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https://www.readbyqxmd.com/read/28821938/depth-of-response-predicts-the-clinical-outcome-of-advanced-her2-positive-gastric-cancer-to-trastuzumab-based-first-line-chemotherapy
#1
Shigenori Kadowaki, Toshiki Masuishi, Tetsuya Eto, Yukiya Narita, Hiroya Taniguchi, Takashi Ura, Masashi Ando, Masahiro Tajika, Yasumasa Niwa, Yasushi Yatabe, Kei Muro
PURPOSE: Accumulating evidence suggests that response-related parameters such as depth of response (DpR) might be associated with survival in colorectal cancer, which has not been shown in gastric cancer. This study aimed to evaluate whether DpR was associated with clinical outcomes in HER2-positive AGC patients treated with trastuzumab-based chemotherapy. METHODS: Fifty-seven HER2-positive AGC patients who were treated with trastuzumab in combination with fluoropyrimidines plus cisplatin therapy as first-line treatment were retrospectively enrolled...
August 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28821558/defective-cyclin-b1-induction-in-trastuzumab-emtansine-t-dm1-acquired-resistance-in-her2-positive-breast-cancer
#2
MohammadA Sabbaghi, Gabriel Gil-Gómez, Cristina Guardia, Sonia Servitja, Oriol Arpi, Sara García-Alonso, Silvia Menéndez, Montserrat Arumi-Uria, Laia Serrano, Marta Salido, Aura Muntasell, Maria Martinez-Garcia, Sandra Zazo, Cristina Chamizo, Paula González-Alonso, Juan Madoz-Gúrpide, Pilar Eroles, Joaquin Arribas, Ignasi Tusquets, Ana Lluch, Atanasio Pandiella, Federico Rojo, Ana Rovira, Joan Albanell
Purpose: Trastuzumab-emtansine (T-DM1) is a standard treatment in advanced HER2 positive breast cancer. However, resistance inevitably occurs. We aimed to identify mechanisms of acquired T-DM1 resistance. <p>Experimental Design: HER2-positive breast cancer cells (HCC1954, HCC1419, SKBR3 and BT474) were treated in a pulse-fashion with T-DM1 to induce a resistant phenotype. Cellular and molecular effects of T-DM1 in parental versus resistant cells were compared. CDK1 kinase activity and cyclin B1 expression were assayed under various conditions...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821484/measurement-and-mathematical-characterization-of-cell-level-pharmacokinetics-of-antibody-drug-conjugates-a-case-study-with-trastuzumab-vc-mmae
#3
Aman P Singh, Dhaval K Shah
The main objective of this work was to understand and mathematically characterize the cellular disposition of a tool ADC, trastuzumab-vc-MMAE (T-vc-MMAE). Towards this goal, three different analytical methods were developed to measure the concentrations of different ADC related analytes in the media and cell lysate. An LC-MS/MS method was developed to quantify unconjugated drug (i.e. MMAE) concentrations, a forced deconjugation method was developed to quantify total drug concentrations, and an ELISA method was developed to quantify total antibody (i...
August 18, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28819024/trastuzumab-increases-her2-uptake-and-cross-presentation-by-dendritic-cells
#4
Victor A Gall, Anne V Philips, Na Qiao, Karen Clise-Dwyer, Alexander A Perakis, Mao Zhang, Guy Travis Clifton, Pariya Sukhumalchandra, Qing Ma, Sangeetha M Reddy, Dihua Yu, Jeffrey J Molldrem, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf
Early phase clinical trials evaluating CD8+ T cell-eliciting, HER2-derived peptide vaccines administered to HER2-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on clinical trials evaluating the E75+GM-CSF and GP2+GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818506/development-and-evaluation-of-%C3%AE-galactosidase-sensitive-antibody-drug-conjugates
#5
Sergii Kolodych, Chloé Michel, Sébastien Delacroix, Oleksandr Koniev, Anthony Ehkirch, Jitka Eberova, Sarah Cianférani, Brigitte Renoux, Wojciech Krezel, Pauline Poinot, Christian D Muller, Sébastien Papot, Alain Wagner
The selective destruction of tumour cells while sparing healthy tissues is one of the main challenges in cancer therapy. Antibody-drug conjugates (ADCs) are arguably the most rapidly expanding class of targeted cancer therapies. Efficient drug conjugation and release technologies are essential for the development of these new therapeutic agents. In response to the ever-increasing demand for efficient drug release systems, we have developed a new class of β-galactosidase-cleavable linkers for ADCs. Within this framework, novel payloads comprising a galactoside linker, the monomethyl auristatin E (MMAE) and cysteine-reactive groups were synthesized, conjugated with trastuzumab and evaluated both in vitro and in vivo...
August 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28814565/trastuzumab-biosimilar-on-track-for-approval
#6
(no author information available yet)
An FDA expert panel recommended approval of Mylan's MYL-14010, a biosimilar candidate for Genentech's trastuzumab, putting it on track to become the first approved biosimilar for cancer. Experts predict that biosimilars will lead to lower drug prices, but caution that the savings won't be as dramatic as that seen with generics.
August 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28809611/short-course-adjuvant-trastuzumab-will-increase-cure-rates-in-patients-with-human-epidermal-growth-factor-receptor-2-positive-breast-cancer
#7
Raymond Pierre Abratt
No abstract text is available yet for this article.
July 28, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28808917/development-of-a-translational-physiologically-based-pharmacokinetic-model-for-antibody-drug-conjugates-a-case-study-with-t-dm1
#8
Antari Khot, Jay Tibbitts, Dan Rock, Dhaval K Shah
Systems pharmacokinetic (PK) models that can characterize and predict whole body disposition of antibody-drug conjugates (ADCs) are needed to support (i) development of reliable exposure-response relationships for ADCs and (ii) selection of ADC targets with optimal tumor and tissue expression profiles. Towards this goal, we have developed a translational physiologically based PK (PBPK) model for ADCs, using T-DM1 as a tool compound. The preclinical PBPK model was developed using rat data. Biodistribution of DM1 in rats was used to develop the small molecule PBPK model, and the PK of conjugated trastuzumab (i...
August 14, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28801824/two-dimensional-capillary-zone-electrophoresis-mass-spectrometry-for-the-characterization-of-intact-monoclonal-antibody-charge-variants-including-deamidation-products
#9
Kevin Jooß, Jens Hühner, Steffen Kiessig, Bernd Moritz, Christian Neusüß
Capillary zone electrophoresis (CZE) is a powerful tool that is progressively being applied for the separation of monoclonal antibody (mAb) charge variants. Mass spectrometry (MS) is the desired detection method concerning identification of mAb variants. In biopharmaceutical applications, there exist optimized and validated electrolyte systems for mAb variant quantification. However, these electrolytes interfere greatly with the electrospray ionization (ESI) process. Here, a heart-cut CZE-CZE-MS setup with an implemented mechanical four-port valve interface was developed that used a generic ε-aminocaproic acid based background electrolyte in the first dimension and acetic acid in the second dimension...
August 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28800870/recent-advances-in-her2-positive-breast-cancer-epigenetics-susceptibility-and-therapeutic-strategies
#10
REVIEW
Heena Singla, Abhilash Ludhiadch, Raman Preet Kaur, Harish Chander, Vinod Kumar, Anjana Munshi
HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28800545/liver-toxicity-of-chemotherapy-and-targeted-therapy-for-breast-cancer-patients-with-hepatitis-virus-infection
#11
Yu Liu, Zhan-Yi Li, Xi Li, Jia-Ni Wang, Qun-Ai Huang, Yong Huang
BACKGROUND: Chemotherapy has greatly improved the prognosis of breast cancer patients. However, it may also result in undesirable side effects such as hepatitis virus reactivation. Little information is available on the liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus (HBV/HCV) infection. METHODS: We performed a retrospective survey of 835 patients diagnosed with breast cancer between January 2010 and December 2015 at our institution...
August 8, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28798274/disparities-of-trastuzumab-use-in-resource-limited-or-resource-abundant-regions-and-its-survival-benefit-on-her2-positive-breast-cancer-a-real-world-study-from-china
#12
Jianbin Li, Shusen Wang, Yongsheng Wang, Xiaojia Wang, Haibo Wang, Jifeng Feng, Qingyuan Zhang, Tao Sun, Quchang Ouyang, Yongmei Yin, Yinhua Liu, Cuizhi Geng, Min Yan, Zefei Jiang
BACKGROUND: Trastuzumab is a key component of therapy for human epidermal growth receptor 2 (HER2) positive breast cancer. Because real-world data are lacking, the present research was conducted to evaluate the the actual use of and the effectiveness of trastuzumab in the real world in China. METHODS: Inpatients with HER2 positive invasive breast cancer from 13 hospitals in Eastern China (2010-2015, n = 1,139) were included in this study. We aimed to assess the actual use of trastuzumab and to evaluate potential efficacy from trastuzumab in real-world research...
August 10, 2017: Oncologist
https://www.readbyqxmd.com/read/28795341/adjuvant-trastuzumab-therapy-for-early-her2-positive-breast-cancer-in-iran-a-cost-effectiveness-and-scenario-analysis-for-an-optimal-treatment-strategy
#13
Amir Ansaripour, Carin A Uyl-de Groot, W Ken Redekop
INTRODUCTION: Clinical guidelines have recommended a 1-year trastuzumab regimen as standard care for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, this recommendation can have a dramatic impact on total drug expenditures in middle-income countries (MICs). We performed a cost-effectiveness analysis from the Iranian healthcare perspective to find an optimum duration of trastuzumab use in Iran. METHOD: We compared four treatment strategies comprising chemotherapy and varying durations of trastuzumab use (no trastuzumab, 6, 9 months, and 1 year), and a Markov model and probabilistic sensitivity analysis were used to estimate the costs and effects of the strategies...
August 9, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28794264/liquid-phase-electron-microscopy-of-molecular-drug-response-in-breast-cancer-cells-reveals-irresponsive-cell-subpopulations-related-to-lack-of-her2-homodimers
#14
Diana B Peckys, Ulrike Korf, Stefan Wiemann, Niels de Jonge
The development of drug resistance in cancer poses a major clinical problem. An example is human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer often treated with anti-HER2 antibody therapies, such as trastuzumab. Since drug resistance is rooted mainly in tumor cell heterogeneity, we examined the drug effect in different subpopulations of SKBR3 breast cancer cells, and compared the results with a drug resistant cell line, HCC1954. Correlative light microscopy and liquid-phase scanning transmission electron microscopy (STEM) were used to quantitatively analyze HER2 responses upon drug binding, whereby many tens of whole cells were imaged...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28791694/improved-prognosis-of-young-patients-with-breast-cancer-undergoing-breast-conserving-surgery
#15
E Botteri, P Veronesi, J Vila, N Rotmensz, V Galimberti, M V Thomazini, G Viale, R Orecchia, A Goldhirsch, O Gentilini
BACKGROUND: The aim of the present study was to evaluate how breast cancer prognosis has evolved over time in young women treated with breast-conserving surgery (BCS). METHODS: Data from patients younger than 40 years who had BCS and whole-breast radiotherapy in a single cancer centre between 1997 and 2010 were analysed. The patients were followed until 2016. Endpoints were local recurrence, any breast cancer-related event and death from any cause. RESULTS: A total of 1331 patients were included in the study...
August 9, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28790306/quantitative-diagnostic-imaging-of-cancer-tissues-by-using-phosphor-integrated-dots-with-ultra-high-brightness
#16
Kohsuke Gonda, Mika Watanabe, Hiroshi Tada, Minoru Miyashita, Yayoi Takahashi-Aoyama, Takashi Kamei, Takanori Ishida, Shin Usami, Hisashi Hirakawa, Yoichiro Kakugawa, Yohei Hamanaka, Ryuichi Yoshida, Akihiko Furuta, Hisatake Okada, Hideki Goda, Hiroshi Negishi, Kensaku Takanashi, Masaru Takahashi, Yuichi Ozaki, Yuka Yoshihara, Yasushi Nakano, Noriaki Ohuchi
The quantitative sensitivity and dynamic range of conventional immunohistochemistry (IHC) with 3,3'-diaminobenzidine (IHC-DAB) used in pathological diagnosis in hospitals are poor, because enzyme activity can affect the IHC-DAB chromogenic reaction. Although fluorescent IHC can effectively increase the quantitative sensitivity of conventional IHC, tissue autofluorescence interferes with the sensitivity. Here, we created new fluorescent nanoparticles called phosphor-integrated dots (PIDs). PIDs have 100-fold greater brightness and a more than 300-fold greater dynamic range than those of commercially available fluorescent nanoparticles, quantum dots, whose fluorescence intensity is comparable to tissue autofluorescence...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790261/-third-and-fourth-line-chemotherapies-including-paclitaxel-and-bevacizumab-for-metastatic-breast-cancer
#17
Marika Sakamoto, Yoshinori Nio, Shiro Imai, Kayo Uesugi, Mikako Tamaoki, Masashi Tamaoki
The present study was designed to estimate the clinical efficacy of bevacizumab(BV)combined with paclitaxel(PTX)(BVPTX) as third- and fourth-line therapies in 31 patients with metastatic breast cancer(MBC). Most patients were previously treated with docetaxel and/or epirubicin. Patients were intravenously treated with BV at 5-10mg/kg and PTX at 3-5mg/kg at 2-3week intervals, and when the effect of BV-PTX was low, other chemotherapeutic agents(CTAs)and/or trastuzumab (Tr)were additionally administered. Twelve MBC patients were treated with BV-PTX alone and 19 MBC patients were treat- ed with other CTAs and/or Tr in addition to BV-PTX...
July 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28781309/congestive-heart-failure-during-osimertinib-treatment-for-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#18
Hiromi Watanabe, Eiki Ichihara, Hirohisa Kano, Kiichiro Ninomiya, Mitsune Tanimoto, Katsuyuki Kiura
We herein report a case of congestive heart failure which developed during osimertinib treatment. A 78-year-old woman presented with mild exertional dyspnea three weeks after starting osimertinib for the treatment of epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer. She was diagnosed with congestive heart failure caused by the osimertinib. In contrast to trastuzumab, a human epidermal growth factor receptor 2 (HER2) monoclonal antibody that often causes cardiac dysfunction, the causal relationship between osimertinib and cardiotoxicity has so far received little attention and thus remains unclear...
August 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28779849/the-necessity-of-intrathecal-chemotherapy-for-the-treatment-of-breast-cancer-patients-with-leptomeningeal-metastasis-a-systematic-review-and-pooled-analysis
#19
Yen-Chien Lee, Chung-Cheng Hsieh, Jen-Pin Chuang, Chung-Yi Li
Leptomeningeal carcinomatosis is a devastating disease. Despite its numerous complications, intrathecal (IT) chemotherapy remains a longstanding treatment for leptomeningeal carcinomatosis. Using case studies with internationally reported results, we attempted to determine the necessity of IT chemotherapy in treating leptomeningeal carcinomatosis. We conducted a systematic review and pooled analysis to compare hormone therapy, chemotherapy, and IT therapy. We excluded articles on IT trastuzumab therapy. We performed our literature search without language restriction...
July 12, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28778090/trastuzumab-distribution-in-an-in-vivo-and-in-vitro-model-of-brain-metastases-of-breast-cancer
#20
Tori B Terrell-Hall, Mohamed Ismail Nounou, Fatema El-Amrawy, Jessica I G Griffith, Paul R Lockman
BACKGROUND: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. METHODS: We characterized the permeability of 125I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model...
July 26, 2017: Oncotarget
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