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https://www.readbyqxmd.com/read/29445113/a-decade-of-progress-in-myelodysplastic-syndrome-with-chromosome-5q-deletion
#1
REVIEW
Alan List, Benjamin L Ebert, Pierre Fenaux
There are few instances in oncology where reciprocal clinical and laboratory translation studies have accelerated the understanding of disease biology and treatment more so than the decade following the Food and Drug Administration (FDA) approval of lenalidomide (Revlimid TM ; Celgene Corporation, Summit, NJ, USA) for the treatment of patients with myelodysplastic syndrome (MDS) and chromosome 5q deletion (del(5q)). Lenalidomide was approved by the FDA in December 2005 on the merits of a multicenter phase 2 study, which demonstrated sustained and prolonged transfusion independence in the majority of participants...
January 30, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29439733/measuring-empathy-in-pediatrics-validation-of-the-visual-care-measure
#2
Michele Arigliani, Luigi Castriotta, Anna Pusiol, Annachiara Titolo, Enrico Petoello, Alberto Brun Peressut, Elisabetta Miorin, Iana Elkina, Federico Marzona, Davide Cucchiaro, Elisa Spanghero, Matteo Pavan, Raffaele Arigliani, Stewart W Mercer, Paola Cogo
BACKGROUND: Empathy is a key element of "Patient and Family Centered Care", a clinical approach recommended by the American Academy of Pediatrics. However, there is a lack of validated tools to evaluate paediatrician empathy. This study aimed to validate the Visual CARE Measure, a patient rated questionnaire measuring physician empathy, in the setting of a Pediatric Emergency Department (ED). METHODS: The empathy of physicians working in the Pediatric ED of the University Hospital of Udine, Italy, was assessed using an Italian translation of the Visual Care Measure...
February 13, 2018: BMC Pediatrics
https://www.readbyqxmd.com/read/29435930/quantum-language-of-microrna-application-for-new-cancer-therapeutic-targets
#3
Yoichi Robertus Fujii
MicroRNA (miRNA) is the noncoding gene: therefore, the miRNA gene inheritably controls protein gene expression through transcriptional and post-transcriptional levels. Aberrant expression of miRNA genes causes various human diseases, especially cancers. Although cancer is a complex disease, cancer/miRNA implication has yet been grasped from the perspective of miRNA profile in bed side. Since miRNA is the mobile genetic element, the clinical verification of miRNA in microvesicle of blood is too much straggle to predict potential cancer/miRNA associations without bioinformatical computing...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29435294/therapy-associated-myelodysplastic-syndrome-with-monosomy-7-arising-in-a-muir-torre-syndrome-patient-carrying-setbp1-mutation
#4
David Ullman, Erin Baumgartner, Nicholas Wnukowski, Gabe Koenig, Fady M Mikhail, Peter Pavlidakey, Deniz Peker
Muir-Torre Syndrome (MTS) is a rare hereditary autosomal dominant cancer syndrome and is linked to hereditary non-polyposis colorectal carcinoma (Lynch Syndrome). Individuals develop various skin neoplasms in addition to colorectal, endometrial and upper gastrointestinal malignancies. Therapy-associated myelodysplastic syndrome (T-MDS) is an aggressive hematologic malignancy and is considered a pre-leukemic phase. T-MDS is associated with prior exposure to chemo- and radiotherapy that potentially results in DNA damage...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29429612/the-effect-of-lenalidomide-on-health-related-quality-of-life-in-patients-with-lower-risk-non-del-5q-myelodysplastic-syndromes-results-from-the-mds-005-study
#5
Valeria Santini, Antonio Almeida, Aristoteles Giagounidis, Uwe Platzbecker, Rena Buckstein, C L Beach, Shien Guo, Arman Altincatal, Chengqing Wu, Pierre Fenaux
BACKGROUND: The phase III MDS-005 study compared lenalidomide versus placebo in red blood cell transfusion-dependent (RBC-TD) patients with lower-risk non-del(5q) myelodysplastic syndromes (MDS), ineligible/refractory to erythropoiesis-stimulating agents. Lenalidomide-treated patients were more likely to achieve transfusion independence (TI) ≥ 8 weeks (26.9% vs. 2.5%; P < .001) and hemoglobin increase ≥ 1.5 g/dL (19.4% vs. 2.5%) versus placebo. PATIENTS AND METHODS: Patients were randomized 2:1 to oral lenalidomide 10 mg once daily or placebo once daily (both on 28-day cycles)...
February 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29411698/lenalidomide-in-non-deletion-5q-lower-risk-myelodysplastic-syndromes-a-glass-quarter-full-or-three-quarters-empty
#6
Rory M Shallis, Amer M Zeidan
No abstract text is available yet for this article.
February 7, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29411666/asxl1-mutations-in-aml-are-associated-with-specific-clinical-and-cytogenetic-characteristics
#7
Katerina Kakosaiou, Fotios Panitsas, Aggeliki Daraki, Maria Pagoni, Paraskevi Apostolou, Agapi Ioannidou, Ioanna Vlachadami, Theodoros Marinakis, Chara Giatra, Diamantina Vasilatou, Constantina Sambani, Vassiliki Pappa, Kalliopi N Manola
Mutations of ASXL1 are early events in acute myeloid leukemia (AML) leukemogenesis and have been associated with unfavorable prognosis. In this study, we investigated the type and frequency of ASXL1 mutations in a large cohort of patients with de novo or secondary AML (s-AML) and looked for correlations with cytogenetic findings and disease features. ASXL1 mutations were associated with older age, s-AML and higher peripheral leukocytosis. We observed more frequent co-occurrence of ASXL1 mutations with trisomy 8 and chromosome 11 aberrations but a negative correlation with myelodysplastic syndromes (MDS)-related cytogenetic abnormalities, especially -5/del(5q) and -7/del(7q)...
February 7, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29408805/ribonuclease-inhibitor-1-regulates-erythropoiesis-by-controlling-gata1-mrna-translation
#8
Vijaykumar Chennupati, Diogo Ft Veiga, Kendle M Maslowski, Nicola Andina, Aubry Tardivel, Eric Chi-Wang Yu, Martina Stilinovic, Cedric Simillion, Michel A Duchosal, Manfredo Quadroni, Irene Roberts, Vijay G Sankaran, H Robson MacDonald, Nicolas Fasel, Anne Angelillo-Scherrer, Pascal Schneider, Trang Hoang, Ramanjaneyulu Allam
Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anaemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anaemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor (RNH1) is an ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases...
February 6, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29377069/megakaryocytes-harbour-the-del-5q-abnormality-despite-complete-clinical-and-cytogenetic-remission-induced-by-lenalidomide-treatment
#9
Christian Scharenberg, Monika Jansson, Leonie Saft, Eva Hellström-Lindberg
The mechanisms underlying lenalidomide-resistance of del(5q) MDS stem cells remain to be elucidated and may include cell-intrinsic as well as microenvironmental causes. Abnormal hypolobated megakaryocytes constitute one of the hallmarks of del(5q) MDS. We hypothesized that these cells have potential implications for the regulation of haematopoietic stem cells (HSC) similarly to what has recently been described for megakaryocytes in the murine system. Therefore, we conducted a study to determine the response of abnormal hypolobated megakaryocytes to lenalidomide therapy...
January 29, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29375856/acute-lymphoblastic-leukemia-secondary-to-myeloproliferative-neoplasms-or-after-lenalidomide-exposure
#10
Ahmad Alhuraiji, Kiran Naqvi, Yang O Huh, Coty Ho, Srdan Verstovsek, Prithviraj Bose
Philadelphia-negative (Ph-) myeloproliferative neoplasms (MPN) do rarely transform to acute lymphoblastic leukemia (ALL). While causality is difficult to establish, a few cases of ALL arising after exposure to lenalidomide for registered indications (multiple myeloma, myelodysplastic syndrome with 5q deletion) have been described in the literature.
January 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29365392/-gene-mutations-from-511-myelodysplastic-syndromes-patients-performed-by-targeted-gene-sequencing
#11
B Li, J Y Wang, J Q Liu, Z X Shi, S L Peng, H J Huang, T J Qin, Z F Xu, Y Zhang, L W Fang, H L Zhang, N B Hu, L J Pan, S Q Qu, Z J Xiao
Objective: To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients. Methods: A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed. Results: Eighty-three distinct mutant genes were found in 511 patients with MDS. Amongst these, the most frequent mutations was associated with epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) , transcription factors (24%) and cell cycle/apoptosis (17%) ...
December 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29359320/refining-remission-evaluation-in-mds-with-isolated-del-5q
#12
EDITORIAL
Marie Bill, Eigil Kjeldsen
No abstract text is available yet for this article.
January 23, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29340104/somatic-mutation-dynamics-in-mds-patients-treated-with-azacitidine-indicate-clonal-selection-in-patients-responders
#13
Kamila Polgarova, Karina Vargova, Vojtech Kulvait, Nina Dusilkova, Lubomir Minarik, Zuzana Zemanova, Michal Pesta, Anna Jonasova, Tomas Stopka
Azacitidine (AZA) for higher risk MDS patients is a standard therapy with limited durability. To monitor mutation dynamics during AZA therapy we utilized massive parallel sequencing of 54 genes previously associated with MDS/AML pathogenesis. Serial sampling before and during AZA therapy of 38 patients (reaching median overall survival 24 months (Mo) with 60% clinical responses) identified 116 somatic pathogenic variants with allele frequency (VAF) exceeding 5%. High accuracy of data was achieved via duplicate libraries from myeloid cells and T-cell controls...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29331635/sotatercept-with-long-term-extension-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-a-phase-2-dose-ranging-trial
#14
Rami Komrokji, Guillermo Garcia-Manero, Lionel Ades, Thomas Prebet, David P Steensma, Joseph G Jurcic, Mikkael A Sekeres, Jesus Berdeja, Michael R Savona, Odile Beyne-Rauzy, Aspasia Stamatoullas, Amy E DeZern, Jacques Delaunay, Gautam Borthakur, Robert Rifkin, Thomas E Boyd, Abderrhamane Laadem, Bond Vo, Jennie Zhang, Marie Puccio-Pick, Kenneth M Attie, Pierre Fenaux, Alan F List
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin receptor type IIA fusion protein that acts as a ligand trap to neutralise negative regulators of late-stage erythropoiesis. The aim of the study was to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label, multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in the USA and France...
January 10, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29322849/safety-profile-of-lenalidomide-in-patients-with-lower-risk-myelodysplastic-syndromes-without-del-5q-results-of-a-phase-3-trial
#15
Antonio Almeida, Pierre Fenaux, Guillermo Garcia-Manero, Stuart L Goldberg, Stefanie Gröpper, Anna Jonasova, Norbert Vey, Carmen Castaneda, Jianhua Zhong, C L Beach, Valeria Santini
The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes (MDS) patients with del(5q) is well-established, but less is known in non-del(5q) patients. We provide safety data from a randomized, phase 3 trial evaluating lenalidomide in 239 patients with lower-risk non-del(5q) MDS ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with placebo, lenalidomide was associated with a higher incidence of grade 3-4 treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection (p = ...
January 11, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29304771/high-bcar1-expression-is-associated-with-early-psa-recurrence-in-erg-negative-prostate-cancer
#16
Asmus Heumann, Nina Heinemann, Claudia Hube-Magg, Dagmar S Lang, Katharina Grupp, Martina Kluth, Sarah Minner, Christina Möller-Koop, Markus Graefen, Hans Heinzer, Maria Christina Tsourlakis, Waldemar Wilczak, Corinna Wittmer, Frank Jacobsen, Hartwig Huland, Ronald Simon, Thorsten Schlomm, Guido Sauter, Stefan Steurer, Patrick Lebok, Andrea Hinsch
BACKGROUND: Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. METHODS: To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples. BCAR1 expression levels were compared with clinical characteristics, PSA recurrence, molecular subtype defined by ERG status and 3p, 5q, 6q and PTEN deletion. RESULTS: BCAR1 staining was barely detectable in normal prostate glands but seen in 77...
January 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29301237/synthesis-and-smo-activity-of-some-novel-benzamide-derivatives
#17
Huaiwei Ding, Kai Chen, Bingke Song, Chenglong Deng, Wei Li, Li Niu, Mengxuan Bai, Hongrui Song, Lijuan Zhang
Two series of benzamides compounds bearing piperidine groups were synthesized and the Gli-luc luciferase activity was screened by Gys-luc luciferase gene detection method. Compound 5q showed promising inhibition of hedgehog (Hh) signaling pathway. To further verify whether the Hh inhibitory activities of the target compounds are derived from their inhibition to the Smoothened (Smo) receptor, the compounds with good potency were evaluated in a fluorescence competitive displacement assays, the results showed the Smo inhibitory potency of these compounds correlated well with their Hh inhibition, which suggested that the observed Hh activity was driven by Smo inhibitors...
December 31, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29296812/loss-of-mdia1-causes-neutropenia-via-attenuated-cd11b-endocytosis-and-increased-neutrophil-adhesion-to-the-endothelium
#18
Yang Mei, Gong Feng, Nina Rahimi, Baobing Zhao, Jingxin Zhang, Lan Cao, Jing Yang, Juehua Gao, Yihua Chen, Ronen Sumagin, William A Muller, Ling Zhang, Peng Ji
Formin protein mDia1 is involved in actin polymerization and plays important roles in the migration and adhesion of hematopoietic cells. The mDia1 encoding gene is located on chromosome 5q, which is commonly deleted in patients with del(5q) myelodysplastic syndromes (MDSs). We previously reported that mice with mDia1 deficiency developed neutropenia that closely mimics MDS. However, the mechanism of neutropenia in these mice and patients with del(5q) MDS remains incompletely defined. Here, we reveal that mDia1 knockout mice show cell-autonomously increased CD11b expression on neutrophils in the peripheral blood and bone marrow...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295644/coincidence-of-5q-deletion-and-the-jak2v617f-mutation-report-of-two-patients-with-overlapping-myelodysplastic-and-myeloproliferative-features-and-review-of-the-literature
#19
Susanne Bürki, Evgenii Shumilov, Nicolas Bonadies, Johanna Flach, Myriam Legros, Yara Banz, Elisabeth Oppliger-Leibundgut, Martin Fiedler, Anne Angelillo-Scherrer, Alicia Rovo, Ulrike Bacher
No abstract text is available yet for this article.
January 3, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29273277/novel-bicd2-mutation-in-a-japanese-family-with-autosomal-dominant-lower-extremity-predominant-spinal-muscular-atrophy-2
#20
Mieko Yoshioka, Naoya Morisada, Daisaku Toyoshima, Hajime Yoshimura, Hisahide Nishio, Kazumoto Iijima, Yasuhiro Takeshima, Tomoko Uehara, Kenjiro Kosaki
INTRODUCTION: The most common form of spinal muscular atrophy (SMA) is a recessive disorder caused by SMN1 mutations in 5q13, whereas the genetic etiologies of non-5q SMA are very heterogenous and largely remain to be elucidated. We present a father and son with atrophy and weakness of the lower leg muscles since infancy. Genetic studies in this family revealed a novel BICD2 mutation causing autosomal dominant lower extremity-predominant SMA type 2. PATIENTS: The proband was the father, aged 30, and the son was aged 3...
December 19, 2017: Brain & Development
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