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https://www.readbyqxmd.com/read/28648785/lc-ms-bioanalysis-of-trastuzumab-and-released-emtansine-using-nano-surface-and-molecular-orientation-limited-nsmol-proteolysis-and-liquid-liquid-partition-in-plasma-of-trastuzumab-emtansine-treated-breast-cancer-patients
#1
Noriko Iwamoto, Akihiko Shimomura, Kenji Tamura, Akinobu Hamada, Takashi Shimada
Antibody-drug conjugates (ADCs) consist of monoclonal antibody and cytotoxic drugs covalently attached via stable crosslinkers, and are prospective antibody drugs for cancer therapy. To cover the overall pharmacokinetic understanding of ADCs, both the antibody and the released drugs are necessary for practical clinical observation. The nano-surface and molecular-orientation limited (nSMOL) proteolysis is a universal approach for antibody bioanalysis that enable Fab-selective proteolysis, which maintains antibody sequence specificity while decreasing excess analyte peptides...
June 19, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28648618/patients-preference-of-trastuzumab-administration-subcutaneous-versus-intravenous-in-her2-positive-metastatic-breast-cancer-results-of-the-randomised-metaspher-study
#2
X Pivot, J P Spano, M Espie, P Cottu, C Jouannaud, V Pottier, L Moreau, J M Extra, A Lortholary, P Rivera, D Spaeth, H Attar-Rabia, C Benkanoun, L Dima-Martinez, N Esposito, J Gligorov
HannaH (NCT00950300) and PrefHer (NCT01401166) studies validated the subcutaneous (H-s.c.) formulation of trastuzumab as effective and safe as intravenous (H-i.v.) and highly preferred by patients in early breast cancer. The present randomised MetaspHer trial (NCT01810393) is the first study assessing patient's preference in metastatic setting. METHODS: Patients with HER2-positive metastatic breast cancer who completed a first line chemotherapy with trastuzumab and achieved a long-term response lasting more than 3 years were randomised to receive 3 cycles of 600-mg fixed-dose adjuvant H-s...
June 22, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28643558/influence-of-anthropometric-characteristics-in-patients-with-her2-positive-breast-cancer-on-initial-plasma-concentrations-of-trastuzumab
#3
Jonathan González García, Fernando Gutiérrez Nicolás, Gloria Julia Nazco Casariego, José Norberto Batista López, Isaac Ceballos Lenza, Ruth Ramos Díaz, Matías Llabrés Martínez
BACKGROUND: Plasma concentrations of trastuzumab <20 µg/mL in patients with gastric cancer are associated with reduced progression-free and overall survival. In breast cancer treatment, this relationship has not yet been studied, but a suboptimal pharmacodynamic exposure to trastuzumab could be a reason for therapeutic failure of treatment of HER2-positive breast cancer. OBJECTIVE: The objective of the present study was to determine the proportion of nonmetastatic HER2-positive breast cancers that do not reach a minimum plasma concentration ( Cmin) of 20 µg/mL after first drug administration, established as therapeutically effective in clinical trials...
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28643145/the-prognostic-value-of-volume-based-parameters-using-18-f-fdg-pet-ct-in-gastric-cancer-according-to-her2-status
#4
Ji Soo Park, Nare Lee, Seung Hoon Beom, Hyo Song Kim, Choong-Kun Lee, Sun Young Rha, Hyun Cheol Chung, Mijin Yun, Arthur Cho, Minkyu Jung
BACKGROUND: We aimed to find the clinical value of metastatic tumor burden evaluated with F18-FDG PET/CT in gastric cancer patients, considering the human epidermal growth factor receptor 2 (HER2) status. METHODS: We retrospectively reviewed 124 patients with locally advanced or metastatic gastric cancer at Yonsei Cancer Center between January 2006 and December 2014 who had undergone baseline FDG PET/CT before first-line chemotherapy. We measured the maximum standardized uptake value from the primary tumor (SUVmax) and whole-body (WB) PET/CT parameters, including WB SUVmax, WB SUVmean, WB metabolic tumor volume (WB MTV), and WB total lesion glycolysis (WB TLG), in all metabolically active metastatic lesions (SUV threshold ≥2...
June 22, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28642833/creating-a-biomarker-panel-for-early-detection-of-chemotherapy-related-cardiac-dysfunction-in-breast-cancer-patients
#5
Krithika Srikanthan, Rebecca Klug, Maria Tirona, Ellen Thompson, Haresh Visweshwar, Nitin Puri, Joseph Shapiro, Komal Sodhi
Cardiotoxicity is an important issue for breast cancer patients receiving anthracycline-trastuzumab therapy in the adjuvant setting. Studies show that 3-36% of patients receiving anthracyclines and/or trastuzumab experience chemotherapy related cardiac dysfunction (CRCD) and approximately 17% of patients must stop chemotherapy due to the consequences of CRCD. There is currently no standardized, clinically verified way to detect CRCD early, but common practices include serial echocardiography and troponin measurements, which can be timely, costly, and not always available in areas where health care resources are scarce...
March 2017: Journal of Clinical & Experimental Cardiology
https://www.readbyqxmd.com/read/28639285/porphyrin-modified-trastuzumab-improves-efficacy-of-her2-targeted-photodynamic-therapy-of-gastric-cancer
#6
Barbara Korsak, Gabriela M Almeida, Sara Rocha, Carla Pereira, Nuno Mendes, Hugo Osório, Patrícia M R Pereira, João M M Rodrigues, Rudolf J Schneider, Bruno Sarmento, João P C Tomé, Carla Oliveira
Gastric cancer (GC) is the 3(rd) deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in ∼20% of GC cases and anti-HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2-positive metastatic GC. This strategy improves GC patients' survival by 2-3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2-positive GC...
June 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28638738/activation-of-the-fcgammareceptoriiia-on-human-natural-killer-cells-leads-to-increased-expression-of-functional-interleukin-21-receptor
#7
Elizabeth L McMichael, Nicholas B Courtney, Megan C Duggan, Robert Wesolowski, Dionisia Quiroga, Sri Vidya Kondadasula, Lakhvir S Atwal, Neela Bhave, Eric Luedke, Alena Cristina Jaime-Ramirez, Amanda R Campbell, Xiaokui Mo, John C Byrd, William E Carson Iii
Natural killer (NK) cells are innate immune effector cells that play a crucial role in immune surveillance and the destruction of cancer cells. NK cells express a low-affinity receptor for the Fc or constant region of immunoglobulin G (FcγRIIIa) and multiple cytokine receptors that respond to antibody-coated targets and cytokines in the tumor microenvironment. In the present work, microarray gene expression analysis revealed that the IL-21 receptor (IL-21R) was strongly upregulated following FcR stimulation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637802/tumor-uptake-of-64-cu-dota-trastuzumab-in-patients-with-metastatic-breast-cancer
#8
Joanne E Mortimer, James R Bading, Jinha M Park, Paul H Frankel, Mary I Carroll, Tri T Tran, Erasmus K Poku, Russell C Rockne, Andrew A Raubitschek, John E Shively, David M Colcher
Purpose: To characterize the relationship between tumor uptake of (64)Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Experimental Design: Women with biopsy-confirmed MBC and not given trastuzumab for [&ge] 2 months underwent complete staging, including (18)F-fluorodeoxyglucose PET/CT. Patients were classified as HER2-positive (HER2+) or negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented IHC of biopsied tumor tissue...
June 21, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28637800/pharmacokinetics-biodistribution-and-radiation-dosimetry-for-89-zr-trastuzumab-in-patients-with-esophagogastric-cancer
#9
Joseph A O'Donoghue, Jason S Lewis, Neeta Pandit-Taskar, Stephen E Fleming, Heiko Schoder, Steven M Larson, Volkan Beylergil, Shutian Ruan, Serge Lyashchenko, Pat B Zanzonico, Wolfgang Andreas Weber, Jorge A Carrasquillo, Yelena Y Janjigian
Trastuzumab with chemotherapy improves clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive esophagogastric adenocarcinoma (EGA). Despite the therapeutic benefit, responses are rarely complete and the majority of patients develop progression. This is the first report evaluating (89)Zr-trastuzumab in HER2-positive EGA in which we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry. Methods: Trastuzumab was conjugated with deferoxamine and radiolabeled with (89)Zr...
June 21, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28636984/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#10
Jian Zhang, Leiping Wang, Zhonghua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Zhimin Shao, Xichun Hu
Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. We initiated the single-center, randomized, open-label, phase II study to determine whether the addition of metronomic cyclophosphamide to docetaxel (T) (w/o trastuzumab) improves overall response rate (ORR) as first-line treatment among patients with non-triple-negative metastatic breast cancer (MBC). Eligible patients with previously untreated non-triple-negative MBC were randomly assigned (1:1) to receive 3-weekly cycles of Metro-TC (T 75mg/m2, d1 plus oral cyclophosphamide 50 mg daily) or T alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636559/resource-utilization-and-cost-saving-analysis-of-subcutaneous-versus-intravenous-trastuzumab-in-early-breast-cancer-patients
#11
Alberto Farolfi, Paolo Silimbani, Davide Gallegati, Elisabetta Petracci, Alessio Schirone, Mattia Altini, Carla Masini
We conducted an economic evaluation of intravenous (IV) vs subcutaneous (SC) trastuzumab for the treatment of patients with early breast cancer (EBC). Data of patients receiving adjuvant IV trastuzumab at our institute in 2014 were used to study three different treatment scenarios: 1) IV trastuzumab, 2) SC trastuzumab, and 3) IV trastuzumab during chemotherapy followed by SC trastuzumab. Our cohort included 114 patients with a median weight of 63.75 kg. Scenario 2 was the most time-saving treatment, with 71...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636558/prognostic-significance-of-clinicopathological-factors-in-early-breast-cancer-20-years-of-follow-up-in-a-single-center-analysis
#12
Valentina Cocciolone, Katia Cannita, Maria Letizia Calandrella, Enrico Ricevuto, Paola Lanfiuti Baldi, Tina Sidoni, Azzurra Irelli, Stefania Paradisi, Laura Pizzorno, Valter Resta, Alberto Bafile, Edoardo Alesse, Alessandra Tessitore, Corrado Ficorella
BACKGROUND: To quantify the effect of traditional prognostic factors [nodal status, estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2)] on long-term outcome of patients with early breast cancer (EBC), treated in clinical practice over a period of about twenty years. RESULTS: 1198 consecutive patients were identified. Median DFS (disease-free survival): ER+/PR±/HER2-, 165 months (mo) if node-negative (N0) and 114mo if node-positive (N+) (p < 0...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630463/the-role-of-antibody-v%C3%AE%C2%BA-framework-3-region-towards-antigen-binding-effects-on-recombinant-production-and-protein-l-binding
#13
Chinh Tran-To Su, Wei-Li Ling, Wai-Heng Lua, Jun-Jie Poh, Samuel Ken-En Gan
Antibody research has traditionally focused on heavy chains, often neglecting the important complementary role of light chains in antibody formation and secretion. In the light chain, the complementarity-determining region 3 (VL-CDR3) is specifically implicated in disease states. By modulating VL-CDR3 exposure on the scaffold through deletions in the framework region 3 (VL-FWR3), we further investigated the effects on secretion in recombinant production and antigen binding kinetics. Our random deletions of two residues in the VL-FWR3 of a Trastuzumab model showed that the single deletions could impact recombinant production without significant effect on Her2 binding...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629338/a-phase-2-randomized-trial-to-evaluate-the-impact-of-a-supervised-exercise-program-on-cardiotoxicity-at-3%C3%A2-months-in-patients-with-her2-overexpressing-breast-cancer-undergoing-adjuvant-treatment-by-trastuzumab-design-of-the-cardapac-study
#14
Quentin Jacquinot, Nathalie Meneveau, Marion Chatot, Franck Bonnetain, Bruno Degano, Malika Bouhaddi, Gilles Dumoulin, Dewi Vernerey, Xavier Pivot, Fabienne Mougin
BACKGROUND: The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer is a poor prognosis. Trastuzumab improves overall survival but is associated with cardiotoxicity, especially a decline in left ventricular ejection fraction (LVEF). In addition, chemotherapy and radiotherapy increase fatigue and pain, decrease physical capacity and health-related quality of life. To date, no study has evaluated the benefits of physical activity on the side effects of treatment in patients with HER2 positive breast cancer...
June 19, 2017: BMC Cancer
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
#15
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/28625044/her2-status-and-its-heterogeneity-in-gastric-carcinoma-of-vietnamese-patients
#16
Dang Anh Thu Phan, Vu Thien Nguyen, Thi Ngoc Ha Hua, Quoc Dat Ngo, Thi Phuong Thao Doan, Sao Trung Nguyen, Anh Tu Thai, Van Thanh Nguyen
Background: Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab. Materials and Methods: We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH...
June 19, 2017: Journal of Pathology and Translational Medicine
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
#17
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...
June 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28623459/blockade-of-cd112r-and-tigit-signaling-sensitizes-human-natural-killer-cell-functions
#18
Feng Xu, Alexander Sunderland, Yue Zhou, Richard D Schulick, Barish H Edil, Yuwen Zhu
Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity...
June 16, 2017: Cancer Immunology, Immunotherapy: CII
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
#19
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/28623237/nice-approves-trastuzumab-emtansine-after-deal-with-drug-company
#20
Zosia Kmietowicz
No abstract text is available yet for this article.
June 15, 2017: BMJ: British Medical Journal
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