Energy restriction and the risk of spontaneous mammary tumors in mice: A meta‐analysis

Dirx, M.J.M.; Zeegers, Maurice P.; Dagnelie, Pieter C.; Bogaard, Ton van den; Brandt, Piet A. van den

doi:10.1002/ijc.11277

Cited by 139 publications

(102 citation statements)

References 31 publications

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“…Prior to the current study, widely documented as the greatest environmental modulator of mammary tumor development in rodents (26). By comparison, unlimited access to high metabolizable energy food increased tumor incidence by only 90%, produced a modest 1.33 relative risk for malignancy, and had no effect on tumor growth (27).…”

Section: Discussionmentioning

confidence: 76%

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Hermes¹,

Delgado²,

Tretiakova³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

178

140

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In a life span study, we examined how the social environment regulates naturally occurring tumor development and malignancy in genetically prone Sprague-Dawley rats. We randomly assigned this gregarious species to live either alone or in groups of five female rats. Mammary tumor burden among social isolates increased to 84 times that of age-matched controls, as did malignancy, specifically a 3.3 relative risk for ductal carcinoma in situ and invasive ductal carcinoma, the most common early breast cancers in women. Importantly, isolation did not extend ovarian function in late middle age; in fact, isolated animals were exposed to lower levels of estrogen and progesterone in the middle-age period of mammary tumor growth, with unchanged tumor estrogen and progesterone receptor status. Isolates, however, did develop significant dysregulation of corticosterone responses to everyday stressors manifest in young adulthood, months before tumor development, and persisting into old age. Among isolates, corticosterone response to an acute stressor was enhanced and recovery was markedly delayed, each associated with increased mammary tumor progression. In addition to being stressed and tumor prone, an array of behavioral measures demonstrated that socially isolated females possessed an anxious, fearful, and vigilant phenotype. Our model provides a framework for studying the interaction of social neglect with genetic risk to identify mechanisms whereby psychosocial stressors increase growth and malignancy of breast cancer.breast cancer ͉ glucocorticoids ͉ physiological stress ͉ psychological stress ͉ social behavior

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Section: Discussionmentioning

confidence: 76%

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Hermes¹,

Delgado²,

Tretiakova³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

178

140

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“…The NXS2 neuroblastoma line in mice induces consistent and reproducible metastases in a pattern that resembles the clinical scenario observed in neuroblastoma patients at advanced stages of the disease (31). Experimental metastases in the liver, kidneys, adrenal gland, and ovaries were observed after 25-30 days of the inoculation with 200,000 NXS2 cells (Table S1) as described in ref.…”

Section: Short-term Starvation Prevents the Death Of Mice But Not Of mentioning

confidence: 75%

“…Experimental metastases in the liver, kidneys, adrenal gland, and ovaries were observed after 25-30 days of the inoculation with 200,000 NXS2 cells (Table S1) as described in ref. 31. The tumor development and survival of the NXS2/STS/Eto group was significantly different from that of the NXS2 group (P Ͻ 0.001; Fig.…”

Section: Short-term Starvation Prevents the Death Of Mice But Not Of mentioning

confidence: 87%

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Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Raffaghello

Lee

Safdie

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

509

496

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Strategies to treat cancer have focused primarily on the killing of tumor cells. Here, we describe a differential stress resistance (DSR) method that focuses instead on protecting the organism but not cancer cells against chemotherapy. Short-term starved S. cerevisiae or cells lacking proto-oncogene homologs were up to 1,000 times better protected against oxidative stress or chemotherapy drugs than cells expressing the oncogene homolog Ras2 val19 . Lowglucose or low-serum media also protected primary glial cells but not six different rat and human glioma and neuroblastoma cancer cell lines against hydrogen peroxide or the chemotherapy drug/ pro-oxidant cyclophosphamide. Finally, short-term starvation provided complete protection to mice but not to injected neuroblastoma cells against a high dose of the chemotherapy drug/prooxidant etoposide. These studies describe a starvation-based DSR strategy to enhance the efficacy of chemotherapy and suggest that specific agents among those that promote oxidative stress and DNA damage have the potential to maximize the differential toxicity to normal and cancer cells.reactive oxygen species ͉ short-term starvation ͉ maintenance mode O ur studies in S. cerevisiae and those of others in worms, flies, and mice have uncovered a strong association between lifespan extension and resistance to oxidative stress (1-6). This resistance is observed in long-lived yeast cells lacking RAS2 and SCH9, the orthologs of components of the human Ras and Akt/S6K pathways (2, 5, 7), and in long-lived worms and mice with reduced activity of homologs of the IGF1 receptor (IGF1R), implicated in many human cancers (8). Notably, the IGF1R functions upstream of Ras and Akt in mammalian cells (3-6). Stress resistance is also observed in model systems in which calorie intake is reduced by at least 30% (9). This reduced calorie intake, also known as calorie restriction (CR) or dietary restriction (DR), has been studied for many years and is known to extend life span in organisms ranging from yeast to mice (10). CR also protects against spontaneous cancers and against carcinogen-induced cancers (10-12), raising the possibility that CR and reduced IGF1 may increase stress resistance by similar mechanisms.Our discovery of the role of Ras2 and Sch9 in the negative regulation of antioxidant and other protective systems together with the association between mutations that activate IGF1R, Ras, or Akt and many human cancers prompted our hypothesis that normal but not cancer cells would respond to starvation or down-regulation of Ras/Akt signaling by entering a stressresistance mode. In fact, one of the major ''hallmarks of cancer cells'' is the self-sufficiency for growth signals (13). In the majority of cancers, this ability to grow or remain in a growth mode even in the absence of growth factors is provided by the hyperactivation of one or several components of the IGF1R, Ras, Akt, and mTor pathways.Here, we tested the hypothesis that short-term starvation (STS) or low glucose/low serum can protect mammalian c...

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“…Along with this life span extension is a reduction in chronic diseases that are common to mankind, reviewed in Hursting et al [6]. A recent meta-analysis of 14 experimental studies found that energy restriction resulted in a 55% reduction in spontaneous tumors in laboratory mice [7]. Calorie restriction inhibited induced mammary tumors in mice [8] and suppressed implanted tumor growth and prolonged survival in energy restricted mice [9].…”

Section: Reviewmentioning

confidence: 99%

Nutrition and cancer: A review of the evidence for an anti-cancer diet

Donaldson¹

2004

Nutr J

551

344

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It has been estimated that 30–40 percent of all cancers can be prevented by lifestyle and dietary measures alone. Obesity, nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes), low fiber intake, consumption of red meat, and imbalance of omega 3 and omega 6 fats all contribute to excess cancer risk. Intake of flax seed, especially its lignan fraction, and abundant portions of fruits and vegetables will lower cancer risk. Allium and cruciferous vegetables are especially beneficial, with broccoli sprouts being the densest source of sulforophane. Protective elements in a cancer prevention diet include selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids (α-carotene, β-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited benefits orally, but could be very beneficial intravenously. Supplementary use of oral digestive enzymes and probiotics also has merit as anticancer dietary measures. When a diet is compiled according to the guidelines here it is likely that there would be at least a 60–70 percent decrease in breast, colorectal, and prostate cancers, and even a 40–50 percent decrease in lung cancer, along with similar reductions in cancers at other sites. Such a diet would be conducive to preventing cancer and would favor recovery from cancer as well.

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Energy restriction and the risk of spontaneous mammary tumors in mice: A meta‐analysis

Cited by 139 publications

References 31 publications

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Nutrition and cancer: A review of the evidence for an anti-cancer diet

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