胃癌细胞对化疗药物和α—干扰素的敏感性试验

目的探讨人胃癌细胞株对不同化疗药物、α－干扰素及其相互配伍的敏感性。方法向体外培养的人胃癌细胞（ＭＧＣ８０－３）中加入不同配伍及不同浓度的化疗药物和α－干扰素,采用ＭＴＴ法检测癌细胞对不同配伍药物的敏感性。结果联合用药较单一用药的相对抑制率明显增高,尤其以氟尿嘧啶、丝裂霉素和表阿霉素３药联合作用的抑制率最高;随药物剂量的增加,各组的抑制率有所增高,α－干扰素与化疗药物合用时,有协同抑制作用,尤其在     

胰腺癌细胞对化疗药物敏感性的测定

目的 探讨人胰腺癌细胞株对常用化疗药物及其相互配伍的敏感性，为临床合理用药提供理论依据。方法 将人胰腺癌细胞株（Ｐ３、ＳＷ１９９０、Ｃａｐａｎ－２）细胞接种于９６孔培养板，分别加入不同配伍及不同浓度的化疗药物，作用一定时间后采用噻唑蓝法（ＭＴＴ法）测定其抗癌敏感性。结果 以５－氟脲嘧啶和丝裂霉素为基本的三联用药在抑制率相当的情况下，其组成中各药物剂量仅为单一用药剂量的１／５０；联合用药方案中以５－     

不同个体膀胱癌组织培养化疗药物敏感性的研究

目的：探讨不同个体膀胱癌对化疗药物的敏感性。方法：采用组织培养药敏测试法，对37例膀胱癌的化疗药物敏感性进行检测。结果：不同化疗药物对不同个体膀胱癌的抑制率差异明显。膀胱癌THP加MMC的敏感率(81．8％)和平均抑制率(67．6％)均高于任何一种单一药物；复发膀胱癌的药物敏感率和平均抑制率均低于初发者；膀胱癌的药物敏感性与分级无关。结论：不同个体膀胱癌对不同化疗药物的敏感性差异明显，复发膀胱癌对化疗药物存在一定的耐受，联合用药可以提高化疗效果。组织培养药敏测试法可有效地为不同个体膀胱癌选择最佳的化疗方案。     

卡介苗与细胞因子或化疗药物联合应用对膀胱癌细胞株BIU-87抑制作用

目的 探讨卡介苗（BCG）与细胞因子或化疗药物联合应用对人膀胱癌细胞株BIU-87的抑制作用。方法 在离体条件下，采用MTT染色法，研究BCG与肿瘤坏死因子、白细胞介素案I、干扰素等细胞因子及丝裂霉素C、阿霉素、噻替派和羟基喜树碱等化疗药物联合应用对膀胱癌细胞株BIU-87的抑制怍用。结果 细胞因子或化疗药物与BCG联合应用能明显增加BCG对BIU-87细胞的毒性作用（P＜0.05）。结论 BCG与细胞因子或化疗药物联合应用对膀胱癌细胞株BIU-87有协同细胞毒作用。     

联合应用9-顺式维甲酸和化疗药物对人胆管癌细胞系QBC939的作用

目的 观察联合应用分化诱导剂9—cis RA和化疗药物对人胆管癌细胞QBC939细胞的作用，为临床诱导分化治疗胆管癌提供实验基础。方法 以10^-6mol／L的9—cis RA作用于培养的人胆管癌细胞系QBC939细胞1、2、3、5d后检测几种常用化疗药物对细胞的杀伤作用。并观察同时加入10^-6mol／L的9—cis RA和化疗药物对QBC939细胞的杀伤作用。结果 同时应用9—cis RA和化疗药物时，对QBC939细胞的杀伤作用与单用化疗药物时无明显差异。9—cis RA作用2d和3d时，化疗药物对QBC939细胞的杀伤作用强于9—cis RA作用前；9—cis RA作用5d时，化疗药物对QBC939细胞的作用较9—cis RA作用前强，但比3d时下降。结论 先用9—cis RA作用后可增强QBC939细胞对化疗药物的敏感性，此作用与9—cis RA作用时间有关。不同联合用药方法的效果不同。     

全反式维甲酸及三氧化二砷诱导肝癌细胞株HepG-2凋亡及与胞内钙相关性研究

目的 观察不同浓度全反式维甲酸(ATRA)与三氧化二砷(As2 O3)单独及联合作用于人肝癌细胞株HepG-2细胞,检测其体外生长增殖抑制率、细胞凋亡率及细胞内钙离子浓度([Ca2+]i)的变化,探讨其诱导肝癌细胞凋亡可能机制.方法 分别及联合应用不同浓度的ATRA(0.1、1.0、10.0 μmol/L)、As2O3(0.5、1.0、2.0μmol/L)处理HepG-2细胞,用噻唑蓝(MTr)法测定不同作用时间细胞增长抑制率;流式细胞仪(FCM)膜联蛋白V/碘化丙锭(Annexin V/PI)双染色法检测细胞凋亡率的变化;采用荧光探针技术(Fluo-3),应用激光共聚焦显微镜,测定细胞内[Ca2+]i的变化.结果 ATRA、As2O3对人肝癌HepG-2细胞增殖有抑制作用,抑制率与药物浓度、作用时间呈正相关,联合用药优于单独用药;ATRA、As2O3能够诱导人肝癌细胞HepG-2的凋亡,随药物作用时间的延长、药物浓度的增高,细胞凋亡率逐渐增高,联合组更明显;作用时间为24、48 h时,细胞内Ca2+荧光强度与药物浓度、作用时间呈正相关,联合组荧光增强更明显,与对照组比较差异有统计学意义(P＜0.01),而作用时间至72 h时,荧光强度又恢复至正常水平(P＞0.05).结论 ATRA、As2O3能够诱导人肝癌细胞HepG-2凋亡,其诱导凋亡分子机制可能与细胞内钙离子浓度变化有关;ATRA、As2O3体外联合应用有协同抗肝癌作用.     

干扰素结合化疗药物对膀胱癌细胞株BIU-87的抑制作用

在离体条件下，采用噻唑蓝（MTT）染色法，观察干扰素（IFN）与丝裂霉素C（MMC）、阿霉素（ADM）、噻替哌（TSPA）和羟基喜树碱（HCPT）等化疗药物联合应用对人类膀胱癌细胞株BIU－87的抑制作用。结果在连续联合用药组，浓度为25000u／ml的IFN与上述药物50％抑制率（ID50－1）剂量联合使用的抑制率分别为57．4％、58．6％、55．3％和64．3％；在序贯联合用药组，将MMC、ADM的ID50－2剂量作用于细胞24h后，再使用浓度为25000u／ml的IFN，24h后两者联合使用的抑制率分别为59．4％和54．3％。认为IFN与MMC等化疗药物联合应用能够取得较好的协同作用，为临床治疗浅表性膀胱肿瘤提供了新的思路。     

胰腺癌辅助治疗

胰腺癌是目前肿瘤死亡的一个重要因素。单独的根治手术常伴有较高的复发率和转移率,需要术后进一步的辅助治疗提高患者生存率。化疗　目前最为肯定的化疗药物为5-FU,其他药物包括丝裂霉素、环磷酰胺、氨甲蝶呤、长春新碱、顺铂及化疗调节药物如亚叶酸、干扰素等。常用化疗方案有FAM(5-FU 阿霉素 丝裂霉素)、5-FU 顺铂、单独用5-FU等。不同方案在胰十二指肠切除术后平均生存期报道不一,均明显高于未化疗组,但其长期存活率与未化疗组无明显差异。目前尚无研究证实联合化疗的效果优于单一药物的化疗。化疗副作用尤其是胃肠道反应也是应重…     

干扰素抗人膀胱癌细胞株增生作用的体外研究

干扰素(IFN)是一种糖蛋白,具有抗增生,抗病毒和免疫调节的作用。一些临床实验表明IFN对表浅膀胱肿瘤有较好的治疗效果。作者通过体外研究,观察各种IFN联合应用及与化疗药物联合应用的抗癌效果。作者采用重组人α干扰素(rHu IFN—α 2C)、重组人γ干扰素(rHuIFN—γ)、天然β干扰素(IFN—β)及细胞毒药物(阿霉素)对17种人膀胱癌细胞株在体外进行实     

抗表皮生长因子受体单克隆抗体对人胰腺癌裸鼠模型的化疗增敏作用

目的 观察鼠抗人EGFR单克隆抗体联合5-氟尿嘧啶(5-Fu)、健择对裸鼠胰腺癌化疗效果的影响.方法 将人胰腺癌肿瘤细胞悬液注射于裸鼠背部皮下,建立肿瘤模型.干预组腹腔分别注射鼠抗人EGFR单克隆抗体(MMAb-2)、5-Fu、健择及其配伍联合用药;对照组腹腔注射生理盐水.干预4周后处死裸鼠,切取肿瘤,测量瘤体积,取肿瘤组织送病理学检查;免疫组化法检测肿瘤组织中bax、bcl-2的表达;免疫荧光法检测肿瘤组织中细胞凋亡指数,评价干预效果.结果 5-Fu、健择联合应用MMAb-2对裸鼠胰腺癌细胞增殖的抑制作用明显增强(P＜0.05),且能提高裸鼠胰腺癌细胞凋亡率(P＜0.05).结论 抗EGFR单克隆抗体能有效提高化疗药物5-Fu、健择对裸鼠胰腺癌细胞抑制作用的敏感性,可明显提高胰腺癌的化疗效果.     

Ⅳ期胃癌转化治疗的研究进展

胃癌是我国最常见的恶性肿瘤之一,临床收治的胃癌患者以进展期为主。近年来,随着药物治疗的进步,对于无法手术的Ⅳ期胃癌采取以药物治疗为主的综合治疗后,可以使部分病例肿瘤降期,从而获得根治手术的机会,部分接受手术治疗的患者从而获得了长期生存的机会。REGATTA研究结果证实,姑息手术+化疗不能改善Ⅳ期胃癌患者的远期生存。新辅...     

Two hour exposure to sodium butyrate sensitizes bladder cancer to anticancer drugs

Objectives:   To investigate the inhibitory effect of sodium butyrate (NaB) on the proliferation of human bladder cancer cell lines and its synergetic effect with anticancer drugs in treating bladder cancer in vitro and in vivo .
Methods:   The inhibitory effects of NaB on human bladder cancer cell lines in vitro and the synergetic effect of NaB with mitomycin c, cisplatin (CDDP) and adriamycin were detected by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Hoechst staining and electron microscopy were used to observe morphology for apoptotic cells after NaB treatment. Fas, bcl-2 and caspase-3 were determined with flow cytometry. In vivo synergetic effects were detected in N-methyl-N-nitrosourea induced bladder cancer model rats.
Results:   NaB significantly inhibited the growth of bladder cancer cell lines in a concentration and time dependent manner. Better results of tumor inhibition have been achieved when NaB was combined with CDDP, mitomycin c and adriamycin, rather than used alone. Furthermore, 2 h exposure to NaB can sensitize bladder cancer to chemotherapy agents. The Bcl-2 expression in bladder cancer cells is decreased and caspase-3 expression increased after NaB treatment. Intravesical application of NaB combined with CDDP can significantly inhibit tumor growth and progression.
Conclusions:   NaB has a direct anticancer effect and can markedly enhance the action of several chemotherapy agents. 2 h expose to NaB can also sensitize bladder cancer to anticancer drugs. NaB may be an excellent candidate agent for intravesical application in treating bladder cancer.     

Fundamental studies on intravesical instillation of interferons in the treatment of bladder cancer

The cytotoxic effect of interferons on T24 cells, the established cell line from human urinary bladder cancer, the distribution of the drugs in blood, urine and tissues of various organs and histopathological change in the bladder mucosa in dogs following intravesical instillation of the drugs, were studied. These studies were conducted to investigate the possible application of each type of interferons to intravesical treatment of superfitial bladder cancer. 1) The cytotoxicity of Ro22-8181 (recombinant human interferon alpha), GKT-beta (recombinant human interferon beta) and KW2202 (recombinant human interferon gamma) on T24 cells was examined by colony formation method and growth inhibition assay. Cytocidal effects of interferons were dependent on dose and exposure time, and GKT-beta is most effective (GKT-beta greater than Ro22-8181 greater than KW2202). Cytostatic effects of GKT-beta were also dependent on dose and exposure time. 2) The interferon levels in blood, urine and tissues were measured by FL-Sindbis system following bladder instillation of GKT-beta or KW2202 in beagle dogs with bilateral cutaneous ureterostomy. No interferons were detected in blood and urine. Bladder mucosa and submucosal layer were observed through a microscope 6 and 10 hours after bladder instillation of GKT-beta or KW2202 in beagle dogs with bilateral cutaneous ureterostomy. Degeneration of bladder mucosa and submucosal layer was scarcely observed. The above results suggest that GKT-beta is a suitable drug for intravesical treatment of bladder cancer.     

Interferons Modify in Vitro Proliferation of Human Bladder Transitional Cell Carcinoma in the Presence of Doxorubicin and Mitomycin C

Purpose

The aim of the present study was to investigate whether interferons with their known antitumor activity modify the response of human bladder carcinoma cells to antitumor drugs.

Materials and Methods

We investigated the in vitro effect of doxorubicin, mitomycin C and the interferons alpha and gamma on cell proliferation in human bladder carcinoma cell lines as measured by 5-bromo-2'-deoxy-uridine (BrdU) incorporation.

Results

Exposure of RT 112 (but not EJ 28) cells for 2 hours to doxorubicin (500 ng./ml.) and mitomycin C (200 ng./ml.) reduced the proliferation rate to 85.9 plus/minus 3.3 percent (n = 4) and 89.3 plus/minus 4.0 percent (n = 4) of control. Treatment for 2 days with interferon alpha and gamma up to the highest concentration (200 U/ml.) showed no effect. The combination of 100 U/ml. interferon alpha and doxorubicin decreased proliferation significantly. At 50 ng./ml. the proliferation rate was decreased to 88.0 plus/minus 5.7 percent of control and at 500 ng./ml. to 67.7 plus/minus 3.1 percent. Thus interferon alpha seems to increase the sensitivity of the cells to doxorubicin. Cells treated with 20 ng./ml. mitomycin C after pretreatment with interferon alpha showed a dramatic decrease in cell proliferation (from 98.8 plus/minus 2.1 percent to 80.2 plus/minus 4.0 percent of control). This decrease was similar in the presence of 200 ng./ml. mitomycin C. Thus mitomycin C seems to render cells more sensitive to the antiproliferative action of interferon alpha. Interferon gamma had only minor effects on the response of the cells to doxorubicin or mitomycin C.

Conclusions

These studies suggest that exposure to interferon alpha increases the efficacy of anticancer drugs in vitro, probably by several mechanisms. Potential consequences of this finding for the therapeutic regime employed for treatment of bladder carcinoma are discussed.     

温热高渗化疗对人胃癌细胞周期和DNA含量的影响

本实验联合应用温热、高渗液、化疗药物体外作用于人胃癌细胞株，应用流式细胞技术检测了作用前后细胞周期、ＤＮＡ含量的变化。结果表明：单独应用高渗液、丝裂霉素Ｃ（ＭＭＣ）或加温对肿瘤细胞有部分抑制作用；随温度的升高；Ｇ_１期细胞逐渐减少，Ｇ_２期＋Ｍ期逐渐增多，ＤＮＡ量逐渐减少，联合作用效应更强，为临床应用提出了细胞学依据。     

复方苦参注射液与5-氟脲嘧啶对大肠癌LoVo细胞生长抑制的作用及其机制

目的 探讨复方苦参注射液与5-氟脲嘧啶对大肠癌LoVo细胞生长抑制的作用及其机制.方法 台盼蓝染色法测定药物对LoVo细胞抑制作用与时间和剂量的关系,用荧光显微镜、流式细胞仪和免疫印迹分析对药物作用进行检测.结果 Annexin V-FITC和PI双染细胞,复方苦参注射液(40μg/L)和5-Fu(5-氟脲嘧啶,12.5 mg/L)共同作用LoVo细胞24 h后,处于正常生长状态为64.3%,凋亡细胞占26.5%与单一使用药物组差异有统计学意义(P＜0.05).复方苦参注射液(40μgg/L)和5-Fu(12.5 mg/L)共同作用时首先激活Caspase-3和Caspase-9,而Caspase-8则是一个晚期事件.结论 复方苦参注射液和5-Fu对LoVo细胞的生长具有协同抑制作用.两种药物的共同作用与单一使用一种药物的作用机制不同.     

人胃癌细胞原位移植裸鼠原发灶与肝转移灶体外化疗药敏性差异

目的：比较人胃癌原位移植裸鼠肝转移模型原发灶、肝转移灶肿瘤细胞对化疗药物敏感性。 方法：将裸鼠皮下传代的SGC-7901细胞株实体瘤组织块移植于裸鼠胃壁,建立人胃癌裸鼠原位移植模型,待其发生肝转移后取胃原发灶、肝转移灶肿瘤细胞,SRB法检测肿瘤细胞对氟尿嘧啶（5-FU）,顺铂（CDDP）,奥沙利铂（L-OHP）,表阿霉素（eADM）,丝裂霉素（MMC）,长春新碱（VCR）,氨甲喋呤（MTX）7种化疗药物的体外敏感性。 结果：成功建立裸鼠原位移植胃癌转移模型,肿瘤原位移植成瘤率100%,肝转移率75%;7种药物中L-OHP,VCR对原发灶肿瘤细胞的抑制率高于肝转移灶,而eADM,MMC对肝转移灶肿瘤细胞的抑制率高于原发灶（均P<0.05）;5-FU,L-OHP,MTX对原发灶与肝转移灶的抑制率具正相关性（r=0.5203;0.4424;0.3851,均P<0.05）。 结论：胃癌原位移植动物的原发灶和肝转移灶细胞的对化疗药物药敏性存在差异,以原发灶药敏检测结果指导针对肝转移灶的治疗可能是不准确的。     

化学治疗药物对大肠癌细胞端粒酶活性的影响

目的：研究常用化学药物对大肠癌细胞HT－29端粒酶活性的影响。方法：利用端粒酶重复扩增实验（TRAP）结合非变性聚丙烯酰胺凝胶电泳银染法。测定HT－29细胞经过几种化学药物（顺铂，阿霉素，吡柔比星，丝裂霉素，5－FU）不同浓度和时间作用后端粒酶活性的变化。结果：当各种药物大剂量处理细胞4h后再祛除药物培养20h,顺铂对酶的活性完全抑制，丝裂霉素，吡柔比星，阿霉素和5－FU无明显抑制作用。而未经20h再培养则无作用；小剂量药物处理细胞6d。其结果同大剂量相似。结论：顺铂对大肠癌HT－29细胞端粒酶活性有明显抑制作用，而其他几种化学药物没有明显的抑制作用。     

An experimental study of anticancer agent sensitivity test in human gastric cancer cell lines by flow cytometry

The purpose of this study is to assess the lethal and kinetic effects of CDDP, ADM, MMC and 5FU on human gastric cancer cell lines, MKN28, MKN45 and KATO III. The lethal effect was examined by growth inhibition test and colony forming test. The DNA content and DNA synthesis rate of individual cells were simultaneously measured by DNA/BrdU double staining method. In growth inhibition test, MKN45 was sensitive to CDDP, and all cell lines were sensitive to ADM, MMC and 5FU. On the other hand, in colony forming test, these cell lines were sensitive to all drugs. In the cell kinetics, CDDP, ADM and MMC yielded a significant increase of G2 phase fraction at 24, 48 and 72 hours, and caused a significant decrease of BrdU labeling index at 48 hours. The changes of G2 phase fraction and BrdU labeling index were correlated well to the lethal effect of CDDP, ADM and MMC. However, 5FU did not cause these changes to the cell lines employed in the cell kinetic study. Therefore, it was suggested that these results of the cell kinetics might be applied to anticancer agent sensitivity test by selecting adequate anticancer drugs.