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trastuzumab

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https://www.readbyqxmd.com/read/28531814/targeting-egfr-her2-heterodimerization-with-a-novel-anti-her2-domain-ii-iii-antibody
#1
Xiaojie Yu, Lingfei Wang, Yafeng Shen, Chao Wang, Yajun Zhang, Yanchun Meng, Yang Yang, Beibei Liang, Bo Zhou, Huajing Wang, Huafeng Wei, Changhai Lei, Shi Hu, Bohua Li
HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2...
May 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28531278/cardiovascular-toxic-effects-of-targeted-cancer-therapy
#2
Kazuko Tajiri, Kazutaka Aonuma, Ikuo Sekine
Over the past decade, there has been a major shift in chemotherapy from non-specific cytotoxic drugs to molecular targeted drug therapies. As more molecular targeted therapies are developed, new types of cardiovascular toxicities induced by targeted therapies are a growing problem. Cardiotoxicity induced by the human epidermal growth factor receptor-2 inhibitor trastuzumab manifests as decreased left ventricular ejection fraction. In contrast to anthracycline treatment, most cardiac events occur during trastuzumab treatment, but are reversed quickly when treatment is interrupted and cardiac intervention is established...
May 20, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28529342/circulating-tumor-cells-and-serum-levels-of-mmp-2-mmp-9-and-vegf-as-markers-of-the-metastatic-process-in-patients-with-high-risk-of-metastatic-progression
#3
Marketa Skerenova, Veronika Mikulova, Otakar Capoun, Tomas Zima, Petra Tesarova
BACKGROUND AND AIMS: Metastases are a severe complication in cancer patients and biomarkers predicting their progression are still lacking for specific groups of patients. HER2 positive breast cancer (HER2 BC) patients on trastuzumab therapy are at risk of the development of unpredictable and often fatal central nervous system (CNS) metastases and castration resistant prostate cancer (CRPC) patients urgently need a marker of disease progression during therapy. Proposed metastatic markers: circulating tumor cells (CTC), serum levels of matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and vascular endothelial growth factor (VEGF) were prospectively studied to confirm their utility in these two narrowly defined groups of cancer patients...
May 16, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28528212/targeted-co-delivery-of-polypyrrole-and-rapamycin-by-trastuzumab-conjugated-liposomes-for-combined-chemo-photothermal-therapy
#4
Hanh Thuy Nguyen, Tuan Hiep Tran, Raj Kumar Thapa, Cao Dai Phung, Beom Soo Shin, Jee-Heon Jeong, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Trastuzumab is a therapeutic monoclonal antibody that selectively recognizes HER2/neu receptor for targeting breast cancers. In this study, we aimed to present a strategy to combine chemo and phototherapy and targeted delivery via monoclonal antibody for enhanced anticancer effects. We co-loaded a chemotherapeutic agent, rapamycin, and a photosensitizer, polypyrrole, in trastuzumab-conjugated liposomes (LRPmAb) for combined chemo-photothermal therapy. LRPmAb had small size (172.2±9.6nm), narrow distribution, and negative ζ-potential (-12...
May 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28527420/factors-predictive-of-locoregional-recurrence-following-neoadjuvant-chemotherapy-in-patients-with-large-operable-or-locally-advanced-breast-cancer-an-analysis-of-the-eortc-10994-big-1-00-study
#5
Pauline Gillon, Nathan Touati, Christel Breton-Callu, Leen Slaets, David Cameron, Hervé Bonnefoi
PURPOSE: Identification of clinicopathological factors predicting for a locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC) could help to decide on the optimal locoregional radiotherapy. The objective of this trial is to identify those factors in the context of a phase III trial (European Organisation for Research and Treatment of Cancer 10994). METHODS: Patients received NAC followed by surgery with or without radiotherapy. Radiotherapy was administered according to pre-specified guidelines...
May 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28526538/trastuzumab-emtansine-versus-treatment-of-physician-s-choice-in-patients-with-previously-treated-her2-positive-metastatic-breast-cancer-th3resa-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#6
Ian E Krop, Sung-Bae Kim, Antonio Gonzalez Martin, Patricia M LoRusso, Jean-Marc Ferrero, Tanja Badovinac-Crnjevic, Silke Hoersch, Melanie Smitt, Hans Wildiers
BACKGROUND: In the randomised, parallel assignment, open-label, phase 3 TH3RESA study, progression-free survival was significantly longer with trastuzumab emtansine versus treatment of physician's choice in previously treated patients with HER2-positive advanced breast cancer. We report results from the final overall survival analysis of the TH3RESA trial. METHODS: Eligible patients for the TH3RESA trial were men and women (aged ≥18 years) with centrally confirmed HER2-positive advanced breast cancer previously treated with both trastuzumab and lapatinib (advanced setting) and a taxane (any setting) and with progression on two or more HER2-directed regimens in the advanced setting...
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526537/trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer
#7
Filippo Montemurro
No abstract text is available yet for this article.
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#8
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526406/trastuzumab-emtansine-suppresses-the-growth-of-her2-positive-small-cell-lung-cancer-in-preclinical-models
#9
Osamu Morimura, Toshiyuki Minami, Takashi Kijima, Shohei Koyama, Tomoyuki Otsuka, Yuhei Kinehara, Akio Osa, Masayoshi Higashiguchi, Kotaro Miyake, Izumi Nagatomo, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
Overcoming chemoresistance is essential for achieving better prognoses in SCLC. Previously, we reported that HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance. HER2-upregulated cisplatin- or etoposide-resistant SCLC cells were sensitive to trastuzumab-mediated ADCC. However, irinotecan-resistant SCLC cells, such as SBC-3/SN-38, were refractory to trastuzumab despite high HER2 expression. To address this issue, we examined the antitumor efficacy of trastuzumab emtansine (T-DM1) on trastuzumab-resistant HER2-positive SCLC...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526187/chemotherapy-may-eradicate-ductal-carcinoma-in-situ-dcis-but-not-the-associated-microcalcifications
#10
H Goldberg, J Zandbank, V Kent, M Leonov-Polak, A Livoff, A Chernihovsky, M Guindy, E Evron
INTRODUCTION: We studied the effect of neoadjuvant chemotherapy (NAC) ± trastuzumab on the ductal carcinoma in situ (DCIS) component in patients with locally advanced breast cancer who achieved pathological complete response (pCR). METHODS: The diagnostic biopsies of 92 consecutive breast cancer patients that were treated with neoadjuvant chemotherapy (NAC) ± trastuzumab were evaluated for the presence of DCIS. Upon completion of NAC, the surgical specimens were evaluated for complete eradication of both the invasive and non-invasive cancer in the breast...
May 4, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28525810/tumor-infiltrating-lymphocytes-in-patients-with-her2-positive-breast-cancer-treated-with-neoadjuvant-chemotherapy-plus-trastuzumab-lapatinib-or-their-combination-a-meta-analysis-of-randomized-controlled-trials
#11
REVIEW
C Solinas, M Ceppi, M Lambertini, M Scartozzi, L Buisseret, S Garaud, D Fumagalli, E de Azambuja, R Salgado, C Sotiriou, K Willard-Gallo, M Ignatiadis
BACKGROUND: A relationship between baseline tumor-infiltrating lymphocytes (TIL) and outcomes has been described in HER2-positive breast cancer. Nevertheless, the magnitude of this association and whether this effect differs based on the type of anti-HER2 agent remain controversial. This meta-analysis investigated the association between baseline TIL and pathologic complete response (pCR) rates in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination...
May 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28521178/impact-of-2013-asco-cap-guidelines-on-her2-determination-of-invasive-breast-cancer-a-single-institution-experience-using-frontline-dual-color-fish
#12
M Ragazzi, A Bisagni, E Gasparini, E Kuhn, C Bassano, I Tamagnini, M Foroni, M Bortesi, G Falco, G Ferrari, L Braglia, L Savoldi, A Bologna, R Di Cicilia, G Bisagni, G Gardini
PURPOSE: The new ASCO/CAP guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2-FISH, introducing the most controversial change to the HER2-equivocal category. We retrospectively evaluated the impact of AC2013 in a cohort of consecutive invasive breast cancers (IBCs) analyzed with frontline dual-color FISH. METHODS: 2788 consecutive IBCs were reclassified based on the AC2013 guidelines. Clinico-pathological features of equivocal IBCs were compared with HER2-negative and HER2-positive IBCs...
May 15, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28516782/exploring-site-specific-n-glycosylation-of-hek293-and-plant-produced-human-iga-isotypes
#13
Kathrin Göritzer, Daniel Maresch, Friedrich Altmann, Christian Obinger, Richard Strasser
The full potential of recombinant Immunoglobulin A as therapeutic antibody is not fully explored, owing to the fact that structure-function relationships of these extensively glycosylated proteins are not well understood. Here, monomeric IgA1, IgA2m(1) and IgA2m(2) variants of the anti-HER2 antibody (IgG1) trastuzumab were expressed in glyco-engineered Nicotiana benthamiana plants and in human HEK293-6E cells. All three IgA isotypes were purified and subjected to biophysical and biochemical characterization...
May 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28514745/combating-acquired-resistance-to-trastuzumab-by-an-anti-erbb2-fully-human-antibody
#14
Chao Wang, Lingfei Wang, Xiaojie Yu, Yajun Zhang, Yanchun Meng, Huajing Wang, Yang Yang, Jie Gao, Huafeng Wei, Jian Zhao, Cuihua Lu, Han Chen, Yanping Sun, Bohua Li
Trastuzumab resistance is a common problem that impedes the effectiveness of trastuzumab in ErbB2-amplified cancers. About 70% of ErbB2-amplified breast cancers do not respond to trastuzumab (de novo resistance), and the majority of the trastuzumab-responsive cancers progress within 1 year (acquired resistance). Different mechanisms exist between de novo and acquired resistance. Innate resistance mechanisms are mainly independent of ErbB2 receptor activity, and acquired resistance involves with alterations depending on ErbB2 activity...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514732/structural-basis-of-a-novel-heterodimeric-fc-for-bispecific-antibody-production
#15
Hudie Wei, Haiyan Cai, Yuhao Jin, Pilin Wang, Qingqing Zhang, Yihui Lin, Weixiao Wang, Jinke Cheng, Naiyan Zeng, Ting Xu, Aiwu Zhou
Bispecific antibodies provide an efficient tool for combinational clinical therapy. Here we have engineered a heterodimeric Fc for bispecific antibodies production by combining the knob-into-hole and electrostatic steering strategies where a bulky hydrophobic residue Phe405 of the IgG CH3 interface is mutated to a charged residue Lys and Lys409 of the corresponding CH3 domain is mutated to Ala. The crystal structure of this Fc heterodimer solved here at 2.7Å resolution revealed how these two mutations resulted a complementary binding interface and explained why F405K mutation could effectively inhibit Fc homodimer formation during protein expression...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514302/safety-and-efficacy-evaluation-of-pertuzumab-in-patients-with-solid-tumors
#16
Chenjing Zhu, Wenwu Ling, Jing Zhang, Hui Gao, Kai Shen, Xuelei Ma
BACKGROUND: The development of targeted therapies benefits patients with certain markers in the treatment of breast cancer. Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. The Food and Drug Administration has approved pertuzumab in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer. METHODS: To assess the safety and efficacy profile of pertuzumab, we searched PubMed and Embase (articles from January 1966 to January 2015) using the keyword "pertuzumab"...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28514062/locoregional-therapy-with-%C3%AE-emitting-trastuzumab-against-peritoneal-metastasis-of-her2-positive-gastric-cancer-in-mice
#17
Huizi Keiko Li, Yukie Morokoshi, Kotaro Nagatsu, Tadashi Kamada, Sumitaka Hasegawa
Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found however that locoregionally administered trastuzumab armed with a radionuclide astatine-211 ((211) At)-emitting α-particle ((211) At-trastuzumab) is effective against HER2-positive PMGC in a xenograft mouse model. We first observed that (211) At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in subcutaneous tumors...
May 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28513856/the-utility-of-a-population-approach-in-drug-drug-interaction-assessments-a-simulation-evaluation
#18
Diane D Wang, Yanke Yu, Nastya Kassir, Min Zhu, William D Hanley, Justin C Earp, Andrew T Chow, Manish Gupta, Chuanpu Hu
This study aims at evaluating the utility of the population pharmacokinetics approach in therapeutic protein drug-drug-interaction (DDI) assessment. Simulations were conducted for 2 representative victim drugs, methotrexate and trastuzumab, using a parallel-group design with and without the interaction drug. The effect of a perpetrator on the exposure of the victim drug is described as the ratio of clearance/apparent clearance of the victim drug given with or without the perpetrator. The power of DDI assessment was calculated as the percentage of runs with 90% confidence interval of the estimated DDI effect within 80% to 125% for the scenarios of no DDI, benchmarked with the noncompartmental approach with intensive sampling...
May 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28512267/exploratory-investigation-of-psca-protein-expression-in-primary-breast-cancer-patients-reveals-a-link-to-her2-neu-overexpression
#19
Theresa Link, Friederike Kuithan, Armin Ehninger, Jan Dominik Kuhlmann, Michael Kramer, Andreas Werner, Axel Gatzweiler, Barbara Richter, Gerhard Ehninger, Gustavo Baretton, Michael Bachmann, Pauline Wimberger, Katrin Friedrich
BACKGROUND: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study. METHODS: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28508152/detection-of-her2-amplification-in-circulating-tumor-cells-of-her2-negative-gastric-cancer-patients
#20
Yuji Mishima, Satoshi Matsusaka, Keisho Chin, Mariko Mikuniya, Sayuri Minowa, Tomoko Takayama, Harumi Shibata, Ryoko Kuniyoshi, Mariko Ogura, Yasuhito Terui, Nobuyuki Mizunuma, Kiyohiko Hatake
A key to the successful use of targeted cancer therapy is the ability to preselect patients who are likely to benefit from the treatment according to molecular markers. Assessment for predicting therapy response is mostly done using tumor biopsies. However, these might not truly represent all of the patient's malignant cells because of tumor heterogeneity and/or clonal evolution during disease progression. One potential strategy that can complement primary tumor biopsy is the analysis of circulating tumor cells (CTCs)...
May 15, 2017: Targeted Oncology
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