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Discovery Medicine

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https://www.readbyqxmd.com/read/28245428/from-vision-to-reality-deploying-the-immune-system-for-treatment-of-sarcoma
#1
Breelyn A Wilky, John M Goldberg
Modern immunotherapy advances including checkpoint inhibitors and adoptive T cell therapy have created a new era of cancer treatment, with significant activities in a wide variety of hematologic and solid cancers. Sarcomas are rare and aggressive malignancies of bone and soft tissue affecting all ages of patients that are usually incurable when refractory to chemotherapy and surgery. However, a subset of patients with metastatic sarcoma will survive for years, suggesting that immune suppression of residual sarcoma cells may be effective in some cases...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245427/microbe-microbe-and-host-microbe-interactions-drive-microbiome-dysbiosis-and-inflammatory-processes
#2
Amy D Proal, Inge A Lindseth, Trevor G Marshall
An extensive microbiome comprised of bacteria, viruses, bacteriophages, and fungi is now understood to persist in nearly every human body site, including tissue and blood. The genomes of these microbes continually interact with the human genome in order to regulate host metabolism. Many components of this microbiome are capable of both commensal and pathogenic activity. They are additionally able to persist in both 'acute' and chronic forms. Inflammatory conditions historically studied separately (autoimmune, neurological and malignant) are now repeatedly tied to a common trend: imbalance or dysbiosis of these microbial ecosystems...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245426/histopathological-evidence-for-the-existence-of-primary-liver-progenitor-cell-cancer-insight-from-cancer-stem-cell-pathobiology
#3
Cheng-Maw Ho, Shu-Li Ho, Chia-Tung Shun, Po-Huang Lee, Ya-Hui Chen, Chin-Sung Chien, Hui-Ling Chen, Rey-Heng Hu
BACKGROUND: Primary liver progenitor cell cancer is a rare disease entity. Current nomenclature of primary liver cancer with prominent progenitor features is not comprehensive. This study was aimed to investigate the existence of this type of primary liver cancer and characterize it immunohistopathologically based on the emerging understanding of cancer stem cell pathobiology. METHODS: Surgical specimens from a primary liver cancer were stained with antibodies against well-defined markers of progenitor cells, stemness, and differentiation toward hepatocytes or cholangiocytes...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245425/intra-arterial-delivery-of-superparamagnetic-iron-oxide-nanoshell-and-polyvinyl-alcohol-based-chemoembolization-system-for-the-treatment-of-liver-tumor
#4
Qi Liang, Yi-Xiang Wang, Jin-Song Ding, Wei He, Ling-Ling Deng, Na Li, Yun-Jie Liao, Zhen Li, Bin Ye, Wei Wang
A superparamagnetic iron oxide (SPIO) nanoshell and polyvinyl alcohol (PVA) based chemoembolization system for anti-cancer drug doxorubicin (DOX) delivery has previously been presented. We have also previously confirmed the feasibility and safety of this multifunctional system for carrying both DOX and SPIO nanoparticles in vitro. However, the pharmacokinetic and the therapeutic efficacy of this novel drug-delivery system in vivo is not yet clear, and as such was the subject of this study. A rabbit liver tumor model was utilized, whereby the tumors were targeted by SPIO/DOX/PVA composite infused via a catheter into the hepatic arteries which supplying blood to the tumor...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245424/the-independent-predictors-of-significant-liver-histological-changes-in-chronic-hepatitis-b-virus-infection-patients-with-persistently-high-normal-or-low-normal-alanine-transaminase-levels
#5
Qiang Li, Chuan Lu, Weixia Li, Yuxian Huang, Liang Chen
OBJECTIVE: To determine the independent predictors of significant liver histological changes (SLHC) defined as inflammatory grade ≥A2 and/or fibrosis stage ≥F2 using the METAVIR scoring system in chronic hepatitis B virus (HBV) infection patients with persistently normal ALT (PNALT) levels. METHODS: We enrolled 392 chronic HBV infection patients with PNALT defined as normal ALT (≤40 IU/L) measured on at least three occasions at intervals of more than 2 months apart over a period of 12 or more months...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245423/reduced-n-acetylglucosaminyltransferase-iii-expression-via-smad3-and-erk-signaling-in-tgf-%C3%AE-1-induced-hcc-emt-model
#6
Cuiju Mo, Tianhua Liu, Shu Zhang, Kun Guo, Meng Li, Xue Qin, Yinkun Liu
N-acetylglucosaminyltransferase III (GnT-III), encoded by the MGAT3 glycogene, is thought to be a tumor metastatic suppressor. Our previous studies found that the mRNA expression level of GnT-III decreased in a hepatocyte growth factor (HGF)-induced hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT) model. However, the molecular mechanism of GnT-III expression is unclear. In the present study, we established an HCC EMT model using the classic inducer transforming growth factor-β1 (TGF-β1) and focused on the Smad3 and Erk signaling pathways...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28147220/intersections-of-pathways-involving-biotin-and-iron-relative-to-therapeutic-mechanisms-for-progressive-multiple-sclerosis
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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