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https://www.readbyqxmd.com/read/28434150/high-sensitive-troponin-t-assay-can-predict-anthracycline-and-trastuzumab-induced-cardiotoxicity-in-breast-cancer-patients
#1
Hiromitsu Kitayama, Tomohiro Kondo, Junko Sugiyama, Kazutomo Kurimoto, Yasuhiro Nishino, Masaya Kawada, Michiaki Hirayama, Yasushi Tsuji
BACKGROUND: Trastuzumab following anthracycline causes cardiotoxicity in up to 28% of patients. Although the cardiotoxicity is often irreversible once cardiac dysfunction is detected, the early predictor has not been established yet. METHODS: We prospectively observed breast cancer patients treated with anthracycline or trastuzumab at Tonan Hospital. All patients underwent echocardiography and blood sampling at baseline, and every three months during chemotherapy...
April 22, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28432515/mri-predicts-pathologic-complete-response-in-her2-positive-breast-cancer-after-neoadjuvant-chemotherapy
#2
Mette S van Ramshorst, Claudette E Loo, Emilie J Groen, Gonneke H Winter-Warnars, Jelle Wesseling, Frederieke van Duijnhoven, Marie-Jeanne T Vrancken Peeters, Gabe S Sonke
BACKGROUND: Neoadjuvant treatment of HER2-positive breast cancer frequently leads to a pathologic complete response (pCR), which is associated with favourable long-term outcome. Treatment regimens typically consist of 6-9 cycles of trastuzumab-based chemotherapy, although many patients achieve early radiologic complete response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles can possibly be reduced. METHODS: We performed a diagnostic accuracy study to determine the association between rCR and pCR in patients with stage II-III HER2-positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at the Netherlands Cancer Institute...
April 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28431161/engineering-a-high-affinity-peptide-binding-site-into-the-anti-cea-mab-m5a
#3
Cindy Zer, Kendra N Avery, Kassondra Meyer, Leah Goodstein, Krzysztof P Bzymek, Gagandeep Singh, John C Williams
We have previously identified a cyclic peptide called meditope which binds to the central cavity of the Fab portion of cetuximab and shown that this peptide binding site can be grafted, or 'meditope-enabled', onto trastuzumab. This peptide has been shown to act as a hitch for the non-covalent attachment of imaging agents to meditope-enabled antibodies. Herein, we explore the process of grafting this peptide binding site onto M5A, an anti-CEA antibody in clinical trials for cancer diagnostics. In order to explore the contributions of the amino acids, we sequentially introduced pairs of amino acid substitutions into the Fab and then we reverse-substituted key residues in the presence of the other substitutions...
April 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28430631/loss-of-steroid-hormone-receptors-is-common-in-malignant-pleural-and-peritoneal-effusions-of-breast-cancer-patients-treated-with-endocrine-therapy
#4
Willemijne A M E Schrijver, Karianne Schuurman, Annelot van Rossum, Ton Peeters, Natalie Ter Hoeve, Wilbert Zwart, Paul J van Diest, Cathy B Moelans
Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive.We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430337/circulating-neuregulin-1-and-galectin-3-can-be-prognostic-markers-in-breast-cancer
#5
Francesca De Iuliis, Gerardo Salerno, Ludovica Taglieri, Rosina Lanza, Patrizia Cardelli, Susanna Scarpa
BACKGROUND: It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. METHODS: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab...
April 14, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28418920/complementary-utility-of-targeted-next-generation-sequencing-and-immunohistochemistry-panels-as-a-screening-platform-to-select-targeted-therapy-for-advanced-gastric-cancer
#6
Hyo Song Kim, Hanna Lee, Su-Jin Shin, Seung-Hoon Beom, Minkyu Jung, Sujin Bae, Eun Young Lee, Kyu Hyun Park, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Woong Sub Koom, Joon Seok Lim, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha, Hyunki Kim, Soonmyung Paik
We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415835/the-role-of-chemotherapy-in-unresectable-or-metastatic-adenocarcinoma-of-the-stomach-and-gastroesophageal-junction
#7
Mustafa Bozkurt, Fatemeh G Amlashi, Mariela Blum Murphy
Gastric cancer including gastro-esophageal junction adenocarcinomas are most challenging and deadly cancers of the gastrointestinal tract. Gastric cancer has a fatality-to-case ratio of 0.66, translating that nearly two thirds of newly diagnosed patients will have disseminated disease and in need of systemic therapy (1). Advanced gastric adenocarcinoma (AGC) is a heterogenous disease with differences in geographical distribution, histopathology, and molecular subtypes. Fluoropyrimidines (5-FU, S-1, and capecitabine), platinum compounds (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), and the topoisomerase inhibitory irinotecan are active drugs against AGC...
April 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28415738/tyrosine-kinase-inhibitor-induced-growth-factor-receptor-upregulation-enhances-the-efficacy-of-near-infrared-targeted-photodynamic-therapy-in-esophageal-adenocarcinoma-cell-lines
#8
Elmire Hartmans, Matthijs D Linssen, Claire Sikkens, Afra Levens, Max J H Witjes, Gooitzen M van Dam, Wouter B Nagengast
Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year survival rates of only 15-25%. Near-infrared targeted photodynamic therapy (NIR-tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to selectively treat malignant cells. In this in vitro report we demonstrate the applicability of antibody-based NIR-tPDT in esophageal adenocarcinoma (EAC), using the phototoxic compounds cetuximab-IRDye700DX and trastuzumab-IRDye700DX, targeting respectively epidermal growth factor receptor 1 (EGFR) and 2 (HER2)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415714/depth-of-response-is-a-significant-predictor-for-long-term-outcome-in-advanced-gastric-cancer-patients-treated-with-trastuzumab
#9
Choong-Kun Lee, Seung-Seob Kim, Saemi Park, Chan Kim, Su Jin Heo, Joon Seok Lim, Hyunki Kim, Hyo Song Kim, Sun Young Rha, Hyun Cheol Chung, Sohee Park, Minkyu Jung
PURPOSE: We aimed to determine and compare the predictive values of depth of response (DpR) and early tumor shrinkage (ETS) on long-term outcomes in gastric cancer patients treated with trastuzumab. RESULTS: From a total of 368 computed tomography examinations, DpR and ETS were evaluated. DpR was a significant tumor-size metric in predicting PFS and OS, and showed better discriminatory ability (higher Cτ indices, 0.6957 for PFS; 0.7191 for OS) than ETS. DpR ≥ 45% (vs...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415567/efficacy-and-safety-of-t-dm1-in-the-common-practice-of-her2-advanced-breast-cancer-setting-a-multicenter-study
#10
Alessandra Fabi, Michelino De Laurentiis, Michele Caruso, Enrichetta Valle, Luca Moscetti, Daniele Santini, Katia Cannita, Luisa Carbognin, Mariangela Ciccarese, Rosalba Rossello, Grazia Arpino, Vita Leonardi, Filippo Montemurro, Nicla La Verde, Daniele Generali, Alberto Zambelli, Giuseppa Scandurra, Michelangelo Russillo, Ida Paris, Anna Maria D'Ottavio, Gianfranco Filippelli, Marianna Giampaglia, Simonetta Stani, Agnese Fabbri, Daniele Alesini, Daniela Cianniello, Diana Giannarelli, Francesco Cognetti
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413662/phase-i-study-of-nanoparticle-albumin-bound-paclitaxel-carboplatin-and-trastuzumab-in-women-with-human-epidermal-growth-factor-receptor-2-overexpressing-breast-cancer
#11
Kenji Tezuka, Tsutomu Takashima, Shinichiro Kashiwagi, Hidemi Kawajiri, Shinya Tokunaga, Seika Tei, Shigehiko Nishimura, Shigehito Yamagata, Satoru Noda, Takeo Nishimori, Yoko Mizuyama, Takeshi Sunami, Katsumi Ikeda, Yoshinari Ogawa, Naoyoshi Onoda, Tetsuro Ishikawa, Shinzoh Kudoh, Minoru Takada, Kosei Hirakawa
Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28412326/no-acute-changes-in-lvef-observed-with-concurrent-trastuzumab-and-breast-radiation-with-low-heart-doses
#12
Shelly X Bian, Mariam P Korah, Taylor R Whitaker, Lingyun Ji, Susan Groshen, Eugene Chung
INTRODUCTION/BACKGROUND: Treatment for HER2-postitive breast cancer often includes trastuzumab, breast/chest wall (CW) radiation (RT), and anthracyclines, all of which have cardiac toxicity. We aimed to evaluate the relationship between heart dose and acute left ventricular ejection fraction (LVEF) changes in patients who received concurrent trastuzumab and breast/CW RT with and without anthracycline use. PATIENTS AND METHODS: We retrospectively reviewed all nonmetastatic breast cancer patients from 2008 to 2015 who received concurrent trastuzumab and breast/CW RT...
March 23, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28409338/fluorine-18-labeling-of-the-her2-targeting-single-domain-antibody-2rs15d-using-a-residualizing-label-and-preclinical-evaluation
#13
Zhengyuan Zhou, Ganesan Vaidyanathan, Darryl McDougald, Choong Mo Kang, Irina Balyasnikova, Nick Devoogdt, Angeline N Ta, Brian R McNaughton, Michael R Zalutsky
PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts...
April 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28405498/cergutuzumab-amunaleukin-cea-il2v-a-cea-targeted-il-2-variant-based-immunocytokine-for-combination-cancer-immunotherapy-overcoming-limitations-of-aldesleukin-and-conventional-il-2-based-immunocytokines
#14
Christian Klein, Inja Waldhauer, Valeria G Nicolini, Anne Freimoser-Grundschober, Tapan Nayak, Danielle J Vugts, Claire Dunn, Marije Bolijn, Jörg Benz, Martine Stihle, Sabine Lang, Michaele Roemmele, Thomas Hofer, Erwin van Puijenbroek, David Wittig, Samuel Moser, Oliver Ast, Peter Brünker, Ingo H Gorr, Sebastian Neumann, Maria Cristina de Vera Mudry, Heather Hinton, Flavio Crameri, Jose Saro, Stefan Evers, Christian Gerdes, Marina Bacac, Guus van Dongen, Ekkehard Moessner, Pablo Umaña
We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector functions. Its molecular design aims to (i) avoid preferential activation of regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii) increase the therapeutic index of IL-2 therapy by (a) preferential retention at the tumor by having a lower dissociation rate from CEA-expressing cancer cells vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405494/overcoming-resistance-to-her2-targeted-therapy-with-a-novel-her2-cd3-bispecific-antibody
#15
Andres Lopez-Albaitero, Hong Xu, Hongfen Guo, Linlin Wang, Zhihao Wu, Hoa Tran, Sarat Chandarlapaty, Maurizio Scaltriti, Yelena Janjigian, Elisa de Stanchina, Nai-Kong V Cheung
T-cell-based therapies have emerged as one of the most clinically effective ways to target solid and non-solid tumors. HER2 is responsible for the oncogenesis and treatment resistance of several human solid tumors. As a member of the HER family of tyrosine kinase receptors, its over-activity confers unfavorable clinical outcome. Targeted therapies directed at this receptor have achieved responses, although development of resistance is common. We explored a novel HER2/CD3 bispecific antibody (HER2-BsAb) platform that while preserving the anti-proliferative effects of trastuzumab, it recruits and activates non-specific circulating T-cells, promoting T cell tumor infiltration and ablating HER2(+) tumors, even when these are resistant to standard HER2-targeted therapies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28402624/near-infrared-photochemoimmunotherapy-by-photoactivatable-bifunctional-antibody-drug-conjugates-targeting-her2-positive-cancer
#16
Kimihiro Ito, Makoto Mitsunaga, Takashi Nishimura, Masayuki Saruta, Takeo Iwamoto, Hisataka Kobayashi, Hisao Tajiri
Near-infrared photoimmunotherapy (NIR-PIT) is a new class of molecular targeted cancer therapy based on antibody-photoabsorber conjugates and NIR light irradiation. Recent studies have shown effective tumor control, including that of human epidermal growth factor receptor 2 (HER2)-positive cancer, by selective molecular targeting with NIR-PIT. However, the depth of NIR light penetration limits its use. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate consisting of the monoclonal antibody trastuzumab linked to the cytotoxic agent maytansinoid DM1...
April 12, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28399902/efficacy-and-safety-of-everolimus-in-combination-with-trastuzumab-and-paclitaxel-in-asian-patients-with-her2-advanced-breast-cancer-in-bolero-1
#17
Masakazu Toi, Zhimin Shao, Sara Hurvitz, Ling-Ming Tseng, Qingyuan Zhang, Kunwei Shen, Donggeng Liu, Jifeng Feng, Binghe Xu, Xiaojia Wang, Keun Seok Lee, Ting Ying Ng, Antonia Ridolfi, Florence Noel-Baron, Francois Ringeisen, Zefei Jiang
BACKGROUND: The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial. METHODS: Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel...
April 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28399109/tyrosine-kinase-targeting-drugs-associated-heart-failure
#18
N Gronich, I Lavi, O Barnett-Griness, W Saliba, D R Abernethy, G Rennert
BACKGROUND: The impact of cancer therapies on cardiac disease in the general adult cancer survivor population is largely unknown. Our objective was to evaluate which tyrosine kinase-targeting drugs are associated with greater risk for new-onset heart failure (HF). METHODS: A nested case-control analysis was conducted within a cohort of 27 992 patients of Clalit Health Services, newly treated with a tyrosine kinase-targeting, and/or chemotherapeutic drug, for a malignant disease, between 1 January 2005 and 31 December 2012...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28398405/-gastric-carcinoma-an-evolutionary-scenario
#19
Fabio Gelsomino, Andrea Spallanzani, Ferdinando De Vita, Maria Di Bartolomeo, Cecilia Gavazzi, Lorenza Rimassa, Stefano Cascinu
Despite the progressive decline of its incidence and mortality over the past decades, gastric cancer remains the forth most common cause of cancer-related death in Europe. While historically gastric adenocarcinoma has been classified according to the Lauren classification in intestinal and diffuse subtype, the knowledge of the complex molecular mechanisms underlying its carcinogenesis has led to new molecular classifications which can represent the starting point for the development of a personalized approach also in this disease...
March 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28398298/corrigendum-photothermal-therapeutic-application-of-gold-nanorods-porphyrin-trastuzumab-complexes-in-her2-positive-breast-cancer
#20
Xinmei Kang, Ximing Guo, Xingjian Niu, Weiwei An, Suhan Li, Zhaoliang Liu, Yue Yang, Na Wang, Qicheng Jiang, Caichuan Yan, Hui Wang, Qingyuan Zhang
No abstract text is available yet for this article.
April 11, 2017: Scientific Reports
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