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current molecular medicine

Heitor S P de Souza, Claudio Fiocchi
Despite unquestionable progress in the management of inflammatory bowel disease (IBD) and the much improved clinical results achievable today in Crohn's disease (CD) and ulcerative colitis (UC) patients, the overall therapeutic outcome remains far from optimal. The main reason of this partial success is that all current medications only block individual components of a highly complex disease process that results from the integration of multiple and incompletely identified pathogenic components. Thus, if further progress is to be achieved in IBD therapeutics and we want to move from the current success rate to nearly 100%, bold new ideas must be entertained and new approaches put into practice...
March 19, 2018: Inflammatory Bowel Diseases
Jelena Krstic, Markus Galhuber, Tim J Schulz, Michael Schupp, Andreas Prokesch
Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the prevalence of liver pathologies is steadily increasing in modern societies, there are currently no approved drugs other than chemotherapeutic intervention in late stage HCC. Hence, there is a pressing need to identify and investigate causative molecular pathways that can yield new therapeutic avenues...
March 20, 2018: International Journal of Molecular Sciences
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
Clyde B Schechter, Aimee M Near, Jinani Jayasekera, Young Chandler, Jeanne S Mandelblatt
BACKGROUND: The Georgetown University-Albert Einstein College of Medicine breast cancer simulation model (Model GE) has evolved over time in structure and function to reflect advances in knowledge about breast cancer, improvements in early detection and treatment technology, and progress in computing resources. This article describes the model and provides examples of model applications. METHODS: The model is a discrete events microsimulation of single-life histories of women from multiple birth cohorts...
April 2018: Medical Decision Making: An International Journal of the Society for Medical Decision Making
Susan Horton, Richard Sullivan, John Flanigan, Kenneth A Fleming, Modupe A Kuti, Lai Meng Looi, Sanjay A Pai, Mark Lawler
Modern, affordable pathology and laboratory medicine (PALM) systems are essential to achieve the 2030 Sustainable Development Goals for health in low-income and middle-income countries (LMICs). In this last in a Series of three papers about PALM in LMICs, we discuss the policy environment and emphasise three crucial high-level actions that are needed to deliver universal health coverage. First, nations need national strategic laboratory plans; second, these plans require adequate financing for implementation; and last, pathologists themselves need to take on leadership roles to advocate for the centrality of PALM to achieve the Sustainable Development Goals for health...
March 14, 2018: Lancet
Dehbia Benkerrou, Matteo Ceccarelli
One of the greatest health threats facing modern medicine is the emergence of new bacterial strains which are increasingly resistant to almost all currently available antibiotics. According to a CDC (Center for Disease Control and Prevention) report published in 2013, 63% of Acinetobacter species have been identified as Multidrug resistant strains. As for other Gram-negative bacteria, the presence of an outer membrane increases the intrinsic resistance of A. baumannii to most antibiotics. The outer membrane of A...
March 15, 2018: Physical Chemistry Chemical Physics: PCCP
Dafina Ilijazi, Mohammad Abufaraj, Melanie R Hassler, Iris E Ertl, David D'Andrea, Shahrokh F Shariat
Bladder cancer (BCa) is the fifth most frequently diagnosed cancer worldwide and is, in fact, the most expensive cancer on a per-patient to treat basis. There is a critical need to implement new tests into clinical practice to improve the quality of clinical care, decrease unnecessary invasive therapies and ultimately save costs. Currently, no molecular or genetic biomarker has been widely integrated into daily clinical practice. However, major milestones have been achieved in our understanding of the molecular alterations in BCa that will provide the basis for integrating molecular and genetic biomarkers into clinical decision making to guide management...
March 15, 2018: Expert Review of Molecular Diagnostics
Justine Marchand, Parisa Heydarizadeh, Benoît Schoefs, Cornelia Spetea
Chloroplasts are endosymbiotic organelles and play crucial roles in energy supply and metabolism of eukaryotic photosynthetic organisms (algae and land plants). They harbor channels and transporters in the envelope and thylakoid membranes, mediating the exchange of ions and metabolites with the cytosol and the chloroplast stroma and between the different chloroplast subcompartments. In secondarily evolved algae, three or four envelope membranes surround the chloroplast, making more complex the exchange of ions and metabolites...
March 14, 2018: Cellular and Molecular Life Sciences: CMLS
Carolina Torres, Paul J Grippo
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as one disease, accumulated evidences point to the clinical heterogeneity of this disease which translates into disparity in outcomes between patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last ten years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles...
March 14, 2018: Annals of Medicine
Seyed Mohammad Hossein Kashfi, Sheema Almozyan, Nicholas Jinks, Bon-Kyoung Koo, Abdolrahman S Nateri
Organoids have extensive applications in many fields ranging from modelling human development and disease, personalised medicine, drug screening, etc. Moreover, in the last few years, several studies have evaluated the capacity of organoids as transplantation sources for therapeutic approaches and regenerative medicine. Nevertheless, depending on the origin of the cells and anatomical complications, an organoid transplant may make tissue regeneration difficult. However, some essential aspects of organoids including the morphological alterations and the growth pattern of the matched tumour and their healthy derived organoids have received less attention...
February 13, 2018: Oncotarget
Mariarosaria Conte, Raffaele De Palma, Lucia Altucci
In recent years, anti-tumor immunotherapy has shown promising results, and immune-oncology is now emerging as the fourth major wave in the treatment of tumors after radiotherapy, chemotherapy and molecular targeted therapy. Understanding the impact of the immune system on neoplastic cells is crucial to improve its effectiveness against cancer. The stratification of patients who might benefit from immunotherapy as well as the personalization of medicine have contributed to the discovery of new immunotherapeutic targets and molecules...
March 10, 2018: International Journal of Biochemistry & Cell Biology
D Bradley Welling, Robert K Jackler
PURPOSE: To review contributions of the American Otological Society (AOS) over the most recent quarter century (1993-2018) and to comment on possible future evolution of the field during the quarter century to come. METHODS: Retrospective review of selected topics from the AOS transactions, distinguished lectureships over the past 25 years, and selective reflection by the authors. Speculation on potential advances of the next quarter century derived from emerging topics in the current literature and foreseeable trends in science and technology are also proffered for consideration (and possible future ridicule)...
April 2018: Otology & Neurotology
Angelo Castello, Laura Olivari, Egesta Lopci
Surgery, radiation therapy and chemotherapy are the oldest modalities for cancer treatment. However, as part of a continuous research in medicine, in order to improve therapeutic precision and biological effectiveness, there is an increasing interest into the use of heavy particle (e.g. protons or heavy ions) in the treatment of solid tumors. However, the restricted availability of the technology has concentrated the expertise in highly specialized centers that take care and treat extreme cases and rare pathologies...
2018: American Journal of Nuclear Medicine and Molecular Imaging
Pooya Mobadersany, Safoora Yousefi, Mohamed Amgad, David A Gutman, Jill S Barnholtz-Sloan, José E Velázquez Vega, Daniel J Brat, Lee A D Cooper
Cancer histology reflects underlying molecular processes and disease progression and contains rich phenotypic information that is predictive of patient outcomes. In this study, we show a computational approach for learning patient outcomes from digital pathology images using deep learning to combine the power of adaptive machine learning algorithms with traditional survival models. We illustrate how these survival convolutional neural networks (SCNNs) can integrate information from both histology images and genomic biomarkers into a single unified framework to predict time-to-event outcomes and show prediction accuracy that surpasses the current clinical paradigm for predicting the overall survival of patients diagnosed with glioma...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Vincenzo Mirabello, Fernando Cortezon-Tamarit, Sofia I Pascu
Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo . A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2 ...
2018: Frontiers in Chemistry
Francesco Ceci, Paolo Castellucci, Stefano Fanti
As precision medicine evolves, the contribution of molecular imaging to the management of prostate cancer (PCa) patients, especially for Positron Emission Tomography (PET) imaging, is gaining importance. Highly successful approaches to measure the expression of the prostate specific membrane antigen (PSMA) have been introduced recently. PSMA, the glutamate carboxypeptidase II (GCP-II), is a membrane bound metallo-peptidase that is overexpressed in 90-100% of PCa cells. Due to its selective over-expression, PSMA is a reliable tissue marker for prostate cancer and is considered an ideal target for tumor specific imaging and therapy...
March 8, 2018: Quarterly Journal of Nuclear Medicine and Molecular Imaging
Agnieszka Zagorska, Anna Partyka, Adam Bucki, Alicja Gawalska, Anna Czopek, Maciej Pawlowski
BACKGROUND: The phosphodiesterase 10 (PDE10) family, identified in 1999, is mainly expressed in the brain, particularly in the striatum, within the medium spiny neurons, nucleus accumbens, and olfactory tubercle. Inhibitors of PDE10 (PDE10-Is) are a conceptually rational subject for medicinal chemistry with potential use in the treatment of psychiatric and neurodegenerative diseases. OBJECTIVE: This review is based on peer-reviewed published articles, and summarizes the cellular and molecular biology of PDE10 as a rational target for psychiatric and neurodegenerative drug discovery...
March 8, 2018: Current Medicinal Chemistry
Xuan-Mei Piao, Young Joon Byun, Wun-Jae Kim, Jayoung Kim
Precision medicine is designed to tailor treatments for individual patients by factoring in each person's specific biology and mechanism of disease. This paradigm shifted from a "one size fits all" approach to "personalized and precision care" requires multiple layers of molecular profiling of biomarkers for accurate diagnosis and prediction of treatment responses. Intensive studies are also being performed to understand the complex and dynamic molecular profiles of bladder cancer. These efforts involve looking bladder cancer mechanism at the multiple levels of the genome, epigenome, transcriptome, proteome, lipidome, metabolome etc...
March 2018: Investigative and Clinical Urology
Yong-Seok Kim, Jae-Sung Ahn, Semi Kim, Hyun-Jin Kim, Shin-Hee Kim, Ju-Seop Kang
Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells...
March 2018: Korean Journal of Physiology & Pharmacology
C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Vladislav Volarevic
BACKGROUND: Pericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still representing cells with intriguing properties. This is mainly because of their heterogeneity in terms of definition, tissue distribution, origin, phenotype and multi-functional properties. The body of knowledge illustrates importance of pericytes in the regulation of homeostatic and healing processes in the body...
March 9, 2018: Journal of Biomedical Science
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