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Discovery Medicine

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https://www.readbyqxmd.com/read/28147220/intersections-of-pathways-involving-biotin-and-iron-relative-to-therapeutic-mechanisms-for-progressive-multiple-sclerosis
#1
Rebecca M Heidker, Mitchell R Emerson, Steven M LeVine
While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147219/preclinical-models-of-esophageal-adenocarcinoma-for-drug-development
#2
David S Liu, Cuong P Duong, Wayne A Phillips, Nicholas J Clemons
The advent of multi-omic profiling of tumors, together with the increasing affordability of high-throughput drug screening programs, has helped usher in a new era of molecular targeted therapies for many solid malignancies. However, there has been limited success in esophageal adenocarcinoma. Until recently, preclinical drug development for this cancer has been largely limited to a small number of cell line models. Now, the increasing availability of patient-derived xenografts and novel metastatic models are helping to bridge the gap between scientific discovery and patient care...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147218/role-of-gut-microbiome-in-ankylosing-spondylitis-an-analysis-of-studies-in-literature
#3
Yong-Yue Xu, Xi Tan, Yi-Ting He, Ying-Yan Zhou, Xiao-Hong He, Run-Yue Huang
OBJECTIVE: Gut microbiome is considered to be involved in the pathogenesis of ankylosing spondylitis (AS). We conducted a comprehensive literature review in this area to facilitate future research. METHODS: We searched all literature in the PubMed database from inception to July 2016. Relevant articles were chosen and analyzed by three independent investigators. RESULTS: The composition of gut microbiome in patients with AS has been identified to be different from healthy populations; however, specific profiles of gut microbiome are not yet clearly known...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147217/ccg-an-integrative-resource-of-cancer-protein-coding-genes-and-long-noncoding-rnas
#4
Mengrong Liu, Yu-Cheng T Yang, Gang Xu, Chang Tan, Zhi John Lu
The identification of cancer genes remains a main aim of cancer research. With the advances of high-throughput sequencing technologies, thousands of novel cancer genes were identified through recurrent mutation analyses and differential expression analyses between normal tissues and tumors in large populations. Many databases were developed to document the cancer genes. However, no public database providing both cancer protein-coding genes and cancer lncRNAs is available presently. Here, we present the Catalogue of Cancer Genes (CCG) database (http://ccg...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147216/an-emerging-role-of-alu-rna-in-geographic-atrophy-pathogenesis-the-implication-for-novel-therapeutic-strategies
#5
Xiying Mao, Wangyi Fang, Qinghuai Liu
It is generally accepted that geographic atrophy (GA), a currently untreatable advanced form of age-related macular degeneration (AMD), is a multifactorial disease resulting in gradual and permanent blindness. Various risk factors are demonstrated to be responsible for its pathogenesis, such as aging, light exposure, and smoking. Molecular components associated with those risk factors form a complex and interwoven network at the confluence of inflammation, highlighting the significance of inflammasome activation in GA progression...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147215/attenuated-synovial-fluid-ghrelin-levels-are-linked-with-cartilage-damage-meniscus-injury-and-clinical-symptoms-in-patients-with-knee-anterior-cruciate-ligament-deficiency
#6
Yu-Cong Zou, Liang-Hua Chen, Yong-Liang Ye, Guang-Gang Yang, Zheng Mao, Dan-Dan Liu, Jun-Qi Chen, Jing-Jie Chen, Gang Liu
BACKGROUND: The meniscus injury and post-traumatic knee osteoarthritis (PTOA) following anterior cruciate ligament (ACL) lesions often cause great burdens to patients. Ghrelin, a recently identified 28-amino-acid peptide, has been shown to inhibit inflammation and perform as a growth factor for chondrocyte. OBJECTIVE: This study was aimed at investigating ghrelin concentration in synovial fluid and its association with the degree of meniscus injury, articular degeneration, and clinical severity in patients suffering from anterior cruciate ligament (ACL) deficiency...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009972/inhibition-of-the-hedgehog-pathway-leads-to-antifibrotic-effects-in-dermal-fibrosis
#7
Hua-Li Cao, Jiong Zhou, Xi-Bei Chen, Lilla Landeck, Jian-Qiang Yang, Jia-Qi Chen, Wei Li, Sui-Qing Cai, Min Zheng, Xiao-Yong Man
Dermal fibrosis is characterized by the activation of the matrix-producing 'positive' myofibroblasts, and the relentless production and deposition of extracellular matrix. The hedgehog pathway has recently been demonstrated to work in a pro-fibrotic manner in systemic sclerosis (SSc). A negative regulator of the hedgehog pathway (Hh), the suppressor of fused (Sufu), was shown to be involved in the activation of fibrotic diseases. However, the exact role of Sufu in fibrosis has not been investigated so far. In our study, we aimed to define the role of sufu in the process of fibrosis using dermal fibroblasts of healthy donors that were cultured in vitro...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009971/dacomitinib-a-new-pan-egfr-inhibitor-is-effective-in-killing-ovarian-cancer-cells
#8
Lei Xu, Huini Wu, Chao Jiang, Hongcai Wang, Bei Gao, Shumei Yan, Yushu Qi, Shufeng Zhou
OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009970/combined-serum-and-eps-urine-proteomic-analysis-using-itraq-technology-for-discovery-of-potential-prostate-cancer-biomarkers
#9
Mo Zhang, Lizhu Chen, Zhengwei Yuan, Zeyu Yang, Yue Li, Liping Shan, Bo Yin, Xiang Fei, Jianing Miao, Yongsheng Song
Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009969/the-role-of-connexin43-in-diabetic-microvascular-complications
#10
Hui Li, Fang Wang
Diabetes mellitus is one of the largest global healthcare problems. People with diabetes have high risk of developing any of the microvascularcomplications, including retinopathy, nephropathy, and neuropathy, which can bring much more serious psychological and economic burden for the diabetic patients. As a consequence of its microvascular complications, diabetes has become the leading cause of blindness, end-stage renal disease, and a variety of debilitating neuropathies. Although the mechanisms involved in the development and progression of these three diabetic microvascular complications are different and have not been completely elucidated, some common histopathological features like increased vascular permeability and apoptosis of specific vascular cells are shared in retinopathy and nephropathy...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009968/the-dielectrophoretic-disassociation-of-chloride-ions-and-the-influence-on-diamagnetic-anisotropy-in-cell-membranes
#11
Marcy C Purnell, Terence J Skrinjar
Chloride channels represent ubiquitously expressed proteins that regulate fundamental cellular processes including membrane potential, maintenance of intracellular pH, and regulation of cell volume. However, mechanisms to modulate this large family of ion channels have remained elusive to date. This large chloride channel family does not appear to operate with selectivity similar to the sodium and potassium channels. These unique channels appear to be bi-directional cotransporters of two or more different molecules or ions across a bilayer phospholipid membrane...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009967/the-role-of-b-cells-in-multiple-sclerosis-more-than-antibodies
#12
Michael Funaro, Mark Messina, Maya Shabbir, Paul Wright, Souhel Najjar, Inna Tabansky, Joel N H Stern
Multiple sclerosis (MS) is a multicomponent disease that is marked by continual inflammation, demyelination and irreparable damage to the central nervous system. While it was long thought to be mediated by T cells, B cells are now understood to be a central component of MS pathology. Dysfunction and aberrant activity of antigen presenting cells, T cells and B cells are all part of the pathophysiology of the disease. B cells and plasma cells contribute to disease progression through multiple mechanisms, including cytokine secretion, antibody production and antigen presentation...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009966/novel-approaches-in-genetic-characterization-and-targeted-therapy-for-brain-metastases
#13
Brandyn A Castro, Ruby Kuang, Priscilla K Brastianos
Metastases to the brain are a common complication of various cancers and are associated with poor prognosis. Management of these patients requires a multidisciplinary approach including whole-brain radiation therapy, stereotactic radiosurgery, surgical resection, chemotherapy, and supportive treatment. Because of recent technological advancements in genomics, our understanding of the genetics of brain metastases is rapidly advancing. This has led to the discovery of many potential genetic therapeutic targets in metastatic brain lesions...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27875674/gene-therapy-approaches-for-the-treatment-of-retinal-disorders
#14
Lolita Petit, Claudio Punzo
There is an impelling need to develop effective therapeutic strategies for patients with retinal disorders. Gleaning from the large quantity of information gathered over the past two decades on the mechanisms governing degeneration of the retina, it is now possible to devise innovative therapies based on retinal gene transfer. Different gene-based approaches are under active investigation. They include strategies to correct the specific genetic defect in inherited retinal diseases, strategies to delay the onset of blindness independently of the disease-causing mutations, and strategies to reactivate residual cells at late stages of the diseases...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#15
Nathan Singh
Immunotherapy using engineered autologous T cells has been attempted for decades, but clinical trials have only recently demonstrated efficacy. The combination of enhanced manufacturing techniques, highly efficient engineering, appropriate target selection and synthetic receptors with potent T cell activating domains has led to the development of highly-active cellular therapy products. B-cell malignancies have served as the paradigmatic diseases to initially evaluate and subsequently hone engineered T cells targeting cancer...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27875672/young-premenopausal-women-with-breast-cancer-especially-estrogen-receptor-negative-are-at-significantly-increased-risk-for-subsequent-ovarian-cancer
#16
Steven Lehrer, Peter H Rheinstein, Sheryl Green, Kenneth E Rosenzweig
BACKGROUND: There is a modest risk of second cancers, among them ovarian cancer, after breast cancer. For BRCA1 and BRCA2 carriers, the risk increases substantially. We have analyzed the risk of ovarian cancer after breast cancer based on patient age and the estrogen receptor (ER) and progesterone receptor (PR) characteristics of the breast tumor. METHODS: The study population was assembled using records from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27875671/immune-mediated-brain-pathology-from-autoantibodies-to-microglia
#17
Jacquelyn Nestor, Adriana Gata-Garcia, Yoshiyuki Arinuma, Yuichiro Fujieda, Czeslawa Kowal, Betty Diamond
Cells and molecules of the immune system contribute to brain pathology as well as to brain homeostasis. We suggest that there are numerous anti-brain antibodies that can cause acute neuronal dysfunction if they penetrate brain parenchyma. Many of these acute immune-mediated insults may alter the homeostatic mechanisms in the brain and initiate pathologic events that no longer depend on the presence of the inciting antibody, but rather on microglial cell activation. This paradigm, if correct, suggests that there may be two potential moments of therapeutic intervention...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27875670/efficacy-of-carfilzomib-in-the-treatment-of-relapsed-and-or-refractory-multiple-myeloma-a-meta-analysis-of-data-from-clinical-trials
#18
Runzhe Chen, Baoan Chen, Xiaoping Zhang, Chong Gao
OBJECTIVE: Recently, carfilzomib has become a promising therapeutic approach for relapsed and (or) refractory multiple myeloma (RRMM), but no study has summarized the overall effect of carfilzomib in RRMM. To explore the role of carfilzomib, we performed a meta-analysis of all known prospective clinical trials to assess the efficacy of carfilzomib in patients with RRMM. METHODS AND MATERIALS: A systematic review of publications was performed on December 15, 2015...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27875669/cancer-screening-of-asymptomatic-individuals-using-18f-fdg-pet-ct-in-china-a-retrospective-study
#19
Jianjing Tong, Yaru Zou, Jie Jiang, Wen Shi, Ranjun Tao, Jing Ye, Yiming Lu, Xufeng Jiang, Weiqing Wang
BACKGROUND: In recent years, the application of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for voluntary cancer screening of asymptomatic individuals is becoming more and more popular in China. However, the utility of such screening is still controversial. METHODS: This study enrolled a total of 1,572 asymptomatic individuals who underwent FDG PET/CT as a part of cancer screening program in Shanghai Ruijin Hospital, between January 2010 and December 2014...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27875668/use-of-a-perclose-proglide-device-for-percutaneous-endovascular-aortic-aneurysm-repair-in-a-general-hospital-experience
#20
Chih-Hsien Lee, Jau-Kang Huang, Ten-Fang Yang
BACKGROUND: This study evaluated the safety and efficacy of percutaneous endovascular aortic aneurysm repair (EVAR) with a Perclose ProGlide device compared with endovascular aortic repair with surgical cutdown of common femoral artery in patients at a general hospital. METHODS: A retrospective clinical study was conducted using data on 10 patients with elective EVAR, 7 patients with percutaneous EVAR, and 9 patients with consecutive rupture abdominal aortic aneurysm treated with emergency EVAR from January 2010 to December 2014...
October 2016: Discovery Medicine
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