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leukemia and resistance insulin

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https://www.readbyqxmd.com/read/28757432/genetic-risk-of-prediabetes-and-diabetes-development-in-chronic-myeloid-leukemia-patients-treated-with-nilotinib
#1
Bruno Martino, Corrado Mammì, Claudia Labate, Silvia Rodi, Domenica Ielo, Manuela Priolo, Maurizio Postorino, Giovanni Tripepi, Francesca Ronco, Carmelo Laganà, Caterina Musolino, Marianna Greco, Giorgio La Nasa, Giovanni Caocci
Impaired fasting glucose (IFG) and type 2 diabetes (T2D) represents adverse events in Chronic Myeloid Leukemia (CML) patients treated with the second-generation tyrosine kinase inhibitor (TKI) nilotinib. A genetic risk score (uGRS) for the prediction of insulin resistance, consisting of 10 multiple single-nucleotide polymorphisms (SNPs), has been proposed. We evaluated the uGRS predictivity in 61 CML patients treated with nilotinib. Patients were genotyped for IRS1, GRB14, ARL15, PPARG, PEPD, ANKRD55/MAP3K1, PDGFC, LYPLAL1, RSPO3, and FAM13A1 genes...
July 28, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28549065/c-elegans-daf-16-foxo-interacts-with-tgf-%C3%A3-bmp-signaling-to-induce-germline-tumor-formation-via-mtorc1-activation
#2
Wenjing Qi, Yijian Yan, Dietmar Pfeifer, Erika Donner V Gromoff, Yimin Wang, Wolfgang Maier, Ralf Baumeister
Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28286608/meta-analysis-of-gene-expression-profiles-in-acute-promyelocytic-leukemia-reveals-involved-pathways
#3
Mahdi Jalili, Ali Salehzadeh-Yazdi, Saeed Mohammadi, Marjan Yaghmaie, Ardeshir Ghavamzadeh, Kamran Alimoghaddam
Background: Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood. Materials and Methods: In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28193268/adipokines-insulin-resistance-and-adiposity-as-a-predictors-of-metabolic-syndrome-in-child-survivors-of-lymphoma-and-acute-lymphoblastic-leukemia-of-a-developing-country
#4
Lourdes Barbosa-Cortés, Mardia López-Alarcón, Juan Manuel Mejía-Aranguré, Miguel Klünder-Klünder, María Del Carmen Rodríguez-Zepeda, Hugo Rivera-Márquez, Alan de la Vega-Martínez, Jorge Martin-Trejo, Juan Shum-Luis, Karina Solis-Labastida, Enrique López-Aguilar, Guadalupe Matute-González, Roberto Bernaldez-Rios
BACKGROUND: There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. METHODS: Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study...
February 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/27859423/from-obesity-to-cancer-a-review-on-proposed-mechanisms
#5
REVIEW
Zoya Tahergorabi, Majid Khazaei, Mitra Moodi, Elham Chamani
Nowadays, obesity is considered as a serious and growing global health problem. It is documented that the overweight and obesity are major risk factors for a series of noncommunicable diseases, and in recent years, the obesity-cancer link has received much attention. Numerous epidemiological studies have shown that obesity is associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment...
December 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27532210/igf1r-derived-pi3k-akt-signaling-maintains-growth-in-a-subset-of-human-t-cell-acute-lymphoblastic-leukemias
#6
Samuel Gusscott, Catherine E Jenkins, Sonya H Lam, Vincenzo Giambra, Michael Pollak, Andrew P Weng
Insulin-like growth factor 1 receptor (IGF1R) is a prevalent signaling pathway in human cancer that supports cell growth/survival and thus contributes to aggressive biological behavior. Much work has gone into development of IGF1R inhibitors; however, candidate agents including small molecule tyrosine kinase inhibitors and blocking antibodies have yet to fulfill their promise clinically. Understanding cellular features that define sensitivity versus resistance are important for effective patient selection and anticipation of outgrowth of a resistant clone...
2016: PloS One
https://www.readbyqxmd.com/read/27362350/acute-activation-of-metabolic-syndrome-components-in-pediatric-acute-lymphoblastic-leukemia-patients-treated-with-dexamethasone
#7
RANDOMIZED CONTROLLED TRIAL
Lidewij T Warris, Erica L T van den Akker, Marc B Bierings, Cor van den Bos, Christian M Zwaan, Sebastiaan D T Sassen, Wim J E Tissing, Margreet A Veening, Rob Pieters, Marry M van den Heuvel-Eibrink
Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone...
2016: PloS One
https://www.readbyqxmd.com/read/27327565/the-influence-of-antineoplastic-treatment-on-the-weight-of-survivors-of-childhood-cancer
#8
Julia Ferrari Carneiro Teixeira, Priscila Dos Santos Maia-Lemos, Mônica Dos Santos Cypriano, Luciana Pellegrini Pisani
PURPOSE: Obesity is a late effect in survivors of childhood cancer and correlates with chronic complications. Survivors of leukemia, brain tumors, and hematopoietic stem cell transplantation are more likely to develop obesity resulting from treatment modalities such as radiotherapy and glucocorticoids. This paper analyzes and integrates the current data available to health professionals in order to clarify strategies that can be used to treat and prevent obesity in childhood cancer survivors...
November 2016: Jornal de Pediatria
https://www.readbyqxmd.com/read/27149630/insulin-signaling-in-insulin-resistance-states-and-cancer-a-modeling-analysis
#9
Alessandro Bertuzzi, Federica Conte, Geltrude Mingrone, Federico Papa, Serenella Salinari, Carmela Sinisgalli
Insulin resistance is the common denominator of several diseases including type 2 diabetes and cancer, and investigating the mechanisms responsible for insulin signaling impairment is of primary importance. A mathematical model of the insulin signaling network (ISN) is proposed and used to investigate the dose-response curves of components of this network. Experimental data of C2C12 myoblasts with phosphatase and tensin homologue (PTEN) suppressed and data of L6 myotubes with induced insulin resistance have been analyzed by the model...
2016: PloS One
https://www.readbyqxmd.com/read/27094350/evaluation-of-endocrine-late-complications-in-childhood-acute-lymphoblastic-leukemia-survivors-a-report-of-a-single-center-experience-and-review-of-the-literature
#10
Cengiz Bayram, Neşe Yaralı, Fatma Demirel, Ali Fettah, Betül Tavil, Abdurrahman Kara, Bahattin Tunç
INTRODUCTION: Improvement in long-term survival in patients with acute lymphoblastic leukemia (ALL) in childhood has led to the need for monitorization of treatment-related morbidity and mortality. In the current study, we aimed to evaluate endocrine side effects of treatment in ALL survivors who were in remission for at least 2 years. METHODS: Sixty patients diagnosed with ALL, who were in remission for at least 2 years, were cross-sectionally evaluated for long-term endocrine complications...
March 1, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/26999465/late-effects-in-patients-with-fanconi-anemia-following-allogeneic-hematopoietic-stem-cell-transplantation-from-alternative-donors
#11
P Anur, D N Friedman, C Sklar, K Oeffinger, M Castiel, J Kearney, B Singh, S E Prockop, N A Kernan, A Scaradavou, R Kobos, K Curran, J Ruggiero, N Zakak, R J O'Reilly, F Boulad
Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD...
July 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/26984439/is-there-an-increased-risk-of-metabolic-syndrome-among-childhood-acute-lymphoblastic-leukemia-survivors-a-developing-country-experience
#12
Sonali Mohapatra, Deepak Bansal, A K Bhalla, Savita Verma Attri, Naresh Sachdeva, Amita Trehan, R K Marwaha
Data on metabolic syndrome (MS) in survivors of childhood acute lymphoblastic leukemia (ALL) from developing countries are lacking. The purpose of this single-center, uncontrolled, observational study was to assess the frequency of MS in our survivors. The survivors of ALL ≤15 years at diagnosis, who had completed therapy ≥2 years earlier, were enrolled. Anthropometric measurements (weight, height, waist circumference), biochemistry (glucose, insulin, triglycerides, high-density lipoprotein [HDL], thyroid function tests, C-reactive protein [CRP], magnesium), measurement of blood pressure, and Tanner staging were performed...
March 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/26919045/inflammation-promotes-expression-of-stemness-related-properties-in-hbv-related-hepatocellular-carcinoma
#13
Te-Sheng Chang, Chi-Long Chen, Yu-Chih Wu, Jun-Jen Liu, Yung Che Kuo, Kam-Fai Lee, Sin-Yi Lin, Sey-En Lin, Shui-Yi Tung, Liang-Mou Kuo, Ying-Huang Tsai, Yen-Hua Huang
The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induced inflammation, may play a crucial role. However, the mechanisms linking inflammation and stemness expression in HCC remain unclear. Here we demonstrated the distinct role of inflammatory mediators in expressions of stemness-related properties involving the pluripotent octamer-binding transcription factor 4 (OCT4) in cell migration and drug resistance of hepatitis B virus-related HCC (HBV-HCC)...
2016: PloS One
https://www.readbyqxmd.com/read/26869355/epigenetics-tet-proteins-and-hypoxia-in-epithelial-mesenchymal-transition-and-tumorigenesis
#14
Hsiao-Fan Chen, Kou-Juey Wu
Hypoxia in tumors is primarily a pathophysiologic consequence of structurally and functionally disturbed microcirculation with inadequate supply of oxygen. Tumor hypoxia is strongly associated with tumor propagation, malignant progression, and resistance to therapy. Aberrant epigenetic regulation plays a crucial role in the process of hypoxia-driven malignant progression. Convert of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease...
March 2016: BioMedicine
https://www.readbyqxmd.com/read/26824435/associations-between-metabolic-risk-factors-and-the-hypothalamic-volume-in-childhood-leukemia-survivors-treated-with-cranial-radiotherapy
#15
Cecilia Follin, Sanaz Gabery, Åsa Petersén, Pia C Sundgren, Isabella Björkman-Burtcher, Jimmy Lätt, Peter Mannfolk, Eva Marie Erfurth
Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation...
2016: PloS One
https://www.readbyqxmd.com/read/26515727/stromal-cells-promote-anti-estrogen-resistance-of-breast-cancer-cells-through-an-insulin-like-growth-factor-binding-protein-5-igfbp5-b-cell-leukemia-lymphoma-3-bcl-3-axis
#16
Benjamin Leyh, Angela Dittmer, Theresia Lange, John W M Martens, Jürgen Dittmer
There is strong evidence that stromal cells promote drug resistance of cancer. Here, we show that mesenchymal stem cells (MSCs) and carcinoma-associated fibroblasts (CAFs) desensitize ERα-positive breast cancer cells to the anti-estrogen fulvestrant. In search for the mechanism, we found that MSCs and CAFs similarly increased the activity of the PI3K/AKT and the JAK/STAT3 pathways and upregulated the expression of integrin β1, IGF1R, HIF1α, CAIX and Bcl-3 in MCF-7 cells. Further analyses revealed that MSCs and CAFs coordinately induce these changes by triggering the downregulation of IGFBP5...
November 17, 2015: Oncotarget
https://www.readbyqxmd.com/read/26487273/halting-pro-survival-autophagy-by-tgf%C3%AE-inhibition-in-bone-marrow-fibroblasts-overcomes-bortezomib-resistance-in-multiple-myeloma-patients
#17
M A Frassanito, K De Veirman, V Desantis, L Di Marzo, D Vergara, S Ruggieri, T Annese, B Nico, E Menu, I Catacchio, R Ria, V Racanelli, M Maffia, E Angelucci, D Derudas, R Fumarulo, F Dammacco, D Ribatti, K Vanderkerken, A Vacca
Bortezomib (bort) has improved overall survival in patients with multiple myeloma (MM), but the majority of them develop drug resistance. In this study, we demonstrate that bone marrow (BM) fibroblasts (cancer-associated fibroblasts; CAFs) from bort-resistant patients are insensitive to bort and protect the RPMI8226 and patients' plasma cells against bort-induced apoptosis. Bort triggers CAFs to produce high levels of interleukin (IL)-6, IL-8, insulin-like growth factor (IGF)-1 and transforming growth factor (TGF) β...
March 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/26450156/inhibition-of-igf1-r-overcomes-igfbp7-induced-chemotherapy-resistance-in-t-all
#18
Isabelle Bartram, Ulrike Erben, Jutta Ortiz-Tanchez, Katja Blunert, Cornelia Schlee, Martin Neumann, Sandra Heesch, Claudia D Baldus
BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with the need for treatment optimization. Previously, high expression of Insulin-like growth factor binding protein 7 (IGFBP7), a member of the IGF system, was identified as negative prognostic factor in adult T-ALL patients. Since aberrant IGFBP7 expression was observed in a variety of neoplasia and was relevant for prognosis in T-ALL, we investigated the functional role of IGFBP7 in Jurkat and Molt-4 cells as in vitro models for T-ALL...
2015: BMC Cancer
https://www.readbyqxmd.com/read/26376678/effects-of-first-and-second-generation-tyrosine-kinase-inhibitor-therapy-on-glucose-and-lipid-metabolism-in-chronic-myeloid-leukemia-patients-a-real-clinical-problem
#19
Alessandra Iurlo, Emanuela Orsi, Daniele Cattaneo, Veronica Resi, Cristina Bucelli, Nicola Orofino, Mariarita Sciumè, Chiara Elena, Valeria Grancini, Dario Consonni, Ester Maria Orlandi, Agostino Cortelezzi
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib. METHODS: The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS...
October 20, 2015: Oncotarget
https://www.readbyqxmd.com/read/26342105/il-18-induced-interaction-between-imp3-and-hur-contributes-to-cox-2-mrna-stabilization-in-acute-myeloid-leukemia
#20
Chiung-Yuan Ko, Wen-Ling Wang, Chien-Feng Li, Yung-Ming Jeng, Yu-Yi Chu, Han-Ying Wang, Joseph T Tseng, Ju-Ming Wang
Acute myeloid leukemia is the majority type presented in leukemia patients. Forcing malignant cells to undergo differentiation is 1 strategy for acute myeloid leukemia therapy. However, the failure of acute myeloid leukemia patients to achieve remission as a result of drug resistance remains a challenge. In this study, we found that the abundances of the proinflammatory cytokine IL-18 and its receptor (IL-18R) correlated with the occurrence of drug resistance in AML patients during standard treatment. Cyclooxygenase 2 (COX-2) has been suggested to have an antiapoptotic role in chemoresistant cancer cells...
January 2016: Journal of Leukocyte Biology
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