scholarly journals Dietary tomato inhibits angiogenesis in TRAMP prostate cancer but is not protective with a Western-style diet in this pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Catherine C. Applegate ◽  
Matthew R. Lowerison ◽  
Emma Hambley ◽  
Pengfei Song ◽  
Matthew A. Wallig ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Body Weight ◽  
Pilot Study ◽  
Tumor Growth ◽  
Blood Perfusion ◽  
Inhibition Of Angiogenesis ◽  
Regulated Gene Expression ◽  
Tomato Powder

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.

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
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Mixed Model ◽  
Blood Perfusion ◽  
Mouse Prostate ◽  
Regulated Gene Expression ◽  
The Impact ◽  
Over Time

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.

scholarly journals A rise in T3/T4 ratio reduces the growth of prostate tumors in a murine model

2020 ◽  
Vol 247 (3) ◽  
pp. 225-238
Author(s):  
Ana Sánchez-Tusie ◽  
Carlos Montes de Oca ◽  
Julia Rodríguez-Castelán ◽  
Evangelina Delgado-González ◽  
Zamira Ortiz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Body Weight ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Cancer Cell Line ◽  
The Body ◽  
Prostate Tumors ◽  
Mouse Prostate

Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is unknown if the increase in the triiodothyronine (T3)/T4 ratio could attenuate prostate tumor development. We assessed T3 effects on thyroid response, histology, proliferation, and apoptosis in the prostate of wild-type (WT) and TRAMP (transgenic adenocarcinoma of the mouse prostate) mice. Physiological doses of T3 were administered in the drinking water (2.5, 5 and 15 µg/100 g body weight) for 6 weeks. None of the doses modified the body weight or serum levels of testosterone, but all of them reduced serum T4 levels by 50%, and the highest dose increased the T3/T4 ratio in TRAMP. In WT, the highest dose of T3 decreased cyclin D1 levels (immunohistochemistry) but did not modify prostate weight or alter the epithelial morphology. In TRAMP, this dose reduced tumor growth by antiproliferative mechanisms independent of apoptosis, but it did not modify the intraluminal or fibromuscular invasion of tumors. In vitro, in the LNCaP prostate cancer cell line, we found that both T3 and T4 increased the number of viable cells (Trypan blue assay), and only T4 response was fully blocked in the presence of an integrin-binding inhibitor peptide (RGD, arginine-glycine-aspartate). In summary, our data show that the prostate was highly sensitive to physiological T3 doses and suggest that in vivo, an increase in the T3/T4 ratio could be associated with the reduced weight of prostate tumors. Longitudinal studies are required to understand the role of thyroid hormones in prostate cancer progression.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

scholarly journals Polar biophenolics in sweet potato greens extract synergize to inhibit prostate cancer cell proliferation and in vivo tumor growth

2013 ◽  
Vol 34 (9) ◽  
pp. 2039-2049 ◽  
Author(s):  
Sushma R. Gundala ◽  
Chunhua Yang ◽  
N. Lakshminarayana ◽  
Ghazia Asif ◽  
Meenakshi V. Gupta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Sweet Potato ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation

Abstract 13143: Safety Evaluation of Therapeutic Angiogenesis With Adipose-derived Regenerative Cells for Ischemic Limb in a Tumor Bearing Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Junya Suzuki ◽  
Yuuki Shimizu ◽  
Kazuhito Tsuzuki ◽  
Zhongyue Pu ◽  
Shukuro Yamaguchi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Imaging System ◽  
Lymphatic Vessels ◽  
Blood Perfusion ◽  
Capillary Density ◽  
Therapeutic Angiogenesis ◽  
Control Group ◽  
In Vivo Bioluminescence Imaging ◽  
Regenerative Cells

Introduction: Implantation of adipose-derived regenerative cells (ADRC) is a promising novel strategy to augment angiogenesis and blood perfusion recovery in ischemic diseases with no other therapeutic option. However, there is a clinical concern underlying therapeutic angiogenesis that implantation of ADRC may promote tumor growth and metastasis via remote angiogenesis. Accordingly, we tested whether therapeutic angiogenesis with ADRC against hindlimb ischemia (HLI) would affect remote tumor growth and angiogenesis in a tumor-bearing mouse ischemic hindlimb model. Methods and results: B16F10-Luc (murine melanoma cells expressing luciferase, 1x106 cells/animal) were implanted to C57BL/6J mice’s (male, 8-10 weeks old, n=10) back. Mice were subjected to unilateral HLI surgery one day after tumor implantation. Then, mice were randomly assigned to the control group or the ADRC group (n=5 for each). ADRC (1x106 cells/animal) or PBS were implanted/injected into ischemic hindlimb muscles one day after the surgery. Blood perfusion recovery in HLI by laser Doppler perfusion imaging system and tumor size by a caliper were measured every week up to 21 days after surgery. At POD 21, tumor weight and luciferase activity in primary tumors obtained by in vivo bioluminescence imaging system were also evaluated. Immunohistochemistry by CD31 or LYVE1 staining was performed to detect feeder arteries or outflow lymphatic vessels in tumors. The results demonstrated that better blood perfusion recovery and more capillary density in HLI was observed in the ADRC group than in the control group (p<0.05, respectively). However, there were no significant differences in terms of tumor volume (p=0.95), tumor weight (p=0.88) and luciferase activity of primary tumor (p=0.92) between those two groups. No sign of distant metastasis was detected by macroscopic and pathological examination, and by in vivo bioluminescence imaging system in both groups. Further study also revealed that capillary density of peritumoral blood vessels or lymphatic vessels was not augmented by ADRC implantation into remote HLI. Conclusions: Our data indicated that therapeutic angiogenesis with ADRC implantation against HLI did not promote remote tumor growth, angiogenesis and metastasis.

scholarly journals LINC00908 negatively regulates microRNA-483-5p to increase TSPYL5 expression and inhibit the development of prostate cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Li Fan ◽  
Hai Li ◽  
Yun Zhang
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Rna Binding ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Omnibus ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
In Vivo Experiments

Abstract Background Accumulating evidence has associated aberrant long non-coding RNAs (lncRNAs) with various human cancers. This study aimed to explore the role of LINC00908 in prostate cancer (PCa) and its possible underlying mechanisms. Methods Microarray data associated with PCa were obtained from the Gene Expression Omnibus (GEO) to screen the differentially expressed genes or lncRNAs. Then, the expression of LINC00908 in PCa tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The localization of LINC00908 in PCa cells was examined by fluorescence in situ hybridization (FISH). The relationship among LINC00908, microRNA (miR)-483-5p, and TSPYL5 was detected by bioinformatics analysis, dual-luciferase reporter assay, RNA pull-down, RNA binding protein immunoprecipitation (RIP), and FISH assays. Cell biological behaviors were assessed after the expression of LINC00908, miR-483-5p, and TSPYL5 was altered in PCa cells. Lastly, tumor growth in nude mice was evaluated. Results Poorly expressed LINC00908 was witnessed in PCa tissues and cells. LINC00908 competitively bound to miR-483-5p to up-regulate the TSPYL5 expression. Overexpression of LINC00908 resulted in reduced PCa cell proliferation, migration and invasion, and promoted apoptosis. Additionally, the suppression on PCa cell proliferation, migration and invasion was induced by up-regulation of TSPYL5 or inhibition of miR-483-5p. In addition, in vivo experiments showed that overexpression of LINC00908 inhibited tumor growth of PCa. Conclusion Overall, LINC00908 could competitively bind to miR-483-5p to increase the expression of TSPYL5, thereby inhibiting the progression of PCa. Therefore, LINC00908 may serve as a novel target for the treatment of PCa.

No influence on tumor growth by intramuscular injection of adipose-derived regenerative cells: safety evaluation of therapeutic angiogenesis with cell therapy

2020 ◽  
Author(s):  
Junya Suzuki ◽  
Yuuki Shimizu ◽  
Kazuhito Tsuzuki ◽  
Zhongyue Pu ◽  
Shingo Narita ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Hind Limb ◽  
Lymphatic Vessels ◽  
Blood Perfusion ◽  
Limb Ischemia ◽  
Therapeutic Angiogenesis ◽  
Tissue Ischemia ◽  
Regenerative Cells ◽  
Ischemic Diseases

Therapeutic angiogenesis with autologous stem/progenitor cells is a promising novel strategy for treatment of severe ischemic diseases. Human clinical trials utilizing autologous adipose-derived regenerative cells (ADRCs) have not reported treatment-related critical adverse effects thus far. However, there is still a large knowledge gap whether treatment of ischemic diseases with angiogenic therapy using ADRCs would promote unfavorable angiogenesis associated with tumors in vivo. Herein, we addressed this clinical question using a mouse hind limb ischemia (HLI) and simultaneous remote tumor implantation model. C57BL/6J background wild-type mice were injected with murine B16F10 melanoma cells on their back, one day before ischemic surgery. These mice were subjected to surgical unilateral hindlimb ischemia, followed by ADRCs implantation or PBS injection into the hindlimb ischemic muscles on the next day. Intramuscular implantation of ADRCs enhanced tissue capillary density and blood flow examined by a laser Doppler blood perfusion analysis in hind limb. However, this therapeutic regimen for ischemic limb using ADRCs did not affect remote melanoma growth nor the density of its feeder artery, angiogenesis and lymphatic vessels compared to the PBS group. In addition, no distant metastases were detected in any of the mice regardless the group. In conclusion, local implantation of ADRCs promotes angiogenesis in response to tissue ischemia in the hind limb without promoting remote tumor growth and related angio/lymphangiogenesis. Therapeutic angiogenesis to the ischemic hind limb using ADRCs seems to be safe regarding remote tumor growth.

Glial-specific retrovirally mediated gas1 gene expression induces glioma cell apoptosis and inhibits tumor growth in vivo

2004 ◽  
Vol 15 (3) ◽  
pp. 483-491 ◽  
Author(s):  
Absalom Zamorano ◽  
Britt Mellström ◽  
Paula Vergara ◽  
José R Naranjo ◽  
José Segovia
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Cell Apoptosis ◽  
Glioma Cell

Human glucagon gene promoter sequences regulating tissue-specific versus nutrient-regulated gene expression

2002 ◽  
Vol 282 (1) ◽  
pp. R173-R183 ◽  
Author(s):  
Min Nian ◽  
Jun Gu ◽  
David M. Irwin ◽  
Daniel J. Drucker
Keyword(s):  
Gene Expression ◽  
Gene Promoter ◽  
Regulatory Sequences ◽  
Dependent Manner ◽  
Specific Expression ◽  
Tissue Specific ◽  
High Fiber ◽  
Fiber Diet ◽  
Regulated Gene Expression

The glucagon-like peptides (GLPs) are synthesized and secreted in a nutrient-dependent manner in rodents; however, the factors regulating human GLP-1 and GLP-2 biosynthesis remain unclear. To understand how nutrients regulate human proglucagon gene expression, we studied the expression of a human proglucagon promoter-growth hormone (GH) transgene in 1.6 human glucagon-GH transgenic mice. Fasting-refeeding significantly decreased and increased the levels of circulating mouse insulin and transgene-derived hGH ( P < 0.05 fasting vs. refeeding) and decreased and upregulated, respectively, the levels of endogenous mouse proglucagon RNA in the ileum but not in the jejunum or colon. High-fiber feeding significantly increased the levels of glucose-stimulated circulating hGH and upregulated levels of mouse intestinal proglucagon gene expression in the jejunum, ileum, and colon ( P < 0.05, 0 vs. 30% fiber diet). In contrast, neither fasting-refeeding nor a high-fiber diet upregulated the expression of the human proglucagon promoter-hGH transgene. These findings demonstrate that human proglucagon gene regulatory sequences specifying tissue-specific expression in gut endocrine cells are not sufficient for recognition of energy-derived signals regulating murine glucagon gene expression in enteroendocrine cells in vivo.

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