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https://www.readbyqxmd.com/read/27923497/in-vivo-anti-inflammatory-activity-and-docking-study-of-newly-synthesized-benzimidazole-derivatives-bearing-oxadiazole-and-morpholine-rings
#1
Ankita Rathore, Raja Sudhakar, Mohamed Jawed Ahsan, Abuzer Ali, Naidu Subbarao, Surender Singh Jadav, Sadiq Umar, M Shahar Yar
In search of potential therapeutics for inflammatory disease, we report herein the synthesis, characterization and anti-inflammatory activities of a new series of 1-{(5-substituted-1,3,4-oxadiazol-2-yl)methyl}-2-(morpholinomethyl)-1H-benzimidazoles (5a-r). The anti-inflammatory activity of the compounds was evaluated using carrageenan induced rat paw edema test. Some compounds showed excellent anti-inflammatory activity in carrageenan induced rat paw edema test. 1-{(5-(2-Chlorophenyl)-1,3,4-oxadiazol-2-yl)methyl}-2-(morpholinomethyl)-1H-benzimidazole (5g) showed maximum anti-inflammatory (74...
November 29, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27914067/5q-syndrome-like-features-as-the-first-manifestation-of-myelodysplastic-syndrome-in-a-patient-with-an-unbalanced-whole-arm-translocation-der-5-19-p10-q10
#2
Hiroshi Ureshino, Haruna Kizuka, Kana Kusaba, Haruhiko Sano, Atsujiro Nishioka, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before...
December 2, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27910026/recurrent-cytogenetic-abnormalities-in-myelodysplastic-syndromes
#3
Meaghan Wall
Cytogenetic analysis has an essential role in diagnosis, classification, and prognosis of myelodysplastic syndromes (MDS). Some cytogenetic abnormalities are sufficiently characteristic of MDS to be considered MDS defining in the appropriate clinical context. MDS with isolated del(5q) is the only molecularly defined MDS subtype. The genes responsible for many aspects of 5q- syndrome, the distinct clinical phenotype associated with this condition, have now been identified. Cytogenetics forms the cornerstone of the most widely adopted prognostic scoring systems in MDS, the international prognostic scoring system (IPSS) and the revised international prognostic scoring system (IPPS-R)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27884971/progression-in-patients-with-low-and-intermediate1-risk-del-5q-myelodysplastic-syndromes-is-predicted-by-a-limited-subset-of-mutations
#4
Christian Scharenberg, Valentina Giai, Andrea Pellagatti, Leonie Saft, Marios Dimitriou, Monica Jansson, Martin Jädersten, Alf Grandien, Iyadh Douagi, Donna S Neuberg, Katarina LeBlanc, Jacqueline Boultwood, Mohsen Karimi, Sten Eirik W Jacobsen, Petter S Woll, Eva Hellström-Lindberg
A high proportion of patients with lower-risk del(5q) myelodysplastic syndromes (MDS) will respond to treatment with lenalidomide. Median duration of transfusion-independence is 2 years with some long-lasting responses, but almost 40% of patients progress to acute leukemia by 5 years after start of treatment. Mechanisms underlying disease progression other than the well-established finding of small TP53-mutated subclones at diagnosis remain unclear. We studied a longitudinal cohort of 35 low- and intermediate-1-risk del(5q) patients treated with lenalidomide (n=22) or not (n=13) by flow cytometric surveillance of hematopoietic stem and progenitor cells (HSPC) subsets, targeted sequencing of mutational patterns, and changes in the bone marrow microenvironment...
November 24, 2016: Haematologica
https://www.readbyqxmd.com/read/27883945/recent-advances-in-the-treatment-of-lower-risk-non-del-5q-myelodysplastic-syndromes-mds
#5
REVIEW
Antonio Almeida, Pierre Fenaux, Alan F List, Azra Raza, Uwe Platzbecker, Valeria Santini
Patients with lower-risk myelodysplastic syndromes (MDS) are affected primarily by symptoms of chronic anemia and fatigue rather than progression to acute myeloid leukemia. Severe thrombocytopenia, although less common in lower-risk MDS, is associated with increased risk of bleeding. For anemic patients, the principal aim of treatment is to improve anemia and decrease red blood cell transfusions. For transfusion-dependent patients with lower-risk MDS without chromosome 5q deletion [non-del(5q) MDS], there are limited effective treatments...
November 13, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27872730/diagnosis-of-del-5q-mds-14-years-after-jak-2-positive-pv-appearance-complete-remission-of-both-diseases-with-lenalidomide-monotherapy
#6
Antonella Vaccarino, Irene Dogliotti, Fabio Marletto, Andrea Demarchi, Mario Bazzan
This is the report of the clinical case of a patient who presents the association of a JAK-2 positive chronic myeloproliferative neoplasia to a subsequent 5q- myelodysplastic syndrome, developed after about 14 years from the first diagnosis. Patient's symptoms had rapidly worsened, and she became transfusion-dependent. Therapy with low-dose Lenalidomide quickly reduced the splenomegaly and completely brought white cells counts, haemoglobin, and platelets back to normal. After more than one year from the start, blood cell count is still normal...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27870387/primary-myelofibrosis-2017-update-on-diagnosis-risk-stratification-and-management
#7
Ayalew Tefferi
: Disease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR or MPL mutation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression and shortened survival. DIAGNOSIS: Diagnosis is based on bone marrow morphology...
December 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27865701/polymorphisms-and-haplotypes-of-the-cyp2b6-detoxification-gene-in-the-predisposition-of-acute-myeloid-leukemia-aml-and-induction-of-its-cytogenetic-abnormalities
#8
Aggeliki Daraki, Katerina Kakosaiou, Sophia Zachaki, Constantina Sambani, Vassiliki Aleporou-Marinou, Panagoula Kollia, Kalliopi N Manola
CYP2B6 is a polymorphic detoxification gene which plays a vital role in the degradation of genotoxic compounds. In this study we hypothesized that inadequate detoxification due to CYP2B6 polymorphisms may contribute to AML. To evaluate the potential impact of CYP2B6 polymorphisms on AML development and induction of its specific chromosomal abnormalities we studied C(777)A and A(785)G polymorphisms for the first time in AML. Furthermore, we investigated the co-existence of the above polymorphisms with G(516)T polymorphism to determine the CYP2B6 high-risk haplotypes in AML susceptibility...
November 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27862375/concomitant-mds-with-isolated-5q-deletion-and-mgus-case-report-and-review-of-molecular-aspects
#9
Florian Nolte, Maximilian Mossner, Johann-Christoph Jann, Daniel Nowak, Tobias Boch, Nadine Zoe Müller, Wolf-Karsten Hofmann, Georgia Metzgeroth
Myelodysplastic syndromes (MDS) are considered oligoclonal hematopoietic stem cell disorders resulting in peripheral cytopenias and an increased risk of developing acute myeloid leukemia (AML). Anemia is present in the majority of cases requiring regular blood transfusion in most patients. The WHO subtype of MDS with isolated deletion (5q) is the first cytogenetically determined entity introduced in the classification of the MDS. This article is protected by copyright. All rights reserved.
November 15, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27856460/architectural-and-functional-heterogeneity-of-hematopoietic-stem-progenitor-cells-in-non-del-5q-myelodysplastic-syndromes
#10
Virginie Chesnais, Marie-Laure Arcangeli, Caroline Delette, Alice Rousseau, Hélène Guermouche, Carine Lefevre, Sabrina Bondu, M'boyba Diop, Meyling Cheok, Nicolas Chapuis, Laurence Legros, Sophie Raynaud, Lise Willems, Didier Bouscary, Evelyne Lauret, Olivier A Bernard, Olivier Kosmider, Françoise Pflumio, Michaela Fontenay
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders in which recurrent mutations define clonal hematopoiesis. The origin of the phenotypic diversity of non del(5q) MDS remains unclear. Here, we investigated the clonal architecture of the CD34+CD38- hematopoietic stem/progenitor cell (HSPC) compartment and interrogated dominant clones for MDS-initiating cells. We found that clones mainly accumulate mutations in a linear succession with retention of a dominant subclone. The clone detected in the long-term culture-initiating cell (LTC-IC) compartment and that reconstitutes short-term human hematopoiesis in xenotransplantation models is usually the dominant clone, which gives rise to the myeloid and to a lesser extent to the lymphoid lineage...
November 16, 2016: Blood
https://www.readbyqxmd.com/read/27849184/ring-chromosome-7-a-rare-structural-abnormality-in-acute-myeloid-leukemia-aml
#11
Kristie Q Liu, Carlos A Tirado
Ring chromosomes, often leading to partial deletions, are found in about 2% of cases of acute myeloid leukemia (AML) and are typically associated with a poor prognosis. Herein, we present the case of a 62-year-old female who showed markedly hypercellular marrow with sheets of myeloblasts, monoblasts, and promonocytes, confirmed by flow cytometry and cases of AML with r(7) have been reported. Analysis of these cases demonstrated that r(7) was a sole abnormality in 20%, a primary abnormality in 14%, and in the context of a complex karyotype in 66%...
2016: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/27824902/efficacy-and-safety-of-lenalidomide-for-treatment-of-low-intermediate-1-risk-myelodysplastic-syndromes-with-or-without-5q-deletion-a-systematic-review-and-meta-analysis
#12
Xin-Yue Lian, Zhi-Hui Zhang, Zhao-Qun Deng, Pin-Fang He, Dong-Ming Yao, Zi-Jun Xu, Xiang-Mei Wen, Lei Yang, Jiang Lin, Jun Qian
BACKGROUND: Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS) with or without 5q deletion. However whether lenalidomide ultimately improves the overall survival (OS) of lower-risk MDS patients and reduces the progression to AML remains controversial. METHOD: A meta-analysis was conducted to examine the efficacy and safety of lenalidomide in the treatment of lower-risk MDS...
2016: PloS One
https://www.readbyqxmd.com/read/27801317/-the-clinical-features-cytogenetic-characteristics-and-survival-analysis-of-550-myelodysplastic-syndromes-in-a-single-center
#13
T T Zhang, A N Sun, J L Pan, D P Wu, H Y Qiu, X W Tang, M Miao, S N Chen
Objective: To retrospectively analyze the clinical features, cytogenetic characteristics and survival of 550 newly diagnosed myelodysplastic syndrome(MDS)patients. Method: By using WHO(2008)criterion for classification, the prognosis of stratification of 550 patients were evaluated according to the IPSS/WPSS/IPSS-R. Results: The median age was 57 years old(range: 12-89 years old). The ratio of male and female was 1.72. In all patients, the median hemoglobin level was 72(22-154)g/L, the median platelet count was 52(3-587)×10(9)/L and the median WBC was 2...
October 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27779547/molecular-analysis-of-single-tumor-glands-using-the-crypt-isolation-method-in-endometrial-carcinomas
#14
Takayuki Nagasawa, Tamotsu Sugai, Tadahiro Shoji, Wataru Habano, Toru Sugiyama
OBJECTIVE: Endometrial adenocarcinomas are characterized by the presence of many single tumor glands in which multiple genetic changes have accumulated. To elucidate the differences in molecular abnormalities among single tumor glands, individual tumor glands were analyzed and microsatellite alterations (loss of heterozygosity (LOH) and microsatellite instability [MSI]) were examined using the crypt isolation method in glands from each tumor from patients with endometrial carcinoma. METHODS: Twenty-five patients with endometrial adenocarcinoma who underwent surgery were included in this study...
November 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27769034/design-synthesis-and-biological-evaluation-of-1-2-4-triazolo-1-5-a-pyrimidines-as-potent-lysine-specific-demethylase-1-lsd1-kdm1a-inhibitors
#15
Shuai Wang, Li-Jie Zhao, Yi-Chao Zheng, Dan-Dan Shen, Er-Fei Miao, Xue-Peng Qiao, Li-Juan Zhao, Ying Liu, Ruilei Huang, Bin Yu, Hong-Min Liu
A new series of [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1 inhibitors were designed, synthesized, and further evaluated for their cytotoxicity against MGC-803, EC109, A549 and PC-9 cells as well as the ability of inhibiting LSD1. Some of these compounds showed potent inhibition toward LSD1 and selectively inhibited growth of A549 and PC-9 cells. Compound 6l potently inhibited growth of PC-9 cells (IC50 = 0.59 μM), about 4-fold more potent than 5-FU. Further SARs studies led to the identification of compounds 6l-m, which had good growth inhibition against all the tested cancer cell lines and were much more potent than 5-FU and GSK2879552...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27750403/immunophenotypic-cytogenetic-and-mutational-characterization-of-cell-lines-derived-from-myelodysplastic-syndrome-patients-after-progression-to-acute-myeloid-leukemia
#16
Anna Palau, Mar Mallo, Laura Palomo, Ines Rodríguez-Hernández, Jeannine Diesch, Diana Campos, Isabel Granada, Jordi Juncà, Hans G Drexler, Francesc Solé, Marcus Buschbeck
Leukemia cell lines have been widely used in the hematology field to unravel mechanistic insights and to test new therapeutic strategies. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases that are characterized by ineffective hematopoiesis and frequent progress to acute myeloid leukemia (AML). A few cell lines have been established from MDS patients after progression to AML but their characterization is incomplete. Here we provide a detailed description of the immunophenotypic profile of the MDS-derived cell lines SKK-1, SKM-1, F-36P; and MOLM-13...
October 17, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27750397/array-cgh-predicts-prognosis-in-plasma-cell-post-transplantation-lymphoproliferative-disorders
#17
Clémentine Sarkozy, Sophie Kaltenbach, Pierre Faurie, Danielle Canioni, Françoise Berger, Alexandra Traverse-Glehen, Hervé Ghesquieres, Gilles Salles, Emmanuel Bachy, Marie-Alexandra Alyanakian, Olivier Hermine, Bénédicte Neven, Elizabeth Macintyre, Serge Romana, Thierry Jo Molina, Felipe Suarez, Vahid Asnafi, Julie Bruneau
Plasma-cell post-transplantation lymphoproliferative disorder (PC-PTLD) is a rare monomorphic PTLD entity divided into plasma cell myeloma (PCM) and plasmacytoma-like lesion (PLL) PTLD. To date, there are no exhaustive published cytogenetic data on PC-PTLD. We report array-based comparative genomic hybridization (aCGH) of 10 cases of PCM and PLL-PTLD. Patients had received kidney (n=6), heart (n=2), lung (n=1) or bone marrow (n=1) transplantation. There were six men and median age at time of PTLD was 56.5 years (3-74)...
October 17, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27733775/epistasis-between-tifab-and-mir-146a-neighboring-genes-in-del-5q-mds
#18
M E Varney, K Choi, L Bolanos, S Christie, J Fang, L H Grimes, J P Maciejewski, J-I Inoue, D T Starczynowski
Leukemia accepted article preview online, 13 October 2016. doi:10.1038/leu.2016.276.
October 13, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27725596/progress-in-the-diagnosis-of-and-therapy-for-mds
#19
Yasuhito Nannya
The WHO classification system of MDS 4(th) edition was recently updated. This revision includes nomenclature changes, reflecting the policy of the revision team to emphasize morphological features over cytopenias. Other changes are 1) taking SF3B1 mutation status into account for the definition criteria of MDS-RS (ring sideroblasts), 2) allowing for one additional cytogenetic abnormality (excluding -7/del (7q)) to be diagnosed as 'MDS with isolated del (5q)', 3) sub-classifying MDS-U according to the reasons for being included in this category, and 4) changing the diagnostic rules for myeloid neoplasms with erythroid blast predominance...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27721163/deletion-5q-is-frequent-in-myelodysplastic-syndrome-mds-patients-diagnosed-with-interstitial-lung-diseases-ild-mayo-clinic-experience
#20
Rama Nanah, Darci Zblewski, Mrinal S Patnaik, Kebede Begna, Rhett Ketterling, Vivek N Iyer, William J Hogan, Mark R Litzow, Aref Al-Kali
A variety of interstitial Lung Diseases (ILD) have been described in patients with myelodysplastic syndromes (MDS) with possible etiologies including autoimmunity, drug related toxicity, and recurrent infections. A comprehensive study of ILD in MDS patients has not been previously performed. Out of 827 consecutive biopsy proven MDS patients seen at our institution from June 1970-May 2010, 18 (2%) were found to have ILD. There was no statistical significance in baseline characteristics between patients with ILD (ILD +) vs those without ILD (ILD-)...
October 3, 2016: Leukemia Research
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