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Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2 被引量:12
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作者 Edgar Staren Takeshi Iwamura +1 位作者 Hubert Appert John Howard 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第1期143-148,共6页
INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relatio... INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10]. 展开更多
关键词 Carcinoma Pancreatic Neoplasms TAXOIDS Antineoplastic Agents Phytogenic Biocompatible Materials Collagen drug Combinations drug resistance Multiple drug resistance Neoplasm Fluorescent Dyes Humans In Vitro LAMININ Neoplasm Invasiveness p-glycoprotein Paclitaxel derivatives Phenotype PROTEOGLYCANS RNA Neoplasm Research Support Non-U.S. Gov't Rhodamine 123 tumor Cells Cultured
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Drug resistance and new therapies in colorectal cancer 被引量:31
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作者 Kevin Van der Jeught Han-Chen Xu +2 位作者 Yu-Jing Li Xiong-Bin Lu Guang Ji 《World Journal of Gastroenterology》 SCIE CAS 2018年第34期3834-3848,共15页
Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The ma... Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo-and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibodydrug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors. 展开更多
关键词 COLORECTAL cancer Therapy resistance antibody-drug CONJUGATES α-amanitin tumor MICROENVIRONMENT Immunotherapy CHECKPOINT inhibitors MICROBIOME
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Carbonic anhydrase XII inhibition overcomes P-glycoprotein-mediated drug resistance: a potential new combination therapy in cancer 被引量:2
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作者 Kathryn F.Tonissen Sally-Ann Poulsen 《Cancer Drug Resistance》 2021年第2期343-355,共13页
Intrinsic or acquired resistance to chemotherapy is a major hurdle in the treatment of cancer.One of the key mechanisms of resistance is the overexpression of the drug efflux transporter P-glycoprotein(Pgp).Pgp overex... Intrinsic or acquired resistance to chemotherapy is a major hurdle in the treatment of cancer.One of the key mechanisms of resistance is the overexpression of the drug efflux transporter P-glycoprotein(Pgp).Pgp overexpression renders a large number of mechanistically unrelated chemotherapies ineffective.Targeting Pgp inhibition directly to overcome drug resistance,although conceptually and mechanistically attractive,has not translated to the clinic,in part because Pgp also has a critical protective function in many healthy tissues.It was recently discovered that carbonic anhydrase XII(CA XII),an enzyme associated with pH regulation in cancer,is co-expressed and co-located with Pgp in drug resistant cancer cells.CA XII is also upregulated by hypoxia,which is another microenvironmental factor that contributes to drug resistance.Here,we review findings that demonstrate modulation of CA XII may offer a promising new approach towards overcoming the longstanding hurdle of drug resistance and therapy failure against solid cancers.This review covers the use of CA XII inhibitors,both small molecule and antibody,in combination with chemotherapeutics that are substrates for Pgp.This combination therapy approach restores the efficacy of chemotherapy in resistant cells and offers a potential new therapeutic window to re-examine the targeting of Pgp as a safe,effective,and novel anticancer strategy. 展开更多
关键词 Carbonic ANHYDRASE XII p-glycoprotein drug resistance tumor MICROENVIRONMENT pH HYPOXIA inhibitor CHEMOTHERAPY
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Imaging probes for non-invasive tumoral detection and functional monitoring of cancer multidrug resistance
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作者 Filipa Mendes Lurdes Gano +3 位作者 Jorge Grilo Susana Cunha Célia Fernandes António Paulo 《Cancer Drug Resistance》 2020年第2期209-224,共16页
Aim:Several cationic radiotracers originally developed as myocardial perfusion agents have shown potential for both early detection of cancer and non-invasive monitoring of multiple drug resistance(MDR)by single photo... Aim:Several cationic radiotracers originally developed as myocardial perfusion agents have shown potential for both early detection of cancer and non-invasive monitoring of multiple drug resistance(MDR)by single photon emission computed tomography.We have introduced two cationic complexes,^(99m)Tc-DMEOP[di-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)]and ^(99m)Tc-TMEOP[tri-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)],which showed excellent preclinical results as cardiac imaging probes,namely a persistent heart uptake with rapid blood and liver clearance.This study aimed at the evaluation of their usefulness for tumoral detection and functional assessment of MDR.Methods:The uptake and efflux kinetics of ^(99m)Tc-DMEOP and ^(99m)Tc-TMEOP were evaluated in human prostate,lung,and breast cancer cell lines,including drug-resistant cell lines that are known to overexpress the MDR P-glycoprotein(Pgp).The effects of MDR modulators were also studied.In vivo studies were performed in xenografted tumor models,and the MDR phenotype of the tumors was confirmed by Western blot.Results:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over time.The uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp and increased in the presence of a Pgp modulator.In nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.Conclusion:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over time.The uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp,and increased in the presence of a Pgp modulator.In nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors. 展开更多
关键词 Noninvasive imaging imaging probes tumoral detection multiple drug resistance p-glycoprotein
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抗Pgp抗体PHMA02在肿瘤临床中的应用研究及预后分析 被引量:8
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作者 许元富 杨纯正 +5 位作者 熊冬生 邵晓枫 王珊 孙云晖 薛艳萍 李维廉 《中国肿瘤临床》 CAS CSCD 北大核心 1999年第9期645-649,共5页
目的:应用单抗PHMA02 对148 例肿瘤患者P- 糖蛋白(Pgp)的表达进行检测,并对该单抗的特异性、检测结果与临床符合率以及预后的准确性进行评估。方法:应用免疫组化法检测了47 例实体瘤标本,应用药敏实验检测15 ... 目的:应用单抗PHMA02 对148 例肿瘤患者P- 糖蛋白(Pgp)的表达进行检测,并对该单抗的特异性、检测结果与临床符合率以及预后的准确性进行评估。方法:应用免疫组化法检测了47 例实体瘤标本,应用药敏实验检测15 例儿童恶性肿瘤;应用间接免疫荧光法、RT- PCR 法和药敏实验检测了101 例急性白血病(AL) 患者;用医学统计软件分析数据。结果:1) 在47 例实体瘤标本中,儿童恶性肿瘤中多药耐药阳性( MDR+) 表达率较高(867 %) ,乳腺癌淋巴结转移灶中MDR+ 表达率为667% ,显著高于乳腺癌原发灶的300 % ( P< 001) 。2) 在101 例急性白血病(AL) 患者中,难治和复发组的MDR+ 表达率(529 % )显著高于初诊组(192 % )( P< 001)。3) 单抗PHMA02 的检测结果与国外同型单抗JSB- 1 的平行检测结果呈正的直线相关( P<005) ,与RT- PCR 的检测结果具有相关性(P< 001) ;部分标本的药敏实验结果与单抗PHMA02 的检测结果基本一致。结论:1) 单抗PHMA02 的检测结果与临床有较好的符合率,可在临床上应用。2)Pgp 在成人肺癌和乳腺癌中均有一? 展开更多
关键词 单克隆抗体 P-糖蛋白 多药耐药 肿瘤 治疗
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MGrl-Ag维持耐药表型与蛋白激酶C有关 被引量:2
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作者 韩英 时永全 +5 位作者 郑悦 聂永战 张宏博 张淼莉 潘伯荣 樊代明 《世界华人消化杂志》 CAS 2001年第5期517-521,共5页
目的探讨MGrl-Ag维持耐药表型与蛋白激酶C的关系, 方法用免疫细胞化学方法检查MGrl-Ag在胃癌SGC7901细胞系及耐药亚系的表达;ELISA及点印迹方法检测胃癌SGC7901细胞系及其耐药亚系细胞培养上清中MGrl-Ag的表达;免疫荧光双标记及共聚焦... 目的探讨MGrl-Ag维持耐药表型与蛋白激酶C的关系, 方法用免疫细胞化学方法检查MGrl-Ag在胃癌SGC7901细胞系及耐药亚系的表达;ELISA及点印迹方法检测胃癌SGC7901细胞系及其耐药亚系细胞培养上清中MGrl-Ag的表达;免疫荧光双标记及共聚焦显微镜技术观察MGrl-Ag与PKCa的相关表达;竞争蛋白结合法检测单克隆抗体MGr-1对PKC活性的影响。结果MGrl-Ag在胃癌SGC7901细胞系及耐药亚系均有表达,以耐药细胞表达明显增多;ELISA及点印迹实验证实在表达MGrl-Ag的细胞培养上清中均可检测到MGrl-Ag;耐药细胞PKCa与MGrl-Ag的相关表达较药敏细胞明显增强;单克隆抗体MGr-1与耐药细胞共同孵育后,耐药细胞PKC的活性减低,以细胞质的PKC降低比较明显。结论 MGrl-Ag可能是一种分泌蛋白,MGrl-Ag维持SGC7901/VCR耐药细胞系的耐药表型可能受PKC信号转导通路的调节。 展开更多
关键词 胃肿瘤 病理学 肿瘤细胞 抗药性 蛋白激酶 MGrl-Ag 单克隆抗体
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TNF-α/NF-κB通路干预对肝癌多药耐药相关P-gp表达的影响 被引量:6
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作者 吴玮 姚敏 +3 位作者 顾星 王以浪 陆少林 姚登福 《南通大学学报(医学版)》 2013年第1期13-17,共5页
目的:探讨肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)单抗及核因子-κB(nuclear factor-κB,NF-κB)/p65siRNA干预NF-κB活化对肝癌HepG2细胞增殖和细胞膜糖蛋白(P-glycoprotein,P-gp)表达的影响。方法:体外培养人HepG2细胞并... 目的:探讨肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)单抗及核因子-κB(nuclear factor-κB,NF-κB)/p65siRNA干预NF-κB活化对肝癌HepG2细胞增殖和细胞膜糖蛋白(P-glycoprotein,P-gp)表达的影响。方法:体外培养人HepG2细胞并给予抗人TNF-α单克隆抗体,以流式细胞术检测细胞凋亡的情况;设计并合成针对NF-κB/p65 siRNA的质粒,在转录水平干扰NF-κB活化,以Western Blot检测P-gp表达。结果:单抗作用后,肝癌细胞凋亡的比率明显增加(P<0.01),用药后细胞株NF-κB表达水平明显降低(P<0.01),与培养液中明显降低的TNF-α水平呈显著正相关(r=0.89,P<0.01);NF-κB/p65 siRNA干预后可下调化疗药物引起的癌细胞NF-κB和P-gp的过表达。结论:以TNF-α单体干预肝癌细胞中NF-κB活化,可使细胞凋亡增加,siRNA可通过特异性抑制NF-κB/p65编码的mRNA,下调P-gp水平,促进肝癌细胞凋亡。 展开更多
关键词 肝癌 肿瘤坏死因子-α单克隆抗体 核因子-ΚB HEPG2细胞 小干扰RNA 多药耐药
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死亡受体5抗体治疗卵巢癌耐药的研究进展
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作者 梁宝权 钱永红 《医学综述》 2015年第4期624-626,共3页
肿瘤坏死因子相关的诱导配体为近年来新发现的凋亡调节的重要蛋白之一。死亡受体5(DR5)为其诱导凋亡的重要受体之一。DR5的结构、组织分布及其可诱导肿瘤细胞凋亡而不影响正常细胞的特性,已成为近年的研究热点。其中DR5单克隆抗体应用... 肿瘤坏死因子相关的诱导配体为近年来新发现的凋亡调节的重要蛋白之一。死亡受体5(DR5)为其诱导凋亡的重要受体之一。DR5的结构、组织分布及其可诱导肿瘤细胞凋亡而不影响正常细胞的特性,已成为近年的研究热点。其中DR5单克隆抗体应用于耐药卵巢癌细胞的治疗,为耐药卵巢癌细胞治疗提供了新的思路。该文将DR5单克隆抗体应用于卵巢癌耐药的研究进展予以综述。 展开更多
关键词 耐药卵巢癌 肿瘤坏死因子相关的凋亡诱导配体 死亡受体5 死亡受体5单克隆抗体
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K562/VCR单克隆多药耐药亚细胞系的建立
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作者 兰志建 汤永民 +4 位作者 宁铂涛 杨世隆 钱柏芹 沈红强 陈英虎 《实用肿瘤杂志》 CAS 北大核心 2004年第4期301-303,共3页
目的 建立耐药性较为均一的 K5 6 2 / VCR多药耐药 (MDR)亚细胞系 ,为更好研究多药耐药性的产生以及逆转机制提供良好的实验材料。方法 采用三种不同的培养方法和有限稀释法对 K5 6 2 / VCR MDR细胞系进行亚克隆培养 ,并用流式细胞仪 ... 目的 建立耐药性较为均一的 K5 6 2 / VCR多药耐药 (MDR)亚细胞系 ,为更好研究多药耐药性的产生以及逆转机制提供良好的实验材料。方法 采用三种不同的培养方法和有限稀释法对 K5 6 2 / VCR MDR细胞系进行亚克隆培养 ,并用流式细胞仪 (FCM)测定 p170的表达情况。结果 加用培养上清或滋养细胞存在的条件下 ,亚克隆效率明显高于无条件培养液 (P<0 .0 5 ,P<0 .0 1)。建立的单克隆 MDR亚细胞系 6株 ,FCM分析证实 p170呈不同程度的表达 ,其中表达最高者为 31.4 % (K5 6 2 / VCR A5 - A1)。结论  (1)耐药细胞系的亚克隆培养需要条件培养液或滋养细胞的支持 ,后者较前者更为有效。 (2 )成功建立了 6株 K5 6 2 / 展开更多
关键词 白血病/病理学 K562细胞 抗体 单克隆 流式细胞术 抗药性 多药 肿瘤细胞 培养的
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Clinical significance of the loss of CD20 antigen on tumor cells in patients with relapsed or refractory follicular lymphoma 被引量:1
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作者 Jean-Marie Michot Alice Buet-Elfassy +13 位作者 Maxime Annereau Julien Lazarovici Alina Danu Clémentine Sarkozy Claude Chahine Camille Bigenwald Jacques Bosq Julien Rossignol Patricia Romano-Martin Capucine Baldini David Ghez Peggy Dartigues Christophe Massard Vincent Ribrag 《Cancer Drug Resistance》 2021年第3期710-718,共9页
Aim:Anti-CD20 monoclonal antibody is a cornerstone therapy for follicular lymphoma.Following anti-CD20 therapy,a potential decrease in CD20 antigen,and therefore a loss of the tumor target might be expected.However,th... Aim:Anti-CD20 monoclonal antibody is a cornerstone therapy for follicular lymphoma.Following anti-CD20 therapy,a potential decrease in CD20 antigen,and therefore a loss of the tumor target might be expected.However,the incidence and clinical significance of CD20 loss on tumor cells in patients with relapsed or refractory follicular lymphoma are unknown.This study aims to investigate the incidence and outcome of patients with relapsed or refractory follicular lymphoma patients harboring the loss of the tumor target,CD20.Methods:All consecutive adult patients with relapsed or refractory follicular lymphoma referred to the Early Drug Department at Gustave Roussy were included.The main objectives were to assess the incidence and prognosis of the loss in expression of CD20 antigen on the surface of tumor cells on patient outcome.Results:Over the study period 2013-2018,131 patients were screened for clinical trials with B-cell malignancies in the early drug department of Gustave Roussy in France.Forty-four patients presented with relapsed or refractory follicular lymphoma and 32 had tumor biopsies at the time of relapse that were retained for analysis.The median(range)age was 67.5 years(55.3-75.3)and the median number of prior anti-cancer systemic therapies was 3(2-4).At the time of relapse,CD20 expression was positive in 84%of tumors(n=27)and negative in 16%of tumors(n=5).At a median follow-up of 18.3(0.6-83.3)months,CD20 negativity was associated with a poorer prognosis with a median overall survival of 8.9 months(95%CI:2.4-19.1)in comparison to CD20 positive patients(28.3 months,95%CI:25.1-75.3 months,P=0.019).Conclusion:The loss of the tumor target antigen,CD20,occurred in 16%of patients with relapse or refractory follicular lymphoma.Due to confounding factors in patients who received anti-CD20 immunotherapy,it was not possible to formally establish the prognostic significance of CD20 negativity.However,we suggest that a check for CD20 antigen positivity nevertheless be performed to adapt subsequent therapies for patients with relapsed or refractory follicular lymphoma. 展开更多
关键词 Follicular lymphoma CD20 tumor antigen anti-CD20 monoclonal antibody cancer drug resistance
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靶向上皮特异性抗原阳性肝癌干细胞单克隆抗体联合顺铂治疗肝癌的实验研究 被引量:3
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作者 何永燕 遇珑 +5 位作者 容雁 孙立新 孙力超 杨治华 冉宇靓 李力 《中华肿瘤杂志》 CAS CSCD 北大核心 2016年第5期333-339,共7页
目的探讨靶向肝癌干细胞单克隆抗体的生物学特征及其联合顺铂治疗肝癌的疗效。方法采用无血清悬浮培养法和PKH26染色法确定肝癌Bel7402-V3细胞中存在肿瘤干细胞。细胞免疫荧光法检测单克隆抗体15D2识别的抗原蛋白与PKH26阳性细胞及上皮... 目的探讨靶向肝癌干细胞单克隆抗体的生物学特征及其联合顺铂治疗肝癌的疗效。方法采用无血清悬浮培养法和PKH26染色法确定肝癌Bel7402-V3细胞中存在肿瘤干细胞。细胞免疫荧光法检测单克隆抗体15D2识别的抗原蛋白与PKH26阳性细胞及上皮特异性抗原(ESA)在Bel7402-V3细胞中的表达情况。无血清悬浮培养法检测流式细胞术分选出的15D2阳性细胞的自我更新能力以及15D2对Bel7402.V3细胞自我更新能力的影响。CCK8法检测15D2对细胞顺铂耐药能力的影响。裸鼠体内治疗实验分析15D2联合顺铂对Bel7402.V3移植瘤生长的抑制作用。结果Bel7402-V3细胞无血清悬浮培养11d后形成的细胞球体中存在单个PKH26阳性细胞。细胞免疫荧光显示,单克隆抗体15D2识别的抗原分子能与PKH26和ESA在Bel7402-V3细胞上共定位。15D2阳性细胞和15D2阴性细胞的体外成球率分别为(30.4±3.4)%和(8.8±1.8)%,差异有统计学意义(P〈0.05)。15D2阳性细胞具有更高的顺铂耐药性,15D2阳性细胞和15D2阴性细胞的半数抑制浓度(IC50)分别为1.014和0.365μmol/L。单克隆抗体15D2能够显著抑制Bel7402.V3细胞的无血清成球,抑制率为37.5%。经15D2处理后的Bel7402-V3细胞,顺铂耐药能力明显下降,其Ic50为0.211μg/ml,而对照组的IC50为0.325μg/ml。抗体体内治疗实验结果显示,50、25、12.5mg/kg15D2组的肿瘤生长抑制率分别为82.6%、71.4%和60.0%,50mg/kg15D2+顺铂组的肿瘤生长抑制率为91.0%,顺铂组的肿瘤生长抑制率为56.7%。结论单克隆抗体15D2是抗肝癌干细胞的功能性单克隆抗体,为肝癌干细胞靶向治疗的候选抗体药物。 展开更多
关键词 肝肿瘤 细胞系 肿瘤 肿瘤干细胞 抗体 单克隆 顺铂 上皮特异性抗原 抗药性
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抗体-细胞毒偶联药物在实体瘤治疗中的耐药机制 被引量:1
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作者 郝月 卫静文 宋正波 《肿瘤学杂志》 CAS 2022年第5期396-401,共6页
新一代的由抗体及细胞毒性成分连接而成的抗体-细胞毒偶联药物在抗肿瘤治疗领域实现新突破,因其具备特异性地结合到抗原表面及内化于肿瘤细胞内产生强大杀伤作用的特点得到广泛关注。目前,针对人表皮生长因子受体2(HER2)阳性患者的Trast... 新一代的由抗体及细胞毒性成分连接而成的抗体-细胞毒偶联药物在抗肿瘤治疗领域实现新突破,因其具备特异性地结合到抗原表面及内化于肿瘤细胞内产生强大杀伤作用的特点得到广泛关注。目前,针对人表皮生长因子受体2(HER2)阳性患者的Trastuzumab emtansine和Trastuzumab deruxtecan已初显成效。随后,针对各种不同靶向基因的偶联药物也在不断探索中。但由于肿瘤抗原水平的表达、药物内吞迁移的抑制、溶酶体功能障碍、药物外排泵以及靶点突变等引发了相关的耐药。全文对抗体-细胞毒偶联药物的耐药机制进行综述。 展开更多
关键词 抗体-细胞毒偶联药物 耐药机制 人表皮生长因子受体2 实体肿瘤
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