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https://www.readbyqxmd.com/read/28741795/a-novel-molecular-mechanism-of-cellular-transformation-via-a-mutant-molecular-chaperone-in-myeloproliferative-neoplasms
#1
REVIEW
Marito Araki, Norio Komatsu
Deregulation of the cytokine-receptor signaling pathway plays a significant role in tumorigenesis. Such deregulation is frequently caused by alterations in the genes involved in the signaling pathway. At the end of 2013, recurrent somatic mutations in the calreticulin (CALR) gene that encodes a molecular chaperone were identified in a subset of patients with Philadelphia-chromosome negative myeloproliferative neoplasms (MPNs). This review focuses on the role of CALR mutations in the oncogenic transformations observed in MPNs...
July 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#2
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28730089/an-international-survey-of-classification-and-treatment-choices-for-group-d-retinoblastoma
#3
Christina Scelfo, Jasmine H Francis, Vikas Khetan, Thomas Jenkins, Brian Marr, David H Abramson, Carol L Shields, Jacob Pe'er, Francis Munier, Jesse Berry, J William Harbour, Andrey Yarovoy, Evandro Lucena, Timothy G Murray, Pooja Bhagia, Evelyn Paysse, Samuray Tuncer, Guillermo L Chantada, Annette C Moll, Tatiana Ushakova, David A Plager, Islamov Ziyovuddin, Carlos A Leal, Miguel A Materin, Xun-Da Ji, Jose W Cursino, Rodrigo Polania, Hayyam Kiratli, Charlotta All-Ericsson, Rejin Kebudi, Santosh G Honavar, Vicktoria Vishnevskia-Dai, Sidnel Epelman, Anthony B Daniels, Jeanie D Ling, Fousseyni Traore, Marco A Ramirez-Ortiz
AIM: To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS: An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28727136/a-multidimensional-view-of-racial-differences-in-access-to-prostate-cancer-care
#4
Craig Evan Pollack, Katrina A Armstrong, Nandita Mitra, Xinwei Chen, Katelyn R Ward, Archana Radhakrishnan, Michelle S Wong, Justin E Bekelman, Charles C Branas, Karin V Rhodes, David T Grande
BACKGROUND: Racial disparities in prostate cancer treatment and outcomes are widespread and poorly understood. In the current study, the authors sought to determine whether access to care, measured across multiple dimensions, contributed to racial differences in prostate cancer. METHODS: The Philadelphia Area Prostate Cancer Access Study (P(2) Access) included 2374 men diagnosed with localized prostate cancer between 2012 and 2014. Men were surveyed to assess their experiences accessing care (response rate of 51...
July 20, 2017: Cancer
https://www.readbyqxmd.com/read/28715553/validation-of-the-children-s-hospital-of-philadelphia-retinopathy-of-prematurity-chop-rop-model
#5
Gil Binenbaum, Gui-Shuang Ying, Lauren A Tomlinson
Importance: The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines. Objective: To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model's sensitivity for treatment-requiring ROP...
July 13, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28711932/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#6
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697706/improving-the-development-monitoring-and-reporting-of-stroke-rehabilitation-research-consensus-based-core-recommendations-from-the-stroke-recovery-and-rehabilitation-roundtable
#7
Marion F Walker, Tammy C Hoffmann, Marian C Brady, Catherine M Dean, Janice J Eng, Amanda J Farrin, Cynthia Felix, Anne Forster, Peter Langhorne, Elizabeth A Lynch, Kathryn A Radford, Katharina S Sunnerhagen, Caroline L Watkins
Recent reviews have demonstrated that the quality of stroke rehabilitation research has continued to improve over the last four decades but despite this progress, there are still many barriers in moving the field forward. Rigorous development, monitoring and complete reporting of interventions in stroke trials are essential in providing rehabilitation evidence that is robust, meaningful and implementable. An international partnership of stroke rehabilitation experts committed to develop consensus-based core recommendations with a remit of addressing the issues identified as limiting stroke rehabilitation research in the areas of developing, monitoring and reporting stroke rehabilitation interventions...
July 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/28697682/a-comfort-assessment-of-existing-cervical-orthoses
#8
Joe Langley, Silvia Pancani, Karen Kilner, Heath Reed, Andy Stanton, Nicola Heron, Simon Judge, Avril McCarthy, Susan Baxter, Claudia Mazzà, Christopher J McDermott
PURPOSE: identify location and intensity of discomfort experienced by healthy participants wearing cervical orthoses. METHOD: convenience sample of 34 healthy participants wore Stro II, Philadelphia, Headmaster, and AspenVista(®) cervical orthoses for four-hour periods. Participants reported discomfort level (scale 0-6) and location. RESULTS: participants reported mean discomfort for all orthoses over the four-hour test between 'a little discomfort' and 'very uncomfortable' (mean discomfort score=1...
July 12, 2017: Ergonomics
https://www.readbyqxmd.com/read/28687420/hepatic-adverse-event-profile-of-inotuzumab-ozogamicin-in-adult-patients-with-relapsed-or-refractory-acute-lymphoblastic-leukaemia-results-from-the-open-label-randomised-phase-3-ino-vate-study
#9
Hagop M Kantarjian, Daniel J DeAngelo, Anjali S Advani, Matthias Stelljes, Partow Kebriaei, Ryan D Cassaday, Akil A Merchant, Naohito Fujishima, Toshiki Uchida, Maria Calbacho, Anna A Ejduk, Susan M O'Brien, Elias J Jabbour, Hui Zhang, Barbara J Sleight, Erik R Vandendries, David I Marks
BACKGROUND: The INO-VATE study demonstrated efficacy and safety of inotuzumab ozogamicin versus standard care in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Here, we report the frequency of, and potential risk factors for, hepatotoxicity in patients in this trial and after treatment and subsequent haemopoietic stem-cell transplantation (HSCT). METHODS: In this open-label, phase 3, multicentre, international study, adults with relapsed or refractory, CD22-positive, Philadelphia chromosome (Ph)-positive or Ph-negative B-cell acute lymphoblastic leukaemia who were due to receive first or second salvage treatment were randomly assigned (1:1) via an interactive voice response system to receive inotuzumab ozogamicin (starting dose 1·8 mg/m(2) per cycle [0·8 mg/m(2) on day 1; 0·5 mg/m(2) on days 8 and 15 of a 21-28 day cycle for ≤6 cycles]) or standard care (either fludarabine plus cytarabine plus granulocyte colony-stimulating factor, mitoxantrone plus cytarabine, or high-dose cytarabine)...
July 4, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28687223/how-to-prevent-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-leukemia-and-myelodysplastic-syndrome
#10
REVIEW
N Yafour, F Beckerich, C E Bulabois, P Chevallier, E Daguindau, C Dumesnil, T Guillaume, A Huynh, S Masouridi Levrat, A L Menard, C Pautas, X Poiré, A Ravinet, M Michallet, A Bazarbachi
Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory hematological malignancies or with persistent molecular or radiological (PET-CT scan) residual disease. For high risk AML and myelodysplasia (MDS), a post transplant maintenance strategy is possible, using hypomethylating agents or tyrosine kinase inhibitors (TKI) anti-FLT3 when the target is present...
July 4, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28683103/combination-therapeutics-of-nilotinib-and-radiation-in-acute-lymphoblastic-leukemia-as-an-effective-method-against-drug-resistance
#11
Kamran Kaveh, Yutaka Takahashi, Michael A Farrar, Guy Storme, Marcucci Guido, Jamie Piepenburg, Jackson Penning, Jasmine Foo, Kevin Z Leder, Susanta K Hui
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI) therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR) in combination with TKI therapy overcome chemo-resistance...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28661715/patient-characteristics-and-temporal-trends-in-police-transport-of-blunt-trauma-patients-a-multicenter-retrospective-cohort-study
#12
Elinore J Kaufman, Sara F Jacoby, Catherine E Sharoky, Brendan G Carr, M Kit Delgado, Patrick M Reilly, Daniel N Holena
BACKGROUND: Police transport (PT) of penetrating trauma patients has the potential to decrease prehospital times for patients with life-threatening hemorrhage and is part of official policy in Philadelphia, Pennsylvania. We hypothesized that rates of PT of bluntly injured patients have increased over the past decade. METHODS: We used Pennsylvania Trauma Outcomes Study registry data from 2006-15 to identify bluntly injured adult patients transported to all 8 trauma centers in Philadelphia...
June 29, 2017: Prehospital Emergency Care
https://www.readbyqxmd.com/read/28654842/haploidentical-hematopoietic-stem-cell-transplantation-for-pediatric-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-the-imatinib-era
#13
Huan Chen, Kai-Yan Liu, Lan-Ping Xu, Yu-Hong Chen, Xiao-Hui Zhang, Yu Wang, Ya-Zhen Qin, Yan-Rong Liu, Yue-Yun Lai, Xiao-Jun Huang
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an important curative option for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who have a poor response to chemotherapy plus imatinib. For such children, if there are no matched related or unrelated donors, alternative donor transplantation may be a choice. The role of haploidentical donor (HID) HSCT in pediatric patients with Ph+ ALL has not been reported. The study population included pediatric patients with Ph+ ALL who underwent HID-HSCT...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28654205/driving-toward-precision-medicine-for-acute-leukemias-are-we-there-yet
#14
Clement Chung, Hilary Ma
Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not shown significant changes over the last few decades. In this review, we present a nonexhaustive key summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28644853/the-novel-phospholipid-mimetic-kpc34-is-highly-active-against-preclinical-models-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#15
Peter M Alexander, David L Caudell, Gregory L Kucera, Kristin M Pladna, Timothy S Pardee
Philadelphia chromosome positive B cell acute lymphoblastic leukemia (Ph+ ALL) is an aggressive cancer of the bone marrow. The addition of tyrosine kinase inhibitors (TKIs) has improved outcomes but many patients still suffer relapse and novel therapeutic agents are needed. KPC34 is an orally available, novel phospholipid conjugate of gemcitabine, rationally designed to overcome multiple mechanisms of resistance, inhibit the classical and novel isoforms of protein kinase C, is able to cross the blood brain barrier and is orally bioavailable...
2017: PloS One
https://www.readbyqxmd.com/read/28637980/satisfaction-with-dietary-life-affects-oral-health-related-quality-of-life-and-subjective-well-being-in-very-elderly-people
#16
Toshimitsu Iinuma, Yasumichi Arai, Midori Takayama, Michiyo Takayama, Yukiko Abe, Yusuke Osawa, Motoko Fukumoto, Yusuke Fukui, Yohei Shioda, Nobuyoshi Hirose, Kazuo Komiyama, Nobuhito Gionhaku
Age-related deterioration in physical and oral health reduces healthy life expectancy and is thus an important problem for very elderly people. We investigated the effects of satisfaction with dietary life (SDL) in everyday life on oral health-related quality of life (OHRQoL) and subjective well-being and examined associations between these factors. We evaluated 426 elders aged 85 years or older. All participants completed a questionnaire that inquired about age, gender, drinking status, body mass index, cognitive function, disability, and comorbidities, among other covariates...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28635971/exercise-among-women-with-ovarian-cancer-a-feasibility-and-pre-post-test-exploratory-pilot-study
#17
Xiaochen Zhang, Daniel McClean, Emily Ko, Mark A Morgan, Kathryn Schmitz
PURPOSE/OBJECTIVES: To establish the feasibility and acceptability of completing a higher dose of the planned physical activity volume among women with ovarian cancer, including those undergoing active treatment. 
. DESIGN: A pre-/post-test exercise intervention. All participants were asked to complete 225 minutes per week of physical activity for 26 weeks. Multiple supports were provided, including exercise DVDs, self-reported logs, and an objective physical activity tracker (Fitbit®)...
May 1, 2017: Oncology Nursing Forum
https://www.readbyqxmd.com/read/28631497/cost-effectiveness-of-blinatumomab-versus-salvage-chemotherapy-in-relapsed-or-refractory-philadelphia-chromosome-negative-b-precursor-acute-lymphoblastic-leukemia-from-a-us-payer-perspective
#18
Thomas E Delea, Jordan Amdahl, Diana Boyko, May Hagiwara, Zachary F Zimmerman, Janet L Franklin, Ze Cong, Guy Hechmati, Anthony Stein
OBJECTIVE: To evaluate the cost-effectiveness of blinatumomab (Blincyto) vs standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective. METHODS: The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs SOC...
July 11, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28627929/design-of-the-hptn-065-tlc-plus-study-a-study-to-evaluate-the-feasibility-of-an-enhanced-test-link-to-care-plus-treat-approach-for-hiv-prevention-in-the-united-states
#19
Theresa Gamble, Bernard Branson, Deborah Donnell, H Irene Hall, Georgette King, Blayne Cutler, Shannon Hader, David Burns, Jason Leider, Angela Fulwood Wood, Kevin G Volpp, Kate Buchacz, Wafaa M El-Sadr
Background/Aims HIV continues to be a major public health threat in the United States, and mathematical modeling has demonstrated that the universal effective use of antiretroviral therapy among all HIV-positive individuals (i.e. the "test and treat" approach) has the potential to control HIV. However, to accomplish this, all the steps that define the HIV care continuum must be achieved at high levels, including HIV testing and diagnosis, linkage to and retention in clinical care, antiretroviral medication initiation, and adherence to achieve and maintain viral suppression...
June 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28608976/tp53-mutation-does-not-confer-a-poor-outcome-in-adult-patients-with-acute-lymphoblastic-leukemia-who-are-treated-with-frontline-hyper-cvad-based-regimens
#20
Rashmi Kanagal-Shamanna, Preetesh Jain, Koichi Takahashi, Nicholas J Short, Guilin Tang, Ghayas C Issa, Farhad Ravandi, Guillermo Garcia-Manero, Cameron C Yin, Rajyalakshmi Luthra, Keyur P Patel, Joseph D Khoury, Guillermo Montalban-Bravo, Koji Sasaki, Tapan M Kadia, Gautam Borthakur, Marina Konopleva, Nitin Jain, Rebecca Garris, Sherry Pierce, William Wierda, Zeev Estrov, Jorge Cortes, Susan O'Brien, Hagop Kantarjian, Elias Jabbour
BACKGROUND: Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome. METHODS: TP53 mutation analysis was performed in 164 newly diagnosed adult patients with ALL using a combination of targeted amplicon-based next-generation sequencing and Sanger sequencing. RESULTS: TP53 mutations were detected in 25 patients (15%), with a median allelic frequency of 42.2% (range, 5...
June 13, 2017: Cancer
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