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https://www.readbyqxmd.com/read/28225558/cutaneous-adnexal-adenocarcinoma-with-exquisite-sensitivity-to-trastuzumab
#1
Timothy J Brown, David J Sher, Lucien A Nedzi, Randall S Hughes, Muhammad S Beg, Jason Mull, Venetia R Sarode, Saad A Khan
BACKGROUND: Cutaneous adnexal adenocarcinoma is a rare cancer that is occasionally human epidermal growth factor receptor-2 (HER-2)-positive, and demonstrates variable response to HER-2 inhibitors. METHODS: We report a case of adnexal adenocarcinoma of the scalp in a 56-year-old man. He underwent wide local excision with cervical node dissection followed by radiation, but had extensive local recurrence. RESULTS: Pathology demonstrated a poorly differentiated adnexal adenocarcinoma with HER-2 overexpression by immunohistochemistry (IHC) and high HER-2 gene amplification by fluorescence in situ hybridization...
February 22, 2017: Head & Neck
https://www.readbyqxmd.com/read/28223426/resistance-mechanism-against-trastuzumab-in-her2-positive-cancer-cells-and-its-negation-by-src-inhibition
#2
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Trastuzumab in combination with chemotherapy is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Several resistance mechanisms against anti-HER2 therapy have been proposed. Src activation has been suggested to be responsible for the resistance of HER2-positive breast cancer. In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from HER2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773)...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223233/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-1-gi-carcinomas
#3
REVIEW
Cindy Neuzillet, Benoît Rousseau, Hemant Kocher, Philippe Bourget, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the molecular biology of cancer cell has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents being more specific to cancer cells were expected to be less toxic than cytotoxic agents. Targeted agents have provided clinical benefit in many GI cancer types...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28216265/implications-of-excess-weight-in-the-cardiotoxicity-of-anthracyclines-and-trastuzumab-in-breast-cancer
#4
Charles Guenancia, Sylvain Ladoire, François Ghiringelli, Luc Rochette, Catherine Vergely, Yves Cottin
No abstract text is available yet for this article.
February 16, 2017: Archives of Cardiovascular Diseases
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
#5
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...
February 16, 2017: Lancet
https://www.readbyqxmd.com/read/28215659/optimal-duration-of-trastuzumab-for-early-her2-positive-breast-cancer
#6
Jennifer M Specht, Nancy E Davidson
No abstract text is available yet for this article.
February 16, 2017: Lancet
https://www.readbyqxmd.com/read/28212372/molecular-biology-of-gastroesophageal-cancers-opportunities-and-challenges
#7
Shaheer Khan, Sameh Mikhail, Joanne Xiu, Mohamed E Salem
Gastroesophageal (GE) malignancies make up a significant and growing segment of newly diagnosed cancers. Approximately 80% of patients who have GE cancers die within 5 years of diagnosis, which means that effective treatments for these malignancies need to be found. Currently, targeted therapies have a minimal role in this disease group. Intensive study of the molecular biology of GE cancers is a relatively new and ongoing venture, but it has already led to a significant increase in our understanding of these malignancies...
January 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28211299/comparison-of-biodistribution-profile-of-monoclonal-antibodies-nanoparticles-and-aptamers-in-rats-with-breast-cancer
#8
Cristal Cerqueira-Coutinho, Sotiris Missailidis, Jéssica Alessandra-Perini, Daniel Escorsim Machado, Jamila Alessandra Perini, Ralph Santos-Oliveira
The use of monoclonal antibodies and aptamers is growing every single day, as the use of nanoparticle systems. Although most of the products are under investigation, there are a few commercialized products available at the market, for human consume. In this study, we have compared three formulations (aptamer anti-MUC1, monoclonal antibody - Trastuzumab and monoclonal antibodies nanoparticles - PLA/PVA/MMT trastuzumab) to identify their profile as also to understand their behavior into an alive biological system...
May 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28208769/localisation-microscopy-of-breast-epithelial-erbb-2-receptors-and-gap-junctions-trafficking-after-%C3%AE-irradiation-neuregulin-1%C3%AE-and-trastuzumab-application
#9
Götz Pilarczyk, Ines Nesnidal, Manuel Gunkel, Margund Bach, Felix Bestvater, Michael Hausmann
In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin- 1 β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ -irradiation or alternatively neuregulin- 1 β application mobilized ErbB receptors in a nucleograde fashion-a process attenuated by trastuzumab antibody application...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208257/hydrophilic-interaction-chromatography-hyphenated-with-mass-spectrometry-a-powerful-analytical-tool-for-the-comparison-of-originator-and-biosimilar-therapeutic-monoclonal-antibodies-at-the-middle-up-level-of-analysis
#10
Valentina D'Atri, Szabolcs Fekete, Alain Beck, Matthew Lauber, Davy Guillarme
The development and approval processes of biosimilar mAbs depend on their comparability to originators. Therefore, analytical comparisons are required to assess structural features and post-translational modifications (PTM) and thereby minimize the risk of being clinically meaningful differences between biosimilar and originator drug products. The glycosylation pattern of mAbs is considered to be an important critical quality attribute (CQA), and several analytical approaches have been proposed that facilitate characterizing and monitoring a glycosylation profile, albeit mainly at a glycan and glycopeptide level of analysis...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28202353/the-potential-clinical-promise-of-multimodality-metronomic-chemotherapy-revealed-by-preclinical-studies-of-metastatic-disease
#11
Robert S Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMS) of cancer or patient-derived xenografts (PDXs)...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28199966/does-dual-her-2-blockade-treatment-increase-the-risk-of-severe-toxicities-of-special-interests-in-breast-cancer-patients-a-meta-analysis-of-randomized-controlled-trials
#12
Shuai Hao, Wuguo Tian, Bo Gao, Yan Jiang, Xiaohua Zhang, Shu Zhang, Lingji Guo, Jianjie Zhao, Gang Zhang, Chunyan Hu, Jie Yan, Donglin Luo
Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer...
February 10, 2017: Oncotarget
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
#13
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...
October 23, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28196634/objective-domain-specific-her2-measurement-in-uterine-and-ovarian-serous-carcinomas-and-its-clinical-significance
#14
Daniel E Carvajal-Hausdorf, Kurt A Schalper, Yalai Bai, Jonathan Black, Alessandro D Santin, David L Rimm
INTRODUCTION: HER2 overexpression/amplification is identified in up to 40% of uterine serous carcinomas (USC) and 10% of ovarian serous carcinomas (OSC). However, clinical trials using various HER2-targeted agents failed to show significant responses. FDA-approved HER2 assays target only the protein's intracellular domain (ICD) and not the extracellular domain (ECD). Previous quantitative studies in breast cancer by our group have shown that ICD of HER2 is expressed in some cases that do not express the HER2 ECD...
February 11, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28193043/removal-of-n-linked-glycosylations-at-acidic-ph-by-pngase-a-facilitates-hydrogen-deuterium-exchange-mass-spectrometry-analysis-of-n-linked-glycoproteins
#15
Pernille Foged Jensen, Gerard Comamala, Morten Beck Trelle, Jeppe Buur Madsen, Thomas J D Jørgensen, Kasper D Rand
Protein glycosylation is the most frequent post-translational modification and is present on more than 50% of eukaryotic proteins. Glycosylation covers a wide subset of modifications involving many types of complex oligosaccharide structures, making structural analysis of glycoproteins and their glycans challenging for most analytical techniques. Hydrogen/deuterium exchange monitored by mass spectrometry is a sensitive technique for investigation of protein conformational dynamics of complex heterogeneous proteins in solution...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28191909/the-influence-of-chemotherapy-on-the-right-ventricle-did-we-forget-something
#16
REVIEW
Marijana Tadic, Cesare Cuspidi, Dagmara Hering, Lucia Venneri, Oleksandr Danylenko
BACKGROUND: A large number of chemotherapy-induced cardiovascular complications were discovered in studies over the last several decades. The focus of the majority of these studies was left ventricular (LV) remodeling. The aim of this article was to provide a comprehensive overview of potential mechanisms of chemotherapy-induced right ventricular (RV) remodeling and summarize clinical studies on this topic. HYPOTHESIS: Chemotherapy induces RV structural, functional, and mechanical changes...
February 13, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28188066/synthesis-and-in-vitro-evaluation-of-sg3227-a-pyrrolobenzodiazepine-dimer-antibody-drug-conjugate-payload-based-on-sibiromycin
#17
Gary C Kemp, Arnaud C Tiberghien, Neki V Patel, Francois D'Hooge, Sanjay M Nilapwar, Lauren R Adams, Simon Corbett, David G Williams, John A Hartley, Philip W Howard
A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro...
January 30, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28187033/prognostic-significance-of-stromal-versus-intratumoral-infiltrating-lymphocytes-in-different-subtypes-of-breast-cancer-treated-with-cytotoxic-neoadjuvant-chemotherapy
#18
Thaer Khoury, Vidya Nagrale, Mateusz Opyrchal, Xuan Peng, Dan Wang, Song Yao
BACKGROUND: The aim of the study was to investigate if there were differences in associations of stromal versus intratumoral tumor infiltrating lymphocytes (TILs) with pathology complete response (pCR) among breast cancer (BC) subtypes treated with neoadjuvant therapy. MATERIALS AND METHODS: The hematoxylin and eosin slides of BC-core biopsy consecutive cases (n=331) were reviewed from a single institution between 2000 and 2014. TIL-stroma (TIL-str) was scored from 0% to 100%...
February 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28186982/avidinox-anchored-biotinylated-trastuzumab-and-pertuzumab-induce-down-modulation-of-erbb2-and-tumor-cell-death-at-concentrations-order-of-magnitude-lower-than-not-anchored-antibodies
#19
Ferdinando Maria Milazzo, Anna Maria Anastasi, Caterina Chiapparino, Antonio Rosi, Barbara Leoni, Loredana Vesci, Fiorella Petronzelli, Rita De Santis
The oxidized version of Avidin, known as AvidinOX, was previously shown to link to tissue proteins upon injection or nebulization, thus becoming a stable receptor for biotinylated therapeutics. AvidinOX is currently under clinical investigation to target radioactive biotin to inoperable tumor lesions (ClinicalTrials.gov NCT02053324). Presently, we show that the anti-ErbB2 monoclonal antibodies Trastuzumab and Pertuzumab can be chemically biotinylated while maintaining their biochemical and biological properties...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186977/pathological-complete-response-of-her2-positive-breast-cancer-to-trastuzumab-and-chemotherapy-can-be-predicted-by-hsd17b4-methylation
#20
Satoshi Fujii, Satoshi Yamashita, Takeshi Yamaguchi, Masato Takahashi, Yasuo Hozumi, Toshikazu Ushijima, Hirofumi Mukai
Human epidermal growth factor (HER) 2-directed therapy is the standard treatment for HER2-positive breast cancer. Patients who achieved a pathological complete response (pCR) to the therapy are associated with excellent disease-free survival. However, few molecular markers are available to predict pCR. Here, we aimed to establish a DNA methylation marker to predict the response to trastuzumab and chemotherapy. A total of 67 patients were divided into screening (n = 21) and validation (n = 46) sets. Genome-wide DNA methylation analysis of the screening set identified eight genomic regions specifically methylated in patients with pCR...
February 6, 2017: Oncotarget
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