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Insulin And Tumor Growth

Mortality Risk High In Diabetic Cancer Patients Using Insulin

Mortality Risk High In Diabetic Cancer Patients Using Insulin

Mortality Risk High in Diabetic Cancer Patients Using Insulin Cancer patients with pre-existing diabetes have a greater risk for death compared with nondiabetics, with the highest mortality observed in those using insulin. For all cancers combined, the authors of a large Danish study found that patients who had diabetes for 2 years, and who had been treated with insulin at the time of cancer diagnosis, had a mortality rate that was about 4 times higher than that of nondiabetics. The higher risk was observed 1 year after being diagnosed with cancer. Conversely, the risk for death was much lower for patients using oral hypoglycemic agents. Compared with nondiabetics, they had an increased mortality risk of about 10% in both men and women. The study has been published in Diabetologia. "From the literature it is evident that diabetes patients, and particularly those treated with insulin, have a higher degree of co-morbidity," commented study author Marit Eika Jrgensen, PhD, professor and research manager at the Steno Diabetes Center, Gentofte, Denmark. There are several factors contributing to this, she told Medscape Medical News. "Cancer is diagnosed at a later and more advanced stage, diabetes patients are offered less aggressive cancer therapy, and cancer surgery mortality is higher with insulin treated diabetes." However, because the patient data was drawn from national registries, for "register-technical" reasons, Dr. Jrgensen explained that they cannot exclude inverse causation within the first 6-12 months after cancer diagnosis, such as if severe cancer or the cancer treatment itself caused the need for insulin treatment. "Theoretically, it can be speculated that hyperinsulinemia, as a result of underlying insulin resistance or exogenous insulin, increases tumor gro Continue reading >>

Insulin-like Growth Factors And Cancer

Insulin-like Growth Factors And Cancer

Home Resources Articles Insulin-Like Growth Factors and Cancer The association between circulating levels of serum or plasma insulin-like growth factor I (IGF-I) and cancer risk has been postulated for some time. Recent control-matched epidemiological studies have strengthened this association. These studies demonstrate that relatively high plasma IGF-I and low IGF binding protein-3 (IGFBP-3) levels are associated with greater risk of breast cancer in pre-menopausal women,1 prostate cancer in men,2 colorectal cancer in men and women,3 and lung cancer in men and women.4 Additional in vitro and in vivo studies reflecting a link between IGF and cancer can be found in references 5-8. The IGF system is an integral part of growth regulation by the body. Abnormalities in all levels of the IGF system have been implicated in carcinogenesis and cellular transformation.8 The ligands of the IGF family, IGF-I and IGF-II, share 50% structural homology to insulin. IGFs act as mitogenic stimulators of cell proliferation as well as suppressors of cellular apoptotic pathways. Under the control of growth hormone (GH), the liver is the primary site of IGF production. IGF-I levels are also influenced by nutrition and developmental stages. Autocrine and paracrine tissue production of IGFs may also contribute to the levels of IGF available for growth regulation. IGFs act through a family of cell surface receptors, including the insulin receptor, the type 1 IGF receptor (IGF-1R) and the type 2 IGF receptor (IGF-2R). IGF-1R is a tyrosine kinase that binds IGF-I with high affinity and binds IGF-II and insulin with much lower affinity. IGF-2R is the cation-independent mannose-6-phosphate receptor that binds IGF-II with high affinity and may act to remove IGF-II from the extracellular environment Continue reading >>

Diabetes, Insulin Use, And Cancer Risk: Are Observational Studies Part Of The Solutionor Part Of The Problem?

Diabetes, Insulin Use, And Cancer Risk: Are Observational Studies Part Of The Solutionor Part Of The Problem?

Diabetes, Insulin Use, and Cancer Risk: Are Observational Studies Part of the Solutionor Part of the Problem? We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Diabetes, Insulin Use, and Cancer Risk: Are Observational Studies Part of the Solutionor Part of the Problem? Cancer has overtaken cardiovascular disease as the leading cause of death in individuals under the age of 65 in the general population, but it is still overshadowed by cardiovascular disease in those with diabetes. People with type 2 diabetes are nonetheless more likely to develop cancerand to die from itthan members of the general population, so cancer should be numbered among the complications of diabetes ( 1 ). Furthermore, the number of cancer victims with diabetes will inevitably rise in proportion to our success in combating vascular disease in the diabetic population. How can the increased cancer risk in diabetes be explained? To begin with, it should be noted that obesity, insulin resistance, and/or increased levels of IGF-1 and insulin are strongly associated with most (but not all) of the diabetes-related cancers in the nondiabetic population ( 1 ). This suggests that hyperglycemia does not play an essential role in the pathogenesis of these tumors, but does not exclude the possibility that it might have secondary effects such as enhanced tumor growth or resistance to anti-tumor therapy. IGF-1 and insulin offer a more plausible mechanistic explanation for Continue reading >>

The Emerging Role Of The Insulin-like Growth Factor Pathway As A Therapeutic Target In Cancer

The Emerging Role Of The Insulin-like Growth Factor Pathway As A Therapeutic Target In Cancer

Conception/design: Paula D. Ryan, Paul E. Goss Administrative support: Paula D. Ryan Collection/assembly of data: Paula D. Ryan Manuscript writing: Paula D. Ryan, Paul E. Goss Final approval of manuscript: Paul E. Goss Disclosure: P.E.G. has acted as a consultant to Novartis, AstraZeneca, and Pfizer, and P.D.R. has acted as a consultant to Pfizer, Genentech, and Novartis. No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article. Learning Objectives After completing this course, the reader will be able to: Discuss the characteristics of the IGF system including its endocrine as well as tissue growth factor properties. Discuss the preclinical background and the rationale for targeting the IGF system in cancer therapy. Discuss ongoing phase I and phase II clinical trials targeting the IGF-IR in solid tumor malignancies. Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com Abstract The insulin-like growth factor signaling pathway is important in many human cancers based on data from experimental models as well as epidemiological studies. Important therapies targeted at this pathway have been or are being developed, including monoclonal antibodies to the insulin-like growth factor-I receptor and small molecule inhibitors of the tyrosine kinase function of this receptor. These investigational therapies are now being studied in clinical trials. Emerging data from phase I trials are encouraging regarding the safety of the monoclonal antibodies. In this manuscript, the rationale for targeting the insulin-like growth factor system is reviewed in addition to a summary of the available clinical trial data. The insulin-like growth factor (IGF) signaling system play Continue reading >>

Sugar And Cancer

Sugar And Cancer

Question: Does sugar feed cancer? Answer: While researchers continue to investigate the connection between sugar and cancer, it remains a source of anxiety-inducing speculation and misinformation in the media and on the internet. Of course, the undeniable answer is that glucose (the form of sugar used most in the body) feeds every cell in the body, and is so important to the function of your brain that the body has several back up strategies to keep blood sugar levels normal. Even without any carbohydrate in the diet, your body will make sugar from other sources, including protein and fat. The idea that sugar could directly fuel the growth of cancer cells can lead some people to avoid all carbohydrate-containing foods. This is counter-productive for anyone struggling to maintain their weight while dealing with side effects of cancer and treatments. More importantly, the inevitable anxiety of trying to completely avoid “all sugar” creates stress. Stress turns on the fight or flight mechanisms, increasing the production of hormones that can raise blood sugar levels and suppress immune function. Both of these things may reduce any possible benefit of eliminating sugar in the first place. Much research shows that it is sugar’s relationship to higher insulin levels and related growth factors that may influence cancer cell growth the most, and increase risk of other chronic diseases. Many types of cancer cells have plenty of insulin receptors, making them respond more than normal cells to insulin’s ability to promote growth. All carbohydrates you eat are broken down to simple sugars in the intestine, where they are absorbed into the blood, increasing blood sugar levels. The pancreas releases insulin in response, which travels throughout the blood stream, and performs Continue reading >>

Role Of The Insulin-like Growth Factor Family In Cancer Development And Progression

Role Of The Insulin-like Growth Factor Family In Cancer Development And Progression

Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression Affiliations of authors: H. Yu, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport; T. Rohan, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY. Correspondence to: Herbert Yu, M.D., Ph.D., Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932 (e-mail: [email protected] ). Search for other works by this author on: Affiliations of authors: H. Yu, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport; T. Rohan, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY. Search for other works by this author on: JNCI: Journal of the National Cancer Institute, Volume 92, Issue 18, 20 September 2000, Pages 14721489, Herbert Yu, Thomas Rohan; Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression, JNCI: Journal of the National Cancer Institute, Volume 92, Issue 18, 20 September 2000, Pages 14721489, The insulin-like growth factors (IGFs) are mitogens that play a pivotal role in regulating cell proliferation, differentiation, and apoptosis. The effects of IGFs are mediated through the IGF-I receptor, which is also involved in cell transformation induced by tumor virus proteins and oncogene products. Six IGF-binding proteins (IGFBPs) can inhibit or enhance the actions of IGFs. These opposing effects are determined by the structures of the binding proteins. The effects of IGFBPs on IGFs are regulated in part by IGFBP proteases. Laboratory studies have shown that IGFs exert strong mitogenic and antiapoptotic actions on various cancer cells. IGFs a Continue reading >>

Insulin And Cancer - Associated Disorders - Diapedia, The Living Textbook Of Diabetes

Insulin And Cancer - Associated Disorders - Diapedia, The Living Textbook Of Diabetes

Insulin has long been known to possess growth-promoting properties, including enhanced cell proliferation (i.e. it is mitogenic). Exposure to high levels of insulin promotes expansion of some cancer cell lines in vitro and cancer growth in some experimental situations. Insulin does not however cause malignant transformation of healthy cells (i.e. it is not mutagenic). Exogenous insulin is often needed to treat type 2 diabetes. In contrast with endogenous insulin, which is largely cleared by the liver, exogenous insulin is delivered into the systemic circulation and thus increases the exposure of peripheral tissues to its effects. Exogenous insulin might thus have the potential to promote the growth of pre-existing cancer foci in certain locations. In line with this, some observational studies report that cancer risk is increased in insulin-treated type 2 diabetes, as compared with other glucose-lowering therapies. This observation has not been confirmed in other studies, however, and the only cancer unequivocally linked to insulin use is carcinoma of the pancreas, almost certainly because this tumour causes worsening of diabetes (reverse causation). This entry reviews the evidence concerning insulin use and cancer; daughter pages consider the evidence relating specifically to human and analogue insulins. Figure 1: Modified from Pollak M. Nature Rev Cancer 8:915-928, 2008Insulin and the insulin growth factors IGF-1 and IGF-2 share a common evolutionary origin, and insulin has growth-promoting as well as metabolic actions. The insulin-IGF axis plays a major role in promoting growth and development of those cancers which overexpress the receptor family on their surface, and hyperinsulinemia has been implicated as a possible causal factor linking obesity and diabetes to ca Continue reading >>

Diabetes And Cancer: What's The Connection?

Diabetes And Cancer: What's The Connection?

When Michelle Hall was diagnosed with breast cancer two years ago, she was shocked. "The standing joke in the family was that I came from a long line of stocky French women who lived forever," says Hall, 62, of Salem, N.H. "We had no breast cancer in the family." Hall had been diagnosed with type 2 diabetes in 2001, so she would have special challenges while facing down cancer. As diseases, cancer and diabetes seem a world away from each other. Yet, numerous studies suggest the conditions are linked. People with diabetes are more likely to be diagnosed with cancer than those without diabetes, but why remains unclear. Scientists are still trying to answer even the most basic questions: Does diabetes cause cancer? If so, what kinds of cancer and how? As the interplay between diabetes and cancer becomes clearer, researchers hope to gain an edge against both diseases. The link between diabetes and cancer may be partially explained by risk factors that underlie and raise the risk of both diseases. Sex: Overall, men are more likely to develop both cancer and type 2 diabetes than women. Weight: Overweight and obese people are more likely to develop cancer than lean people. The association between type 2 diabetes and weight is also well established. While it's clear that losing weight reduces the risk for type 2 diabetes, less is known about whether weight loss combats cancer. Diet: Eating patterns that are thought to help prevent and treat type 2 diabeteslimited red and processed meats and abundant vegetables, fruits, and whole grainsare also associated with a lower risk for many types of cancer. Exercise: Studies show that regular physical activity lowers the risk of developing several types of cancer. Likewise, 30 minutes of moderate-intensity exercise per day can reduce th Continue reading >>

Hyperglycemia Promotes Insulin-independent Ovarian Tumor Growth

Hyperglycemia Promotes Insulin-independent Ovarian Tumor Growth

Hyperglycemia promotes insulin-independent ovarian tumor growth Author links open overlay panel Lisa D.Kellenberger JimPetrik The role for elevated glucose in ovarian cancer proliferation and tumorigenesis is explored. Hyperglycemia, independent of insulin drives ovarian cancer progression Culturing cells in supraphysiological glucose significantly impacts cell function. Epithelial ovarian cancer (EOC) is notoriously difficult to diagnose in its earlier and more treatable stages, making it one of the deadliest cancers in women. Comorbid diabetes is associated with poor prognosis in EOC and pro-growth insulin signalling is often considered to be the driving factor. However, EOC cells are also highly glycolytic and insulin-independent glucose uptake is essential to their metabolism. Evidence of gluconeogenesis in cancer in vivo suggests that the normal concentration of circulating glucose does not meet the energy demands of the tumor and may therefore be a limiting factor in cancer cell metabolism. Diabetics have elevated blood glucose that has the potential to meet these energy demands and facilitate cancer progression. To determine whether hyperglycemia is a potentially modifiable factor independent of insulin, orthotopic ovarian tumors were induced in mice with acute Type 1 (hypo-insulinemic) or Type 2 (hyper-insulinemic) diabetes. Hyperglycemia accelerated the growth of ovarian tumors in a glucose concentration-dependent manner and significantly shortened overall survival. Reciprocally, the presence of a tumor improved impaired glucose tolerance in both Type 1 and Type 2 diabetes. In mice with chronic Type 1 diabetes, hyperglycemia limited tumor growth without changing overall survival, indicating that systemic metabolic stress can accelerate time to death independen Continue reading >>

Sugar And Cancer

Sugar And Cancer

Question: Does sugar feed cancer? Answer: While researchers continue to investigate the connection between sugar and cancer, it remains a source of anxiety-inducing speculation and misinformation in the media and on the internet. Of course, the undeniable answer is that glucose (the form of sugar used most in the body) feeds every cell in the body, and is so important to the function of your brain that the body has several back up strategies to keep blood sugar levels normal. Even without any carbohydrate in the diet, your body will make sugar from other sources, including protein and fat. The idea that sugar could directly fuel the growth of cancer cells can lead some people to avoid all carbohydrate-containing foods. This is counter-productive for anyone struggling to maintain their weight while dealing with side effects of cancer and treatments. More importantly, the inevitable anxiety of trying to completely avoid “all sugar” creates stress. Stress turns on the fight or flight mechanisms, increasing the production of hormones that can raise blood sugar levels and suppress immune function. Both of these things may reduce any possible benefit of eliminating sugar in the first place. Much research shows that it is sugar’s relationship to higher insulin levels and related growth factors that may influence cancer cell growth the most, and increase risk of other chronic diseases. Many types of cancer cells have plenty of insulin receptors, making them respond more than normal cells to insulin’s ability to promote growth. All carbohydrates you eat are broken down to simple sugars in the intestine, where they are absorbed into the blood, increasing blood sugar levels. The pancreas releases insulin in response, which travels throughout the blood stream, and performs Continue reading >>

The Insulin/cancer Connection

The Insulin/cancer Connection

Most people recognize insulin as a beneficial hormone. It helps remove sugar (glucose) from the blood into cells where it is used to power energy or is stored as surplus fat. For years, Life Extension® has discussed the role of excess insulin as a culprit involved in metabolic syndrome, which increases degenerative disease risk. In particular, high levels of insulin are now recognized as important contributors to the development and progression of many kinds of cancer.1-3 How has such a vital, natural hormone been converted from life-supporting friend to deadly foe? The answer lies with the nation’s love affair with calories, particularly those derived from simple sugars and refined carbohydrates. Americans eat so many of these dangerous foods that 50% are overweight, 30% are obese, and 10% already have type II diabetes.2 Studies in the past decade have revealed a close connection between body size, type II diabetes, and many cancers.2,3 For example, consuming a diet rich in readily digested sugars and carbohydrates increases the risk of developing the most common form of breast cancer by 36% to 41%.4 A consistent finding across a broad spectrum of common malignancies reveals that higher blood insulin, often caused by chronically elevated blood glucose, results in increased cancer risk. For example, prostate cancer incidence is 2.55-fold greater in men with the highest blood insulin levels.5 The Emerging Connection between Obesity, Insulin, and Cancer As people gain weight, their fat cells begin to pour out cytokines that generate inflammation throughout the body.3,6 This leads to the phenomenon called “insulin resistance,” in which cells lose their ability to move glucose from the blood and into cells under the influence of normal blood levels of insulin.3 As a Continue reading >>

Frontiers | Insulin/insulin-like Growth Factors In Cancer: New Roles For The Aryl Hydrocarbon Receptor, Tumor Resistance Mechanisms, And New Blocking Strategies | Endocrinology

Frontiers | Insulin/insulin-like Growth Factors In Cancer: New Roles For The Aryl Hydrocarbon Receptor, Tumor Resistance Mechanisms, And New Blocking Strategies | Endocrinology

Front. Endocrinol., 02 February 2015 | Insulin/insulin-like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms, and new blocking strategies Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA The insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor (IR) are receptor tyrosine kinases that are expressed in cancer cells. The results of different studies indicate that tumor proliferation and survival is dependent on the IGF1R and IR, and that their inhibition leads to reductions in proliferation and increases in cell death. Molecular targeting therapies that have been used in solid tumors include anti-IGF1R antibodies, anti-IGF1/IGF2 antibodies, and small molecule inhibitors that suppress IGF1R and IR kinase activity. New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 to integrin 3 receptors in some cancer cells. Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR) ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose proliferation and survival are dependent on insulin/IGF signaling. Novel aspects of IGF1R/IR in cancer, such as biased agonism, integrin 3 signaling, AHR, and new therapeutic targeting strategies will be discussed. A Short History of Insulin/IGFs in Cancer The early evidence linking the IGF1R to cancer was the finding that the transformation of mouse embryo fibroblasts (MEFs) by many, but not all, tested oncogenes requires an intact Igf1r gene. For instance, the SV40 large T antigen, H-Ras, EWS/FLI-1, and c-Src transform wild type, but not Igf1 Continue reading >>

Obesity And Cancer, A Case For Insulin Signaling

Obesity And Cancer, A Case For Insulin Signaling

Cell Death & Disease volume 6, page e2037 (2015) Obesity is a worldwide epidemic, with the number of overweight and obese individuals climbing from just over 500 million in 2008 to 1.9 billion in 2014. Type 2 diabetes (T2D), cardiovascular disease and non-alcoholic fatty liver disease have long been associated with the obese state, whereas cancer is quickly emerging as another pathological consequence of this disease. Globally, at least 2.8 million people die each year from being overweight or obese. It is estimated that by 2020 being overweight or obese will surpass the health burden of tobacco consumption. Increase in the body mass index (BMI) in overweight (BMI>25 kg/m2) and obese (BMI>30 kg/m2) individuals is a result of adipose tissue (AT) expansion, which can lead to fat comprising >50% of the body weight in the morbidly obese. Extensive research over the last several years has painted a very complex picture of AT biology. One clear link between AT expansion and etiology of diseases like T2D and cancer is the development of insulin resistance (IR) and hyperinsulinemia. This review focuses on defining the link between obesity, IR and cancer. Hyperinsulinemia, along with the other obesity-related factors, is linked to the development of several types of cancers. Insulin, signaling through insulin receptor A, has direct oncogenic effects on cancer cells. Insulin-lowering drugs, such as metformin, may prove to be useful in lowering insulin levels and insulin resistance, decreasing body weight and improving cancer outcomes in patients with obesity and type 2 diabetes. How are the PI3K-AKT and the Ras-MAPK pathways regulated by INSR-A in normal epithelial cells and in cancer? How should obesity and T2D be treated in order to minimize the risk of cancer development, spe Continue reading >>

What Is The Role Of Insulin In Tumors/cancer Development?

What Is The Role Of Insulin In Tumors/cancer Development?

Actually, many factors potentially contribute to the role of insulin in the development and progression of cancer. These include hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, inflammatory and angiogenic adipokines and cytokines, and the gut microbiome Epidemiological studies have shown that hyperinsulinemia and hyperglycemia associated with type 2 DM are linked to an increased risk of several types of cancer, especially the liver and pancreas. Hyperinsulinemia and the exposure of the liver to high insulin concentrations in the portal circulation plays the major role. This is because insulin binds to and activates the related insulin-like growth factor-I (IGF-I) receptor (80% homology with insulin receptor. This leads to more potent mitogenic and transforming activities. moreover, insulin decreases IGF-I-binding proteins (IGF-BP1) resulting in increased free IGF-I, the biologically active form of the growth factor. Besides, The action of insulin in malignant cells is favored by mechanisms acting at both the receptor and post-receptor level. Insulin receptors are overexpressed in cancer cells. The IR may be expressed in two different isoforms, A and B. In malignant cells, IR isoform A (IR-A) expression is predominant and its activation, in contrast to the IR-B isoform, causes more mitogenic than metabolic effects. By binding to the overexpressed IR-A, insulin may favor cancer progression and facilitates the growth of tumors by increasing cell proliferation. Continue reading >>

Insulin And Cancer. - Pubmed - Ncbi

Insulin And Cancer. - Pubmed - Ncbi

239 Glenville Road, Greenwich, CT 06831, USA. [email protected] Obesity has recently been linked to mortality from the majority of cancers. The insulin/insulin-like growth factor (IGF) system may partly explain this effect. The metabolic syndrome, associated with hyperinsulinemia, may modulate this effect. Recent evidence supports the role of insulin and IGF-1 as important growth factors, acting through the tyrosine kinase growth factor cascade in enhancing tumor cell proliferation. In addition, the metabolic syndrome associated with a chronic inflammatory state and accompanying cytokine abnormalities may also contribute to tumor progression. Growing links between insulin and the etiology as well as prognosis in colon, prostate, pancreatic, and, particularly, breast cancer are reviewed. Of particular concern is the evidence that elevated IGF-1 may interfere with cancer therapy, adversely affecting prognosis. The role of insulin is of concern because of the increasing levels of obesity and the associated metabolic syndrome. Weight gain, through typical Western diet; limited levels of activity; and, more recently, stress-related changes in neuroendocrine function may lead to insulin resistance and hyperinsulinemia. The opportunity for a multidisciplinary approach involving nutrition, exercise, and stress reduction in an integrative setting may be crucial to limiting the insulin-resistant state and improving cancer outcomes. Continue reading >>

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