Search

Background: Several studies have recently highlighted important roles for adipose tissue in cancer. However, few have examined adipose tissue cholesterol, and no study has been performed in breast adipose tissue associated with breast tumors., Objectives: The present work was designed to determine if breast adipose tissue cholesterol from the tumor-surrounding area is associated with breast cancer aggressiveness., Methods: Between 2009 and 2011, 215 breast adipose tissue samples were collected at the Tours University Hospital (France) during surgery of women (aged 28-89 y) with invasive breast cancer. Associations of free cholesterol (FC), esterified cholesterol (EC), and total cholesterol (TC) amounts with clinical variables (age, BMI, and treated or untreated hypercholesterolemia) and tumor aggressiveness parameters [phenotype, grade, presence of inflammatory breast cancer (IBC), and multifocality] were tested using Student's t test and after ANOVA., Results: The predominant form of cholesterol in adipose tissue was FC, and 50% of patients had no detectable EC. The adipose tissue FC content (μg/mg total lipid) was 18% greater in patients >70 y old than in those 40-49 y old (P < 0.05) and the TC content tended to be 12% greater in untreated hypercholesterolemic patients than in normocholesterolemic patients (P = 0.06). Breast adipose cholesterol concentrations were increased in tissues obtained from patients with human-epidermal-growth-factor-receptor-2 (HER2) phenotype (+13% FC; P < 0.05 compared with luminal A), IBC (+15% FC; P = 0.06 compared with noninflammatory tumors), as well as with multifocal triple-negative tumors (+34% FC, P < 0.05; +30% TC, P < 0.05, compared with unifocal triple-negative tumors). Among patients with triple-negative tumors, hypercholesterolemia was significantly more common (P < 0.05) in patients with multifocal tumors (64%) than in patients with unifocal tumors (25%)., Conclusions: This study is the first of this magnitude that analyzes cholesterol concentrations in adipose tissue from female breast cancer patients. An increase in breast adipose tissue cholesterol content may contribute to breast cancer aggressiveness (HER2 phenotype, multifocality of triple-negative tumors, and IBC)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: Since it is thought that breast adipose tissue could influence breast cancer clinical presentation, we wanted to characterize specifically the relationship between breast adipose tissue fatty acid profile and Inflammatory Breast cancer (IBC)., Methods: Two hundred thirty-four women presenting with breast cancer were managed in our centre between January 2009 and December 2011. Breast adipose tissue specimens were collected during breast surgery. We established the biochemical profile of adipose tissue fatty acids (FA) by gas chromatography and assessed whether there were differences in function of the presence of breast inflammation or not., Results: We found that IBC was associated with decreased levels in breast adipose tissue of eicosapentaenoic acid (EPA), one of the two main polyunsaturated n-3 fatty acids (n-3 PUFA) of marine origin, but also with decreased levels of Gamma Linolenic acid (GLA). Inversely, an increase in palmitic acid levels was associated with IBC., Conclusion: These differences in lipid content may contribute to the occurrence of breast cancer inflammation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Long-chain omega-3 polyunsaturated fatty acids are thought to inhibit the development of breast cancer. We investigated the effects of docosahexaenoic and eicosapentaenoic acids on the proliferation of MDA-MB-231 human mammary epithelial cells. Both docosahexaenoic and eicosapentaenoic acids decreased cell growth with a higher efficiency for docosahexaenoic acid (87% at 100 microM versus 74% for eicosapentaenoic acid). The effect on specific cell cycle phases was studied. G2/M duration was markedly increased by docosahexaenoic and by eicosapentaenoic acids (respectively by more than seven- and six-fold at 50 microM) when cells were synchronized at the G1/S boundary and released in the cell cycle. In contrast, there was no alteration of G1 or S phases. The expression of cyclin A, cyclin B1 and cyclin-dependent kinase 1, the regulators required for the progression from G2 to mitosis, were all decreased by these fatty acids (western blot). Since omega-3 fatty acids had no effect on the S phase, thus ruling out an involvement of cyclin A in their anti-proliferative effect, we examined whether the regulation of the cyclin-dependent kinase 1-cyclin B1 complex was altered. Upon omega-3 fatty acids treatment, cyclin B1 phosphorylation was inhibited and the expression of the cell division cycle 25C phosphatase, which dephosphorylates cyclin-dependent kinase 1, was decreased. We conclude that the anti-proliferative effect of omega-3 fatty acids occurs via the regulation of the cyclin-dependent kinase 1-cyclin B1 complex.

As part of a clinical research project, proliferative parameters were studied in primary breast cancer: standardization and technical validation of thymidine kinase (TK), thymidylate synthase (TS) and protein tyrosine kinase (PTK) are described. A total of 633 frozen tumor specimens, available in four institutions, was analyzed in three flow cytometry laboratories for DNA content and percentage of S-phase cells (%S) measurement. 1) The standardization step consisted in developing a common protocol for sample preparation; then, common cell suspensions were analyzed in order to perform an inter-laboratory control. Objective guidelines were elaborated to interpret DNA histograms in breast carcinoma. 2) DNA-aneuploidy was observed in 61% of cases of the retrospective series. Compared with DNA-aneuploid tumors, mean %S was significantly lower in case of DNA-diploidy (respectively: 6.4% and 2.2%, p < 0.001). When compared between the four institutions, %S distributions did not differ significantly. 3) %S is strongly correlated with TK, TS and PTK and high percentages were also observed in high grade tumors or tumor without hormone receptors. These results show that a standardization in using flow cytometers and DNA software allows multicenter studies.

Accumulated evidence suggests that increased endogenous opioid activities may facilitate the onset of hibernation. The present study investigated the change in thermoregulatory responses following ICV infusion of morphine or [D-Ala2]-Met enkephalinamide (EK) in unanesthetized, unrestrained Columbian ground squirrels (Spermophilus columbianus) during its annual hibernation cycle. In the nonhibernating phase, low doses of either morphine (less than 160 micrograms) or EK (less than 400 micrograms) elicited a dose-related hyperthermia and an increase in heat production, whereas a higher dose of opiates caused hypothermia and a decrease in metabolic rate. Naloxone (5 mg/kg, SC) pretreatment reduced or reversed both the hyper- and hypothermic responses to opiates. Lower ambient temperature (5 degrees C) enhanced the hypothermic response and attenuated the hyperthermic response. In the hibernating phase, euthermic ground squirrels exhibited a reduced responsiveness to exogenous opiates: the hyperthermic response to low dose of morphine (10 micrograms) was significantly reduced and hyperthermia, rather than hypothermia was observed at the highest dose of morphine (160 micrograms). The reduced responsiveness to opiates observed during the hibernating phase seems to suggest a reduction in opiate receptor efficacy which is in agreement with the contention that an increase in endogenous opioid activities may be incumbent with the commencement of hibernation.

Previous studies showed that acute treatment with aminophylline (AMPY) significantly elevated maximum thermogenesis and improved cold tolerance in rats and man in severe cold. However, the exact mechanism by which AMPY enhances thermogenesis was unknown. Rats receiving enprofylline (ENPRO) (1.5 and 15 mg/kg, i.p.), a selective phosphodiesterase inhibitor, failed to show enhanced thermogenesis. In contrast, treatment with a selective adenosine receptor antagonist, 8-phenyltheophylline(8-PT; 2.5 to 10 mg/kg, i.p.), significantly increased (p less than 0.05) thermogenesis and cold tolerance. However, the maximal thermogenic effect by optimal dose of 8-PT (5 mg/kg) was significantly lower than that with optimal dose of AMPY (18.7 mg/kg, i.p.); the deficit could be eradicated by combining optimal 8-PT dose with a low dose of AMPY (1.25 mg/kg), but not with ENPRO. These results indicate that the thermogenic effect of AMPY is not by inhibition of phosphodiesterase but at least partially by antagonism of adenosine receptors. It is also apparent that older mechanisms in addition to adenosine antagonism are also involved in AMPY's thermogenic action.

Even though the existence of the blood-borne "hibernation induction trigger" has been reported in the 13-lined ground squirrel, transfusion of plasma from hibernating rodents with other hibernating species as the recipients failed to induce the occurrence of summer hibernation. In order to verify whether the response to the "trigger" substance is species specific, the present study was carried out to compare the effect of plasma from hibernating Richardson's ground squirrels on the incidence of summer hibernation in both juvenile Richardson's and adult 13-lined ground squirrels. In two series of experiments, 13-lined ground squirrels entered hibernation quite readily independent of the treatment. The rate of occurrence of hibernation ranged from 78% after sham injection to 86% after warm saline, fresh summer active plasma, and fresh hibernating plasma, respectively. There were no differences in the number of hibernation bouts and the number of days in hibernation after each treatment. In contrast, none of the juvenile Richardson's ground squirrels entered hibernation after any of the treatments up to the end of the 8-week observation period. These results not only argue against the existence of blood-borne "trigger" substance, at least in the Richardson's ground squirrel, but also caution against the use of the 13-lined ground squirrel as a standard test animal for the bioassay of the "trigger" substance.

In an attempt to further elucidate the mechanisms of fasting-depressed maximum thermogenesis and cold tolerance, norepinephrine (NE)-stimulated non-shivering thermogenesis (NST) in cold-acclimated rats was used as a functional index of possible alterations in adrenergic efficacy after fasting. Fasting decreased the magnitude of maximum NE-Stimulated NST by 18.2% [6.87 +/- 0.47 Kcal (Kg X 75 X min)-1 well-fed vs. 5.81 +/- 0.39 Kcal (Kg X 75 X min)-1 fasted], but the apparent adrenergic binding affinity was not affected [Ke = 0.43 micrograms NE min-1 well-fed vs. 0.55 micrograms NE min-1 fasted]. Pretreatment with aminophylline [15 mg Kg-1, i.p.], a phosphodiesterase inhibitor, restored the fasting-depressed NE-stimulated NST to the fed level. The results suggest that the depression of maximum thermogenesis after fasting is not due to changes in adrenergic binding characteristics but to alteration in cAMP production/degradation, resulting in decreased substrate mobilization for thermogenesis.