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https://www.readbyqxmd.com/read/29334369/dual-gene-activation-and-knockout-screen-reveals-directional-dependencies-in-genetic-networks
#1
Michael Boettcher, Ruilin Tian, James A Blau, Evan Markegard, Ryan T Wagner, David Wu, Xiulei Mo, Anne Biton, Noah Zaitlen, Haian Fu, Frank McCormick, Martin Kampmann, Michael T McManus
Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair...
January 15, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29316888/the-preventive-effect-of-sensorimotor-and-vibration-exercises-on-the-onset-of-oxaliplatin-or-vinca-alkaloid-induced-peripheral-neuropathies-stop
#2
Fiona Streckmann, Maryam Balke, Helmar C Lehmann, Vanessa Rustler, Christina Koliamitra, Thomas Elter, Michael Hallek, Michael Leitzmann, Tilman Steinmetz, Petra Heinen, Freerk T Baumann, Wilhelm Bloch
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and clinically relevant side effect of chemotherapy. Approximately 50% of all leukemia, lymphoma, colorectal- and breast cancer patients are affected. CIPN is induced by neurotoxic chemotherapeutic agents and can manifest with sensory and/or motor deficits. It is associated with significant disability and poor recovery. Common symptoms include pain, altered sensation, reduced or absent reflexes, muscle weakness, reduced balance control and insecure gait...
January 10, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29296741/osteonecrosis-in-children-and-adolescents-with-acute-lymphoblastic-leukemia-a-therapeutic-challenge
#3
REVIEW
Michaela Kuhlen, Marina Kunstreich, Kathinka Krull, Roland Meisel, Arndt Borkhardt
Osteonecrosis (ON) represents one of the most common and debilitating sequelae of antileukemic treatment in children and adolescents with acute lymphoblastic leukemia (ALL). Systematic screening strategies can focus on early detection and intervention to prevent ON from progressing to stages associated with pain and functional impairment. These strategies hold promise for reducing ON-associated morbidity without the risk of impairing leukemia control. Herein, we critically reviewed clinical data on pharmacological, nonpharmacological/nonsurgical, and surgical (including cellular) treatment options for ON, which are covered in the literature and/or are conceivable based on the supposed underlying ON pathophysiology...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29286560/modifying-bone-mineral-density-physical-function-and-quality-of-life-in-children-with-acute-lymphoblastic-leukemia
#4
Cheryl L Cox, Liang Zhu, Sue C Kaste, Kumar Srivastava, Linda Barnes, Paul C Nathan, Robert J Wells, Kirsten K Ness
BACKGROUND: The early effects of childhood acute lymphoblastic leukemia (ALL) include decreased physical function, bone mineral density (BMD/g/cm2 ), and health-related quality of life (HRQL). We assessed the capacity of a physical therapy and motivation-based intervention, beginning after diagnosis and continuing through the end of treatment, to positively modify these factors. PROCEDURE: A 2.5-year randomized controlled trial of 73 patients aged 4-18.99 years within 10 days of ALL diagnosis assessed BMD at baseline (T0 ) and end of therapy (T3 ), strength, range of motion, endurance, motor skills, and HRQL at baseline (T0 ), 8 (T1 ), 15 (T2 ), and 135 (T3 ) weeks...
December 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29260390/parent-perspectives-and-preferences-for-strategies-regarding-nonsedated-mri-scans-in-a-pediatric-oncology-population
#5
Breya Walker, Heather M Conklin, Doralina L Anghelescu, Lacey P Hall, Wilburn E Reddick, Robert Ogg, Lisa M Jacola
PURPOSE: Children with cancer frequently require MRI scans for clinical purposes. Sedation with general anesthesia (GA) is often used to promote compliance, reduce motion, and alleviate anxiety. The use of GA for MRI scans is costly in terms of time, personnel, and medications. In addition, prominent risks are associated with anesthesia exposure in patients with complex medical conditions. Successful behavioral interventions have been implemented in clinical research settings to promote scan success and compliance...
December 19, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29248669/imaging-of-subclinical-haemopoiesis-after-stem-cell-transplantation-in-patients-with-haematological-malignancies-a-prospective-pilot-study
#6
Kirsten M Williams, Jennifer Holter-Chakrabarty, Liza Lindenberg, Quyen Duong, Sara K Vesely, Chuong T Nguyen, Joseph P Havlicek, Karen Kurdziel, Juan Gea-Banacloche, Frank I Lin, Daniele N Avila, George Selby, Christopher G Kanakry, Shibo Li, Teresa Scordino, Stephen Adler, Catherine M Bollard, Peter Choyke, Ronald E Gress
BACKGROUND: Haemopoietic stem-cell transplantation (HSCT) eradicates host haemopoiesis before venous infusion of haemopoietic stem cells (HSCs). The pathway to cellular recovery has been difficult to study in human beings because of risks associated with interventions during aplasia. We investigated whether 18F-fluorothymidine (18F-FLT) imaging was safe during allogenic HSCT and allowed visualisation of early cellular proliferation and detection of patterns of cellular engraftment after HSCT...
December 13, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29235095/immune-cells-regulate-vegf-signaling-via-release-of-vegf-and-antagonistic-soluble-vegf-receptor-1
#7
Timm Hoeres, Martin Wilhelm, Manfred Smetak, Elisabeth Holzmann, Gundula Schulze-Tanzil, Josef Birkmann
Vascular endothelial growth factor (VEGF) is an important regulator of physiological and pathological angiogenesis. Beside malignant and stromal cells, local immune cells shape VEGF signaling in the tumor microenvironment. Aminobisphosphonates like zoledronic acid (Zol) are drugs known to inhibit osteoclast activity and bone resorption, but also have immunomodulatory and anti-tumor effects. These properties have previously been linked to the downregulation of VEGF and interference with tumor neo-angiogenesis...
December 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29212732/the-role-of-rituximab-in-chronic-lymphocytic-leukemia-treatment-and-the-potential-utility-of-biosimilars
#8
REVIEW
Jennifer R Brown, Florence Cymbalista, Jeff Sharman, Ira Jacobs, Pilar Nava-Parada, Anthony Mato
Chronic lymphocytic leukemia (CLL) is managed with observation for asymptomatic or clinically silent disease; pharmacologic intervention is generally required for symptomatic patients with clinically significant adenopathy or cytopenia. In the front-line treatment of CLL, the current standard-of-care includes chemotherapy in combination with an anti-CD20 monoclonal antibody (e.g., rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the evolving treatment paradigm toward targeted therapy, it is likely that rituximab (plus chemotherapy), with or without targeted agents, will retain a significant role in CLL treatment...
December 6, 2017: Oncologist
https://www.readbyqxmd.com/read/29212628/mobile-health-intervention-to-increase-oral-cancer-therapy-adherence-in-patients-with-chronic-myeloid-leukemia-the-remind-system-clinical-feasibility-and-acceptability-assessment
#9
Amanda Pereira-Salgado, Jennifer A Westwood, Lahiru Russell, Anna Ugalde, Bronwen Ortlepp, John F Seymour, Phyllis Butow, Lawrence Cavedon, Kevin Ong, Sanchia Aranda, Sibilah Breen, Suzanne Kirsa, Andrew Dunlevie, Penelope Schofield
BACKGROUND: Optimal dosing of oral tyrosine kinase inhibitor therapy is critical to treatment success and survival of patients with chronic myeloid leukemia (CML). Drug intolerance secondary to toxicities and nonadherence are significant factors in treatment failure. OBJECTIVE: The objective of this study was to develop and pilot-test the clinical feasibility and acceptability of a mobile health system (REMIND) to increase oral drug adherence and patient symptom self-management among people with CML (chronic phase)...
December 6, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/29210593/front-line-treatment-of-patients-with-chronic-lymphocytic-leukemia-a-systematic-review-and-network-meta-analysis
#10
Yingxin Xu, Kyle Fahrbach, Emily Dorman, Simona Baculea, Sarah Côté, Suzy van Sanden, Joris Diels
AIM: A systematic literature review and network meta-analysis were conducted to determine the relative efficacy and safety of interventions for treatment-naive chronic lymphocytic leukemia patients, as comparative evidence is scarce. MATERIALS & METHODS: Relative treatment effects of progression-free survival, overall survival and safety outcomes were estimated via network meta-analysis based on data identified via systematic literature review. RESULTS: Ibrutinib was superior in all pairwise comparisons for progression-free survival (probability to be better [P] range: overall population: 69-100%; fludarabine-ineligible population: 69-100%) and overall survival (P range: overall: 89-100%; fludarabine-ineligible: 91-100%) and had the highest probability of being best for all outcomes...
December 6, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/29169241/gut-reactions-how-the-blood-brain-barrier-connects-the-microbiome-and-the-brain
#11
Aric F Logsdon, Michelle A Erickson, Elizabeth M Rhea, Therese S Salameh, William A Banks
A growing body of evidence indicates that the microbiome interacts with the central nervous system (CNS) and can regulate many of its functions. One mechanism for this interaction is at the level of the blood-brain barriers (BBBs). In this minireview, we examine the several ways the microbiome is known to interact with the CNS barriers. Bacteria can directly release factors into the systemic circulation or can translocate into blood. Once in the blood, the microbiome and its factors can alter peripheral immune cells to promote interactions with the BBB and ultimately with other elements of the neurovascular unit...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29105850/cost-effectiveness-analysis-of-interventions-for-prevention-of-invasive-aspergillosis-among-leukemia-patients-during-hospital-construction-activities
#12
Juan Felipe Combariza, Luis Fernando Toro, John Jairo Orozco, Marcos Arango
OBJECTIVES: Invasive Aspergillosis (IA) is a serious problem among hematological patients and it is associated with high mortality. This situation can worsen at times of hospital construction, however there are several preventive measures available. This work aims to define the cost-effectiveness of some of these interventions. PATIENTS AND METHODS: A decision tree model was used, it was divided into four arms according to each one of the interventions performed...
November 6, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29088977/pharmacologic-measures-in-the-prevention-of-left-ventricular-dysfunction-associated-with-molecular-targeted-therapies-in-the-treatment-of-cancer-patients
#13
Gil Awada, Evandro de Azambuja, Ahmad Awada
Left ventricular dysfunction (LVD) is an infrequent but significant side effect of certain molecular-targeted cancer therapies and may lead to treatment modification and impact on disease prognosis. There may be a role for beta blockers (BB), angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in the prevention of LVD. Areas covered: There are multiple definitions for LVD based on clinical and/or imaging features. Molecular-targeted therapies cause reversible LVD. Therapies with well-reported LVD are inhibitors of human epidermal growth factor 2 (HER2), angiogenesis, Abelson murine leukemia viral oncogene homolog (ABL) and the proteasome...
November 1, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29049751/hope-as-a-predictor-of-anxiety-and-depressive-symptoms-following-pediatric-cancer-diagnosis
#14
Julie N Germann, David Leonard, Corey L Heath, Sunita M Stewart, Patrick J Leavey
To examine hope and its components of agency and pathways as predictors of anxiety and depressive symptoms in children receiving cancer treatment.  Sixty patients (mean standard deviation age = 13.3 (2.7); 57% male) completed Snyder's Hope Scales, the Children's Depression Inventory, and the State-Trait Anxiety Inventory at diagnosis and 3 month intervals for 1 year following pediatric cancer diagnosis. Parents also completed Snyder's Hope Scales. Linear mixed-effect regression was used to assess hope's role in longitudinal models of symptoms of depression and anxiety...
July 17, 2017: Journal of Pediatric Psychology
https://www.readbyqxmd.com/read/29046955/the-relationship-between-child-and-caregiver-sleep-in-acute-lymphoblastic-leukemia-maintenance
#15
Lauren C Daniel, Colleen M Walsh, Lisa J Meltzer, Lamia P Barakat, Jacqueline D Kloss
PURPOSE: The purposes of this study are to describe sleep quality and sleep disturbance among caregivers of children in the maintenance phase of acute lymphoblastic leukemia (ALL) and to examine the relationship between sleep quality, child sleep disturbance, and caregiver guilt and worry. METHODS: Caregivers of 68 children with ALL, ages 3 to 12 years old, completed measures of caregiver guilt and worry, caregiver sleep quality, and child's developmental history and sleep habits...
October 18, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29045268/early-nutrition-intervention-attenuates-weight-gain-for-pediatric-acute-lymphoblastic-leukemia-patients-in-maintenance-therapy
#16
Rachel Hill, Tyler Hamby, Lisa Bashore, Stefanie Rapisand, Kari Galipp, Kenneth Heym, W Paul Bowman
Obesity following treatment of pediatric acute lymphoblastic leukemia (ALL) has become a significant long-term concern. Excessive weight gain often occurs during treatment, particularly during induction and the first 6 months of maintenance therapy, and it may be potentially modifiable. This retrospective study aimed to evaluate the impact of an early, 3-visit nutrition intervention on weight gain during maintenance therapy in ALL patients. Medical records of the intervention group were compared with historical controls who were treated on the same ALL treatment protocols during an earlier time period...
October 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29031316/identifying-the-unmet-supportive-care-needs-with-concomitant-influencing-factors-in-adult-acute-leukemia-patients-in-china
#17
Fang-Fang Yu, Yan-Ni Bai, Hua He, Li Zhu, Rui-Li Zhang, Hong-Xia Jiao, Qiao-Yan Li, Ju-Fang Fu
PURPOSE: To understand the supportive care needs (SCNs), with associated influencing factors, related to five unmet need dimensions in adult Acute Leukemia (AL) patients, in China. METHODS: This multi-center cross-sectional study enrolled 340 pathologically confirmed adult, Chinese AL patients who were requested to complete a self-reported questionnaire, detailing demographic information, general status and physical functions, and Supportive Care Needs Survey-Short Form 34 (SCNS-SF34), revealing their unmet SCNs...
October 2017: European Journal of Oncology Nursing: the Official Journal of European Oncology Nursing Society
https://www.readbyqxmd.com/read/28991134/isolated-testicular-recurrence-of-aml-in-patients-with-chronic-gvhd-1-year-following-allogeneic-stem-cell-transplant
#18
Brian N Dang, Satiro De Oliveira, LaVette Bowles, Theodore B Moore
BACKGROUND: Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. DESIGN/METHOD: Case Series and review of the literature. RESULTS: We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD...
November 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28939454/outcome-and-minimal-residual-disease-monitoring-in-patients-with-t-16-21-acute-myelogenous-leukemia-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#19
Ya-Zhen Qin, Yao Chen, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Huan Chen, Xiao-Su Zhao, Kai-Yan Liu, Xiao-Jun Huang
Patients with t(16;21) acute myelogenous leukemia (AML) who receive chemotherapy have poor outcomes. The treatment efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) must be identified, and the usefulness of minimal residual disease (MRD) monitoring requires evaluation. Fourteen consecutive patients with t(16;21) AML undergoing allo-HSCT at our institution were included in this study. Translocation liposarcoma- ETS-related gene (TLS-ERG) transcript levels were serially monitored for a median of 15 months (range, 3-51 months) after allo-HSCT...
September 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28837377/economic-evaluation-of-rituximab-in-addition-to-standard-of-care-chemotherapy-for-adult-patients-with-acute-lymphoblastic-leukemia
#20
Julian Nam, Robert Milenkovski, Simon Yunger, Marc Geirnaert, Kristjan Paulson, Matthew Seftel
AIMS: Acute lymphoblastic leukemia (ALL) is an aggressive form of leukemia with a poor prognosis in adult patients. The addition of the monoclonal antibody rituximab to standard chemotherapy has been shown to improve survival in adults with ALL. However, it is unknown whether the addition of rituximab is cost-effective. The objective was to determine the economic impact of rituximab in addition to standard of care (SOC) chemotherapy vs SOC alone in newly-diagnosed Philadelphia chromosome-negative, CD20-positive, B-cell precursor ALL...
September 18, 2017: Journal of Medical Economics
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