白花蛇舌草豆甾醇对肝癌细胞的体内外抑制作用及对其增殖周期、凋亡的影响

目的:研究白花蛇舌草豆甾醇(stigmasterol from Hedyotis diffusa willd.,SHD)对人肝癌细胞SMMC-7721、BEL-7402的体外抑制作用,对肝癌H22的体内抑制作用及对其增殖周期、凋亡的影响。方法:MTT法评价SHD对人肝癌细胞SMMC-7721、BEL-7402的抑制率变化规律。昆明雄性小鼠60只,随机取10只为正常对照组,余接种H22瘤株,随机分为模型对照组、5-FU阳性对照组(30mg/kg)和高中低剂量SHD给药组(剂量分别为15、30、60mg/kg),腹腔给药10 d后,比较各组瘤重抑制率、H22细胞周期分布、凋亡率。结果:SHD对SMMC-7721、BEL-7402细胞具有体外抑制作用;SHD显著抑制H22肿瘤,增加G0-G1期细胞比例,降低G2/M期细胞比例,促进肿瘤细胞凋亡。结论:SHD在体外、体内均具有抑制肝癌细胞的作用,此作用与阻滞肿瘤细胞增殖周期,促进肿瘤细胞凋亡有关。     

The Wnt connection to tumorigenesis

Wnt signaling has been identified as one of the key signaling pathways in cancer, regulating cell growth, motility and differentiation. Because of its widespread activation in diverse human tumor diseases, the Wnt pathway has gained considerable and growing interest in tumor research over recent years. Evidence that altered Wnt signaling is important for human tumor development came from three major findings: (i) the tumor suppressor adenomatous polyposis coli (APC) binds to the Wnt pathway component beta-catenin and is involved in its degradation, (ii) mutations of APC in colon tumors lead to stabilization of the beta-catenin protein and (iii) tumor-associated mutations of beta-catenin in colorectal cancer as well as in other tumor types lead to its stabilisation, qualifying beta-catenin as a proto-oncogene. Here we will describe the biochemical interactions which shape the Wnt pathway and focus on its role in tumorigenesis.     

基于TRAIL的肿瘤治疗策略进展

肿瘤坏死因子相关凋亡诱导配体(TRAIL)能选择性诱导肿瘤细胞凋亡,且对机体正常组织细胞无毒副作用,被认为是一种非常有潜力的抗癌药物。我们简要介绍TRAIL及其配体诱导细胞凋亡的机制、肿瘤细胞对TRAIL的耐受机制及其克服策略。     

叶酰多聚谷氨酸合成酶与肿瘤耐药

叶酰多聚谷氨酸合成酶(folyl-polyglutamate synthetase,FPGS)是近几年来研究比较多的肿瘤耐药靶酶之一。随着人们对其在基因组学和蛋白组学研究的逐渐深入,涉及FPGS(分胞浆型cFPGS和线粒体型mFPGS两种异构体)与肿瘤耐药的研究也越来越多。本文就FPGS结构、功能、生化特点及其与肿瘤耐药关系作一综述,并探讨其在临床的应用前景和意义。     

NKG2D及其配体在肿瘤免疫中的研究进展

活化性受体NKG2D（natural-killer group 2,member D）及其配体在NK、γδ＋T和CD8＋T细胞介导的肿瘤免疫应答中扮演了重要角色。深入理解NKG2D及其配体在肿瘤免疫中的作用有助于临床预防和治疗肿瘤。该文阐述了NKG2D的分子结构特性、表达调控及其配体的分类和表达调控;主要介绍了NKG2D及其配体在肿瘤免疫中的作用;最后分析了NKG2D免疫途径中存在的问题和治疗应用前景。     

成纤维细胞激活蛋白α与肿瘤发展进程的研究

肿瘤微环境对肿瘤的发生、发展具有重要的意义。选择性表达于肿瘤微环境重要组成部分——肿瘤相关成纤维细胞（carcinoma associated fibroblasts,CAFs）表面的成纤维细胞激活蛋白α（fibroblast activation protein-α,FAPα）广泛参与了肿瘤的生长、侵袭、转移以及肿瘤细胞外基质重建、血管生成、免疫逃逸等过程,从而促进了肿瘤的发展进程。FAPα具有蛋白水解酶活性,并作用于细胞信号通路,但FAPα在肿瘤微环境中发挥功能的具体分子机制还有待进一步研究。由于FAPα的表达具有肿瘤组织特异性,因此,以FAPα作为肿瘤基质标志物,对肿瘤进行病理诊断和免疫治疗将成为新兴的研究靶点。对FAPα的主要生物学性状进行概述,并综述了其对肿瘤细胞的生长、侵袭、转移以及肿瘤细胞外基质重建、血管生成、免疫逃逸等方面的重要影响。     

激光捕获显微切割在肿瘤多组学研究中的应用进展

当今社会,肿瘤因其高发病率和高死亡率成为威胁人类健康的重要疾病,研究者们对其发病机制及治疗手段的研究和探索也在不断深入。随着单细胞多组学测序技术的发展,肿瘤组织的异质性问题逐渐被研究人员所认识。为了解决这一问题,激光捕获显微切割（laser capture microdissection,LCM）技术应运而生。LCM技术是一种在显微镜直视下从器官或组织中准确获取某种特定的细胞群或单个细胞的样本收集技术。LCM技术结合多种分子生物学手段可以对异质性组织进行多组学研究,丰富了现有的肿瘤蛋白质组学、基因组学以及转录组学图谱,因此,LCM技术成为研究特异性表达及分子机制的有力工具,在肿瘤学领域得到广泛应用。基于此,对LCM的原理、优势及其在肿瘤多组学研究中的应用进行了综述,并对其未来可能的发展方向进行了展望,以期为肿瘤的研究和治疗提供新的思路。     

Recombinant CBD-HepII polypeptide of fibronectin inhibits alphavbeta3 signaling and hematogenous metastasis of tumor

The interaction of integrin αvβ3 and its ligands are crucial for tumor metastasis. Recombinant CBD-HepII polypeptide of fibronectin, designated as CH50, suppressed the binding of tumor cells to ECM molecules, and abolished the promoting effect of soluble fibronectin and fibrinogen on tumor cell adhesion to ECM molecules. The underlying mechanisms involve the blockade and downregulation of αvβ3 and its co-receptor syndecan 1 by CH50. The activation of FAK, upregulation of cdc2, the production and activation of MMP-2 and MMP-9 by ECM molecules-stimulated tumor cells were inhibited by CH50. CH50 reduced the tumor cell arrest during blood flow, and also inhibited the invasive ability of tumor cells. The in vivo expressed CH50 suppressed the lung metastasis of circulating tumor cells, and prolonged the survival of mice after tumor cell inoculation. These findings suggest a prospective utility of CH50 in the gene therapy for prevention of tumor metastasis.     

Possible role of hyaluronectin on cell adhesion in rat histiocytoma.

Distribution of hyaluronectin, a 68-kDa cell surface glycoprotein, has been demonstrated in normal peritoneal, alveolar macrophages as well as in macrophages of the AK-5 tumor cell line. AK-5, a transplantable histiocytic tumor cell line, is a mixture of four different populations and can be grown in both ascites and solid tumors. We are able to demonstrate a differential expression of hyaluronectin on the cell surface of these subpopulations of AK-5 when studied by immunocytochemical staining followed by cytofluorometric analysis. Cell fractions responsible for developing both ascites and solid tumors contain higher amounts of hyaluronectin than fractions which are capable of producing only ascites, suggesting its involvement in solid tumor formation. Furthermore, we established a secretory nature of hyaluronectin as it can be detected in the serum-free medium of AK-5 cells. Since it is localized on the cell surface and secreted into the medium, the cell adhesiveness of hyaluronectin has been examined. Hyaluronectin coating on the plates allowed more cells to attach, which could be specifically blocked by the antibody raised against hyaluronectin, indicating its possible role in cell attachment. The adhesive property of hyaluronectin and its role in tumor formation was further confirmed. The pretreatment of AK-5 cells with hyaluronectin antibody abolished their capacity to grow as solid tumors; however, the cells retained their capacity to grow as ascites tumor. We discuss our observations of hyaluronectin as a cell attachment protein and its specific role on tumor formation.     

Sialylation of 3-methylcholanthrene-induced fibrosarcoma determines antitumor immune responses during immunoediting

Sialylation of tumor cells is involved in various aspects of their malignancy (proliferation, motility, invasion, and metastasis); however, its effect on the process of immunoediting that affects tumor cell immunogenicity has not been studied. We have shown that in mice with impaired immunoediting, such as in IL-1α(-/-) and IFNγ(-/-) mice, 3-methylcholanthrene-induced fibrosarcoma cells are immunogenic and concomitantly bear low levels of surface sialylation, whereas tumor cells derived from wild type mice are nonimmunogenic and bear higher levels of surface sialylation. To study immune mechanisms whose interaction with tumor cells involves surface sialic acid residues, we used highly sialylated 3-methylcholanthrene-induced nonimmunogenic fibrosarcoma cell lines from wild type mice, which were treated with sialidase to mimic immunogenic tumor cell variants. In vivo and in vitro experiments revealed that desialylation of tumor cells reduced their growth and induced cytotoxicity by NK cells. Moreover, sialidase-treated tumor cells better activated NK cells for IFN-γ secretion. The NKG2D-activating receptor on NK cells was shown to be involved in interactions with desialylated ligands on tumor cells, the nature of which is still not known. Thus, the degree of sialylation on tumor cells, which is selected during the process of immunoediting, has possibly evolved as an important mechanism of tumor cells with low intrinsic immunogenicity or select for tumor cells that can evade the immune system or subvert its function. When immunoediting is impaired, such as in IFN-γ(-/-) and IL-1α(-/-) mice, the overt tumor consists of desialylayed tumor cells that interact better with immunosurveillance cells.     

Interchange of amino acids between tumor and host.

During the growth of a tumor, there are very relevant changes in the metabolism of the host to produce the metabolites rapidly consumed by the tumor. In this context, the exchanges of amino acids between the tumor and its host are especially important; however, they have received little attention. A rigorous study must provide data on the growth curve of the tumor, as well as on amino acid levels in tumor cells, plasma, and metabolically relevant tissues and organs from the host during the whole growth of the tumor. The main conclusions arising from a complete study in a tumor model are discussed.     

植物肿瘤的研究进展及其应用前景

植物肿瘤是肿瘤细胞研究的重要内容之一。结合国内外关于植物肿瘤研究的最新进展,主要对植物肿瘤的定义、种类、产生的机理及其各个方面的应用进行了归纳和探讨,并就植物肿瘤的研究和应用前景进行了展望,希望为肿瘤及其相关研究提供理论参考。     

COX-2及其抑制剂在肿瘤防治中的作用

环氧化酶（cyclooxygenase,COX）是前列腺素合成途径中主要的限速酶之一,参与炎症、发热、出凝血等病理生理过程。COX-2在肿瘤发生发展、转移、凋亡抑制及促进肿瘤血管生成等方面发挥重要作用,己成为肿瘤防治的一个新靶点;COX-2及其抑制剂在肿瘤预防、放疗、化疗、生物疗法中具有广阔应用前景。本文就COX-2及其抑制剂在肿瘤防治中的进展作一详细综述。     

The rationale and practice of CTL therapy against cancer in the mouse and human

It is essential to investigate and elucidate the immune response especially T cell response to either syngeneic or autologous tumor for establishing a rational immunotherapy of cancer. We reported that major immune effector cells capable of inducing tumor regression are cytotoxic T lymphocytes (CTL). We found that there are at least two distinct CTL subsets directed to syngeneic tumor. One CTL subset which is selectively induced by syngeneic solid tumor is independent from CD4 positive helper T cells but requires a soluble factor (s) released from macrophage-like accessory cells designated killer T cell activating factor (KAF) in its induction and generation directed to the homologous tumor. The other CTL subset which is usually induced by syngeneic tumor of hematocytic origin is dependent on CD4 positive helper T cells in its induction. On the basis of our findings regarding the induction and activation mechanism of CTL to syngeneic tumors in the mouse, we have investigated the mechanisms of human CTL generation to autochthonous tumor in peripheral blood mononuclear cells of cancer patients. It was found that the nature of human CTL and its generation to autochthonous tumor are similar to those of murine CTL to syngeneic solid tumor. We are now establishing a rational cancer specific immunotherapy utilizing intravenous passive cell transfer of in vitro activated CTL to autochthonous tumor into an original cancer patient.     

Tumor cell killing by macrophages activated in vitro with lymphocyte mediators. III. Inhibition by cytochalasins, colchicine, and vinblastine.

The effect of cytochalasin A and B, colchicine and vinblastine on tumor cell killing by macrophages activated in vitro with lymphocyte mediators was examined. Both cytochalasins reversibly inhibited the killing of tumor cells by activated macrophages. Kinetic studies with cytochalasin B suggested that this drug exerts its effect on an early step of the cytotoxic process. Additional studies revealed that the drug inhibited the binding of tumor cells by activated macrophages.Colchicine inhibited both the binding and the killing of tumor cells by activated macrophages, whereas its structural analogue, lumicolchicine, had no effect on either macrophage function.Vinblastine also inhibited the binding and killing of tumor cells. However, this drug no longer inhibited tumor cell binding at low concentrations (<10^?6M) that still inhibited tumor cell killing. Further, vinblastine inhibited tumor cell killing when added late to an ongoing cytolytic reaction.These results suggest that the cytochalasins, colchicine and vinblastine inhibit macrophage mediated cytotoxicity by preventing intimate contact between the effector macrophages and their targets. In addition, vinblastine also appears to inhibit a later step of the cytolytic process, possibly the secretion of a cytotoxic macrophage product.     

Primary giant cell tumor of soft tissue. Report of a case with fine needle aspiration cytologic and histologic findings

BACKGROUND: So-called primary giant cell tumor of soft tissue of low malignant potential is the rare soft tissue analogue of giant cell tumor of bone, occurring primarily in superficial soft tissue. To our knowledge, the cytologic findings in bulky giant cell tumor of deep soft tissue were described only once, and no further report on the subcutaneous giant cell tumor could be retrieved from the literature. CASE: A 58-year-old woman presented with a well-demarcated, 1.5-cm-diameter dermal tumor. Fine needle aspiration smears contained numerous osteoclastlike giant cells and mononuclear cells showing bland and vesicular nuclei. A small fragment of branching vasculature and 1 mitosis were found. Those cytologic findings were enough to suggest a diagnosis of giant cell tumor of soft tissue, confirmed as a deep dermal giant cell on surgical resection. CONCLUSION: Primary giant cell tumor of soft tissue of low malignant potential should be considered in the differential diagnosis of bland-looking giant cell-rich lesions. Awareness of its existence and knowledge of its cytologic features are important for a correct preoperative cytologic diagnosis.     

X-ray diagnosis of the spread of cancer of the esophagus to the trachea and major bronchi

X-ray and endoscopic investigations were compared in 80 operated on patients to estimate the role of the x-ray method for a choice of adequate therapeutic tactics for esophageal cancer patients. Operations were explorative or palliative resulting from the involvement of the tracheobronchial tree in a tumor process. The efficacy of the x-ray method in the detection of tracheal compression by an esophageal tumor is higher than that of tracheobronchoscopy which in its turn, has its advantages in the determination of tumor spreading to the left major bronchus.     

Toxicity of para-aminobenzhydrazide and its influence on nucleic acid biosynthesis in cultures of normal and tumor cells

We have investigated cytotoxic action of p-aminobenzhydrazide and its influence on biosynthesis of nucleic acids in cultures of intact cells, tumor cells and intact cells stimulated by phytohemagglutinin. p-Aminobenzhydrazide is considered as a representative of hydrazine's derivatives (in particular, of hydrazine sulphate). We compare its action with that of a typical cytotoxic agent such as iododeoxyuridine. We have found that p-aminobenzhydrazide influences biosynthesis of nucleic acids in the same way as iododeoxyuridine. However it acts toxically on tumor cells though it is not toxic for intact cells so that its action is different as compared to that of cytotoxic agents. Specific toxic action of aminobenzhydrazide on tumor cells may be due to the enhancement of antitumor activity substances of this compound and absence of such enhancement of side toxic effects.     

双歧杆菌及其发酵液的抗肿瘤机制的研究

目的 通过比较双歧杆菌及其发酵液的抗肿瘤作用,对其抑瘤作用和相关机制进行初步探讨。方法 取BALB／c小鼠,分别予H22细胞和S180细胞腹腔荷瘤,荷瘤后给予不同的治疗。分别观察2种肿瘤细胞荷瘤小鼠的生存期。右腋下荷瘤后,进行病理切片观察。MTT法计算给予不同方法后的抑瘤率。并计算淋巴细胞转化率。制备电镜标本。观察其超微结构。结果 双歧杆菌死菌液、活菌液能够延长荷瘤小鼠的生存期,而双歧杆菌发酵液不能延长其生存期,病理切片可见作用后的肿瘤组织内部和间质有大量炎性细胞浸润。双歧杆菌死菌液、活菌液对肿瘤细胞株有抑杀作用。电镜观察死菌液作用后的H22细胞可见典型的凋亡表现。结论 双歧杆菌死菌液、活菌液在体内外均有较好的抑瘤作用,其发酵液并未显示出抑瘤作用。说明双歧杆菌的抗肿瘤作用主要来源于菌体的作用。