BackgroundAtherosclerotic cardiovascular diseases are the leading cause of death in the United States. A reduction in cholesterol with 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statin) significantly reduces mortality and morbidity. Statins may be associated with cognitive impairment or dementia. Our aim was to study the association of cognitive impairment or dementia in patients who were on a statin.MethodsElectronic medical records of 3,500 adult patients in our suburban internal medicine office were reviewed.ResultsThere were 720 (20.6%) patients in the statin treatment group. Dementia or cognitive impairment was an associated comorbid condition in 7.9% patients in the statin treatment group compared to 3.1% patients in the non-statin group (P < 0.001). Analysis of all of the patients with cognitive impairment or dementia showed that among the age ranges of 51 years through 100 years, the patients in the statin treatment group had a higher prevalence of cognitive impairment or dementia compared to the non-statin group. In the statin treatment group, we found significantly higher prevalence of hyperlipidemia (86.3%), hypertension (69.6%), diabetes mellitus (36.0%), osteoarthritis (31.5%), coronary artery disease (26.1%), hypothyroidism (21.5%) and depression (19.3%) compared to the non-statin group (P < 0.001). About 39.9% of the patients with dementia or cognitive impairment were on statin therapy compared to 18.9% patients who had no dementia or cognitive impairment and were on statin therapy (P < 0.001). Among the patients with cognitive deficit or dementia in the statin treatment group, the majority of the patients were either on atorvastatin (43.9%) or simvastatin (35.1%), followed by rosuvastatin (12.2%) and pravastatin (8.8%). We found greater odds of dementia or cognitive impairment with each year increase in age (1.3 times), in women (2.2 times), African American race (2.7 times), non-consumption of moderate amount of alcohol (two times), diabetes mellitus (1.6 times), hypothyroidism (1.7 times), cerebrovascular accident (3.2 times), and other rheumatological diseases (1.8 times).ConclusionsThe association of dementia or cognitive impairment was significantly higher in the patients who were on statin therapy compared to the patients who were not on a statin.

No abstract

PURPOSE:Stromal vascular fraction (SVF) is used in breast reconstruction in FDA clinically approved studies. In SVF, adipose derived stem cells (ASC) may play a role in wound healing. In patients following chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. Previous work in our laboratory demonstrated that direct exposure to Paclitaxel (PTX) has cytotoxic effects on ASCs by decreasing proliferation and multipotency. This study examined human ASCs pretreated with PTX and then exposed to a washout period (no PTX) of 8 days to evaluate 1) the influence on ASC function after chemotherapy cessation and 2) influence on tumor cell growth in ASC co-culture. METHODS:IRB-approved human ASCs were isolated and MDA-MB-231 cells (breast cancer cell line) were treated with PTX at different concentrations. Cell proliferation, viability, and migration were measured by growth curves, MTT assays, and scratch assays. ASCs were cultured in derivative-specific differentiation media with or without PTX (1uM) for 3 weeks. Adipogenic and endothelial differentiation were measured by quantitative RT-PCR, Oil-Red-O staining and cord formation on Matrigel, respectively. MDA-MB-231 cells and ASCs were co-cultured at equal cell numbers. ASC conditional media were collected every 3 days from ASCs, both no-PTX treatment control and PTX treated -washout groups. RESULTS:Following cessation and washout of PTX, 2.4-fold (0.1uM) and 4.0-fold (1uM) lower proliferation rates were observed in ASC when compared with a no-PTX treatment control group. In comparison with no-PTX untreated controls, PTX treated -washout ASC had decreased cell migration (relative scratch width: 29±10% vs. 86±4%, p<0.05). PTX treated -washout ASCs compared to no-PTX ASC treatment group demonstrated: 1) decreased rates of adipogenic differentiation with lower Oil-Red-O positive stained lipid droplets and decreased mRNA levels of PPAR-γ, LPL; and 2) decreased rates of endothelial differentiation with decreased cord formation on Matrigel with decreased levels of CD31, vWF and eNOS. In a second series of studies, MDA-MB-231 cells treated with PTX treated -washout ASC conditional medium (ASC-CM) for 8 days (indirect co-culture) exhibited a decrease in cell growth (10 fold in PTX pre-treated CM; p<0.01). The cumulative population doubling time was longer for the ASC-CM (PTX pre-treated) compared to conditional medium from ASC with no exposure to PTX (5.89±0.38 day vs. 1.61±0.04 day, p<0.01). In direct co-culture with both ASC and MDA-MB-231, total cellular mRNA expression of Caspase 3 (1.7 fold, p<0.01) was increased while mRNA expression of the breast cancer marker SNCG (1.6 fold, P<0.05) was decreased compared to respective cell types cultured separately for 7 days. CONCLUSION:Our results showed that ASCs after PTX treated -washout had decreased proliferation and multi-lineage differentiation rates. Direct ASC contact and conditional medium from PTX treated -washout ASCs suppressed tumor cell growth. These results may provide insight into associated p...

Background: Following neoadjuvant or adjuvant chemotherapy for breast cancer resections, poor soft tissue wound healing can pose a major clinical challenge. Adipose-derived stem cells (ASCs) in clinically applied stromal vascular fractions are considered to play a positive role in wound healing (SVF) as evidenced by their increasing use in breast reconstructive procedures. Our study evaluated the potential confounding effects of Paclitaxel (PTX) on ASC proliferation and differentiation capacities and if PTX treated ASCs may subsequently influence tumor cell viability. Methods: IRB-approved human ASCs were isolated and treated with PTX at different concentrations. Proliferation, cell viability, and cell migration rates were measured by growth curves, MTT assays and scratch assays. ASCs were cultured in derivative-specific differentiation media with or without PTX (1uM) for 3 weeks. Adipogenic, osteogenic and endothelial differentiation levels were measured by quantitative RT-PCR, Oil-Red-O, Alizarin Red staining and cord formation on Matrigel, respectively. MDA-MB-231 (breast cancer cell line) and ASCs were co-cultured at equal cell numbers. ASC conditional media were collected every 3 days from ASC no-PTX treatment and PTX treated - washout groups. Results: PTX decreased proliferation of ASCs in a dose- and time-dependent manner. PTX treatment down-regulated the capacity of ASCs for adipogenic, osteogenic and endothelial differentiation (p&lt;0.05 vs. control). In comparison with controls, PTX treated ASCs had decreased cell migration (relative scratch width, p&lt;0.05 vs. control). Following cessation and washout of PTX after 8 days, treated ASCs exhibited cell growth and differentiating ability, but their capacity was suppressed compared to controls. The cumulative population doubling time was longer for cells co-cultured with PTX treated-washout ASC conditional media. (p&lt;0.01 vs. no-PTX treatment group). Total cellular mRNA expressions of epithelial cell adhesion molecule (EPCAM), synuclein gamma (breast cancer specific protein 1; SNCG) and tumor necrosis factor alpha (TNF-α) were down-regulated in MDA-MB-231 cells when co-cultured directly with PTX treated ASC or indirectly with PTX treated-washout ASC conditional media (p&lt;0.05 vs. control). In cells co-cultured for 3 days, VEGF proteins released in conditioned medium were decreased compared with single cultures (p&lt;0.01 vs. control). Conclusion: Our results indicate that: 1) PTX inhibited ASC proliferation and decreased the multipotency differentiating capacity; and 2) Direct contact or treatment with conditional media from PTX treated ASCs suppressed tumor cell growth. In evaluating autologous ASCs for reconstructive procedures, this study may provide insight into poor soft tissue wound healing immediately following the removal of chemotherapy as well as decreased recurrence in breast cancer patients. Citation Format: William M. Harris, Michael Plastini, Telisha Ortiz, Nikolas Kappy, Jefferson Benites, Shaohua Chang, A. Lelani Fahey, Martha S. Matthews, Alexandre Hageboutros, Jeffrey P. Carpenter, Spencer Brown, Ping Zhang. Adipose-derived stem cells after Paclitaxel treatment demonstrate decreased function and suppression of breast cancer cell viability. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4077. doi:10.1158/1538-7445.AM2015-4077