ｍｉｃｒｏＲＮＡ与神经胶质瘤的研究进展

ｍｉｃｒｏＲＮＡ（ｍｉＲＮＡ）是近年来发现的一类长度为１９～２５个核苷酸的非编码小分子ＲＮＡ。它主要通过与靶基因ｍＲＮＡ３′ＵＴＲ完全或不完全配对,导致靶标ｍＲＮＡ降解或转录后翻译抑制,从而参与个体发育、细胞凋亡、增殖及分化等生理过程。最近的研究表明,ｍｉＲＮＡｓ可通过调控其靶基因参与的信号通路,调节肿瘤的形成和发展,发挥着类似于癌基因或抑癌基因的功能。多种不同类型的ｍｉＲＮＡｓ在胶质瘤细胞中都有表达,可通过上调或下调相应的ｍｉＲＮＡｓ诱导胶质瘤细胞的凋亡或抑制其增殖。因此,研究胶质瘤细胞ｍｉＲＮＡｓ的表达谱,可能为胶质瘤的诊断和治疗提供新的策略。本文主要对神经胶质瘤ｍｉＲＮＡｓ的表达及其诊断和治疗领域的进展作一综述。     

自制抗p185c-erbB-2单克隆抗体的应用研究

癌基因ｃ -ｅｒｂＢ -２的扩增及其产物 ｐ１８５ｃ -ｅｒｂＢ -２（ｐ１８５）的过度表达与多种肿瘤 (如乳腺癌、卵巢癌、肺癌、膀胱癌、胃癌等 )的发生发展密切相关 ,而且ｐ１８５表达尚与肿瘤的预后、复发及患者生存期有一定关系 ,也与肿瘤对治疗的敏感性相关 ,同时 ｐ１８５也被认为是肿瘤特异性治疗的靶目标。因此 ,针对癌基因蛋白 ｐ１８５的研究已成为肿瘤诊断、治疗的又一途径。为了进一步研究ｐ１８５在肿瘤发生过程中的致癌机制以及作为肿瘤治疗的靶分子的可能性 ,本文利用在国内首先成功研制的抗ｐ１８５单克隆抗体（ＭｃＡｂ）…     

胶质瘤微血管定量和nm23表达的临床意义

肿瘤组织微血管计数（ｍｉｃｒｏｂｌｏｏｄｖｅｓｓｅｌｃｏｕｎ－ｔａｔｉｏｎ，ＭＶＣ）可反映肿瘤的血管生成情况，在判断预后、筛选高危复发或转移病人及指导治疗方面有较大应用价值［１］。ｎｍ２３是一种新的与肿瘤转移抑制有关的基因，其表达在多种人类肿瘤发生、...     

肝细胞生长刺激物质(HSS)介导阿霉素对人肝癌细胞裸鼠移植瘤的作用及其对c-met癌基因的影响

目的　为了解ＨＳＳ介导化疗药物阿霉素（ＡＤＭ） 对人肝癌裸鼠移植瘤作用及其对ｃｍｅｔ 癌基因的影响。方法　裸鼠移植瘤腹腔内注射化疗药物及ＨＳＳ２ 周,病理学检查、免疫组化法检查ｃｍｅｔ 癌基因。结果　中剂量ＡＤＭ（０．２５ μｇ／ｇｂｗ）联合ＨＳＳ抑瘤率达７２％ （Ｐ＜０ ．０１） ,单用大剂量ＡＤＭ（０．５０ μｇ／ｇｂｗ）无明显作用（Ｐ＞ ０．０５） ,但不良反应明显,单用ＨＳＳ无抑瘤及刺激增生作用。裸鼠移植瘤组织表达ｃｍｅｔ 癌基因,ＨＳＳ单用组对ｃｍｅｔ 影响不大,中剂量联合组ｃｍｅｔ 表达明显。结论　ＨＳＳ介导中剂量ＡＤＭ 的抑瘤效用可能与影响ｃｍｅｔ 的表达有关。     

肿瘤抑制基因P—ten／MMAC 1

癌基因激活和抑癌基因失活是各种肿瘤发生、发展的基础。到目前为止，已发现了多种癌基因和抑癌基因，现就最新发现的肿瘤抑制基因Ｐｔｅｎ／ＭＭＡＣ１的研究情况作一概述。１Ｐｔｅｎ／ＭＭＡＣ１的发现与结构随着对肿瘤研究的不断深入，人们已认识到肿瘤的发生除与...     

程序性细胞死亡因子4在肿瘤中的研究进展

程序性细胞死亡因子4(PDCD4)为新近发现的抑癌基因,其表达受PDCD4基因甲基化、多种微小RNA的抑制.PDCD4编码的蛋白质可增强多种肿瘤细胞对抗肿瘤药物的敏感性,抑制肿瘤的发生发展和侵袭转移进程,在多种肿瘤中发挥重要作用,有望成为临床上判断肿瘤预后的重要指标.     

人膀胱移行细胞癌c－myc、Ha－ras mRNA异常表达与临床肿瘤生物学行为的对照研究

目的探讨ｃ－ｍｙｃ、Ｈａ－ｒａｓ癌基因在人膀胱移行细胞癌中的表达及其与肿瘤恶性程度和临床特性的关系。方法应用地高辛（Ｄｉｇ）标记的ｃＤＮＡ探针对５１例膀胱移行细胞癌石蜡切片进行ｃ－ｍｙｃ、Ｈａ－ｒａｓｍＲＮＡ原位杂交检测。结果ｃ－ｍｙｃｍＲＮＡ阳性表达率为６２．７５％（３２／５１），Ｈａ－ｒａｓ为７０．５９％（３６／５１）。两者阳性率或阳性强度随恶性程度升高而增加。在临床分期较高的肿瘤中，两者亦呈高表达。结论ｃ－ｍｙｃ、ｎａ－ｒａｓ癌基因参与人膀胱移行细胞癌恶性转化过程，其异常表达可能与恶性程度及肿瘤浸润程度也有关系。     

端粒酶催化亚基hTERT在肿瘤治疗中的研究进展

人端粒酶催化亚基hTERT基因转录的从头激活是端粒酶活化的限速步骤，受到多种癌基因和抑癌基因产物的精密调控。构建hTERT启动子调控抗肿瘤基因的逆转录病毒载体，使抗肿瘤基因在端粒酶阳性的肿瘤细胞内定向表达，有望用于肿瘤基因治疗。本文首先简单介绍了hTERT蛋白的结构和表达调控机制，然后对其在肿瘤发生发展中的生物治疗的功能作一简要综述。     

miR-21与消化系统肿瘤

microRNA（miRNA）是一类内源性非编码蛋白短链RNA,参与细胞增殖、分化、凋亡等多种重要活动的调控。近来研究发现miRNA具有癌基因或抑癌基因样作用,参与多种恶性肿瘤的演进,是肿瘤发生、发展过程中的重要分子,其中miR-21最受关注。miR-21在消化系统肿瘤如食管癌、胃癌、肝癌、胆管癌、胰腺癌、结直肠癌等的细胞或组织中表达上调,发挥着类似于癌基因的作用。miR-21通过对靶基因的调控,增强了肿瘤细胞的增殖、浸润及转移能力,并与消化系统肿瘤患者的无复发时间与总生存时间密切相关。目前体外研究证实,miR-21抑制物能够提高恶性肿瘤细胞对化疗药物的敏感性,使化疗药物的杀伤肿瘤效果更加明显,而miR-21类似物,可抵消一部分化疗药物的疗效,从而提示抑制miR-21的表达或阻碍miR-21与靶基因的相互作用在消化系统肿瘤的治疗中具有广阔的应用前景。本文就miR-21在消化系统肿瘤的调控机制、增殖与凋亡、侵袭、耐药与转移中的作用,及其临床价值作一综述。      

癌基因表达的调节与抗癌药研究

肿瘤化疗已有几十年历史,它对癌症治疗起了重要作用。但由于传统的化疗药物大都是以杀伤细胞为其生物学基础,因此抗癌药物多为一些高毒物质、缺乏选择性,不能充分发挥其效应。近年来人们发现癌基因在肿瘤发生、发展过程中起着十分重要的作用,试图由此开辟一条治疗肿瘤的新途径。本文就近年来癌基因研究资料,重点讨论癌基因表达与肿瘤形成和抗癌药研究的关系,进而阐明癌基因的研究,为寻找新一代肿瘤化疗药物提供线索。     

MicroRNA与肿瘤免疫关系的研究进展

MicroRNA又称miRNA,是真核生物细胞中一类非编码小分子RNA,主要在转录后水平发挥调控靶基因的作用。MicroRNA参与调节细胞生长、发育、分化、增殖和凋亡等生命过程,影响着几乎所有的信号通路,参与各种生理病理过程,特别在肿瘤的发生和发展中发挥着重要的调节作用。研究MicroRNA与肿瘤的关系是近年来备受各界关注的热点之一。特别是对机体抗肿瘤的免疫学方面的影响,而这些方面的重大突破将为肿瘤的诊断和治疗提供新的思路。本文就MicroRNA的生物学功能及其对机体抗肿瘤免疫机制的影响进行综述。      

二甲双胍辅助治疗合并2型糖尿病的恶性肿瘤患者的专家共识（2022年版）

恶性肿瘤是近年来慢性非传染性疾病死亡的主要原因,也是影响人类预期寿命的最重要原因,其治疗效果差,预后不良。二甲双胍为2型糖尿病首选的降糖药物,其抗肿瘤的作用得到越来越多同行的认可。然而,目前国内外缺乏独立的临床指南、共识及大型前瞻性临床试验。本共识旨在为二甲双胍在抗肿瘤方面的临床应用提供参考。对于大多数合并2型糖尿病的恶性肿瘤患者,推荐联合使用二甲双胍治疗,可以辅助抗肿瘤及增强化疗药物敏感性,降低多种恶性肿瘤的发病率、转移率,从而降低死亡率;对于少部分合并2型糖尿病的恶性肿瘤患者,不推荐也不反对使用二甲双胍,如雌激素受体（estrogen receptor,ER）阴性或三阴性乳腺癌;对于大部分不合并糖尿病的恶性肿瘤患者,不推荐使用二甲双胍,如肺癌、结直肠癌、前列腺癌等;而对于极少部分不合并糖尿病的恶性肿瘤患者,在充分知情同意的情况下,可使用二甲双胍。     

微小RNA let-7与食管癌

微小RNA(miRNA)的发现为食管癌的诊断和治疗开辟了新的思路.let-7是目前研究最为广泛的miRNA之一,在多种肿瘤中表达下调.let-7能够靶向高迁移率蛋白A2 (HMGA2)从而抑制细胞增殖,发挥抑癌基因的作用.研究发现分化程度越低的细胞,let-7表达水平越低,其有望作为低分化肿瘤的标志.此外,let-7与食管癌放化疗敏感性也密切相关.     

丙泊酚抗肿瘤作用及分子机制在肺癌中的研究进展

肺癌是最常见的恶性肿瘤,手术切除是治疗肺癌的主要手段,但术后仍会有术后肿瘤复发与转移的可能。丙泊酚是最常用的静脉全麻药物,近年来越来越多的文献表明,丙泊酚对肺癌患者有延长生存期的作用。本文通过检索相关文献,总结丙泊酚通过调控微小RNA(MicroRNA,miRNA)和环状RNA(circular RNA,circRNA)从而调节多种信号通路发挥直接抗肿瘤作用;丙泊酚促进T细胞分化提高免疫力,减少炎症介质间接抑制肿瘤细胞活性;丙泊酚还可以提高肿瘤细胞对化疗药物的敏感性,发挥间接抗肿瘤作用。此外,临床试验也证实,丙泊酚可能因其抗肿瘤特性与癌症患者术后生存密切相关。因此,肺癌手术麻醉中使用丙泊酚静脉全麻药可能更为适合,但仍需要大样本前瞻性临床试验去证实。     

Expression of the TNF-alpha gene on mouse lung carcinoma cells suppresses spontaneous lung metastasis without affecting tumorigenicity

Forced expression of TNF-alpha in tumor cells has been shown to inhibit their tumor growth in vivo through a number of mechanism such as activation of an immune system and induction of an apoptotic process. We re-examined the anti-tumor effects caused by the TNF-alpha gene transfer using high-metastatic, murine lung carcinoma A11 cells. Expressed TNF-alpha molecules remained on cell surface and were not secreted into culture supernatants in vitro. Syngeneic immunocompetent mice developed tumors of TNF-alpha-expressed A11 cells and the growth of their subcutaneous tumors was not different from that of parent tumors. Spleen of the mice that developed TNF-alpha-expressed A11 tumors was significantly larger than that of the mice bearing parent tumors, but relative ratios of each cell population were not different. In contrast to subcutaneous tumors, the number of spontaneous lung foci metastasized from the subcutaneous TNF-alpha-expressed A11 tumors was markedly reduced compared with that from parent tumors. Expressed TNF-alpha on tumors is released by matrix metalloproteinases from surrounding tissues and anti-tumor effects by TNF-alpha can be influenced by local environmental conditions.     

Anti-tumor effects of interleukin-2 and interleukin-1 in mice transplanted with different syngeneic tumors

We have studied the anti-tumor effects of human recombinant IL-2, alone or in association with LAK cells, in mice transplanted subcutaneously (s.c.) with the following syngeneic tumors: highly metastatic Friend leukemia cells (FLC), nonmetastatic FLC, lymphoma RBL-5 cells and HeJ16 fibrosarcoma cells. In these tumor models, peri-tumoral injections of IL-2 were more effective in inhibiting tumor growth than a systemic treatment. Although s.c. IL-2 treatment resulted in marked inhibition of tumor growth in mice injected s.c. with highly metastatic FLC, it was not effective in inhibiting growth of FLC in the liver and spleen. IL-2 therapy was more effective at increasing survival time in mice transplanted with non-metastatic FLC or with RBL-5 cells. In mice transplanted with HeJ16 fibrosarcomas, s.c. IL-2 treatment resulted in highly significant anti-tumor effect and survival of 70% of tumor-injected mice. No general correlation was found between in vitro sensitivity or resistance to the cytolytic activity of LAK cells and the anti-tumor effects observed in vivo. Subcutaneous injection of IL-1 beta in mice transplanted with highly metastatic FLC resulted in a marked increase in survival time and inhibition of metastatic tumor growth in liver and spleen. Combined treatment of IL-1 beta and IL-2 produced a synergistic anti-tumor effect: 60% of mice injected with highly metastatic FLC survived. Combined IL-1/IL-2 treatments exerted no anti-tumor activity either in DBA/2 mice injected with antibody to Thy 1.2 antigen or in nude mice, indicating that T cells play important roles during IL-1/IL-2 therapy. In vitro treatment of FLC with IL-1 beta resulted in a slight inhibition of cell multiplication, whereas even high doses of IL-2 did not affect FLC multiplication. Our results indicate that local combined treatments with IL-1 and IL-2 can induce potent, host-dependent (T cell-mediated) anti-tumor effects against highly malignant tumors.     

Correlation between the sensitivity or resistance to IL-2 and the response to cyclophosphamide of 4 tumors transplantable in the same murine host

We have studied the anti-tumor response to cyclophosphamide (CTX) in DBA/2 mice transplanted s.c. with 4 tumors exhibiting different responses to IL-2: ESb lymphoma and Friend leukemia cells (non-responsive or poorly responsive, respectively), pI I-R-Eb and Eb lymphoma cells (both highly responsive to IL-2). CTX injections on days 7, 14 and 21 resulted in a significant anti-tumor response in mice transplanted s.c. with Friend leukemia cells or ESb cells, whereas no anti-tumor effect was observed in mice injected with Eb or pI I-R-Eb cells. All 4 tumor cell lines were equally sensitive to the cytotoxic effects of mafosfamide, an in vitro active analogue of CTX. To define the host mechanisms responsible for the lack of an anti-tumor effect of CTX in mice transplanted with IL-2-responsive tumors, we studied several aspects of the spontaneous or IL-2-induced anti-tumor response in mice transplanted with pI I-R-Eb cells. Injection of monoclonal antibodies (MAbs) to IFN-γ completely abolished the anti-tumor effects of IL-2. Using a Winn assay, clear-cut anti-tumor activity was found in spleen cells from mice transplanted with the IL-2-responsive tumors. This activity was abolished by CTX, which also abrogated the anti-tumor response to IL-2 in mice injected with pI I-R-Eb cells. Our results indicate an inverse correlation between sensitivity to IL-2 and response to CTX and emphasize the importance of initial host-tumor interaction in determining the type of response to IL-2 or CTX. © 1995 Wiley-Liss, Inc.     

二甲基塞来昔布抗肿瘤作用的研究进展

近年来,国内外大量文献报道,传统的非甾体抗炎药物塞来昔布可以通过COX-2依赖或非依赖机制在多种恶性肿瘤中发挥抗肿瘤作用。但是,塞来昔布通过抑制COX-2可以减少血管中前列环素的产生,从而导致血栓形成事件。而2,5-二甲基塞来昔布（DMC）作为塞来昔布的紧密衍生物,尽管缺乏COX-2抑制功能,显示出比塞来昔布高20%~50%的肿瘤抑制活性,并且可能避免心血管毒性,因此,可能更适合用于恶性肿瘤的治疗。其可以通过诱导内质网应激、抑制增殖、诱导细胞凋亡、影响细胞周期、抗血管生成以及增加药物敏感性等机制发挥肿瘤抑制活性。本文对二甲基塞来昔布抗肿瘤作用的研究进展进行了详尽综述,为相关研究提供参考。