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Sven O Dahms, Fatih Demir, Pitter F Huesgen, Karina Thorn, Hans Brandstetter
BACKGROUND: Vitamin K (VK)-dependent proteases are major players in blood coagulation including the initiation as well as the regulation of the cascade. Five different members of this protease family have been described comprising the coagulation factors VII (FVII), IX (FIX), X (FX), protein C (PC) and prothrombin (FII). FVII, FIX, FX and PC share a typical domain architecture with a N-terminal Gla (γ-carboxyglutamate)-domain, two EGF (epidermal growth factor-like)-domains and a C-terminal trypsin-like serine protease (SP)-domain...
January 15, 2019: Journal of Thrombosis and Haemostasis: JTH
Shota Tanaka, Samantha Luk, Juri Kiyokawa, Maristela L Onozato, A John Iafrate, Khalid Shah, Robert L Martuza, Samuel D Rabkin, Tracy T Batchelor, Daniel P Cahill, Andrew S Chi, Hiroaki Wakimoto
Intratumoural heterogeneity underlies tumour escape from molecularly targeted therapy in glioblastoma. A cell-based model preserving the evolving molecular profiles of a tumour during treatment is key to understanding the recurrence mechanisms and development of strategies to overcome resistance. In this study, we established a matched pair of glioblastoma stem-like cell (GSC) cultures from patient glioblastoma samples before and after epidermal growth factor receptor (EGFR)-targeted therapy. A patient with recurrent glioblastoma (MGG70R) harboring focal, high-level EGFR amplification received the irreversible EGFR tyrosine kinase inhibitor dacomitinib...
January 15, 2019: Scientific Reports
Sarah C Starossom, Juliana Campo Garcia, Tim Woelfle, Silvina Romero-Suarez, Marta Olah, Fumihiro Watanabe, Li Cao, Ada Yeste, John J Tukker, Francisco J Quintana, Jaime Imitola, Franziska Witzel, Dietmar Schmitz, Markus Morkel, Friedemann Paul, Carmen Infante-Duarte, Samia J Khoury
In demyelinating diseases including multiple sclerosis (MS), neural stem cells (NSCs) can replace damaged oligodendrocytes if the local microenvironment supports the required differentiation process. Although chitinase-like proteins (CLPs) form part of this microenvironment, their function in this differentiation process is unknown. Here, we demonstrate that murine Chitinase 3-like-3 (Chi3l3/Ym1), human Chi3L1 and Chit1 induce oligodendrogenesis. In mice, Chi3l3 is highly expressed in the subventricular zone, a stem cell niche of the adult brain, and in inflammatory brain lesions during experimental autoimmune encephalomyelitis (EAE)...
January 15, 2019: Nature Communications
Xiaomei Liao, Xingqian Luo, Lei Dai, Haijun Huang, Xing Guo
Objective: To prepare adipose-derived stem cells (ADSCs) and chitosan chloride (CSCl) gel complex to study the biocompatibility and the feasibility of repairing the wounds of deep partial thickness scald in rats. Methods: ADSCs were prepared by enzymogen digestion and differential adherence method from the subcutaneous adipose tissue of SPF grade 6-week-old male Sprague Dawley (SD) rats. Temperature sensitive CSCl gel was prepared by mixing CSCl, β glycerol phosphate, and hydroxyethyl cellulose in 8∶2∶2...
January 1, 2019: Chinese Journal of Reparative and Reconstructive Surgery
Shengwu Zheng, Zijing Du, Xiongmei Huang, Jing Zhuang, Genhui Lin, Yu Yang, Xin Ding, Tao Zan
Objective: To investigate whether desferrioxamine (DFO) can enhance the homing of bone marrow mesenchymal stem cells (BMSCs) and improve neovascularization in random flaps of rats. Methods: BMSCs and fibroblasts (FB) of luciferase transgenic Lewis rats were isolated and cultured. Forty 4-week-old Lewis male rats were used to form a 10 cm×3 cm rectangular flap on their back. The experimental animals were randomly divided into 4 groups with 10 rats in each group: in group A, 200 μL PBS were injected through retrobulbar venous plexus; in group B, 200 μL FB with a concentration of 1×10 6 cells/mL were injected; in group C, 200 μL BMSCs with a concentration of 1×10 6 cells/mL were injected; in group D, cells transplantation was the same as that in group C, after cells transplantation, DFO [100 mg/(kg·d)] were injected intraperitoneally for 7 days...
January 1, 2019: Chinese Journal of Reparative and Reconstructive Surgery
Jiangdian Song, Jie Tian, Lina Zhang, Xiujuan Qu, Wei Qian, Bin Zheng, Lina Zhang, Jia Zhao, Meng Niu, Mu Zhou, Lei Cui, Yunpeng Liu, Mingfang Zhao
OBJECTIVES: To establish a pre-therapy prognostic index model (PIM) of the first-line chemotherapy aiming to achieve accurate prediction of time to progression (TTP) and overall survival among the patients diagnosed with locally advanced (stage III) or distant metastasis (stage IV) lung squamous cell carcinoma (LSCC). METHODS: Ninety-six LSCC patients treated with first-line chemotherapy were retrospectively enrolled to build the model. Fourteen epidermal growth factor receptor (EGFR)-mutant LSCC patients treated with first-line EGFR-tyrosine kinase inhibitor (TKI) therapy were enrolled for validation dataset...
January 14, 2019: European Radiology
Tomas Buchler, Renata Chloupkova, Alexandr Poprach, Ondrej Fiala, Igor Kiss, Katerina Kopeckova, Ladislav Dusek, Veronika Veskrnova, Lubomir Slavicek, Milan Kohoutek, Jindrich Finek, Marek Svoboda, Lubos Petruzelka, Bohuslav Melichar
Purpose: Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear. Methods: A national registry of targeted therapies was used to analyze baseline characteristics and outcomes of patients with mCRC and wild-type KRAS exon 2 status who received bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first- and second-line treatment in either sequence...
2019: Cancer Management and Research
Silvia Antolín, Benigno Acea, Luis Albaina, Ángel Concha, Paz Santiago, Tomás García-Caballero, Joaquín J Mosquera, José Ramón Varela, Rafaela Soler, Lourdes Calvo
Objective: The aim of this study was to evaluate the efficacy, cardiotoxicity profile and long-term benefits of neoadjuvant therapy in human epidermal growth factor receptor 2-positive operable breast cancer patients. Patients and methods: A total of 142 patients diagnosed from 2005 to 2016 were included in the study. The treatment consisted of a sequential regimen of taxanes and anthracyclines plus trastuzumab. The clinical and pathological responses were evaluated and correlated with clinical and biological factors...
2019: Breast Cancer: Targets and Therapy
Naoya Shindo, Hirokazu Fuchida, Mami Sato, Kosuke Watari, Tomohiro Shibata, Keiko Kuwata, Chizuru Miura, Kei Okamoto, Yuji Hatsuyama, Keisuke Tokunaga, Seiichi Sakamoto, Satoshi Morimoto, Yoshito Abe, Mitsunori Shiroishi, Jose M M Caaveiro, Tadashi Ueda, Tomonori Tamura, Naoya Matsunaga, Takaharu Nakao, Satoru Koyanagi, Shigehiro Ohdo, Yasuchika Yamaguchi, Itaru Hamachi, Mayumi Ono, Akio Ojida
Irreversible inhibition of disease-associated proteins with small molecules is a powerful approach for achieving increased and sustained pharmacological potency. Here, we introduce α-chlorofluoroacetamide (CFA) as a novel warhead of targeted covalent inhibitor (TCI). Despite weak intrinsic reactivity, CFA-appended quinazoline showed high reactivity toward Cys797 of epidermal growth factor receptor (EGFR). In cells, CFA-quinazoline showed higher target specificity for EGFR than the corresponding Michael acceptors in a wide concentration range (0...
January 14, 2019: Nature Chemical Biology
Pablo Martinez, Solange Peters, Timothy Stammers, Jean-Charles Soria
Immunotherapy has fundamentally changed the treatment landscape for many patients with cancer. Monoclonal antibodies targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 immune checkpoints have received regulatory approval across a wide range of tumor types, including non-small cell lung cancer (NSCLC). Indeed, treatment approaches for a majority of patients with newly diagnosed metastatic NSCLC are evolving rapidly. Only for the small proportion of patients with metastatic NSCLC and genomic-driven tumors with epidermal growth factor receptor or anaplastic lymphoma kinase sensitizing mutations (5-15%), and possibly BRAF mutations and ROS rearrangements, have initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the preferred therapy...
January 14, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xiaohua Gu, Qiang Zhang, Yun-Bo Chu, Yi-Yang Zhao, Yan-Jun Zhang, David Kuo, Betty Su, Bin Wu
PURPOSE: Tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the standard treatments for Chinese patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation. However, the economic impact is unclear yet in China. MATERIALS AND METHODS: A decision-analytic model was developed to simulate 1-month patient transitions in a 10-year time horizon from Chinese heath care system perspective. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC], gefitinib, erlotinib, and afatinib) among NSCLC patients harboring EGFR mutations were estimated and assessed via indirect comparisons...
January 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Kuo-Hsuan Hsu, Yen-Hsiang Huang, Jeng-Sen Tseng, Kun-Chieh Chen, Wen-Hui Ku, Kang-Yi Su, Jeremy J W Chen, Huei-Wen Chen, Sung-Liang Yu, Tsung-Ying Yang, Gee-Chen Chang
OBJECTIVES: The main objective was to investigate the relationship between Programmed cell Death-ligand 1 (PD-L1) expression levels and the frequency of primary resistance to Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor (TKI) in treatment naïve advanced EGFR-mutant lung adenocarcinoma patients. MATERIALS AND METHODS: From 2012-2017, we enrolled advanced EGFR-mutant lung adenocarcinoma patients who displayed primary resistance to EGFR-TKI therapy, along with patients with disease control, and patients experiencing either stable disease or partial response to EGFR-TKI treatment...
January 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Hanako Hasegawa, Hiroyuki Yasuda, Junko Hamamoto, Keita Masuzawa, Tetsuo Tani, Shigenari Nukaga, Toshiyuki Hirano, Keigo Kobayashi, Tadashi Manabe, Hideki Terai, Shinnosuke Ikemura, Ichiro Kawada, Katsuhiko Naoki, Kenzo Soejima
OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation-positive lung cancer accounts for a significant subgroup of non-small cell lung cancers (NSCLC). Approximately 4-10% of EGFR mutations in NSCLC are EGFR exon 20 insertion mutations, which are reportedly associated with resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. NSCLC patients carrying these mutations are rarely treated with EGFR-TKIs. The purpose of this study was to evaluate the efficacy of afatinib or osimertinib plus cetuximab combination therapy in experimental NSCLC models with EGFR exon 20 insertion mutations...
January 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Ya-Lan Wu, Qian Zhao, Lei Deng, Yan Zhang, Xiao-Juan Zhou, Yan-Ying Li, Min Yu, Lin Zhou, Bing-Wen Zou, You Lu, Yong-Mei Liu
OBJECTIVE: To evaluate the influence of a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment on the clinical features of leptomeningeal metastasis (LM) progression and outcome in advanced non-small cell lung cancer (NSCLC) patients. METHODS: We retrospectively evaluated advanced NSCLC patients receiving effective first-generation EGFR TKI treatment (e.g., treatment > 6 months) at our institution between January 2008 and February 2014...
January 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Paola Fincheira, Andrés Quiroz
Volatile organic compounds (VOCs) released from bacterial species have been reported as plant growth inducers. In this sense, Lactuca sativa was used as model vegetable to prospect the effects of 2-nonanone released by Bacillus sp. BCT9 at cellular and organ structure level, so we present preliminary results about the physiological effects. In this study, 2-day-old L. sativa were exposed to 2-nonanone for 10 days under two delivery systems: 1) 2-nonanone (abrupt delivery) and 2) 2-nonanone + lanolin (controlled delivery)...
February 2019: Microbiological Research
Xiangtao Yan, Huijuan Wang, Peng Li, Guowei Zhang, Mina Zhang, Jinpo Yang, Xiaojuan Zhang, Xuanxuan Zheng, Zhiyong Ma
OBJECTIVE: The objective of this study was to investigate whether first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy improves the prognosis of patients with advanced non-small cell lung cancer (NSCLC) who harbour low-abundance EGFR mutations. PATIENTS AND METHODS: We retrospectively analysed the clinical data of 76 patients with advanced NSCLC who harboured low-abundance EGFR mutations...
February 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Mónica G Mendoza-Rodríguez, Jorge T Ayala-Sumuano, Lázaro García-Morales, Horacio Zamudio-Meza, Eloy A Pérez-Yepez, Isaura Meza
The mechanisms behind the induction of malignancy and chemoresistance in breast cancer cells are still not completely understood. Inflammation is associated with the induction of malignancy in different types of cancer and is highlighted as an important factor for chemoresistance. In previous work, we demonstrated that the inflammatory cytokine interleukin 1β (IL-1β)-induced upregulation of genes was associated with chemoresistance in breast cancer cells. Here, we evaluated the participation and the expression profile of TP63 in the induction of resistance to cisplatin...
January 11, 2019: International Journal of Molecular Sciences
Vikram Rao A/L B Vasanth Rao, Sean Hong Tan, Mayuren Candasamy, Subrat Kumar Bhattamisra
Diabetic nephropathy (DN) is a major cause of end-stage renal disease and affects a large number of individuals with diabetes. However, the development of specific treatments for DN has not yet been identified. Hence, this review is concisely designed to understand the molecular pathways leading to DN in order to develop suitable therapeutic strategies. Extensive literature search have been carried in regard with the pathogenesis and pathophysiology of DN, drug targets and updates on clinical trials, the consequences associated with DN and the potential biomarkers for diagnosis and prediction of DN are discussed in this review...
January 2019: Diabetes & Metabolic Syndrome
D L Luo, J H Yan, Y Ge, L X Yan, J Chen, J Xu, X L Luo, Y H Liu
Objective: To investigate MAML2 gene-translocation in primary pulmonary mucoepidermoid carcinoma (PMEC) and pulmanary adenosquamous carcinoma, and the optimal diagnostic immunohistiochemical (IHC) panel in distinguishing PMEC from adenosqumous carcinoma. Methods: Twenty-four cases of PMEC and 44 adenosqumous carcinoma diagnosed in the Guangdong General Hospital were tested for MAML2 translocation by fluorescent in-situ hybridization (FISH) using tissue array. An IHC panel including TTF1, Napsin A, CK5/6, p63, p40 and Ki-67 was performed on the cohort...
January 8, 2019: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Masumi Iijima, Kyoko Araki, Quishi Liu, Masaharu Somiya, Shun'ichi Kuroda
Antibody drugs have been important therapeutic agents for treating various diseases, such as cancer, rheumatism, and hypercholesterolemia, for the last three decades. Despite showing excellent therapeutic efficacy with good safety in vivo, they require high doses. We have developed a ∼30-nm bio-nanocapsule (ZZ-BNC) consisting of hepatitis B virus envelope L protein fused with the tandem form of protein A-derived IgG Fc-binding Z domain (ZZ-L protein), for tethering antibodies in an oriented immobilization manner...
January 11, 2019: Acta Biomaterialia
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