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https://www.readbyqxmd.com/read/29046141/generation-and-characterization-of-a-bispecific-antibody-targeting-both-pd-1-and-c-met
#1
Yi Wu, Min Yu, Zujun Sun, Weihua Hou, Yuxiong Wang, Qingyun Yuan, Wei Mo
Bispecific antibodies, BsAbs, are molecules with the ability to bind to two different epitopes on the same or different antigens. The goal of this study was to create a novel bispecific antibody targeting both cellular-mesenchymal to epithelial transition factor(c-MET) and programmed death-1(PD-1) as an anti-cancer therapeutic candidate. Upon binding to the c-MET antigen on a tumor cell and the PD-1 antigen on a T cell, a BsAb can redirect T cells for tumor killing. Based on the original sequences of PD-1 and c-MET mAbs, a BsAb gene was designed, and cloned into the pCEP4 vector...
October 17, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29045907/reactive-neutrophil-responses-dependent-on-the-receptor-tyrosine-kinase-c-met-limit-cancer-immunotherapy
#2
Nicole Glodde, Tobias Bald, Debby van den Boorn-Konijnenberg, Kyohei Nakamura, Jake S O'Donnell, Sabrina Szczepanski, Maria Brandes, Sarah Eickhoff, Indrajit Das, Naveen Shridhar, Daniel Hinze, Meri Rogava, Tetje C van der Sluis, Janne J Ruotsalainen, Evelyn Gaffal, Jennifer Landsberg, Kerstin U Ludwig, Christoph Wilhelm, Monika Riek-Burchardt, Andreas J Müller, Christoffer Gebhardt, Richard A Scolyer, Georgina V Long, Viktor Janzen, Michele W L Teng, Wolfgang Kastenmüller, Massimiliano Mazzone, Mark J Smyth, Thomas Tüting, Michael Hölzel
Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic to target oncogenic signaling in tumor cells. We found that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in murine cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045894/from-oncogene-interference-to-neutrophil-immune-modulation
#3
Vincenzo Bronte
Oncogenes can aid tumor progression in a cancer cell-extrinsic way. In this issue of Immunity, Glodde et al. (2017) demonstrate that interference with c-MET tyrosine kinase receptor can relieve neutrophil-dependent immune suppression and unleash the effectiveness of immunotherapy even in the context of c-MET-independent tumors.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045509/the-antibody-drug-conjugate-target-landscape-across-a-broad-range-of-tumour-types
#4
K L Moek, D J A de Groot, E G E de Vries, R S N Fehrmann
Background: Antibody-drug conjugates (ADCs), consisting of an antibody designed against a specific target at the cell membrane linked with a cytotoxic agent, are an emerging class of therapeutics. Since ADC tumour cell targets do not have to be drivers of tumour growth, ADCs are potentially relevant for a wide range of tumours currently lacking clear oncogenic drivers. Therefore, we aimed to define the landscape of ADC targets in a broad range of tumours. Materials and methods: PubMed and ClinicalTrials...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29039556/huaier-extract-enhances-the-treatment-efficacy-of-paclitaxel-in-breast-cancer-cells-via-the-nf-%C3%AE%C2%BAb-i%C3%AE%C2%BAb%C3%AE-pathway
#5
Liu Yang, Zhenchuan Song, Xinle Wang, Wei Yang, Meiqi Wang, Huan Liu
Breast cancer is considered as the most common malignant disease in women. Huaier extract, a type of traditional Chinese medicine, has been found to have antitumor activity. In the present study, we aimed to investigate whether the combined treatments of paclitaxel and Huaier extract may improve treatment efficacy in breast cancer cells. Human breast cancer cell lines MCF-7 and MDA-MB-231 were used to evaluate the antitumor efficacy of Huaier extract and paclitaxel both in vitro and in vivo. Using proliferation assays and flow cytometry, we found that both Huaier extract and paclitaxel decreased cell viability and induced cell apoptosis in a time- and dose-dependent manner...
October 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29032032/enzyme-inhibitory-activities-an-insight-into-the-structure-activity-relationship-of-biscoumarin-derivatives
#6
Muhammad Faisal, Aamer Saeed, Danish Shahzad, Tanzeela Abdul Fattah, Bhajan Lal, Pervaiz Ali Channar, Jamaluddin Mahar, Shomaila Saeed, Parvez Ali Mahesar, Fayaz Ali Larik
Biscoumarin derivatives, a dimeric form of coumarin, are well known derivatives of coumarin, occurred in the bioactive metabolites of marine and terrestrial organisms. On account of pharmacological and biological applications, biscoumarins have long been the subject of innumerable enzyme inhibition studies. In this review the pros and cons of enzyme inhibition studies of biscoumarins as urease inhibitors, aromatase inhibitors, NPPs, α-glucosidase inhibitors, α-amylase inhibitors, HIV-1 integrase inhibition, steroid sulfatase inhibitors and c-Met inhibitors are discussed in a systematic way...
October 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29028616/simultaneous-determination-of-a-novel-c-met-axl-dual-target-small-molecule-inhibitor-bpi-9016m-and-its-metabolites-in-human-plasma-by-liquid-chromatography-tandem-mass-spectrometry-application-in-a-pharmacokinetic-study-in-chinese-advanced-solid-tumor-patients
#7
Xinge Cui, Xin Zheng, Ji Jiang, Fenlai Tan, Lieming Ding, Pei Hu
BPI-9016M is a novel dual-target small-molecule inhibitor targeting c-Met and AXL, which was developed by Betta Pharmaceuticals Co., Ltd (Hangzhou, China). It has great potential in the treatment of advanced cancer. A high throughput quantitation method, based on liquid chromatography-tandem mass spectrometry, was developed and validated for the simultaneous determination of BPI-9016M and its main metabolite, M1 and M2-2, in human plasma with a sample preparation method of precipitation of protein. Liquid chromatographic separation was performed with a gradient elution of formic acid-10mM ammonium acetate aqueous solution (1:1000, v/v) and acetonitrile at a flow rate of 0...
October 8, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29026705/role-of-recepteur-d-origine-nantais-on-gastric-cancer-development-and-progression
#8
REVIEW
Sung Yeul Yang, Thi Thinh Nguyen, Trong Thuan Ung, Young Do Jung
Recepteur d'origine nantais (RON) is a receptor tyrosine kinase belonging to the subfamily of which c-MET is the prototype. Large epidemiologic studies have confirmed the strong association between RON and gastric cancer development. Constitutive activation of RON signaling directly correlates with tumorigenic phenotypes of gastric cancer and a poor survival rate in advanced gastric cancer patients. In this review, we focus on recent evidence of the aberrant expression and activation of RON in gastric cancer tumors and provide insights into the mechanism of RON signaling associated with gastric cancer progression and metastasis...
September 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/29022361/interactions-of-quercetin-with-receptor-tyrosine-kinases-associated-with-human-lung-carcinoma
#9
Bincy Baby, Priya Antony, Ranjit Vijayan
Lung cancer is a deadly form of cancer with high morbidity and mortality rates. Deregulated receptor tyrosine kinases (RTKs) are frequently associated with the formation and development of lung carcinoma. Quercetin is a major dietary flavonoid that has been shown to induce cell growth inhibition and apoptosis in human lung cancer cell lines. In the current study, four major overexpressed RTKs - EGFR, FGFR1, IGF1R and c-Met - involved in human lung cancer were investigated. Molecular docking was employed to identify the binding orientation and inhibitory potential of quercetin in these RTKs...
October 12, 2017: Natural Product Research
https://www.readbyqxmd.com/read/29017538/hgf-potentiates-extracellular-matrix-driven-migration-of-human-myoblasts-involvement-of-matrix-metalloproteinases-and-mapk-erk-pathway
#10
Mariela Natacha González, Wallace de Mello, Gillian S Butler-Browne, Suse Dayse Silva-Barbosa, Vincent Mouly, Wilson Savino, Ingo Riederer
BACKGROUND: The hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration. METHODS: We evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF...
October 10, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28983602/the-role-of-tgf%C3%AE-%C3%A2-hgf%C3%A2-smad4-axis-in-regulating-the-proliferation-of-mouse-airway-progenitor-cells
#11
Xue Li, Li Yang, Xin Sun, Junping Wu, Yu Li, Qiuyang Zhang, Yingchao Zhang, Kuan Li, Qi Wu, Huaiyong Chen
The interaction between airway epithelial progenitor cells and their microenvironment is critical for maintaining lung homeostasis. This microenvironment includes fibroblast cells, which support the growth of airway progenitor cells. However, the mechanism of this support is not fully understood. In the present study, the authors observed that inhibition of transforming growth factor (TGF)‑β signal with SB431542 promotes the expression of hepatocyte growth factor (HGF) in fibroblast cells. The HGF receptor, c‑Met, is expressed on airway progenitor cells; HGF promotes the colony‑forming ability of airway progenitor cells...
September 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28983474/helicobacter-pylori-caga-protein-negatively-regulates-autophagy-and-promotes-inflammatory-response-via-c-met-pi3k-akt-mtor-signaling-pathway
#12
Na Li, Bin Tang, Yin-Ping Jia, Pan Zhu, Yuan Zhuang, Yao Fang, Qian Li, Kun Wang, Wei-Jun Zhang, Gang Guo, Tong-Jian Wang, You-Jun Feng, Bin Qiao, Xu-Hu Mao, Quan-Ming Zou
Cytotoxin-associated-gene A (CagA) of Helicobacter pylori (H. pylori) is a virulence factor that plays critical roles in H. pylori-induced gastric inflammation. In the present study, gastric biopsies were used for genotyping cagA and vacA genes, determining the autophagic activity, and the severity of gastric inflammation response. It was revealed that autophagy in gastric mucosal tissues infected with cagA(+)H. pylori strains was lower than the levels produced by cagA(-)H. pylori strains, accompanied with accumulation of SQSTM1 and decreased LAMP1 expression...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28978033/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#13
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28973887/cross-activating-c-met-%C3%AE-1-integrin-complex-drives-metastasis-and-invasive-resistance-in-cancer
#14
Arman Jahangiri, Alan Nguyen, Ankush Chandra, Maxim K Sidorov, Garima Yagnik, Jonathan Rick, Sung Won Han, William Chen, Patrick M Flanigan, Dina Schneidman-Duhovny, Smita Mascharak, Michael De Lay, Brandon Imber, Catherine C Park, Kunio Matsumoto, Kan Lu, Gabriele Bergers, Andrej Sali, William A Weiss, Manish K Aghi
The molecular underpinnings of invasion, a hallmark of cancer, have been defined in terms of individual mediators but crucial interactions between these mediators remain undefined. In xenograft models and patient specimens, we identified a c-Met/β1 integrin complex that formed during significant invasive oncologic processes: breast cancer metastases and glioblastoma invasive resistance to antiangiogenic VEGF neutralizing antibody, bevacizumab. Inducing c-Met/β1 complex formation through an engineered inducible heterodimerization system promoted features crucial to overcoming stressors during metastases or antiangiogenic therapy: migration in the primary site, survival under hypoxia, and extravasation out of circulation...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28968960/the-long-non-coding-rna-neat1-enhances-epithelial-to-mesenchymal-transition-and-chemoresistance-via-the-mir-34a-c-met-axis-in-renal-cell-carcinoma
#15
Fei Liu, Na Chen, Yanchun Gong, Ruihai Xiao, Weichao Wang, Zhengyue Pan
Long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in various cancers. Although the lncRNA nuclear enriched abundant transcript 1 (NEAT1) has been associated with tumorigenesis, its functions in renal cell carcinoma (RCC) have not been elucidated. We determined that NEAT1 is up-regulated in RCC tissue compared to corresponding non-tumor tissue. High NEAT1 expression was associated with tumor progression and poor survival in RCC patients. NEAT1 knockdown suppressed RCC cell proliferation by inhibiting cell cycle progression, and inhibited RCC cell migration and invasion by reversing the epithelial-to-mesenchymal transition phenotype...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966724/correlation-between-c-met-and-aldh1-contributes-to-the-survival-and-tumor-sphere-formation-of-aldh1-positive-breast-cancer-stem-cells-and-predicts-poor-clinical-outcome-in-breast-cancer
#16
Yuka Nozaki, Shoma Tamori, Masahiro Inada, Reika Katayama, Hiromi Nakane, Osamu Minamishima, Yuka Onodera, Makoto Abe, Shota Shiina, Kei Tamura, Daichi Kodama, Keiko Sato, Yasushi Hara, Ryo Abe, Ryoko Takasawa, Atsushi Yoshimori, Nariyoshi Shinomiya, Sei-Ichi Tanuma, Kazunori Akimoto
c-Met is a receptor-type tyrosine kinase, which is involved in a wide range of cellular responses such as proliferation, motility, migration and invasion. It has been reported to be overexpressed in various cancers. However, the role of c-Met in breast cancer stem cells (CSCs) still remains unclear. We herein, show that c-Met expression is significantly elevated in Basal-like type of breast cancer in comparison with other subtypes. High expression of c-Met strongly correlated with the expression of two CSC markers, ALDH1A3 and CD133 in breast cancers...
July 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28961841/dual-met-and-erbb-inhibition-overcomes-intratumor-plasticity-in-osimertinib-resistant-advanced-non-small-cell-lung-cancer-nsclc
#17
A Martinez-Marti, E Felip, J Matito, E Mereu, A Navarro, S Cedrés, N Pardo, A Martinez de Castro, J Remon, J M Miquel, A Guillaumet-Adkins, E Nadal, G Rodriguez-Esteban, O Arqués, R Fasani, P Nuciforo, H Heyn, A Villanueva, H G Palmer, A Vivancos
Background: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance. Methods: For Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient-derived orthotopic xenograft tumors corresponding to the different treatment arms were used...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28961833/biomarkers-predict-enhanced-clinical-outcomes-with-afatinib-versus-methotrexate-in-patients-with-second-line-recurrent-and-or-metastatic-head-and-neck-cancer
#18
E E W Cohen, L F Licitra, B Burtness, J Fayette, T Gauler, P M Clement, J J Grau, J M Del Campo, A Mailliez, R I Haddad, J B Vermorken, M Tahara, J Guigay, L Geoffrois, M C Merlano, N Dupuis, N Krämer, X J Cong, N Gibson, F Solca, E Ehrnrooth, J-P H Machiels
Background: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. Patients and methods: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week)...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28945796/cabozantinib-and-dastinib-exert-anti-tumor-activity-in-alveolar-soft-part-sarcoma
#19
Kenta Mukaihara, Yu Tanabe, Daisuke Kubota, Keisuke Akaike, Takuo Hayashi, Kaoru Mogushi, Masaki Hosoya, Shingo Sato, Eisuke Kobayashi, Taketo Okubo, Youngji Kim, Shinji Kohsaka, Tsuyoshi Saito, Kazuo Kaneko, Yoshiyuki Suehara
BACKGROUND: Alveolar soft part sarcoma (ASPS) is an extremely rare metastatic soft tissue tumor with a poor prognosis for which no effective systemic therapies have yet been established. Therefore, the development of novel effective treatment approaches is required. Tyrosine kinases (TKs) are being increasingly used as therapeutic targets in a variety of cancers. The purpose of this study was to identify novel therapeutic target TKs and to clarify the efficacy of TK inhibitors (TKIs) in the treatment of ASPS...
2017: PloS One
https://www.readbyqxmd.com/read/28939129/salvianolic-acid-a-reverses-cisplatin-resistance-in-lung-cancer-a549-cells-by-targeting-c-met-and-attenuating-akt-mtor-pathway
#20
Xia-Li Tang, Li Yan, Ling Zhu, De-Min Jiao, Jun Chen, Qing-Yong Chen
Drug resistance is one of the leading causes of chemotherapy failure in non-small cell lung cancer (NSCLC) treatment. The purpose of this study was to investigate the role of c-met in human lung cancer cisplatin resistance cell line (A549/DDP) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. In this study, we found that A549/DDP cells exert up-regulation of c-met by activating the Akt/mTOR signaling pathway. We also show that SAA could increase the chemotherapeutic efficacy of cisplatin, suggesting a synergistic effect of SAA and cisplatin...
September 6, 2017: Journal of Pharmacological Sciences
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