scholarly journals Dietary Tomato Inhibits Tumor Angiogenesis in the TRAMP Model of Prostate Cancer but Is Not Protective With a Western-Style Diet

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 260-260
Author(s):  
Catherine Applegate ◽  
Matthew Lowerison ◽  
Emma Hambley ◽  
Pengfei Song ◽  
John Erdman

Abstract Objectives The objective of this study was to investigate the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa. We hypothesized that TP would be protective against PCa growth. Methods Diets (either CON [17.2% kcal from fat] or OB [44.6% kcal from fat] both with and without 10% TP) were fed to transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (n = 5/dietary group) from weaning. Tumor growth was monitored by weekly ultrasound scanning, at which time novel ultrasound microvessel images (UMI) were captured to quantitatively measure tumor blood perfusion over time. Animals were euthanized after 5 weeks of tumor growth, and tissues were collected for measurement of protein (HIF-1α, TNFα) and gene (ar, srd5a1, srd5a2) expression. Data were analyzed to determine differences between CON diets (without TP + with 10% TP) and OB diets (without TP + with 10% TP) and to evaluate the impact of 10% TP on outcome measures both independent of TP (No TP vs. TP) as well as within CON and OB diets (interaction effect of diet*TP) by mixed model ANCOVA with body weight as a covariate. Results UMI results showed good agreement with gold-standard immunohistochemistry quantification of endothelial cell density, indicating that this technique can be applied to non-invasively and longitudinally monitor tumor blood perfusion in vivo. Greater body weight (P = 0.029) and OB diets (P = 0.008) were associated with earlier age at tumor detection, and greater body weight was positively associated with tumor growth (P = 0.001). TP significantly inhibited prostate tumor angiogenesis (P = 0.043), but this inhibition differentially affected measured outcomes depending on CON or OB diets. TP led to reduced tumor growth (P = 0.004), intratumoral inflammation (TNFα; P = 0.019), and intratumoral androgen-regulated gene expression (srd5a1, srd5a2; P = 0.030 and P = 0.016, respectively) when incorporated with the CON diet but greater tumor growth and intratumoral gene expression when incorporated with the OB diet. Conclusions Results from this study show that protective benefits from dietary tomato are lost, or may become deleterious, when combined with a Western-style diet. Funding Sources CA was supported by the NIH NIBIB. MRL and PS were partially supported by NIH NCI.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Catherine C. Applegate ◽  
Matthew R. Lowerison ◽  
Emma Hambley ◽  
Pengfei Song ◽  
Matthew A. Wallig ◽  
...  

AbstractProstate cancer (PCa) remains the second most diagnosed cancer worldwide. Higher body weight is associated with chronic inflammation, increased angiogenesis, and treatment-resistant tumor phenotypes. Dietary tomato reduces PCa risk, which may be due to tomato inhibition of angiogenesis and disruption of androgen signaling. This pilot study investigated the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa (TRAMP). Ultrasound microvessel imaging (UMI) results showed good agreement with gold-standard immunohistochemistry quantification of endothelial cell density, indicating that this technique can be applied to non-invasively monitor tumor blood perfusion in vivo. Greater body weight was positively associated with tumor growth. We also found that TP significantly inhibited prostate tumor angiogenesis but that this inhibition differentially affected measured outcomes depending on CON or OB diets. TP led to reduced tumor growth, intratumoral inflammation, and intratumoral androgen-regulated gene expression (srd5a1, srd5a2) when incorporated with the CON diet but greater tumor growth and intratumoral gene expression when incorporated with the OB diet. Results from this study show that protective benefits from dietary tomato are lost, or may become deleterious, when combined with a Western-style diet.


2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 63-64
Author(s):  
Amanda J Hubbard ◽  
Jason Sawyer ◽  
Reinaldo F Cooke ◽  
Jenny Jennings ◽  
Courtney L Daigle

Abstract This study evaluated the impact of mixing cattle from two sources of feedlot steers (n = 96) on feeding and lying behavior. Angus crossbred steers (n = 48 McG and n = 48 BCS), similar in genetic composition, were transported (833.64 ± 85.29 km) to a feedlot 39-d prior to mixing where the two sources were housed without visual or tactile contact. Steers, blocked by source and stratified by d -34 body weight, were randomly assigned to one of 12 pens (n = 8 steers/pen) for the 42-d study. Pens were assigned to one of two treatments (n = 6 pens/treatment): 1) NOMIX—100% of cattle from McG (n = 3 pens) or BCS (n = 3 pens) and, 2) MIX—50% of cattle from BCS and 50% from McG (n = 6 pens). Instantaneous scan sampling (n = 61 scans/d; 10 min intervals) recorded the number of steers per pen eating and lying on d1, 2, 3, 4, 5, 6, 7, 8, 9, 14, 15, 16, 21, 22, 23, 28, 29, 36, and 37 after mixing. Proportion of steers lying varied across time (P < 0.0001); however, a greater proportion of steers laid down on d1 compared to d7, 8, 9, 16, and 28 (P < 0.03). The proportion of steers observed eating increased over time (P < 0.0001). Fewer steers ate on d1 than d9, 14, 15, 28, 29, and 36 (all P < 0.01). More steers were observed eating on d8 and 16 than the first seven days (all P < 0.01) and on d37 than the first 6 days (all P < 0.02). While there was no impact of mixing, data indicate that handling and sorting cattle into new pens impacts eating and lying behavior and it takes approximately a week for behavior to stabilize.


2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 17-18
Author(s):  
Amanda J Hubbard ◽  
Jason Sawyer ◽  
Reinaldo F Cooke ◽  
Jenny Jennings ◽  
Courtney L Daigle

Abstract This study evaluated the impact of mixing cattle from two sources of feedlot steers (n = 96) on feeding and lying behavior. Angus crossbred steers (n = 48 McG and n = 48 BCS), similar in genetic composition, were transported (833.64 ± 85.29 km) to a feedlot 39-d prior to mixing where the two sources were housed without visual or tactile contact. Steers, blocked by source and stratified by d -34 body weight, were randomly assigned to one of 12 pens (n = 8 steers/pen) for the 42-d study. Pens were assigned to one of two treatments (n = 6 pens/treatment): 1) NOMIX—100% of cattle from McG (n = 3 pens) or BCS (n = 3 pens) and, 2) MIX—50% of cattle from BCS and 50% from McG (n = 6 pens). Instantaneous scan sampling (n = 61 scans/d; 10 min intervals) recorded the number of steers per pen eating and lying on d1, 2, 3, 4, 5, 6, 7, 8, 9, 14, 15, 16, 21, 22, 23, 28, 29, 36, and 37 after mixing. Proportion of steers lying varied across time (P < 0.0001); however, a greater proportion of steers laid down on d1 compared to d7, 8, 9, 16, and 28 (P < 0.03). The proportion of steers observed eating increased over time (P < 0.0001). Fewer steers ate on d1 than d9, 14, 15, 28, 29, and 36 (all P < 0.01). More steers were observed eating on d8 and 16 than the first seven days (all P < 0.01) and on d37 than the first 6 days (all P < 0.02). While there was no impact of mixing, data indicate that handling and sorting cattle into new pens impacts eating and lying behavior and it takes approximately a week for behavior to stabilize.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Nicolaas P. Pronk ◽  
A. Lauren Crain ◽  
Jeffrey J. VanWormer ◽  
Brian C. Martinson ◽  
Jackie L. Boucher ◽  
...  

Objective.To determine the accuracy of self-reported body weight prior to and following a weight loss intervention including daily self-weighing among obese employees.Methods.As part of a 6-month randomized controlled trial including a no-treatment control group, an intervention group received a series of coaching calls, daily self-weighing, and interactive telemonitoring. The primary outcome variable was the absolute discrepancy between self-reported and measured body weight at baseline and at 6 months. We used general linear mixed model regression to estimate changes and differences between study groups over time.Results.At baseline, study participants underreported their weight by an average of 2.06 (se=0.33) lbs. The intervention group self-reported a smaller absolute body weight discrepancy at followup than the control group.Conclusions.The discrepancy between self-reported and measured body weight appears to be relatively small, may be improved through daily self-monitoring using immediate-feedback telehealth technology, and negligibly impacts change in body weight.


Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2679
Author(s):  
Lihuai Yu ◽  
Hongmin Li ◽  
Zhong Peng ◽  
Yuzhu Ge ◽  
Jun Liu ◽  
...  

This study examined the impact of early weaning on antioxidant function in piglets. A total of 40 Duroc × Landrace × Large White, 21-day-old piglets (half male and half female) were divided into suckling groups (SG) and weaning groups (WG). Piglets in WG were weaned at the 21st day, while the piglets in SG continued to get breastfed. Eight piglets from each group were randomly selected and slaughtered at 24th-day (SG3, WG3) and 28th-day old (SG7, WG7). The body weight, liver index, hepatocyte morphology, antioxidant enzymes activity, gene expression of antioxidant enzymes, and Nrf2 signaling in the liver of piglets were measured. The results showed that weaning caused decreased body weight (p < 0.01), lower liver weight (p < 0.01), and decreased the liver organ index (p < 0.05) of piglets. The area and size of hepatocytes in the WG group was smaller than that in the SG group (p < 0.05). We also observed that weaning reduced the activity of superoxide dismutase (SOD) and catalase (CAT) (p < 0.05) in the liver of piglets. Relative to the SG3 group, the gene expression of GSH-Px in liver of WG3 was significantly reduced (p < 0.05). The gene expression of Nrf2 in the SG3 group was higher than that in the WG3 group (p < 0.01). The gene expression of NQO1 in the SG7 group was higher than that in the WG7 group (p < 0.05). In conclusion, weaning resulted in lower weight, slowed liver development, and reduced antioxidant enzymes activity, thereby impairing liver antioxidant function and suppressing piglet growth.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244793
Author(s):  
Elisa S. Na ◽  
Daniel D. Lam ◽  
Eva Yokosawa ◽  
Jessica M. Adams ◽  
David P. Olson ◽  
...  

Enhancer redundancy has been postulated to provide a buffer for gene expression against genetic and environmental perturbations. While work in Drosophila has identified functionally overlapping enhancers, work in mammalian models has been limited. Recently, we have identified two partially redundant enhancers, nPE1 and nPE2, that drive proopiomelanocortin gene expression in the hypothalamus. Here we demonstrate that deletion of nPE1 produces mild obesity while knockout of nPE2 has no discernible metabolic phenotypes. Additionally, we show that acute leptin administration has significant effects on nPE1 knockout mice, with food intake and body weight change significantly impacted by peripheral leptin treatment. nPE1 knockout mice became less responsive to leptin treatment over time as percent body weight change increased over 2 week exposure to peripheral leptin. Both Pomc and Agrp mRNA were not differentially affected by chronic leptin treatment however we did see a decrease in Pomc and Agrp mRNA in both nPE1 and nPE2 knockout calorie restricted mice as compared to calorie restricted PBS-treated WT mice. Collectively, these data suggest dynamic regulation of Pomc by nPE1 such that mice with nPE1 knockout become less responsive to the anorectic effects of leptin treatment over time. Our results also support our earlier findings in which nPE2 may only be critical in adult mice that lack nPE1, indicating that these neural enhancers work synergistically to influence metabolism.


2019 ◽  
Vol 5 (1) ◽  
pp. 205521731983725 ◽  
Author(s):  
RH Gross ◽  
SH Sillau ◽  
AE Miller ◽  
C Farrell ◽  
SC Krieger

Background The Multiple Sclerosis Severity Score (MSSS), combining the Expanded Disability Status Scale (EDSS) and disease duration, attempts to stratify multiple sclerosis (MS) patients based on their rate of progression. Its prognostic ability in the individual patient remains unproven. Objectives To assess the stability of MSSS within individual persons with MS in a longitudinal cohort, to evaluate whether certain factors influence MSSS variability, and to explore the ability of MSSS to predict future ambulatory function. Methods A single-center retrospective review was performed of patients following a single provider for at least 8 years. Mixed model regression modeled MSSS over time. A Kaplan–Meier survival plot was fitted, using change of baseline MSSS by at least one decile as the event. Cox modeling assessed the influence of baseline clinical and demographic factors on the hazard of changing MSSS by at least one decile. Linear models evaluated the impact of baseline EDSS, baseline MSSS, and other factors on the Timed 25-Foot Walk (T25FW). Results Out of 122 patients, 68 (55.7%) deviated from baseline MSSS by at least one decile. Final T25FW had slightly weaker correlation to baseline MSSS than to baseline EDSS, which was moderately strongly correlated with future log T25FW. Conclusion Individual MSSS scores often vary over time. Clinicians should exercise caution when using MSSS to prognosticate.


2021 ◽  
Author(s):  
Jørn Henrik Vold ◽  
Fatemeh Chalabianloo ◽  
Christer F. Aas ◽  
Else-Marie Løberg ◽  
Kjell Arne Johansson ◽  
...  

Abstract BackgroundContinuous use of amphetamines, alcohol, benzodiazepines, cannabis, cocaine, or opioids contributes to health impairments, increased morbidity, and overdose deaths among patients with substance use disorders (SUDs). This study evaluates the impact of inpatient detoxification, specialized opioid agonist therapy (OAT), and low-threshold municipality care on substance use over time. MethodsWe used data from a cohort of SUD patients in Norway through health assessments of self-reported substance use and sociodemographic and clinical factors. A total of 881 substance use measurements, including type and amount of substances, were assessed from 708 SUD patients in 2016-2020. Substance use for individual and total substances was calculated, creating a substance use severity index (SUSI) ranging from zero (no use) to one (daily use). We defined baseline as the first substance use measurement when the measurements were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyze associations between the SUSI and inpatient detoxification, specialized OAT compared with low-threshold municipality care, as well as the factors like injecting substance use, gender, and age, presented with coefficients and 95% confidence intervals (CI).ResultsNeither inpatient detoxification (mean SUSI change: 0.01, -0.03;0.04) nor specialized OAT (0.03, -0.09;0.14) compared with low-threshold municipality care were associated with changes in substance use over time. Patients who were over 60 years of age (mean SUSI difference: -0.06, -0.13;0.00) had a lower SUSI than those under 30 years of age, while patients who injected substances had a higher SUSI than those who did not inject substances (0.18, 0.15;0.20) at baseline. The mean SUSI for the individual substances were 0.50 (standard deviation (SD): 0.38) for cannabis, 0.40 (0.37) for benzodiazepines, 0.33 (0.34) for amphetamines and cocaine, 0.31 (0.29) for alcohol, and 0.22 (0.31) for opioids at baseline. The mean SUSI of all substances was 0.35 (0.20). Conclusion The present study demonstrates that neither inpatient detoxification nor specialized OAT compared to low-threshold municipality care were associated with changes in substance use over time. Future research needs to evaluate the impact on substance use and healthy survival of multiple health care interventions to this patient group.


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