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Discovery Medicine

Chanhee Han, Gary Altwerger, Gulden Menderes, Kaitlin Haines, Jacqueline Feinberg, Salvatore Lopez, Aranzazu Manzano, Joyce Varughese, Alessandro D Santin
Carcinosarcomas (CSs) of the uterus and ovary are rare biologically aggressive tumors with poor prognosis. The development of novel, effective treatment strategies against CSs of the female genital tract remains an unmet medical need. Whole-exome sequencing studies have recently demonstrated mutations or aberrant activation of multiple genes/pathways in CSs including HER2, PI3K/AKT/mTOR, EGFR, MAPK, genes related to histones and chromatin structure, and genes related to cell-cycle regulation. The carcinomatous component of these biphasic tumors is suggested to be the catalyst in CS tumorigenesis...
June 2018: Discovery Medicine
Amy D Proal, Trevor G Marshall
The theory of autoimmunity was developed at a time when the human body was regarded as largely sterile. Antibodies in patients with chronic inflammatory disease could consequently not be tied to persistent human pathogens. The concept of the "autoantibody" was created to reconcile this phenomenon. Today, however, the discovery of the human microbiome has revolutionized our understanding of human biology. Humans are superorganisms that harbor trillions of persistent microbial cells. Indeed, vast human microbiomes have been detected in human tissue and blood...
June 2018: Discovery Medicine
Fernanda A C Takeuti, Fernando de S F Guimaraes, Paulo de S F Guimaraes
Vitamin D (VD) is a steroid prohormone that regulates the body's calcium and phosphate levels in bone mineralization. It is also well described as a fat-soluble vitamin playing an important role in immunomodulation, regulation of cytokines, and cell proliferation. Thus, VD is a powerful hormone with pleiotropic effects, which acts to maintain optimal health. Recent studies demonstrate that VD deficiency is associated with the development of cardiovascular diseases, autoimmune disorders, and various types of cancer, each associated with increased mortality rates...
June 2018: Discovery Medicine
Wushuang Du, Shuofeng Hu, Shangli Cai, Yu Wang, Liangliang Wu, Danyang Sun, Shunchang Jiao, Yi Hu
PURPOSE: Immunotherapy against malignant tumors has shown considerable clinical efficacy, especially agents targeting the programmed death 1 (PD-1) pathway. In this study, we set out to dynamically determine the relationships between clinical benefit and changes in immune biomarkers on peripheral blood monocular cells (PBMCs) and try to establish a model to predict the response at an early stage of treatment. EXPERIMENTAL DESIGN: All patients recruited from December 2016 to July 2017 were treated in the Cancer Center of the Chinese People's Liberation Army General Hospital with nivolumab or pembrolizumab, and with or without chemotherapy...
June 2018: Discovery Medicine
Changxue Ji, Shuai Ju, Jinwei Qiang
Autophagy is a conserved lysosomal degradation pathway that regulates cell survival and death in order to maintain cellular homeostasis. Dysfunctional autophagy is associated with different types of cancer, making it an attractive therapeutic target. Mammalian target of rapamycin (mTOR) signaling negatively regulates autophagy and suppresses the efficacy of certain cancer therapeutic agents. NVP-BEZ235 is a dual inhibitor of the PI3K/mTOR signaling pathway and exhibits anti-cancer activities; it also induced autophagy and inhibited proliferation in colorectal adenoma HT-29 cells...
June 2018: Discovery Medicine
Matthew E Spector, Janice L Farlow, Catherine T Haring, J Chad Brenner, Andrew C Birkeland
Head and neck cancers consist of a heterogeneous group of cancers that are difficult to treat successfully. Limited screening options result in patients being diagnosed at advanced stages at presentation, and difficulty with treatment options and post-treatment surveillance can lead to poor outcomes. In this setting, tools for early and precise detection of disease will be highly valuable. Liquid biopsies, or use of analytes in blood, saliva, and other body fluid samples, provide new avenues for cancer screening with the potential for early detection, treatment modification, and surveillance of head and neck cancers...
May 2018: Discovery Medicine
Kevin Duh, Michael G Funaro, William DeGouveia, Sonia Bahlani, Dominic Pappas, Souhel Najjar, Inna Tabansky, Robert Moldwin, Joel N H Stern
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a condition causing intense pelvic pain and urinary symptoms. While it is thought to affect millions of people and significantly impair quality of life, difficulty with diagnosis and a lack of reliably effective treatment options leave much progress to be made in managing this condition. We describe what is currently known about the immunological and neurological basis of this disease, focusing on the interactions between the immune and nervous system...
May 2018: Discovery Medicine
Antonio M Serafin, Angela Chinhengo, Pedro Fernandez, John M Akudugu
No unambiguous role of the involvement of uroplasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in prostate cancer has emerged, with current evidence suggesting that neither biomarker is likely of significant clinical value, save as an overall contributor. In this study, we attempt to discriminate prostate cancer from non-cancer in a cohort of plasma samples, using the Imubind ELISA assay. In this cohort, PAI-1 levels are higher in prostate cancer patients than healthy donors; uPA levels are higher in healthy donors than prostate cancer patients; and the uPA/PAI-1 ratio is higher in healthy donors than in prostate cancer patients...
May 2018: Discovery Medicine
Uma Keyal, Yeqiang Liu, Anil Kumar Bhatta
Inflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal tract with unknown etiology and pathogenesis. It includes Crohn's disease (CD) and ulcerative colitis (UC). Approximately one-third of the patients with IBD are seen to develop extraintestinal manifestations, among which cutaneous manifestations are the most common and should be managed in close collaboration with a dermatologist. Depending upon the nature of the association, skin conditions associated with IBD can be listed under 4 categories: specific, reactive, secondary to malnutrition or malabsorption, and secondary to drug therapy...
May 2018: Discovery Medicine
Jing Liu, Jia-Xin Shen, Hua-Tao Wu, Xiao-Li Li, Xiao-Fen Wen, Cai-Wen Du, Guo-Jun Zhang
PURPOSE: Extracellular matrix (ECM) is an important component of tumor microenvironment and plays critical roles in cancer development and metastasis, in which collagen is the major structural protein. Collagen type I alpha 1 (COL1A1) is reportedly associated with the development of several human diseases. However, the functions and mechanisms of cellular expression of COL1A1 in breast cancer remain unknown. The purpose of this study is to investigate the cellular expression of COL1A1 in breast cancer cells and patients, and its role in the development and metastasis of breast cancer...
May 2018: Discovery Medicine
Jagadeesh K Venkatesan, Céline Falentin-Daudré, Amélie Leroux, Véronique Migonney, Magali Cucchiarini
Injuries occurring in orthopedic tissues do not completely heal if left untreated due to their imperfect self abilities for spontaneous repair. As most of the current clinical treatments often fail to fully restore the damaged tissues, there is a critical need to develop potent alternatives to activate the processes of repair in sites of orthopedic lesions. In this regard, combining gene therapy approaches with tissue engineering procedures to generate therapeutic gene vector-guided delivery systems, especially those based on mechanically stable solid scaffolds, is an attractive strategy to provide off-the-shelf compounds for the convenient spatiotemporal expression of candidate agents in orthopedic tissue defects...
April 2018: Discovery Medicine
Soumyadip Das, Saba Haq, Suresh Ramakrishna
Ran-binding protein in the microtubule-organizing center (RanBPM) is an evolutionarily conserved, nucleocytoplasmic scaffolding protein involved in various cellular processes and several signal transduction pathways. RanBPM has a crucial role in mediating disease pathology by interacting with diverse proteins to regulate their functions. Previously, we compiled diverse cellular functions of RanBPM. Since then the functions of RanBPM have increased exponentially. In this article, we have updated the functions of RanBPM through its manifold interactions that have been investigated to date, according to their roles in protein stability, transcriptional activity, cellular development, neurobiology, and the cell cycle...
April 2018: Discovery Medicine
Yanli He, Xiulian Li, Cui Hao, Pengjiao Zeng, Meng Zhang, Yong Liu, Yajing Chang, Lijuan Zhang
Grifola frondosa, a species of Basidiomycotina, is an edible medicinal mushroom with a large fruiting body characterized by overlapping caps. The β-glucan is the major biologically active component in G. frondosa polysaccharide (GFP) or D-fraction, which has been studied extensively for nearly 30 years. GFP was approved as an adjunctive therapeutic drug in China for treating cancers in 2010. In this article, based on the search results of Chinese VIP, CNKI, and Wanfang databases, 105 independent animal studies were summarized...
April 2018: Discovery Medicine
Xiangfang Meng, Wei Ding, Xijun Wu, Pingwei Di
In clinical practice, the vertebral arteries of a patient are often found to be not equal in size and the basilar artery may not be situated in the center. Our observational study showed that vertebral dominance and basilar bending are common, and their occurrence is related to advanced age and hypertension. The right vertebral dominance tends to coincide with left basilar bending, and, vice versa, the left vertebral dominance tends to coincide with right basilar bending. The left vertebral dominance is more common than the right dominance...
April 2018: Discovery Medicine
Sayad Navid Alavi, Vaia Florou, Gabriel Tinoco, Jonathan C Trent, Breelyn A Wilky
Soft tissue sarcomas (STS) are a heterogeneous group of over 100 histologically and genetically distinct mesenchymal tumors. Standard of care for metastatic STS has historically relied on anthracycline-based chemotherapy regimens. Although effective for some patients, conventional chemotherapeutic agents used in STS are associated with substantial toxicity and also are not equally effective in all histologic subtypes of sarcoma. Pazopanib is an orally active antiangiogenic drug that is approved for non-adipogenic sarcomas after failure of at least one line of previous chemotherapy, and has a relatively favorable toxicity profile...
March 2018: Discovery Medicine
Xiaolong Song, Huiyan Qu, Yong Wang, Tianshu Yang, Jingfeng Rong, Hua Zhou
Stem cells are a promising solution for the treatment of heart failure due to their ability to repopulate injured myocardium and restore cardiac function. However, many hindrances (such as low survival/viability and integration of transplanted cells, poor homing and cardiac differentiation efficiency, and inadequate cell retention and engraftment) compromise the full regenerative potential provided by stem cells. Therefore, it is necessary to optimize stem cell/progenitor therapy to improve clinical efficacy...
March 2018: Discovery Medicine
Nan Li, Deping Han, Jia Sun, Yumeng Li, Jin Zhang, Yali Zhang, Meng Liu, Renjia Peng, Haoxun Wang, Zhongmian Zhang, Jian Wang, Zongwen Liu, Jun Ma
Myeloid-derived suppressor cells (MDSCs) are thought to play a critical immunosuppressive role in tumorigenesis. In this project, we aimed to investigate subset alteration of MDSCs in gastric cancer (GC), and the effects of epirubicin (EPI) and paclitaxel (TAX) on MDSCs. The frequencies of MDSC subsets in peripheral blood were observed by using flow cytometry after treatment with EPI- or TAX- based chemotherapy in GC patients. After treatment with EPI or TAX in vitro, the subsets, apoptosis, cell cycle, and MAPK and NF-κB protein expressions of mouse bone marrow MDSCs were analyzed...
March 2018: Discovery Medicine
Chenyue Zhang, Shu Dong, Lei Wang, Songlin Yu, Yuwei Zheng, Yanyan Geng, Xiaoheng Shen, Haifeng Ying, Yuanbiao Guo, Jinming Yu, Qinglong Deng, Zhiqiang Meng, Zhaoshen Li, Hao Chen, Yehua Shen, Qiwen Chen
OBJECTIVE: We conducted a multicenter cohort study to investigate the prognostic value of some commonly-used laboratory indices in advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: A multicenter cohort study was conducted from 2004 to 2013. The associations between laboratory indices and prognosis of advanced PDAC were examined. RESULTS: This cohort consisted of 553 females (36.2%) and 973 males (63.8%). Patients at cancer stage III and IV were 595 (39...
March 2018: Discovery Medicine
Brittany L Adler, Lisa Christopher-Stine
The inflammatory myopathies, which include dermatomyositis, polymyositis, and the immune-mediated necrotizing myopathies, are a heterogeneous group of autoimmune diseases that manifest with muscle, skin, or lung damage. Collectively, these autoimmune diseases result from loss of tolerance to a select group of self-antigens, although the precise mechanism through which this occurs is not known. Infection, malignancy, and certain medications including statins and the immune checkpoint inhibitors used in cancer therapy have been identified as potential immunologic triggers of the inflammatory myopathies...
February 2018: Discovery Medicine
Cristhiam Mauricio Rojas-Hernandez, Thein Hlaing Oo
"Anemias beyond iron, vitamin B12, and folate deficiencies" covers a wide array of everything which lies beyond commonly seen anemias caused by deficiencies of three micronutrients. Although anemias due to deficiencies of iron, B12, and folate are common in daily practice and account for at least one-third of anemia etiologies in older adults, it is not uncommon to encounter other nutritional and toxin-induced underproduction anemias. The combination of thorough clinical examination, careful peripheral blood smear review, and judicious selection of supporting laboratory studies is typically sufficient to make an assertive diagnosis of those cases...
February 2018: Discovery Medicine
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