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Integrin apoptosis

Chuanyi Zhang, Xinzhou Deng, Li Qiu, Feng Peng, Shanshan Geng, Li Shen, Zhiguo Luo
Radiotherapy has played a limited role for the treatment of human esophageal cancer owing to the risk of tumor radioresistance. Core 1 β1, 3-galactosyltransferase (C1GalT1), which catalyzes the formation of core 1 O-glycan structures, is frequently overexpressed during tumorigenesis. However, the exact effects and mechanisms of C1GalT1 in the radioresistance of esophageal cancer remain unclear. In this study, Public databases and our data revealed that C1GalT1 expression was up-regulated in esophageal cancer tissues and was associated with poor survival...
2018: Journal of Cancer
Luca Liberale, Maria Bertolotto, Federico Carbone, Paola Contini, Patricia Wüst, Giovanni Spinella, Bianca Pane, Domenico Palombo, Aldo Bonaventura, Aldo Pende, François Mach, Franco Dallegri, Giovanni G Camici, Fabrizio Montecucco
BACKGROUND: Neutrophil functions have been shown to be modulated by adipocytokines during atherogenesis. The immuno-regulatory role of resistin on neutrophil-mediated activities in atherosclerotic patients remains elusive. Here, we aimed at exploring the association between serum levels of resistin and neutrophil products either in the systemic circulation or within plaques in a cohort of patients with severe carotid plaque stenosis undergoing endarterectomy. In addition, we assessed the effects of resistin on neutrophil pro-atherosclerotic functions in vitro...
July 24, 2018: International Journal of Cardiology
Ting Zhang, Chang-Yan Li, Jing-Jing Jia, Jie-Shan Chi, Da Zhou, Jian-Zhou Li, Xiao-Ma Liu, Jun Zhang, Li Yi
Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra, which results in brain damage. Integrin αvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion. We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle (CeNP) (bLXW7-CeNP) plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than CeNPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively...
February 2018: Current medical science
Khalid Bashir Dar, Aashiq Hussain Bhat, Shajrul Amin, Syed Anjum, Bilal Ahmad Reshi, Mohammad Afzal Zargar, Akbar Masood, Showkat Ahmad Ganie
Protein-protein interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer...
August 2, 2018: Current Cancer Drug Targets
Ruiwen Cao, Yongliang Liu, Qing Wang, Qianqian Zhang, Dinglong Yang, Hui Liu, Yi Qu, Jianmin Zhao
Seawater acidification (OA) and cadmium (Cd) has the potential to lead to immunosuppression effect on marine bivalves. However, the interaction between these two environmental stressors on immune system of marine bivalves has received limited attention. In order to evaluate the defense responses of oysters under the combined exposure to OA and cadmium, the oysters Crassostrea gigas were exposed to 10 μg/L Cd at three pH levels (8.1, 7.8 and 7.6) for 31 days. Results showed that OA exposure alone led to increased DNA damage, apoptosis rate and ROS production of hemocytes...
July 29, 2018: Fish & Shellfish Immunology
Alberto Purwada, Shivem B Shah, Wendy Béguelin, Avery August, Ari M Melnick, Ankur Singh
Most antigen discovery and vaccine development aimed at driving functional B cell responses rely on mouse immunizations studies. To date, there is no 3D ex vivo immune tissues, which are capable of driving antigen-specific B cell responses to rapidly determine the humoral immunogenicity of antigens, understand the role of extracellular matrix in humoral immunity, and generate high affinity antibody responses. This can be attributed to the complexity of B cell differentiation and affinity maturation process in the germinal center (GC) reaction, which makes these highly specialized cells susceptible to rapid apoptosis ex vivo...
June 26, 2018: Biomaterials
Ping Wang, Yuan Zhou, Jian-Qiang Yang, Lilla Landeck, Min Min, Xi-Bei Chen, Jia-Qi Chen, Wei Li, Sui-Qing Cai, Min Zheng, Xiao-Yong Man
OBJECTIVES: Sprouty (SPRY) 1 is one of the SPRY proteins that inhibits signalling from various growth factors pathways and has also been known as a tumour suppressor in various malignancies. However, no study elucidates the role of SPRY1 in the skin. Our study was conducted to determine the function of SPRY1 in human keratinocytes and the epidermis. MATERIALS AND METHODS: In vitro primary cultured epidermal keratinocytes were used to investigate the proliferation, differentiation and apoptosis of these cells...
July 23, 2018: Cell Proliferation
Seung Woo Chung, Jeong Uk Choi, Young Seok Cho, Ha Rin Kim, Tae Hyung Won, Peter Dimitrion, Ok-Cheol Jeon, Seong Who Kim, In-San Kim, Sang Yoon Kim, Youngro Byun
Tumor heterogeneity is associated with the therapeutic failures of targeted therapies. To overcome such heterogeneity, a novel targeted therapy is proposed that could kill tumor populations with diverse phenotypes by delivering nonselective cytotoxins to target-positive cells as well as to the surrounding tumor cells via a recurrent bystander killing effect. A representative prodrug is prepared that targets integrin αvβ3 and releases cytotoxins upon entering cells or by caspase-3. This allows the prodrug to kill integrin αvβ3-positive cells and upregulate caspase-3, which in turn, activates the prodrug to release a cytotoxin that could subsequently diffuse into and kill the neighboring tumor cells...
July 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Linshui Zhou, Xin Lv, Junchao Yang, Yuanhong Zhu, Zhen Wang, Tingzhen Xu
Lung cancer is one of the most common malignant tumors and also the leading cause of cancer-related deaths in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib, have been used in the therapy of lung cancer. However, the acquisition of drug resistance is a major limitation in the clinical efficiency of EGFR-TKIs. Epithelial-mesenchymal transition (EMT) has been demonstrated to be an underlying mechanism of acquired resistance. A previous study has reported that Napsin A expression can inhibit EMT in lung cancer cells...
August 2018: Oncology Letters
Yangyang Ji, Hui Li, Fang Wang, Linglan Gu
Activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) had been linked to inhibition on the proliferation and apoptosis in a few cancer cell lines. However, limited data exists regarding the role of PPARβ/δ in nasopharyngeal carcinoma (NPC). This study was undertaken to determine the effect of PPARβ/δ on cell proliferation, anchorage-dependent clonogenicity, and ectopic xenografts in the human NPC cell lines. Gene and protein expression of PPARβ/δ were reduced specifically in the poor- and un-differentiated NPC cell lines as compared with the control NP-69 cells...
2018: Frontiers in Pharmacology
Hualong Qin, Jun Zhou, Jingjing Xu, Li Cheng, Zaixiang Tang, Haitao Ma, Feng Guo
Background: Lung cancer is a leading public health issue worldwide. Although therapeutic approaches have improved drastically in the last decades, the prognosis of lung cancer patients remains suboptimal. The canonical nuclear transcription factor kappa B (NF-κB) signalling pathway is critical in the carcinogenesis of lung cancer. The non-canonical NF-κB signalling pathway (represented by RelB) has attracted increasing attention in the pathogenesis of haematological and epithelial malignancies...
2018: Cancer Cell International
Xiurong Gao, Hui Yang, Min Wu, Kun Shi, Cheng Zhou, Jinrong Peng, Qian Yang
Tumor growth inhibition and adverse effect reduction together with metastasis alleviation are still the challenges that need to be overcome in cancer chemotherapy. Combinational therapy provides an alternative solution for these challenges. Nanoparticles are the ideal carriers for combinational therapy due to their versatile drug loading capacities and versatile tumor-targeting strategies. In this study, a cRGDfk modified nanogel system has been utilized to coload lidocaine, a voltage-gated Na+ channels inhibitor, and cisplatin, a common anticancer drug to obtain a tumor-targeted dual drugs-loaded nanogel system...
August 1, 2018: ACS Applied Materials & Interfaces
Marc-Andre Urbahn, Sonja Charlotte Kaup, Friedrich Reusswig, Irena Krüger, Martina Spelleken, Kerstin Jurk, Meike Klier, Philipp A Lang, Margitta Elvers
Sepsis is a systemic inflammatory disorder with organ dysfunction and represents the leading cause of mortality in non-coronary intensive care units. A key player in septic shock is Tumor Necrosis Factor-alpha (TNF-α). Phospholipase (PL)D1 is involved in the regulation of TNF-α upon ischemia/reperfusion injury in mice. In this study we analyzed the impact of PLD1 in the regulation of TNF-α, inflammation and organ damage in experimental sepsis. PLD1 deficiency increased survival of mice and decreased vital organ damage after LPS injections...
July 3, 2018: Scientific Reports
Kazutaka Kitamura, Kayoko Sato, Motoji Sawabe, Masayuki Yoshida, Nobuhisa Hagiwara
BACKGROUND: Adhesion molecules have essential roles in the development of atherosclerosis. We investigated whether P-selectin glycoprotein ligand-1 (PSGL-1)-expressing CD4 T cells contribute to plaque instability in acute coronary syndrome (ACS).Methods and Results:We studied the adhesion molecules on CD4 T cells from consecutive patients with ACS treated with thrombus-aspirating device and compared them with healthy controls (n=48 each). Blood, thrombi, and plaque samples from the culprit coronary arteries were collected by thrombus aspiration performed during emergency coronary artery angiography...
July 25, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
Jaeyeon Choi, Wissam Beaino, Ronald Fecek, Kellsye Fabian, Charles M Laymon, Brenda Kurland, Walter Storkus, Carolyn J Anderson
Very late antigen-4 (VLA-4; also known as integrin α4β1) is expressed at high levels in aggressive and metastatic melanoma tumors and may provide an ideal target for imaging and targeted radiotherapy. 177 Lu-DOTA-PEG4-LLP2A (177 Lu-LLP2A) shows high affinity for VLA-4 and had high uptake in B16F10 mouse melanoma tumors in vivo. Here, we report efficacy studies of 177 Lu-LLP2A, alone and combined with immune checkpoint inhibitors (ICI) in B16F10 tumor-bearing mice. Methods: B16F10 tumor cells (1 x 106) were implanted subcutaneously in C57BL/6 mice...
June 29, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Mingchun Luan, Xin He, Xiaohua Huang, Qiaoshu Zhang, Keli Ma
Within the extracellular domains of metastasis suppressor CD82, the large extracellular loop (EC2) has received much of the attention and its structure and function have been studied in detail. However, little attention has been given to the small extracellular loop (EC1 domain). To investigate the function role of EC1 in metastasis suppression of CD82, the peptide mimicking EC1 amino acid sequence (EC1-mP) was synthesized and its effect on cancer cells behavior was examined. Here, we reported that EC1-mP strongly inhibited cancer cell migration in vitro, attnuated the ability of cancer cells adhesion to fibronectin, and induced the apoptosis...
July 2, 2018: Biochemical and Biophysical Research Communications
Caitlin W Brown, John J Amante, Arthur M Mercurio
Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid-repair enzyme glutathione peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the α6β4 integrin, which sustains GPX4 expression...
June 22, 2018: Journal of Biological Chemistry
Yingfan Liang, Hongwei Chen, Ling Ji, Jinfu Du, Xiaofan Xie, Xiang Li, Yongliang Lou
Talin is a key component molecule of the extracellular matrix-integrin-cytoskeleton. It serves an important role in the activation of integrin, which, in turn, is known to mediate physiological and pathological processes, including cell adhesion, growth, tumorigenesis, and metastasis. In vertebrates, there are two Talin genes, Talin1 and Talin2. Talin1 is known to regulate focal adhesion dynamics, cell migration and cell invasion; however, the precise role of Talin2 in cancer remains unclear. In the present study, the functional role of Talin2 was examined in the MDA-MB-231 breast cancer cell line...
July 2018: Oncology Letters
Weixun Zhou, Yan Huang, Jinping Lai, Jun Lu, Michael Feely, Xiuli Liu
An increasing number of drugs including monoclonal antibodies and small molecules, either anti-inflammatory or immunity-enhancing, have been developed to treat human diseases and the number of medications in these classes is likely to expand in the future. The two most commonly used categories of such therapies are the anti-inflammatory group (anti- tumor necrosis factor (TNF) α, anti-interleukins/interleukin receptors, and anti-integrin bodies) and the anti-tumoral agents (immune checkpoint inhibitors, anti-CD20, and anti-endothelial growth factor)...
June 2018: Gastroenterology Research
Kang Qi, Xiangdong Li, Yongjian Geng, Hehe Cui, Chen Jin, Peihe Wang, Yue Li, Yuejin Yang
OBJECTIVE: Endothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial barrier disruption, by induction of Angptl4-mediated protection of endothelial barrier integrity...
2018: PloS One
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