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Breast Cancer Herceptin

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https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#1
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28826287/docetaxel-loaded-nanostructured-lipid-carriers-functionalized-with-trastuzumab-herceptin-for-her2-positive-breast-cancer-cells
#2
Jaleh Varshosaz, Mohammad Ali Davoudi, Sara Rasoul-Amini
The aim of the present study was to prepare Herceptin targeted nanostructured lipid carriers (NLCs) of docetaxel (DTX). Herceptin was conjugated by chemical and physical methods to NLCs prepared by solvent extraction technique followed by probe sonication. Different types of fatty amines were used in construction of NLCs. The NLCs were characterized for their antibody coupling efficiency, particle size, zeta potential, polydispersity index, drug entrapment efficiency and drug release profiles. The toxicity of NLCs on MDA-MB-468 (HER2 negative receptor) and BT-474 (HER2 positive) breast cancer cell lines was evaluated by MTT assay...
August 21, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28783505/surface-modification-of-docetaxel-nanocrystals-with-her2-antibody-to-enhance-cell-growth-inhibition-in-breast-cancer-cells
#3
Jin-Seok Choi, Jeong-Sook Park
Here, we describe docetaxel nanocrystals (DTX-NCs) surface-modified with Herceptin(®) (HCT) for combination cancer therapy. Using nano-precipitation and adsorption method, DTX-NCs and HCT-DTX-NCs were successfully prepared. The morphologies of DTX-NCs and HCT-DTX-NCs were characterized by field emission scanning electron microscopy (FE-SEM). The particle size and surface charge were evaluated by zeta-sizer and zeta-potential, respectively. Moreover, DTX-NCs and HCT-DTX-NCs were evaluated in terms of an in vitro drug release, cellular uptake and cytotoxicity...
July 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28663873/autofluorescence-imaging-captures-heterogeneous-drug-response-differences-between-2d-and-3d-breast-cancer-cultures
#4
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/28625777/safety-and-tolerability-of-subcutaneous-trastuzumab-for-the-adjuvant-treatment-of-human-epidermal-growth-factor-receptor-2-positive-early-breast-cancer-safeher-phase-iii-study-s-primary-analysis-of-2573-patients
#5
MULTICENTER STUDY
J Gligorov, B Ataseven, M Verrill, M De Laurentiis, K H Jung, H A Azim, N Al-Sakaff, S Lauer, M Shing, X Pivot
AIM: To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin(®) SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). METHODS: Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28624696/superimposable-outcomes-for-sequential-and-concomitant-administration-of-adjuvant-trastuzumab-in%C3%A2-her2-positive-breast-cancer-results-from-the-signal-phare-prospective-cohort
#6
RANDOMIZED CONTROLLED TRIAL
Xavier Pivot, Pierre Fumoleau, Jean-Yves Pierga, Suzette Delaloge, Hervé Bonnefoi, Thomas Bachelot, Christelle Jouannaud, Hugues Bourgeois, Maria Rios, Patrick Soulié, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Pierre Kerbrat, David Cox, Céline Faure-Mercier, Iris Pauporte, Joseph Gligorov, Elsa Curtit, Julie Henriques, Sophie Paget-Bailly, Gilles Romieu
AIM: Adjuvant clinical trials in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer have assessed either sequential or concomitant incorporation of trastuzumab with chemotherapy; only the North Central Cancer Treatment Group (NCCTG)-N9831 trial prospectively compared both modalities. In routine trastuzumab has been incorporated into a concurrent regimen with taxane chemotherapy instead of sequential modality on the basis of a positive risk-benefit ratio. This present study assessed sequential versus concomitant administration of adjuvant trastuzumab...
August 2017: European Journal of Cancer
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
#7
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...
June 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28454094/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#8
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28377827/anti-yo-mediated-paraneoplastic-cerebellar-degeneration-associated-with-pseudobulbar-affect-in-a-patient-with-breast-cancer
#9
Allison N Martin, Patrick M Dillon, David E Jones, David R Brenin, David A Lapides
Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28335434/induction-of-g2m-arrest-by-flavokawain-a-a-kava-chalcone-increases-the-responsiveness-of-her2-overexpressing-breast-cancer-cells-to-herceptin
#10
Danielle D Jandial, Lauren S Krill, Lixia Chen, Chunli Wu, Yu Ke, Jun Xie, Bang H Hoang, Xiaolin Zi
HER2/neu positive breast tumors predict a high mortality and comprise 25%-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2-overexpressing breast cancer cell lines (i.e., SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e., MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has a minimal effect on the growth of non-malignant breast epithelial MCF10A cells. FKA induces G2M arrest in cell cycle progression of HER2-overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and downregulation of expression of Myt1 and Wee1 leading to increased Cdc2 kinase activities...
March 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28327075/magnetic-nanobubbles-with-potential-for-targeted-drug-delivery-and-trimodal-imaging-in-breast-cancer-an-in-vitro-study
#11
Weixiang Song, Yindeng Luo, Yajing Zhao, Xinjie Liu, Jiannong Zhao, Jie Luo, Qunxia Zhang, Haitao Ran, Zhigang Wang, Dajing Guo
AIM: The aim of this study was to improve tumor-targeted therapy for breast cancer by designing magnetic nanobubbles with the potential for targeted drug delivery and multimodal imaging. MATERIALS & METHODS: Herceptin-decorated and ultrasmall superparamagnetic iron oxide (USPIO)/paclitaxel (PTX)-embedded nanobubbles (PTX-USPIO-HER-NBs) were manufactured by combining a modified double-emulsion evaporation process with carbodiimide technique. PTX-USPIO-HER-NBs were examined for characterization, specific cell-targeting ability and multimodal imaging...
May 2017: Nanomedicine
https://www.readbyqxmd.com/read/28286614/is-there-any-concordance-between-of-ihc-with-fish-in-her2-positive-breast-cancer-patients
#12
Mehrdad Payandeh, Masoud Sadeghi, Edris Sadeghi, Alireza Janbakhsh
Background: In developed or developing countries, the most common cancer in women is breast cancer with a pick in 40-50 years in Asia. Herein, we compared the association between IHC with FISH in HER2-positive breast cancer patients and affection of trastuzumab on disease free survival and overall survival (OS). Subjects and Methods: Immunohistochemical (IHC) analysis of hormone receptors and HER2 was performed in 133 patients with breast cancer between 2003 and 2014. Patients were selected for Herceptin adjuvant treatment, according to IHC 3+ or FISH+...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28247220/what-quality-of-life-issues-do-women-with-ductal-carcinoma-in-situ-dcis-consider-important-when-making-treatment-decisions
#13
Rebecca Mercieca-Bebber, Madeleine T King, Miriam M Boxer, Andrew Spillane, Zoë E Winters, Phyllis N Butow, Joan McPherson, Claudia Rutherford
PURPOSE: To explore quality-of-life (QOL) issues considered important when deciding on treatment for ductal carcinoma in situ (DCIS). METHODS: Breast Cancer Network of Australia members diagnosed with DCIS in the past 5 years (self-identified) participated in an online survey (Sep-Nov 2015). From a list of 74 QOL issues, participants selected all issues they experienced during DCIS diagnosis, treatment or recovery, then the issues they felt important to making a DCIS treatment decision, and completed the Health Literacy Questionnaire (HLQ)...
February 28, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28223691/cellular-glycosylation-affects-herceptin-binding-and-sensitivity-of-breast-cancer-cells-to-doxorubicin-and-growth-factors
#14
Diluka Peiris, Alexander F Spector, Hannah Lomax-Browne, Tayebeh Azimi, Bala Ramesh, Marilena Loizidou, Hazel Welch, Miriam V Dwek
Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28215665/11-years-follow-up-of-trastuzumab-after-adjuvant-chemotherapy-in-her2-positive-early-breast-cancer-final-analysis-of-the-herceptin-adjuvant-hera-trial
#15
David Cameron, Martine J Piccart-Gebhart, Richard D Gelber, Marion Procter, Aron Goldhirsch, Evandro de Azambuja, Gilberto Castro, Michael Untch, Ian Smith, Luca Gianni, Jose Baselga, Nedal Al-Sakaff, Sabine Lauer, Eleanor McFadden, Brian Leyland-Jones, Richard Bell, Mitch Dowsett, Christian Jackisch
BACKGROUND: Clinical trials have shown that trastuzumab, a recombinant monoclonal antibody against HER2 receptor, significantly improves overall survival and disease-free survival in women with HER2-positive early breast cancer, but long-term follow-up data are needed. We report the results of comparing observation with two durations of trastuzumab treatment at a median follow-up of 11 years, for patients enrolled in the HERA (HERceptin Adjuvant) trial. METHODS: HERA (BIG 1-01) is an international, multicentre, open-label, phase 3 randomised trial of 5102 women with HER2-positive early breast cancer, who were enrolled from hospitals in 39 countries between Dec 7, 2001, and June 20, 2005...
March 25, 2017: Lancet
https://www.readbyqxmd.com/read/28199174/role-of-troponins-i-and-t-and-n-terminal-prohormone-of-brain-natriuretic-peptide-in-monitoring-cardiac-safety-of-patients-with-early-stage-human-epidermal-growth-factor-receptor-2-positive-breast-cancer-receiving-trastuzumab-a-herceptin-adjuvant-study-cardiac
#16
Dimitrios Zardavas, Thomas M Suter, Dirk J Van Veldhuisen, Jutta Steinseifer, Johannes Noe, Sabine Lauer, Nedal Al-Sakaff, Martine J Piccart-Gebhart, Evandro de Azambuja
Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study...
March 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28197225/herceptin-responsive-lung-adenocarcinoma-in-the-setting-of-bilateral-synchronous-lung-primaries-and-breast-carcinoma
#17
Gerard J Fitzmaurice, Michael Moore, Waris Ahmad, Ronan J Ryan
The incidence of human epidermal growth factor receptor 2 (Her-2) mutations in lung adenocarcinoma is approximately 3%; however, its significance in the management of these lung cancers remains under investigation. We describe an incidental but unique opportunity to evaluate the response to treatment with herceptin in a patient with bilateral synchronous lung primaries in conjunction with breast carcinoma. Interval imaging following surgical resection of the squamous cell carcinoma while on herceptin treatment delineated the radiological regression of the Her-2 positive lung adenocarcinoma...
January 2017: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/28191701/near-infrared-light-and-ph-dual-responsive-targeted-drug-carrier-based-on-core-crosslinked-polyaniline-nanoparticles-for-intracellular-delivery-of-cisplatin
#18
Chaoqun You, Hongshuai Wu, Minxing Wang, Yawen Zhang, Jingwen Wang, Yanghui Luo, Lihai Zhai, Baiwang Sun, Xiangyang Zhang, Jin Zhu
Biodegradable polymeric nanoparticles have received growing interest as one of the most promising agents for drug delivery. In the present work, functional and core-crosslinked poly(ethylene glycol) with poly(ϵ-caprolactone) (PEG5k -PCL10k ) block copolymer and lecithin as biodegradable polymer doped with polyaniline was used to assemble nanoparticles which were prepared for targeted delivery and controlled release of cisplatin. The morphology of the polyaniline nanoparticles was determined by dynamic light scattering and the prepared nanoparticles showed a size of 83(±1) nm and a uniform spherical shape...
February 13, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28156181/formation-of-multimeric-antibodies-for-self-delivery-of-active-monomers
#19
Yaron Dekel, Yossy Machluf, Tal Gefen, Gennady Eidelshtein, Alexander Kotlyar, Yaron Bram, Ehud Shahar, Farah Reslane, Elina Aizenshtein, Jacob Pitcovski
Proteins and peptides have been used as drugs for almost a century. Technological advances in the past 30 years have enabled the production of pure, stable proteins in vast amounts. In contrast, administration of proteins based on their native active conformation (and thus necessitating the use of subcutaneous injections) has remained solely unchanged. The therapeutic anti-HER2 humanized monoclonal immunoglobulin (IgG) Trastuzumab (Herceptin) is a first line of the treatment for breast cancer. Chicken IgY is a commercially important polyclonal antibody (Ab)...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28111342/development-of-a-highly-specific-her2-monoclonal-antibody-for-immunohistochemistry-using-protein-microarray-chips
#20
Lili Qi, Lixin Zhou, Mingmin Lu, Kehu Yuan, Zhongwu Li, Guiyin Wu, Xiaozheng Huang, Yi Shen, Min Zhao, Wei Fu, Boyang Chu, Guangli Wang, Fangfang Ren, Donghui Ma, Jian Chen
HER2 is an orphan receptor tyrosine kinase of the EGFR families and is considered to be a key tumor driver gene [1]. Breast cancer and gastric cancer with HER2 amplification can be effectively treated by its neutralizing antibody, Herceptin. In clinic, Immunohistochemistry (IHC) was used as the primary screening method to diagnose HER2 amplification [2]. However, recent evidence suggested that the frequently used rabbit HER2 antibody 4B5 cross reacted with another family member HER4 [3]. IHC staining with 4B5 also indicated that there was strong non-specific cytoplasmic and nuclear signals in normal gastric mucosal cells and some gastric cancer samples...
March 4, 2017: Biochemical and Biophysical Research Communications
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