BackgroundObesity is associated with an increased risk of breast cancer recurrence and cancer death. Recurrent cancers arise from the pool of residual tumor cells, or minimal residual disease (MRD), that survives primary treatment and persists in the host. Whether the association of obesity with recurrence risk is causal is unknown, and the impact of obesity on MRD and breast cancer recurrence has not been reported in humans or in animal models.MethodsDoxycycline-inducible primary mammary tumors were generated in intact MMTV-rtTA;TetO-HER2/neu (MTB/TAN) mice or orthotopic recipients fed a high-fat diet (HFD; 60% kcal from fat) or a control low-fat diet (LFD; 10% kcal from fat). Following oncogene downregulation and tumor regression, mice were followed for clinical recurrence. Body weight was measured twice weekly and used to segregate HFD mice into obese (i.e., responders) and lean (i.e., nonresponders) study arms, and obesity was correlated with body fat percentage, glucose tolerance (measured using intraperitoneal glucose tolerance tests), serum biomarkers (measured by enzyme-linked immunosorbent assay), and tissue transcriptomics (assessed by RNA sequencing). MRD was quantified by droplet digital PCR.ResultsHFD-Obese mice weighed significantly more than HFD-Lean and LFD control mice (p < 0.001) and had increased body fat percentage (p < 0.001). Obese mice exhibited fasting hyperglycemia, hyperinsulinemia, and impaired glucose tolerance, as well as decreased serum levels of adiponectin and increased levels of leptin, resistin, and insulin-like growth factor 1. Tumor recurrence was accelerated in HFD-Obese mice compared with HFD-Lean and LFD control mice (median relapse-free survival 53.0 days vs. 87.0 days vs. 80.0 days, log-rank p < 0.001; HFD-Obese compared with HFD-Lean HR 2.52, 95% CI 1.52–4.16; HFD-Obese compared with LFD HR 2.27, 95% CI 1.42–3.63). HFD-Obese mice harbored a significantly greater number of residual tumor cells than HFD-Lean and LFD mice (12,550 ± 991 vs. 7339 ± 2182 vs. 4793 ± 1618 cells, p < 0.001).ConclusionThese studies provide a genetically engineered mouse model for study of the association of diet-induced obesity with breast cancer recurrence. They demonstrate that this model recapitulates physiological changes characteristic of obese patients, establish that the association between obesity and recurrence risk is causal in nature, and suggest that obesity is associated with the increased survival and persistence of residual tumor cells.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1087-7) contains supplementary material, which is available to authorized users.
Background: Human immunodeficiency virus (HIV) infection is characterized by decrease in CD4 cell count and immunodeficiency, leading to opportunistic infections (OIs) and tumors. Objective of this study was to find out any association between thyroid function abnormality and CD4 count, duration of disease and ART drugs.Methods: Among 300 HIV/AIDS Persons attending ART centre, M.Y. Hospital, or attending general OPD, or admitted as in patients Dept. of Medicine, MGM Medical College and M.Y. Hospital, Indore, India.Results: Amongst 300 HIV patients,62 (20.66%) had thyroid dysfunction, most common being subclinical hypothyroidism (24/300, 8.0%) followed by sick euthyroid (17/300, 5.6%) and subclinical hyperthyroidism (13/300, 4.3%). Overt hypothyroidism was present in 5 of 300 (1.66%) patients and overt hyperthyroidism was present in 3 of 300 (1.0%) patients. 25 of 152 (16.44%) and 37 of 148 (25%) male and female HIV patients had thyroid function abnormality. Thyroid dysfunction was significantly more observed in old HIV patients (42/150, 28.0%) than in newly diagnosed HIV patient’s group (20/150, 13.33%).Conclusions: This prevalence being fairly high, it can be suggested that all retro positive patients, recently diagnosed and on treatment also may be subjected for routine thyroid function testing.
Background: Metabolic syndrome is described by the clustering of several risk factors for cardiovascular disease such as hypertension, dyslipidemia, obesity, Insulin resistance, and high fasting plasma glucose. Objective of this study was to determine the frequency and evaluate the components of metabolic syndrome in post-menopausal women.Methods: This Descriptive study was conducted in OPD as well as IPD of Department of Medicine, Sri Siddhartha Medical college Hospital and Research Centre, Tumkur After obtaining written informed consent. Period of study was 24 months. Purposive sampling was used.Results: Mean age of post-menopausal women was 54.19±8.454 years. Mean age of menopause was 45.41±2.428. Majority of patients between were between 45-50 years (33.7%). There were high number of women (34.6%) whose postmenopausal duration ranged between 6-10 years. In our study 10(9.6%) postmenopausal women had type 2 DM and 15(14.4%) postmenopausal women had HTN. Metabolic syndrome was present in 65(62.5%) postmenopausal women and absent in 39(37.5%) postmenopausal women. Waist circumference >80 cm (68.3) was the most prevalent component of metabolic syndrome followed by HDL <50 mg/dl (53.8%), BP>130/80 mmHg (51%) triglycerides >150 mg/dl (44.2%)/ and FBS>100 mg/dl (39.4%). There was statistical significance observed between the components of metabolic syndrome and metabolic syndrome in postmenopausal women.Conclusions: The prevalence of metabolic syndrome was high in our study. The components of metabolic syndrome such as waist circumference, FBS, blood pressure, triglycerides were significantly raised and HDL levels were significantly reduced in post-menopausal women with metabolic syndrome.
Background: Microalbuminuria, defined as 30–300 mg/day of albumin excretion in urine is a common finding in ICU patients and has shown not only as a predictor of organ failure but prolonged intensive care unit (ICU) stay. Objective of the study was to determine the prediction of acute kidney injury using urine microalbuminuria and to determine the presence of urine microalbuminuria and relationship between ICU length of stay.Methods: The present study is conducted on patients admitted to Medical ICU in SDMCMSH, Dharwad from December 2016 to November 2017. 75 patients who met the inclusion and exclusion criteria were included in the study.Results: The present study included 75 patients, among which 50 were males and 25 were females. The mean age was 60.2years. AKI was developed more in non-diabetics than diabetics and non-hypertensives than hypertensives. The median urine microalbumin at admission in AKI was 80.9 and at 48 hr was130.1 predicted the AKI mean (1.79) in 59 patients with a p value of <0.001 using Mann Whitney test and P value statistically significant.Conclusions: Urine microalbuminuria at 48 hr has predicted AKI in 59 patients with median of 130.1 with statistical significance. Urine microalbuminuria of high value in AKI is directly proportional to prolonged ICU stay. At 48 hours of admission, increased levels of microalbuminuria compared at admission and 48 hour, indicates its prognostic significance among AKI and NON-AKI’s in ICU patients.
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