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https://www.readbyqxmd.com/read/28550308/fortilin-binds-ire1%C3%AE-and-prevents-er-stress-from-signaling-apoptotic-cell-death
#1
Decha Pinkaew, Abhijnan Chattopadhyay, Matthew D King, Preedakorn Chunhacha, Zhihe Liu, Heather L Stevenson, Yanjie Chen, Patuma Sinthujaroen, Owen M McDougal, Ken Fujise
The endoplasmic reticulum, the cytoplasmic organelle that matures a massive amount of nascent secretory polypeptides, is particularly sensitive to stress. Endoplasmic reticulum stress causes unfolded proteins to populate the organelle, eliciting the unfolded protein response. During the unfolded protein response, GRP78-an endoplasmic reticulum master stress regulator-detaches from three endoplasmic reticulum stress sensors (IRE1α, PERK, and ATF6) and allows them to activate the apoptotic signaling pathway...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548889/therapy-of-advanced-non-small-cell-lung-cancer-with-an-sn-38-anti-trop-2-drug-conjugate-sacituzumab-govitecan
#2
Rebecca Suk Heist, Michael J Guarino, Gregory Masters, W Thomas Purcell, Alexander N Starodub, Leora Horn, Ronald J Scheff, Aditya Bardia, Wells A Messersmith, Jordan Berlin, Allyson J Ocean, Serengulam V Govindan, Pius Maliakal, Boyd Mudenda, William A Wegener, Robert M Sharkey, David M Goldenberg, D Ross Camidge
Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points...
May 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28518134/asic1-and-asic3-contribute-to-acidity-induced-emt-of-pancreatic-cancer-through-activating-ca-2-rhoa-pathway
#3
Shuai Zhu, Hai-Yun Zhou, Shi-Chang Deng, Shi-Jiang Deng, Chi He, Xiang Li, Jing-Yuan Chen, Yan Jin, Zhuang-Li Hu, Fang Wang, Chun-You Wang, Gang Zhao
Extracellular acid can have important effects on cancer cells. Acid-sensing ion channels (ASICs), which emerged as key receptors for extracellular acidic pH, are differently expressed during various diseases and have been implicated in underlying pathogenesis. This study reports that ASIC1 and ASIC3 are mainly expressed on membrane of pancreatic cancer cells and upregulated in pancreatic cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward current, which is required for elevation of intracellular Ca(2+) concentration ([Ca(2+)]i)...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28516961/supracricoid-partial-laryngectomy-with-crico-hyoido-epiglottopexy-for-glottic-carcinoma-with-anterior-commissure-involvement
#4
I Atallah, E Berta, A Coffre, J Villa, E Reyt, C A Righini
Glottic cancers discovered at an early stage (T1-T2) can be treated with either radiotherapy or surgery. The aim of our study is to analyse survival and functional results of supra-cricoid partial laryngectomy (SCPL) with crico-hyoido-epiglottopexy (CHEP) as surgical treatment for glottic carcinoma with anterior commissure involvement. We performed a retrospective study (1996-2013) which included patients who underwent SCPL-CHEP for glottic squamous cell carcinoma with involvement of the anterior commissure...
June 2017: Acta Otorhinolaryngologica Italica
https://www.readbyqxmd.com/read/28514439/haematopoietic-stem-and-progenitor-cells-from-human-pluripotent-stem-cells
#5
Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A Goettel, Erik Serrao, R Grant Rowe, Mohan Malleshaiah, Irene Wong, Patricia Sousa, Ted N Zhu, Andrea Ditadi, Gordon Keller, Alan N Engelman, Scott B Snapper, Sergei Doulatov, George Q Daley
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28507054/glutamine-transporters-are-targets-of-multiple-oncogenic-signaling-pathways-in-prostate-cancer
#6
Mark A White, Chenchu Lin, Kimal Rajapakshe, Jianrong Dong, Yan Shi, Efrosini Tsouko, Ratna Mukhopadhyay, Diana Jasso, Wajahat Dawood, Cristian Coarfa, Daniel E Frigo
Despite the known importance of androgen receptor (AR) signaling in prostate cancer (PCa), the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in PCa cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in PCa...
May 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28504697/the-transcriptional-coactivator-taz-regulates-reciprocal-differentiation-of-th17-cells-and-treg-cells
#7
Jing Geng, Shujuan Yu, Hao Zhao, Xiufeng Sun, Xun Li, Ping Wang, Xiaolin Xiong, Lixin Hong, Changchuan Xie, Jiahui Gao, Yiran Shi, Jiaqi Peng, Randy L Johnson, Nengming Xiao, Linrong Lu, Jiahuai Han, Dawang Zhou, Lanfen Chen
An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under TH17 cell-inducing conditions and was required for TH17 differentiation and TH17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation...
May 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28504250/curcumin-enhances-vascular-contractility-via-induction-of-myocardin-in-mouse-smooth-muscle-cells
#8
Shao-Wei Sun, Wen-Juan Tong, Zi-Fen Guo, Qin-Hui Tuo, Xiao-Yong Lei, Cai-Ping Zhang, Duan-Fang Liao, Jian-Xiong Chen
A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin (100 mg·kg-1·d-1, ig) for 6 weeks, the contractile responses of the thoracic aorta to KCl and phenylephrine were significantly enhanced compared with the control group. Furthermore, the contractility of vascular smooth muscle (SM) was significantly enhanced after incubation in curcumin (25 μmol/L) for 4 days, which was accompanied by upregulated expression of SM marker contractile proteins SM22α and SM α-actin...
May 1, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28503858/ldtr-is-a-master-regulator-of-gene-expression-in-liberibacter-asiaticus
#9
Fernando A Pagliai, Janelle F Coyle, Sharan Kapoor, Claudio F Gonzalez, Graciela L Lorca
Huanglongbing or citrus greening disease is causing devastation to the citrus industry. Liberibacter asiaticus, an obligate intracellular pathogen of citrus, is one the causative agents of the disease. Most of the knowledge about this bacterium has been deduced from the in silico exploration of its genomic sequence. L. asiaticus differentially expresses genes during its transmission from the psyllid vector, Diaphorina citri, to the plant. However, the regulatory mechanisms for the adaptation of the bacterium into either hosts remain unknown...
May 15, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28501492/ldh-inhibition-impacts-on-heat-shock-response-and-induces-senescence-of-hepatocellular-carcinoma-cells
#10
Marcella Manerba, Lorenza Di Ianni, Marzia Govoni, Marinella Roberti, Maurizio Recanatini, Giuseppina Di Stefano
In normal cells, heat shock response (HSR) is rapidly induced in response to a variety of harmful conditions and represents one of the most efficient defense mechanism. In cancer tissues, constitutive activation converts HSR into a life-threatening process, which plays a major role in helping cell survival and proliferation. Overexpression of heat shock proteins (HSPs) has been widely reported in human cancers and was found to correlate with tumor progression. Hepatocellular carcinoma is one of the conditions in which HSR activation was shown to have the highest clinical significance...
May 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28494858/mtorc1-balances-cellular-amino-acid-supply-with-demand-for-protein-synthesis-through-post-transcriptional-control-of-atf4
#11
Yeonwoo Park, Andrea Reyna-Neyra, Lucas Philippe, Carson C Thoreen
The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5' UTR...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28493823/hepatitis-c-virus-core-protein-targets-4e-bp1-expression-and-phosphorylation-and-potentiates-myc-induced-liver-carcinogenesis-in-transgenic-mice
#12
Cosette Abdallah, Charlène Lejamtel, Nassima Benzoubir, Serena Battaglia, Nazha Sidahmed-Adrar, Christophe Desterke, Matthieu Lemasson, Arielle R Rosenberg, Didier Samuel, Christian Bréchot, Delphine Pflieger, François Le Naour, Marie-Françoise Bourgeade
Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28485720/herpesvirus-micrornas-for-use-in-gene-therapy-immune-evasion-strategies
#13
REVIEW
S T F Bots, R C Hoeben
Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft may therefore require life-long treatment with immunosuppressive drugs. An alternative approach to reduce graft rejection could involve the use of immune-evasion molecules. Expression of such molecules in cells of the graft may subvert recognition by the host's immune system...
May 9, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28481226/neonatal-expression-of-rna-binding-protein-igf2bp3-regulates-the-human-fetal-adult-megakaryocyte-transition
#14
Kamaleldin E Elagib, Chih-Huan Lu, Goar Mosoyan, Shadi Khalil, Ewelina Zasadzińska, Daniel R Foltz, Peter Balogh, Alejandro A Gru, Deborah A Fuchs, Lisa M Rimsza, Els Verhoeyen, Miriam Sansó, Robert P Fisher, Camelia Iancu-Rubin, Adam N Goldfarb
Hematopoietic transitions that accompany fetal development, such as erythroid globin chain switching, play important roles in normal physiology and disease development. In the megakaryocyte lineage, human fetal progenitors do not execute the adult morphogenesis program of enlargement, polyploidization, and proplatelet formation. Although these defects decline with gestational stage, they remain sufficiently severe at birth to predispose newborns to thrombocytopenia. These defects may also contribute to inferior platelet recovery after cord blood stem cell transplantation and may underlie inefficient platelet production by megakaryocytes derived from pluripotent stem cells...
May 8, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28469165/the-regulatory-t-cell-transcription-factor-foxp3-protects-against-crescentic-glomerulonephritis
#15
Chen Yang, Xiao-Ru Huang, Erik Fung, Hua-Feng Liu, Hui-Yao Lan
Regulatory T cells (Tregs) have been shown to play a protective role in glomerulonephritis (GN) and Foxp3 is a master transcription factor in Treg development. In this study, we examined the functional role and mechanisms of Foxp3 in a mouse model of accelerated anti-glomerular basement membrane (anti-GBM) GN induced in antigen-primed Foxp3 transgenic (Tg) mice. Compared with littermate of wildtype (WT) mice in which induced severe crescentic GN developed with progressive renal dysfunction, Foxp3 Tg mice had reduced crescent formation, urinary protein excretion, plasma creatinine and decline in creatinine clearance...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28463873/transcriptional-circuits-in-b-cell-transformation
#16
Yeguang Hu, Toshimi Yoshida, Katia Georgopoulos
PURPOSE OF REVIEW: Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process...
April 29, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28461502/mef2d-haploinsufficiency-downregulates-the-nrf2-pathway-and-renders-photoreceptors-susceptible-to-light-induced-oxidative-stress
#17
Saumya Nagar, Sarah M Noveral, Dorit Trudler, Kevin M Lopez, Scott R McKercher, Xuemei Han, John R Yates, Juan C Piña-Crespo, Nobuki Nakanishi, Takumi Satoh, Shu-Ichi Okamoto, Stuart A Lipton
Gaining mechanistic insight into interaction between causative factors of complex multifactorial diseases involving photoreceptor damage might aid in devising effective therapies. Oxidative stress is one of the potential unifying mechanisms for interplay between genetic and environmental factors that contribute to photoreceptor pathology. Interestingly, the transcription factor myocyte enhancer factor 2d (MEF2D) is known to be important in photoreceptor survival, as knockout of this transcription factor results in loss of photoreceptors in mice...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28456549/the-interplay-between-the-cellular-hypoxic-response-and-notch-signaling
#18
Sebastian K-J Landor, Urban Lendahl
The ability to sense and adapt to low oxygen levels (hypoxia) is central for most organisms and cell types. At the center of this process is a molecular mechanism, the cellular hypoxic response, in which the hypoxia inducible factors (HIFs) are stabilized by hypoxia, allowing the HIF proteins to act as master transcriptional regulators to adjust the cell to a low oxygen environment. In recent years, it has become increasingly appreciated that the cellular hypoxic response does not always operate in splendid isolation, but intersects with signaling mechanisms such as Notch signaling, a key regulatory signaling mechanism operating in most cell types controlling stem cell maintenance and differentiation...
April 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28456517/proprotein-convertase-inhibition-paralyzing-the-cell-s-master-switches
#19
Andres J Klein-Szanto, Daniel E Bassi
Proprotein convertases are serine proteases responsible for the cleavage and subsequent activation of protein substrates, many of them relevant for the development of an ample variety of diseases. Seven of the PCs, including furin and PACE4, recognize and hydrolyze the C-terminal end of the general sequence RXRR/KXR, whereas PCSK-9 recognizes a series of non-basic amino acids. In some systems, PC-mediated substrate activation results in the development of pathological processes, such as cancer, endocrinopathies, and cardiovascular and infectious diseases...
April 26, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28455430/endocrine-targets-of-hypoxia-inducible-factors
#20
Hsiu-Chi Lee, S-J Sean Tsai
Endocrine is an important and tightly regulated system for maintaining body homeostasis. Endocrine glands produce hormones, which are released into blood stream to guide the target cells responding to all sorts of stimulations. For maintaining body homeostasis, the secretion and activity of a particular hormone needs to be adjusted in responding to environmental challenges such as changes in nutritional status or chronic stress. Hypoxia, a status caused by reduced oxygen availability or imbalance of oxygen consumption/supply in an organ or within a cell, is a stress that affects many physiological and pathological processes...
April 28, 2017: Journal of Endocrinology
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