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lymphoma leukemia insulin

Deeksha Vishwamitra, Suraj Konnath George, Ping Shi, Ahmed O Kaseb, Hesham M Amin
The insulin-like growth factor (IGF) signaling system plays key roles in the establishment and progression of different types of cancer. In agreement with this idea, substantial evidence has shown that the type I IGF receptor (IGF-IR) and its primary ligand IGF-I are important for maintaining the survival of malignant cells of hematopoietic origin. In this review, we discuss current understanding of the role of IGF-IR signaling in cancer with a focus on the hematological neoplasms. We also address the emergence of IGF-IR as a potential therapeutic target for the treatment of different types of cancer including plasma cell myeloma, leukemia, and lymphoma...
September 19, 2016: Oncotarget
Cody P Coyne, Lakshmi Narayanan
PURPOSE: Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. MATERIALS AND METHODS: The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate...
2016: Drug Design, Development and Therapy
Changjiang Ying, Xiaoyan Zhou, Zhenzhen Chang, Hongwei Ling, Xingbo Cheng, Wei Li
Blood glucose fluctuation is associated with diabetic nephropathy. However, the mechanism by which blood glucose fluctuation accelerates renal injury is not fully understood. The aim of the present study was to assess the effects of blood glucose fluctuation on diabetic nephropathy in rats and investigate its underlying mechanism. Diabetes in the rats was induced by a high sugar, high-fat diet, and a single dose of STZ (35 mg/kg)-injected intraperitoneally. Unstable blood sugar models were induced by subcutaneous insulin injection and intravenous glucose injection alternately...
July 2016: Endocrine
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
Philipp Ofer, Isabel Heidegger, Iris E Eder, Bernd Schöpf, Hannes Neuwirt, Stephan Geley, Helmut Klocker, Petra Massoner
The IGF network with its main receptors IGF receptor 1 (IGF1R) and insulin receptor (INSR) is of major importance for cancer initiation and progression. To date, clinical studies targeting this network were disappointing and call for thorough analysis of the IGF network in cancer models. We highlight the oncogenic effects controlled by IGF1R and INSR in prostate cancer cells and show similarities as well as differences after receptor knockdown (KD). In PC3 prostate cancer cells stably transduced with inducible short hairpin RNAs, targeting IGF1R or INSR attenuated cell growth and proliferation ultimately driving cells into apoptosis...
December 2015: Molecular Endocrinology
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
Lingling Lu, Feng Wang, Lulu He, Yao Xue, Yaping Wang, Heng Zhang, Liucheng Rong, Meilin Wang, Zhengdong Zhang, Yongjun Fang, Hongjun Miao
BACKGROUND/AIMS: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman...
2015: Cellular Physiology and Biochemistry
Kirsi Jahnukainen, Risto Heikkinen, Markus Henriksson, Sture Andersson, Kaisa K Ivaska, Leena-Riitta Puukko-Viertomies, Outi Mäkitie
BACKGROUND: We evaluated the body composition and its association with hypogonadism in adult male long-term acute lymphoblastic leukemia (ALL) survivors. METHODS: The cohort included 49 long-term male ALL survivors and 55 age-matched healthy controls. Fat and lean mass was assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for adipokines and testicular endocrine markers. RESULTS: As compared with controls, the ALL survivors (median age 29 years, range 25-38), assessed 10-28 years after ALL diagnosis, had higher percentages of body (p < 0...
2015: Hormone Research in Pædiatrics
Mateus Milani, Angelo Brunelli Albertoni Laranjeira, Jaíra Ferreira de Vasconcellos, Silvia Regina Brandalise, Alexandre Eduardo Nowill, José Andrés Yunes
Current monitoring of acute lymphoblastic leukemia (ALL) in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, precluding its use. Conversely, plasma levels of Hsp90 showed low background and linear correlation to FACS results. In another experiment, we compared Hsp90 levels with percentage of hCD45+ cells in blood, bone marrow, liver and spleen of animals weekly sacrificed...
2015: PloS One
Maria Dalamaga, Gerasimos S Christodoulatos
Higher body mass index and adiposopathy have been associated with increased risk of hematologic malignancies such as leukemia, multiple myeloma, myeloproliferative disorders, Hodgkin's and non-Hodgkin's lymphoma, and myelodysplastic syndromes. Adiponectin is a multimeric protein of the white adipose tissue presenting anti-inflammatory, insulin-sensitizing, anti-atherogenic, cardioprotective, and anti-neoplastic properties. Its anti-neoplastic actions are manifested via two mechanisms: (i) direct action on tumor cells by enhancing receptor-mediated signaling pathways and (ii) indirect action by regulating inflammatory responses, influencing cancer angiogenesis, and modulating insulin sensitivity at the target tissue site...
July 2015: Hormone Molecular Biology and Clinical Investigation
Christina Wei, Manigandan S Thyagiarajan, Linda P Hunt, Julian P H Shield, Michael C G Stevens, Elizabeth C Crowne
BACKGROUND: Survivors of childhood acute lymphoblastic leukaemia (ALL) treated with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have a high cardiometabolic risk despite lacking overt clinical obesity. This study characterised body composition using different methodologies and explored associations with reduced insulin sensitivities in a group of ALL survivors treated with/without HSCT/TBI. PROCEDURE: Survivors of childhood ALL treated with HSCT/TBI (n = 20,10 M) were compared with Chemotherapy-only (n = 31), and an obese non-leukaemic controls (n = 30)...
November 2015: Pediatric Blood & Cancer
Veronica Brady, Sonali Thosani, Shouhou Zhou, Roland Bassett, Naifa Lamki Busaidy, Victor Lavis
BACKGROUND: Hyperglycemia occurs in cancer patients receiving high-dose steroids with cyclophosphamide, doxorubicin, vincristine, and dexamethasone (hyper-CVAD) protocol. The purpose of our study was to determine insulin requirements in patients with hyperglycemia on hyper-CVAD therapy using a systematic algorithm. SUBJECTS AND METHODS: We did a retrospective chart review of 23 leukemia inpatients with hyperglycemia (two glucose values >250 mg/dL) on hyper-CVAD chemotherapy managed by the Endocrine Diabetes Inpatient Team algorithm...
December 2014: Diabetes Technology & Therapeutics
Christina Wei, Manigandan Thyagiarajan, Linda Hunt, Rachel Cox, Karin Bradley, Ruth Elson, Julian Hamilton-Shield, Michael Stevens, Elizabeth Crowne
BACKGROUND: Impaired glucose tolerance (IGT) and diabetes mellitus (DM) occur more frequently after bone marrow transplantation and total body irradiation (BMT/TBI), but the mechanism is unclear. This study investigates insulin sensitivity, β-cell reserve and pancreatic volume in adult survivors of childhood acute lymphoblastic leukaemia (ALL). METHOD: Survivors (aged 16-26 years) of ALL treated with BMT/TBI (10-14·4 Gy) Group 1 (n = 20, 10 m) were compared with a chemotherapy-only Group 2 (n = 28, 11 m)...
January 2015: Clinical Endocrinology
Noran M Abu-Ouf, Mohammed M Jan
Metabolic syndrome is a common complication encountered in children surviving acute lymphoblastic leukaemia (ALL). Affected patients develop obesity, insulin resistance, hypertension, and hyperlipidemia. Metabolic syndrome is a consequence of multiple factors, particularly hormonal imbalance induced by various ALL treatments. This review aims to evaluate the risk factors and mechanisms leading to the development of metabolic syndrome. Further research is needed to improve our understanding of the mechanisms leading to insulin resistance and the associated endothelial and adipose tissue dysfunction...
March 2015: Obesity Research & Clinical Practice
Yonatan Yeshayahu, Dror Koltin, Jill Hamilton, Paul C Nathan, Stacey Urbach
Medication-induced diabetes (MID) is seen in children treated for acute lymphoblastic leukemia (ALL) mostly during induction, due to the use of l-asparaginase and glucocorticoids. Our objective was to assess whether MID during induction, is a risk factor for future impaired glucose tolerance (IGT), diabetes, or metabolic syndrome. Ninety survivors of pediatric ALL, ages 10 yr and older were recruited, 30 with history of MID and 60 controls. Waist/height ratio >0.5 was considered as an increased risk for central adiposity and insulin resistance...
March 2015: Pediatric Diabetes
Kerri A Nottage, Kirsten K Ness, Chenghong Li, Deokumar Srivastava, Leslie L Robison, Melissa M Hudson
Adult survivors of childhood acute lymphoblastic leukaemia (ALL) have a four-fold excess risk of mortality from cardiovascular disease. This cardiovascular risk has not been fully characterized. ALL survivors [n = 784, median age 31·7 years (18·9-59·1)] in the St. Jude Lifetime Cohort Study underwent evaluation for cardiovascular risk and metabolic syndrome (MetS) according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Comparisons were made to 777 age-, sex-, and race-matched controls from the National Health and Nutrition Examination Survey (NHANES)...
May 2014: British Journal of Haematology
Serap Kirkiz, Nese Yarali, Ozlem Arman Bilir, Bahattin Tunc
OBJECTIVE: To report a rare side effect of metformin, an oral antidiabetic drug that is used for the treatment of type 2 diabetes mellitus. CLINICAL PRESENTATION AND INTERVENTION: A 17-year-old boy was hospitalized for receiving acute lymphoblastic leukemia treatment that was composed of vincristine, L-asparaginase, daunorubicin, and prednisone. Hyperglycemia was determined without any clinical sign and metformin was started for steroid-induced insulin resistance...
2014: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
Zhiwei Huang, Zhijia Fang, Hong Zhen, Li Zhou, Hesham M Amin, Ping Shi
It has been recently shown that the type I insulin-like growth factor receptor (IGF-IR) contributes significantly to the survival of T lymphoblastic leukemia/lymphoma (T-LBL) cells, and it was therefore suggested that IGF-IR could represent a legitimate therapeutic target in this aggressive disease. Picropodophyllin (PPP) is a potent, selective inhibitor of IGF-IR that is currently used with notable success in clinical trials that include patients with aggressive types of epithelial tumors. In the present study, we tested the effects of PPP on Jurkat and Molt-3 cells; two prototype T-LBL cell lines...
August 2014: Leukemia & Lymphoma
Jeremy Michals Schraw, Yong Quan Dong, Mehmet Fatih Okcu, Michael E Scheurer, Michele R Forman
Milk formula feeding can elevate insulin-like growth factor-1 levels, possibly impacting leukemogenesis. The intent of the current study is to examine the associations between infant feeding practices and age at introduction of solids on risk of childhood acute lymphoblastic leukemia (ALL). Incident cases of infant and childhood (aged ≤14 years) ALL (n = 142) were enrolled in a case-control study. Cases were frequency matched on age, sex, race, and ethnicity to two sets of controls (n = 284 total). Multivariable logistic regression was used to determine the association between infant feeding practices and age at the introduction of solids and the odds ratio of ALL...
January 2014: Cancer Causes & Control: CCC
Giovanni De Pergola, Franco Silvestris
The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours...
2013: Journal of Obesity
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