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P-glycoprotein mdr breast cancer immunohistochemistry tumor

Fengchun Tian, Fatima Zohra Dahmani, Jianan Qiao, Jiang Ni, Hui Xiong, Tengfei Liu, Jianping Zhou, Jing Yao
Several obstacles are currently impeding the successful treatment of breast cancer, namely impaired drug accumulation into the tumor site, toxicity to normal cells and narrow therapeutic index of chemotherapy, multidrug resistance (MDR) and the metastatic spread of cancer cells through the blood and lymphatic vessels. In this regard, we designed a novel multifunctional nano-sized drug delivery system based on LyP-1 peptide-modified low-molecular-weight heparin-quercetin conjugate (PLQ). This nanosystem was developed for targeted co-delivery of multiple anticancer drugs to p32-overexpressing tumor cells and peritumoral lymphatic vessels, using LyP-1 peptide as active targeting ligand, with the aim to achieve a targeted combinatorial chemo/angiostatic therapy and MDR reversal...
June 3, 2018: Acta Biomaterialia
Anna M Badowska-Kozakiewicz, Maria Sobol, Janusz Patera
Introduction: Overexpression of the mdr-1 gene is the earliest discovered mechanism of multidrug resistance, which is associated with P-glycoprotein (P-gp) - a cell membrane protein responsible for the efflux of drugs of various structures out of cancer cells. Although the expression of P-glycoprotein has been demonstrated in many cancer types, its relation to markers of hypoxia such as HIF-1α, EPO-R or EPO in invasive breast cancer is not well established. The aim of this research was to analyze the co-expression of P-glycoprotein and the markers of tissue hypoxia HIF-1α, EPO, and EPO-R by immunohistochemistry in invasive breast cancer classified according to the presence of steroid receptors and the HER2 receptors...
October 2017: Archives of Medical Science: AMS
C Li, H-G Xue, L-J Feng, M-L Wang, P Wang, X-D Gai
OBJECTIVE: Multidrug resistance (MDR) is a major cause of chemotherapy failure in the treatment of cancer patients. This study aimed to determine whether saikosaponin D (SSd) can enhance the efficacy of the anticancer drug doxorubicin (Dox) both in vitro and in vivo and whether SSd can alter Dox pharmacokinetics in the serum of mice. MATERIALS AND METHODS: MCF-7/adr cells were used to investigate the effect of SSd on reversing MDR. Cell viability was assessed by MTT assay...
October 2017: European Review for Medical and Pharmacological Sciences
Wenjuan Wang, Liping Zou, Danmei Zhou, Zhongwen Zhou, Feng Tang, Zude Xu, Xiuping Liu
Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp) exhibit enhanced invasive/metastatic ability as compared with the sensitive cells. We aimed to clarify the mechanism underlying this observation and found that during the development of drug resistance to adriamycin in MCF7 cells, the elevated expression of UCH-L1 coincides with the up-regulation of MDR1, CD147, MMP2, and MMP9 as well as increased cellular migration/invasion. Overexpression of UCH-L1 in MCF7 cells up-regulated MDR1, CD147, MMP2, and MMP9, which conferred MDR and promoted migration/invasion...
September 2016: Molecular Carcinogenesis
Weiquan Li, Maomin Song
Chemotherapy is commonly used for the treatment of breast cancer. However, the resistance to chemotherapeutic agents, often mediated by multidrug resistance (MDR) mechanisms, is a common occurrence. The present study examined the expression of several MDR-related proteins (MRPs) in invasive ductal carcinoma (IDC) of the breast, and assessed their association with clinicopathological variables and their prognostic significance. In addition, immunohistochemistry was used to measure the expression of MRP, p-glycoprotein (P-gp), topoisomerase 2α (Topo2α), thymidylate synthase (TS) and glutathione-S-transferase π (GST-π) in 156 resected IDCs of the breast...
November 2014: Oncology Letters
Ting Yang, Fei Chen, Feifei Xu, Fengliang Wang, Qingqing Xu, Yun Chen
BACKGROUND: P-glycoprotein (P-gp) can efflux drugs from cancer cells, and its overexpression is commonly associated with multi-drug resistance (MDR). Thus, the accurate quantification of P-gp would help predict the response to chemotherapy and for prognosis of breast cancer patients. METHODS: An advanced liquid chromatography-tandem mass spectrometry (LC/MS/MS)-based targeted proteomics assay was developed and validated for monitoring P-gp levels in breast tissue...
September 25, 2014: Clinica Chimica Acta; International Journal of Clinical Chemistry
Wen-Rui Wu, Rui Zhang, Xiang-De Shi, Man-Sheng Zhu, Lei-Bo Xu, Hong Zeng, Chao Liu
The Notch signaling pathway has been reported to play crucial roles in inhibiting hepatocyte differentiation and allowing formation of intrahepatic bile ducts. However, little is known about its significance in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to investigate the effects of Notch1 expression in ICC tissues and cells. The expression of Notch1 was examined in paraffin-embedded sections of ICC (n=44) by immunohistochemistry. Notch1 was knocked down by RNA interference (RNAi) in cultured ICC cells (RBE and HCCC-9810)...
June 2014: Oncology Reports
Si-Ying Chen, Sa-Sa Hu, Qian Dong, Jiang-Xia Cai, Wei-Peng Zhang, Jin-Yao Sun, Tao-Tao Wang, Jiao Xie, Hai-Rong He, Jian-Feng Xing, Jun Lu, Ya-Lin Dong
BACKGROUND: Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. METHODS: The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX...
2013: Asian Pacific Journal of Cancer Prevention: APJCP
Sang Hyub Lee, Haeryoung Kim, Jin-Hyeok Hwang, Hye Seung Lee, Jai Young Cho, Yoo-Seok Yoon, Ho-Seong Han
The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal even after complete resection, with most recurrences occurring within 1-2 years postoperatively. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been demonstrated to play major roles in multidrug resistance (MDR) of cancers. In this study, we evaluated the expression statuses and the clinical significance of MDR1 (ABCB1), MDR-associated proteins (MRPs/ABCC) 1, 2 and 3, and breast cancer resistance protein (BCRP/ABCG2) in 67 surgically resected PDACs by immunohistochemistry...
March 2012: Pathology International
Lara Milane, Zhenfeng Duan, Mansoor Amiji
The treatment of multi-drug resistant (MDR) cancer is a clinical challenge. Many MDR cells over-express epidermal growth factor receptor (EGFR). We exploit this expression through the development of EGFR-targeted, polymer blend nanocarriers for the treatment of MDR cancer using paclitaxel (a common chemotherapeutic agent) and lonidamine (an experimental drug; mitochondrial hexokinase 2 inhibitor). An orthotopic model of MDR human breast cancer was developed in nude mice and used to evaluate the safety and efficacy of nanoparticle treatment...
2011: PloS One
N Yu Lukyanova, N V Rusetskya, N A Tregubova, V F Chekhun
AIM: To compare ultrastructure, phenotypic profile and cell cycle progression of MCF-7 human breast cancer cells and MCF7 sublines resistant to cisplatin (MCF-7/DDP) and doxorubicin (MCF-7/DOX). METHODS: MTT-test, immunocytochemistry, flow cytometry, electron microscopy. RESULTS: The development of drug resistance to cisplatin and doxorubicin in MCF-7 cells upon the culturing of the initial cells with the raising concentrations of cytostatics was accompanied by the increase in cells adhesion, the increasing differentiation grade and the loss of steroid hormone receptors...
June 2009: Experimental Oncology
Arzu Saglam, Mutlu Hayran, Aysegul H Uner
Multidrug resistance (MDR) is defined as resistance of tumor cells to a wide spectrum of structurally and functionally unrelated drugs. One of the most important mechanisms in mediating MDR is that involving cellular drug efflux transporters. Drug resistance is a common and formidable obstacle to therapy in mature T/NK-cell lymphomas and the MDR phenotype is thought to be one of the contributing mechanisms. In this study we assessed the immunohistochemical expression of P-gp (P-glycoprotein), MRP-1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) in 45 mature T/NK-cell lymphomas diagnosed at our hospital...
September 2008: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
S B Sergieva, K V Timcheva, N D Hadjiolov
PURPOSE: To evaluate the clinical application of (99m) Tc-methoxyisobutylisonitrile (MIBI) scintigraphy as a functional method for assessment of multidrug resistance (MDR) in breast cancer patients and the correlation of these results with P-glycoprotein (P-gp) overexpression and objective response to chemotherapy. PATIENTS AND METHODS: 22 women, 35-68 years old with breast cancer, suitable for neoadjuvant chemotherapy were included onto this study. Two or three cycles of neoadjuvant chemotherapy were administered (FEC in 15 and CMF in 7 patients)...
January 2006: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
S Rybárová, I Hodorová, M Hajduková, K Schmidtová, J Mojzis, K Kajo, Z Kviatkovská, L Plank, M Benický, A Mirossay, E Biros, N Bobrov, M Wagnerová, A Berc, L Mirossay
The aim of this work was to determine the expression of the multidrug resistance (MDR) proteins, namely MDR1 (P-glycoprotein), MRP1 (multidrug resistance-related protein) and LRP (lung resistance-related protein), in 87 samples of breast carcinoma. Detection of these proteins was provided by using indirect enzymatic immunohistochemistry. Our findings were compared with the other clinical and pathological parameters: expression of Her2/neu, estrogen receptor status (ER), progesteron receptor status (PR), histological grade and regional lymph node status...
2006: Neoplasma
Federica Di Nicolantonio, Stuart J Mercer, Louise A Knight, Francis G Gabriel, Pauline A Whitehouse, Sanjay Sharma, Augusta Fernando, Sharon Glaysher, Silvana Di Palma, Penny Johnson, Shaw S Somers, Simon Toh, Bernie Higgins, Alan Lamont, Tim Gulliford, Jeremy Hurren, Constantinos Yiangou, Ian A Cree
BACKGROUND: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. METHODS: Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days)...
July 18, 2005: BMC Cancer
Eleonora Aronica, Jan A Gorter, Sandra Redeker, Erwin A van Vliet, Marja Ramkema, George L Scheffer, Rik J Scheper, Paul van der Valk, Sieger Leenstra, Johannes C Baayen, Wim G M Spliet, Dirk Troost
PURPOSE: Breast cancer resistance protein (BCRP) is a half adenosine triphosphate (ATP)-binding cassette (ABC) transporter expressed on cellular membranes and included in the group of multidrug resistant (MDR)-related proteins. Recently, upregulation of different MDR proteins has been shown in human epilepsy-associated conditions. This study investigated the expression and cellular distribution of BCRP in human control and epileptic brain, including a large number of both neoplastic and nonneoplastic specimens from patients with chronic pharmacoresistant epilepsy...
June 2005: Epilepsia
Federica Di Nicolantonio, Louise A Knight, Pauline A Whitehouse, Stuart J Mercer, Sanjay Sharma, Peter A Charlton, David Norris, Ian A Cree
XR5944 (MLN944) is a novel DNA targeting agent with potent antitumor activity, both in vitro and in vivo, against several murine and human tumor models. We have used an ATP-tumor chemosensitivity assay to assess the ex vivo sensitivity of a variety of solid tumors (n = 90) and a CCRF-CEM leukemia cell line selected with XR5944. Differences in gene expression between the parental CCRF-CEM and the resistant subline were investigated by quantitative reverse transcription-PCR. Immunohistochemistry for topoisomerases I and IIalpha and multidrug resistance (MDR1) protein was done on those tumors for which tissue was available (n = 32)...
December 2004: Molecular Cancer Therapeutics
Jing Jin, Feng-Peng Wang, Huailing Wei, Gengtao Liu
PURPOSE: The present study aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), in vitro and in vivo. METHODS: Drug sensitivity was determined using the MTT assay. The in vivo effect of Tet was investigated using nude mice grafted with sensitive and resistant KB human epidermoid cancer cells. Doxorubicin (Dox) accumulation was analyzed by fluorospectrophotometry and the protein and mRNA levels of P-glycoprotein (P-gp) were determined by immunocytochemistry and RT-PCR, respectively...
February 2005: Cancer Chemotherapy and Pharmacology
Muhammad Mubashar, Kevin J Harrington, Khurram S Chaudhary, El-Nasir Lalani, Gordon W Stamp, A Michael Peters
The effect of toremifene on P-glycoprotein-mediated multidrug resistance (MDR) in breast and head and neck cancer cell lines was measured in vitro and in vivo. Pgp expression was low and high, respectively, in drug-sensitive (MCF7-S, KB) and drug-resistant (MCF7-R, MCF7-R1, KBV1) cell lines. Toremifene (7.5 microM) significantly enhanced cytoplasmic and nuclear accumulation of doxorubicin in drug-resistant cells. Toremifene (10 microM) increased the in vitro cytotoxicity of doxorubicin in drug-resistant breast cancer cells (13-fold and 21-fold for MCF7-R and MCF7-R1, respectively) without affecting the sensitivity of MCF7-S cells...
2004: Acta Oncologica
Xue-mei Zhang, Zhen-wei Zhang, Hua Wu
OBJECTIVE: To assess the correlation between uptake of (99)Tc(m)-MIBI and expression level of multidrug resistant protein in breast cancer. METHODS: Thirty pathologically confirmed patients with primary invasive ductal carcinoma were examined by (99)Tc(m)-MIBI scintigraphy at 15 min and 90 min after injecting the tracer. The uptake of (99)Tc(m)-MIBI at the region of interest (ROI) was evaluated as tumor to normal background (T/N) ratio. Retention index (RI) was calculated from the early uptake ratio (EUR) and updelayed take ratio (DUR)...
June 2004: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
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