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胃印戒细胞癌与黏液腺癌生物学特征及分子病理学机制的比较研究
目的:以胃癌组织学生长方式分型和癌细胞功能分化表型研究为基础,从形态、机能与蛋白分子水平相结合的层次,探讨胃印戒细胞癌和黏液腺癌浸润转移的生物学规律及相关分子病理学机制.方法:本系列研究标本全部取自中国医科大学肿瘤研究所存档石蜡标本和冰冻标本.在病理形态学观察的基础上,采用酶组织化学、黏液组织化学和免疫组织化学、流式细胞技术(FCM)结合分子生物学方法检测并比较上述两型胃癌相关基因编码蛋白表达、癌细胞DNA倍体、增生细胞动力学,微卫星不稳定性和杂合性丢失等分子生物学特征.结果:近40 a研究发现,胃印戒细胞癌好发于中青年女性,组织学上倾向于弥漫性生长,以吸收-黏液分泌功能双向分化(AMPFDT)为主,生长依赖雌激素,好发卵巢和子宫颈转移.胃黏液腺癌多见于50岁以上男性,倾向于团块状或巢状生长,功能分化上表现为AMPFDT型和黏液分泌功能分化型(MSFDT)两种类型,生长不依赖雌激素,以腹膜广泛浸润生长为主要特点,层粘蛋白及其受体和Ⅳ型胶原、CD44 V6、PTEN蛋白表达显著高于胃印戒细胞癌.两型胃癌酸性磷酸酶(ACP)和血管内皮生长因子(VEGF)无显著差异.结论:胃印戒细胞癌和黏液腺癌虽都以旺盛的黏液分泌能力为主要特征,但他们在病理形态、超微结构、生长浸润方式、功能分化和基因表达等不同层次均具有不同的表现,提示上述两型胃癌可能具有不同的癌变机制,以此为基础开展有关早期诊断和预后评估的肿瘤标志物研究对上述两型胃癌的临床治疗有科学的指导意义.
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BAK基因过表达对胃癌细胞的诱导凋亡作用及其分子机制
目的:探讨转染外源性BAK基因及其过表达对胃癌细胞的诱导凋亡作用和分子机制.方法:构建携带有BAK基因的真核表达载体并转染胃癌MKN-45细胞1-5d后,RT-PCR和Western Blotting法检测BAK基因表达;细胞计数、MTT比色法检测癌细胞生长活性,流式细胞仪分析细胞周期时相改变,透射电镜、末端TdT酶标记技术检测癌细胞凋亡;比色法检测癌细胞内Caspase-3活性改变.结果:转染1-5 d后,癌细胞BAK mRNA和蛋白表达水平显著增强(P<0.01),癌细胞体外生长抑制11.6-35.3%(P<0.01),增生活性抑制10.2-32.4%(P<0.01),细胞周期出现G0/G1期阻滞,部分癌细胞出现胞体缩小、核固缩等凋亡形态学改变,凋亡率为21.4%(P<0.01);癌细胞Caspase-3活性增强4.45倍(P<0.01).结论:转染外源性BAK基因使其过表达能激活Caspase-3,显著诱导胃癌MKN-45细胞凋亡,有望成为胃癌治疗的新途径.
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心律失常的分子机制和基因治疗研究进展
心律失常是全世界非常关注的重大公共卫生问题,也是我国重大疾病防治领域亟待解决的课题.国内外学者在药物、射频消融术、心脏起搏器、植入型心律转复除颤器(ICD)等心律失常治疗领域不懈努力,取得瞩目的成就.而基因治疗是当今生物医学发展的一个重要里程碑.它不仅是早期干预心脏病的新手段,也是当今"再生医学"研究领域的重要组成部分.基会项目:国家自然科学基金(30760079);新疆维吾尔自治区自然科学基金(2009211B18)
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癫癎发生的分子机制研究进展
癫癎是严重危害人类健康的神经系统常见病,以大量神经元反复发作的异常放电引起中枢神经系统短暂性功能失常为主要特征.病因多样,机制复杂.截至目前,癫痫治疗虽然取得了很大进展,但足手段仍然十分有限,且只能控制癫癎发作,却不能从根本上遏制疾病的发生或者完全根治疾病.
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噪声暴露引起耳蜗损伤机制的研究
噪声是常见的职业性伤害和听力致残因素,预防噪声性耳聋的发生及降低其听觉损害的程度一直是我们研究的重要课题。近年的研究发现噪声暴露可引起耳蜗内活性氧、活性氮自由基及金属蛋白酶增加,毛细胞内DNA损伤,Caspase-3激活,AIF及EndoG的转移等一系列变化,终导致毛细胞死亡,以凋亡为主。噪声损伤机制的研究为预防和治疗噪声性耳聋开辟了新的思路。
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PDGF-B链基因表达的调控及其在常见心血管疾病中的意义
血小板源生长因子(platelet-derived growth factor,PDGF)是机体普遍存在的促分裂剂,系由两种肽链(A链、B链)组成的同型或异型二聚体.依不同的细胞来源,有3种形式:PDGF-AA,PDGF-AB和PDGF-BB.PDGF-A链和-B链分别由PDGF-A链基因和-B链基因编码.PDGF-B链主要由内皮细胞和巨噬细胞产生,其基因表达调控异常与常见心血管疾病的发生发展存在着密切关系,内皮细胞功能紊乱日益受到重视,而内皮细胞仅表达B链,本文就其表达调控,尤其是转录调控的研究进展和应用作一概述.
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Elemene is a new anticancer drug isolated from a Chinese traditional medicine Curcuma aromatica. In previous work, we discovered that tumor cell vaccine (TCV) treated with oleum Curcuma aromatica or elemene could induce significant immunoprophylactic effect against a variety of aminal tumor strains and the method of preparation of elemene combo-TCV(EC-TCV) already got China's inventive patent. In this paper we further studied the active immunotherapeutic effect and the possible cellular/molecular mechanisms of EC-TCV immunization. The results were as follows:(1) EC-TCV immunization showed significant therapeutic effects (P<0.05) against murine Ca761 syngeneic mammary carcinoma (H-2k) and HCa-F allogeneic hepatic carcinoma (H-2-) models; (2) The spleen cells of Hca-F EC-TCV immunized mice displayed higher cytotoxicity and IL-12 level while the secretion of IL-10 was decreased (P<0.05); (3) Similar to heat shock, elemene(E), mitomycin C(MMC) and glutaraldehyde (G) could act alone as stressor, and induce significant changes of the expression of membrane heat shock proteins(HSP70 or/and HSP90) on L615 leukemia and HCa-F hepatoma cells and the EC-TCVs (E+MMC+G treated in combination) showed the highest level of membrane HSPs expression (P<0.05 or P<0.01 );(4) The HSP70-peptide complex isolated from HCa-F EC-TCV through ADP-agarose affinity chromatographic system could induce active immunoprotection against lethal dose challenge of HCa-F hepatic cancer cell but could not protect against the cross challenge of lethal dose of L615 leukemia. The results indicated that the immunoprotective effect of EC-TCV was in some extent tumor-specific, MHC-nonrestricted, and HSPs might play an important role in its molecular mechanisms.
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中药抗肿瘤转移的分子机制研究进展
肿瘤转移过程从西医的观点来说包括,瘤细胞从瘤体脱离;瘤细胞向周围组织浸润;瘤细胞侵入血管及淋巴管并在循环系统存活;瘤细胞在新的血管淋巴管内附壁停留、着床;瘤细胞穿出管壁形成微小转移灶,转移瘤血管生长及转移灶扩大.
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Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis.