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https://www.readbyqxmd.com/read/28654080/studying-cell-cycle-regulated-gene-expression-by-two-complementary-cell-synchronization-protocols
#1
Aintzane Apraiz, Jone Mitxelena, Ana Zubiaga
The gene expression program of the cell cycle represents a critical step for understanding cell cycle-dependent processes and their role in diseases such as cancer. Cell cycle-regulated gene expression analysis depends on cell synchronization into specific phases. Here we describe a method utilizing two complementary synchronization protocols that is commonly used for studying periodic variation of gene expression during the cell cycle. Both procedures are based on transiently blocking the cell cycle in one defined point...
June 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28647558/durable-chimerism-and-long-term-survival-following-unrelated-umbilical-cord-blood-transplantation-for-pediatric-hemophagocytic-lymphohistiocytosis-a-single-center-experience
#2
Sachit A Patel, Heather A Allewelt, Jesse D Troy, Paul L Martin, Timothy A Driscoll, Vinod K Prasad, Joanne Kurtzberg, Kristin M Page, Suhag H Parikh
Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, CNS disease, increased inflammatory markers and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH with reported survival ranging from 50-70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplant related mortality associated with conventional MAC are major barriers to success...
June 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28643460/periodic-limb-movement-in-sleep-and-sickle-cell-disease-a-neglected-association
#3
Ana C Cabañas-Pedro, Suely Roizenblatt, Altay A L de Souza, Sérgio Tufik, Maria S Figueiredo
High frequency of periodic limb movements in sleep (PLMS) has been described among children with sickle cell disease (SCD), but there is little information about PLMS among adults with SCD. We aim to determine the frequency of PLMS among adults with SCD and to identify possible associations with iron status and haemolytic parameters. We analysed polysomnography on 99 adults: 74 with sickle cell anaemia (HbSS), 19 with HbSC (double heterozygosis HbS and HbC) and 6 with HbS-beta thalassaemia. Laboratory data were collected close to the time of the polysomnography examination...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28643377/randomized-feasibility-trial-to-improve-hydroxyurea-adherence-in-youth-ages-10-18-years-through-community-health-workers-the-habit-study
#4
Nancy S Green, Deepa Manwani, Sergio Matos, April Hicks, Luisa Soto, Yina Castillo, Karen Ireland, Yvonne Stennett, Sally Findley, Haomiao Jia, Arlene Smaldone
INTRODUCTION: The main therapeutic intervention for sickle cell disease (SCD) is hydroxyurea (HU). The effect of HU is largely through dose-dependent induction of fetal hemoglobin (HbF). Poor HU adherence is common among adolescents. METHODS: Our 6-month, two-site pilot intervention trial, "HABIT," was led by culturally aligned community health workers (CHWs). CHWs performed support primarily through home visits, augmented by tailored text message reminders. Dyads of youth with SCD ages 10-18 years and a parent were enrolled...
June 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28641125/an-altered-redox-environment-assisted-by-over-expression-of-fetal-hemoglobins-protects-from-inflammatory-colitis-and-reduces-inflammatory-cytokine-expression
#5
R M Gorczynski, C Alexander, K Brandenburg, Z Chen, A Heini, D Neumann, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, Kai Yu, U Zahringer, I Khatri
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents...
June 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28639471/an-enhancer-haplotype-may-influence-bcl11a-expression-levels-and-the-response-to-hydroxyurea-in-%C3%AE-thalassemia-patients
#6
Nahal Maroofi, Azita Azarkeivan, Soosan Banihashemi, Saeid Mohammadparast, Ali Aghajanirefah, Mehdi Banan
AIM: To identify the BCL11A intron-2 enhancer linkage disequilibrium (LD) block, harboring two previously identified SNPs, associating with the hydroxyurea response in β-thalassemia patients and the functional significance of this region. MATERIALS & METHODS: Several neighboring SNPs were genotyped in our cohort. The associating LD block was identified, and its function studied in K562 erythroid cells via CRISPR/Cas9 genome editing. RESULTS: A haplotype harboring three tag SNPs correlated significantly with the HU-response and BCL11A transcript levels in the patients' reticulocytes...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28638723/low-dose-methotrexate-in-sickle-cell-disease-a-pilot-study-with-rationale-borrowed-from-rheumatoid-arthritis
#7
Silvia R Brandalise, Rosemary Assis, Angelo B A Laranjeira, José Andrés Yunes, Pedro O de Campos-Lima
BACKGROUND: Inflammation is a major feature of sickle cell disease (SCD). Low-dose methotrexate (MTX) has long been used in chronic inflammatory diseases. This pilot study examined the MTX effect on acute vaso-occlusive pain crises (VOC) in SCD patients. METHODS: Fourteen adults on hydroxyurea with severe and refractory VOC received one intramuscular injection of 10 mg of MTX per week for 12 weeks. A single weekly dose of 5 mg of leucovorin was administered orally 48 h after each MTX injection...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28632807/transverse-melanonychia-and-palmar-hyperpigmentation-secondary-to-hydroxyurea-therapy
#8
Jason Schoenfeld, Brittain H Tulbert, Carrie Ann Cusack
No abstract text is available yet for this article.
May 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28632788/high-throughput-identification-and-rational-design-of-synergistic-small-molecule-pairs-for-combating-and-bypassing-antibiotic-resistance
#9
Morgan A Wambaugh, Viplendra P S Shakya, Adam J Lewis, Matthew A Mulvey, Jessica C S Brown
Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28628689/aggressive-skin-cancers-occurring-in-patients-treated-with-the-janus-kinase-inhibitor-ruxolitinib
#10
Adam B Blechman, Christine E Cabell, Christine H Weinberger, Anna Duckworth, Justin J Leitenberger, Fiona O Zwald, Mark A Russell
<p>The Food and Drug Administration approved Ruxolitinib in 2011 for the treatment of primary myelofibrosis. Five-year safety data showed a higher incidence of skin cancer in patients treated with Ruxolitinib compared to best available therapy for myelofibrosis. This report presents a series of five patients with history of myelofibrosis treated with Ruxolitinib who subsequently developed numerous skin cancers with aggressive biological behavior. Each patient in this report was treated by a Mohs surgeon affiliated with an academic institution...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28628639/small-molecule-inhibitors-uncover-synthetic-genetic-interactions-of-human-flap-endonuclease-1-fen1-with-dna-damage-response-genes
#11
Thomas A Ward, Peter J McHugh, Stephen T Durant
Flap endonuclease 1 (FEN1) is a structure selective endonuclease required for proficient DNA replication and the repair of DNA damage. Cellularly active inhibitors of this enzyme have previously been shown to induce a DNA damage response and, ultimately, cell death. High-throughput screens of human cancer cell-lines identify colorectal and gastric cell-lines with microsatellite instability (MSI) as enriched for cellular sensitivity to N-hydroxyurea series inhibitors of FEN1, but not the PARP inhibitor olaparib or other inhibitors of the DNA damage response...
2017: PloS One
https://www.readbyqxmd.com/read/28626540/acute-crises-and-complications-of-sickle-cell-anemia-among-patients-attending-a-pediatric-tertiary-unit-in-kinshasa-democratic-republic-of-congo
#12
Michel Ntetani Aloni, Bertin Tshimanga Kadima, Pépé Mfutu Ekulu, Aléine Nzazi Budiongo, René Makuala Ngiyulu, Jean Lambert Gini-Ehungu
In the Democratic Republic of Congo, the incidence of sickle cell anemia (SCA) is estimated to affect 30,000 to 40,000 neonates per year. However, there is paucity of data on acute clinical manifestations in sickle cell children. In these circumstances, it is difficult to develop a health care policy for an adequate management of sickle cell patients. This was a seven years' retrospective study of children admitted with acute sickle cell crisis in the Department of Pediatrics in University Hospital of Kinshasa, Kinshasa, the Democratic Republic of Congo...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28624910/clinical-pharmacology-and-clinical-trials-of-ribonucleotide-reductase-inhibitors-is-it-a-viable-cancer-therapy
#13
REVIEW
Mukundan Baskar Mannargudi, Subrata Deb
PURPOSE: Ribonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation. METHODS: This review mainly focuses on several biological and chemical RR inhibitors (e.g., siRNA, GTI-2040, GTI-2501, triapine, gemcitabine, and clofarabine) that have been evaluated in clinical trials with promising anticancer activity from 1960's till 2016...
June 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28614773/assessment-of-neurotoxicity-of-pharmacological-compounds-during-early-neural-development-of-human-embryonic-stem-cells
#14
H Y Kang, E J Hong, H S Kang, C Ahn, E B Jeung
Human embryonic stem cells (hESCs), with the potential for differentiation, have been used to evaluate the embryotoxicity of various compounds. The effects of pharmacological compounds (cytosine arabinoside, 5-fluorouracil, hydroxyurea, indomethacin, and dexamethasone) on neurogenesis of hESCs over 28 days were examined based on cytotoxicity (half-maximal inhibitory concentration of viability, IC50) and expression of neural markers. Cytosine arabinoside, 5-fluorouracil, and hydroxyurea showed strong cytotoxicity (IC50 < 10 μM), whereas indomethacin and dexamethasone had weaker cytotoxic effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28612449/changes-in-urine-albumin-to-creatinine-ratio-with-the-initiation-of-hydroxyurea-therapy-among-children-and-adolescents-with-sickle-cell-disease
#15
Sarah Tehseen, Clinton H Joiner, Peter A Lane, Marianne E Yee
BACKGROUND: Renal damage is a progressive complication of sickle cell disease (SCD) that begins in childhood and may progress to renal failure and early mortality in 12% of adults with hemoglobin SS (HbSS) SCD. Early sickle nephropathy is characterized by hyperfiltration and microalbuminuria; therefore, urine albumin to creatinine ratio (ACR) is an effective screening tool for its detection. PROCEDURE: This study investigated the effect of hydroxyurea (HU) therapy on urine ACR levels among children with SCD...
June 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28587497/accelerated-leukemic-transformation-after-haplo-identical-transplantation-for-hydroxyurea-treated-sickle-cell-disease
#16
Murali Janakiram, Amit Verma, Yanhua Wang, Anjali Budhathoki, Jaime Suarez Londono, Irina Murakhovskaya, Ira Braunschweig, Caterina P Minniti
No abstract text is available yet for this article.
June 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28585003/secondary-breast-carcinoma-after-completely-remitted-chronic-myeloid-leukemia-following-targeted-tyrosine-kinase-inhibitor-therapy
#17
Linlin Pan, Junwu Duan, Weiqiang Qiao, Lirong Bi, Di Wu, Zhimin Fan, Ming Yang
We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed...
June 5, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28584711/quercetin-reduces-hydroxyurea-induced-cytotoxicity-in-immortalized-mouse-aortic-endothelial-cells
#18
Zachary M Kiser, Monica D M McGee, Racquel J Wright, Alexander Quarshie, Gale W Newman, Karen R Randall, Jonathan K Stiles, Adel Driss, Jacqueline M Hibbert
BACKGROUND: Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage...
2017: PeerJ
https://www.readbyqxmd.com/read/28584607/essential-thrombocythemia-in-a-two-year-old-child-responsive-to-hydroxyurea-but-not-aspirin
#19
Tariq N Aladily, Randa S Mohammad, Ali Al-Khader, Abdalla S Awidi
Essential thrombocythemia (ET) is a myeloproliferative neoplasm that occurs mostly in patients above the age of 50 years. Its incidence in children is very rare, with around 100 cases reported in the literature. High-risk patients are defined by previous life threatening major thrombotic or severe hemorrhagic complication or age > 60. Those patients probably benefit from cytoreductive therapy. On the other hand, antiplatelet drugs are recommended for patients with low risk group. Although rare, ET should be considered in the differential diagnosis of persistent thrombocytosis in children, even at a very young age...
May 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/28582589/macrocytosis-secondary-to-hydroxyurea-therapy
#20
Francisco O Conrado, Amy L Weeden, Abbie L Speas, Mary K Leissinger
A 10-year-old, male neutered Shetland Sheepdog was presented to the University of Florida for evaluation of a well-granulated mast cell tumor. Hydroxyurea therapy was instituted and serial CBCs showed persistent mild anemia and macrocytosis without a corresponding increase in polychromasia. The dog's MCV increased progressively, reaching its highest value of 100.0 fL after 6 months of treatment, and a diagnosis of macrocytosis associated with hydroxyurea therapy was made. The dog's increase in MCV was prominent, and rapidly decreased after the drug was discontinued, consistent with previous observations in human and canine subjects treated with hydroxyurea...
June 5, 2017: Veterinary Clinical Pathology
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