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https://www.readbyqxmd.com/read/28822237/beyond-genomics-targeting-the-epigenome-in-diffuse-large-b-cell-lymphoma
#1
REVIEW
Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced...
August 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28822049/potential-for-diagnosis-versus-therapy-monitoring-of-attention-deficit-hyperactivity-disorder-a-new-epigenetic-biomarker-interacting-with-both-genotype-and-auto-immunity
#2
Walter Adriani, Emilia Romano, Mariangela Pucci, Esterina Pascale, Luca Cerniglia, Silvia Cimino, Renata Tambelli, Paolo Curatolo, Oleg Granstrem, Mauro Maccarrone, Giovanni Laviola, Claudio D'Addario
In view of the need for easily accessible biomarkers, we evaluated in ADHD children the epigenetic status of the 5'-untranslated region (UTR) in the SLC6A3 gene, coding for human dopamine transporter (DAT). We analysed buccal swabs and sera from 30 children who met DSM-IV-TR criteria for ADHD, assigned to treatment according to severity. Methylation levels at six-selected CpG sites (among which, a CGGCGGCGG and a CGCG motif), alone or in combination with serum titers in auto-antibodies against dopamine transporter (DAT aAbs), were analysed for correlation with CGAS scores (by clinicians) and Conners' scales (by parents), collected at recruitment and after 6 weeks...
August 18, 2017: European Child & Adolescent Psychiatry
https://www.readbyqxmd.com/read/28821714/gadd45a-plays-a-protective-role-against-temozolomide-treatment-in-glioblastoma-cells
#3
Hsiao-Han Wang, Tsuey-Yu Chang, Wei-Chen Lin, Kuo-Chen Wei, Jyh-Wei Shin
Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821643/changes-in-the-excitability-of-neocortical-neurons-in-a-mouse-model-of-amyotrophic-lateral-sclerosis-are-not-specific-to-corticospinal-neurons-and-are-modulated-by-advancing-disease
#4
Juhyun Kim, Ethan G Hughes, Ashwin S Shetty, Paola Arlotta, Loyal A Goff, Dwight E Bergles, Solange P Brown
Cell-type specific changes in neuronal excitability have been proposed to contribute to the selective degeneration of corticospinal neurons in amyotrophic lateral sclerosis (ALS) and to neocortical hyperexcitability, a prominent feature of both inherited and sporadic variants of the disease, but the mechanisms underlying selective loss of specific cell types in ALS are not known. We analyzed the physiological properties of distinct classes of cortical neurons in the motor cortex of hSOD1(G93A) mice of both sexes and found that they all exhibit increases in intrinsic excitability that depend on disease stage...
August 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#5
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821607/two-plant-derived-aporphinoid-alkaloids-exert-their-antifungal-activity-by-disrupting-mitochondrial-iron-sulfur-cluster-biosynthesis
#6
Siddharth K Tripathi, Tao Xu, Qin Feng, Bharathi Avula, Xiaomin Shi, Xuewen Pan, Melanie M Mask, Scott R Baerson, Melissa R Jacob, Ranga Rao Ravu, Shabana I Khan, Xing-Cong Li, Ikhlas A Khan, Alice M Clark, Ameeta K Agarwal
Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens Candida albicans and Cryptococcus neoformans However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821567/chronic-spinal-cord-changes-in-a-high-fat-diet-fed-male-rat-model-of-thoracic-spinal-contusion
#7
Redin A Spann, William J Lawson, Raymond J Grill, Michael R Garrett, Bernadette E Grayson
Individuals that suffer injury to the spinal cord can result in long-term, debilitating sequelae. Spinal cord injured patients have increased risk for the development of metabolic disease which can further hinder the effectiveness of treatments to rehabilitate the cord and improve quality of life. In the present study, we sought to understand the impact of high-fat diet induced obesity on spinal cord injury (SCI) by examining transcriptome changes in the area of the injury and rostral and caudal to site of damage 12 weeks after injury...
August 18, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28821028/targeted-gene-delivery-of-polyethyleneimine-grafted-chitosan-with-rgd-dendrimer-peptide-in-%C3%AE-v%C3%AE-3-integrin-overexpressing-tumor-cells
#8
Young-Min Kim, Seong-Cheol Park, Mi-Kyeong Jang
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820886/circulating-mirnas-in-sepsis-a-network-under-attack-an-in-silico-prediction-of-the-potential-existence-of-mirna-sponges-in-sepsis
#9
Catalin Vasilescu, Mihnea Dragomir, Mihai Tanase, Dana Giza, Raluca Purnichescu-Purtan, Meng Chen, Sai-Ching Jim Yeung, George A Calin
Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and treatment. A large panel of small non-coding microRNAs was reported to modulate the immune response in sepsis but have not been tested in clinical practice. Large-scale identification of microRNA networks in sepsis might reveal a new biological mechanism that can be also targeted by gene therapy. Therefore, the main objective of this study is to perform a comparison of the miRNA network between septic patients and healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28820758/lack-of-association-between-interleukin-28b-polymorphism-and-vertical-transmission-of-hepatitis-c
#10
Afrodite Psaros Einberg, Ann-Sofi Duberg, Olga Filipovich, Jessica Nyström, Anton Zhirkov, Erwin Daniel Brenndörfer, Lars Frelin, Elena Rukoiatkina, Yuriy Lobzin, Matti Sällberg, Björn Fischler, Anton Lutckii
OBJECTIVES: Single genetic nucleotide polymorphism (rs12979860) near the gene for Interleukin 28B (IL28B), is known to be of importance for frequency of spontaneous clearance and treatment outcome in interferon based therapies in patients with hepatitis C virus (HCV) infection. The aim of this study was to investigate if IL28B polymorphism in children and/or their mothers plays a role in vertical transmission of HCV (HCV-VT). METHODS: Plasma samples from 59 infected women, 76 uninfected children born to infected mothers, and 47 children with known vertically transmitted HCV infection, were analysed for IL28B polymorphism and classified by the IL28B genotype (C/C, C/T and T/T) as well as by viral genotype...
August 17, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28820502/oligonucleotides-targeting-periostin-ameliorates-pulmonary-fibrosis
#11
A Tomaru, T Kobayashi, J A Hinneh, P B Tonto, C N D' Alessandro-Gabazza, H Fujimoto, K Fujiwara, Y Takahashi, M Ohnishi, T Yasuma, K Nishihama, M Yoshino, K Takao, M Toda, T Totoki, Y Takei, K Yoshikawa, O Taguchi, E C Gabazza
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3 to 4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here, we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibit lung fibrosis by direct administration into the lung by intranasal route...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28820501/interleukin-armed-chimeric-antigen-receptor-modified-t-cells-for-cancer-immunotherapy
#12
REVIEW
Y Huang, D Li, D-Y Qin, H-F Gou, W Wei, Y-S Wang, Y-Q Wei, W Wang
Chimeric antigen receptor-modified T cells (CAR-T) are endowed with cytotoxic specificity to tumor cells. Although CAR-T-based cancer immunotherapy presents curable therapeutic potential for hematological malignancies, achieving substantial efficacy for solid tumors remain challenging. Researchers have exploited many strategies to enhance the anti-tumor efficacy of CAR-T cells for solid tumors, among which cytokine-armed CAR-T cells improve the proliferation, survival, homing and other properties of CAR-T cells...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28820434/neuroprotective-and-nerve-regenerative-approaches-for-treatment-of-erectile-dysfunction-after-cavernous-nerve-injury
#13
REVIEW
Jeffrey D Campbell, Arthur L Burnett
Erectile dysfunction (ED) is a significant cause of reduced quality of life in men and their partners. Cavernous nerve injury (CNI) during pelvic surgery results in ED in greater than 50% of patients, regardless of additional patient factors. ED related to CNI is difficult to treat and typically poorly responsive to first- and second-line therapeutic options. Recently, a significant amount of research has been devoted to exploring neuroprotective and neuroregenerative approaches to salvage erectile function in patients with CNI...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28820389/hippo-pathway-brief-overview-of-its-relevance-in-cancer
#14
A L Zygulska, K Krzemieniecki, P Pierzchalski
The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820323/non-surgical-model-for-alveolar-bone-regeneration-by-bone-morphogenetic-protein-2-7-gene-therapy
#15
Mariko Kawai, Yo-Hei Kataoka, Junya Sonobe, Hiromitsu Yamamoto, Masakazu Inubushi, Takuya Ishimoto, Takayoshi Nakano, Hiroki Maruyama, Jun-Ichi Miyazaki, Toshio Yamamoto, Kazuhisa Bessho, Kiyoshi Ohura
BACKGROUND: Alveolar bone is a critical tissue for tooth retention; however, once alveolar bone is lost, it may not spontaneously regenerate. Currently, bone grafts or artificial bone are commonly used for alveolar bone regeneration therapy. However, these therapies require surgical procedures, which present risks, particularly in aged patients. Therefore, the development of alveolar bone regeneration techniques that do not require surgical procedures is critical. It is well known that stem cells present in the periosteal and periodontal ligament may be induced to differentiate into osteogenic cells...
August 18, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28820183/technique-of-retinal-gene-therapy-delivery-of-viral-vector-into-the-subretinal-space
#16
K Xue, M Groppe, A P Salvetti, R E MacLaren
PurposeSafe and reproducible delivery of gene therapy vector into the subretinal space is essential for successful targeting of the retinal pigment epithelium (RPE) and photoreceptors. The success of surgery is critical for the clinical efficacy of retinal gene therapy. Iatrogenic detachment of the degenerate (often adherent) retina in patients with hereditary retinal degenerations and small volume (eg, 0.1 ml) subretinal injections pose new surgical challenges.MethodsOur subretinal gene therapy technique involved pre-operative planning with optical coherence tomography (OCT) and autofluorescence (AF) imaging, 23 G pars plana vitrectomy, internal limiting membrane staining with Membrane Blue Dual (DORC BV, Zuidland, Netherlands), a two-step subretinal injection using a 41 G Teflon tipped cannula (DORC) first with normal saline to create a parafoveal bleb followed by slow infusion of viral vector via the same self-sealing retinotomy...
August 18, 2017: Eye
https://www.readbyqxmd.com/read/28820180/osteogenesis-imperfecta
#17
REVIEW
Joan C Marini, Antonella Forlino, Hans Peter Bächinger, Nick J Bishop, Peter H Byers, Anne De Paepe, Francois Fassier, Nadja Fratzl-Zelman, Kenneth M Kozloff, Deborah Krakow, Kathleen Montpetit, Oliver Semler
Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure...
August 18, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28820179/effects-of-dck-knockdown-on-proliferation-apoptosis-and-tumorigenicity-in-vivo-of-cervical-cancer-hela-cells
#18
Q-Y Shang, C-S Wu, H-R Gao
The present study explored the effect that deoxycytidine kinase (DCK) knockdown had on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells. Human cervical cancer HeLa cells that had received no prior treatment were selected from the HeLa group. The HeLa-negative control (NC) group consisted of cells that had undergone an empty vector treatment, and finally the HeLa-short hairpin RNA (shRNA) group included cells that were treated by means of shRNA-DCK expression. DCK expressions were evaluated by quantitative real-time polymerase chain reaction in addition to western blotting assays...
August 18, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28820170/paradoxical-worsening-of-a-case-of-tb-subretinal-abscess-with-serpiginous-like-choroiditis-following-the-initiation-of-antitubercular-therapy
#19
Sudha K Ganesh, B Sowkath Ali
A 37-year-old immunocompetent male patient presented with the blurring of vision, both eyes for the past1 year. Fundus examination revealed bilateral multiple subretinal abscesses with areas of healed serpiginous-like choroiditis. Laboratory investigations showed positive tuberculin skin test, positive QuantiFERON TB-Gold Test, and high resolution computed tomography chest showed enlarged mediastinal lymph nodes. The aqueous sample revealed polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis (MTB) (MPB64 genome)...
August 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28819848/capture-and-genetic-analysis-of-circulating-tumor-cells-using-a-magnetic-separation-device-magnetic-sifter
#20
Chin Chun Ooi, Seung-Min Park, Dawson J Wong, Sanjiv S Gambhir, Shan X Wang
Circulating tumor cells (CTCs) are currently widely studied for their potential application as part of a liquid biopsy. These cells are shed from the primary tumor into the circulation, and are postulated to provide insight into the molecular makeup of the actual tumor in a minimally invasive manner. However, they are extremely rare in blood, with typical concentrations of 1-100 in a milliliter of blood; hence, a need exists for a rapid and high-purity method for isolating CTCs from whole blood. Here, we describe the application of a microfabricated magnetic sifter toward isolation of CTCs from whole blood at volumetric flow rates of 10 mL/h, along with the use of a PDMS-based nanowell system for single-cell gene expression profiling...
2017: Methods in Molecular Biology
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