A new method for uniform local heating deep in body using ultrasound phased-array system

A new method for targeted heating of deep tissue was developed by using an ultrasound phased-array system which can generate various multiple foci patterns by electronically changing its amplitude or phase pattern. This method involves using a technique of combining switching and rotating of multiple foci patterns to create a uniform temperature over tissue volumes in various size. Using this method, the target tissue deep in the body can be heated to a specified temperature, which gives conditions for thermo-sensitive liposomes release. A simulation study for a 108-element, spherically sectioned array was performed to determine an optimal heating scheme from a set of multiple focus fields which were produced by inputting different combinations of phases and amplitudes. Comparisons of a static multiple foci field, the switched fields and the switched-rotated fields indicated that the technique of combining switching and rotating of multiple foci patterns has advantages of both lowering the peak temperature and evening the temperature distribution. The simulation results also show that the therapeutic heating zones in various size employing the combined method. These results offer significant data for designing thermotherapy equipment for tumor-specific drug release with thermo-sensitive liposomes.     

肿瘤特征基因筛选与调控网络构建

提出了一种肿瘤特征基因筛选和基因调控网络的构建方法.首先提取在肿瘤组织和正常组织中表达差别明显的277个基因,通过P-tree决策树方法找出多组肿瘤特征基因,然后结合现有文献中已被实验验证参与了肿瘤形成过程的基因,利用相关系数方法在肿瘤特征基因集中选出与之共通路的基因子集,并用贝叶斯网络方法建立基因间的调控关系,从而建立对肿瘤特征基因间调控关系的预测模型.     

Construction and expression of retroviruses encoding dual drug resistance genes in human umbilical cord blood CD34+ cells

A series of retro viral vectors encoding humanmdr1 gene alone as wetl as in combination with either humanmgmt gene or human mutantSer ³¹-dhfr gene are engineered. The resultant retroviruses are used to transduce human umbilical cord blood CD34⁺ cetls. It has been shown that expression of dual drug resistance genes in transduced cetls confers a broad range of resistance to both kinds of corresponding drugs. These data suggest a rationale for the use of such double chemoresistance gene constructs in anin vivo model in which transduced hematopoietic cetls will acquire multiple protection against the cytotoxic side effects of combination chemotherapy and may have future application in chemoprotection of normal tissues, thus killing tumor cetls more effectivety.     

恶性肿瘤中IGFBP-rP1的抑癌基因作用机制及其可能的临床实用价值

胰岛素样生长因子结合蛋白相关蛋白1(IGFBP-rP1)是近年来恶性肿瘤的研究热点.本文主要综述IGFBP-rP1在恶性肿瘤中的抑癌基因作用机制及可能的临床实用价值.IGFBP-rP1在恶性肿瘤中的作用广泛涉及细胞的增殖、衰老、凋亡、分化、血管生成等多方面,研究指出IGFBP-rP1可缩短细胞增殖周期并影响非停泊性生长从而抑制增殖,降低致瘤能力;调节BRAF-MEKERK信号通路及pRB、HSP60等相关蛋白的表达从而影响衰老及凋亡;主要通过IGF依赖方式抑制血管生成;而且IGFBP-rP1表达下降跟肿瘤细胞分化程度降低有关.研究显示IGFBP-rP1有一定的临床实用价值,如其表达量跟恶性肿瘤的进展相关,低表达提示某些化疗药物抵抗,可提示预后.而在恶性肿瘤中特异性地上调IGFBP-rP1,可抑制肿瘤增殖及血管生成、诱导细胞衰老凋亡、提高肿瘤分化程度及化疗敏感性,具有治疗意义,但研究者们还在努力探究,争取早日找到一种临床有效的靶向IGFBP-rP1的基因治疗方法.     

基于TCMSP抗肿瘤中药小分子EGFR-TKI的研究

目的研究分析中药小分子表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)的抗肿瘤情况。方法挖掘中药系统药理学数据库与分析平台(TCMSP)中药小分子表皮生长因子受体抑制剂,利用反向分子对接服务器(DRAR-CPI)进行靶点验证。结果木犀草素、槲皮素、金雀异黄酮、表没食子儿茶素没食子酸酯、漆黄素5种中药小分子与表皮生长因子受体(EGFR)结合良好。结论中药小分子EGFR-TKI能从多个靶点、多种途径抑制肿瘤细胞的生长和扩散,利用中药小分子开发新一代多靶点EGFR-TKI具有广阔的前景。     

DNA甲基化研究进展

DNA甲基化已成为阐明正常和病理基因表达现象的重要机制,因而已成为当前分子生物学的研究热点之一。对DNA甲基化的转录抑制机制、在肿瘤发生中的作用、与细胞衰老和凋亡的关系、抑制剂以及分析方法等方面的研究新进展进行了综述。     

Chemotherapy and immunotherapy of malignant glioma: molecular mechanisms and clinical perspectives

Despite the considerable progress in modern tumor therapy, the prognosis for patients with glioblastoma, the most frequent malignant brain tumor, has not been substantially improved. Although cytoreductive surgery and radiotherapy are the mainstays of treatment for malignant glioma at present, novel cytotoxic drugs and immunotherapeutic approaches hold great promise as effective weapons against these malignancies. Thus, great efforts are being made to enhance antitumoral efficacy by combining various cytotoxic agents, by novel routes of drug administration, or by combining anticancer drugs and immune modulators. Immunotherapeutic approaches include cytotoxic cytokines, targeted antibodies, and vaccination strategies. However, the success of most of these experimental therapies is prevented by the marked molecular resistance of glioma cells to diverse cytotoxic agents or by glioma-associated immunosuppression. One promising experimental strategy to target glioma is the employment of death ligands such as CD95 (Fas/Apo1) ligand or Apo2 ligand (TRAIL). Specific proapoptotic approaches may overcome many of the obvious obstacles to a satisfactory management of malignant brain tumors. Received 8 March 1999; received after revision 27 May 1999; accepted 14 June 1999     

Blocking of lectin-like adhesion molecules on pulmonary cells inhibits lung sarcoma L-1 colonization in BALB/c-mice

Summary Adhesion and inhibition experiments with pulmonary cells of BALB/c-mouse origin and syngeneic sarcoma L-1 cells indicated that L-fucose specific lectin-like adhesion molecules, presumably situated on pulmonary cell surfaces are (at least partly) responsible for the specificity of this cell-cell interaction. Addition of specific sugars and glycoconjugates (L-fucose and fucoidan, respectively) to the incubation medium evidently inhibited the adhesion process as quantified using radiolabelled tumor cells. Unspecific carbohydrates (e.g. D-galactose) did not affect the cellular interaction. In vivo, repeated administration of fucoidan (but not of unspecific glycoconjugates) significantly inhibited the settling of metastatic sarcoma L-1 cells in the lungs of BALB/c-mice. Therefore, when lectin-like adhesion molecules on pulmonary cells were blocked with competitive glycoconjugates, tumor cell colonization of the lung could be significantly inhibited.