Overview of the biochemical and genetic processes in malignant mesothelioma

Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.     

p53和p21^WAF—l在贲门癌变过程中的表达及关系

目的 探讨p53、p21^WAF—l蛋白与贲门癌发生发展的关系及其相互关系。方法 采用免疫组化方法检测26例贲门粘膜轻度炎症、28例重度炎症、21例不典型增生和60例贲门腺癌组织中p53、p21^WAF—l蛋白的表达状况。结果 ①随贲门上皮病变的加重，p53蛋白的阳性表达率呈上升趋势。从轻度炎症→重度炎症→不典型增生→腺癌，p53蛋白的阳性表达率分别为15．4％、39．1％、57．1％和66．7％。②贲门腺癌中p53多为高表达(55％)，与其他各组比较差异显。③不典型增生中p21^WAF—l蛋白表达最强，腺癌组p21^WAF—l阳性表达率21．6％明显低于轻度炎症组和不典型增生组。④p53、p21^WAF—l蛋白表达一致占51．8％，表达不一致占48．1％，两表达无显相关性。结论p53、p21^WAF—l在贲门癌发生发展中起重要作用。在贲门癌变过程中，p21^WAF—l的诱导存在着不依赖p53的途径。     

泛素连接酶在皮肤黑素瘤的研究进展

皮肤黑素瘤是一种起源于皮肤黑素细胞的恶性肿瘤,具有高度增殖性和侵袭性,并常发生转移.尽管近年来皮肤恶性黑素瘤的治疗取得很大进展,但晚期黑素瘤患者预后依然很差.泛素蛋白酶体系统可通过调节细胞内蛋白对各种生理过程进行调控,泛素连接酶是泛素化过程中识别底物特异性的酶,可作为癌基因或抑癌基因参与黑素瘤发病机制,能够调节各种不同的信号通路和多种在黑素瘤发展中起重要作用的蛋白.因此,针对泛素连接酶的分子靶向治疗是目前研究黑素瘤的热点之一.     

甲状腺癌的分子生物学研究进展

甲状腺癌是内分泌系统最常见的恶性肿瘤,多发于女性患者。不同病理类型的甲状腺癌,其生物学行为不同,且发病比较隐匿,故目前对甲状腺癌的早期诊断仍比较困难。近年来随着分子生物学的发展,对甲状腺癌的肿瘤标志物、癌基因及分子治疗研究较多。本文将对这三个方面的研究进展作一综述。     

Relationship between loss of heterozygosity of deleted in colorectal carcinoma gene microsatellites and prognosis of colorectal adenocarcinoma

AIM: To investigate the relationship between the loss of heterozygosity (LOH) of microsatellites on the deleted in colorectal carcinoma (DCC) gene and prognosis of colorectal adenocarcinoma.METHODS: A retrospective study of 58 colorectal adenocarcinoma cases with follow-up data and paired control normal mucosal tissues from 1983 to 1985 from files from the West China University of Medical Sciences Department of Pathology was carried out by PCR microsatellite analysis. Sixteen, 35, and seven cases had well-, moderately, and poorly differentiated tumors, respectively; 11, 30, and 17 cases were staged as Dukes’ A, B, and C, respectively.RESULTS: LOH of DCC microsatellites was detected in 18 cases (31.0%). The 5-year survival rate between LOH-positive and LOH-negative patients was 44.4% and 77.5%, respectively (P < 0.05). The results suggest that LOH of DCC microsatellites correlate with prognosis but not with differentiation (P > 0.05) and Dukes’ stage (P > 0.05) in colorectal adenocarcinoma.CONCLUSION: LOH of DCC microsatellites may be a marker of malignancy. Combined with the traditional prognostic indicators, LOH can predict prognosis of colorectal adenocarcinoma.     

红景天甙对缺氧状态下兔肺动脉平滑肌细胞增殖和c-fos、c-myc原癌基因表达的影响

目的:研究红景天甙(salidroside, Sal)对缺氧( 2%～3%)状态下兔肺动脉平滑肌细胞(PASMC)增殖、DNA合成、细胞周期和c-fos,c-myc 原癌基因表达的影响.方法:应用细胞培养、四唑盐比色试验(MTT)、[3H] -胸腺嘧啶核苷([3H]-TdR)掺入、细胞周期测定和斑点杂交的方法.结果:发现缺氧24 h可直接刺激PASMC,使MTT之OD值增加95%(P＜0.05),[3H]-T dR的掺入量增加140%(P＜0.01);在缺氧的PASMC培养液中加入Sal(1200 μg/mL)可抑制缺氧的这种促增殖作用,PASMC的MTT之OD值与[3H]-TdR掺入量与缺氧组相比显著下降(P＜0.05);流式细胞分析显示缺氧24 h PASMC G2/M期细胞比例比常氧组明显增多(P＜0.01),G0/G1期细胞比例明显减少(P＜0.05),与缺氧组相比Sal可增多PASMC G0/G1期细胞比例,减少G2/M期细胞比例(P＜0.05);缺氧可促进c-fos,c-myc原癌基因表达,该效应可被Sal所抑制.结论:红景天甙可抑制缺氧所致的PASMC增殖、DNA合成、进入G2/M期的细胞比例和c-fos,c-myc原癌基因表达.     

miR-21与妇科肿瘤关系的研究进展

微小RNA (miRNA)是一类分布十分广泛的内源性非编码RNA,在动物、植物和病毒中广泛存在.miRNA与肿瘤的发生、发展和预后有关,并在肿瘤的增殖、分化及凋亡等方面有重要的作用.大量研究结果表明,许多miRNA可作为原癌基因或抑癌基因,在肿瘤的发生和发展中发挥重要作用,其中miR-21最受重视.miR-21作为较早...     

葡萄胎恶变预测的研究进展

妊娠滋养细胞疾病（GTD）是一组具有不同临床、形态学和生物学特性的异质性疾病,其共同特征为滋养层异常。葡萄胎虽属于妊娠滋养细胞疾病中的良性病变,但有潜在恶变的危险。目前主要依据密切监测血清人绒毛膜促性腺激素（hCG）衰减曲线来检查潜在的恶性病变。最近几年,随着实验室诊断技术的改进和各项检测设备的发展,有关能早期发现葡萄胎恶变的遗传学、各项生化指标及影像学改变的报道越来越多,试图获得精确而早期的疾病诊断。简述这些有意义的葡萄胎恶变预后指标。     

三氧化二砷抑制体外培养小鼠气道成纤维细胞增殖及c-myc与c-sis表达

目的：探讨三氧化二砷 (As2O3))对体外培养的小鼠气道成纤维细胞 (FB)增殖及原癌基因c-myc与c-sis表达的影响。 方法： 按不同药物分7组，在体外培养的FB中分别加入浓度为0.25、0.5、1.0、2.0和4.0 μmol/L的As2O3，在1、3、5和7 d后用记数法观察FB生长情况，并用流式细胞仪（FCM）检测不同浓度药物 对各组FB增殖的影响及各组c-myc与c-sis的阳性表达率。 结果： 各种实验浓度的As2O3对FB均有抑制作用，并有时间剂量效应。流式细胞仪分析显示，随着浓度的增高，G1期细胞比例逐渐增高，G2/M期细胞比例降低，浓度为2.0和4.0 μmol/L的As2O3能显著抑制c-myc与c-sis的表达。 结论： As2O3能抑制FB的增生，其机理可能与其下调c-myc与c-sis的表达有关。     

Natural mechanisms protecting against cancer

Carcinogenesis is a multistage process. At each step of this process, there are natural mechanisms protecting against development of cancer. The majority of cancers in humans is induced by carcinogenic factors present in our environment including our food. However, some natural substances present in our diet or synthesized in our cells are able to block, trap or decompose reactive oxygen species (ROS) participating in carcinogenesis. Carcinogens can also be removed from our cells. If DNA damage occurs, it is repaired in most of the cases. Unrepaired DNA alterations can be fixed as mutations in proliferating cells only and mutations of very few strategic genes can induce tumor formation, the most relevant are those activating proto-oncogenes and inactivating tumor suppressor genes. A series of mutations and/or epigenetic changes is required to drive transformation of a normal cell into malignant tumor. The apparently unrestricted growth has to be accompanied by a mechanism preserving telomeres which otherwise shorten with succeeding cell divisions leading to growth arrest. Tumor can not develop beyond the size of 1–2 mm in diameter without the induction of angiogenesis which is regulated by natural inhibitors. To invade the surrounding tissues epithelial tumor cells have to lose some adhesion molecules keeping them attached to each other and to produce enzymes able to dissolve the elements of the basement membrane. On the other hand, acquisition of other adhesion molecules enables interaction of circulating tumor cells with endothelial cells facilitating extravasation and metastasis. One of the last barriers protecting against cancer is the activity of the immune system. Both innate and adaptive immunity participates in anti-tumor effects including the activity of natural killer (NK) cells, natural killer T cells, macrophages, neutrophils and eosinophils, complement, various cytokines, specific antibodies, and specific T cytotoxic cells. Upon activation neutrophils and macrophages are able to kill tumor cells but they can also release ROS, angiogenic and immunosuppressive substances. Many cytokines belonging to different families display anti-tumor activity but their role in natural anti-tumor defense remains largely to be established.