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中药对恶性肿瘤细胞信号转导通路的影响及其作用机理研究的进展
细胞信号转导通路(cellular signal transduction pathway)是指细胞接受外界信号,通过一整套特定的机制,将胞外信号转导为胞内信号,终调节特定基因表达,并引起细胞的应答反应.
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宫颈涂片中少见恶性肿瘤细胞的诊断及鉴别诊断
病例 11.临床资料:患者女,44岁.体检发现子宫肌瘤1年,下腹痛、阴道出血3个月.妇科检查:外阴(-),阴道处女膜内上方可及3个结节,直径分别为1.0、2.0和2.5 cm,其中一个位于前壁尿道口下缘.
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光动力学疗法诱导肿瘤细胞凋亡机制的研究进展
光动力学疗法(photodynamic therapy,PDT)是指光敏剂选择性地聚集在肿瘤组织中,接受光照后在细胞内产生活性氧物质,而导致肿瘤细胞凋亡或坏死的一种治疗方法.迄今为止,加拿大、美国、法国、荷兰、德国和日本等国家已先后批准PDT用于一些恶性肿瘤的治疗[1].随着PDT作用机制的深入了解和研究,其应用前景也将更为广阔.
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乳腺癌血行微小转移研究进展
转移是肿瘤相关性死亡的主要原因.转移的过程包括肿瘤细胞从原发病灶脱落、侵入血管、在循环中停留、游离出血管、定位于远隔器官、增殖形成转移灶,肿瘤细胞必须顺利完成这一系列过程才能终形成远处转移灶[1].大约有25%未发生淋巴结转移的局灶性乳腺癌患者终发展成远处转移;相反,至少有30%伴有腋窝淋巴结转移的乳腺癌患者在初始治疗之后的5一lO年内未出现远处转移[2].这些数据说明乳腺癌发生血行转移是独立于淋巴结转移途径的.并且血行转移可能发生于疾病进程的早期阶段.微小转移指存在于淋巴结、外周血、骨髓巾的不能被常规手段检测到的肿瘤细胞,其中存在于血循环中的微小转移为循环肿瘤细胞(circulating tumor cell,CTC),存在于骨髓中的微小转移为播散肿瘤细胞(disseminated tumor cells,DTC).
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结直肠癌外周血循环肿瘤细胞的研究进展
我国结直肠癌发病率居恶性肿瘤中第3位,且以每年4.2%的速度上升,5年生存率约为27%[1].结直肠癌患者中早期诊断的患者仅约11%左右[2],大多数患者在就诊时已经出现远期转移.肿瘤转移是一个涉及多步骤多因素的复杂过程,具有转移潜能的肿瘤细胞脱离原发病灶,以极少的数量转移到血液、骨髓、淋巴结或远处器官中,运用常规的检测手段难以发现,这种现象称为肿瘤的微转移(Micro-metastasis).肿瘤细胞的脱落、侵袭并进入血液循环是肿瘤转移的初阶段,并为终形成肿瘤转移病灶提供了可能.因此,在外周血中检测循环肿瘤细胞(circulating tumor cells,CTC)逐渐成为临床研究的热点.本文就CTC在结直肠癌的检测、应用及新的研究方向等方面进行综述.
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循环肿瘤细胞检测在前列腺癌诊治中的价值
前列腺癌是欧美国家发病率高的男性恶性肿瘤之一,其病死率仅次于肺癌,居第2位。近年来,我国随着人口老龄化和饮食结构等因素的变化,前列腺癌的发病率和病死率呈逐年上升的趋势。检测外周血液中循环肿瘤细胞( circulating tumor cells,CTCs)是一种具有巨大发展潜力的无创诊断和实时疗效监测手段,对于前列腺癌患者早期转移和复发的筛查、诊断有重要意义。 CTCs是指自发或因诊疗操作由实体瘤或转移灶释放进入外周血循环的肿瘤细胞,由于CTCs具有与肿瘤原发灶相似的基因型和表型,通过观察CTCs的数量变化及其分子特性,分析CTCs的分子表观遗传学特征,进行基因检测有助于判断病情以及决定肿瘤治疗方案,对于前列腺癌个体化治疗具有重要的临床意义[1]。
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Objective: To study the vaccine potency of gene-modified tumor cells. Methods: The EL-4 lymphoma was transduced with recombinant retrovirus containing the murine GM-CSF gene or B7-1 gene. The effect of gene transduction on antitumor immunity was investigated. Results: Flow cytometry analysis showed that expression of their surface marker between wild-type EL-4 cells and gene transduced tumor cells was the same except for CD80 positive in B7-1 gene transduced cells. GM-CSF gene or B7-1 gene transduced EL-4 cells resulted in remarkable loss of tumorigenicity in syngenetic mice. The systemic protective immunity was induced against the challenge with EL-4/wt cells. Therapeutic vaccine with EL-4/GM-CSF or EL/7-1 cells could retard the growth of established early-stage EL-4/wt tumor significantly, but not retard the growth of late-stage EL-4/wt tumor. Irradiated GM-CSF gene transduced EL-4 cells showed strong vaccine effect against EL-4 cell challenge, but irradiated B7-1 gene transduced EL-4 cells showed weak vaccine effect. Remarkable cooperative antitumor effect against EL-4 cell challenge was observed when both irradiated EL-4/GM-CSF and EL-4/B7-1 were inoculated together. Conclusion: GM-CSF gene or B7-1 gene transduced combination of the two kinds of vaccine may have potential application value in human cancer treatment.
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Objective: To establish a fluoregenic probe quantitative RT-PCR (FQ-RT-PCR) method for detection of the expression of MDR1 gene in tumor cells and to investigate the expression of MDR1 gene in patients with lung cancer. Methods: The fluorogenic quantitative RT-PCR method for detection of the expression of MDR1 gene was established. K562/ADM and K562 cell lines or 45 tumor tissues from patients with lung cancer were examined on PE Applied Biosystems 7700 Sequence Detection machine. Results: the average levels of MDR1 gene expression in K562/ADM cells and K562 cells were (6.86±0.65)× 107copies/mg RNA and (8.49±0.67)×105 copies/mg RNA, respectively. The former was 80.8 times greater than the latter. Each sample was measured 10 times and the coefficient variation (CV) was 9.5% and 7.9%, respectively. Various levels of MDR1 gene expression were detected in 12 of 45 patients with lung cancer. Conclusion: Quantitative detection of MDR1 gene expression in tumor cells was achieved by using FQ-RT-PCR. FQ-RT-PCR is an accurate, and sensitive method and easy to perform. Using this method, low levels of MDR1 gene expression could be detected in 24% of the patients with lung cancer.
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专题演讲-W3药物和环境毒物的免疫毒性与神经毒性
Toxicity to the immune system encompasses suppression or enhancement of the immune response. Suppression of the immune response can lead to decreased host resistance to infectious agents or tumor cells. Enhancing the immune response can exaggerate autoimmune diseases or hypersensitivity.
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重组人生长激素对人胃肠道肿瘤细胞生长影响实验研究
人生长激素(hGH)具有促进蛋白质合成,加速脂肪酸分解氧化,纠正负氮平衡,调节免疫功能的作用.重组人生长激素(rhGH)对消化道恶性肿瘤患者术后进行代谢调理治疗,明显促进了肿瘤患者的康复.但人生长激素(hGH)作为一种生长因子能促进正常细胞的增生分裂,故有学者认为它可以促进肿瘤细胞的生长.因而肿瘤患者术后能否使用rhGH存在争议.本研究通过体外实验探讨rhGH对人胃、直肠癌细胞株BGC823、HR8348生长的影响以及建立裸鼠人胃癌细胞移植瘤模型探讨rhGH在体内对人胃癌细胞生长的影响,为临床胃、直肠癌患者术后能否应用rhGH进行代谢调理提供一定的参考.
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循环肿瘤细胞检测分子标志物的研究现状及进展
循环肿瘤细胞(circulating tumor cells,CTCs)指自发或因诊疗操作由实体瘤或转移灶释放进入外周血循环的肿瘤细胞.这些进入循环的肿瘤细胞大部分在机体免疫识别及杀伤等作用下发生凋亡,极少数存活下来形成微小癌栓,在一定条件下发展为转移灶.
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骨转移瘤系统性分子靶向治疗靶点与药理学制剂研究
骨转移瘤骨骼微环境中,肿瘤细胞分泌多种细胞因子促进溶骨活性,而溶骨后释放的储存于骨内的生长因子又促进肿瘤细胞生长与侵袭,从而形成骨质破坏“恶性循环”。虽然骨骼微环境可造成骨质破坏的“恶性循环”,但也为骨转移瘤治疗提供了许多潜在性靶点。骨转移瘤分子靶点以核因子?κB受体活化因子(receptor activator of nuclear factor?κB, RANK)-核因子?κB受体活化因子配体(RANK ligand, RANKL)-骨保护素(osteoprotegerin, OPG)系统研究得为广泛与深入。骨转移瘤细胞可以促进骨基质细胞表达RANKL并抑制OPG的表达,RANKL与OPG比例失调是诱发骨质破坏的重要因素。溶骨产生的转移生长因子β在介导“恶性循环”中的作用越来越突出,转移生长因子β可以促进肿瘤细胞发生上皮-间质转变、血管生成以及免疫抑制。Src家族激酶、内皮素A受体、基质金属蛋白酶以及组蛋白酶K等均为骨转移瘤治疗的潜在性靶点。以狄诺塞麦为代表的靶向药理学制剂的本质均为阻断骨转移瘤骨质破坏“恶性循环”。骨转移瘤靶向制剂除了可以抑制骨转移瘤细胞骨质破坏外,部分还可以产生直接抗原发肿瘤效应,它们在延迟骨相关事件发生、延长患者生存期以及终提高患者生存质量方面发挥着重要作用。骨转移瘤患者已经可以从系统性分子靶向治疗中受益,进一步研发系统性靶向制剂对改善患者治疗选择、增强疗效具有重要意义。
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Ionizing Radiation Induces HMGB1 Cytoplasmic Translocation and Extracellular Release
Objective A nucleosomal protein,HMGBI,can be secreted by activated immune cells or passively released by dying cells,thereby amplifying rigorous inflammatory responses.In this study we aimed to test the possibility that radiation similarly induces cytoplasmic HMGB1 translocation and release.Methods Human skin fibroblast (GM0639) and bronchial epithelial (16HBE) cells and rats were exposed to X-ray radiation,and HMGB1 translocation and release were then assessed by immunocytochemistry and immunoassay,respectively.Results At a wide dose range(4.0-12.0 Gy),X-ray radiation induced a dramatic cytoplasmic HMGB1 translocation,and triggered a time-and dose-dependent HMGB1 release both in vitro and in vivo.The radiation-mediated HMGB1 release was also associated with noticeable chromosomal DNA damage and loss of cell viability.Conclusions Radiation induces HMGB1 cytoplasmic translocation and extracellular release through active secretion and passive leakage processes.
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中药诱导肿瘤细胞自噬及其分子机制
自噬是细胞膜结构吞噬自身的细胞质形成自噬体,并与溶酶体结合对细胞内蛋白质和细胞器降解的过程.自噬参与细胞诸多生理和病理过程,其与肿瘤发生密切相关.近年来对细胞自噬在肿瘤中的作用及其作为抗肿瘤药物的作用机制的研究有了较大进展,特别是某些中药及有效成分如姜黄素、苦参碱、雷公藤内酯等能诱导肿瘤细胞自噬,自噬将成为肿瘤研究的一个新热点.现将自噬的分子机制、自噬与肿瘤、中药诱导肿瘤细胞自噬及其分子机制的研究进展做一综述.
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Biomechanical Studies on Murine Erythroleukemia Cell Line after p53 Gene Transfer
We studied the role of p53 gene in the biorheologiy and biology in murine erythroleukemia cell line ( MEL), with the goal of understanding the influence of this tumor suppressor gene on the deformability and metastasis of tumor cells,. Experiments were performed on MEL - M and MEL - W, which expressed a mutant p53 gene and over - expressed the wild - type p53 gene, respectively, as well as the MEL cells transfected with an empty plasmid.
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射频消融治疗肝癌对残存癌细胞侵袭转移和机体免疫功能的影响
1996年Rossi等报道应用射频消融(radiofrequency ablation,RFA)治疗肝癌后,RFA治疗肝癌得到迅速普及应用,其原理是通过针型电极输出高频率射频波,使组织内离子产生快速振动,摩擦产热,局部温度可达90~120℃,靶区肿瘤组织细胞发生热凝固性变性和坏死,从而达到杀灭肿瘤的目的[1].
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蛋白激酶C对肿瘤细胞粘附性影响的研究进展
侵袭和转移是恶性肿瘤的重要生物学行为之一,是成功治疗肿瘤的大障碍.粘附是肿瘤细胞侵袭的第一步,是调节某些肿瘤细胞转移的重要步骤,这种行为可能会影响转移过程中的几个阶段.
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乳腺癌患者循环肿瘤细胞的检测及其临床应用
肿瘤转移是乳腺癌治疗失败的主要原因之一.肿瘤细胞进入外周血是发生远处转移的前提,早在1896年,Ashworth在1例因癌症死亡的患者外周血中发现了类似肿瘤的细胞,并首次提出了循环肿瘤细胞(circulating tumor cell,CTC)的概念.进入循环未被清除的肿瘤细胞可相互聚集形成微小癌栓,并在一定条件下发展为转移灶.越来越多的学者开始关注循环肿瘤细胞方面的研究,近年来,有关乳腺癌患者CTC检测及其临床应用的研究已取得了长足的进展.
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乳腺癌患者循环肿瘤细胞的检测及其临床应用
肿瘤转移是乳腺癌治疗失败的主要原因之一.肿瘤细胞进入外周血是发生远处转移的前提,早在1896年,Ashworth在1例因癌症死亡的患者外周血中发现了类似肿瘤的细胞,并首次提出了循环肿瘤细胞(circulating tumor cell,CTC)的概念.进入循环未被清除的肿瘤细胞可相互聚集形成微小癌栓,并在一定条件下发展为转移灶.越来越多的学者开始关注循环肿瘤细胞方面的研究,近年来,有关乳腺癌患者CTC检测及其临床应用的研究已取得了长足的进展.
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疫苗注射部位发生原发性皮肤间变性大细胞淋巴瘤一例
患者男,79岁,左上臂注射甲型流感疫苗后2个月,于注射部位出现红色结节,逐渐增大破溃.皮损组织病理检查:表皮内有淋巴细胞浸润,真皮内有大量密集淋巴细胞形成团块,细胞较大,胞质淡染,胞核有异形和核分裂.免疫组化染色:CD3、CD5和LCA阳性细胞各占90%,CD20和CD56均阴性,CD30阳性细胞占90%,CD10少量阳性,细胞角蛋白1-3、上皮膜抗原和突触囊泡蛋白阴性,间变性淋巴瘤激酶阴性,Ki-67阳性细胞为80%.诊断:注射甲型流感疫苗后注射局部原发性皮肤间变性大细胞淋巴瘤.