Controlling Hyperglycemia as an Adjunct to Cancer Therapy

Krone, Cheryl A.; Ely, J. T. A.

doi:10.1177/1534735404274167

Cited by 70 publications

(59 citation statements)

References 56 publications

(62 reference statements)

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“…A number of epidemiological studies have shown a direct association between breast cancer risk and the consumption of sweet foods with high glycaemic index (Lubin et al 1981, Landa et al 1994, Potischman et al 2002, Tavani et al 2006. Studies have also provided evidence that high carbohydrate intake is associated with poorer survival after diagnosis for early breast cancer (Krone & Ely 2005). Animal models of diabetes have also shown an increase in susceptibility to chemically induced mammary tumours (Shafie & Grantham 1981).…”

Section: Introductionmentioning

confidence: 98%

Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase

Zeng¹,

Biernacka²,

Holly³

et al. 2010

Endocrine-Related Cancer

104

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The prognosis for women with breast cancer is adversely affected by the comorbidities of obesity and diabetes mellitus (DM), which are conditions associated with elevated levels of circulating fatty acids, hyperglycaemia and hyperinsulinaemia. We investigated the effects of exposure of nonmalignant and malignant human breast epithelial cells to elevated levels of fatty acids and glucose on their growth, survival and response to chemotherapeutic agents. We found that palmitate induced cell death in the non-malignant cells but not in the malignant cells, which was abrogated through the inhibition of ceramide production and by oleate but not by IGF1. Fatty acid synthase (FAS) is responsible for the de novo synthesis of fatty acids from sugars, and is over-expressed in many epithelial cancers. Abundance of FAS was higher in malignant cells than in non-malignant cells, and was up-regulated by IGF1 in both cell types. IGF-induced growth of non-malignant cells was unaffected by suppression of FAS expression, whereas that of malignant cells was blocked as was their resistance to palmitate-induced cell death. Palmitate did not affect cell proliferation, whereas oleate promoted the growth of non-malignant cells but had the opposite effect, that is, inhibition of IGF1-induced growth of malignant cells. However, when the phosphatidylinositol 3-kinase pathway was inhibited, oleate enhanced IGF1-induced growth in both cell types. Hyperglycaemia conferred resistance on malignant cells, but not on non-malignant cells, to chemotherapy-induced cell death. This resistance was overcome by inhibiting FAS or ceramide production. Understanding the mechanisms involved in the associations between obesity, DM and breast cancer may lead to more effective treatment regimens and new therapeutic targets.

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Section: Introductionmentioning

confidence: 98%

Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase

Zeng¹,

Biernacka²,

Holly³

et al. 2010

Endocrine-Related Cancer

104

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show abstract

“…Epidemiological studies corroborate the adverse role of highinsulinemic nutrition, insulin and IR in the malignant state: high intake of sugar and refined carbohydrates and elevated blood glucose were found to be strongly associated with the risk of cancer [117] and with poorer survival after diagnosis for early breast cancer [118]. Also, chronic exogenous insulin therapy significantly increases the risk of colorectal cancer among type 2 diabetes patients [119].…”

Section: Insulin and Cancermentioning

confidence: 52%

Significant Dietary Changes during Human Evolution and the Development of Cancer: From Cells in Trouble to Cells Causing Trouble

Köpp¹

2017

J Carcinog Mutagen

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In all western societies, mortality rates from cancer are high and even increasing. In striking contrast, cancer rates are very rare and even non-existent in primitive cultures, like hunter-gatherer (HG) populations. HGs are free of disease as long as they adhere to their traditional low-insulinemic "Paleolithic" nutrition. With acculturation and transition to current high-carbohydrate/high-insulinemic "Western" diets (HCHIDs), cancer develops in high rates. This paper follows the question of how significant nutritional changes, brought about by the Agricultural revolution, may cause development of cancer. The evidence presented shows that the switch from a Paleolithic to a Western nutrition has brought about significant metabolic perturbations, like an abnormally increased activation of the insulinlike growth factor system, the sympathetic nervous system and the renin-angiotensin-system, an increased expression of HIF-1α and other more, all of which are deeply involved in cancer development through promotion of proliferation, angiogenesis, inflammation, macrophage infiltration, metastasis and inhibition of apoptosis.In addition, HCHIDs generate oxidative stress which may cause mitochondrial damage and genomic instability, and may interfere with normal stem cell development. Faulty redox signaling is suggested to play a significant role in cancer development: hydrogen peroxide, generated at low concentrations, represents an important chemical mediator in the regulation of various cellular signal transduction processes, including stem cell development. Oxidative stress may be sensed by cells as redox signaling. Faulty "redox signaling" is proposed to affect normal stem cell development by sustained activation of uncoupling protein 2, leading to inhibition of differentiation ("maturation arrest"), sustained uncontrolled proliferation, and glycolysis with high expression of hexokinase II, typical features of cancer. In summary, an abnormal diet-related activation of various metabolic systems, together with faulty redox signaling, is suggested to play a pivotal role in cancer development.

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“…We believe that the paleolithic ketogenic diet by excluding "non-paleolithic" food components normalizes the pathological permeability of the intestines as also seen in a published case of Crohn's disease [22], and likely through the normalization of intestinal permeability results in lowering inflammatory factors (as also showed in our previous case reports). In addition, ketosis, based on animal meat and fat may ensure optimal supply and bioavailability of vitamins, including vitamin C [33] the high blood level of which is important for the proper functioning of the immune system and also convey antitumor effects [34].…”

Section: Discussionmentioning

confidence: 99%

Complete Cessation of Recurrent Cervical Intraepithelial Neoplasia (CIN) by the Paleolithic Ketogenic Diet: A Case Report

Tóth¹,

Schimmer²

2018

JCRT

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Background: Ketogenic diets have repeatedly been suggested for the treatment of cancer. To date, only a few case studies reporting long term benefits associated with such diets have been published. Case report: Here we present a case where recurrent cervical intraepithelial neoplasia (CIN), a premalignant condition of cervical cancer, was successfully treated with the paleolithic ketogenic diet. The patient had a history of high grade CIN in 2011, which was successfully treated with cervical conization and fractional curettage. In October 2015 she was found to have a recurrence of high grade CIN (HSIL: High Grade Squamous Intraepithelial Lesion). The patient was then commenced on the paleolithic ketogenic diet and her repeat Pap (Papanicolaou) smear three months later was found to have reverted to normal. The patient has remained on the paleolithic ketogenic diet for 26 months, her repeat smears have stayed normal, and she is free of symptoms and side effects. Conclusion: We conclude that the diet was effective and safe in this patient. As a major benefit the patient was able to avoid a hysterectomy, which is the standard treatment for recurrent high-grade CIN. We believe that the paleolithic ketogenic diet combines benefits of both paleolithic and classical ketogenic diets, while excluding their disadvantages.

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Controlling Hyperglycemia as an Adjunct to Cancer Therapy

Cited by 70 publications

References 56 publications

Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase

Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase

Significant Dietary Changes during Human Evolution and the Development of Cancer: From Cells in Trouble to Cells Causing Trouble

Complete Cessation of Recurrent Cervical Intraepithelial Neoplasia (CIN) by the Paleolithic Ketogenic Diet: A Case Report

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