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1.
2.
膀胱癌组织P-gp,GST-π和TOPO-Ⅱ表达评估灌注化疗 总被引:1,自引:0,他引:1
目的:探讨膀胱癌的多药耐药性(MDR),指导灌注化疗用药。方法:采用免疫组化法检测44例膀胱癌病理标本中P-糖蛋白(P-gp)、谷胱肽S转移酶(GST-π)和拓扑异构酶(TOPO—Ⅱ)的表达,评估肿瘤耐药谱。结果:①P-gp检测显示,54.5%的病例对阿毒索、丝裂毒索、长春新碱等抗生索类和生物碱类抗癌药高耐药。②GST-π检测显示仅34.1%的病例对顺铂、环磷酰胺等高耐药,而反有56.8%的病例对该类药无耐药或低度耐药。③TOPO-Ⅱ检测显示对阿霉索、柔红毒索、VP16等TOPO-Ⅱ抑制剂类抗癌药,仅13.6%的病例高度耐药,29.5%中度耐药。56.8%低度耐药。结论:检测膀胱癌MDR,了解多药耐药谱,可指导灌注化疗用药。 相似文献
3.
N. ASKAR T. CIRPAN E. TOPRAK B. KARABULUT† N. SELVI‡ M.C. TEREK R. USLU† U.A. SANLI† & E. GOKER† 《International journal of gynecological cancer》2006,16(4):1552-1556
The objective of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) on topoisomerase II levels using western blotting method on MDAH 2774 ovarian carcinoma cell culture. Experimental designs were established to determine the cytotoxic effects of As(2)O(3) on MDAH 2774 cells and the IC50 (fatal dose for the 50% of cells) value. Cytotoxicity experiments were carried out using various concentrations of As(2)O(3). The 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and trypan blue dye-exclusion tests were used to evaluate cytotoxicity. Topoisomerase II expressions were investigated using western blotting method with various concentrations of As(2)O(3). Densitometric analysis of topoisomerase 2 bands was carried out using Quantity One 1-D analysis software (Bio-Rad USA, Life Science Research, Hercules, CA). IC50 value of As(2)O(3) was found to be 5 x 10(-6) M for MDAH 2774 cells. When the bands were evaluated, it was observed that there was a decrease in topoisomerase II levels in MDAH 2774 cells with increasing concentrations of As(2)O(3). It was also observed by the densitometric analysis that topoisomerase II expression ratios of MDAH 2774 cells were decreased by approximately 50% at this concentration. Topoisomerase II levels were significantly decreased with the increasing concentrations of As(2)O(3). Inhibition of topoisomerase II enzyme was one of the antiproliferative influence mechanisms of As(2)O(3). 相似文献
4.
拓扑替康在卵巢癌治疗中的新进展 总被引:1,自引:0,他引:1
拓扑替康是一种新的半合成喜树碱衍生物 ,通过抑制拓扑异构酶Ⅰ而产生抗肿瘤作用。大量研究表明拓扑替康对卵巢癌尤其是经铂类药物化疗失败 ,复发的卵巢癌患者有较好疗效。本文就拓扑替康在卵巢癌临床应用中的新进展进行综述。 相似文献
5.
The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: report of a synergistic effect between topotecan and radiation 总被引:1,自引:0,他引:1
Summary Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not made a major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors are a relatively new group of chemotherapy drugs with a novel mechanism of action. Drugs in this group currently undergoing clinical trials are the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is substantial preclinical and some clinical evidence to suggest that these drugs could be useful in the treatment of CNS malignancies. Preclinical studies with the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic activity in a variety of CNS malignancies. In addition, Topotecan has good CNS penetration in primates, and recent preliminary phase I and II clinical trials of Topotecan in pediatric and adult CNS malignancies have been promising. In this paper, we describe the unique mechanism of action, antineoplastic activity, and radiosensitizing properties of Topo I inhibitors. We present the first report demonstrating potentiation of radiation lethality by Topotecan in a human glioma (1354) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects. Two clinical trials which utilize concurrent Topotecan and radiation in the treatment of pediatric and adult CNS malignancies are discussed. 相似文献
6.
Chang HJ Batts KP Lloyd RV Sebo TJ Thompson GB Lohse CM Pankratz SV 《Endocrine pathology》2000,11(3):229-241
Nonfunctioning islet cell tumors or pancreatic endocrine tumors are the most common type of malignant islet cell tumor. Although
previously detected usually at an advanced stage because of mass effect, the early detection rate of small localized disease
has been increasing. To date it has been difficult to predict the clinical behavior in localized regional nonfunctioning tumors.
To investigate potential markers predicting malignancy and poor prognosis in nonfunctioning pancreatic endocrine tumors, we
analyzed the expression of Ki-67, topoisomerase IIα (Topollα), and p27, as well as a variety of clinicopathologic parameters
in 76 cases of nonfunctioning islet cell tumors (23 benign cases and 53 malignant cases). Ki-67, Topollα, and p27 labeling
indices were significantly different between benign and malignant tumors. Expression of Ki-67, Topollα, and p27 were associated
with survival in patients with a malignant tumor in a univariate setting. However, only p27 and Topollα were jointly associated
with survival in multivariate analysis. Immunohistochemical staining for p27, Topollα, and Ki-67 can be helpful in the diagnosis
of nonfunctioning pancreatic endocrine tumor. Analysis of p27 and Topollα may also have potential utility as prognostic factors
for malignant tumors. 相似文献
7.
Bashir Lawal Yu-Cheng Kuo Harshita Khedkar Ntlotlang Mokgautsi Maryam Rachmawati Sumitra Alexander TH Wu Hsu-Shan Huang 《American journal of cancer research》2022,12(11):5140
Acute myeloid leukemia (AML) is a type of leukemia with an aggressive phenotype, that commonly occurs in adults and with disappointing treatment outcomes. Genetic alterations were implicated in the etiology of cancers and form the basis for defining patient prognoses and guiding targeted therapies. In the present study, we leveraged bulk and single-cell RNA sequencing datasets from AML patients to determine the clinical significance of Fms-related receptor tyrosine kinase 3 (FLT3) alterations on the T-cell phenotype and immune response of AML patients. Subsequently, we evaluated the therapeutic potential of Lwk-n019, a novel small-molecule derivative of thiochromeno[2,3-c]quinolin-12-one. Our results suggested that FLT3 plays an important role in the progression, aggressive phenotype, and worse immune response of patients. An FLT3 mutation was associated with dysfunctional T-cell phenotypes, and high risk and shorter survival of AML patients. Our findings further suggested that the aggressiveness of AML and the prognostic role of FLT3 are associated with the co-occurrence of NPM1 and DNMT3A mutations. Lwk-n019 demonstrated dose-dependent anticancer activities against various leukemia cancer cell lines. Lwk-n019 demonstrated highly selective kinase inhibitory activities against the wild-type FLT3 (D835V) and mutant FLT3 (internal tandem duplication (ITD), D835V) with >95% and 99% inhibitory levels, respectively. Moreover, the compound demonstrated the best binding constant (Kd value) of 0.77 µM against FLT3 (ITD, 835V). In addition, Lwk-n019 significantly inhibited the activities of both the topoisomerase I (TOPI) and TOPII enzymes, with higher TOPI inhibitory activity than camptothecin, a clinical inhibitor. While the jejunum, duodenum, cecum, and colon were prime sites of absorption, Lwk-n019 achieved maximum concentration (Cmax), Vd, blood/plasma ratio, time to maximum concentration (Tmax), area under the receiver operating concentration curve (AUC)(0-24), and AUC(0-∞) values of 0.665 µg/mL, 5.21 Vc, L/kg, 1.5 h, 6634.7, and 6909.2, respectively. In conclusion, Lwk-n019 demonstrated anticancer activities via multi-target inhibition of TOPs and kinases with high inhibition preference for mutant ITD-FLT3. The present pioneer study provides a basis for advanced optimization of drug potency, selectivity, specificity, and other properties desired of anticancer drug leads. Studies are ongoing to determine the full therapeutic properties of Lwk-n019 and the detailed mechanisms of FLT3 in TOP inhibition. 相似文献
8.
目的研究海南地不容(Stephania hainanensis H. S. Lo et Y. Tsoong)生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的影响,筛选出有效的抗肿瘤化合物以及其敏感细胞株;分析其生物碱的构效关系。方法采用MTT法检测不同浓度的海南地不容生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的抑制率;通过查阅国内外相关文献,分析海南地不容生物碱抗肿瘤活性的基本构效关系。结果 MTT结果显示荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁对人肝癌Hep G-2、乳腺癌MCF-7和胃癌SGC-7901细胞的增值分别具有不同程度的剂量依赖性的抑制作用,各给药组分吸光度值与空白对照组比具有显著性差异(P <0. 01),与阳性对照比较无明显统计学差异(P> 0. 05);海南地不容生物碱结构中的1,2-亚甲二氧基、N-亚甲基等取代基以及其化学结构的平面性对其抗肿瘤活性有重要影响。结论海南地不容中具有明显抗肿瘤作用的生物碱为荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁,其敏感细胞株均为乳... 相似文献
9.
拓扑异构酶I(topoisomeraseI,TopoI)参与DNA复制、转录等过程,是抗癌药研究的重要靶点,其相关药物在临床肿瘤化疗中广泛应用,基于抑制拓扑异构酶I的药物设计是新型抗癌药研究的重要策略。喜树碱衍生物仍然是此类药物研究的重点,目前的研究显示,许多非喜树碱结构的化合物也表现出对TopoI的抑制作用,成为此类药物研究的新亮点。本文总结基于T0p0I作用靶点的抗癌药物的作用机制、合成设计及构效关系方面的研究进展,以期为促进相关药物研究提供参考。 相似文献
10.
DNA拓扑异构酶Ⅰ抑制剂诱导鼻咽癌上皮细胞凋亡的实验研究 总被引:1,自引:0,他引:1
拟从细胞凋亡角度出发,探讨能够诱导鼻咽癌上皮细胞凋亡的因素,为有效地防治该恶性肿瘤提供新的思路。方法:光镜下观察细胞的形态变化;流式细胞仪检测细胞周期变化及亚二倍体比例;DNA凝胶电泳及二苯胺法测定DNA片段化程度。结果:一定浓度的拓朴异构酶Ⅰ(Topoiso-meraseⅠ,TOPOⅠ)抑制剂喜树碱(Camptothecin,CPT)体外作用于人低分化鼻咽癌上皮细胞系CNE-2Z细胞一定时间后,镜下可见细胞体积缩小,染色质凝聚,胞膜突起及凋亡小体形成等形态变化。2~10μmol/L的CPT分别作用12小时后作流式细胞仪检测,亚二倍体比例均为30%左右;各浓度分别作用24小时,亚二倍体比例均为50%左右;同时细胞周期有明显的变化,主要表现为G2/M期细胞减少。DNA琼脂糖凝胶电泳呈典型的梯形带。结论:拓朴异构酶Ⅰ抑制剂CPT对人低分化鼻咽癌上皮细胞具有明显的凋亡诱导作用。 相似文献