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https://www.readbyqxmd.com/read/28319882/pain-characteristics-as-important-contributing-factors-to-upper-limb-dysfunctions-in-breast-cancer-survivors-at-long-term
#1
An De Groef, Mira Meeus, Tessa De Vrieze, Lore Vos, Marijke Van Kampen, Marie-Rose Christiaens, Patrick Neven, Inge Geraerts, Nele Devoogdt
PURPOSE: The aim of this study was to explore the treatment, patient, and impairment-related risk factors associated with upper limb dysfunctions in breast cancer survivors. METHODS: A cross-sectional study was performed in 274 women treated for breast cancer. The following risk factors were analysed by bivariable and multivariable analysis: 1) treatment-related variables (type of surgery, levels of lymph node dissected, radiotherapy, chemotherapy, hormone therapy and trastuzumab); 2) patient's related variables (age and Body Mass Index); 3) and finally impairment-related variables such as pain (intensity, quality and pressure hypersensitivity, signs of central sensitisation, the degree of pain catastrophizing and vigilance and awareness to pain), active ROM and upper limb strength were investigated...
March 14, 2017: Musculoskelet Sci Pract
https://www.readbyqxmd.com/read/28319364/a-new-spin-on-antibody-drug-conjugates-trastuzumab-fulvestrant-colloidal-drug-aggregates-target-her2-positive-cells
#2
Ahil N Ganesh, Christopher Mclaughlin, Da Duan, Brian K Shoichet, Molly S Shoichet
While the formation of colloidal aggregates leads to artifacts in early drug discovery, their composition makes them attrac-tive as nanoparticle formulations for targeted drug delivery as the entire nanoparticle is composed of drug. The typical tran-sient stability of colloidal aggregates has inhibited exploiting this property. To overcome this limitation, we investigated a series of proteins to stabilize colloidal aggregates of the chemotherapeutic, fulvestrant, including: bovine serum albumin, a generic human immunoglobulin G, and trastuzumab, a therapeutic anti-human epidermal growth factor receptor 2 anti-body...
March 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28315060/results-of-a-phase-ib-trial-of-combination-immunotherapy-with-a-cd8-%C3%A2-t-cell-eliciting-vaccine-and-trastuzumab-in-breast-cancer-patients
#3
G Travis Clifton, Jennifer K Litton, Karen Arrington, Sathibalan Ponniah, Nuhad K Ibrahim, Victor Gall, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf
BACKGROUND: CD8+ T cell-eliciting vaccines are being investigated in breast cancer patients. Preclinical data showed that trastuzumab increases the susceptibility of tumor cells to lysis by vaccine-generated CD8+ T cells, suggesting potential benefit of a combination immunotherapy strategy. The current trial was undertaken to demonstrate the safety of this approach. METHODS: This study was designed as a dose-escalation trial enrolling clinically disease-free, human leukocyte antigen A2+ or A3+ , human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients...
March 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28303026/strategies-and-challenges-for-the-next-generation-of-antibody-drug-conjugates
#4
REVIEW
Alain Beck, Liliane Goetsch, Charles Dumontet, Nathalie Corvaïa
Antibody-drug conjugates (ADCs) are one of the fastest growing classes of oncology therapeutics. After half a century of research, the approvals of brentuximab vedotin (in 2011) and trastuzumab emtansine (in 2013) have paved the way for ongoing clinical trials that are evaluating more than 60 further ADC candidates. The limited success of first-generation ADCs (developed in the early 2000s) informed strategies to bring second-generation ADCs to the market, which have higher levels of cytotoxic drug conjugation, lower levels of naked antibodies and more-stable linkers between the drug and the antibody...
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28301577/correction-yes1-signaling-mediates-the-resistance-to-trastuzumab-lap-atinib-in-breast-cancer
#5
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0171356.].
2017: PloS One
https://www.readbyqxmd.com/read/28298546/64cu-mm-302-positron-emission-tomography-quantifies-variability-of-enhanced-permeability-and-retention-of-nanoparticles-in-relation-to-treatment-response-in-patients-with-metastatic-breast-cancer
#6
Helen Lee, Anthony F Shields, Barry A Siegel, Kathy D Miller, Ian Krop, Cynthia X Ma, Patricia M LoRusso, Pamela N Munster, Karen Campbell, Daniel F Gaddy, Shannon C Leonard, Elena Geretti, Stephanie J Blocker, Dmitri B Kirpotin, Victor Moyo, Thomas J Wickham, Bart S Hendriks
PURPOSE: Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR and its variability in human tumors is highly debated and has been proposed as an explanation for variable responses to therapeutic nanoparticles in clinical studies. EXPERIMENTAL DESIGN: We assessed the EPR effect in patients using a 64Cu-labeled nanoparticle, 64Cu-MM-302 (64Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), and imaging by Positron Emission Tomography/Computed Tomography (PET/CT)...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28296619/drifts-in-adcc-related-quality-attributes-of-herceptin%C3%A2-impact-on-development-of-a-trastuzumab-biosimilar
#7
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 two 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 biological properties by standard or state-of-the-art analytical methods, using multiple lots expiring between March 2015 and December 2019...
March 15, 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
#8
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...
March 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28291814/are-life-saving-anticancer-drugs-reaching-all-patients-patterns-and-discrepancies-of-trastuzumab-use-in-the-european-union-and-the-usa
#9
Felipe Ades, Christelle Senterre, Dimitrios Zardavas, Evandro de Azambuja, Razvan Popescu, Martine Piccart
BACKGROUND: The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the uptake of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA. METHODS: Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab treatments per year was estimated using trastuzumab procurement data for each country...
2017: PloS One
https://www.readbyqxmd.com/read/28289045/efficacy-and-safety-of-lapatinib-and-trastuzumab-for-her2-positive-breast-cancer-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#10
Zhi-Qiao Xu, Yan Zhang, Ning Li, Pei-Jie Liu, Ling Gao, Xin Gao, Xiao-Jing Tie
OBJECTIVES: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour actively in models of HER2-positive breast cancer. However, the efficacy of trastuzumab in combination with lapatinib remains controversial. Therefore, we conducted this meta-analysis to compare combination treatment with lapatinib and trastuzumab to trastuzumab or lapatinib alone in the treatment of HER2-positive breast cancer...
March 13, 2017: BMJ Open
https://www.readbyqxmd.com/read/28286614/is-there-any-concordance-between-of-ihc-with-fish-in-her2-positive-breast-cancer-patients
#11
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/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#12
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28286209/esophageal-adenocarcinoma-cells-and-xenograft-tumors-exposed-to-erb-b2-receptor-tyrosine-kinase-2-and-3-inhibitors-activate-transforming-growth-factor-beta-signaling-which-induces-epithelial-to-mesenchymal-transition
#13
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft (PDX) tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28285949/considerations-in-cardio-oncology-multiple-mobile-left-sided-cardiac-thrombi-in-chemotherapy-induced-cardiomyopathy
#14
Toshinori Minamishima, Kenichi Matsushita, Hiromu Morikubo, Aoi Isaka, Noriko Matsushita, Hidehito Endo, Hiroshi Kubota, Konomi Sakata, Toru Satoh, Hideaki Yoshino
With advances in cancer chemotherapy, the importance of the new clinical discipline of cardio-oncology, which is concerned with the cardiac effects of chemotherapy, is increasing. Herein we describe the case of a 48-year-old woman with a history of breast cancer who presented with symptoms of heart failure due to chemotherapy-induced cardiomyopathy. Treatment for the patient's breast cancer had included surgery and chemotherapy with anthracyclines and trastuzumab. Echocardiography revealed multiple mobile thrombi in the left ventricle and atrium...
March 10, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28284008/effective-and-persistent-antitumor-activity-of-her2-directed-car-t-cells-against-gastric-cancer-cells-in-vitro-and-xenotransplanted-tumors-in-vivo
#15
Yanjing Song, Chuan Tong, Yao Wang, Yunhe Gao, Hanren Dai, Yelei Guo, Xudong Zhao, Yi Wang, Zizheng Wang, Weidong Han, Lin Chen
Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties...
March 10, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28283503/her2-tumor-molecular-subtypes-predict-response-to-dual-her2-blockade
#16
(no author information available yet)
Trastuzumab plus lapatinib achieves the highest response rates in HER2-enriched HER2(+) breast tumors.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28281922/a-high-performance-non-radioactive-potency-assay-for-measuring-cytotoxicity-a-full-substitute-of-the-chromium-release-assay-targeting-the-regulatory-compliance-objective
#17
Alexis Rossignol, Véronique Bonnaudet, Béatrice Clémenceau, Henri Vié, Laurent Bretaudeau
Standardized and biologically relevant potency assays are required by the regulatory authorities for the characterization and quality control of therapeutic antibodies. As critical mechanisms of action (MoA) of antibodies, the antibody-dependent cell-meditated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) must be characterized by appropriate potency assays. The current reference method for measuring cytotoxicity is the (51)Cr-release method. However, radioactivity handling is difficult to implement in an industrial context because of environmental and operator protection constraints...
February 8, 2017: MAbs
https://www.readbyqxmd.com/read/28279941/long-term-outcome-of-the-remagus-02-trial-a-multicenter-randomised-phase-ii-trial-in-locally-advanced-breast-cancer%C3%A2-patients-treated-with-neoadjuvant-chemotherapy-with-or-without-celecoxib-or-trastuzumab-according-to-her2-status
#18
Sylvie Giacchetti, Anne-Sophie Hamy, Suzette Delaloge, Etienne Brain, Frédérique Berger, Brigitte Sigal-Zafrani, Marie-Christine Mathieu, Philippe Bertheau, Jean Marc Guinebretière, Mahasti Saghatchian, Florence Lerebours, Chafouny Mazouni, Olivier Tembo, Marc Espié, Fabien Reyal, Michel Marty, Bernard Asselain, Jean-Yves Pierga
BACKGROUND: The REMAGUS-02 multicenter randomised phase II trial showed that the addition to neoadjuvant chemotherapy (NAC) of trastuzumab in patients with localised HER2-positive breast cancer (BC) increased the pathological complete response (pCR) rate and that the addition of celecoxib in HER2-negative cases did not increase the pCR rate. We report here the long-term follow-up results for disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: From 2004 to 2007, 340 stage II-III BC patients were randomly assigned to receive neoadjuvant EC-T (four cycles of epirubicin-cyclophosphamide followed by four cycles of docetaxel) +/- celecoxib in HER2-negative cases (n = 220) and ± trastuzumab in HER2-positive cases (n = 120)...
March 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28279471/current-progress-in-human-epidermal-growth-factor-receptor-2-targeted-therapies-in%C3%A2-esophagogastric-cancer
#19
REVIEW
Yelena Y Janjigian, Maria Ignez Braghiroli
Esophagogastric cancer is a worldwide health problem. The addition of the epidermal growth factor receptor 2 (HER2)-directed antibody trastuzumab to chemotherapy increased the overall survival of patients with metastatic HER2-positive esophagogastric cancer. This article discusses the available data to support HER2 as validated biomarker and recently completed and ongoing clinical trials of HER2-directed agents in metastatic and localized disease. Also reviewed is the mechanisms of resistance for HER2-directed therapy and ongoing research strategies including new imaging techniques and studies with patient-derived xenografts...
April 2017: Surgical Oncology Clinics of North America
https://www.readbyqxmd.com/read/28271563/gastric-cancer-managment-kinases-as-a-target-therapy
#20
Batoul Farran, Susanne Müller, Raquel C Montenegro
The molecular diagnostics revolution has reshaped the practice of oncology by facilitating the identification of genetic, epigenetic and proteomic modifications correlated with cancer, thus delineating 'oncomaps' for various cancer types. These advances have enhanced our understanding of gastric cancer, one of the most fatal diseases worldwide, and culminated in the approval of novel molecular therapies such as trastuzumab. Gastric tumours display recurrent aberrations in key kinase oncogenes such as Her2, EGFR, PI3K, mTOR or c-Met, suggesting that these receptors are amenable to inhibition using specific drug agents...
March 7, 2017: Clinical and Experimental Pharmacology & Physiology
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