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https://www.readbyqxmd.com/read/28635648/deoxyelephantopin-and-isodeoxyelephantopin-as-potential-anticancer-agents-with-effects-on-multiple-signaling-pathways
#1
REVIEW
Tahir Mehmood, Amara Maryam, Hamed A Ghramh, Muhammad Khan, Tonghui Ma
Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of "Elephantopus scaber and Elephantopus carolinianus", traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635440/adding-an-accredited-exercise-physiologist-role-to-a-new-model-of-care-at-a-secure-extended-care-mental-health-service-a-qualitative-study
#2
Trentham Furness, Jude Hewavasam, Jakqui Barnfield, Brian McKenna, Corey Joseph
BACKGROUND: Accredited exercise physiologists (AEPs) are emerging as essential members of allied health in the management of non-communicable chronic diseases. People diagnosed with severe mental illness (SMI) are at greater risk of cardiovascular diseases. Secure extended care units (SECUs) provide treatment, supervision and support for people with SMI whose needs cannot be met adequately in the community. However, the role of AEPs in SECUs has not been described. AIM: Describe the processes and outcomes of adding an AEP to a new model of care at a SECU...
March 1, 2017: Journal of Mental Health
https://www.readbyqxmd.com/read/28634578/neonatal-venous-thromboembolism
#3
REVIEW
Kristina M Haley
Neonates are the pediatric population at highest risk for development of venous thromboembolism (VTE), and the incidence of VTE in the neonatal population is increasing. This is especially true in the critically ill population. Several large studies indicate that the incidence of neonatal VTE is up almost threefold in the last two decades. Central lines, fluid fluctuations, sepsis, liver dysfunction, and inflammation contribute to the risk profile for VTE development in ill neonates. In addition, the neonatal hemostatic system is different from that of older children and adults...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28634291/rhodium-metalloinsertor-binding-generates-a-lesion-with-selective-cytotoxicity-for-mismatch-repair-deficient-cells
#4
Julie M Bailis, Alyson G Weidmann, Natalie F Mariano, Jacqueline K Barton
The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)](2+) (Rh-PPO)...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28634236/alternative-evolutionary-pathways-for-drug-resistant-small-colony-variant-mutants-in-staphylococcus-aureus
#5
Sha Cao, Douglas L Huseby, Gerrit Brandis, Diarmaid Hughes
Staphylococcus aureus is known to generate small colony variants (SCVs) that are resistant to aminoglycoside antibiotics and can cause persistent and recurrent infections. The SCV phenotype is unstable, and compensatory mutations lead to restored growth, usually with loss of resistance. However, the evolution of improved growth, by mechanisms that avoid loss of antibiotic resistance, is very poorly understood. By selection with serial passaging, we isolated and characterized different classes of extragenic suppressor mutations that compensate for the slow growth of small colony variants...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28634175/interrelations-between-3-hydroxypropionate-and-propionate-metabolism-in-rat-liver-relevance-to-disorders-of-propionyl-coa-metabolism
#6
Kirkland A Wilson, Yong Han, Miaoqi Zhang, Jeremy Hess, Kimberly A Chapman, Gary W Cline, Gregory P Tochtrop, Henri Brunengraber, Guo-Fang Zhang
Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds and ammonium accumulate in body fluids of patients with disorders of propionyl-CoA metabolism, such as propionic acidemia. Although liver transplantation alleviates hyperammonemia, high concentrations of propionate, 3HP and methylcitrate persist in body fluids. We hypothesized that conserved metabolic perturbations occurring in transplanted patients result from the simultaneous presence of propionate and 3HP in body fluids. We investigated the interrelations of propionate and 3HP metabolism in perfused livers from normal rats using metabolomic and stable isotopic technologies...
June 20, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28634044/mir-218-suppresses-gastric-cancer-cell-cycle-progression-through-the-cdk6-cyclin-d1-e2f1-axis-in-a-feedback-loop
#7
Min Deng, Chao Zeng, Xihong Lu, Xiusheng He, Ruixin Zhang, Qinwei Qiu, Guopei Zheng, Xiaoting Jia, Hao Liu, Zhimin He
Studies in several cancers have suggested that miR-218 has anti-tumor activities, but its function is yet to be elucidated. In this study, we investigated the regulation and function of miR-218 (miR-218-5p) in the cell cycle progression of gastric cancer (GC). We found that miR-218 could suppress proliferation of gastric cancer cells, induce cell cycle arrest at the G1 phase and inhibit tumor growth and metastasis in vivo. We also demonstrated that miR-218 specifically targeted the 3'-UTR regions of CDK6 and cyclin D1 and inhibited the expression of these molecules, which in turn repressesed the pRb/E2F1 signaling pathway...
June 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28634043/the-roles-of-integrin-%C3%AE-v%C3%AE-6-in-cancer
#8
Jun Niu, Zequn Li
Integrins are a family of heterodimeric cell surface receptors that are expressed in most cells, where they mediate cell-cell and cell-extracellular matrix (ECM) interactions. Integrin αvβ6 is a heterodimer with αv and β6 subunits. It is epithelial-specific and strongly induced during wound healing, inflammation and carcinogenesis. Integrin αvβ6 is considered to be a prognostic indicator because it is up-regulated in various types of cancers and integrin αvβ6 expression correlates with the survival time of patients...
June 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28634037/clinical-benefit-of-drugs-targeting-mitochondrial-function-as-an-adjunct-to-reperfusion-in-st-segment-elevation-myocardial-infarction-a-meta-analysis-of-randomized-clinical-trials
#9
Gianluca Campo, Rita Pavasini, Giampaolo Morciano, A Michael Lincoff, C Michael Gibson, Masafumi Kitakaze, Jacob Lonborg, Amrita Ahluwalia, Hideki Ishii, Michael Frenneaux, Michel Ovize, Marcello Galvani, Dan Atar, Borja Ibanez, Giampaolo Cerisano, Simone Biscaglia, Brandon J Neil, Masanori Asakura, Thomas Engstrom, Daniel A Jones, Dana Dawson, Roberto Ferrari, Paolo Pinton, Filippo Ottani
AIMS: To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. METHODS: Inclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo...
June 13, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28633926/synergic-stimulation-of-serotonin-5-ht1a-receptor-and-%C3%AE-2-adrenoceptors-for-neuropathic-pain-relief-preclinical-effects-of-2-substituted-imidazoline-derivatives
#10
Lorenzo Di Cesare Mannelli, Carla Ghelardini, Laura Micheli, Fabio Del Bello, Mario Giannella, Alessandro Piergentili, Wilma Quaglia
Neuropathic pain affects millions of people causing disability and impairing quality of life. Commonly used analgesics are generally characterized by limited therapeutic outcomes. The serotonin 5-HT1A receptor and the α2 adrenergic receptors are involved in central nociceptive mechanisms with a pivotal role in the inhibitory descending pain pathway. Since their stimulation may modulate the nervous signaling altered by neuropathies, the purpose of the present research is the study of the combined activation of 5-HT1A and α2 receptors by rationally designed imidazoline ligands ((S)-1 and 2-5) in a rat model of neuropathic pain (chronic constriction injury - CCI)...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28633670/preclinical-anti-myeloma-activity-of-edo-s101-a-new-bendamustine-derived-molecule-with-added-hdaci-activity-through-potent-dna-damage-induction-and-impairment-of-dna-repair
#11
Ana-Alicia López-Iglesias, Ana B Herrero, Marta Chesi, Laura San-Segundo, Lorena González-Méndez, Susana Hernández-García, Irena Misiewicz-Krzeminska, Dalia Quwaider, Montserrat Martín-Sánchez, Daniel Primo, Teresa Paíno, P Leif Bergsagel, Thomas Mehrling, Marcos González-Díaz, Jesús F San-Miguel, María-Victoria Mateos, Norma C Gutiérrez, Mercedes Garayoa, Enrique M Ocio
BACKGROUND: Despite recent advances in the treatment of multiple myeloma (MM), the prognosis of most patients remains poor, and resistance to traditional and new drugs frequently occurs. EDO-S101 is a novel therapeutic agent conceived as the fusion of a histone deacetylase inhibitor radical to bendamustine, with the aim of potentiating its alkylating activity. METHODS: The efficacy of EDO-S101 was evaluated in vitro, ex vivo and in vivo, alone, and in combination with standard anti-myeloma agents...
June 20, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#12
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28633632/antagonizing-mir-455-3p-inhibits-chemoresistance-and-aggressiveness-in-esophageal-squamous-cell-carcinoma
#13
Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
BACKGROUND: The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. METHODS: A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness...
June 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28633552/cabozantinib-for-the-treatment-of-kidney-cancer
#14
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib is a small molecule tyrosine kinase inhibitor that initially showed activity in medullary thyroid cancer and was recently approved by the Food and Drug Administration for the treatment of metastatic renal cell carcinoma after progression on first line therapy. Areas Covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator...
June 21, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28633446/genetic-indicators-of-drug-resistance-in-the-highly-repetitive-genome-of-trichomonas-vaginalis
#15
Martina Bradic, Sally D Warring, Grace E Tooley, Paul Scheid, William E Secor, Kirkwood M Land, Po-Jung Huang, Ting-Wen Chen, Chi-Ching Lee, Petrus Tang, Steven A Sullivan, Jane M Carlton
Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance...
June 19, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28633144/standardized-renal-endpoints-for-perioperative-clinical-trials-the-standardized-endpoints-in-perioperative-medicine-initiative
#16
David R McIlroy, Andrew D Shaw, Paul S Myles
Perioperative acute kidney injury is a common problem. While clinical trials seek to evaluate the impact of interventions on a variety of primary and secondary endpoints with the aim of implementing this knowledge to improve perioperative outcomes, the use of valid and relevant endpoints within clinical trials is of critical importance to achieving this goal. Suitable endpoints must be validated for the study population and in light of the clinical context under investigation while also considering regulatory requirements that govern the licensing of new therapeutic agents as well as the values of patients whose outcomes we seek to improve...
June 21, 2017: Nephron
https://www.readbyqxmd.com/read/28633062/blue-light-induced-reactive-oxygen-species-from-flavin-mononucleotide-and-flavin-adenine-dinucleotide-on-lethality-of-hela-cells
#17
Ming-Yeh Yang, Chih-Jui Chang, Liang-Yü Chen
Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm)...
June 13, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28632966/characterizing-alzheimer-s-disease-through-metabolomics-and-investigating-anti-alzheimer-s-disease-effects-of-natural-products
#18
REVIEW
Lunzhao Yi, Wenbin Liu, Zhe Wang, Dabing Ren, Weijun Peng
Alzheimer's disease (AD) is the most common cause of dementia in elderly people and is among the greatest healthcare challenges of the 21st century. However, the etiology and pathogenesis of AD remain poorly understood, and no curative treatments are available to slow down or stop the degenerative effects of AD. As a high-throughput approach, metabolomics is gaining significant attention in AD research, because it has a powerful potential to discover novel biomarkers, unravel new therapeutic targets for AD, and identify perturbed metabolic pathways involved in AD progression...
June 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28632924/metabolomics-as-a-driver-in-advancing-precision-medicine-in-sepsis
#19
Michelle Eckerle, Lilliam Ambroggio, Michael Puskarich, Brent Winston, Alan E Jones, Theodore J Standiford, Kathleen A Stringer
OBJECTIVE: The objective of this review is to explain the science of metabolomics-a science of systems biology that measures and studies endogenous small molecules (metabolites) that are present in a single biological sample-and its application to the diagnosis and treatment of sepsis. In addition, we discuss how discovery through metabolomics can contribute to the development of precision medicine targets for this complex disease state and the potential avenues for those new discoveries to be applied in the clinical environment...
June 20, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28632792/identification-of-cell-proliferation-immune-response-and-cell-migration-as-critical-pathways-in-a-prognostic-signature-for-her2-er%C3%AE-breast-cancer
#20
Jeffrey C Liu, Miriam Zacksenhouse, Andrea Eisen, Sharon Nofech-Mozes, Eldad Zacksenhaus
BACKGROUND: Multi-gene prognostic signatures derived from primary tumor biopsies can guide clinicians in designing an appropriate course of treatment. Identifying genes and pathways most essential to a signature performance may facilitate clinical application, provide insights into cancer progression, and uncover potentially new therapeutic targets. We previously developed a 17-gene prognostic signature (HTICS) for HER2+:ERα- breast cancer patients, using genes that are differentially expressed in tumor initiating cells (TICs) versus non-TICs from MMTV-Her2/neu mammary tumors...
2017: PloS One
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