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https://www.readbyqxmd.com/read/29069935/trastuzumab-modified-dm1-loaded-nanoparticles-for-her2-breast-cancer-treatment-an-in-vitro-and-in-vivo-study
#1
Ling Rong, Shuping Zhou, Xinkuang Liu, Amin Li, Tao Jing, Xueke Liu, Yinci Zhang, Shiyu Cai, Xiaolong Tang
BACKGROUND: Emtansine (DM1) is a highly potent anti-microtubule agent that has shown promising results for breast cancer treatment, but side effects limit its widespread clinical use. In this research, a new nano-drug was developed to integrate DM1 agent with antibody targeting. METHODS: A system of novel nanoparticles (NPs) DM1-NPs-trastuzumab (DM1-NPs-Tmab) of DM1 combined with (anti-HER2 antibody, Herceptin®, Trastuzumab) was developed for HER2(+) breast cancer treatment, and its physical characterization and antitumor biological activity were investigated...
October 25, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29040918/tumor-cryoablation-in-combination-with-natural-killer-cells-therapy-and-herceptin-in-patients-with-her2-overexpressing-recurrent-breast-cancer
#2
Shuzhen Liang, Lizhi Niu, Kecheng Xu, Xiaohua Wang, Yingqing Liang, Mingjie Zhang, Jibing Chen, Mao Lin
In this study, we investigated the clinical benefits of a combination of tumor cryoablation with natural killer (NK) cells therapy and Herceptin for human epidermal growth factor (HER) 2-overexpressing recurrent breast cancer. From May 2015 to May 2016, 48 patients who met the enrollment criteria were assigned to three groups (n=16): cryoablation group (group I), cryoablation-NK cells therapy group (group II) and cryoablation-NK cells therapy-Herceptin group (group III). Safety and short-term effects were evaluated...
October 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29038808/decoration-of-trastuzumab-with-short-oligonucleotides-synthesis-and-detailed-characterization
#3
A M Carvalho, A Manicardi, C Véliz Montes, S B Gunnoo, R J Schneider, A Madder
Trastuzumab (Herceptin®) is an FDA-approved therapeutic antibody currently employed in the treatment of metastatic stages of breast cancer. Herein, we propose a simple, fast and cost-effective methodology to conjugate trastuzumab with 22-mer 5' thiol-modified oligonucleotides using a bifunctional crosslinker. The conjugates were successfully characterized by MALDI-ToF MS and SDS-PAGE, obviating the need for enzymatic digestion and difficult chromatographic separations. Furthermore, ELISA was performed to ensure that trastuzumab activity is not affected by oligonucleotide conjugation...
October 31, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29017563/herceptin%C3%A2-trastuzumab-in-her2-positive-early-breast-cancer-protocol-for-a-systematic-review-and-cumulative-network-meta-analysis
#4
Florence R Wilson, Megan E Coombes, Quinlan Wylie, Mariya Yurchenko, Christine Brezden-Masley, Brian Hutton, Becky Skidmore, Chris Cameron
BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive disease that makes up about 20% of all invasive breast cancers. HER2+ breast cancer is associated with poor prognosis and high mortality rates, but the development of HER2-targeted therapies, such as originator trastuzumab (Herceptin®), has substantially improved patient survival. Numerous clinical trials and reviews have investigated the efficacy of HER2-targeted therapies over the past few decades; however, no study has specifically investigated the vast body of evidence on trastuzumab in comparison to chemotherapy regimens, endocrine therapies, and other targeted therapies...
October 10, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28968001/oxetane-grafts-installed-site-selectively-on-native-disulfides-to-enhance-protein-stability-and-activity-in%C3%A2-vivo
#5
Nuria Martínez-Sáez, Shuang Sun, Davide Oldrini, Pietro Sormanni, Omar Boutureira, Filippo Carboni, Ismael Compañón, Michael J Deery, Michele Vendruscolo, Francisco Corzana, Roberto Adamo, Gonçalo J L Bernardes
A four-membered oxygen ring (oxetane) can be readily grafted into native peptides and proteins through site-selective bis-alkylation of cysteine residues present as disulfides under mild and biocompatible conditions. The selective installation of the oxetane graft enhances stability and activity, as demonstrated for a range of biologically relevant cyclic peptides, including somatostatin, proteins, and antibodies, such as a Fab arm of the antibody Herceptin and a designed antibody DesAb-Aβ against the human Amyloid-β peptide...
October 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28963915/efficacy-and-safety-of-subcutaneous-trastuzumab-and-intravenous-trastuzumab-as-part-of-adjuvant-therapy-for-her2-positive-early-breast-cancer-final-analysis-of-the-randomised-two-cohort-prefher-study
#6
X Pivot, S Verma, L Fallowfield, V Müller, M Lichinitser, V Jenkins, A Sánchez Muñoz, Z Machackova, S Osborne, J Gligorov
AIM: To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166). PATIENTS AND METHODS: Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin(®) SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin(®) [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks...
September 27, 2017: European Journal of Cancer
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
#7
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/28936679/-the-herceptin%C3%A2-case-a-case-of-falsification-of-medicinal-products-to-a-greater-extent
#8
REVIEW
Renz Streit
Falsified medicines are a raising problem for the German drug market. The complex distribution channels across the European market facilitates the introduction of falsified and stolen medicines into the legal supply chain and may pose a risk for patients. The "Herceptin® case" from 2014 of falsified medicines of Italian origin demonstrates how complex distribution systems have been misused by criminal organizations in order to introduce stolen and thus falsified medicines via the parallel trade into the market, and which measures the authorities and the parallel-traders in the national and European network have taken to ensure patient safety...
September 21, 2017: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
https://www.readbyqxmd.com/read/28935106/chemoenzymatic-glycan-remodeling-of-natural-and-recombinant-glycoproteins
#9
Qiang Yang, Lai-Xi Wang
N-glycosylation plays important roles in modulating the biological functions of glycoproteins, such as protein folding, stability, and immunogenicity. However, acquiring homogeneous glycoforms of glycoproteins has been a challenging task for functional studies and therapeutic applications. In this chapter, we describe an efficient chemoenzymatic glycan remodeling protocol for making homogeneous glycoproteins that involves enzymatic deglycosylation and subsequent reglycosylation procedures. Two therapeutic glycoproteins, Herceptin (trastuzumab, a therapeutic monoclonal antibody) and erythropoietin (EPO, a glycoprotein hormone), were chosen as the model systems...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#10
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/28856027/cutaneous-erythema-at-scar-site-of-modified-radical-mastectomy-an-unexpected-manifestation-of-recurrent-carcinoma
#11
Awrad Mohammed-Reda Nasralla, Mohammed Abdulirazzaq Al-Duhileb, Ali Jamal-Aldein Arini, Samir Sami Amr
A 44-year-old woman presented with marked erythema over right mastectomy scar, while on Herceptin therapy. She had neoadjuvant chemotherapy, modified radical mastectomy, and radiotherapy less than one year earlier for the treatment of invasive ductal carcinoma. On physical examination, no palpable masses were detected in the erythematous skin. A biopsy revealed permeation of the skin lymphatics by emboli of metastatic ductal carcinoma, similar to what is seen in inflammatory carcinoma. The involved skin was excised, followed by immediate reconstruction with transverse rectus abdominis muscle (TRAM) flap...
2017: Case Reports in Surgery
https://www.readbyqxmd.com/read/28826287/docetaxel-loaded-nanostructured-lipid-carriers-functionalized-with-trastuzumab-herceptin-for-her2-positive-breast-cancer-cells
#12
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
#13
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/28776899/an-alternative-sterility-assessment-for-parenteral-drug-products-using-isothermal-microcalorimetry
#14
D Brueckner, S Krähenbühl, U Zuber, G Bonkat, O Braissant
AIMS: Production and release of injectable drug solutions are highly regulated since the administration of injectables bypasses natural body barriers. The sterility test is the last opportunity of product quality assessment. However, sterility is currently assessed by visual inspection (VI) that is time consuming and somewhat subjective. Therefore, we assessed isothermal microcalorimetry (IMC) as a replacement for the VI of the filtration based state-of-the-art sterility control. METHODS AND RESULTS: We used ATCC strains and house isolates to artificially contaminate frequently produced monoclonal antibodies (Avastin, Mabthera, Herceptin)...
August 4, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28750054/assisted-design-of-antibody-and-protein-therapeutics-adapt
#15
Victor Vivcharuk, Jason Baardsnes, Christophe Deprez, Traian Sulea, Maria Jaramillo, Christopher R Corbeil, Alaka Mullick, Joanne Magoon, Anne Marcil, Yves Durocher, Maureen D O'Connor-McCourt, Enrico O Purisima
Effective biologic therapeutics require binding affinities that are fine-tuned to their disease-related molecular target. The ADAPT (Assisted Design of Antibody and Protein Therapeutics) platform aids in the selection of mutants that improve/modulate the affinity of antibodies and other biologics. It uses a consensus z-score from three scoring functions and interleaves computational predictions with experimental validation, significantly enhancing the robustness of the design and selection of mutants. The platform was tested on three antibody Fab-antigen systems that spanned a wide range of initial binding affinities: bH1-VEGF-A (44 nM), bH1-HER2 (3...
2017: PloS One
https://www.readbyqxmd.com/read/28663873/autofluorescence-imaging-captures-heterogeneous-drug-response-differences-between-2d-and-3d-breast-cancer-cultures
#16
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/28642830/a-rare-case-of-esophageal-adenocarcinoma-with-urinary-bladder-metastasis
#17
Heather Katz, Rahoma E Saad, Krista Denning, Toni O Pacioles
Metastatic esophageal adenocarcinoma to the urinary bladder is extremely rare. We describe a previously healthy 49-year-old female with recent diagnosis of adenocarcinoma of the gastroesophageal junction with metastatic disease to the liver. Biopsy was positive for human epidermal growth factor receptor 2 (HER2) by Fluorescence In Situ Hybridization (FISH). She received six cycles of Cisplatin, 5-Fluorouracil, and Herceptin and subsequently developed symptomatic anemia and hematuria. Cystoscopy with retroflexion was performed and she received a transurethral resection of bladder tumor with fulguration...
2017: Case Reports in Gastrointestinal Medicine
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
#18
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
#19
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
#20
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
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