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https://www.readbyqxmd.com/read/28783505/surface-modification-of-docetaxel-nanocrystals-with-her2-antibody-to-enhance-cell-growth-inhibition-in-breast-cancer-cells
#1
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
#2
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
#3
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
#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/28642830/a-rare-case-of-esophageal-adenocarcinoma-with-urinary-bladder-metastasis
#5
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
#6
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...
June 15, 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
#7
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
#8
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/28619527/expression-of-full-length-her2-protein-in-sf9-insect-cells-and-its-presentation-on-the-surface-of-budded-virus-like-particles
#9
Lisa Nika, Jakob Wallner, Dieter Palmberger, Krisztina Koczka, Karola Vorauer-Uhl, Reingard Grabherr
Biomarkers of cancer are often glycosylated membrane receptor proteins present on the cellular surface. In order to develop new antibodies for cancer diagnostics or treatment, it is a main pre-requisite that these target proteins are available in a native conformation. However, membrane receptor proteins are notoriously difficult to produce due to their hydrophobic nature and complex architecture. Here, we used the baculovirus-insect cell expression system to produce budded virus-like particles (VLPs) as the scaffold for the presentation of complex membrane proteins...
August 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28588175/her2-status-in-gastric-and-gastroesophageal-junction-adenocarcinoma
#10
F A Rima, M Hussain, N Haque, R K Dewan, N Rahman, M A Jinnah, R Jeba, F Chowdhury
Gastric carcinoma is a biologically heterogenous disease and survival varies among the patients with same stage. Recent studies have shown that a subset of gastric and gastroesophageal junction adenocarcinoma over express the HER2/neu protein and these patients can be treated by monoclonal antibody against HER2/neu protein. The purpose of this study was to detect the frequency of HER2 expression in gastric and gastroesophageal junction adenocarcinoma and to evaluate the relationship between HER2 expression and clinicopathological features in these patients...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28454094/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#11
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
#12
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
#13
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
#14
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/28296619/drifts-in-adcc-related-quality-attributes-of-herceptin%C3%A2-impact-on-development-of-a-trastuzumab-biosimilar
#15
Seokkyun Kim, Jinsu Song, Seungkyu Park, Sunyoung Ham, Kyungyeol Paek, Minjung Kang, Yunjung Chae, Heewon Seo, Hyung-Chan Kim, Michael Flores
A biosimilar product needs to demonstrate biosimilarity to the originator reference product, and the quality profile of the latter should be monitored throughout the period of the biosimilar's development to match the quality attributes of the 2 products that relate to efficacy and safety. For the development of a biosimilar version of trastuzumab, the reference product, Herceptin®, was extensively characterized for the main physicochemical and biologic properties by standard or state-of-the-art analytical methods, using multiple lots expiring between March 2015 and December 2019...
May 2017: MAbs
https://www.readbyqxmd.com/read/28294622/tracking-antibody-distribution-with-near-infrared-fluorescent-dyes-impact-of-dye-structure-and-degree-of-labeling-on-plasma-clearance
#16
Cornelius Cilliers, Ian Nessler, Nikolas Christodolu, Greg M Thurber
Monoclonal antibodies labeled with near-infrared (NIR) fluorophores have potential use in disease detection, intraoperative imaging, and pharmacokinetic characterization of therapeutic antibodies in both the preclinical and clinical setting. Recent work has shown conjugation of NIR fluorophores to antibodies can potentially alter antibody disposition at a sufficiently high degree of labeling (DoL); however, other reports show minimal impact after labeling with NIR fluorophores. In this work, we label two clinically approved antibodies, Herceptin (trastuzumab) and Avastin (bevacizumab), with NIR dyes IRDye 800CW (800CW) or Alexa Fluor 680 (AF680), at 1...
May 1, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28286614/is-there-any-concordance-between-of-ihc-with-fish-in-her2-positive-breast-cancer-patients
#17
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/28263844/a-high-throughput-bioluminescent-assay-to-monitor-the-deamidation-of-asparagine-and-isomerization-of-aspartate-residues-in-therapeutic-proteins-and-antibodies
#18
Kevin Hsiao, Juliano Alves, Rushikesh Patel, Monica Adams, Vishal Nashine, Said Goueli
Since the introduction of Herceptin and Rituximab in 1986, therapeutic antibodies have gained tremendous momentum in the treatment of broad range of several diseases such as cancer and inflammation. Selection of the clinical candidate mAb usually starts with large-scale in vitro screening and profiling of multiple mAbs to identify candidates that show high in vitro or in vivo activity, and thus it is necessarily to identify and eliminate potentially unstable mAbs during the lead selection process. Antibodies undergo a variety of degradation reactions that may result in compromised bioactivity and safety profile...
March 2, 2017: Journal of Pharmaceutical Sciences
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
#19
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
#20
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
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