苯甲酸雌二醇治疗膀胱癌的实验研究

 本实验用苯甲酸雌二醇对小鼠可移植性膀胱癌模型BST739进行了实验治疗观察，结果表明BST739对苯甲酸雌二醇具有敏感性，其抑瘤率为61.3%。而丙酸睾丸素对BST739具有促进作用，抑瘤率为-44.8%，提示雌激素苯甲酸雌二醇对膀胱肿瘤具有治疗意义。     

特异性抗膀胱癌单克隆抗体对膀胱肿瘤的临床研究

 采用一组特异性抗膀胱癌单克隆抗体MAb（T₁₆、M₃₄₄、T₁₃₈、T₄₃），以APAAP免疫细胞化学方法，对63例膀胱移行细胞癌及10例非肿瘤患者的膀胱冲洗液作了研究。T₁₆在全部63份标本呈阳性。随着肿瘤分期、分级的升高，M₃₄₄阳性率逐渐降低，T₁₃₈及T₄₃阳性率逐渐升高。此三种MAb与肿瘤复发也有一定的对应关系。尿细胞学与MAb联合应用，可弥补相互间的不足，使肿瘤检出率进一步提高。结果表明：M₃₄₄、T₁₃₈及T₄₃MAb的阳性表达与肿瘤的分期、分级及预后密切相关，可作为膀胱肿瘤恶性程度、复发及早期诊断的估价指标。     

平阳霉素与硒联用对小鼠移植瘤局部瘤体注射效果的实验研究

 采取BLM_A5与SeO₂合用对C₅₇BL/6小鼠移植的黑色素瘤B₁₆进行局部瘤体注射的治疗实验，结果：BLM_A5与SeO₂单用抑瘤率分别为79.24%，74.00%，BLM_A5＋SeO₂水剂抑瘤率为94.04%（P＜0.05）其乳剂为97.83%（P＜0.01），可见SeO₂增强了BLM_A5的抗癌作用。     

香菇多糖对肺癌患者免疫功能的调节作用

 应用香菇多糖治疗化疗后休疗期肺癌患者30例，观察治疗前后细胞免疫和体液免疫变化，结果显示治疗前后各项体液免疫指标均无明显改变。NK细胞，CD₃⁺细胞，CD₄⁺细胞的百分率显著增加（P＜0．05），淋巴细胞转化率增加，CD₈⁺细胞百分率下降，CD₄⁺/CD₈⁺细胞比值上升。提示香菇多糖对肺癌患者免疫功能有正向调节作用。     

一种新的胃癌相关抗原的研究

 取含胃癌单抗MG₉的小鼠腹水，经DEAE—52离子交换层折后，获得纯化的MG₉（IgG₁）56.8mg，与溴化氢活化的Sepharose4B偶联制备免疫吸附剂，用亲和层析的方法从胃癌组织中纯化出MG₉相应抗原，经外源性凝集素识别，高碘酸氧化，电泳考马斯蓝染色，乙酰苏丹黑10B染色，免疫印渍及氨基酸组成分析等实验证实MG₉相应抗原是一种新的胃癌相关糖蛋白，分子量110～120kd．血清ELISA法检测结果提示对胃肠肿瘤的临床诊断有一定意义．     

膀胱移行上皮癌患者血尿β2-微球蛋白临床分析

 我们利用放免法测定了38例膀胱移行上皮癌患者的血、尿β₂-微球蛋白（β_-mG），结果表明:膀胱癌患者血尿β₂-mG均明显高于健康人，并且膀胱癌患者血尿β₂-mG含量随肿瘤分级增加而增高。     

中国拟青霉(Cn80-2)的抗肿瘤作用和毒性

 体内试验表明，Cn80-2菌丝体注射剂对多种动物移植性肿瘤有显著的抑制作用，每天ip20～25mg/kg，连续7～10天，对白血病L₁₂₁₀、P₉₈₈，以及Lewis肺癌有明显抑制效应，但是对小鼠艾氏腹水癌及肉瘤180无效。在体外试验，Cn80-2对人子宫颈癌Hela细胞有直接杀伤作用，IC₅₀为1.25mg/ml，经该药处理的Hela细胞的活体成癌率显著降低。。     

肝癌患者接受131Ⅰ-HAb18（Fab'）2导向治疗的安全性研究

 为解决不能手术切除的中晚期肝癌患者的治疗问题，我们将对人肝癌细胞有高亲和力的抗人肝癌单克隆抗体HAb₁₈（Fab'）₂与1311偶联，制成导向治疗药物，用于肝癌治疗。通过对治疗前后血常规、肝、肾及甲状腺功能的对比观察，探讨其治疗的安全性。     

三氧化二砷诱导人肝癌细胞株SMMC-7721凋亡的实验研究

 MTT法、AO/EB荧光染色法和流式细胞仪分析法观察As₂O₃对人肝癌细胞林SMMC-7721的作用.结果发现:As₂O₃可显著抑制SMMC-7721细胞的生长;经药物作用后,AO/EB染色时,肝癌细胞在显微镜下呈现典型的凋亡形态学改变;在流式细胞仪上可见亚G_l峰;凋亡呈剂量,时间依赖性特点;As₂O₃使细胞周期阻止于G₂/M期.以上表明:As₂O₃可诱导人肝癌细胞株凋亡,可望为临床应用砷剂治疗肝癌提供实验依据.     

氧化勒碱及双稠吡咯啶生物碱对肺癌A549细胞作用后核仁形成的观察

 本实验用抗癌药氧化勒碱（Oxyavicine）和双稠吡咯啶生物碱（Pyrrolizidine alkaloids）作用于肺癌A₅₄₉细胞后，观察了肺癌A₅₄₉细胞银染核仁形成区（Ag—stained Nucleolar Organizer Regions，AgNOR_s）的变化。结果表明，药物作用后的肺癌A₅₄₉细胞AgNOR_s数目减少，而团块型AgNOR_s的数目增多。经统计学检验，将用药组与对照组比较，有显著性差异。实验结果提示，药物等能干扰癌细胞增殖和DNA合成的因素，能使癌细胞AgNOR_s发生改变；表明细胞核AgNOR_s的观察不仅在肿瘤类型、良恶性鉴别等方面有重要价值，且在抗癌药物作用效果方面也可展示其前景。     

毕赤酵母表达重组人内皮抑素对小鼠肺腺癌LA795生长和转移的抑制作用

背景与目的：肿瘤的生长和转移有赖于新生血管的生成,内皮抑素能抑制肿瘤的血管生成。本研究旨在观察毕巴斯德酵母（pichia.pastoris.GS115)分泌表达的重组人内皮抑素（recombinant human endostatin,rhES)对小鼠肺腺癌LA795生长和转换的抑制作用。方法：挑取一株高效分泌表达rhES的毕赤巴斯德酵母菌株,利用甲醇进行大量诱导表达;用肝素亲和层析的方法纯化目的蛋白;将接种LA795肺腺癌细胞的T739小鼠随机分成两组,分别给予rhES和PBS皮下注射,每日1次,连续14天;观察两组小鼠肿瘤生长情况,测量肿瘤体积大小,并观察两组小鼠肿瘤肺部转移情况。结果：经甲醇诱导的毕赤巴斯德酵母菌株高效分泌表达了rhES;动物实验研究发现rhES能显著抑制小鼠肺腺癌LA795的生长,rhES治疗组肿瘤大小与对照组比较具有显著性差异（P＜0．001）,抑瘤率达到66．4％,并且有效抑制了肿瘤的肺部转移。结论：利用毕赤酵母作为宿主分泌表达的rhES具有良好的生物学活性,可显著抑制小鼠肺腺癌LA795的生长和转移。     

TGFβ1质粒DNA直接瘤内注射地小鼠肿瘤生长的影响

目的探讨裸ＤＮＡ质粒ＰＭＡＭｎｅｏ－ＴＧＦβ１小人直接注射后的表达及其对肿瘤生长的影响。方法 肺腺癌细胞株ＬＭ３小鼠背部皮下接种,两周后瘤。瘤体内多点多次直接注入质粒ＤＮＡＰＭＡＭｎｅｏＴＧＦβ１,并设空质粒和生理盐水注射组为对照,观察肿瘤生长情况。于第８周将小鼠处死,取新鲜的铰瘤组织提取ＲＮＡ,行Ｎｏｒｔｈｅｒｎ杂交,并病理制片观察肿瘤组织结构的变化。结果ＴＧＦβ基因治疗组肿瘤生长速度增快,但各     

Thermotolerance of tumors MA737 and LA795 of mice

The effects of splitted heating of tumor, alone or in combination with local radiation, were studied on mouse mammary cancer MA737 in JB 2 mice and lung cancer LA795 in 739 mice. Hyperthermia was done by immersing the tumor-bearing foot into a water bath at 44 +/- 0.2 degrees C. When combined with radiation, 8 Mev beta irradiation from a linear accelerator was given. The response was assessed by tumor growth retardation calculated according to a special computer program. A priming dose of 5 to 6-minute exposure to 44 degrees C was followed, after various time intervals (1, 4, 5, 24 hr), by a longer exposure. Thermotolerance was induced in these two animal tumor models. Tolerance to heat, however, did not affect the combined effect of hyperthermia and radiation. Electron microscopic examination of the treated tumors confirmed the synergistic killing effect of the combined treatment.     

Protective effects of amphotericin B against spontaneous and transplantable murine tumors.

Two tumor systems were used to test prophylactic effects of amphotericin B (AmB). When 0.5 mg AmB was given ip every 2 weeks to AKR mice beginning at 8 weeks of age, the 50% tumor incidence for spontaneous lymphoma development was delayed 2-3 months. In the second tumor system, BALB/c mice received injections of either 20 or 50 mug AmB before receiving MOPC-315-C cells sc. The mice given the low dose of AmB demonstrated a decreased tumor incidence and a reduced tumor growth rate, when compared with controls. Opposite effects were found for the group administered the high dose; tumor incidence and rate of growth were increased.     

TNP-470联合重组人内皮抑素抑制小鼠肺腺癌生长的研究

目的:观察TNP470和重组人内皮抑素（recombinant human endostatin,rhES）联合治疗对小鼠肺腺癌LA795肿瘤生长的抑制作用。方法: 用甲醇诱导能高效分泌表达重组人内皮抑素（rhES）的毕赤酵母菌株分泌表达rhES，将皮下接种LA795肺腺癌细胞的T739雄性近交系小鼠随机分成3组，每组各10只，分别给予PBS，rhES及TNP470+rhES皮下注射，每日1次，连续14 d；观察各组小鼠肿瘤生长情况，游标卡尺测量肿瘤体积大小。断颈处死小鼠，原位肿瘤免疫组化观察肿瘤内部微血管密度（microvessel density, MVD）。结果: 经甲醇诱导，毕赤酵母重组菌分泌表达rhES，并应用肝素亲和层析将其纯化；动物试验显示与PBS对照组比较，rhES治疗组及rhES＋TNP470治疗组均明显抑制小鼠肿瘤的生长（P<0.01），TNP470+rhES组与rhES组比较亦有显著性差异（P<0.01）。原位肿瘤免疫组化显示联合治疗组抑制血管生成更显著（P<0.01）。结论: TNP470联合rhES治疗对小鼠肺腺癌LA795生长的抑制效果比单独使用rhES的治疗效果更佳，具有良好的协同治疗作用     

Cell-mediated immune responses to transplanted tumors in mice chronically exposed to cigarette smoke.

C57BL and BALB/c mice were exposed to fresh cigarette smoke for 7-8 minutes per day for varying periods up to 30 weeks before subcutaneous or intratracheal inoculation of viable tumor cells. The growth rates of subcutaneous tumors in the mice exposed to smoke were significantly higher than those of controls and more lung metastases were noted. Enhanced tumor growth rates in the respiratory tracts of smoke-exposed mice were evidenced by the markedly increased death rates in these animals after the intratracheal inoculation of tumor cells. Increased tumor growth rates in mice that inhaled smoke were assoicated with depressed tumor-specific cytotoxic responses in both spleens and regional lymph nodes. Short-term exposure (10 wk) of mice to cigarette smoke resulted in decreased tumor growth rates concomitant with enhanced cytotoxic responses.     

Hormone dependency of a serially transplantable human prostatic cancer (HONDA) in nude mice

Human prostatic cancer (HONDA) serially transplanted in nude mice grew well in male mice but not at all in untreated female mice or in castrated male mice. Progressive growth in female mice was obtained by i.m. administration of 1 mg of testosterone twice a week. Estradiol inhibited the growth of the tumor in male mice to some extent; however, some growth was observed. The tumor in untreated male mice retained the histological features of poorly differentiated adenocarcinoma. Tumors in castrated male mice showed reduction in size of tumor cell nests with relative overgrowth of stroma. The tumor in androgenized female mice consisted of columnar epithelial cells with large nuclei and more abundant cytoplasms and a large glandular lumen, showing histology of moderately differentiated adenocarcinoma. High levels of human prostatic acid phosphatase (PAP) were detected in sera from untreated male mice. Testosterone markedly increased the content of serum PAP of androgenized female mice. Estradiol reduced the levels of PAP in sera from untreated male mice regardless of the tumor weight. High-affinity androgen receptors were present in cytosol and in nuclear extract of the tumor in untreated male mice. No measurable amount of progesterone or estrogen receptors was present in cytosol from untreated male mice.     

Isozyme pattern in serially xenotransplanted childhood tumors

Growth rate, histological course, and polymorphic enzyme pattern (glucose 6-phosphate dehydrogenase, glucose phosphate isomerase, and phosphofructokinase) were studied in eight childhood tumors xenotransplanted serially to nude mice. The growth rate of these tumors (three nephroblastomas, one hypercalcemic renal tumor, three rhabdomyosarcomas, and one malignant histiocytosis) appeared stable for any one particular tumor line. The time interval between two grafts varied from 1 to 3 weeks to 1 to 2 months in correlation with the clinical course of each malignant process. Histological changes were mostly in relation with a progressive dedifferentiation of the grafts. Immunoneutralization of glucose-6-phosphate dehydrogenase and glucose phosphate isomerase made possible the quantification of the stroma reaction in the grafts. A series of ten passages showed the amount of stroma to be constant for a given tumor type but variable from one tumor type to another, except for the malignant histiocytosis which showed an increase in stroma constituent after the sixth passage. One nephroblastoma tumor line showed, during the third passage, a sudden acceleration in the growth rate and complete transformation of the histological and isozymic patterns, which were interpreted as being the result of a murine lymphoma. The fibroblastic form of phosphofructokinase increased in every tumor line, whatever the tumor type. This change may be linked to a progressive dedifferentiation during the passage.     

Determinants of tissue estradiol levels and biologic responsiveness in breast tumors

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10–50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.