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https://www.readbyqxmd.com/read/29330437/a-computational-assay-of-estrogen-receptor-%C3%AE-antagonists-reveals-the-key-common-structural-traits-of-drugs-effectively-fighting-refractory-breast-cancers
#1
Matic Pavlin, Angelo Spinello, Marzia Pennati, Nadia Zaffaroni, Silvia Gobbi, Alessandra Bisi, Giorgio Colombo, Alessandra Magistrato
Somatic mutations of the Estrogen Receptor α (ERα) occur with an up to 40% incidence in ER sensitive breast cancer (BC) patients undergoing prolonged endocrine treatments. These polymorphisms are implicated in acquired resistance, disease relapse, and increased mortality rates, hence representing a current major clinical challenge. Here, multi-microseconds (12.5 µs) molecular dynamics simulations revealed that recurrent ERα polymorphisms (i. e. L536Q, Y537S, Y537N, D538G) (mERα) are constitutively active in their apo form and that they prompt the selection of an agonist (active)-like conformation even upon antagonists binding...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330221/minimal-measurable-residual-disease-in-aml-consensus-document-from-eln-mrd-working-party
#2
Gerrit J Schuurhuis, Michael Heuser, Sylvie Freeman, Marie-Christine Béné, Francesco Buccisano, Jacqueline Cloos, David Grimwade, Torsten Haferlach, Robert K Hills, Christopher S Hourigan, Jeffrey L Jorgensen, Wolfgang Kern, Francis Lacombe, Luca Maurillo, Claude Preudhomme, Bert A van der Reijden, Christian Thiede, Adriano Venditti, Paresh Vyas, Brent L Wood, Roland B Walter, Konstanze Döhner, Gail J Roboz, Gert J Ossenkoppele
Measurable residual disease (MRD, previously termed minimal residual disease) is an independent, post-diagnosis, prognostic indicator in acute myeloid leukemia (AML) that is important for risk stratification and treatment planning, in conjunction with other well-established clinical, cytogenetic, and molecular data assessed at diagnosis. MRD can be evaluated using a variety of multi-parameter flow cytometry (MFC) and molecular protocols but, to date, these approaches have not been qualitatively or quantitatively standardized, making their use in clinical practice challenging...
January 12, 2018: Blood
https://www.readbyqxmd.com/read/29327808/the-rocky-road-to-personalized-medicine-in-acute-myeloid-leukaemia
#3
REVIEW
Bryan Brinda, Irum Khan, Brian Parkin, Heiko Konig
Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly toxic induction and consolidation chemotherapy...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29321536/enzymes-of-the-one-carbon-folate-metabolism-as-anticancer-targets-predicted-by-survival-rate-analysis
#4
Jun Koseki, Masamitsu Konno, Ayumu Asai, Hugh Colvin, Koichi Kawamoto, Naohiro Nishida, Daisuke Sakai, Toshihiro Kudo, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
The significance of mitochondrial metabolism in cancer cells has recently been gaining attention. Among other findings, One-carbon folate metabolism has been reported to be closely associated with cellular characteristics in cancer. To study molecular targets for efficient cancer therapy, we investigated the association between the expressions of genes that code enzymes involved in one-carbon metabolism and survival rate of patients with adenocarcinomas of the colorectum and lung. Patients with high expression of genes that control the metabolic cycle of tetrahydrofolate (THF) in mitochondria, SHMT2, MTHFD2, and ALDH1L2, have a shorter overall survival rate compared with patients with low expression of these genes...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318965/current-status-of-molecular-imaging-in-infections
#5
Martina Sollini, Chiara Lauri, Roberto Boni, Elena Lazzeri, Paola Anna Erba, Alberto Signore
There is an increased need to find non-invasive tools for early diagnosis and follow-up of infections. Nuclear medicine techniques may be used to diagnose, localize and evaluate the severity and the extent of infections before the occurrence of anatomical abnormalities. This review focuses on different approaches based on radiolabelled cells, peptides and antibodies or [18F]FDG to image infective diseases in agreement with what is being jointly evaluated by the European Association of Nuclear Medicine (EANM)...
January 9, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29315421/development-of-a-new-comprehensive-and-reliable-endometrial-receptivity-map-er-map-er-grade-based-on-rt-qpcr-gene-expression-analysis
#6
M Enciso, J P Carrascosa, J Sarasa, P A Martínez-Ortiz, S Munné, J A Horcajadas, J Aizpurua
STUDY QUESTION: Is it possible to determine the receptivity status of an endometrium by combined quantitative reverse transcription PCR (RT-qPCR) expression analysis of genes involved in endometrial proliferation and immunity? SUMMARY ANSWER: The new ER Map®/ER Grade® test can predict endometrial receptivity status by RT-qPCR using a new panel of genes involved in endometrial proliferation and the maternal immune response associated to embryonic implantation. WHAT IS KNOWN ALREADY: The human endometrium reaches a receptive status adequate for embryonic implantation around Days 19-21 of the menstrual cycle...
January 5, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29311125/molecular-biomarkers-in-the-clinical-management-of-prostate-cancer
#7
Aaron M Udager, Scott A Tomlins
Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29310970/lithium-stress-and-resilience-in-bipolar-disorder-deciphering-this-key-homeostatic-synaptic-plasticity-regulator
#8
REVIEW
Rodrigo Machado-Vieira
BACKGROUND: Lithium is the lightest metal and the only mood stabilizer that has been used for over half a century for the treatment of bipolar disorder (BD). As a small ion, lithium is omnipresent, and consequently, its molecular mechanisms and targets are widespread. Currently, lithium is a crucial pharmacotherapy for the treatment of acute mood episodes, prophylactic therapy, and suicide prevention in BD. Besides, lithium blood level is the most widely used biomarker in clinical psychiatry...
December 22, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29300757/the-effects-of-alternative-splicing-on-mirna-binding-sites-in-bladder-cancer
#9
Seonggyun Han, Dongwook Kim, Manu Shivakumar, Young-Ji Lee, Tullika Garg, Jason E Miller, Ju Han Kim, Dokyoon Kim, Younghee Lee
Eukaryotic organisms have developed a variety of mechanisms to regulate translation post-transcriptionally, including but not limited to the use of miRNA silencing in many species. One method of post-transcriptional regulation is through miRNAs that bind to the 3' UTRs to regulate mRNA abundance and influence protein expression. Therefore, the diversity of mRNA 3' UTRs mediating miRNA binding sites influence miRNA-mediated regulation. Alternative polyadenylation, by shortening mRNA isoforms, increases the diversity of 3' UTRs; moreover, short mRNA isoforms elude miRNA-medicated repression...
2018: PloS One
https://www.readbyqxmd.com/read/29300102/curcumin-and-melanoma-from-chemistry-to-medicine
#10
Seyed Mohammad Nabavi, Gian Luigi Russo, Idolo Tedesco, Maria Daglia, Ilkay Erdogan Orhan, Seyed Fazel Nabavi, Anupam Bishayee, Kalyan C Nagulapalli Venkata, Mohammad Abdollahi, Zohreh Hajheydari
Melanoma is the most deadly form of skin cancer, with about 48,000 deaths each year worldwide. Growing evidence suggests that individual nutrients or dietary patterns might have important roles in the prevention of melanoma. Considering that melanoma is a potentially life-threatening cancer, novel protective and adjuvant treatments are needed to improve its prognosis. Curcumin is a bioactive substance extracted from rhizome of Curcuma longa L. Its global market is expected to grow in the next few years, especially in the pharmaceutical industry, due to its numerous physiological and pharmacological properties...
January 4, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29299623/bioprospection-of-culturable-endophytic-fungi-associated-with-the-ornamental-plant-pachystachys-lutea
#11
Amanda da Silva Ribeiro, Julio Cesar Polonio, Alessandra Tenório Costa, Caroline Menicoze Dos Santos, Sandro Augusto Rhoden, João Lúcio Azevedo, João Alencar Pamphile
Endophytes are fungi and bacteria that inhabit plant tissues without causing disease. Endophytes have characteristics that are important for the health of the plant and have been isolated from several plants of economic and medicinal interest but rarely from ornamental plants. The current study isolates and identifies endophytic fungi from the leaves of Pachystachys lutea and evaluates the antagonistic activity of these endophytes as well as cellulase production by the endophytes. Fungi were isolated by fragmentation from surface-disinfected leaves and were identified by the sequencing of the ITS gene and the genes coding for EF 1-α and β-tubulin followed by multilocus sequence analysis...
January 3, 2018: Current Microbiology
https://www.readbyqxmd.com/read/29287687/an-overview-of-the-possible-therapeutic-role-of-sumoylation-in-the-treatment-of-alzheimer-s-disease
#12
REVIEW
S Marcelli, E Ficulle, L Piccolo, M Corbo, M Feligioni
Nowadays, Alzheimer's disease (AD) is recognized as a multifactorial neurological pathology whose complexity is the cause of our still low achievements in the understanding of the associated mechanisms as well the discovery of a possible definitive cure. Clinicians are aware of the few possibilities offered by medicine to cure Alzheimer's patients, restore their memory and take them back to normal life. Unfortunately, the therapeutic tools available today are not able to contrast the pathology. In the last years the tendency of the research is to formulate new hypotheses that can help to develop future effective drugs...
December 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29287304/the-tumor-like-phenotype-of-rheumatoid-synovium-molecular-profiling-and-prospects-for-precision-medicine
#13
REVIEW
Sungyong You, Jung Hee Koh, Lin Leng, Wan-Uk Kim, Richard Bucala
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by a destructive hyperplasia of synovium. Fibroblast-like synoviocytes (FLS) are a major component of synovial pannus and actively participate in the pathologic progression of RA. How rheumatoid FLS acquire and sustain such a uniquely aggressive phenotype remains poorly understood. We describe the current state of knowledge of the molecular alterations in rheumatoid FLS at the genomic, epigenomic, transcriptomic, proteomic, and metabolomic levels, which offers a comprehensive and complementary reconstruction of the potential pathways leading to rheumatoid pannus...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29283402/real-time-monitoring-and-analysis-of-zebrafish-electrocardiogram-with-anomaly-detection
#14
Michael Lenning, Joseph Fortunato, Tai Le, Isaac Clark, Ang Sherpa, Soyeon Yi, Peter Hofsteen, Geethapriya Thamilarasu, Jingchun Yang, Xiaolei Xu, Huy-Dung Han, Tzung K Hsiai, Hung Cao
Heart disease is the leading cause of mortality in the U.S. with approximately 610,000 people dying every year. Effective therapies for many cardiac diseases are lacking, largely due to an incomplete understanding of their genetic basis and underlying molecular mechanisms. Zebrafish (Danio rerio) are an excellent model system for studying heart disease as they enable a forward genetic approach to tackle this unmet medical need. In recent years, our team has been employing electrocardiogram (ECG) as an efficient tool to study the zebrafish heart along with conventional approaches, such as immunohistochemistry, DNA and protein analyses...
December 28, 2017: Sensors
https://www.readbyqxmd.com/read/29279290/minimizing-the-effects-of-oxygen-interference-on-l-lactate-sensors-by-a-single-amino-acid-mutation-in-aerococcus-viridansl-lactate-oxidase
#15
Kentaro Hiraka, Katsuhiro Kojima, Chi-En Lin, Wakako Tsugawa, Ryutaro Asano, Jeffrey T La Belle, Koji Sode
l-lactate biosensors employing l-lactate oxidase (LOx) have been developed mainly to measure l-lactate concentration for clinical diagnostics, sports medicine, and the food industry. Some l-lactate biosensors employ artificial electron mediators, but these can negatively impact the detection of l-lactate by competing with the primary electron acceptor: molecular oxygen. In this paper, a strategic approach to engineering an AvLOx that minimizes the effects of oxygen interference on sensor strips was reported...
December 14, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29278599/meeting-report-from-the-2016-11th-biennial-ovarian-cancer-research-symposium-mechanisms-of-initiation-and-progression-of-ovarian-cancers
#16
Jeremy Chien, Geeta Mehta
OBJECTIVE: The aim of this study was to review the latest research advances on the mechanisms of initiation and progression of ovarian cancer. METHODS: At the 11th Biennial Ovarian Cancer Research Symposium, which was held in Seattle, Washington in September 2016, leaders in ovarian cancer research convened to present and discuss current advances and future directions in ovarian cancer research. RESULTS: One session was dedicated to Mechanisms of Initiation and Progression of Ovarian Cancer, and included a keynote presentation from Dr Ronny Drapkin, MD (University of Pennsylvania), and an invited oral presentation from Laising Yen, PhD (Baylor College of Medicine)...
November 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29277263/genetics-of-human-epilepsies-continuing-progress
#17
Pierre Szepetowski
Numerous epilepsy genes have been identified in the last years, mostly in the (rare) monogenic forms and thanks to the increased availability and the decreased cost of next-generation sequencing approaches. Besides the somehow expected group of epilepsy genes encoding various ion channel subunits (e.g. sodium or potassium channel subunits, or GABA receptors, or glutamate-gated NMDA receptors), more diversity has emerged recently, with novel epilepsy genes encoding proteins playing a wide range of physiological roles at the cellular and molecular levels, such as synaptic proteins, members of the mTOR pathway, or proteins involved in chromatin remodeling...
December 22, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29259858/in-vivo-quantification-of-amyloid-burden-in-ttr-related-cardiac-amyloidosis
#18
Alexander Marco Kollikowski, Florian Kahles, Svetlana Kintsler, Sandra Hamada, Sebastian Reith, Ruth Knüchel, Christoph Röcken, Felix Manuel Mottaghy, Nikolaus Marx, Mathias Burgmaier
Cardiac transthyretin-related (ATTR) amyloidosis is a severe cardiomyopathy for which therapeutic approaches are currently under development. Because non-invasive imaging techniques such as cardiac magnetic resonance imaging and echocardiography are non-specific, the diagnosis of ATTR amyloidosis is still based on myocardial biopsy. Thus, diagnosis of ATTR amyloidosis is difficult in patients refusing myocardial biopsy. Furthermore, myocardial biopsy does not allow 3D-mapping and quantification of myocardial ATTR amyloid...
November 2017: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/29259556/the-oncopig-cancer-model-as-a-complementary-tool-for-phenotypic-drug-discovery
#19
REVIEW
Natalia V Segatto, Mariana H Remião, Kyle M Schachtschneider, Fabiana K Seixas, Lawrence B Schook, Tiago Collares
The screening of potential therapeutic compounds using phenotypic drug discovery (PDD) is being embraced once again by researchers and pharmaceutical companies as an approach to enhance the development of new effective therapeutics. Before the genomics and molecular biology era and the consecutive emergence of targeted-drug discovery approaches, PDD was the most common platform used for drug discovery. PDD, also known as phenotypic screening, consists of screening potential compounds in either in vitro cellular or in vivo animal models to identify compounds resulting in a desirable phenotypic change...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29258335/targeting-of-microbubbles-contrast-agents-for-ultrasound-molecular-imaging
#20
Shiying Wang, John A Hossack, Alexander L Klibanov
For contrast ultrasound imaging, the most efficient contrast agents comprise highly compressible gas-filled microbubbles. These micrometer-sized particles are typically filled with low-solubility perfluorocarbon gases, and coated with a thin shell, often a lipid monolayer. These particles circulate in the bloodstream for several minutes; they demonstrate good safety and are already in widespread clinical use as blood pool agents with very low dosage necessary (sub-mg per injection). As ultrasound is an ubiquitous medical imaging modality, with tens of millions of exams conducted annually, its use for molecular/targeted imaging of biomarkers of disease may enable wider implementation of personalized medicine applications, precision medicine, non-invasive quantification of biomarkers, targeted guidance of biopsy and therapy in real time...
December 20, 2017: Journal of Drug Targeting
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