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Herceptin resistance

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https://www.readbyqxmd.com/read/29736306/lmo4-mediates-trastuzumab-resistance-in-her2-positive-breast-cancer-cells
#1
Keshuo Ding, Zhengsheng Wu, Xiaocan Li, Youjing Sheng, Xiaonan Wang, Sheng Tan
Breast cancer is the leading cause of cancer-related mortality in women worldwide. Trastuzumab (Herceptin) is an effective antibody drug for HER2 positive breast cancer; de novo or acquired trastuzumab resistance retarded the use of trastuzumab for at least 70% of HER2 positive breast cancers. In this study, we reported LMO4 (a member of LIM-only proteins) promoted trastuzumab resistance in human breast cancer cells. Over-expression of LMO4 was observed in acquired trastuzumab resistance breast cancer cells SKBR3 HR and BT474 HR...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29671404/regulation-of-dual-specificity-phosphatases-in-breast-cancer-during-initial-treatment-with-herceptin-a-boolean-model-analysis
#2
Petronela Buiga, Ari Elson, Lydia Tabernero, Jean-Marc Schwartz
BACKGROUND: 25% of breast cancer patients suffer from aggressive HER2-positive tumours that are characterised by overexpression of the HER2 protein or by its increased tyrosine kinase activity. Herceptin is a major drug used to treat HER2 positive breast cancer. Understanding the molecular events that occur when breast cancer cells are exposed to Herceptin is therefore of significant importance. Dual specificity phosphatases (DUSPs) are central regulators of cell signalling that function downstream of HER2, but their role in the cellular response to Herceptin is mostly unknown...
April 11, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29574771/monoclonal-antibody-based-therapeutics-targeting-the-epidermal-growth-factor-receptor-family-from-herceptin-to-pan-her
#3
REVIEW
Shima Moradi-Kalbolandi, Aysooda Hosseinzade, Malihe Salehi, Parnaz Merikhian, Leila Farahmand
OBJECTIVES: Monoclonal antibody-based of cancer therapy has been considered as one of the most successful therapeutic strategies for both haematologic malignancies and solid tumours in the last two decades. Epidermal growth factor receptor (EGFR) family signalling pathways play a key role in the regulation of cell proliferation, survival and differentiation. Hence, anti-EGFR family mAbs is one of the most promising approaches in cancer therapy. KEY FINDINGS: Here, recent advances in anti-EGFR mAb including approved or successfully tested in preclinical and clinical studies have been reviewed...
March 25, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29534020/copper-free-click-chemistry-based-synthesis-and-characterization-of-carbonic-anhydrase-ix-anchored-albumin-paclitaxel-nanoparticles-for-targeting-tumor-hypoxia
#4
Katyayani Tatiparti, Samaresh Sau, Kaustubh A Gawde, Arun K Iyer
Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of the logical and economical approaches is to develop a tumor hypoxia-targeting drug formulation platform for selective delivery of payload to the drug-resistant and invasive cell population of TNBC tumors...
March 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29434878/progesterone-impairs-herceptin-effect-on-breast-cancer-cells
#5
Kamila Kitowska, Agnieszka Kowalska, Magdalena Mieszkowska, Dominika Piasecka, Andrzej C Skladanowski, Hanna M Romanska, Rafal Sadej
Breast cancer (BCa) is the most common cancer affecting women worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in ~20-25% of invasive ductal breast carcinomas and is associated with the more aggressive phenotype. Herceptin, a humanized antibody against HER2, is a standard therapy in HER2-overexpressing cases. Approximately one-third of patients relapse despite treatment. Therefore numerous studies have investigated the molecular mechanisms associated with Herceptin resistance...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29408336/long-non-coding-rna-uca1-desensitizes-breast-cancer-cells-to-trastuzumab-by-impeding-mir-18a-repression-of-yes-associated-protein-1
#6
Hua-Yu Zhu, Wen-Dong Bai, Xing-Ming Ye, An-Gang Yang, Lin-Tao Jia
Breast cancer resistance to the monoclonal erbB2/HER2 antibody trastuzumab (or herceptin) has become a significant obstacle in clinical targeted therapy of HER2-positive breast cancer. Previous research demonstrated that such drug resistance may be related to dysregulation of miRNA expression. Here, we found that knockdown of the long non-coding RNA, urothelial cancer associated 1 (UCA1), can promote the sensitivity of human breast cancer cells to trastuzumab. Mechanistically, UCA1 knockdown upregulated miR-18a and promoted miR-18a repression of Yes-associated protein 1 (YAP1)...
February 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#7
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
March 2018: Oncogene
https://www.readbyqxmd.com/read/29281678/the-natural-compound-jatrophone-interferes-with-wnt-%C3%AE-catenin-signaling-and-inhibits-proliferation-and-emt-in-human-triple-negative-breast-cancer
#8
Iram Fatima, Ikbale El-Ayachi, Ling Taotao, M Angeles Lillo, Raya Krutilina, Tiffany N Seagroves, Tomasz W Radaszkiewicz, Miroslav Hutnan, Vitezslav Bryja, Susan A Krum, Fatima Rivas, Gustavo A Miranda-Carboni
Metastatic breast cancer is the leading cause of worldwide cancer-related deaths among women. Triple negative breast cancers (TNBC) are highly metastatic and are devoid of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) amplification. TNBCs are unresponsive to Herceptin and/or anti-estrogen therapies and too often become highly chemoresistant when exposed to standard chemotherapy. TNBCs frequently metastasize to the lung and brain. We have previously shown that TNBCs are active for oncogenic Wnt10b/β-catenin signaling and that WNT10B ligand and its downstream target HMGA2 are predictive of poorer outcomes and are strongly associated with chemoresistant TNBC metastatic disease...
2017: PloS One
https://www.readbyqxmd.com/read/28945315/quantitating-adcc-against-adherent-cells-impedance-based-detection-is-superior-to-release-membrane-permeability-or-caspase-activation-assays-in-resolving-antibody-dose-response
#9
Gábor Tóth, János Szöllősi, György Vereb
Monoclonal antibody-based immunotherapeutics will dominate Pharma's next generation of blockbuster drugs, and Fc-associated functions, including antibody dependent cellular cytotoxicity (ADCC) are among the highly desired activities mediated by these antibodies. Therefore, quantitative evaluation of ADCC is required during drug development. Our objective was to find the most suitable and reliable nonradioactive method for quantitative analysis of in vitro ADCC against adherent cells, which often serve as models for solid tumors...
September 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28663873/autofluorescence-imaging-captures-heterogeneous-drug-response-differences-between-2d-and-3d-breast-cancer-cultures
#10
T M Cannon, A T Shah, M C Skala
Two-photon microscopy of cellular autofluorescence intensity and lifetime (optical metabolic imaging, or OMI) is a promising tool for preclinical drug development. OMI, which exploits the endogenous fluorescence from the metabolic coenzymes NAD(P)H and FAD, is sensitive to changes in cell metabolism produced by drug treatment. Previous studies have shown that drug response, genetic expression, cell-cell communication, and cell signaling in 3D culture match those of the original in vivo tumor, but not those of 2D culture...
March 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28623430/a-phase-i-ii-study-of-suberoylanilide-hydroxamic-acid-saha-in-combination-with-trastuzumab-herceptin-in-patients-with-advanced-metastatic-and-or-local-chest-wall-recurrent-her2-amplified-breast-cancer-a-trial-of-the-ecog-acrin-cancer-research-group-e1104
#11
Lori J Goldstein, Fengmin Zhao, Molin Wang, Ramona F Swaby, Joseph A Sparano, Neal J Meropol, Kapil N Bhalla, Christine M Pellegrino, R Katherine Alpaugh, Carla I Falkson, Paula Klein, George W Sledge
PURPOSE: Suberoylanilide hydroxamic acid (SAHA; vorinostat), a small molecule inhibitor of histone deacetylase, attenuates signaling pathways known to confer trastuzumab resistance. A combination of SAHA and trastuzumab may be a promising strategy to improve the efficacy of trastuzumab against breast cancer. In this Phase I/II study, we evaluated the toxicity and response rate after treatment with SAHA and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with trastuzumab-resistant progressive disease...
September 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28045951/an-experimental-analysis-of-the-molecular-effects-of-trastuzumab-herceptin-and-fulvestrant-falsodex-as-single-agents-or-in-combination-on-human-hr-her2-breast-cancer-cell-lines-and-mouse-tumor-xenografts
#12
Qing Chen, Ziyi Weng, Yunshu Lu, Yijun Jia, Longlong Ding, Fang Bai, Meixin Ge, Qing Lin, Kejin Wu
PURPOSE: To investigate the effects of trastuzumab (herceptin) and fulvestrant (falsodex) either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue. METHODS: Cells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecular events that resulted in an inhibition of cell proliferation and cell cycle progression or in an increased rate of apoptosis were studied...
2017: PloS One
https://www.readbyqxmd.com/read/27993117/role-of-genomic-alterations-in-her2-positive-breast-carcinoma-focus-on-susceptibility-and-trastuzumab-therapy
#13
Heena Singla, Sourav Kalra, Preeti Kheterpal, Vinod Kumar, Anjana Munshi
BACKGROUND: Breast cancer is the most frequently diagnosed life-threatening malignancy among women, across the globe. HER2 positive is a distinct breast cancer subtype, on account of its unique biology and physiological behavior. RESULTS: Amplification of HER2 oncogene/polysomy 17 leads to HER2 overexpression that is a significant causal implication in HER2 positive breast cancer. HER2 gene variants, as well as other genes/gene variants, are involved in its overexpression, disease prognosis and in predicting the susceptibility towards HER2 positive breast cancer...
2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27813707/development-and-preclinical-studies-of-64-cu-nota-pertuzumab-f-ab-2-for-imaging-changes-in-tumor-her2-expression-associated-with-response-to-trastuzumab-by-pet-ct
#14
Karen Lam, Conrad Chan, Raymond M Reilly
We previously reported that microSPECT/CT imaging with 111 In-labeled pertuzumab detected decreased HER2 expression in human breast cancer (BC) xenografts in athymic mice associated with response to treatment with trastuzumab (Herceptin). Our aim was to extend these results to PET/CT by constructing F(ab')2 of pertuzumab modified with NOTA chelators for complexing 64 Cu. The effect of the administered mass (5-200 µg) of 64 Cu-NOTA-pertuzumab F(ab')2 was studied in NOD/SCID mice engrafted with HER2-positive SK-OV-3 human ovarian cancer xenografts...
January 2017: MAbs
https://www.readbyqxmd.com/read/27770268/sensitizing-effect-of-juglone-is-mediated-by-down-regulation-of-notch1-signaling-pathway-in-trastuzumab-resistant-skbr3-cells
#15
Soraya Sajadimajd, Razieh Yazdanparast
Trastuzumab (Herceptin) monoclonal antibody directed against HER2 receptor has been administered as a treatment for metastatic HER2 positive breast cancer. The problematic issue in treatment of HER2 positive breast cancer cells is commonly the induction of resistance to trastuzumab which might be due to modulation of some vital signaling elements such as Notch1 and Pin1. In this study, we were aimed to investigate whether the cross talk between pin1 and Notch1 has a role in this event. Our results indicated that the expression level of Pin1 in resistant SKBR3 cells increased by about twofold relative to sensitive SKBR3 cells...
January 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27726101/lapatinib-resistance-in-her2-cancers-latest-findings-and-new-concepts-on-molecular-mechanisms
#16
REVIEW
Huiping Shi, Weili Zhang, Qiaoming Zhi, Min Jiang
In the era of new and mostly effective molecular targeted therapies, human epidermal growth factor receptor 2 positive (HER2+) cancers are still intractable diseases. Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor, has greatly improved breast cancer prognosis in recent years after the initial introduction of trastuzumab (Herceptin). However, clinical evidence indicates the existence of both primary unresponsiveness and secondary lapatinib resistance, which leads to the failure of this agent in HER2+ cancer patients...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27721408/cytoplasmic-gper-translocation-in-cancer-associated-fibroblasts-mediates-camp-pka-creb-glycolytic-axis-to-confer-tumor-cells-with-multidrug-resistance
#17
T Yu, G Yang, Y Hou, X Tang, C Wu, X-A Wu, L Guo, Q Zhu, H Luo, Y-E Du, S Wen, L Xu, J Yin, G Tu, M Liu
Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs...
April 2017: Oncogene
https://www.readbyqxmd.com/read/27669438/cxcr4-inhibitors-could-benefit-to-her2-but-not-to-triple-negative-breast-cancer-patients
#18
S Lefort, A Thuleau, Y Kieffer, P Sirven, I Bieche, E Marangoni, A Vincent-Salomon, F Mechta-Grigoriou
The CXCR4 receptor and its ligand CXCL12 (also named stromal cell-derived factor 1, SDF1) have a critical role in chemotaxis and homing, key steps in cancer metastasis. Although myofibroblasts expressing CXCL12 are associated with the presence of axillary metastases in HER2 breast cancers (BC), the therapeutic interest of targeting CXCR4/CXCL12 axis in the different BC subtypes remains unclear. Here, we investigate this question by testing antitumor activity of CXCR4 inhibitors in patient-derived xenografts (PDX), which faithfully reproduce human tumor properties...
March 2, 2017: Oncogene
https://www.readbyqxmd.com/read/27318091/downregulation-of-microrna-206-promotes-invasion-and-angiogenesis-of-triple-negative-breast-cancer
#19
Zhongxing Liang, Xuehai Bian, Hyunsuk Shim
Triple negative breast tumors don't respond to Tamoxifen and Herceptin, two of the most effective medications for treating breast cancer. Additionally, triple negative breast cancer (TNBC) intrinsically resists or will eventually acquire resistance to chemotherapy. The purpose of this study is to understand better the molecular basis of TNBC as well as develop new therapeutic strategies against it. Here, we analyzed miRNA-206 expression levels in breast cancer cell lines and tissues. In addition, we investigated whether miR-206 mimics inhibited TNBC tumor invasion and angiogenesis...
August 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27304609/novel-hybrid-compound-of-a-plinabulin-prodrug-with-an-igg-binding-peptide-for-generating-a-tumor-selective-noncovalent-type-antibody-drug-conjugate
#20
Kyohei Muguruma, Fumika Yakushiji, Ryosuke Kawamata, Daichi Akiyama, Risako Arima, Takuya Shirasaka, Yamato Kikkawa, Akihiro Taguchi, Kentaro Takayama, Takeshi Fukuhara, Tetsuro Watabe, Yuji Ito, Yoshio Hayashi
Although several approaches for making antibody-drug conjugates (ADC) have been developed, it has yet to be reported that an antibody binding peptide such as Z33 from protein A is utilized as the pivotal unit to generate the noncovalent-type ADC (NC-ADC). Herein we aim to establish a novel probe for NC-ADC by synthesizing the Z33-conjugated antitumor agent, plinabulin. Due to the different solubility of two components, including hydrophobic plinabulin and hydrophilic Z33, an innovative method with a solid-supported disulfide coupling reagent is required for the synthesis of the target compounds with prominent efficiency (29% isolated yield)...
July 20, 2016: Bioconjugate Chemistry
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