血红蛋白抗肿瘤作用的实验研究进展

最近研究发现,血红蛋白在肿瘤治疗,器官灌注,骨髓细胞造血,外科手术抗体克方面有良好的应用前景。本文综述血红蛋白在肿瘤治疗方面的实验研究进展。     

几茶素抑制二甲基肼诱发小鼠大肠癌的实验研究

昆明小鼠随机分成7组．1-5组小鼠皮下注射DMH，剂量20mg／kg体重。每周1次，连续20wk．第2-5组于注射前1wk开始灌胃几茶素1mg，2mg．4mg、EGCG2mg／每只／每日。第6组给几茶素3mg作为对照组．每周连续灌胃5次至23wk。第7组为溶剂对照组。27wk处死小鼠．结果显示：2组对照小鼠未发生肿瘤。DMH组大肠层发生率为80％，     

生漆多糖抗肿瘤作用的实验研究

目的　观察生漆多糖 (CPS M )的抗肿瘤活性。方法　采用抗肿瘤体外试验和体内试验。结果　体外试验MTT法显示生漆多糖对人体肝癌细胞 (BEL 74 0 2 )有一定的的杀灭作用 ;体内试验表明生漆多糖对S180 和EAC荷瘤小鼠抑瘤率达 6 0 %左右 (P <0 .0 1) ,生漆多糖与 5 氟尿嘧啶 (5 Fu)伍用 ,能提高荷瘤小鼠抑瘤率 ,对 5 Fu所致的荷瘤小鼠胸腺、脾脏重量萎缩有明显的保护作用 ,对 5 Fu引起的骨髓抑制、中性粒细胞减少 ,体重减轻均有不同程度的拮抗作用 (P <0 .0 5～P <0 .0 1)。结论　生漆多糖对荷瘤小鼠有较强的抗肿瘤作用 ,它能提高荷瘤小鼠免疫功能 ,拮抗 5 Fu所致的骨髓和免疫抑制。     

IL—18的抗肿瘤作用

白细胞介素－18（IL－18）是近年发现的新型细胞因子,具有诱生IFN－γ,增强NK细胞活性,增强Th1型免疫反应,抗肿瘤作用等多种生物学功能,是一种应用前景较好的抗肿瘤细胞因子,综述IL－18的发现与来源,理化特性,生物学活性及抗肿瘤机理。     

DDC提高纳米级阿霉素磺油乳剂抗肿瘤作用的实验研究

目的：探讨二乙基二硫代氨基甲酸酯（DDC）对提高纳米级阿霉素碘油乳剂在体内外的抗肿瘤作用。方法：用MTT试验评价纳米级阿霉素碘油乳剂对耐药细胞及肿瘤细胞的杀灭作用，用SD大鼠建立Walk-256肝癌模型，通过肝动脉分别注入生理盐水、阿霉素、纳米级阿霉素碘油乳剂，DDC加纳米级阿霉素碘油乳剂以及DDC加阿霉素脂质体碘油乳剂，分别测定各组的肿瘤生长率和小鼠生命延长率。结果：经过DDC预处理后，阿霉素对阿霉素耐药肿瘤细胞SGC7901／CVR和SGC790／WT的IC50（μg/ml）分别从原来的18．40降至0．74和4．00降至0．32。未经DDC处理过的各组平均肿瘤生长率远高于预先用DDC处理过的各组（P＜0．01）。而小鼠生命延长率则明显低于预先用DDC处理过的各组（P＜0．05）。结论：用DDC预先处理抑制肿瘤细胞中的超氧化物歧化酶（SOD）可提高阿霉素的抗肿瘤作用。     

癌复康冲剂抗肿瘤作用的实验研究

将中药制剂癌复康冲剂与阿霉素(ADM)，环磷酰胺(CTX)及顺铂(DDP)进行伍用实验，结果表明癌复康冲剂能增加化疗药物的抑癌活性，同时可降低化疗药物的毒副反应，提高机体的免疫力。     

温敏磁性材料居里点效应肿瘤的实验研究

从体外用高频电磁声诱导植入小鼠瘤体内的具有较低居里点温度磁性材料产热，研究瘤体的温度变化和该加热方法对瘤体的影响等。结果表明：此方法可用于肿瘤的内加热定向治疗。     

环氧化酶-2抑制剂抗肿瘤作用研究现状

环氧化酶-2(COX-2)参与了肿瘤发生、发展和转移，COX-2抑制剂通过多种机制发挥其抗肿瘤作用，选择性COX-2抑制剂对多种人类肿瘤有预防和治疗作用，有可能为肿瘤预防和治疗提供新方法和途径。     

禹余粮抗肿瘤作用的实验研究

禹余粮抗肿瘤作用的实验研究＊侯琦陈维宁张薇高尔李华洲吕欣然关键词禹余粮，中药抗肿瘤实验，动物实验，细胞Ｓ１８０禹余粮（Ｌｉｍｏｎｉｔｅ）又名禹粮石，俗称木鱼石，是一种珍稀矿物药，《神农本草经》列为上品，《本草纲目》记载“炼饵服之，轻身延年不老，除邪气...     

新城鸡瘟病毒治疗肉瘤180小鼠的实验研究

肉瘤１８０（Ｓ_１８０）细胞注入到小鼠腹腔中制得荷瘤鼠模型，用新城鸡瘟病毒（ＮＤＶ）Ｂ１株治疗，观察１个月。青年鼠（７周龄）生存率达７６．７％，而老龄鼠（１年龄）和未经治疗的青年鼠均１００％死亡。病毒在Ｓ１８０腹水中基本不繁殖。进一步观察发现，经ＮＤＶ治疗的荷瘤鼠，７周龄鼠血清干扰素增高、ＮＫ细胞活性增强，而１年龄鼠中则未观察到此现象。７周龄鼠治疗后第４天可检测出抗病毒抗体，第８天时效价达１：１６００。用ＮＤＶ体外感染巨噬细胞也可诱生出较高浓度干扰素。结果提示，干扰素增高、ＮＫ细胞活性增强可能与抗肿瘤疗效有关，而抗病毒抗体与疗效间的关系，尚需进一步研究。     

狼毒蛋煎剂毒性及抑瘤效应的实验研究

目的 :研究狼毒蛋煎剂的毒性和对肉瘤S180 、HepA肿瘤细胞的抑瘤作用。方法 :①半数致死量(LD50 )毒性实验 ;②抑制HepA肿瘤细胞实验 ;③抑制肉瘤S180 实验。结果 :毒性实验 :口服狼毒蛋煎剂组LD50 >12 0 ,腹腔注射狼毒蛋煎剂组LD50 为 4 9113;口服狼毒煎剂组LD50 >12 0 ,腹腔注射狼毒煎剂组LD50 为 1 86 6 8。抑制HepA肿瘤实验 :狼毒蛋煎剂组瘤重 (0 714± 0 149)g ,5 FU组平均瘤重(0 52 1± 0 114)g ,生理盐水组平均瘤重 (9 82± 0 2 13)g。狼毒煎剂组与生理盐水组相比P <0 .0 5。抑制肉瘤S180 实验狼毒蛋煎剂组平均瘤重 1 17g ,生理盐水组平均重 2 4 6g ,两组比较P <0 .0 1。结论 :狼毒蛋煎剂能安全有效地抑制HepA肿瘤细胞和肉瘤S180 。     

e4声动力治疗小鼠S180肉瘤的实验研究

 目的： 本文研究超声激活声敏剂e4对在体小鼠S180肉瘤的杀伤作用。方法：荷瘤小鼠腹腔注射e4(40mg/kg),6小时后用频率为1.0MHz超声波照射肿瘤区域180s, 超声强度分3组：0.4W/cm², 0.8W/cm²,1.6W/cm²。以空白对照组,单纯超声组（超声强度为1.6W/cm²）,单纯声敏剂组为对照组,每两天测量肿瘤大小,12天后剥离肉瘤并称重比较。结果 ：e4在小鼠体内经超声激活后可明显抑制肿瘤生长。在超声强度为0.4W/cm²～0.8W/cm²范围时,e4对肿瘤的抑制作用随声强的增加疗效亦增加。结论 ：e4声动力治疗对小鼠S180肉瘤有明显杀伤或抑制作用,在一定范围内其作用大小与超声强度正相关。声动力疗法有望成为临床治疗肿瘤的新方法。     

Antitumor Activity and Pharmacokinetics of Estra-1,3,5 (10)-Triene-3,17{beta}-Diol, 3-Benzoate, 17-((4-(4-(Bis (2-Chioroethyl)Amino)Phenyl)-1-Oxobutoxy) Acetate) (Bestrabucil) in Human Tumor Xenografts Serially Transplanted into Nude Mice

Bestrabucil (KM2210), the benzoate of an estradiol-chlorambucilconjugate, was used experimental cancer chemotherapy against13 human tumor xenografts serially transplanted into nude mice,and its pharmacokinetics was studied. The tumors were one esophageal,two gastric, six colon, one cholecystic and three breast carcinomas.Two tumor tissue fragments approximately 3x3x3 mm were inoculatedinto BALB/cA nude mice, which were then treated with KM2210at doses of 100, 200 and 300 mg/Kg/day orally starting 24 hrafter the transplantation or when the tumor reached a weightof 100–300 mg. The concentration of KM2210 and its derivativesin the tumor xenografts, normal muscular tissue and blood wereassayed by high performance liquid chroma-tography. Six out of 13 xenografts were found to be sensitive to KM2210.The concentrations of KM2210 and its derivatives in the tumortissues of the sensitive xenografts were five to 10 times higherthan those in blood and muscular tissue, and the antitumor activitycorrelated well with the area under the curve of active metabolitesof KM2210 in the tumor.     

Antitumoral Effect of Irinotecan (CPT-11) on an Experimental Model of Malignant Neuroectodermal Tumor

Irinotecan (CPT-11) is a topoisomerase I inhibitor with antitumor activity on a wide variety of neoplasms in several preclinical studies, but it showed poor efficacy in patients with nervous system tumors. We have carried out an experimental study in order to evaluate the effect of CPT-11 on the growth of a subcutaneously implanted malignant neuroectodermal tumor, after administration by different routes. The results showed that CPT-11 administration by intraperitoneal injections (at dose 10mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period – one course – to a total of two courses) had no significant antitumor effect. Nevertheless, continuous infusion by intraperitoneal osmotic minipump over 28 days (at an infusion rate of 4.4g/h) showed a significant delay in tumor growth in 4 weeks of the implantation. The best antitumor effects were observed after CPT-11 intratumoral administration (at dose of 5mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period, to a total of three courses) reaching tumor regression in the treated animals. These results suggest the utility of CPT-11, by means of intralesional administration, on malignant tumors of the nervous system.     

Expression Behavior of 85-kDa Membrane Protein in Adriamycin-resistant Tumor Cells and the Inhibition of Human Tumor Growth in Athymic Mice by MRK-20 Monoclonal Antibody against the Protein

Treatment of tumors with monoclonal antibodies against tumor antigen is one of the selective modalities for cancer therapy. We examined the therapeutic effect of MRK-20 (IgG₁), a murine monoclonal antibody against resistance-associated 85-kDa membrane protein. The 85-kDa protein is expressed on the surface of multidrug-resistant cells induced by adriamycin. This protein is also expressed in some multiple-drug-resistant cells, including atypical multidrug-resistant cells. The protein, once lost during long-term culture without adriamycin, was rapidly induced by treatment with adriamycin but not with vinblastine or etoposide, suggesting a close relationship of the protein with adriamycin resistance but not with multidrug resistance. The antibody MRK-20 suppressed the growth of subcutaneously implanted tumors expressing the 85-kDa protein. Adriamycin-resistant human ovarian tumor 2780AD and innately resistant human erythroleukemia HEL cells in athymic mice were completely cured by treatment with MRK-20 antibody when the antibody was administered i.v. 2 days after s.c. tumor implantation. On the other hand, MRK-20 did not show any effect on the growth of the 85-kDa protein-negative A2780 human ovarian tumor. These results indicate that the effect of MRK-20 is highly specific to cells expressing 85-kDa protein.     

全身照射（TBI）在骨髓移植治疗实体瘤中的作用（附7例报告）

报告１９９２～１９９４年采用自身骨髓移植方法，治疗高危组恶性淋巴瘤患者７例，全部进行了大剂量化疗及全身照射。处方剂量达ＳＧｙ、双肺为７Ｇｙ，无１例发生放射性肺炎、无相关死亡。本组患者最长生存为４６个月，与非骨髓移植治疗相比，其治疗方法明显优于前者。     

Celltracks® AutoPrep® 系统检测循环肿瘤细胞的可行性分析*

目前,越来越多的研究表明Celltracks® AutoPrep® 系统会漏检非典型上皮特性的循环肿瘤细胞（CTCs）,这部分CTCs比单纯表达上皮特性的CTCs具有更强的侵袭和转移能力,对患者的疗效和预后判断具有更高的价值。本文主要综述CelltracksAutoPrep系统与ISET技术的对比研究及EpCAM表达、混合肿瘤细胞、上皮间质转化（EMT）肿瘤细胞、循环肿瘤干细胞和不可逆EMT+肿瘤细胞对Celltracks® AutoPrep® 系统检出率的影响,分析Celltracks® AutoPrep® 系统检测CTCs的可行性。     

新型铂（Ⅱ）类配合物对结肠癌SW620 细胞系的体外抗癌活性研究*

目的：本实验研究了两种新型铂（Ⅱ）类配合物（2,3- 吡啶二羧酸二水合铂、2,3- 吡嗪二羧酸二水合铂）对结肠癌SW620 细胞系的体外抗癌活性及其对细胞凋亡的影响。同时与奥沙利铂作一对照,以明确该两种新型铂（Ⅱ）类配合物是否具有更好的体外抑瘤效果。方法：采用人结肠癌细胞系SW620 作为研究对象,三种药物分别以不同浓度作用于对数生长期的SW620细胞24h、48h 后,应用软琼脂糖集落形成试验检测集落形成抑制率,以AnnexinV/PI双染法测定细胞凋亡率,以扫描电镜观测三种
药物作用后细胞形态和超微结构的改变。结果：软琼脂糖细胞集落形成抑制率实验显示出奥沙利铂、吡嗪、吡啶三种药物做用24h 后对 SW620 细胞系的半数抑制浓度（IC 50）分别为 266.51,176.18,159.25μ mol/L,48h 的IC 50分别为 158.84,161.27,125.67μ mol/L,其药物作用强度为吡啶>吡嗪>Oxa,有显著性差异（P<0.01）。AnnexinV/PI双染法显示出三种药物均可诱导SW620 细胞产生凋亡,其作用呈浓度和时间依赖性,并且随药物作用浓度及时间延长死亡细胞增多,作用强度为吡啶> 吡嗪>Oxa,有显著性差异（P<0.01）。电镜下可见细胞典型早晚期细胞凋亡特征。结论：这两种新型铂（Ⅱ）配合物对结肠癌SW620 细胞系显示出良好的体外抑瘤效果,该作用呈浓度和时间依赖性,并且强于奥沙利铂。药物作用靶点之一在于诱导细胞产生凋亡。     

Effects of K-ras Gene Mutations in the Development of Lung Lesions Induced by 4-(N- Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone in A/J Mice

The relationship between the development of peripheral lung lesions induced by tobacco-specific 4-( N -methyl- N -nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and K- ras gene mutation in A/J mice, and the correlations between histological alterations and the course of lung lesion development after NNK treatment and K- ras gene mutation were investigated. The acquisition of a selective growth advantage by the lung lesions with mutations was also examined using immunohistochemical labeling with bromodeoxyuridine. Thirty female 5 weeks old A/J mice were each injected intraperitoneally with a single dose of NNK (100 mg/kg body weight) and subdivided into 6 groups according to the time after NNK treatment. The lung lesions were characterized histologically as alveolar/bronchiolar hyperplasia, adenoma and adenocarcinoma, and point mutations in codons 12 and 61 of the K- ras gene were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and dideoxy sequencing methods. K- ras gene mutations were identified in 7 (58.3%) of 12 hyperplasias, 42 (75.0%) of 56 adenomas and 3 (75.0%) of 4 adenocarcinomas. The most frequent K- ras gene mutation was a G-to-A transition at the second base of codon 12 and this accounted for 86.5% of all the mutations detected. Neither the frequency of activation of this gene nor the specific mutation was affected by the time after NNK treatment and there was no positive correlation between the proliferative activity of lung lesions and the presence of K- ras gene mutations. Thus, K- ras gene mutation is closely associated with the development of NNK-induced peripheral lung lesions in A/J mice, but it plays no role in the selective growth advantage of these lesions.