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leukemia and resistance insulin

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
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
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...
June 18, 2016: Jornal de Pediatria
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
Cengiz Bayram, Neşe Yaralı, Ali Fettah, Fatma Demirel, Betül Tavil, Abdurrahman Kara, Bahattin Tunç
INTRODUCTION: Improvement in long-term survival in patients with acute childhood lymphoblastic leukemia (ALL) has led to the need for monitorization of treatment related morbidity and mortality. In tne current study, we aimed to evaluate endocrine side effects of treatment in ALL survivors who were in remission for at least two years. METHODS: Sixty patients diagnosed with acute lymphoblastic leukemia, who were in remission for at least two years, were cross-sectionally evaluated for long-term endocrine compliations...
April 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
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
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
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
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
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
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
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
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
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
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
Michal Rihacek, Julie Bienertova-Vasku, Dalibor Valik, Jaroslav Sterba, Katerina Pilatova, Lenka Zdrazilova-Dubska
B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma...
2015: BioMed Research International
Eyad Hamoudeh, Amer M Zeidan, Lisa Barbarotta, Nina Rosano
Diabetes mellitus (DM) and cancer are disorders of global importance. Multiple epidemiologic studies show that diabetic patients have an increased risk of developing cancer of different types. Myelodysplastic syndromes (MDS) are among the most common hematologic malignancies and include a heterogeneous group of hematopoietic neoplasms characterized by dysplastic changes, low blood counts, and an increased risk of progression to acute myeloid leukemia. Potential epigenetic and metabolic interferences between DM and MDS have been reported but are poorly understood...
2016: Current Diabetes Reviews
Andrey G Berdyshev, Halyna V Kosiakova, Oleksandra V Onopchenko, Rostislav R Panchuk, Rostislav S Stoika, Nadiya M Hula
N-Stearoylethanolamine (NSE) is a minor lipid that belongs to the N-Acylethanolamines family that mediates a wide range of biological processes. This study investigates the mechanisms of anti-inflammatory action of NSE on different model systems. Namely, we estimated the effect of NSE on inflammatory cytokines mRNA level (leukemia cells L1210), cytokines content (serum and LPS-stimulated macrophages) and nuclear translocation of NF-κB (peritoneal macrophages LPS-stimulated and isolated from rats with obesity-induced insulin resistance)...
September 2015: Prostaglandins & Other Lipid Mediators
Nina Brandt, Hayley M O'Neill, Maximilian Kleinert, Peter Schjerling, Erik Vernet, Gregory R Steinberg, Erik A Richter, Sebastian B Jørgensen
Members of the IL-6 family, IL-6 and ciliary neurotrophic factor (CNTF), have been shown to increase glucose uptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member, leukemia inhibitory factor (LIF), are not well characterized. Effects of LIF on skeletal muscle glucose uptake and palmitate oxidation and signaling were investigated in ex vivo incubated mouse soleus and EDL muscles from muscle-specific AMPKα2 kinase-dead, muscle-specific SOCS3 knockout, and lean and high-fat-fed mice...
July 15, 2015: American Journal of Physiology. Endocrinology and Metabolism
Kevin Chu Foy, Megan J Miller, Jay Overholser, Siobhan M Donnelly, Rita Nahta, Pravin Tp Kaumaya
The insulin-like growth factor-1 receptor (IGF-1R) plays a crucial role in cellular growth, proliferation, transformation, and inhibition of apoptosis. A myriad of human cancer types have been shown to overexpress IGF-1R, including breast and pancreatic adenocarcinoma. IGF-1R signaling interferes with numerous receptor pathways, rendering tumor cells resistant to chemotherapy, anti-hormonal therapy, and epidermal growth factor receptor (EGFR, also known as HER-1) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2, (ERBB2, best known as HER-2) -targeted therapies...
November 2014: Oncoimmunology
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