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https://www.readbyqxmd.com/read/28726777/humanin-g-hng-protects-age-related-macular-degeneration-amd-transmitochondrial-arpe-19-cybrids-from-mitochondrial-and-cellular-damage
#1
Sonali Nashine, Pinchas Cohen, Marilyn Chwa, Stephanie Lu, Anthony B Nesburn, Baruch D Kuppermann, M Cristina Kenney
Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726770/a-model-for-the-regulation-of-follicular-dendritic-cells-predicts-invariant-reciprocal-time-decay-of-post-vaccine-antibody-response
#2
Anthony Almudevar
Follicular dendritic cells (FDC) play a crucial role in the regulation of humoral immunity. They are believed to be responsible for long-term persistence of antibody, due to their role in antibody response induction and their ability to retain antigen in immunogenic form for long periods. In this article, a regulatory control model is proposed which links persistence of humoral immunity with cellular processes associated with FDCs. The argument is comprised of three elements. The first is a literature review of population-level studies of post-vaccination antibody persistence...
July 20, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28725635/implications-of-micrornas-in-oncolytic-virotherapy
#3
REVIEW
Xavier Bofill-De Ros, Maria Rovira-Rigau, Cristina Fillat
MicroRNAs (miRNAs) are an abundant class of small non-coding RNA molecules (~22 nt) that can repress gene expression. Deregulation of certain miRNAs is widely recognized as a robust biomarker for many neoplasms, as well as an important player in tumorigenesis and the establishment of tumoral microenvironments. The downregulation of specific miRNAs in tumors has been exploited as a mechanism to provide selectivity to oncolytic viruses or gene-based therapies. miRNA response elements recognizing miRNAs expressed in specific tissues, but downregulated in tumors, have been inserted into the 3'UTR of viral genes to promote the degradation of these viral mRNAs in healthy tissue, but not in tumor cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#4
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28724955/mushroom-lectin-overcomes-hepatitis-b-virus-tolerance-via-tlr6-signaling
#5
Meina He, Dan Su, Qinghong Liu, Wenjuan Gao, Youmin Kang
Currently, chronic hepatitis B virus (HBV) infection remains a serious public health problem in the world. Recombinant HBV vaccine, as a preventive strategy against HBV infection, generates high antibody level, but it is not effective to activate innate and cellular immunity for chronic HBV infection therapy. Lectins from mushroom are natural and active proteins which have been shown important biological functions. However, little is known about the immunological mechanism engaged by mushroom lectins. Here we report that, lectin from Pleurotus ostreatus (POL) stimulated innate response by activating Toll-like receptor 6 signal pathway of dendritic cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724772/binding-of-hsv-1-ul20-to-godz-affects-its-palmitoylation-and-is-essential-for-infectivity-and-proper-targeting-and-localization-of-ul20-and-gk
#6
Shaohui Wang, Kevin R Mott, Kolja Wawrowsky, Konstantin G Kousoulas, Bernhard Luscher, Homayon Ghiasi
HSV-1 UL20 plays a crucial role in the envelopment of the cytoplasmic virion and its egress. It is a non-glycosylated envelope protein that is regulated as a γ1 gene. Two-hybrid and pull-down assays demonstrated that UL20, but no other HSV-1 gene-encoded proteins, binds specifically to GODZ (a.k.a.: DHHC3), a cellular Golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein. A catalytically inactive dominant-negative GODZ construct significantly reduced HSV-1 replication in vitro and affected the localization of UL20 and gK and their interactions but not gC...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724615/glioblastoma-cellular-cross-talk-converges-on-nf-%C3%AE%C2%BAb-to-attenuate-egfr-inhibitor-sensitivity
#7
Ciro Zanca, Genaro R Villa, Jorge A Benitez, Amy Haseley Thorne, Tomoyuki Koga, Matteo D'Antonio, Shiro Ikegami, Jianhui Ma, Antonia D Boyer, Afsheen Banisadr, Nathan M Jameson, Alison D Parisian, Olesja V Eliseeva, Gabriela F Barnabe, Feng Liu, Sihan Wu, Huijun Yang, Jill Wykosky, Kelly A Frazer, Vladislav V Verkhusha, Maria G Isaguliants, William A Weiss, Timothy C Gahman, Andrew K Shiau, Clark C Chen, Paul S Mischel, Webster K Cavenee, Frank B Furnari
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs)...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28724539/racial-and-ethnic-disparities-in-hematologic-malignancies
#8
Kedar Kirtane, Stephanie J Lee
Racial and ethnic disparities in patients with solid malignancies have been well documented. Less is known about these disparities in patients with hematologic malignancies. With the advent of novel chemotherapeutics and targeted molecular, cellular, and immunologic therapies, it is important to identify differences in care that may lead to disparate outcomes. This review provides a critical appraisal of the empirical research on racial and ethnic disparities in incidence, survival, and outcomes in patients with hematologic malignancies...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28724340/pharmacological-therapeutics-in-friedreich-ataxia-the-present-state
#9
Cassandra Strawser, Kimberly Schadt, Lauren Hauser, Ashley McCormick, Mckenzie Wells, Jane Larkindale, Hong Lin, David R Lynch
Friedreich ataxia (FRDA) is a progressive, inherited, neurodegenerative disease for which there is currently no cure or approved treatment. FRDA is caused by deficits in the production and expression of frataxin, a protein found in the mitochondria that is most likely responsible for regulating iron-sulfur cluster enzymes within the cell. A decrease in frataxin causes dysfunction of adenosine triphosphate synthesis, accumulation of mitochondrial iron, and other events leading to downstream cellular dysfunction...
July 20, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28723624/lncrna-ancr-down-regulation-promotes-tgf-%C3%AE-induced-emt-and-metastasis-in-breast-cancer
#10
Zhongwei Li, Meichen Dong, Dongmei Fan, Pingfu Hou, Hongyuan Li, Lingxia Liu, Cong Lin, Jiwei Liu, Liangping Su, Lan Wu, Xiaoxue Li, Baiqu Huang, Jun Lu, Yu Zhang
Epithelial to mesenchymal transition (EMT) is a progression of cellular plasticity critical for development, differentiation, cancer cells migration and tumor metastasis. As a well-studied factor, TGF-β participates in EMT and involves in physiological and pathological functions of tumor progression. Accumulating evidence indicates that long noncoding RNAs(lncRNAs) play crucial roles in EMT and tumor metastasis. Here, we find that lncRNA ANCR participates in TGF-β1-induced EMT. By our ChIP and Real-time PCR assays, we reveal that TGF-β1 down-regulates ANCR expression by increasing HDAC3 enrichment at ANCR promoter region, which decreases both H3 and H4 acetylation of ANCR promoter...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723234/flexible-small-molecular-anti-estrogens-with-n-n-dialkylated-2-5-diethoxy-4-morpholinoaniline-scaffold-targets-multiple-estrogen-receptor-conformations
#11
Bethany K Asare, Emmanuel Yawson, Rajendram V Rajnarayanan
Estrogen mediates various cellular processes including cell proliferation, differentiation, growth and mammary gland function. Estrogen Receptors (ERs) are expressed in 70% of breast cancers. Consequently, estrogen mediated ER signaling plays a critical role in breast cancer diagnosis, prognosis, and treatment. Estrogen Receptors are ligand-triggered transcription factors. However, in the absence of a cognate estrogenic ligand, ERs can be activated by a variety of other extracellular signals. Tamoxifen, an anti-estrogen that selectively targets ER, induces substantial regression of breast tumors and an increase in disease-free survival...
July 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28722477/advances-toward-lsd1-inhibitors-for-cancer-therapy
#12
Xiaoli Fu, Peng Zhang, Bin Yu
LSD1 has become an important biologically validated epigenetic target for cancer therapy since its identification in 2004. LSD1 mediates many cellular signaling pathways and is involved in the initiation and development of cancers. Aberrant overexpression of LSD1 has been observed in different types of cancers, and inactivation by small molecules suppresses cancer cell differentiation, proliferation, invasion and migration. To date, a large number of LSD1 inhibitors have been reported, RG6016, GSK-2879552, INCB059872, IMG-7289 and CC-90011 are currently undergoing clinical assessment for the treatment of acute myeloid leukemia, small-cell lung cancer, etc...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28721828/mir-149-as-a-potential-molecular-target-for-cancer
#13
Suet Hui Ow, Pei Jou Chua, Boon Huat Bay
MicroRNAs (miRNAs) are small, non-coding nucleotides that regulate the expression of proteins. They play major roles in fundamental cellular processes. Aberrant expression of miRNAs has been frequently detected in cancers. miR-149 has been implicated in tumor progression by regulating cellular proliferation, migration, invasion, epithelial-mesenchymal-transition and chemoresistance. There have been reports that miR-149 can function both as an oncogene or tumor suppressor, depending on the type of cancer, thereby giving rise to the possibility of utilizing miR-149 mimics and inhibitors for cancer therapy...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721060/clinical-use-of-lenvatinib-in-combination-with-everolimus-for-the-treatment-of-advanced-renal-cell-carcinoma
#14
REVIEW
Alessandro Leonetti, Francesco Leonardi, Melissa Bersanelli, Sebastiano Buti
INTRODUCTION: Renal cell carcinoma (RCC) represents 2%-3% of all cancers in adults, and its pathogenesis is mainly related to altered cellular response to hypoxia. Lenvatinib, a novel multitarget tyrosine kinase inhibitor (TKI), represents a therapeutic option, in combination with mammalian target of rapamycin (mTOR) inhibitor everolimus, for the treatment of metastatic RCC (mRCC). AIM: The objective of this article is to review the evidence about the treatment of mRCC with combination of lenvatinib plus everolimus...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28720686/oncolytic-virus-induced-cell-death-and-immunity-a-match-made-in-heaven
#15
REVIEW
Jolien De Munck, Alex Binks, Iain A McNeish, Joeri L Aerts
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28720666/inactivation-of-receptor-tyrosine-kinases-reverts-aberrant-dna-methylation-in-acute-myeloid-leukemia
#16
Na Shen, Fei Yan, Jiuxia Pang, Na Zhao, Naseema Gangat, Lai-Chu Wu, Ann M Bode, Aref Al-Kali, Mark R Litzow, Shujun Liu
Purpose: Receptor tyrosine kinases (RTKs) are frequently deregulated in leukemia, yet the biological consequences of this deregulation remain elusive. The mechanisms underlying aberrant methylation, a hallmark of leukemia, are not fully understood. Here we investigated the role of RTKs in methylation abnormalities and characterized the hypomethylating activities of RTK inhibitors.<br />Experimental Design: Whether and how RTKs regulate expression of DNA methyltransferases (DNMTs), tumor suppressor genes (TSGs) as well as global and gene specific DNA methylation were examined...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28719907/tumor-heterogeneity-in-lymphomas-a-different-breed
#17
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28719670/suppressive-effect-of-amp-activated-protein-kinase-on-the-epithelial-mesenchymal-transition-in-retinal-pigment-epithelial-cells
#18
Ryo Matoba, Yuki Morizane, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Ryoichi Araki, Mika Hosogi, Tomoko Yonezawa, Fumio Shiraga
The epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a central role in the development of proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK), a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF)-α (10 ng/ml) and transforming growth factor (TGF)-β2 (5 ng/ml)...
2017: PloS One
https://www.readbyqxmd.com/read/28719632/viscum-album-neutralizes-tumor-induced-immunosuppression-in-a-human-in-vitro-cell-model
#19
Carmen Steinborn, Amy Marisa Klemd, Ann-Sophie Sanchez-Campillo, Sophie Rieger, Marieke Scheffen, Barbara Sauer, Manuel Garcia-Käufer, Konrad Urech, Marie Follo, Annekathrin Ücker, Gunver Sophia Kienle, Roman Huber, Carsten Gründemann
Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays...
2017: PloS One
https://www.readbyqxmd.com/read/28719551/annulus-fibrosus-repair-using-high-density-collagen-gel-an-in-vivo-ovine-model
#20
Brenton Pennicooke, Ibrahim Hussain, Connor Berlin, Stephen R Sloan, Brandon Borde, Yu Moriguchi, Gernot Lang, Rodrigo Navarro-Ramirez, Jonathan Cheetham, Lawrence J Bonassar, Roger Härtl
STUDY DESIGN: Ovine in vivo study. OBJECTIVE: To perform lateral approach lumbar surgery in an ovine model to administer an injectable riboflavin (RF) cross-linked high-density collagen (HDC) gel and to assess its ability to mitigate intervertebral disc (IVD) degeneration after induced annulus fibrosus (AF) injury. SUMMARY OF BACKGROUND DATA: Biological-based injectable gels have shown efficacy in restoring biomechanical, radiographic, and histological parameters in IVD-injured animal models...
July 17, 2017: Spine
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