Bioelectrical impedance phase angle as a prognostic indicator in breast cancer

<p>Abstract</p> <p>Background</p> <p>Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive, and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by bioelectrical impedance analysis (BIA), detects changes in tissue electrical properties and has been hypothesized to be a marker of malnutrition. Since malnutrition can be found in patients with breast cancer, we investigated the prognostic role of phase angle in breast cancer.</p> <p>Methods</p> <p>We evaluated a case series of 259 histologically confirmed breast cancer patients treated at Cancer Treatment Centers of America. Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of stage at diagnosis and prior treatment history. Survival was calculated as the time interval between the date of first patient visit to the hospital and the date of death from any cause or date of last contact/last known to be alive.</p> <p>Results</p> <p>Of 259 patients, 81 were newly diagnosed at our hospital while 178 had received prior treatment elsewhere. 56 had stage I disease at diagnosis, 110 had stage II, 46 had stage III and 34 had stage IV. The median age at diagnosis was 49 years (range 25 – 74 years). The median phase angle score was 5.6 (range = 1.5 – 8.9). Patients with phase angle <= 5.6 had a median survival of 23.1 months (95% CI: 14.2 to 31.9; n = 129), while those > 5.6 had 49.9 months (95% CI: 35.6 to 77.8; n = 130); the difference being statistically significant (p = 0.031). Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that every one unit increase in phase angle score was associated with a relative risk of 0.82 (95% CI: 0.68 to 0.99, P = 0.041). Stage at diagnosis (p = 0.006) and prior treatment history (p = 0.001) were also predictive of survival independent of each other and phase angle.</p> <p>Conclusion</p> <p>This study demonstrates that BIA-derived phase angle is an independent prognostic indicator in patients with breast cancer. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with breast cancer.</p

Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice

Introduction High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice. Methods The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion. Results Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion. Conclusions Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice

Cathepsin E Deficiency Impairs Autophagic Proteolysis in Macrophages

Cathepsin E is an endosomal aspartic proteinase that is predominantly expressed in immune-related cells. Recently, we showed that macrophages derived from cathepsin E-deficient (CatE-/-) mice display accumulation of lysosomal membrane proteins and abnormal membrane trafficking. In this study, we demonstrated that CatE-/- macrophages exhibit abnormalities in autophagy, a bulk degradation system for aggregated proteins and damaged organelles. CatE-/- macrophages showed increased accumulation of autophagy marker proteins such as LC3 and p62, and polyubiquitinated proteins. Cathepsin E deficiency also altered autophagy-related signaling pathways such as those mediated by the mammalian target of rapamycin (mTOR), Akt, and extracellular signal-related kinase (ERK). Furthermore, immunofluorescence microscopy analyses showed that LC3-positive vesicles were merged with acidic compartments in wild-type macrophages, but not in CatE-/- macrophages, indicating inhibition of fusion of autophagosome with lysosomes in CatE-/- cells. Delayed degradation of LC3 protein was also observed under starvation-induced conditions. Since the autophagy system is involved in the degradation of damaged mitochondria, we examined the accumulation of damaged mitochondria in CatE-/- macrophages. Several mitochondrial abnormalities such as decreased intracellular ATP levels, depolarized mitochondrial membrane potential, and decreased mitochondrial oxygen consumption were observed. Such mitochondrial dysfunction likely led to the accompanying oxidative stress. In fact, CatE-/- macrophages showed increased reactive oxygen species (ROS) production and up-regulation of oxidized peroxiredoxin-6, but decreased antioxidant glutathione. These results indicate that cathepsin E deficiency causes autophagy impairment concomitantly with increased aberrant mitochondria as well as increased oxidative stress

Dietary Fat, Fiber, Vegetable, and Micronutrients Are Associated With Overall Survival in Postmenopausal Women Diagnosed With Breast Cancer

Relatively few studies have assessed the relationship between dietary intakes and survival after breast cancer diagnosis. We investigated the influence of diet, including dietary fat (percentage energy), fiber, vegetable, and fruit intakes, and micronutrients (folate, carotenoids, and vitamin C) on overall survival in women diagnosed with breast cancer. Subjects were postmenopausal women diagnosed with breast cancer (N = 516) between 1994 and 1995 with a mean survival time of 80 mo (SD: 18). Subjects completed a food frequency questionnaire for the year prior to diagnosis. Cox proportional hazards models were used to measure the relationship between dietary intakes and death due to any cause after breast cancer diagnosis. In the multivariate analysis, we found that the hazard ratio [HR and 95% confidence interval (CI)] of dying in the highest tertile compared to the lowest tertile of total fat, fiber, vegetable, and fruit was 3.12 (95% CI = 1.79-5.44), 0.48 (95% CI = 0.27-0.86), 0.57 (95% CI = 0.35-0.94), and 0.63 (95% CI = 0.38-1.05), respectively (

Dietary approaches for weight loss with increased intakes of fruit, vegetables and dairy products

Aim: To assess the effectiveness of specific advice for increasing fruit, vegetable and dairy intake in free-living men participating in a weight loss study.Methods: Subjects were randomised to one of two 12-week weight loss diets, either the WELL with daily targets of four serves of fruit, four serves of vegetables and three serves of dairy or a low fat diet (LF) with general advice to increase fruit and vegetable intake. Three-day food group diaries and a food frequency questionnaire assessed intake.Results: Fifty-four overweight/obese male adults completed the study (WELL, n = 27; LF, n = 27; body mass index (mean &plusmn; standard deviation), 30.4 &plusmn; 2.5 kg/m2; age, 47.7 &plusmn; 9.5 years). There was no difference in mean weight change between groups (WELL, &minus;4.8 &plusmn; 3.3 kg; LF, &minus;4.6 &plusmn; 3.1 kg). Subjects on the WELL diet had greater (mean difference &plusmn; standard error) fruit (0.7 &plusmn; 0.2 serves/day), vegetable (1.2 &plusmn; 0.2 serves/day) and dairy (1.1 &plusmn; 0.1 serves/day) intakes than the LF group (measured by the food group diaries) (all P &lt; 0.01). The WELL group reached the daily target for fruit from week 1 (4.7 &plusmn; 1.4 serves/day), vegetables by week 6 (4.1 &plusmn; 1.5 serves/day) and for dairy by week 8 (3.0 &plusmn; 0.8 serves/day).Conclusions: Providing specific dietary targets to men for weight loss appears to promote greater consumption of fruit, vegetable and dairy foods than providing general dietary advice. Meeting dietary targets appears to require different adjustment periods depending on the food type.<br /