An experimental model of diabetes and cancer in rats

Cocca, Claudia; Martin, G. Saint; Rivera, Elena; Davio, Carlos; Cricco, G.; Lemos, B; Fitzsimons, Carlos P.; Gutiérrez, Alicia Beatriz; Levin, Emanuel; Levin, R; Croci, Máximo; Bergoc, Rosa

doi:10.1016/s0959-8049(97)10077-6

Cited by 21 publications

(11 citation statements)

References 28 publications

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“…None of the tumors in the control group (batch K) showed regression, whereas only 1 out of 40 (2%) remained stable. The TAM group (batch J) showed that 48% (16/33) of tumors regressed, some totally, in agreement with the experiments performed in other studies using the same tumor model (11,15,16). When rats were treated with compounds A and B, no tumor regressed, indicating that these compounds failed to act as inhibitors of tumoral growth.…”

Section: Resultssupporting

confidence: 87%

Antitumoral activity of a new series of 5,6‐dihydrobenzo( a)carbazoles

et al. 2002

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The overlapping of three-dimensional structures of 5,6-dihydrobenzo(a)carbazole (DHBC) derivatives over the structure of 4-hydroxytamoxifen (4-OH-TAM), by means of the MDL CHEMLAB 11.0 computational program, shows a reasonable structural and spatial resemblance. This finding raised the hypothesis of their possible antitumoral activity, similar to that of tamoxifen (TAM). A number of DHBCs with an alkyl chain and a second basic nitrogen as substituent were synthesized in our laboratory and their possible antitumoral activity was tested by means of: 1) competitive radioligand assays to determine relative drug affinity for the estrogen receptor (ER); 2) in vivo studies, giving the synthetic drugs subcutaneously (1 mg kg-1 day-1) to Sprague-Dawley rats with N-nitroso-N-methylurea (NMU)-induced mammary tumors; and 3) in vitro cell proliferation experiments employing the soft agar clonogenic technique. Besides, studies on toxicity and histopathological analyses of organs and tumors from treated animals were performed. Results obtained showed that: 1) relative binding affinities (RBA) for the ER were similar to that of TAM; 2) some structures showed significant antitumoral activity and induced tumoral regression similar to TAM; and 3) these compounds had in vitro inhibitory effect on cell proliferation. Even though all the compounds of the series of synthesized DHBCs showed affinity for the ER similar to TAM, the results of in vivo experiments confirmed the crucial role of hydroxyl groups in the molecule and of the interatomic distance between them, similar to that of estradiol, as well as the necessary presence of the aminoalkyl chain on the annular N atom. However, the effect of alkyl chain enlargement in the nitrogen substituent on the biological activity of those drugs is as yet unclear.

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Section: Resultssupporting

confidence: 87%

Antitumoral activity of a new series of 5,6‐dihydrobenzo( a)carbazoles

et al. 2002

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“…Given the inverse relationship between prostate cancer and HbA1c, this result may not be surprising. However, streptozotocin-induced diabetes also leads to inhibited growth of pancreatic and breast cancers in animal models (16,36,170). These results suggest that although tumors avidly take up glucose, delivering more glucose to tumors in the setting of hyperglycemia does not increase tumor growth.…”

Section: B Hyperglycemiamentioning

confidence: 99%

Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality

Gallagher

2015

Physiological Reviews

656

434

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Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes.

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“…10,11 Experiments with insulin-deficient (diabetic) animals have shown that insulin promotes tumor growth and development in xenograft models and in chemical models of carcinogenesis. [12][13][14][15][16][17] In addition, elevated insulin levels lead to a reduction in serum SHBG levels, and hence to increases in levels of bioavailable testosterone and estradiol [18][19][20] -factors that have all been associated with an increased risk of breast cancer among postmenopausal women. 21,22 It has thus been hypothesized that, especially among postmenopausal women, the increase of breast cancer risk related to physically inactivity and excess body weight might at least in part be due to elevated insulin levels.…”

mentioning

confidence: 99%

Serum C‐peptide levels and breast cancer risk: Results from the European prospective investigation into cancer and nutrition (EPIC)

Verheus

Peeters

Rinaldi

et al. 2006

Intl Journal of Cancer

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It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide-a marker for pancreatic insulin secretion-in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR) 5 0.70, (95% confidence interval (CI), 0.39-1.24); p trend 5 0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR 5 2.03, (95% CI, 1.20-3.43); p trend 5 0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk. ' 2006 Wiley-Liss, Inc.Key words: C-peptide; breast cancer; prospective; cohort; EPIC Excess body weight is a well-established risk factor for breast cancer among postmenopausal women, 1,2 whereas among both pre and postmenopausal women, regular physical activity has been generally associated with a reduced risk.

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An experimental model of diabetes and cancer in rats

Cited by 21 publications

References 28 publications

Antitumoral activity of a new series of 5,6‐dihydrobenzo( a)carbazoles

Antitumoral activity of a new series of 5,6‐dihydrobenzo( a)carbazoles

Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality

Serum C‐peptide levels and breast cancer risk: Results from the European prospective investigation into cancer and nutrition (EPIC)

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