近红外荧光染料对胃癌细胞的特异性识别*

测试近红外荧光(near infrared fluorescence,NIRF)染料IR-783对胃癌细胞的特异性识别。将转染荧光素酶luciferase的人胃癌传代细胞SGC-7901皮下移植于裸鼠,7 d后分别使用NIRF染料IR-783和荧光素酶底物进行活体荧光成像和生物发光,测定肿瘤部位ROI(region of interest)值,连续检测并绘制NIRF强度与生物发光强度相关性曲线;选择前期建立的胃癌PDX(patient-derived tumor xenografs,PDX)模型免疫组织化学检测肿瘤组织中CEA与CK8/18的表达,确定移植瘤与原发肿瘤病理学一致性;将SGC-7901细胞和来自PDX模型的胃癌细胞分别培养24 h,分别加入线粒体示踪剂(mito-tracker)或溶酶体示踪剂(lyso-tracker),30 min后加入IR-783染料,在荧光显微镜下观察近IR-783染料在胃癌细胞中的结合部位;将正常胃上皮细胞分别与转染GFP的SGC-7901细胞和来自PDX模型的胃癌细胞共培养24 h后,加入IR-783染料,在荧光显微镜下观察近IR-783染料对胃癌细胞的特异性识别。活体成像结果显示,IR-783染料能够特异性的聚集于人胃癌裸鼠移植瘤部位;NIRF强度与luciferase强度的相关性达99%以上;PDX肿瘤与原发肿瘤中CEA与CK8/18表达均呈强阳性;荧光显微镜下检测到NIRF染料不仅能够特异性识别传代胃癌细胞,同时也能识别来自PDX模型的肿瘤细胞,并优先集聚在肿瘤细胞的线粒体与溶酶体中。近红外荧光染料IR-783能够特异性识别胃癌细胞,可用于胃癌模型的成像研究,是肿瘤治疗的一种潜在工具。     

A comparison of the effects of the optical isomers of isoproterenol on energy metabolism in a mouse sarcoma

Summary Disturbance to energy production in the S180 sarcoma (CB) by optical isomers of isoproterenol was assessed from altered adenine nucleotide levels at 1 h. The L-isomer almost halved the ATP level and lowered the energy charge significantly; the D-isomer was inactive. Dependence of tumor injury on cytochrome P-450 activity appears unlikely.One of us (GRNJ) thanks the Department of Surgery, Medical School, Kings's College Hospital, London, England, for the provision of experimental facilities; the Institute of Biochemistry, German Cancer Research Centre, Heidelberg, FRG, for permitting the measurement of metabolites; the Cancer Research Campaign, London, UK, for a part-time grant; and Zyma GmbH, München, FRG, and the estate of the late Dr Lucie Polak for additional financial support.     

新型抗癌药——硒化多烯脂肪酸多相脂质体的研究

用作者首次合成的几种硒化多烯脂肪酸,分别制成乳剂和多相脂质体,进行动物体内抗癌活性实验,结果表明,硒化亚油酸乳剂(62)在200mg/(kg·d)的剂量下对S_(180)。实体瘤的抑制率为28.7％,而其多相脂质体(118)在相同剂量下对肿瘤的抑制率为45.1％;硒化蓖酸乳剂(92)在200mg/(kg·d)的剂量下对肿瘤的抑制率为33.3％,而其多相脂质体(114)在400mg/(kg·d)剂量下的抑瘤率则达61.4％,说明当将药物包封于脂质体后,可使其毒性下降,抗癌活性明显升高。     

γTNFβ体外杀伤肿瘤细胞的研究

用ＭＰＧ吸附层析法所制备的ＨｕＩＦＮ－γ／ＨｕＴＮＦβ重组双功能杂交蛋白（简称γＴＮＦβ）［１］去处理人宫颈癌细胞株ＭＥ１８０、胃癌细胞株７９０１和肺癌细胞株Ｇ６，结果表明此杂交蛋白对这三个细胞株都有明显的杀伤作用，其杀伤率显著高于同剂量的ＩＦＮ－γ或ＴＮＦ－β；用３Ｈ－ＴｄＲ掺入法观察γＴＮＦβ在不同时间、不同剂量条件下对Ｇ６的增殖抑制，可得到同样的结论。用γＴＮＦβ与丝裂霉素Ｃ（Ｍｉｔｏ－Ｃ）一起处理胃癌７９０１细胞，结果表明在Ｍｉｔｏ－Ｃ１．０μｇ／ｍＬ浓度以下、γＴＮＦβ５０ｕ／ｍＬ浓度以下，两者具有良好的抑病协同效应。用γＴＮＦβ处理胃癌、肺癌细胞以及ｙγＴＮＦβ与化学细胞毒性药物协同抑癌尚未见有报道。本文的结果为深入研究γＴＮＦβ可能具有更有效的抗癌效应提供了实验依据。     

Retroviruses released from a human tumor xenograft in nude mice induce colony-stimulating factor (CSF) activity in human fibroblastic cells

Summary A human colony-stimulating factor (CSF)-producing tumor transplanted into athymic nude mice released retroviruses in vitro. The viruses induced CSF activity in human fibroblastic cell lines.     

桑黄菌质多糖体外抑瘤及抗环磷酰胺致突变的作用

采用MTT法研究桑黄固态发酵菌质多糖（PISPS）对肝癌细胞（HepG-2）、乳腺癌细胞（MCF-7）生长的抑制作用，测定出多糖对细胞生长的最高抑制率为59．18％、55．39%，半数抑制浓度为196.9、162．5μg／mL，且随药物浓度的增加抑制率有增大的趋势，与正常组比较作用较为显著（P〈0．05）；选用小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验，对多糖的抗环磷酰胺（CP）致突变作用进行评价，结果表明桑黄菌质多糖使环磷酰胺诱发的细胞微核率和精子畸形率明显降低（P〈0．01）．     

钙阻断剂与肿瘤治疗

抗药性是肿瘤化疗的最大障碍之一,具抗药性的肿瘤细胞药物外排功能很强,而钙阻断剂能抑制抗癌药物从抗药性肿癌细胞排出,导致细胞抗药性减弱,可用于肿囊化疗,有潜在的临床应用价值,但有副作用。故应寻求毒副作用小类似钙阻断剂的其他修饰物以促进肿癌化疗。     

A pyruvate kinase variant in different mouse transplanted tumors

Summary Mouse transplanted tumors, in contrast to normal tissues, contain a pyruvate kinase (PK) variant sensitive to the inhibitory action of L-cysteine and less sensitive to saturated fatty acids than the normal enzyme. In selected normal and tumor materials two fractions of PK were separated. Fraction A (20–30% (NH₄)₂SO₄ saturation) dominated in normal liver, and fraction B (50–60% (NH₄)₂SO₄ saturation) in skeletal muscles and Ehrlich ascites tumor. Only this fraction B from tumor material was sensitive to L-cysteine, and seems to contain a tumor-specific PK variant which might be considered as a marker of neoplastic transformation in a broad spectrum of mouse experimental tumors.     

蛋白酶抑制剂在肿瘤治疗中的作用研究

蛋白酶及其抑制剂是非常重要的信号分子,涉及多个关键的人体生理代谢途径,在体内受到严格的调控.蛋白酶抑制剂活性的紊乱可导致多种疾病,诸如心血管和炎症疾病、癌症和神经系统障碍等.已知蛋白酶在肿瘤细胞侵袭和转移过程中扮演着重要的角色.细胞外基质和基底膜重塑是癌细胞侵袭转移过程中的关键环节,这个过程需多个蛋白水解酶的表达和激活.蛋白酶抑制剂的应用在一定程度上可减少由蛋白酶水解引起的肿瘤细胞的侵袭和转移,且它的抑制作用具有不同程度的特异性,可以减缓肿瘤恶性发展的进程.文章对蛋白酶及其抑制剂的靶向治疗药物及临床应用研究进展进行了综述.     

Dialdehyde starch nanoparticles as antitumor drug delivery system: An in vitro, in vivo, and immunohistological evaluation

Sustaining the release of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner is a potentially powerful technology. A new drug carrier-dialdehyde starch nanoparticle (DASNP) that can sustain the loading and release of 5-fluorouracil (5-Fu) antitumor drug is reported in this study. IR spectrophotometer and 1H NMR confirmed the formation of aldehyde groups, and scan electron microscope determinations showed that the dialdehyde starch nanoparticles obtained had an average diameter of 90 nm. 5-Fu, the model drug, was conjugated into nanoparticles by aldehyde groups. These 5-Fu-binding nanoparticles significantly enhanced breast cancer cell (MCF-7) inhibition in vitro compared with free 5-Fu. After subcutaneous 0 injection in the breast tumor-loaded rats, 5-Fu-DASNP exhibited remarkable tumor-inhibitory efficacy determined by measuring tumor weight in vivo. The tumor inhibition of 5-Fu-DASNP was 61%±6%, whereas that of free 5-Fu was only 42%±4%. Bcl-2/Bax immunohistochem-istry studies indicated that 5-Fu-DASNP remarkably induced tumor tissue necrosis. These results demonstrated that the DASNP prepared in this work is a potentially effective drug carrier.