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https://www.readbyqxmd.com/read/29227918/synthesis-anti-inflammatory-p38%C3%AE-map-kinase-inhibitory-activities-and-molecular-docking-studies-of-quinoxaline-derivatives-containing-triazole-moiety
#1
Sana Tariq, Ozair Alam, Mohd Amir
A new series of 3-[2-(5-mercapto-4-phenyl-4H-1,2,4-traiazol-3-yl)ethyl] quinoxalin-2(1H)-one (5a-v) derivatives was synthesized and subjected to in vitro evaluation for anti-inflammatory activity (BSA anti-denaturation assay) and p38α MAPK inhibition. Few selected compounds (5a, 5e, 5f, 5g, 5h, 5l, 5q and 5u) were studied for their in vivo anti-inflammatory activity, ulcerogenicity and lipid peroxidation potential. Compounds 5e and 5f were found to be the most active in the series showing 83.45% and 84.15% anti-inflammatory activity respectively when compared to diclofenac sodium (83...
December 2, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29223809/cadmium-induces-bnip3-dependent-autophagy-in-chicken-spleen-by-modulating-mir-33-ampk-axis
#2
Menghao Chen, Xiaojing Li, Ruifeng Fan, Jie Yang, Xi Jin, Sattar Hamid, Shiwen Xu
Cadmium (Cd), a widespread environmental pollutant, has toxic effects on organs including spleen. However, the underlying mechanisms of Cd induced spleen toxicity and the roles of micro-RNA (miRNA) in this process remain poorly understood. To investigate this, cadmium chloride (CdCl2, 10 mg/kg) was administered in the diet of chickens for 90 days. Electron microscopy, qPCR and Western blot were performed. Results showed that Cd exposure suppressed miR-33-5q which increased the levels of AMPK. Subsequently, significant decrease in AKT/mTOR signaling and HSP70 were observed...
December 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/29222326/acquired-ribosomopathies-in-leukemia-and-solid-tumors
#3
REVIEW
Adrianna Vlachos
A mutation in the gene encoding the small subunit-associated ribosomal protein RPS19, leading to RPS19 haploinsufficiency, is one of the ribosomal protein gene defects responsible for the rare inherited bone marrow failure syndrome Diamond Blackfan anemia (DBA). Additional inherited and acquired defects in ribosomal proteins (RPs) continue to be identified and are the basis for a new class of diseases called the ribosomopathies. Acquired RPS14 haploinsufficiency has been found to be causative of the bone marrow failure found in 5q- myelodysplastic syndromes...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222293/current-treatment-algorithm-for-the-management-of-lower-risk-mds
#4
REVIEW
Aristoteles Giagounidis
Lower risk myelodysplastic syndromes (MDS), defined as MDS with a Revised International Prognostic Scoring System score ≤3.5 points, will remain a challenging entity in 2018. Supportive care continues to be the linchpin of treatment, although the options to reduce transfusion needs are broadening. To achieve red blood cell transfusion independence in non-del(5q) patients, erythropoiesis-stimulating agents remain a mainstay of therapy as long as endogenous erythropoietin levels are <500 U/L (and preferably <200 U/L)...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29204428/case-of-gastric-neuroendocrine-carcinoma-showing-an-interesting-tumorigenic-pathway
#5
Noriyuki Uesugi, Ryo Sugimoto, Makoto Eizuka, Yasuko Fujita, Mitsumasa Osakabe, Keisuke Koeda, Takashi Kosaka, Shunichi Yanai, Kazuyuki Ishida, Akira Sasaki, Takayuki Matsumoto, Tamotsu Sugai
Here, we report a case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway. A 57-year-old Japanese woman presented with epigastric tenderness, and distal gastrectomy was performed. In the surgical specimen, histologically, the tumor tissue was composed of three subtypes of tumor components showing different histological architecture and cellular atypia, diagnosed as neuroendocrine tumor (NET) G2, NET G3, and neuroendocrine carcinoma (NEC) components. Immunohistochemically, the Ki-67-positive rates of NET G2, NET G3, and NEC components were 6...
November 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/29196078/allogeneic-stem-cell-transplantation-for-myelodysplastic-patients-with-a-5q-deletion
#6
Laurent Garderet, Dimitris Ziagkos, Anja van Biezen, Simona Iacobelli, Jürgen Finke, Johan Maertens, Liisa Volin, Per Ljungman, Patrice Chevallier, Jakob Passweg, Nicolaas Schaap, Dietrich Beelen, Arnon Nagler, Didier Blaise, Xavier Poiré, Ibrahim Yakoub-Agha, Stig Lenhoff, Charles Craddock, Rik Schots, Alessandro Rambaldi, Jaime Sanz, Pavel Jindra, Ghulam J Mufti, Marie Robin, Nicolaus Kröger
The deletion (5q) karyotype [del (5q)] in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities [del (5q)+] are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+. A total of 162 patients, of median age 54 (9-73) years, having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75)...
November 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29179485/cost-effectiveness-analysis-of-fecal-microbiota-transplantation-for-inflammatory-bowel-disease
#7
Ting Zhang, Jie Xiang, Bota Cui, Zhi He, Pan Li, Hai Chen, Lijuan Xu, Guozhong Ji, Yongzhan Nie, Kaichun Wu, Daiming Fan, Guangming Huang, Jianling Bai, Faming Zhang
There is a lack of health economics evidence on the use of fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD). This study aims to evaluate the cost-effectiveness before (with conventional therapy) and after introducing FMT for treating IBD. 104 patients with IBD received FMT were recruited. Health status was evaluated by European dimension health table (ED-5Q). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB) were calculated by different age groups, genders, smoking status, and disease subtypes...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29165769/current-views-of-chromosomal-abnormalities-in-pediatric-acute-myeloid-leukemia-aml
#8
L-H Shi, P Ma, J-S Liu, Y Li, Y-F Wang, M-F Guo, W Liu
Chromosomal abnormalities are an attractive avenue for the screening of various disorders especially related to carcinogens like acute myeloid leukemia (AML). The cytogenetic findings like Karyotypic patterns are common in pediatric patients. On the other hand, monosomal karyotype (MK) and complex karyotype (CK) are more common in older patients. Further, recent studies have revealed direct proportion between the number of chromosome abnormalities and mortality rates in both pediatric as well as old patients affected by AML...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29156680/vemurafenib-resistance-via-de-novo-rbm-genes-mutations-and-chromosome-5-aberrations-is-overcome-by-combined-therapy-with-palbociclib-in-thyroid-carcinoma-with-braf-v600e
#9
Zeus A Antonello, Nancy Hsu, Manoj Bhasin, Giovanni Roti, Mukta Joshi, Paul Van Hummelen, Emily Ye, Agnes S Lo, S Ananth Karumanchi, Christine R Bryke, Carmelo Nucera
Purpose: Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF(V600E) represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF(WT/V600E)-positive PTC patient-derived cells with P16(-/-) (CDKN2A(-/-))...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137233/outcome-of-patients-treated-for-myelodysplastic-syndromes-with-5q-deletion-after-failure-of-lenalidomide-therapy
#10
Thomas Prebet, Thomas Cluzeau, Sophie Park, Mikkael A Sekeres, Ulrich Germing, Lionel Ades, Uwe Platzbecker, Katharina Gotze, Norbert Vey, Esther Oliva, Mary M Sugrue, Cecile Bally, Charikleia Kelaidi, Najla Al Ali, Pierre Fenaux, Steven D Gore, Rami Komrokji
While lenalidomide (LEN) is the standard of care for the lower-risk myelodysplastic syndromes (MDS) patients with deletion 5q, 35% will not respond to or do not tolerate the drug. Moreover, most of the patients will lose their response after a few years. Defining the outcome of patients with LEN failure and determining the impact of subsequent therapies is therefore important to develop alternative strategies. Based on an international collaboration, we were able to compile a total of 392 patient cases of lower-risk MDS patients with 5q deletion and to analyze their outcome after failure of lenalidomide...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29118268/azacitidine-in-lower-risk-myelodysplastic-syndromes-a-meta-analysis-of-data-from-prospective-studies
#11
Rami Komrokji, Arlene S Swern, David Grinblatt, Roger M Lyons, Magnus Tobiasson, Lewis R Silverman, Hamid Sayar, Ravi Vij, Albert Fliss, Nora Tu, Mary M Sugrue
BACKGROUND: After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS...
November 8, 2017: Oncologist
https://www.readbyqxmd.com/read/29116620/microwave-assisted-synthesis-antioxidant-and-antimicrobial-evaluation-of-2-indolinone-based-bis-1-2-3-triazole-derivatives
#12
Dongamanti Ashok, Srinivas Gundu, Vikas Kumar Aamate, Mohan Gandhi Devulapally
A series of 2-indolinone-based bis-1,2,3-triazole derivatives have been synthesized in excellent yields via microwave-assisted, copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction of O-, N-propargylated indolinone derivatives with in situ generated organic azides. The antioxidant activity of the synthesized compounds was evaluated by DPPH, NO and [Formula: see text] radical scavenging methods. Among the compounds screened for antioxidant activity, compounds 5e, 5f and 5o showed excellent radical scavenging activity more than the standard drugs ascorbic acid and BHT...
November 7, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/29108298/myelodysplastic-syndromes-advantages-of-a-combined-cytogenetic-and-molecular-diagnostic-workup
#13
Elena Ciabatti, Angelo Valetto, Veronica Bertini, Maria Immacolata Ferreri, Alice Guazzelli, Susanna Grassi, Francesca Guerrini, Iacopo Petrini, Maria Rita Metelli, Maria Adelaide Caligo, Simona Rossi, Sara Galimberti
In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29079134/impact-of-chromosome-alterations-genetic-mutations-and-clonal-hematopoiesis-of-indeterminate-potential-chip-on-the-classification-and-risk-stratification-of-mds
#14
REVIEW
Bani Bandana Ganguly, Debasis Banerjee, Mohan B Agarwal
The advent of technological development has undoubtedly advanced biological and molecular inputs for better understanding the heterogeneous hematopoietic pre-malignant disorder of the stem cells known as myelodysplastic syndromes (MDS). Chromosomal rearrangements, including del(3q/5q/7q/11q/12p/20q), loss of 5/7/Y, trisomy 8/19, i(17q), etc. frequently detected in MDS with variable frequencies and combinations, are the integral components of the 5-tier risk-stratification and WHO-2016 classification. Observations on mutations in genes involved in RNA-splicing, DNA methylation, chromatin modification, transcription factor, signal transduction/kinases, RAS pathway, cohesin complex, DNA repair and other pathways have given insights in independent effects and biological interaction of co-occurrence on disease-phenotype and treatment outcome...
October 16, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29052049/photophysicochemical-calf-thymus-dna-binding-and-in-vitro-photocytotoxicity-properties-of-tetra-morpholinoethoxy-substituted-phthalocyanines-and-their-water-soluble-quaternized-derivatives
#15
Halit Koçan, Kerem Kaya, İbrahim Özçeşmeci, B Şebnem Sesalan, Meltem Göksel, Mahmut Durmuş, Ayfer Kalkan Burat
In this study, morpholinoethoxy-substituted metal-free (3), zinc(II) (4) and indium(III) (5) phthalocyanines were synthesized. These phthalocyanines were converted to their water-soluble quaternized derivatives (3Q-5Q) using excess methyl iodide as a quaternization agent. All these phthalocyanines (Pcs) were characterized by elemental analysis and different spectroscopic methods such as FT-IR, (1)H NMR, UV-Vis and mass spectrometry. The photophysical and photochemical properties such as fluorescence and generation of singlet oxygen were investigated for determination of these phthalocyanines as photosensitizers in photodynamic therapy (PDT) applications...
December 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29025586/prognostic-classification-of-mds-is-improved-by-the-inclusion-of-fish-panel-testing-with-conventional-cytogenetics
#16
Prajakta Kokate, Rupa Dalvi, Neeraja Koppaka, Swarna Mandava
Cytogenetics is a critical independent prognostic factor in myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ hybridization (FISH) Panel Testing are extensively used for the prognostic stratification of MDS, although the FISH test is not yet a bona fide component of the International Prognostic Scoring System (IPSS). The present study compares the utility of CC and FISH to detect chromosomal anomalies and in prognostic categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/-7q, +8 and -20q was performed on whole blood or bone marrow samples from 136 patients with MDS...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28989590/cytogenetic-abnormalities-in-myelodysplastic-syndromes-an-overview
#17
REVIEW
Mohammad Faizan Zahid, Umair Arshad Malik, Momena Sohail, Irfan Nazir Hassan, Sara Ali, Muhammad Hamza Saad Shaukat
Karyotype is one of the main constituents of the International Prognostic Scoring System (IPSS) and revised-IPSS that are the cornerstones for the prognostication of patients with myelodysplastic syndromes (MDS). Del(5q), -7/del(7q), +8 and -Y are among the most extensively studied cytogenetic abnormalities in MDS. The same applies for normal karyotype. There are hundreds of other rare cytogenetic abnormalities that have been reported in MDS, included but not limited to -X, 3q abnormalities, +13/del(13q), i(17q), +21/-21...
July 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28983837/treatment-advances-in-spinal-muscular-atrophy
#18
REVIEW
Diana Bharucha-Goebel, Petra Kaufmann
PURPOSE OF REVIEW: Spinal muscular atrophy (SMA) is a genetic disorder of motor neurons in the anterior horns of the spinal cord and brainstem that results in muscle atrophy and weakness. SMA is an autosomal recessive disease linked to deletions of the SMN1 gene on chromosome 5q. Humans have a duplicate gene (SMN2) whose product can mitigate disease severity, leading to the variability in severity and age of onset of disease, and is therefore a target for drug development. RECENT FINDINGS: Advances in preclinical and clinical trials have paved the way for novel therapeutic options for SMA patients, including many currently in clinical trials...
October 6, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28983059/pro-inflammatory-proteins-s100a9-and-tnf%C3%AE-suppress-erythropoietin-elaboration-in-myelodysplastic-syndromes
#19
Thomas Cluzeau, Kathy L McGraw, Brittany Irvine, Erico Masala, Lionel Ades, Ashley A Basiorka, Jaroslaw P Maciejewski, Patrick Auberger, Sheng Wei, Pierre Fenaux, Valeria Santini, Alan List
Accumulating evidence implicates innate immune activation in the pathobiology of myelodysplastic syndromes. A key myeloid related inflammatory protein, S100A9, serves as a Toll-like receptor ligand regulating TNFα and IL-1β production. The role of MDS-related inflammatory proteins in endogenous Epo regulation and response to erythroid stimulating agents or lenalidomide has not been investigated. The HepG2 hepatoma cell line was used to investigate in vitro Epo elaboration. Serum collected from 311 MDS patients were investigated (125 prior to erythroid stimulating agents and 186 prior to lenalidomide)...
October 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28982058/transcriptome-analysis-of-cd34-cells-from-myelodysplastic-syndrome-patients
#20
Ruiming Ou, Jing Huang, Huijuan Shen, Zhi Liu, Yangmin Zhu, Qi Zhong, Liling Zheng, Mengdong Yao, Yanling She, Shanyao Zhou, Rui Chen, Cheng Li, Qing Zhang, Shuang Liu
The myelodysplastic syndrome (MDS) represents a heterogeneous group of clonal hematologic stem cell disorders with the characteristic of ineffective hematopoiesis leading to low blood counts, and a risk of progression to acute myeloid leukemia (AML). To understand specific molecular characteristics of different MDS subtypes with del(5q), we analyzed the gene expression profiles of CD34+ cells from MDS patients of different databases and its enriched pathways. 44 genes, such as MME and RAG1, and eight related pathways were identified to be commonly changed, indicating their conserved roles in MDS development...
November 2017: Leukemia Research
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