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Discovery Medicine

Van Anh Trinh, Jocelyn Joseph, Wen-Jen Hwu
Since their approval by regulatory agencies worldwide, the anti-PD-1 monoclonal antibodies (mAbs), as monotherapy or in combination with ipilimumab, have become the standard frontline therapy for advanced BRAF-wild-type melanoma and an eminent rival to targeted therapy in the first-line setting for unresectable BRAF-mutated melanoma. Mature survival data from randomized phase 3 trials have emerged, confirming their position in the current treatment schema for advanced melanoma. Recently, the clinical utility of anti-PD-1 agents has extended into other disease settings, such as resected high-risk melanomas, non-cutaneous subtypes, and brain metastases...
January 2018: Discovery Medicine
Jennie A Hamilton, Hui-Chen Hsu, John D Mountz
Type I interferons (IFNs) have a prominent role in many aspects of normal innate and adaptive immunity and autoimmunity. However, cell-type specific information about type I IFN expression and autocrine/paracrine signaling is sparse and mostly focused on non-lymphocyte and non-immune cell populations. A major function of B cells is cytokine production, but surprisingly, type I IFN production by B cells in systemic lupus erythematosus (SLE) has not been thoroughly investigated. This is due, in part, to the established view that plasmacytoid dendritic cells (pDCs) are the primary source of pathogenic type I IFN in lupus...
January 2018: Discovery Medicine
Bei-Bei Yang, Hua Xiao, Xiao-Jie Li, Min Zheng
OBJECTIVES: To evaluate the safety and efficacy of etanercept (ETN) plus methotrexate (MTX) in patients with rhupus without using corticosteroids. METHODS: Twenty rhupus patients [meeting the criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)] who had never been treated with corticosteroids, DMARDs, or biological agents with a 28-joint Disease Activity Score (DAS28) >3.2 and lupus nephritis determined from histopathological specimens were enrolled...
January 2018: Discovery Medicine
Chen Wang, Xing-Fei Yu
In recent decades, the incidence rate of breast cancer has increased dramatically worldwide and has become one of the most prevalent cancers in women. According to the global data provided by the WHO, there were more than 1.7 million new cases of breast cancer in 2012, accounting for 25% of all reported cancer cases and 15% of all reported deaths among females. To most young patients, especially those younger than 40 years of age, chemotherapy should be taken into consideration as a treatment modality, even if the tumor size is small or without lymphatic metastasis...
January 2018: Discovery Medicine
Uma Maheswari Selvaraj, Ann M Stowe
Stroke, which occurs during a loss of blood flow to the brain, is a global disease that accounts for 10% of yearly mortality. But stroke is also a leading cause of long-term adult disability, with recovery continuing for months to years after initial stroke onset. This long-term functional recovery from stroke encompasses changes in neuronal structure and function, and occurs throughout the post-stroke brain. Much less understood is whether the adaptive immune cells that infiltrated the brain during acute post-stroke neuroinflammation remain long-term, and if their presence supports or hinders functional recovery...
December 2017: Discovery Medicine
Marie Beitelshees, Andrew Hill, Pooya Rostami, Charles H Jones, Blaine A Pfeifer
Over time, there has been a growing interest in the application of gene therapy within the healthcare industry as demonstrated by the nearly 3,000 clinical trials associated with gene therapy that are listed in However, there are various difficulties associated with gene therapy that have limited the realization of licensed gene therapies to only a handful of treatments. Furthermore, efforts to develop gene therapeutics have been narrowly focused and most clinical trials have sought to develop treatments for cancer (64...
December 2017: Discovery Medicine
Khusbu Keyal, Xin Liao, Guodong Liu, Shuai Yang, Fang Wang
Vitrectomy is considered the standard therapy for the treatment of posterior segment disease; however, after a significant improvement of the visual acuity, there is a reduction in visual acuity due to cataract formation, which requires further surgery. Nuclear sclerotic cataract (NSC) is the most common type of cataract seen after vitrectomy. The pathogenesis of post-vitrectomy NSC is unclear; several hypotheses have been formulated without any conclusions. In order to correct post-vitrectomy NSC, phacoemulsification with intraocular lens implantation is performed...
December 2017: Discovery Medicine
Yong Gao, Xin-Hong Liao, Yan Ma, Lu Lu, Li-Yan Wei, Xue Yan
RATIONALE AND OBJECTIVES: This study aims to investigate the feasibility and performance of a two-step scoring system of ultrasound imaging in the diagnosis of prostate cancer. MATERIAL AND METHODS: 75 patients with 888 consecutive histopathologically verified lesions were included in this study. Step 1, an initial 5-point scoring system was developed based on conventional transrectal ultrasound (TRUS). Step 2, a final scoring system was evaluated according to contrast-enhanced transrectal ultrasound (CE-TRUS)...
December 2017: Discovery Medicine
David A Reardon, Kai Wucherpfennig, E Antonio Chiocca
The successful eradication of multiple tumor types, often in a durable manner, has recently validated the bona fide potential of an effectively mobilized immune response as a cancer therapy. Critical questions at present, therefore, include deciphering why some patients respond while others do not, as well as why certain cancers respond while others like glioblastoma do not. Glioblastoma remains a major unmet need in medical oncology and is considered incurable with less than 10% of patients surviving five years from diagnosis...
November 2017: Discovery Medicine
Peta Pentony, Laurence Duquenne, Katherine Dutton, Kulveer Mankia, Hanna Gul, Edward Vital, Paul Emery
It is well established that the autoantibodies that characterize both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are present systemically years before patients develop disease. In both these autoimmune rheumatic diseases, evidence is growing that local autoimmune processes occur at epithelial surfaces potentially initiating localized autoimmunity. For RA, these are mucosal surfaces including the oral mucosa, lung, and gut. At the oral mucosa and lung, risk factors such as periodontal disease and smoking may contribute to autoimmunity by driving the local generation of citrullinated autoantigens...
November 2017: Discovery Medicine
Francesca Reggiani, Francesco Bertolini
Recent preclinical and clinical data accumulate evidence indicating that obesity may worsen the incidence, severity, and mortality of many types of cancer, including breast cancer. In the present review, we discuss the candidate players in this dangerous relationship, namely adipose tissue-related chronic inflammation, immune cell dysregulation, angiogenesis, extracellular matrix stiffness, and genomic instability. Finally, we review some novel therapeutic approaches currently under investigation to prevent and blunt the effects of obesity in breast cancer development and progression, namely caloric restriction, immune checkpoint inhibition, browning of white adipose tissue, and modulation of the microbiota and the immune cell metabolism...
November 2017: Discovery Medicine
Mengli Sun, Xiaoqing Yan, Anyun Feng, Xuemei Wu, Enling Ye, Huiying Wu, Xuemian Lu, Hong Yang
PURPOSE: 17α-hydroxylase/17,20-lyase deficiency is a rare disease caused by mutation of the CYP17A1 gene, resulting in hypertension, hypokalemia, alkalosis, female hypogonadism, and male pseudohermaphroditism. Here we report a case of a 15-year-old girl with 17α-hydroxylase/17,20-lyase deficiency, and analyze her clinical and molecular genetic characteristics. PATIENT AND METHODS: A 15-year-old Chinese girl had fever, fatigue, high blood pressure, and blood potassium level being significantly lower than normal...
November 2017: Discovery Medicine
Peter D Burbelo, Jason M Keller, Michael J Iadarola
Comprehensive, robust, and inexpensive clinical tools are needed to monitor human health and disease. In this review, we propose how a standardized, high-performance antibody testing platform directed against a broad panel of antigenic targets could fulfill an important niche in personalized medicine. The panel is envisioned to encompass a defined set of diverse protein antigens known to be associated with cancer, autoimmune diseases, and infectious diseases, including proteins derived from bacterial pathogens and the human virome...
October 2017: Discovery Medicine
Sarah E Sinnett, Steven J Gray
Rett Syndrome (RTT) is an X chromosome-linked neurodevelopmental disorder caused by inactivating mutations in the transcription regulator methyl CpG-binding protein 2 (MeCP2). Multiple studies have independently explored the therapeutic potential of adeno-associated viral (AAV) vector-mediated MECP2 gene transfer in mouse models of RTT. Historically, the primary risk anticipated for viral vector-mediated MECP2 gene transfer in vivo has been toxicity caused by supraphysiological expression of exogenous MeCP2...
October 2017: Discovery Medicine
Steven Lehrer, Peter H Rheinstein
Quite a number of experimental treatments, which are based on conventionally accepted understandings of Alzheimer's disease, have not yielded expected results. Therefore, conventionally accepted understanding of the mechanisms of the disease may be inadequate or even wrong. The characteristic amyloid plaques and tau tangles in the brain may be a result, not a cause. Alzheimer's disease is more likely the product of neuroinflammation and deranged brain wound healing. If so, a hypothesized treatment, intranasal glucocorticoids, might be effective...
October 2017: Discovery Medicine
Yong-Liang Chu, Yi-Qi Jiang, Si-Long Sun, Bao-Lin Zheng, Wan-Sheng Xiong, Wen-Jie Li, Xiu-Min Chen, Mao-Jie Wang, Qing-Chun Huang, Run-Yue Huang
OBJECTIVE: This study was designed to determine the differential profiles of long non-coding RNAs (lncRNAs) between rheumatoid arthritis (RA) and gouty arthritis (GA), which may lead to the discovery of specific biomarkers for RA diagnosis and treatment in the future. METHODS: The profiles of lncRNAs were determined by Agilent microarray. Bioinformatics analyses, including Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, of the large dataset obtained from microarray experiments were performed...
October 2017: Discovery Medicine
Amanda J Craig, Johann von Felden, Augusto Villanueva
Liver cancer has the highest increase in incidence and mortality of all cancers in the United States in recent decades. A major effort has been taken over the last 10 years to understand molecular heterogeneity between tumors of different patients through the development of mutation signatures and molecular classifications. More recently, attention has shifted to understanding intra-tumor heterogeneity (ITH). Several possibilities exist as to the underlying mechanisms that drive ITH in liver cancer, including cancer stem cells (CSCs) and neutral and clonal evolution...
September 2017: Discovery Medicine
Thein Hlaing Oo, Cristhiam Mauricio Rojas-Hernandez
Pernicious anemia (PA) is an autoimmune disease of multifactorial etiologies characterized by autoimmune chronic atrophic gastritis, cobalamin deficiency (CD) due to defective absorption of dietary cobalamin from the terminal ileum, and by the presence of intrinsic factor and parietal cell antibodies. PA is a very common cause of CD-related anemia worldwide. Despite advances in the understanding molecular biology and pathophysiology of PA, the diagnosis of PA remains challenging in many circumstances for many clinicians because of its diverse clinical manifestations and the limitations of currently available diagnostic tools...
September 2017: Discovery Medicine
Lingbo Kong, Yu Lu, Siyu Zhang, Yuemin Nan, Liang Qiao
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. The nutrients play important roles in the development and progression of NAFLD. High-calorie diet, especially the diet rich in saturated fatty acids and cholesterol, as well as sugary drinks with high fructose content, induces hepatic steatosis and triggers progression of steatohepatitis, fibrosis, and even hepatocellular carcinoma. Disordered micronutrient status and gut microbiota are also involved in the pathogenesis of NAFLD...
September 2017: Discovery Medicine
Zhaobin Cai, Keyang Xu, Yan Li, Yuanlin Lv, Jianfeng Bao, Liang Qiao
Hepatocellular carcinoma (HCC) is one of the most common malignancies and a major cause of cancer-related deaths. HCC often has an insidious onset, fast progression, and high tendency of metastasis and recurrence, hence it is a highly fatal malignant tumor. The origin of HCC is still a topic of debate but studies over the past decade have clearly identified liver cancer stem cells (LCSCs) being a cardinal source of liver cancer. LCSCs are a small subset of cells with the unlimited ability of self-renewal, differentiation, and uncontrollable growth...
September 2017: Discovery Medicine
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