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https://www.readbyqxmd.com/read/28108597/bispecific-antibodies-and-antibody-drug-conjugates-adcs-bridging-her2-and-prolactin-receptor-improve-efficacy-of-her2-adcs
#1
Julian Andreev, Nithya Thambi, Andres E Perez Bay, Frank J Delfino, Joel H Martin, Marcus P Kelly, Jessica R Kirshner, Ashique Rafique, Arthur Kunz, Thomas Nittoli, Douglas MacDonald, Christopher Daly, William Olson, Gavin Thurston
The properties of cell surface proteins targeted by Antibody-drug conjugates (ADCs) have not been fully exploited; of particular importance are the rate of internalization and the route of intracellular trafficking. In this study we compared the trafficking of HER2, which is the target of the clinically approved ADC ado-trastuzumab emtansine (T-DM1), with that of prolactin receptor (PRLR), another potential target in breast cancer. In contrast to HER2, we found that PRLR is rapidly and constitutively internalized, and traffics efficiently to lysosomes, where it is degraded...
January 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28105873/loco-regional-morbidity-after-breast-conservation-and-axillary-lymph-node-dissection-for-early-breast-cancer-with-or-without-regional-nodes-radiotherapy-perspectives-in-modern-breast-cancer-treatment-the-skagen-trial-1-is-active
#2
Hanne Melgaard Nielsen, Rasmus Blechingberg Friis, Søren Linnet, Birgitte Vrou Offersen
BACKGROUND: Axillary lymph node dissection (ALND) and adjuvant radiotherapy (RT) in early breast cancer are associated with a risk of morbidity, including lymphedema and impaired shoulder mobility. The aim of this study was to evaluate loco-regional morbidity after breast conserving surgery (BCS), ALND, taxane-based chemotherapy and whole breast irradiation (WBI) with or without regional nodes RT. MATERIAL AND METHODS: Eligible patients had BCS and ALND from 2007 to 2012 followed by adjuvant taxane-based chemotherapy and if indicated, trastuzumab and endocrine treatment...
January 20, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28105352/conversion-therapy-of-gastric-cancer-with-massive-malignant-ascites-and-ovarian-metastases-by-systemic-and-intraperitoneal-chemotherapy
#3
Tomohiro Kondo, Hiromitsu Kitayama, Junko Sugiyama, Michiaki Hirayama, Yoshinori Suzuki, Yumiko Oyamada, Yasushi Tsuji
Intravenous and intraperitoneal paclitaxel with S-1 is showing promising results in gastric cancer with peritoneal metastases. We herein report a successful conversion of unresectable to resectable disease using combination chemotherapy with trastuzumab. The patient was a 39-year-old woman with human epidermal growth factor receptor 2-positive gastric cancer with peritoneal, pulmonary and bilateral ovarian metastases. After 6 cycles of S-1 plus cisplatin with trastuzumab, followed by 15 cycles of intravenous and intraperitoneal paclitaxel with S-1 and trastuzumab, the pulmonary and peritoneal metastases exhibited complete response and no evidence of malignancy was found on diagnostic laparoscopy...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28104744/spect-ct-imaging-of-the-novel-her2-targeted-peptide-probe-99mtc-hynic-h6f-in-breast-cancer-mouse-models
#4
Liqiang Li, Yue Wu, Zihua Wang, Bing Jia, Zhiyuan Hu, Chengyan Dong, Fan Wang
OBJECTIVES: Overexpression of human epidermal growth factor receptor 2 (HER2) plays important roles in tumorigenesis and tumor progression in breast cancer. Nuclear imaging of HER2 expression in tumors might detect all HER2-positive tumors throughout the body and guide HER2-targeted therapies for patients. We therefore aimed to develop a HER2-targeted peptide probe for breast cancer imaging. A novel single-photon emission computed tomography (SPECT) imaging probe, (99m)Tc-HYNIC-H6F, was prepared and then evaluated in breast cancer animal models...
January 19, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28104715/detailed-echocardiographic-phenotyping-in-breast-cancer-patients-associations-with-ejection-fraction-decline-recovery-and-heart-failure-symptoms-over-3-years-of-followup
#5
Hari K Narayan, Brian S Finkelman, Benjamin French, Theodore Plappert, David Hyman, Amanda M Smith, Kenneth B Margulies, Bonnie Ky
BACKGROUND: -Cardiovascular disease in breast cancer patients is of growing concern. The longitudinal effects of commonly used therapies, including doxorubicin and trastuzumab, on cardiac remodeling and function remain unknown in this population. We sought to define the changes in echocardiographic parameters of structure, function, and ventricular-arterial (VA) coupling, and their associations with left ventricular ejection fraction (LVEF) and heart failure (HF) symptoms. METHODS: -In a longitudinal prospective cohort study of 277 breast cancer participants receiving doxorubicin (Dox), trastuzumab (Tras), or both (Dox+Tras), we obtained 1,249 echocardiograms over a median followup of 2...
January 19, 2017: Circulation
https://www.readbyqxmd.com/read/28102883/exploring-prognostic-factors-for-her2-positive-metastatic-breast-cancer-a-retrospective-cohort-study-in-a-major-swiss-hospital
#6
Lilian Bringolf, Bernhard Pestalozzi, Daniel Fink, Konstantin Dedes
BACKGROUND: Trastuzumab (Herceptin®, Roche) has significantly improved the prognosis of patients with HER2-positive metastatic breast cancer. Some patients remain in remission for many years. However, there are no prognostic markers associated with long-term survival. This study aimed to analyse treatment patterns of HER2-positive metastatic breast cancer at a single institution and explore prognostic factors for long-term survival after HER2-targeted treatment. PATIENTS AND METHODS: This was a retrospective cohort study of all patients with HER2-positive metastatic breast cancer receiving first-line treatment with HER2-targeted therapy between 2004 and 2014 at the University Hospital of Zurich (n = 81)...
January 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#7
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28099174/discordance-rate-in-estrogen-receptor-progesterone-receptor-her2-status-and-ki67-index-between-primary-unifocal-and-multiple-homogenous-breast-carcinomas-and-synchronous-axillary-lymph-node-metastases-have-an-impact-on-therapeutic-decision
#8
Rares Georgescu, Monica Boros, Denisa Moncea, Orsolya Bauer, Marius-Florin Coros, Adela Oprea, Cosmin Moldovan, Cristian Podoleanu, Simona Stolnicu
BACKGROUND: We aimed to demonstrate that in breast carcinomas the tumor profile is not stable during the metastatic process, with impact on therapeutic decisions. MATERIALS AND METHODS: We analyzed the estrogen receptor (ER), progesterone receptor (PR), and HER2 status and Ki67 index in 41 primary unifocal (PU) and 37 primary multiple (PM) breast carcinomas with identical immunohistochemical profiles among multiple tumor foci and the matched axillary lymph node metastases...
January 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28094573/advanced-gastric-adenocarcinoma-optimizing-therapy-options
#9
Dilsa Mizrak Kaya, Kazuto Harada, Yusuke Shimodaira, Fatemeh G Amlashi, Quan Lin, Jaffer A Ajani
Gastric adenocarcinoma (GAC) is the fifth most common cancer and third leading cause of cancer related mortality worldwide. When localized, cure is achievable with surgery and adjunctive therapies in some patients, however, once advanced, GAC is not a curable condition. Only two targeted agents (trastuzumab and ramucirumab) have been approved and apatinib was approved only in China. Because of the heterogeneous nature of GAC, it is not possible to assess a standard therapeutic approach. Areas Covered: In this review, we aimed to describe the optimal systemic therapy regimens for advanced GAC...
January 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28092723/pertuzumab-and-breast-cancer-another-piece-in-the-anti-her2-puzzle
#10
Dr Lorenzo Gerratana, Dr Marta Bonotto, Dr Claudia Bozza, Dr Elena Ongaro, Dr Valentina Fanotto, Dr Giacomo Pelizzari, Prof Fabio Puglisi
The mechanism of action of pertuzumab, a recombinant anti-HER2 humanized monoclonal antibody, is complementary to trastuzumab's. On June 8, 2012, the Food and Drug Administration approved the combination of pertuzumab with trastuzumab and docetaxel as first-line treatment of HER2-positive metastatic breast cancer. Furthermore, pertuzumab is the first drug to be approved in the neoadjuvant setting using a pathological complete response as an endpoint. Areas covered: The review provides insights into the main mechanisms of action of pertuzumab...
January 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28091366/trastuzumab-emtansine-and-cost-based-decision-making
#11
EDITORIAL
The Lancet
No abstract text is available yet for this article.
January 7, 2017: Lancet
https://www.readbyqxmd.com/read/28088282/conjugation-site-analysis-of-antibody-drug-conjugates-adcs-by-signature-ion-fingerprinting-and-normalized-area-quantitation-approach-using-nano-liquid-chromatography-coupled-to-high-resolution-mass-spectrometry
#12
Hua Sang, Gaoyuan Lu, Yazhong Liu, Qiyue Hu, Weifeng Xing, Dongbing Cui, Fang Zhou, Jingwei Zhang, Haiping Hao, Guangji Wang, Hui Ye
Trastuzumab-MCC-DM1 (T-DM1) is an antibody-drug conjugate (ADC) that consists of a monoclonal antibody (mAb) trastuzumab non-cleavably linked to a cytotoxic drug DM1. During production, the DM1 agents were conjugated to the lysine residues of the mAb in a non-specific manner, yielding a heterogeneous mixture of ADC molecules that differ with respect to both the number and the conjugation sites of DM1 per mAb molecule. Since drug conjugation sites of ADC can significantly impact properties such as stability and pharmacokinetic behaviors, a rapid and reliable approach for conjugation site analysis of ADCs is highly demanded...
February 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28087106/charge-variant-analysis-of-proposed-biosimilar-to-trastuzumab
#13
Pravinkumar Dakshinamurthy, Pavithra Mukunda, Bhargav Prasad Kodaganti, Bharath Ravindra Shenoy, Bairavabalakumar Natarajan, Amol Maliwalave, Vivek Halan, Sathyabalan Murugesan, Sunit Maity
Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28081544/nomogram-to-predict-pathologic-complete-response-in-her2-positive-breast-cancer-treated-with-neoadjuvant-systemic-therapy
#14
Takeo Fujii, Takahiro Kogawa, Jimin Wu, Aysegul A Sahin, Dian D Liu, Mariana Chavez-MacGregor, Sharon H Giordano, Akshara Raghavendra, Rushmy K Murthy, Debu Tripathy, Yu Shen, Jose-Miguel Yamal, Naoto T Ueno
BACKGROUND: Pathologic complete response (pCR) is associated with improved survival outcomes in patients with HER2-positive primary breast cancer. We developed a nomogram to predict the probability of pCR rates by using oestrogen receptor (ER) expression, progesterone receptor (PR) expression and HER2/CEP17 ratio as continuous variables. METHODS: We retrospectively reviewed patients with stages I-III HER2-positive invasive breast cancer who had definitive surgery in 1999-2015 and received neoadjuvant systemic therapy (NST)...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28078656/biosimilars-for-the-treatment-of-cancer-a-systematic-review-of-published-evidence
#15
REVIEW
Ira Jacobs, Reginald Ewesuedo, Sadiq Lula, Charles Zacharchuk
BACKGROUND: Biologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access. OBJECTIVES: The purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer. METHODS: MEDLINE(®), Embase(®), and ISI Web of Science(®) databases were searched to September 2015...
January 11, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28074265/pharmacokinetic-and-exposure-response-analyses-of-pertuzumab-in-combination-with-trastuzumab-and-docetaxel-during-neoadjuvant-treatment-of-her2-%C3%A2-early-breast-cancer
#16
Angelica L Quartino, Hanbin Li, Jin Y Jin, D Russell Wada, Mark C Benyunes, Virginia McNally, Lucia Viganò, Ihsan Nijem, Bert L Lum, Amit Garg
PURPOSE: The NeoSphere trial evaluated pertuzumab in the neoadjuvant setting [early breast cancer (EBC)] with pathological complete response (pCR) as the primary efficacy end point. This analysis of pertuzumab aimed to (1) compare its pharmacokinetics (PK) in patients with EBC versus advanced cancers, (2) to further evaluate PK drug-drug interactions (DDIs) when given in combination with trastuzumab, and (3) to assess the relationship between exposure and efficacy to assess the clinical dosing regimen in the EBC patients...
January 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28071616/presenting-features-treatment-patterns-and-outcomes-of-patients-with-breast-cancer-in-pakistan-experience-at-a-university-hospital
#17
S Kumar, A J Shaikh, Y A Rashid, N Masood, Atv Mohammed, U Z Malik, G Haider, N Niamutullah, S Khan
BACKGROUND: Breast cancer is the most common cancer in Pakistani women. We report the presenting features, treatment patterns and survival of breast cancer from a University Hospital in Southern Pakistan and compare the data with international population based studies. MATERIALS AND METHODS: Medical records of patients diagnosed to have breast cancer between January 1999 and November 2008 were reviewed retrospectively. RESULTS: A total of 845 patients were identified...
April 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28070095/two-cases-of-unresectable-advanced-her2-positive-gastric-cancer-perforation-during-chemotherapy-with-trastuzumab
#18
Katsunori Matsueda, Tatsuya Toyokawa, Yuya Ueda, Shinya Endo, Masahiro Sakata, Isao Fujita, Jouichiro Horii, Takako Murakami
Case 1 was a 70-year-old man, and case 2 was a 65-year-old woman. Both were diagnosed with type 2 advanced HER2-positive gastric cancer. Capecitabine, cisplatin, and trastuzumab (HXP therapy) were administered to both patients. However, both patients developed peritonitis caused by gastric cancer perforation during HXP therapy on day 38 for case 1 and day 8 for case 2. Emergency omentum filling and gastric segmental resection were performed for both patients. The same chemotherapy regimen was continued after the surgery, and partial response was observed in both patients...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28069112/-immunohistochemical-assessment-of-her2-expression-in-gastric-cancer-a-clinicopathologic-study-of-93-cases
#19
Isabel Alvarado-Cabrero, Sara Gil-Hernández, Ana Ruelas-Perea, Diego Villaverde-Rodríguez, José Roberto Montes-Ochoa, Rafael Medrano-Guzmán
BACKGROUND: Gastric cancer in Mexico is ranked third in both males and females. Most patients present clinically with advanced disease and treatment options are sparse. HER2 overexpression in gastric cancer is related to poor outcome. Immunohistochemical testing for HER2 is becoming the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab. OBJECTIVES: To determine the frequency of HER2 overexpression in patients with gastric cancer in the Hospital de Oncología del Centro Médico Nacional, Siglo XXI and its association with other histopathological findings...
January 6, 2017: Cirugia y Cirujanos
https://www.readbyqxmd.com/read/28067257/enhanced-tumor-targeting-selectivity-by-modulating-bispecific-antibody-binding-affinity-and-format-valence
#20
Yariv Mazor, Kris F Sachsenmeier, Chunning Yang, Anna Hansen, Jessica Filderman, Kathy Mulgrew, Herren Wu, William F Dall'Acqua
Bispecific antibodies are considered attractive bio-therapeutic agents owing to their ability to target two distinct disease mediators. Cross-arm avidity targeting of antigen double-positive cancer cells over single-positive normal tissue is believed to enhance the therapeutic efficacy, restrict major escape mechanisms and increase tumor-targeting selectivity, leading to reduced systemic toxicity and improved therapeutic index. However, the interplay of factors regulating target selectivity is not well understood and often overlooked when developing clinically relevant bispecific therapeutics...
January 9, 2017: Scientific Reports
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