in experimental models in vitro and in vivo. In the culture of rat aortic rings on fibronectin, suramin dose-dependently inhibited vascular cell growth, achieving the maximal effect (mean − 88% versus controls, P < 0.05) at 400 μg/ml. Image analysis showed that suramin could inhibit microvessel sprouting in fibrin from rat aortic rings as evaluated by the ratio between the cellular area and the mean gray value of the sample (sprouting index); suramin at 50 μg/ml significantly reduced the sprouting index from the control value of 0.35 ± 0.04 to 0.14 ± 0.02 mm²/gray level (P < 0.05). Likewise, the area occupied by cells was 19.2 ± 1.8 mm² as compared with 41.8 ± 4.2 mm² in controls (P < 0.05). In the rat model of neovascularization induced in the cornea by chemical injury, suramin at 1.6 mg/eye per day reduced the length of blood vessels (0.7 ± 0.1 mm as compared with 1.5 ± 0.1 mm in controls, P < 0.05). In the same model the ratio between the area of blood vessels and the total area of the cornea (area fraction score) was decreased by suramin from 0.19 ± 0.02 in controls to 0.03 ± 0.003 (P < 0.05). Suramin given i.p. at 30 mg/kg per day markedly inhibited the neovascularization induced in the rat mesentery by compound 48/80 or conditioned medium from cells secreting the angiogenic protein fibroblast growth factor-3 (FGF-3). The area fraction score in control rats treated with compound 48/80 was 0.31 ± 0.03, and this was reduced to 0.07 ± 0.01 by suramin (P < 0.05). After i.p. administration of FGF-3 the area fraction score was reduced by suramin from 0.29 ± 0.03 to 0.05 ± 0.01 (P < 0.05). These results provide evidence that suramin exerts inhibitory effects on angiogenesis in both in vitro and in vivo models. Received: 9 January 1998 / Accepted: 29 June 1998     

重组人血管内皮抑制素治疗恶性肿瘤的研究进展

重组人血管内皮抑制素(恩度)是一种广谱的抗血管生成分子靶向药物,主要循证证据为联合化疗治疗晚期非小细胞肺癌(NSCLC).近年来,重组人血管内皮抑制素用于治疗多种恶性肿瘤的研究逐渐增多,并取得了较好的疗效.此外,有关重组人血管内皮抑制素联合治疗手段、给药途径、给药方法的研究逐渐开展,有利于其合理应用.     

Effect of trauma of implantation of metastatic tumor in bone in mice

We studied the influence of surgical trauma to the iliac bone on the implantation of I. V. injected tumor cells, which formed tumor in the surgical wounds of 27/84 mice (32%). None of these mice or nonsurgical mice developed tumor in the opposite or uninjured pelvic bone (P < 0.0001). When different numbers (10⁵, 5 × 10⁵, and 10 × 10⁵) of TA3Ha cells were injected I. V. immediately after surgery, the frequency of tumor formation showed an increase (respectively, 32%, 63%, 71%). As the interval between induction of trauma and tumor cell injection was increased from 0 to 15 days, the frequency of tumor formation declined from 32% to 0%. These results suggest that the healing wound is a privileged site for experimental metastasis, particularly in the early stages. It is likely that the proteins in the blood clotting cascade are involved in local tumor implantation. © 1994 Wiley-Liss, Inc.     

胶质瘤中微RNA研究进展

微RNA(microRNA,miR)可在转录后水平负调控靶基因表达,miR异常表达与肿瘤生成密切相关.对胶质瘤中多个miR异常表达及其机制的研究将对进一步探讨胶质瘤的分子病理及其诊治开拓新途径.     

Evaluation of the antitumoral effect of dihydrocucurbitacin-B in both in vitro and in vivo models

Aims  We evaluated both in vitro and in vivo antitumoral properties of an isolated compound from Wilbrandia ebracteata, dihydrocucurbitacin-B (DHCB), using B16F10 cells (murine melanoma). Materials and methods  We made use of MTT and ³H-Thymidine assays to investigate the cell viability and cell proliferation, flow cytometry analysis to monitor cell cycle and apoptosis, western blot analysis to evaluate the expression of cell cycle proteins, imunofluorescence analysis and in vivo tumor growth and metastasis. Results  Dihydrocucurbitacin-B significantly reduced cell proliferation without important effects on cells viability. DHCB lead cells to accumulate in G2/M phases accompanied by the appearance of polyploid cells, confirmed by fluorescence assays that demonstrated a remarkable alteration in the cell cytoskeleton and formation of binuclear cells. Annexin-V-FITC incorporation demonstrated that DHCB did not induce apoptosis. About 10 μg/mL DHCB was found to decrease cyclin-A, and especially in cyclin-B1. The in vivo experiments showed that DHCB treatment (once a day up to 12 days; p.o.) was able to reduce the tumor growth and lung metastasis up to 83.5 and 50.3%, respectively. Conclusions  Dihydrocucurbitacin-B reduces cell proliferation due to a decrease in the expression of cyclins, mainly cyclin-B1 and disruption of the actin cytoskeleton, arresting B16F10 cells in G2/M phase. Taken together, the in vitro and in vivo experiments suggest that DHCB was effective against cancer, however, it remains to be proved if DHCB will be a good candidate for drug development.     

中国乳腺癌患者生活质量研究进展

生活质量（qualityoflife,QOL）又译作生命质量、生存质量,它是在世界卫生组织提倡的健康新概念“人们在躯体上、精神上及社会生活中处于一种完好的状态,而不仅仅是没有患病和衰弱”的基础上构建的,是医学模式由生物医学模式向生物一心理一社会医学模式转变的体现。西方发达国家已将此概念广泛应用于临床试验、卫生政策制定和卫生资源效益评价等众多领域。生存质量已作为评价肿瘤患者术后状况的首选指标。     

Survey of changes in dietary preferences in cancer patients in China

Objective The aim of this study was to investigate the changes in dietary preferences in cancer patients in China and to determine the need for encouraging the adherence to a sensible diet among such patients.Methods A total of 468 cancer patients were interviewed using a self-designed questionnaire focusing on changes in the intake of specific foods. Data were analyzed using SPSS 16.0. Results Most patients completely avoided roosters and carp(73.1%), condiments(51.9%), and meat of aquatic species(40.4%). All other types of the specific foods were completely avoided by different subpopulations of the patients.Conclusion In addition to focusing on disease treatment, medical professionals need to help cancer patients overcome barriers associated with the customs of avoiding specific foods encompassed by the term ”fawu” and provide them with dietary guidance in order to prevent negative nutritional effects.     

新疆维吾尔族妇女宫颈病变中DAPK表达的研究

[目的]探讨DAPK基因与新疆维吾尔族妇女宫颈病变的相关关系。[方法]选取维吾尔族妇女正常或炎症的宫颈组织30例、CINⅠ30例、CINⅡ/Ⅲ30例、宫颈鳞癌组织30例采用免疫组化SP法检测DAPK蛋白表达;为了进一步验证DAPK蛋白表达水平,采用逆转录聚合酶链反应（RT-PCR）法检测正常或炎症的宫颈组织10例、CINⅠ10例、CINⅡ/Ⅲ15例、宫颈鳞癌组织20例中mRNA的表达。[结果]DAPK的蛋白表达率在正常或炎症的宫颈组织、CINⅠ、CINⅡ/Ⅲ、宫颈鳞癌组织中分别为93.3%、83.3%、60.0%、33.3%,SCC组阳性表达率明显减少（P〈0.05）;四组mRNA的表达率分别为90.0%、90.0%、46.7%、10.0%,SCC组阳性表达率明显减少（P〈0.05）。宫颈组织中DAPK在蛋白水平和mRNA水平的表达均和宫颈病变程度成负关（P〈0.05）。[结论]新疆维吾尔族妇女宫颈病变组织中DAPK蛋白和mRNA水平均随病变程度加深而减少;DAPK蛋白检测可能为宫颈癌的早期诊断提供依据。