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Discovery Medicine

Sung Hugh Choi, Khalid Shah
Redundant survival signaling pathways and their crosstalk within tumor and/or between tumor and their microenvironment are key impediments to developing effective targeted therapies for cancer. Therefore developing therapeutics that target multiple receptor signaling pathways in tumors and utilizing efficient platforms to deliver such therapeutics are critical to the success of future targeted therapies. During the past two decades, a number of bifunctional multi-targeting antibodies, fusion proteins, and oncolytic viruses have been developed and various stem cell types have been engineered to efficiently deliver them to tumors...
September 2016: Discovery Medicine
Nathan S Hart, Melinda Fitzgerald
Red-near-infrared light has been used for a range of therapeutic purposes. However, clinical trials of near-infrared laser light for treatment of stroke were abandoned after failing interim futility analyses. Lack of efficacy has been attributed to sub-optimal treatment parameters and low penetrance of light to affected brain regions. Here, we assess penetrance of wavelengths from 450-880 nm in human post-mortem samples, and demonstrate that human skin, skull bone and brain transmits therapeutically relevant quantities of light from external sources at wavelengths above 600nm...
September 2016: Discovery Medicine
Junhui Shen, Jianfeng He, Fang Wang
In the past decades, much investigation has been done on the role of lipids in the development and progression of age-related macular degeneration (AMD). The lipids involved in those research studies had included PUFAs, phospholipids, sphingolipids, cholesterol, lipid protein, etc. There are a large number of clinical research studies on the association of PUFAs with the development and progression of AMD. The relationship between cholesterol level and AMD has been explored for decades and much data and analysis results have been obtained...
September 2016: Discovery Medicine
Zhi-Bo Xie, Lie Yao, Chen Jin, De-Liang Fu
Detection of circulating tumor cells (CTCs) has become widely used as a liquid biopsy for many patients. In pancreatic cancer patients, there have been a number of published reports on the efficacy of CTCs in the diagnosis and prognosis of pancreatic cancer, and in the evaluation of response to treatment. We systematically reviewed the diagnosis efficiency and prognostic value of CTCs reported in the literature. We found that the frequency of CTCs is rare, limited to a certain degree by the current enrichment and detection methodologies...
September 2016: Discovery Medicine
Radka Saldova
Many pathogens exist in metabolically inactive, non-culturable, cell-wall-deficient (CWD) forms that allow them to survive in conditions not conducive for growth. These forms were found in both cancer and chronic inflammatory autoimmune diseases. This review presents several novel concepts about how chronic inflammatory response and cancer develops from CWD infection, involvement and role of the immune system and other 'omics' systems and how to better diagnose, treat and even cure these conditions. This concept shows that CWD forms of intracellular microbes could also be evolutionary advantageous spreading through the host without using the classical replication route...
September 2016: Discovery Medicine
Shuxin Shang, Lu Sun, Wei Li, Xue Qin, Shu Zhang, Yinkun Liu
Fucosylated glycans play a critical role in cell biology processes during the occurrence and development of tumor, such as cell signal transduction, cellular differentiation, ligand-receptor interactions, and metastasis formation. Fucosylated haptoglobin (Hp) was reported to be increased in hepatocellular carcinoma (HCC). In this study, we aimed to develop a convenient and sensitive AAL@Magbeads-based Hp ELISA assay to rapidly detect fucosylated Hp in 270 serum samples from HCC patients and normal controls...
September 2016: Discovery Medicine
Denghe Liu, Lu Sun, Xue Qin, Tianhua Liu, Shu Zhang, Yinkun Liu, Shan Li, Kun Guo
OBJECTIVE: Reprogramming energy metabolism has been defined as the ninth hallmark of cancer; glucose deprivation might be a novel, feasible and effective approach for cancer treatment. However, the comprehensive illustration of behavior alteration of hepatocellular carcinoma (HCC) cells induced by glucose restriction is lacking and associated molecular mechanism is still unclear. METHODS: Three human HCC cell lines were cultured with normal control (25.0 mM D-glucose) and low glucose (5...
September 2016: Discovery Medicine
Benjamine Arellano, David J Graber, Charles L Sentman
Autoimmune disorders are long-term diseases that adversely affect the quality of life for patients, and they are one of the top ten leading causes of death. While each autoimmune disorder is unique, they all are caused by a breakdown of tolerance against endogenous proteins. This leads to auto-inflammatory events that promote the destruction of organs in a humoral and cellular immune mediated manner. Treatment options for autoimmunity can involve the use of chemical and biologic agents that suppress inflammation...
August 2016: Discovery Medicine
David Boczkowski, Smita K Nair
The concept that RNA has played a major role in the evolution of life stems from the "RNA World" hypothesis. This role of RNA was not immediately appreciated. Similarly, the scientific community has just recently begun to recognize the true potential of RNA as the drug of choice for gene therapy, cellular reprogramming and vaccination. While it is perhaps the most unstable of the three most commonly used biotherapeutics, the others being DNA and protein, the advantages that using RNA presents are now being realized at a high rate...
August 2016: Discovery Medicine
Aswin Somasundaram, Mark A Socinski, Liza C Villaruz
Immunotherapy has revolutionized the therapeutic landscape of advanced lung cancer. The adaptive immune system has developed a sophisticated method of tumor growth control, but T-cell activation is regulated by various checkpoints. Blockade of the immune checkpoints with therapies targeting the PD-1 pathway, such as nivolumab and pembrolizumab, has been validated as a therapeutic approach in non-small cell lung cancer. Newer therapies and novel combinations are also being evaluated, and the use of biomarkers in conjunction with these drugs is an area of active investigation...
August 2016: Discovery Medicine
Jessica Brian, Krissy Doyle-Thomas, Danielle Baribeau, Evdokia Anagnostou
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by marked heterogeneity in biology, expression, and response to treatment. The past decade has yielded considerable progress in understanding the underlying biological mechanisms, in characterizing the earliest behavioral phenotype(s), and in developing and evaluating effective treatments for ASD. This review highlights recent research advances in genetics and neuroimaging, as well as in novel behavioral and psychopharmacological treatment approaches, arguing for the value of trans-disciplinary initiatives to move the field forward exponentially...
August 2016: Discovery Medicine
Steven Lehrer, Peter H Rheinstein
A derangement of brain wound healing may cause some cases of Alzheimer's disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer's disease. Our hypothesis -- Alzheimer's disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models...
August 2016: Discovery Medicine
Na Fu, Xuemin Niu, Yang Wang, Huijuan Du, Baoyu Wang, Jinghua Du, Ya Li, Rongqi Wang, Yuguo Zhang, Suxian Zhao, Dianxing Sun, Liang Qiao, Yuemin Nan
Long non-coding RNA (LncRNA)-activated by transforming growth factor-beta (LncRNA-ATB) is a key regulator of transforming growth factor-beta (TGF-β) signaling pathway, and is positively correlated with the development of liver cirrhosis and vascular invasion of hepatocellular carcinoma (HCC). However, the role of LncRNA-ATB in hepatitis C virus (HCV)-related liver fibrosis remains largely unknown. In the present study, we confirmed a high expression level of LncRNA-ATB in the liver tissues and plasma samples of patients with HCV-related hepatic fibrosis, and the plasma level of LncRNA-ATB was significantly correlated with liver fibrosis stages...
August 2016: Discovery Medicine
Miao Qu, Stephan Kruse, Heinz Pitsch, Norbert Pallua, Mahtab Nourbakhsh
Experimental studies of burns are primarily performed with animal models that have important anatomical and physiological differences relative to human systems. The aim of this study was to develop a human experimental burn model using composite tissue obtained from bariatric surgery. We established a new protocol to maintain viable sections of human cutaneous and subcutaneous (sub/cutaneous) tissue in vitro. Under the conditions selected, multiparametric flow cytometry and histological analysis confirmed the viability and integrity of the human sub/cutaneous tissue for at least 5 days...
August 2016: Discovery Medicine
Jing Xu, Bi-Cheng Zhang, Xiang-Long Li, Wen-Hong Xu, Juan Zhou, Li Shen, Qi-Chun Wei
Multidrug resistance (MDR) to Doxorubicin (DOX) remains a major obstacle to successful cancer treatment. The present study sought to overcome the MDR of lung cancer cells and achieve radiosensitization by developing a composite DOX-loaded micelle (M-DOX). M-DOX containing PEG-PCL/Pluronic P105 was prepared by the solvent evaporation method. Lung cancer cell line A549 was adopted in this study. In vitro cytotoxicity, cellular uptake behavior, subcellular distribution, and radiosensitivity were evaluated by the treatment with M-DOX, and free DOX was used as a control...
August 2016: Discovery Medicine
SaÏd C Azoury, Richard C Gilmore, Vivek Shukla
Squamous cell carcinoma is one of the most frequent tumors of the head and neck and often presents at an advanced-stage. Traditionally, treatment for head and neck squamous cell carcinoma (HNSCC) has included surgery, radiation, and chemotherapy depending on both the site and stage of disease. Although the treatment approach for local disease is often standardized, the management of recurrent and advanced disease is evolving. A better understanding of the molecular mechanisms of HNSCC has led to numerous promising investigations and the push for the development of novel therapies...
June 2016: Discovery Medicine
Magali Cucchiarini
Even though gene therapy made its way through the clinics to treat a number of human pathologies since the early years of experimental research and despite the recent approval of the first gene-based product (Glybera) in Europe, the safe and effective use of gene transfer vectors remains a challenge in human gene therapy due to the existence of barriers in the host organism. While work is under active investigation to improve the gene transfer systems themselves, the use of controlled release approaches may offer alternative, convenient tools of vector delivery to achieve a performant gene transfer in vivo while overcoming the various physiological barriers that preclude its wide use in patients...
June 2016: Discovery Medicine
Wenbo Meng, Bing Bai, Zhongtian Bai, Yan Li, Ping Yue, Xun Li, Liang Qiao
Human hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. Alpha-fetoprotein (AFP) is perhaps the best-defined tumor marker for HCC, and as such, it is widely used in clinical settings as an adjuvant diagnostic and prognostic tool. Up to 70% of HCC cases exhibit elevated serum level of AFP, but its pathophysiological functions in HCC are poorly defined. It is now known that AFP is not just a fetal form of carrier protein and a tumor marker, it is also critically involved in the regulation of several important cellular functions, such as cell growth, differentiation, apoptosis, angiogenesis, and immune regulation...
June 2016: Discovery Medicine
Monika Joshi, Sumanta K Pal, Joseph J Drabick
After decades of disappointments, the use of immunotherapy in cancer has finally come of age and resulted in a real paradigm shift in cancer treatment across many tumor types. With the advent of novel immunotherapies based on increasing understanding of the human immune system, cure has become a real possibility for many patients. The development of cancer vaccines, immune checkpoint inhibitors, chimeric antigen receptor T cell, oncolytic virus based immunotherapy to name a few have given hope to patients. One of the most exciting developments in the era of immunotherapy has been the discovery of checkpoint inhibitors causing blockade of two important immune pathways -- cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death receptor-1 (PD-1), resulting in empowerment of anti-tumor immunity...
June 2016: Discovery Medicine
Yong Gao, Xiao Yan, Mengyun Lai, Peng Guo, Yafei Wu, Shangyong Zhu
RATIONALE AND OBJECTIVES: Accurate staging forms the basis for the successful management of maxillary sinus carcinoma. The purpose of this study was to compare the efficacy of ultrasonography and computed tomography (CT) for detection and T-staging of maxillary sinus carcinoma. MATERIAL AND METHODS: T-staging of maxillary sinus carcinoma by ultrasonography and CT was studied in 37 patients: 25 with squamous cell carcinoma and 12 with tumors of other histologic types...
June 2016: Discovery Medicine
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