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https://www.readbyqxmd.com/read/29333017/correlation-of-hormone-receptor-and-human-epidermal-growth-factor-receptor-2-neu-expression-in-breast-cancer-with-various-clinicopathologic-factors
#1
Cherry Bansal, Aarti Sharma, Mukta Pujani, Meenu Pujani, Kiran Lata Sharma, A N Srivastava, U S Singh
Background: A significant development in the breast carcinoma management is the correlation between the presence of hormone receptors in the tumor and response to hormonal therapy and chemotherapy. Human epidermal growth factor receptor-2/neu (Her-2/neu) overexpression also serves as a very useful parameter to predict response to herceptin. Aim of Study: The study was conducted to correlate immunohistochemical expression of markers such as estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu with various clinicopathologic parameters...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29330636/a-randomised-trial-comparing-the-pharmacokinetics-and-safety-of-the-biosimilar-ct-p6-with-reference-trastuzumab
#2
Francisco J Esteva, Justin Stebbing, Rebecca N Wood-Horrall, Peter J Winkle, Sung Young Lee, Sang Joon Lee
PURPOSE: Access to trastuzumab, a valuable anti-cancer treatment, can be limited by cost. The primary aim of this study was to evaluate and compare the PK profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference trastuzumab (Herceptin®) in healthy subjects. Secondary study aims included comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in these subjects. METHODS: We performed a single-dose, randomised, double-blind, parallel group study (NCT02665637) comparing CT-P6 with reference trastuzumab (6 mg/kg, 90 min intravenous infusion) in 70 healthy adult males...
January 12, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29328489/antibody-nanoparticle-conjugate-constructed-with-trastuzumab-and-nanoparticle-albumin-bound-paclitaxel-for-targeted-therapy-of-human-epidermal-growth-factor-receptor%C3%A2-2-positive-gastric-cancer
#3
Jian Xiong, Shuhua Han, Shuang Ding, Jingchao He, Haijun Zhang
Gastric cancer (GC) is the most lethal malignancy in the digestive system. This study investigated an antibody-nanoparticle conjugate (ANC) constructed with trastuzumab (Herceptin®) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane®) (trastuzumab/nab‑paclitaxel) as a novel strategy of targeted therapy for human epidermal growth factor receptor 2 (HER2) positive GC. The ANC was fabricated with trastuzumab and nab‑paclitaxel by a 'one-step' synthesis using EDC/NHS. In vitro antitumor efficacy was evaluated by cell viability, apoptosis rate and cell cycle of HER2-positive GC NCI‑N87 cells and compared with paclitaxel (Taxol®), nab‑paclitaxel and trastuzumab/nab‑paclitaxel...
January 9, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#4
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29311294/glycoengineering-of-antibody-herceptin-through-yeast-expression-and-in-vitro-enzymatic-glycosylation
#5
Chiu-Ping Liu, Tsung-I Tsai, Ting Cheng, Vidya S Shivatare, Chung-Yi Wu, Chung-Yi Wu, Chi-Huey Wong
Monoclonal antibodies (mAbs) have been developed as therapeutics, especially for the treatment of cancer, inflammation, and infectious diseases. Because the glycosylation of mAbs in the Fc region influences their interaction with effector cells that kill antibody-targeted cells, and the current method of antibody production is relatively expensive, efforts have been directed toward the development of alternative expressing systems capable of large-scale production of mAbs with desirable glycoforms. In this study, we demonstrate that the mAb trastuzumab expressed in glycoengineered P...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29305325/modeling-trastuzumab-related-cardiotoxicity-in-vitro-using-human-stem-cell-derived-cardiomyocytes
#6
Yosuke K Kurokawa, Michael R Shang, Rose T Yin, Steven C George
Trastuzumab (Herceptin®), a monoclonal antibody against the ErbB2 (HER2) receptor, has significantly improved clinical outcomes for HER2+ breast cancer patients. However, the drug also has known cardiotoxic side effects through mechanisms that are not fully understood. Here we utilized human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) to model trastuzumab-related cardiotoxicity in vitro. We demonstrate that cardiotoxic effects of ErbB2 inhibition by trastuzumab can be recapitulated only when the cardioprotective effects of ErbB2/4 signaling is observed...
January 2, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29302970/tailor-making-fluorescent-hyaluronic-acid-microgels-via-combining-microfluidics-and-photoclick-chemistry-for-sustained-and-localized-delivery-of-herceptin-in-tumor
#7
Jing Chen, Ke Huang, Qijun Chen, Chao Deng, Jian Zhang, Zhiyuan Zhong
Antibody therapeutics though representing a most used biomedicine suffers from poor in vivo stability, rapid degradation, and frequent injections. Here, we report that fluorescent hyaluronic acid microgels (HMGs) tailor-made by combining microfluidics and "tetrazole-alkene" photoclick chemistry enable sustained and localized delivery of Herceptin in ovarian tumor. HMGs were obtained with defined size (25-50 μm), narrow size distribution, high stability, and strong green fluorescence. Notably, HMGs exhibited a remarkably high loading of proteins like Herceptin and IgG with a loading efficiency exceeding 90% at a theoretical protein loading content of 30 wt...
January 5, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29301815/triple-receptor-positive-primary-neuroendocrine-carcinoma-of-breast-in-a-young-patient
#8
Manu Vats, Vivek Sachan, Sahaj Prajapati, Shramana Mandal
Primary neuroendocrine carcinoma of breast is a very rare malignancy and preoperative diagnosis is difficult by clinical examination alone.Most oftenly, histopathological examination (HPE) and immunohistochemistry (IHC) studies are required to establish the diagnosis. We describe here a case of a primary neuroendocrine carcinoma of right breast in a 32-year-old woman. The patient underwent a right modified radical mastectomy, and the diagnosis was conclusively established postoperatively by the HPE and IHC reports...
January 4, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29281678/the-natural-compound-jatrophone-interferes-with-wnt-%C3%AE-catenin-signaling-and-inhibits-proliferation-and-emt-in-human-triple-negative-breast-cancer
#9
Iram Fatima, Ikbale El-Ayachi, Ling Taotao, M Angeles Lillo, Raya Krutilina, Tiffany N Seagroves, Tomasz W Radaszkiewicz, Miroslav Hutnan, Vitezslav Bryja, Susan A Krum, Fatima Rivas, Gustavo A Miranda-Carboni
Metastatic breast cancer is the leading cause of worldwide cancer-related deaths among women. Triple negative breast cancers (TNBC) are highly metastatic and are devoid of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) amplification. TNBCs are unresponsive to Herceptin and/or anti-estrogen therapies and too often become highly chemoresistant when exposed to standard chemotherapy. TNBCs frequently metastasize to the lung and brain. We have previously shown that TNBCs are active for oncogenic Wnt10b/β-catenin signaling and that WNT10B ligand and its downstream target HMGA2 are predictive of poorer outcomes and are strongly associated with chemoresistant TNBC metastatic disease...
2017: PloS One
https://www.readbyqxmd.com/read/29277785/establishment-of-a-patient-derived-xenograft-for-development-of-personalized-her2-targeting-therapy-in-gastric-cancer
#10
Seol Hwa Shin, Seok Soon Park, Eun Jin Ju, Jin Park, Eun Jeong Ko, Jung Jin Hwang, Young-Ah Suh, Se Jin Jang, Jung Shin Lee, Bong-Kook Ko, Kyu-Tae Kim, Jong-Seo Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
BACKGROUND/AIM: To maximize success rate for development of HER2-targeted therapeutics, patient-derived xenograft (PDX) models reflecting HER2-positive gastric cancer (HER2+ GC) patients were established. MATERIALS AND METHODS: GC tissues obtained from surgery of GC patients were implanted into immune-deficient mice, and tumor tissue of HER2+ PDXs were verified of the patient-mimic HER2 expression by immunohistochemistry and explored for the feasibility by testing with Herceptin, the approved therapeutics and novel HER2 antibody therapeutics being developed...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29276266/financial-effect-of-a-drug-distribution-model-change-on-a-health-system
#11
Erin M Turingan, Bijan C Mekoba, Samuel M Eberwein, Patricia A Roberts, Ashley L Pappas, Jennifer L Cruz, Lindsey B Amerine
Background: Drug manufacturers change distribution models based on patient safety and product integrity needs. These model changes can limit health-system access to medications, and the financial impact on health systems can be significant. Objective: The primary aim of this study was to determine the health-system financial impact of a manufacturer's change from open to limited distribution for bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin). The secondary aim was to identify opportunities to shift administration to outpatient settings to support formulary change...
June 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/29245056/subcutaneous-trastuzumab-herceptin-versus-intravenous-trastuzumab-for-the-treatment-of-patients-with-her2-positive-breast-cancer-a-time-motion-and-cost-assessment-study-in-a-lean-operating-day-care-oncology-unit
#12
Wiebren A A Tjalma, Tom Van den Mooter, Tim Mertens, Valerie Bastiaens, Manon T Huizing, Konstantinos Papadimitriou
OBJECTIVE: The subcutaneous (SC) formulation of trastuzumab represents an alternative to the intravenous (IV) infusion in the treatment of patients with HER2-positive metastatic and early breast cancer. We compared the two formulations in terms of time and cost differential. STUDY DESING: We conducted a time, motion and cost assessment study in a lean operating day care oncology unit to determine and compare the time and costs of trastuzumab SC versus IV administration in patients with HER2-positive breast cancer...
December 7, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29216514/modulation-of-in-vitro-phagocytic-uptake-and-immunogenicity-potential-of-modified-herceptin%C3%A2-conjugated-plga-peg-nanoparticles-for-drug-delivery
#13
Apurva Badkas, Evan Frank, Zilan Zhou, Mina Jafari, Harish Chandra, Vishnu Sriram, Joo-Youp Lee, Jagjit S Yadav
There is an increasing interest in engineered nanoparticle (NP) conjugates for targeted and controlled drug delivery. However, the practical applications of these NP delivery vehicles remain constrained because of their reactivity with the body's immune system defenses resulting in undesirable off-target effects. In this study, poly(D,L lactide-co-glycolide) (PLGA)-b-polyethylene glycol (PEG) NPs conjugated to different quantities of the commercial antibody Herceptin® meant to target HER2-positive breast cancer cells were studied for their immune cell uptake and immunogenic properties (using murine macrophages and human dendritic cells)...
December 4, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29173039/engineered-aglycosylated-full-length-igg-fc-variants-exhibiting-improved-fc%C3%AE-riiia-binding-and-tumor-cell-clearance
#14
Migyeong Jo, Hyeong Sun Kwon, Kwang-Hoon Lee, Ji Chul Lee, Sang Taek Jung
FcγRIIIa, which is predominantly expressed on the surface of natural killer cells, plays a key role in antibody-dependent cell-mediated cytotoxicity (ADCC), a major effector function of therapeutic IgG antibodies that results in the death of aberrant cells. Despite the potential uses of aglycosylated IgG antibodies, which can be easily produced in bacteria and do not have complicated glycan heterogeneity issues, they show negligible binding to FcγRIIIa and abolish the activation of immune leukocytes for tumor cell clearance, in sharp contrast to most glycosylated IgG antibodies used in the clinical setting...
November 27, 2017: MAbs
https://www.readbyqxmd.com/read/29172171/trastuzumab-for-metastatic-breast-cancer-real-world-outcomes-from-an-australian-whole-of-population-cohort-2001-2016
#15
Benjamin Daniels, Belinda E Kiely, Sarah J Lord, Nehmat Houssami, Christine Y Lu, Robyn L Ward, Sallie-Anne Pearson
PURPOSE: Outcomes for patients treated in clinical trials may not reflect the experience in routine clinical care. We aim to describe the real-world treatment patterns and overall survival (OS) for women receiving trastuzumab for metastatic breast cancer (MBC). METHODS: Retrospective, whole-of-population cohort study using demographic, dispensing, and medical services data for women in the Herceptin Program for HER2+MBC. We estimated time on trastuzumab and OS from first dispensing of trastuzumab for MBC and rates of cardiac monitoring prior to and during treatment...
November 21, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29163501/herceptin-enhances-the-antitumor-effect-of-natural-killer-cells-on-breast-cancer-cells-expressing-human-epidermal-growth-factor-receptor-2
#16
Xiao Tian, Feng Wei, Limei Wang, Wenwen Yu, Naining Zhang, Xinwei Zhang, Ying Han, Jinpu Yu, Xiubao Ren
Optimal adoptive cell therapy (ACT) should contribute to effective cancer treatment. The unique ability of natural killer (NK) cells to kill cancer cells independent of major histocompatibility requirement makes them suitable as ACT tools. Herceptin, an antihuman epidermal growth factor receptor-2 (anti-HER2) monoclonal antibody, is used to treat HER2+ breast cancer. However, it has limited effectiveness and possible severe cardiotoxicity. Given that Herceptin may increase the cytotoxicity of lymphocytes, we explored the possible augmentation of NK cell cytotoxicity against HER2+ breast cancer cells by Herceptin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29069935/trastuzumab-modified-dm1-loaded-nanoparticles-for-her2-breast-cancer-treatment-an-in-vitro-and-in-vivo-study
#17
Ling Rong, Shuping Zhou, Xinkuang Liu, Amin Li, Tao Jing, Xueke Liu, Yinci Zhang, Shiyu Cai, Xiaolong Tang
BACKGROUND: Emtansine (DM1) is a highly potent anti-microtubule agent that has shown promising results for breast cancer treatment, but side effects limit its widespread clinical use. In this research, a new nano-drug was developed to integrate DM1 agent with antibody targeting. METHODS: A system of novel nanoparticles (NPs) DM1-NPs-trastuzumab (DM1-NPs-Tmab) of DM1 combined with (anti-HER2 antibody, Herceptin®, Trastuzumab) was developed for HER2(+) breast cancer treatment, and its physical characterization and antitumor biological activity were investigated...
October 25, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29040918/tumor-cryoablation-in-combination-with-natural-killer-cells-therapy-and-herceptin-in-patients-with-her2-overexpressing-recurrent-breast-cancer
#18
Shuzhen Liang, Lizhi Niu, Kecheng Xu, Xiaohua Wang, Yingqing Liang, Mingjie Zhang, Jibing Chen, Mao Lin
In this study, we investigated the clinical benefits of a combination of tumor cryoablation with natural killer (NK) cells therapy and Herceptin for human epidermal growth factor (HER) 2-overexpressing recurrent breast cancer. From May 2015 to May 2016, 48 patients who met the enrollment criteria were assigned to three groups (n=16): cryoablation group (group I), cryoablation-NK cells therapy group (group II) and cryoablation-NK cells therapy-Herceptin group (group III). Safety and short-term effects were evaluated...
December 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29038808/decoration-of-trastuzumab-with-short-oligonucleotides-synthesis-and-detailed-characterization
#19
A M Carvalho, A Manicardi, C Véliz Montes, S B Gunnoo, R J Schneider, A Madder
Trastuzumab (Herceptin®) is an FDA-approved therapeutic antibody currently employed in the treatment of metastatic stages of breast cancer. Herein, we propose a simple, fast and cost-effective methodology to conjugate trastuzumab with 22-mer 5' thiol-modified oligonucleotides using a bifunctional crosslinker. The conjugates were successfully characterized by MALDI-ToF MS and SDS-PAGE, obviating the need for enzymatic digestion and difficult chromatographic separations. Furthermore, ELISA was performed to ensure that trastuzumab activity is not affected by oligonucleotide conjugation...
October 31, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29017563/herceptin%C3%A2-trastuzumab-in-her2-positive-early-breast-cancer-protocol-for-a-systematic-review-and-cumulative-network-meta-analysis
#20
Florence R Wilson, Megan E Coombes, Quinlan Wylie, Mariya Yurchenko, Christine Brezden-Masley, Brian Hutton, Becky Skidmore, Chris Cameron
BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive disease that makes up about 20% of all invasive breast cancers. HER2+ breast cancer is associated with poor prognosis and high mortality rates, but the development of HER2-targeted therapies, such as originator trastuzumab (Herceptin®), has substantially improved patient survival. Numerous clinical trials and reviews have investigated the efficacy of HER2-targeted therapies over the past few decades; however, no study has specifically investigated the vast body of evidence on trastuzumab in comparison to chemotherapy regimens, endocrine therapies, and other targeted therapies...
October 10, 2017: Systematic Reviews
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