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Discovery Medicine

Jovana Ranko Gotovac, Kenji Mark Fujihara, Wayne Allen Phillips, Nicholas James Clemons
The transforming growth factor β (TGFβ) signaling pathway governs physiological homeostasis in the gastrointestinal system and its deregulation can lead to a diverse range of human pathologies including juvenile polyposis syndrome and tumor initiation, progression, and metastasis. In gastrointestinal malignancies, tumor cells evade the known tumor suppressive effects of TGFβ signaling through frequent inactivation of the pathway. Paradoxically, tumor cells utilize TGFβ-mediated regulation of epithelial-mesenchymal transition and immunomodulation to facilitate the invasive and migratory phenotype of gastrointestinal cancers and avoid immunosurveillance...
September 2018: Discovery Medicine
Hugh O'Connor, John MacSharry, Yensi Flores Bueso, Sinéad Lindsay, Emma L Kavanagh, Mark Tangney, Marguerite Clyne, Radka Saldova, Amanda McCann
Breast cancer is the second most common cancer in women. Recent evidence identifies a unique microbiome in breast tissue; a site previously thought to be sterile. The identification that this microbiome varies considerably from healthy subjects to cancer patients has prompted investigations into the role of specific bacterial species in oncogenesis. Indeed, certain bacteria have been shown to aid cancer development in vitro by promoting genomic instability, invasion, and chemotherapy resistance. However, the in vivo role of the breast microbiome in cancer appears to be more complex, involving numerous interactions between its constituent species and host cells...
September 2018: Discovery Medicine
Kaitlin C McLoughlin, Zachary J Brown, Yashvita Shukla, Vivek Shukla
A growing understanding of the immune system and its anti-tumor functions has been imperative for the comprehension of malignant processes and beneficial in the pursuit of effective cancer treatments. To defend the body, immune cells must be able to differentiate between self and foreign cells using checkpoints, allowing the immune cells to attack foreign cells. Among the different types of immune target therapies recently developed, checkpoint inhibitors have come to the forefront in cancer treatment, encouraging their study in numerous different types of cancer, including hepato-pancreato-biliary malignancies (HPB)...
September 2018: Discovery Medicine
Rizwan Ahmed, Zahra Omidian, Thomas Donner, Abdel Rahiam A Hamad
CD5+ B cells expand in many autoimmune diseases, including type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Furthermore, CD5+ B cells contain important subsets: IL-10-producing B-reg cells, FasL-expressing subset, and the majority of pre-naive B cells. In addition, they are major sources of natural autoantibodies, which are polyreactive and autoreactive. Thus, CD5+ B cells are clearly loaded with autoimmune clues that are yet to be unlocked and understood. We hypothesize that human CD5+ B cells are likely to yield enormously important novel information about the role of B cells in autoimmune disease if analyzed using the new technological advances in molecular biology and genomics...
September 2018: Discovery Medicine
Hong Li, Xia Zhang, Long Gao, Jie Min, Yali Zhang, Ren Zhang, Yucheng Yang
Tumor necrosis factor alpha (TNF-α) regulates the expression of proinflammatory cytokines and apoptosis in thyroids. miR-155-5p is upregulated in circulating microvesicles in patients with autoimmune thyroiditis. However, the function and molecular mechanisms of TNF-α and miR-155-5p in the initiation and progression of subacute thyroiditis are largely unknown. Herein, we determined serum TNF-α levels in subacute thyroiditis patients and normal healthy controls by ELISA assay. Proliferation and apoptosis of rat thyroid follicle FRTL-5 cells were determined by MTT, TUNEL, and annexin V staining assays...
September 2018: Discovery Medicine
Stefania Maraka, Filip Janku
Primary brain tumors can harbor v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene alterations. BRAF is a serine/threonine kinase protein and is a downstream effector of the Ras-Raf-MEK extracellular signal-regulated kinase (ERK) signaling pathway, which is responsible for cell division and differentiation. BRAF-V600E mutations are most commonly found in pleomorphic xanthoastrocytoma, ganglioglioma, epithelioid glioblastoma, and gliomas diagnosed at a younger age; BRAF-KIAA1549 fusion is the most common BRAF alteration in pilocytic astrocytoma...
August 2018: Discovery Medicine
Gulden Menderes, Salvatore Lopez, Chanhee Han, Gary Altwerger, Stepan Gysler, Joyce Varughese, Peter E Schwartz, Alessandro D Santin
Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that accounts for up to 40% of all endometrial cancer-related deaths. Recent whole-exome sequencing studies have revealed HER2/neu amplification in 27-44% of USC patients, supporting HER2 as an attractive pathway for target therapies based on monoclonal antibodies or tyrosine kinase inhibitors. Preclinical studies and a recently published prospective randomized trial with trastuzumab in combination with chemotherapy demonstrated promising results with anti-HER2-targeted therapies in advanced and recurrent USC patients...
August 2018: Discovery Medicine
Woo Jae Shin, Russell K Pachynski
Chemerin is a relatively newly described, yet increasingly studied multifunctional protein that mediates a variety of important biological functions. With significant roles in immune trafficking and adipo/angiogenesis, chemerin has gained traction in recent years for its potential functions in cancer, tumorigenesis, and immune surveillance. Chemerin's main chemotactic cellular receptor, CMKLR1, is expressed on both immune cells and malignant tumor cells, while a second non-signaling receptor, CCRL2, may act to help concentrate chemerin along activated endothelial cells and at sites of inflammation...
August 2018: Discovery Medicine
Sushma Jonna, Giuseppe Giaccone, Deepa S Subramaniam
Historically, advanced lung cancer conferred a poor prognosis, and chemotherapy only improved outcomes in patients with good performance status. The identification of certain molecular subtypes of non-small cell lung cancer changed the treatment paradigm by incorporating tumor genomic information into clinical decision-making. To meet the demands of this emerging approach, genomic technology rapidly expanded in an effort to detect specific driver mutations. While polymerase-chain reaction testing, immunohistochemistry, and fluorescent-in-situ hybridization have been standard-of-care, next-generation sequencing is increasingly replacing older technologies...
August 2018: Discovery Medicine
Xiaoyi Zhang, Yong Ye, Chunjie Yang, Hui Gong, Yang Li, Guoping Zhang, Jie Yuan, Yunzeng Zou
We aimed to study urotensin II (UII) in acute myocardial infarction (AMI) patients before and after percutaneous coronary intervention (PCI) and to investigate its interaction with angiotensin II (ATII) in post-AMI myocardial remodeling. In this clinical study, 63 AMI patients and 66 controls were included. Levels of UII, ATII, and NT-B-type natriuretic peptide (NT-BNP) were determined. Participants were followed up for 2 years to observe clinical outcomes. In cell biology experiments, ATII and UII were added into cardiomyocytes and fibroblasts individually or in combination...
August 2018: 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
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