Read by QxMD icon Read


Sarah Löw, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma limited to the brain, spinal cord, leptomeninges, and eyes. The majority of patients are immunocompetent, with a median age of 65 years at diagnosis. Historically, whole-brain radiation therapy (WBRT) was the first and sole treatment for PCNSL. Today, due to the recognized neurotoxicity of WBRT, this modality is usually avoided in the treatment. Most chemotherapy regimens are based on high-dose methotrexate plus the anti-CD20 monoclonal antibody rituximab, leading to high response rates, but 5-year survival is still poor at approximately 30% compared with other extranodal lymphomas...
February 2018: Seminars in Neurology
Anna Wallerstedt, Peter Strom, Henrik Gronberg, Tobias Nordstrom, Martin Eklund
Background: Studies have shown that 5α-reductase inhibitors (5-ARIs) decrease the risk for low-grade prostate cancer (PC), but results are conflicting concerning high-grade PCs. The objective of the present study is to evaluate the association between 5-ARI treatment for lower urinary tract symptoms and the risk for PC. Methods: This is a population-based prospective study on all men age 40 years and older with at least one prostate-specific antigen (PSA) test in Stockholm County from January 2007 until December 2015...
March 14, 2018: Journal of the National Cancer Institute
Darshan Khangura, L Romayne Kurukulasuriya, Adam Whaley-Connell, James R Sowers
The presence of hypertension in individuals with type 2 diabetes augments the risk for cardiovascular morbidity and mortality. In this regard, data support that management of hypertension in this high-risk population is a critical risk reduction strategy. In recent years, a number of work groups have redefined hypertension, management strategies, and targets. In this context, there is still considerable discussion on an appropriate target for blood pressure in the diabetic population. However, despite this discussion on target blood pressure, it is widely recognized that there is considerable residual risk for heightened cardiovascular events in the hypertensive, diabetic population despite widespread awareness and treatment...
March 14, 2018: American Journal of Hypertension
Negiin Pourafshar, Ashkan Karimi, Xuerong Wen, Eric Sobel, Shirin Pourafshar, Nikhil Agrawal, Emma Segal, Rajesh Mohandas, Mark S Segal
Background: Monitoring of mycophenolic acid (MPA) levels may be useful for effective mycophenolate mofetil (MMF) dosing. However, whether commonly obtained trough levels are an acceptable method of surveillance remains debatable. We hypothesized that trough levels of MPA would be a poor predictor of area under the curve (AUC) for MPA. Methods: A total of 51 patients with lupus nephritis who were on MMF 1500 mg twice a day and had a 4-h AUC done were included in this study...
March 13, 2018: Nephrology, Dialysis, Transplantation
Vassilis E Papadopoulos, Georgia Nikolopoulou, Ivi Antoniadou, Antonia Karachaliou, Giovanna Arianoglou, Evangelia Emmanouilidou, S Pablo Sardi, Leonidas Stefanis, Kostas Vekrellis
Glucocerebrosidase gene (GBA) mutations are the most common genetic contributor to Parkinson's Disease (PD) and are associated with decreased Glucocerebrosidase (GCase) enzymatic activity in PD. PD patients without GBA mutations also exhibit lower levels of GCase activity in the central nervous system (CNS) suggesting a potential contribution of the enzyme activity in disease pathogenesis, possibly by alteration of lysosomal function. α-synuclein, a protein with a central role in PD pathogenesis, has been shown to be secreted partly in association with exosomes...
March 14, 2018: Human Molecular Genetics
Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
Ian Thompson, Phyllis Goodman, Catherine Tangen
No abstract text is available yet for this article.
March 14, 2018: Journal of the National Cancer Institute
Tristan Pascart, Frédéric Lioté
This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management...
March 13, 2018: Rheumatology
Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Ana M Molina, Thomas E Hutson, Dmitry Nosov, Piotr Tomczak, Oleg Lipatov, Cora N Sternberg, Robert Motzer, Tim Eisen
BACKGROUND: Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 tyrosine kinases. This open-label, crossover clinical study (AV-951-09-902) provided access to tivozanib for patients who progressed on sorafenib in TIVO-1, comparing tivozanib with sorafenib in patients with advanced renal cell carcinoma (RCC). METHODS: Patients enrolled in this single-arm, phase 2 crossover study were previously randomised to sorafenib on TIVO-1, progressed and then crossed over to tivozanib...
March 13, 2018: European Journal of Cancer
Silvia Salerno, Aída Nelly García-Argáez, Elisabetta Barresi, Sabrina Taliani, Francesca Simorini, Concettina La Motta, Giorgio Amendola, Stefano Tomassi, Sandro Cosconati, Ettore Novellino, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via
Inhibition of angiogenesis via blocking vascular endothelial growth factor receptor (VEGFR) signaling pathway emerged as an established approach in anticancer therapy. So far, many monoclonal antibodies and ATP-competitive small molecule inhibitors have been clinically validated and approved. In this study, structure-activity relationships (SAR) within the 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidine class of kinase inhibitors were further refined by the synthesis and biological evaluation of new compounds 1-21 featuring different substitution patterns on the pendant phenyl moiety, combined with H, OCH3 , or Cl at 8-position...
March 7, 2018: European Journal of Medicinal Chemistry
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
Evgenii Tcyganov, Jerome Mastio, Eric Chen, Dmitry I Gabrilovich
In recent years, myeloid-derived suppressor cells (MDSC) have emerged as one of the major inhibitors of immune effector cell function in cancer. MDSC represent a heterogeneous population of largely immature myeloid cells that are characterized by a pathological state of activation and display potent immune suppressive activity. Two major subsets of MDSC have been identified: monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC). PMN-MSDC share phenotypic and morphologic features with neutrophils, whereas M-MDSC are similar to monocytes and are characterized by high plasticity...
March 13, 2018: Current Opinion in Immunology
Peng Liu, Teng-Fei Zhou, Bao-An Qiu, Ying-Xiang Yang, Yong-Jian Zhu, Yang An, Wen-Chao Zhao, Yin-Tao Wu, Peng-Fei Ma, Jing-Bo Li, Nian-Xin Xia
Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies, accounting for about 3% of all gastrointestinal tumors. GATA5 is a transcription factor capable of suppressing the development of various human cancer types. Transcriptional inactivation and CpG island (CGI) methylation of GATA3 and GATA5, two members of the GATA family of transcription factors, have been observed in some human cancers. But whether high-density CGI methylation of GATA5 is associated with the clinical course of CCA patients has not been clarified...
March 13, 2018: Translational Oncology
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Julianne Teresa Djordjevic, Sophie Lev
Invasive fungal diseases pose a serious threat, and new drugs are urgently needed. In this issue of Cell Chemical Biology, Pries et al. (2018) identified benzamide- and picolinamide-based small-molecule inhibitors with antifungal properties, including some active against pathogenic Candida species. These compounds target an essential component of the fungal secretion machinery, suggesting a new approach to antifungal development.
March 15, 2018: Cell Chemical Biology
Soo Lim, Robert H Eckel, Kwang Kon Koh
The final goal in the management of patients with type 2 diabetes (T2D) is reduction in cardiovascular (CV) complications and total mortality. Various factors including hyperglycemia contribute to these complications and mortality directly and indirectly. In recent years, large-scale CV outcome trials with new antidiabetic medications, such as dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, and sodium glucose cotransporter-2 (SGLT2) inhibitors, have been completed...
March 8, 2018: Atherosclerosis
Dong-Keon Lee, Ji-Hee Kim, Joohwan Kim, Seunghwan Choi, MinSik Park, Wonjin Park, Suji Kim, Kyu-Sun Lee, Taesam Kim, Jiwon Jung, Yoon Kyung Choi, Kwon-Soo Ha, Moo-Ho Won, Timothy R Billiar, Young-Guen Kwon, Young-Myeong Kim
Regulated in development and DNA damage responses (REDD)-1, an inhibitor of mammalian target of rapamycin (mTOR), is induced by various cell stressors, including LPS, a major player in the pathogenesis of endotoxemic shock. However, the pathologic role of REDD-1 in endotoxemia is largely unknown. We found that LPS increased REDD-1 expression, nuclear transcription factor-κB (NF-κB) activation, and inflammation and that these responses were suppressed by REDD-1 knockdown and in REDD-1+/- macrophages. REDD-1 overexpression stimulated NF-κB-dependent inflammation without additional LPS stimulation...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Eva Jover, Ana Silvente, Francisco Marín, José Martínez-González, Mar Orriols, Carlos M Martinez, Carmen María Puche, Mariano Valdés, Cristina Rodriguez, Diana Hernández-Romero
Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia (HPM)-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by HPM conditioning...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jared T Hammill, Deepak Bhasin, Daniel C Scott, Jaeki Min, Yizhe Chen, Yan Lu, Lei Yang, Ho Shin Kim, Michele C Connelly, Courtney Hammill, Gloria Holbrook, Cynthia Jeffries, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg)...
March 16, 2018: Journal of Medicinal Chemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"