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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
Xing Yang, Qian Hu, Lan-Xin Hu, Xiao-Rong Lin, Jie-Qiong Liu, Xiao Lin, Xiao-Xiao Dinglin, Jia-Yi Zeng, Hai Hu, Man-Li Luo, He-Rui Yao
Chemotherapy is a cornerstone treatment for early and advanced stage breast cancer patients. However, resistance to chemotherapy remains a major obstacle, resulting in disease relapse and progression. Emerging studies demonstrated that miRNAs regulate chemotherapy-induced epithelial-mesenchymal transition (EMT) and drug resistance, but the underlying mechanisms remain unclear. Here we established a doxorubicin-resistant breast cancer cell line MCF-7/Adr, and found these cells exhibited an EMT phenotype featured by a fibroblast-like morphology, increased the capacity of migration and invasion, and underwent the changes of molecular markers of EMT including E-cadherin, N-cadherin, and vimentin...
September 2017: Discovery Medicine
Justina X Caushi, Kellie N Smith
The use of immunotherapy in the treatment of cancer has resulted in a paradigm shift in clinical outcomes and in the correlative biomarkers that are most useful to evaluate in cancer patients. While several immunotherapeutic approaches have shown great promise, and several checkpoint inhibitors have been approved in the first and second line setting for multiple cancer types, major challenges remain in identifying the population of patients most likely to respond and in accurately monitoring clinical response while patients are receiving treatment...
August 2017: Discovery Medicine
Edward A Copelan, Michael R Grunwald, Srinivasa R Sanikommu, Mohammad J Hussain, Belinda Avalos
Myelodysplastic syndrome (MDS) is a heterogeneous group of malignant disorders of blood cell production occurring predominantly in elderly patients. While low intensity treatments are appropriate initially in most patients with favorable prognoses, hematopoietic cell transplantation (HCT) is the only curative therapy and is the best therapy for many higher risk patients. In patients who present with lower-risk disease, HCT may be considered at the time of meaningful disease progression. In patients receiving hypomethylating treatment, outcome of HCT is best when performed during response, and HCT is less effective when performed after resistance occurs...
August 2017: Discovery Medicine
Shigeo Koido, Masato Okamoto, Masanori Kobayashi, Shigetaka Shimodaira, Haruo Sugiyama
Pancreatic ductal adenocarcinoma (PDA) is characterized by a very poor prognosis, despite novel chemotherapeutic treatments. Moreover, the majority of PDA patients with complete surgical resection show recurrence within 5 years of resection. Therefore, new targeted cancer vaccines are urgently needed to extend PDA patient survival. The Wilms' tumor 1 (WT1) antigen was identified as an excellent antigen in a list of 75 tumor-associated antigens by a National Cancer Institute prioritization project based on several factors, such as therapeutic function...
August 2017: Discovery Medicine
Marianne Strazza, Adam Mor
Subsets of T cells can be classified by the functions executed or by the anatomic location at which they operate. In vitro analysis of T cell subsets and even commercial kits for subset separation often incorporate chemokine receptors into the panel of markers to distinguish among them, but what is the functional significance of these receptors? In this review, we discuss chemokine receptors that are expressed exclusively on different T cell subsets as well as those that are commonly expressed across subsets with the goal of linking receptor expression to cellular localization and intended cellular function...
August 2017: Discovery Medicine
Ying Zhang, Zhaoyong Liu
The first STAT family member, STAT1, is an essential component of interferon (IFN)-signaling, which mediates several cellular functions in response to stimulation by cytokines, growth factors, and hormones, such as the IFNs and IL-6. The role and significance of STAT1 in cancer biology have been studied for a decade. The majority of evidence shows that activating STAT1 plays a tumor suppressor role in cancer cells. Nevertheless, results from some experiments and clinical studies suggest that STAT1 also exerts tumor promoter effects under specific conditions...
August 2017: Discovery Medicine
Yuquan Tao, Feng Cai, Liang Shan, Hongyuan Jiang, Lifang Ma, Yongchun Yu
The Hippo signaling is a highly conserved pathway that plays important roles in tumorigenesis, stem cell self-renewal and differentiation, organ size control, and many other biological processes. Functions of the Hippo signaling pathway are regulated by complicated intracellular and extracellular signaling networks. When activated, the Hippo pathway functions as a tumor suppressor. However, dysregulation of this pathway contributes to increased cell proliferation and decreased apoptosis and differentiation...
August 2017: Discovery Medicine
Mark W Ball
Despite advances in systemic therapy for metastatic renal cell carcinoma, durable responses remain rare and surgical management remains a mainstay of treatment for many patients with metastatic disease. Management of the primary tumor in metastatic patients can occur as 1) palliative nephrectomy for symptomatic patients in whom cure is not achievable, 2) cytoreductive nephrectomy before systemic therapy, or 3) consolidative nephrectomy after systemic therapy. Palliative nephrectomy is rarely performed in centers where angioembolization is available...
June 2017: Discovery Medicine
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