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https://www.readbyqxmd.com/read/29456713/-in-vitro-study-on-the-role-of-sox9-in-trastuzumab-resistance-of-adenocarcinoma-of-the-esophagogastric-junction
#1
Yingcai Hong, Huaisheng Chen, Zhanpeng Rao, Bin Peng, Hong Hu, Shaolin Lin, Zhenglei Xu
Trastuzumab is recommended for the treatment of human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagogastric junction (AEG) in combination with chemotherapy; however, drug resistance has severely affected its clinical application. The present study aimed to investigate the effect of sex determining region Y-box 9 (SOX9), a prognostic marker in adjuvant oncological settings, on AEG cell proliferation and apoptosis in the presence or absence of trastuzumab. Furthermore, the molecular mechanism underlying the role of SOX9 in trastuzumab resistance was explored...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456473/adverse-events-of-trastuzumab-emtansine-t-dm1-in-the-treatment-of-her2-positive-breast-cancer-patients
#2
REVIEW
Lidia Kowalczyk, Rupert Bartsch, Christian F Singer, Alex Farr
The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1)...
December 2017: Breast Care
https://www.readbyqxmd.com/read/29454478/usefulness-of-integrating-heart-failure-risk-factors-into-impairment-of-global-longitudinal-strain-to-predict-anthracycline-related-cardiac-dysfunction
#3
M Wesley Milks, Michael R Velez, Nishaki Mehta, Abiodun Ishola, Thomas Van Houten, Vedat O Yildiz, Raquel Reinbolt, Maryam Lustberg, Sakima A Smith, David A Orsinelli
The prediction of cancer therapeutics-related cardiac dysfunction (CTRCD) is an essential aspect of care for individuals who receive potentially cardiotoxic oncologic treatments. Certain clinical risk factors have been described for incident CTRCD, and measurement of left ventricular (LV) longitudinal strain by speckle tracking 2-dimensional echocardiography (2DE) is the best-validated myocardial mechanical imaging assessment to detect subtle changes in LV function during cancer treatment. However, the direct integration of clinical and imaging risk factors to predict CTRCD has not yet been extensively examined...
January 12, 2018: American Journal of Cardiology
https://www.readbyqxmd.com/read/29451302/comparing-cytotoxic-backbones-for-first-line-trastuzumab-containing-regimens-in-her2-positive-advanced-esophagogastric-cancer-a-meta-analysis
#4
Emil Ter Veer, Aafke Creemers, Laura de Waal, Martijn G H van Oijen, Hanneke W M van Laarhoven
According to the ToGA study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for HER2-positive advanced esophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive esophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in-situ-hybridisation...
February 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29448072/a-phase-iii-study-comparing-sb3-a-proposed-trastuzumab-biosimilar-and-trastuzumab-reference-product-in-her2-positive-early-breast-cancer-treated-with-neoadjuvant-adjuvant-treatment-final-safety-immunogenicity-and-survival-results
#5
X Pivot, I Bondarenko, Z Nowecki, M Dvorkin, E Trishkina, J-H Ahn, S-A Im, T Sarosiek, S Chatterjee, M Z Wojtukiewicz, Y Shparyk, V Moiseyenko, M Bello, V Semiglazov, Y Lee, J Lim
BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide)...
February 12, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29445928/efficacy-and-safety-of-trastuzumab-lapatinib-and-paclitaxel-neoadjuvant-treatment-with-or-without-prolonged-exposure-to-anti-her2-therapy-and-with-or-without-hormone-therapy-for-her2-positive-primary-breast-cancer-a-randomised-five-arm-multicentre-open-label
#6
N Masuda, M Toi, N Yamamoto, H Iwata, K Kuroi, H Bando, S Ohtani, T Takano, K Inoue, Y Yanagita, H Kasai, S Morita, T Sakurai, S Ohno
BACKGROUND: Dual blockade of HER2 promises increased pathological complete response (pCR) rate compared with single blockade in the presence of chemotherapy for HER2-positive (+) primary breast cancer. Many questions remain regarding optimal duration of treatment and combination impact of endocrine therapy for luminal HER2 disease. METHODS: We designed a randomised phase II, five-arm study to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks) followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks) with/without prolongation of anti-HER2 therapy prior to chemotherapy (18 vs...
February 14, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29445216/evaluation-of-her2-specific-peptide-ligand-for-its-employment-as-radiolabeled-imaging-probe
#7
Hadis Honarvar, Enrica Calce, Nunzianna Doti, Emma Langella, Anna Orlova, Jos Buijs, Valentina D'Amato, Roberto Bianco, Michele Saviano, Vladimir Tolmachev, Stefania De Luca
HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29443503/dual-color-bioluminescent-sensor-proteins-for-therapeutic-drug-monitoring-of-anti-tumor-antibodies
#8
Martijn van Rosmalen, Yan Ni, Daan F M Vervoort, Remco Arts, Susann Katrina Julie Ludwig, Maarten Merkx
Monitoring the levels of therapeutic antibodies in individual patients would allow patient-specific dose optimization, with the potential for major therapeutic and financial benefits. Our group recently developed a new platform of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor) that allow antibody detection directly in blood plasma. In this study we targeted four clinically important therapeutic antibodies, the Her2-receptor targeting trastuzumab, the anti-CD20 antibodies rituximab and obinutuzumab, and the EGFR-blocking cetuximab...
February 14, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29440297/mi130004-a-novel-antibody-drug-conjugate-combining-trastuzumab-with-a-molecule-of-marine-origin-shows-outstanding-in-vivo-activity-against-her2-expressing-tumors
#9
Pablo M Aviles, Juan Manuel Dominguez, María José Guillén-Navarro, Maria Jose Muñoz-Alonso, Cristina Mateo, Raquel Rodriguez-Acebes, Jose Manuel Molina-Guijarro, Andrés Francesch, Juan Fernando Martínez-Leal, Simon Munt, Carlos M Galmarini, Carmen Cuevas
In the search for novel payloads to design new antibody-drug conjugates (ADCs), marine compounds represent an interesting opportunity given their unique chemical features. PM050489 is a marine compound that binds β-tubulin at a new site and disrupts the microtubule network hence leading to mitotic aberrations and cell death. PM050489 has been conjugated to trastuzumab via Cys residues through a non-cleavable linker and the resulting ADC, named MI130004, has been studied. Analysis of MI130004 delivered data consistent with the presence of two molecules of PM050489 per antibody molecule, likely bound to both sides of the intermolecular disulfide bond connecting the antibody light and heavy chains...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29439009/her2-testing-of-gastro-oesophageal-adenocarcinoma-a-commentary-and-guidance-document-from-the-association-of-clinical-pathologists-molecular-pathology-and-diagnostics-committee
#10
REVIEW
Newton A C S Wong, Fernanda Amary, Rachel Butler, Richard Byers, David Gonzalez, Harry R Haynes, Mohammad Ilyas, Manuel Salto-Tellez, Philippe Taniere
The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma...
February 8, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29437282/phagocytosis-of-antibody-opsonized-tumor-cells-leads-to-the-formation-of-a-discrete-vacuolar-compartment-in-macrophages
#11
Ramraj Velmurugan, Sreevidhya Ramakrishnan, Mingin Kim, Raimund J Ober, E Sally Ward
Despite the rapidly expanding use of antibody-based therapeutics to treat cancer, knowledge of the cellular processes following phagocytosis of antibody-opsonized tumor cells is limited. Here we report the formation of a phagosome-associated vacuole that is observed in macrophages as these degradative compartments mature following phagocytosis of HER2-positive cancer cells in the presence of the HER2-specific antibody, trastuzumab. We demonstrate that this vacuole is a distinct organelle that is closely apposed to the phagosome...
February 13, 2018: Traffic
https://www.readbyqxmd.com/read/29435713/incidence-of-infusion-hypersensitivity-reaction-after-withholding-dexamethasone-premedication-in-early-breast-cancer-patients-not-experiencing-two-previous-cycles-of-infusion-hypersensitivity-reaction-for-weekly-paclitaxel-chemotherapy
#12
Napa Parinyanitikul, Walailuk Tanpipattanakul, Nattaya Poovorawan, Thanapoom Rattananupong, Poranee Laoitthi, Piyada Sithidetphaiboon, Suebpong Thanasanvimon, Virote Sriuranpong
BACKGROUND: Premedication with dexamethasone is an essential part of the prevention of hypersensitivity reaction (HSR) associated with taxane administration. However, the possibility of stopping dexamethasone premedication has been investigated in previous studies to reduce the steroid's adverse events; however, either the result or the particular protocol was limited. Thus, our study aimed to evaluate the incidence of HSR after dexamethasone premedication discontinuation after lack of HSR in two previous weekly paclitaxel infusions...
February 12, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29434980/augmentation-of-antibody-dependent-cellular-cytotoxicity-with-defucosylated-monoclonal-antibodies-in-patients-with-gi-tract-cancer
#13
Takahiro Nakajima, Hirokazu Okayama, Mai Ashizawa, Masaru Noda, Keita Aoto, Motonobu Saito, Tomoyuki Monma, Shinji Ohki, Masahiko Shibata, Seiichi Takenoshita, Koji Kono
Enhancement of antibody-dependent cellular cytotoxicity (ADCC) with some modalities may be a promising approach to enhance the efficacy of therapeutic monoclonal antibodies (mAbs). It has previously been demonstrated that the removal of fucose from antibody oligosaccharides (defucosylation) leads to augmentation of ADCC activity. To establish clinically relevant evidence of this procedure, the present study evaluated trastuzumab- and cetuximab-mediated ADCC by comparing defucosylated mAbs with conventional mAbs using peripheral blood mononuclear cells (PBMCs)...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433963/pertuzumab-and-trastuzumab-with-or-without-metronomic-chemotherapy-for-older-patients-with-her2-positive-metastatic-breast-cancer-eortc-75111-10114-an-open-label-randomised-phase-2-trial-from-the-elderly-task-force-breast-cancer-group
#14
Hans Wildiers, Konstantinos Tryfonidis, Lissandra Dal Lago, Peter Vuylsteke, Giuseppe Curigliano, Simon Waters, Barbara Brouwers, Sevilay Altintas, Nathan Touati, Fatima Cardoso, Etienne Brain
BACKGROUND: Despite the high incidence of metastatic breast cancer and its related mortality in the elderly population, our knowledge about optimal treatment for older patients with cancer is far from adequate. We aimed to evaluate the efficacy of dual anti-HER2 treatment with or without metronomic chemotherapy in older patients with HER2-positive metastatic breast cancer. METHODS: We did a multicentre, open-label, randomised, phase 2 trial in 30 centres from eight countries in Europe, in patients with histologically proven, HER2-positive metastatic breast cancer, without previous chemotherapy for metastatic disease, who were 70 years or older, or 60 years or older with confirmed functional restrictions defined by protocol, and had a life expectancy of more than 12 weeks and a performance status according to WHO scale of 0-3...
February 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29430233/durable-and-complete-response-to-herceptin-monotherapy-in-patients-with-metastatic-gastroesophageal-cancer
#15
Brenen P Swofford, Tomislav Dragovich
Gastroesophageal cancer is the sixth leading cause of cancer-related death worldwide. The 2 most common histologies are squamous cell carcinoma and adenocarcinoma, which has seen an increase in incidence correlating with an increase in obesity in developed countries. Gastroesophageal adenocarcinoma has a preponderance to metastasize early, making it a highly lethal cancer with a low 5-year survival rate of ∼15-25%. Therefore, for the majority of patients, treatment focuses on palliation and prolongation of survival...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29429038/pharmacodynamic-modeling-of-cardiac-biomarkers-in-breast-cancer-patients-treated-with-anthracycline-and-trastuzumab-regimens
#16
Aurelia H M de Vries Schultink, Annelies H Boekhout, Jourik A Gietema, Artur M Burylo, Thomas P C Dorlo, J G Coen van Hasselt, Jan H M Schellens, Alwin D R Huitema
Trastuzumab is associated with cardiotoxicity, manifesting as a decrease of the left-ventricular ejection fraction (LVEF). Administration of anthracyclines prior to trastuzumab increases risk of cardiotoxicity. High-sensitive troponin T and N-terminal-pro-brain natriuretic peptide (NT-proBNP) are molecular markers that may allow earlier detection of drug-induced cardiotoxicity. In this analysis we aimed to quantify the kinetics and exposure-response relationships of LVEF, troponin T and NT-proBNP measurements, in patients receiving anthracycline and trastuzumab...
February 10, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29427213/treatment-strategies-in-octogenarians-with-early-stage-high-risk-breast-cancer
#17
Anita Mamtani, Julie J Gonzalez, Dayna T Neo, Robb S Friedman, Abram Recht, Michele R Hacker, Ranjna Sharma
BACKGROUND: Octogenarians with early-stage breast cancer often have low-risk tumor biology. However, optimal treatment strategies for those with high-risk biology remain unclear. METHODS: We reviewed the records of women ages 80-89 years with biopsy-proven, Stage I-II invasive breast cancer who were referred for surgical evaluation from January 2001 through December 2010. High-risk was defined as human epidermal growth factor receptor-positive (HER2+), triple-negative (TN), or histologic grade 3 disease...
February 9, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29426804/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biologic-therapies-an-infectious-diseases-perspective-cell-surface-receptors-and-associated-signaling-pathways
#18
REVIEW
J Aguilar-Company, M Fernández-Ruiz, R García-Campelo, A C Garrido-Castro, I Ruiz-Camps
BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest preventive recommendations...
February 6, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29426769/synthesis-and-evaluation-of-bifunctional-tetrahydroxamate-chelators-for-labeling-antibodies-with-89zr-for-imaging-with-positron-emission-tomography
#19
Julie Rousseau, Zhengxing Zhang, Xiaozhu Wang, Chengcheng Zhang, Joseph Lau, Etienne Rousseau, Milena Čolović, Navjit Hundal-Jabal, François Bénard, Kuo-Shyan Lin
Two novel bifunctional tetrahydroxamate chelators 3 and 4 were synthesized and evaluated for labeling antibodies with 89Zr for positron emission tomography imaging. Compared to previously reported tetrahydroxamate chelators 1 and 2 with an iminodiacetamide backbone, 3 and 4 were based on an extended iminodipropionamide and dipropylenetriamine backbone, respectively. Trastuzumab conjugates of 3 and 4 were efficiently labeled with 89Zr (>95% radiochemical yield). The in vitro plasma stability of 89Zr-4-Trastuzumab and especially 89Zr-3-Trastuzumab was greatly improved over previously reported 89Zr-1-Trastuzumab and 89Zr-2-Trastuzumab, but their demetalation remained higher and faster than 89Zr-deferoxamine (DFO)-Trastuzumab...
February 2, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29425028/high-throughput-cysteine-scanning-to-identify-stable-antibody-conjugation-sites-for-maleimide-and-disulfide-based-linkers
#20
Rachana Ohri, Sunil Bhakta, Aimee Fourie-O'Donohue, Josefa Dela Cruz-Chuh, Siao Ping Tsai, Ryan Cook, Binqing Wei, Carl Ng, Athena W Wong, Aaron B Bos, Farzam Farahi, Jiten Bhakta, Thomas H Pillow, Helga Raab, Richard Vandlen, Paul Polakis, Yichin Liu, Hans Erickson, Jagath R Junutula, Katherine R Kozak
THIOMAB antibody technology utilizes cysteine residues engineered onto an antibody to allow for site-specific conjugation. The technology has enabled the exploration of different attachment sites on the antibody in combination with small molecules, peptides, or proteins to yield antibody conjugates with unique properties. As reported previously ( Shen , B. Q. , et al. ( 2012 ) Nat. Biotechnol. 30 , 184 - 189 ; Pillow , T. H. , et al. ( 2017 ) Chem. Sci. 8 , 366 - 370 ), the specific location of the site of conjugation on an antibody can impact the stability of the linkage to the engineered cysteine for both thio-succinimide and disulfide bonds...
February 9, 2018: Bioconjugate Chemistry
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