鼻咽癌的演变与某些相关癌基因及抑癌基因

目的：探讨癌基因(C—erbB2，C—myc，EBV，CDK4)和抑癌基因(E—CD，p16，p53)在鼻咽癌演变中的相互关系。方法：复习近期国内外有关癌基因和抑癌基因在鼻咽癌中的关系，作一综述。结果：癌基因和抑癌基因在鼻咽中相互制约。结论：抑癌基因的低表达和癌基因的过表达在鼻咽癌中起重要作用。     

Gut Bacteria of Columbia livia Are a Potential Source of Anti-Tumour Molecules

Objectives: The overall aim was to determine whether gut bacteria of Columbia livia are a potential source of antitumour molecules. Methods: Faecal and gut microbiota of Columbia livia were isolated, identified and conditioned media were prepared containing metabolites. Growth inhibition, lactate dehydrogenase cytotoxicity and cell survival assays were accomplished against cervical cancer cells. Next, liquid-chromatography mass spectrometry was conducted to elucidate the molecules present. Results: A plethora of bacteria from faecal matter and gastrointestinal tract were isolated. Selected conditioned media exhibited potent anticancer effects and displayed cytotoxicity to cervical cancer cells at IC50 concentration of 10.65 and 15.19 µg/ml. Moreover, cells treated with conditioned media exhibited morphological changes, including cell shrinking and rounding; indicative of apoptosis, when compared to untreated cells. A total of 111 and 71 molecules were revealed from these gut and faecal metabolites. The identity of 60 molecules were revealed including, dihydroxymelphalan. Nonetheless, 122 molecules remain unidentified and are the subject of future studies. Conclusion: These findings suggest that gut bacteria of Columbia livia possess molecules, which may have anticancer activities. Further in silico testing and/or high throughput screening will determine potential anticancer properties of these molecules.     

Analysis of metastatic spread and growth of tumor cells in mice with depressed natural killer activity by anti-asialo GMl antibody or anticancer agents

Summary The mechanism of artificial and spontaneous metastases of tumor was analyzed in B16 melanoma cells and C57BL/6 mice by using anti-asialo GM1 antibody and anticancer agents. Single administrations of 500 g anti-asialo GM1 antibody resulted in significantly decreased NK activity in spleen cells of C57BL/6 mice, lasting 10 days from the day following administration. Treatment with anti-asialo GM1 antibody never decreased the function of T lymphocytes measured by blastogenesis with phytohemagglutinin or T cell growth factor. The tumoricidal functions of activated macrophages but not of resident macrophages were decreased by in vivo treatment with anti-asialo GM1 antibody.The anti-asialo GM1 antibody was evaluated in terms of the enhancing effect on pulmonary metastases with regard to the timing of administration. Treatment with anti-asialo GM1 antibody 1 day before or on the day of tumor inoculation resulted in a substantial increase in the number of artificial pulmonary metastases. In the experimental system of spontaneous metastases, anti-asialo GM1 antibody most effectively increased the number of pulmonary metastases when administered 1–2 weeks before the removal of primary tumor, when the tumor cells are thought to be released into blood circulation from the primary site. In addition, accelerated growth of transplanted tumors at the primary site was observed in mice treated with anti-asialo GM1 antibody. These results strongly suggest that anti-asialo GM1 antibody enhances the incidence of in vivo tumor metastases and the growth of transplanted tumor mainly by suppressing the function of NK cells.The maximum effective dose (MED) of mitomycin C or its derivative (M-83) suppressed NK activity significantly, and pretreatment with these anticancer agents enhanced the growth of the artificial pulmonary and liver metastases. In contrast, the MED of cDDP showed no effect on the NK activity or the numbers of pulmonary and liver metastases. These results indicate that the depression of NK activity induced by chemotherapy results in the promotion of metastatic disease.From these studies it can be concluded that NK cells have a key role in the control of metastases of malignant disease, and that support of NK activity is very important for the prevention of metastases.     

癌克利的抗癌作用实验研究

癌克利口服液是从中药提制的复方制剂，对小鼠肝癌Ｈ２２及小鼠白血病Ｐ３８８进行抑癌作用观察。经三次重复实验，结果表明对Ｈ２２及Ｐ３８８均显示明显的抑制效果，为进行临床应用和深入的基础研究提供了依据     

合成聚肽膜渗透抗癌药物的研究

本文制备了聚谷氨酸苄酯膜，并进行皂化，得到了谷氨酸苄酯－谷氨酸共聚物膜．研究了不同聚合物膜对两种抗癌药物５－氟脲嘧啶（５Ｆｕ）及２－羟乙基－氧甲基－５－氟脲嘧啶（２－ＨＥＯＭ－５－ＦＵ）的渗透性能。结果表明Ｐ１（ＢＬＧ－ＬＧＡ）膜渗透５－Ｆｕ和２－ＨＥＯＭ－５－Ｆｕ的渗透系数分别是ＰＢＬＧ膜的４和１６倍，且Ｐ２（ＢＬＧ－ＬＧＡ）膜的渗透系数分别是ＰＢＬＧ膜的１３和２６倍．     

具抗癌活性的鬼桕毒电子自旋标记物的生物学作用——研究Ⅰ.对细胞生长的抑制试验

用鬼桕毒自旋标记衍生物对子宫颈癌细胞(Hela)、乳地鼠肾传代细胞(BHK)和人胚肺成纤维细胞(KMB)进行了体外抑制试验,发现鬼桕毒自旋标记衍生物在用量为0.1mg时,对Hela、BHK细胞有较强的抑制作用。     

Thioredoxin reductase as a novel molecular target for cancer therapy

Tumor cell proliferation, de-differentiation, and progression depend on a complex combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. The understanding of these complex mechanisms should lead to the identification of potential targets for therapeutic intervention. Redox-sensitive signaling factors also regulate multiple cellular processes including proliferation, cell cycle, and pro-survival signaling cascades, suggesting their potential as molecular targets for anticancer agents. These observations suggest that redox-sensitive signaling factors may be potential novel molecular markers. We hypothesized that thioredoxin reductase-1 (TR), a component of several redox-regulated pathways, may represent a potential molecular target candidate in response to agents that induce oxidative stress. There have been numerous biological studies over the last decade investigating the cell biological, biochemical, and genetic properties of TR both in culture and in in vivo models. In addition, using a series of permanent cell lines that express either a wild-type TR or a dominant mutant TR gene or a chemical agent that inhibits TR we demonstrated that TR meets most criteria that would identify a molecular target. Based on these results we believe TR is a potential molecular target and discuss potential clinical possibilities.     

Antiproliferative activity of contragestazol (DL111-IT) in murine and human tumor models in vitro and in vivo

Purposes: To evaluate the antiproliferative activity of contragestazol (DL111-IT) in vitro and in vivo and to elucidate potential molecular mechanisms. Methods: Cell killing ability of DL111-IT was measured by MTT/Trypan blue exclusion method and murine and human tumor models; cell cycle was analyzed by flow cytometry; pRb, CDK4 and Cyclin D1 expressions were detected by western blotting. Results: DL111-IT exhibited high efficiency on cell growth inhibition of 12 cancer cell lines, the IC₅₀ values were 4.1–19.7 μg/ml. In Sarcoma-180 (S180) and Hepatoma-22 (H22) tumor bearing mice models, the inhibition rates were 55.9 and 55.6%, respectively, at the doses of DL111-IT 12.5–50.0 mg/kg for 9 days consecutive administration. Human ovarian carcinoma (HO-8910) xenograft study showed that, nine administrations (within 15 days) of DL111-IT (12.5–50.0 mg/kg) significantly inhibited tumor growth with the inhibition rates ranging from 17.0 to 64.3%. DL111-IT induced G1 arrest and overexpression of pRb, CDK4 and Cyclin D1 were observed in HO-8910 cell line, suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT. Conclusions: DL111-IT could inhibit the proliferation of cancer cells both in vitro and in vivo via a cell cycle regulation pathway.     

Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death

We have previously identified the naturally occurring non-toxic antitussive phthalideisoquinoline alkaloid, noscapine as a tubulin-binding agent that arrests mitosis and induces apoptosis. Here we present high-yield efficient synthetic methods and an evaluation of anticancer activity of halogenated noscapine analogs. Our results show that all analogs display higher tubulin-binding activity than noscapine and inhibit proliferation of human cancer cells (MCF-7, MDA-MB-231 and CEM). Surprisingly, the bromo-analog is ∼40-fold more potent than noscapine in inhibiting cellular proliferation of MCF-7 cells. The ability of these analogs to inhibit cellular proliferation is mediated by cell cycle arrest at the G₂/M phase, in that all analogs except 9-iodonoscapine, caused selective mitotic arrest with a higher efficiency than noscapine followed by apoptotic cell death as shown by immunofluorescence and quantitative FACS analyses. Furthermore, our results reveal the appearance of numerous fragmented nuclei as evidenced by DAPI staining. Thus, our data indicate a great potential of these compounds for studying microtubule-mediated processes and as chemotherapeutic agents for the management of human cancers.