35 results on '"Hsueh-Li Tan"'
Search Results
2. Data from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
- Author
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
- Abstract
The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9′,10′-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at 3 weeks of age, TRAMP:Bco2+/+ and TRAMP:Bco2−/− mice were fed either AIN-93G control, or semipurified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2−/− mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2+/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared with the control-fed mice. Although Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (Pinteraction = 0.0004 and 0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anticancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis. Cancer Prev Res; 10(2); 161–9. ©2016 AACR.
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- 2023
3. Supplemental Figure 3 from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
- Abstract
Pathological progression in the TRAMP mouse prostate.
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- 2023
4. Supplemental Figure 1 from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
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Serum Lycopene Concentrations.
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- 2023
5. Supplementary Table S1 from Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
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Steven K. Clinton, Nancy E. Moran, John W. Erdman, Dennis K. Pearl, Jennifer M. Thomas-Ahner, Hsueh-Li Tan, and Lei Wan
- Abstract
Supplementary Table S1. Murine prostatic carcinogenesis gene codeset gene list
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- 2023
6. Supplemental Figure 4 from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
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Distribution of highest pathologic grade.
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- 2023
7. Supplemental Tables 1 and 2 from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
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Weight tables.
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- 2023
8. Supplementary Table S2 from Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
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Steven K. Clinton, Nancy E. Moran, John W. Erdman, Dennis K. Pearl, Jennifer M. Thomas-Ahner, Hsueh-Li Tan, and Lei Wan
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Supplementary Table S2. Gene expression significantly impacted by genotype (TRAMP vs. WT mice)
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- 2023
9. Supplementary Table S4 from Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
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Steven K. Clinton, Nancy E. Moran, John W. Erdman, Dennis K. Pearl, Jennifer M. Thomas-Ahner, Hsueh-Li Tan, and Lei Wan
- Abstract
Supplementary Table S4. Canonical pathways predicted to be significantly different in early prostate carcinogenesis and in response to castration.
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- 2023
10. Supplemental Methods from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
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SV40 IHC methods.
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- 2023
11. Supplemental Figure 5 from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
- Abstract
SV40 expression.
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- 2023
12. Supplemental Figure S1 from Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
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Steven K. Clinton, Nancy E. Moran, John W. Erdman, Dennis K. Pearl, Jennifer M. Thomas-Ahner, Hsueh-Li Tan, and Lei Wan
- Abstract
Supplemental Figure S1. Final urogenital tract weights and plasma lycopene concentrations in intact, castrated, and testosterone-repleted WT and TRAMP mice fed either control, tomato-, or lycopene-containing diets.
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- 2023
13. Supplemental References from Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
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Steven K. Clinton, Nancy E. Moran, John W. Erdman, Dennis K. Pearl, Jennifer M. Thomas-Ahner, Hsueh-Li Tan, and Lei Wan
- Abstract
Supplemental References
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- 2023
14. Supplemental Figure 2 from β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, Gregory S. Young, John W. Erdman, Jessica L. Cooperstone, Nancy E. Moran, Jennifer M. Thomas-Ahner, and Hsueh-Li Tan
- Abstract
Lycopene precursor concentrations in mouse serum.
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- 2023
15. Supplementary Table 1 from Rb Loss Is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma
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Tamara L. Lotan, Angelo M. De Marzo, William B. Isaacs, Wennuan Liu, George J. Netto, Jonathan I. Epstein, Christopher D. Gocke, Stacy Mosier, Jessica Hicks, Nilesh Gupta, Wenle Wang, Hameed A. Rahimi, Akshay Sood, and Hsueh-Li Tan
- Abstract
PDF file - 82K, Supplementary Table 1: RB1 status (from high density SNP microarray, Reference 30) and Rb protein status across castrate resistant prostate cancer metastases. n = negative, p = positive, LOH = loss of heterozygosity.
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- 2023
16. Supplementary Figure S2 from Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
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Tamara L. Lotan, Angelo M. De Marzo, Elai Davicioni, Edward M. Schaeffer, R. Jeffrey Karnes, Robert L. Vessella, Rohit Mehra, Jun Luo, William B. Isaacs, George J. Netto, Jonathan I. Epstein, Nilesh Gupta, Jessica Hicks, Zaid Haddad, Hsueh-Li Tan, Mohammed Alshalalfa, Carlos L. Morais, and Harrison Tsai
- Abstract
Supplementary Figure S2: The ratio of CDKN2A/CCND1 is not as tightly correlated with Rb functional and genetic status in publicly available data from castate resistant prostate cancer (CRPC) metastases in rapid autopsy cohort.
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- 2023
17. Supplementary Figure S4 from Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
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Tamara L. Lotan, Angelo M. De Marzo, Elai Davicioni, Edward M. Schaeffer, R. Jeffrey Karnes, Robert L. Vessella, Rohit Mehra, Jun Luo, William B. Isaacs, George J. Netto, Jonathan I. Epstein, Nilesh Gupta, Jessica Hicks, Zaid Haddad, Hsueh-Li Tan, Mohammed Alshalalfa, Carlos L. Morais, and Harrison Tsai
- Abstract
Supplementary Figure S4: A high ratio of CDKN2A/CCND1 is associated with shorter interval to development of metastasis among high risk surgically treated men receiving adjuvant androgen deprivation therapy (ADT).
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- 2023
18. Supplementary Figure S1 from Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
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Tamara L. Lotan, Angelo M. De Marzo, Elai Davicioni, Edward M. Schaeffer, R. Jeffrey Karnes, Robert L. Vessella, Rohit Mehra, Jun Luo, William B. Isaacs, George J. Netto, Jonathan I. Epstein, Nilesh Gupta, Jessica Hicks, Zaid Haddad, Hsueh-Li Tan, Mohammed Alshalalfa, Carlos L. Morais, and Harrison Tsai
- Abstract
Supplementary Figure S1: The ratio of CDKN2A/CCND1 reflects Rb functional and genetic status and distinguishes small cell carcinoma from prostatic adenocarcinoma in publicly available data from patient derived xenografts (PDX).
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- 2023
19. Data from Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
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Tamara L. Lotan, Angelo M. De Marzo, Elai Davicioni, Edward M. Schaeffer, R. Jeffrey Karnes, Robert L. Vessella, Rohit Mehra, Jun Luo, William B. Isaacs, George J. Netto, Jonathan I. Epstein, Nilesh Gupta, Jessica Hicks, Zaid Haddad, Hsueh-Li Tan, Mohammed Alshalalfa, Carlos L. Morais, and Harrison Tsai
- Abstract
Purpose: Small-cell neuroendocrine differentiation in prostatic carcinoma is an increasingly common resistance mechanism to potent androgen deprivation therapy (ADT), but can be difficult to identify morphologically. We investigated whether cyclin D1 and p16 expression can inform on Rb functional status and distinguish small-cell carcinoma from adenocarcinoma.Experimental Design: We used gene expression data and immunohistochemistry to examine cyclin D1 and p16 levels in patient-derived xenografts (PDX), and prostatic small-cell carcinoma and adenocarcinoma specimens.Results: Using PDX, we show proof-of-concept that a high ratio of p16 to cyclin D1 gene expression reflects underlying Rb functional loss and distinguishes morphologically identified small-cell carcinoma from prostatic adenocarcinoma in patient specimens (n = 13 and 9, respectively). At the protein level, cyclin D1, but not p16, was useful to distinguish small-cell carcinoma from adenocarcinoma. Overall, 88% (36/41) of small-cell carcinomas showed cyclin D1 loss by immunostaining compared with 2% (2/94) of Gleason score 7–10 primary adenocarcinomas at radical prostatectomy, 9% (4/44) of Gleason score 9–10 primary adenocarcinomas at needle biopsy, and 7% (8/115) of individual metastases from 39 patients at autopsy. Though rare adenocarcinomas showed cyclin D1 loss, many of these were associated with clinical features of small-cell carcinoma, and in a cohort of men treated with adjuvant ADT who developed metastasis, lower cyclin D1 gene expression was associated with more rapid onset of metastasis and death.Conclusions: Cyclin D1 loss identifies prostate tumors with small-cell differentiation and may identify a small subset of adenocarcinomas with poor prognosis. Clin Cancer Res; 21(24); 5619–29. ©2015 AACR.
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- 2023
20. supplemental figure legend and Materials and Methods from Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
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Tamara L. Lotan, Angelo M. De Marzo, Elai Davicioni, Edward M. Schaeffer, R. Jeffrey Karnes, Robert L. Vessella, Rohit Mehra, Jun Luo, William B. Isaacs, George J. Netto, Jonathan I. Epstein, Nilesh Gupta, Jessica Hicks, Zaid Haddad, Hsueh-Li Tan, Mohammed Alshalalfa, Carlos L. Morais, and Harrison Tsai
- Abstract
supplemental figure legend and Materials and Methods
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- 2023
21. Data from Rb Loss Is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma
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Tamara L. Lotan, Angelo M. De Marzo, William B. Isaacs, Wennuan Liu, George J. Netto, Jonathan I. Epstein, Christopher D. Gocke, Stacy Mosier, Jessica Hicks, Nilesh Gupta, Wenle Wang, Hameed A. Rahimi, Akshay Sood, and Hsueh-Li Tan
- Abstract
Purpose: Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor.Experimental Design: We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin-fixed paraffin-embedded specimens.Results: We found retinoblastoma (Rb) protein loss in 90% of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in 63% of small cell carcinomas (17 of 27), with 38% (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation.Conclusions: Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target. Clin Cancer Res; 20(4); 890–903. ©2013 AACR.
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- 2023
22. Supplementary Figure 1 from Rb Loss Is Characteristic of Prostatic Small Cell Neuroendocrine Carcinoma
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Tamara L. Lotan, Angelo M. De Marzo, William B. Isaacs, Wennuan Liu, George J. Netto, Jonathan I. Epstein, Christopher D. Gocke, Stacy Mosier, Jessica Hicks, Nilesh Gupta, Wenle Wang, Hameed A. Rahimi, Akshay Sood, and Hsueh-Li Tan
- Abstract
PDF file - 284K, Supplementary Figure S1: (A) High grade prostatic adenocarcinoma with neuroendocrine differentiation by diffuse expression of immunohistochemical markers. This case shows lack of small cell differentiation by hematoxylin and eosin staining (left panel, 200x and inset) based on presence of prominent nucleoli and abundant cytoplasms, without nuclear molding. However, neuroendocrine immunohistochemical markers are diffusely positive (middle panel). Rb protein is present in this case (right panel). (B) Large cell neuroendocrine prostate carcinoma (LCNEC) shows cords and trabeculae of cells, but with abundant pink cytoplasm, which is inconsistent with a diagnosis of small cell carcinoma (left panel and inset). Neuroendocrine markers are diffusely positive (middle panel), however Rb protein is preserved (right panel). (C) Castrate resistant prostate cancer metastasis from autopsy study that has been previously reported (reference 30). This liver metastasis from case 30 (Supplementary Table 1) is heterogeneously positive for Rb protein, with one nodule staining positive (lower left) and nearby nodules staining negative, despite Rb protein in endothelial cells (arrowhead) as an internal positive control. Additional liver and bone tumors from this patient were found to have homozygous deletion of RB1, suggesting inter-metastatic heterogeneity in RB1 status.
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- 2023
23. Supplementary Figure S3 from Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
- Author
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Tamara L. Lotan, Angelo M. De Marzo, Elai Davicioni, Edward M. Schaeffer, R. Jeffrey Karnes, Robert L. Vessella, Rohit Mehra, Jun Luo, William B. Isaacs, George J. Netto, Jonathan I. Epstein, Nilesh Gupta, Jessica Hicks, Zaid Haddad, Hsueh-Li Tan, Mohammed Alshalalfa, Carlos L. Morais, and Harrison Tsai
- Abstract
Supplementary Figure S3: Short-term and neo-adjuvant androgen deprivation therapy (ADT) has not exhibited direct effects on CCND1, CDKN2A, or RB1 in past gene expression studies of prostatic adenocarcinomas.
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- 2023
24. Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
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Jennifer M. Thomas-Ahner, Lei Wan, Steven K. Clinton, Dennis K. Pearl, Nancy E. Moran, Hsueh-Li Tan, and John W. Erdman
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Male ,Cancer Research ,medicine.medical_specialty ,Carcinogenesis ,medicine.drug_class ,Mice, Transgenic ,Adenocarcinoma ,Biology ,Real-Time Polymerase Chain Reaction ,Neuroendocrine differentiation ,Article ,Immunoenzyme Techniques ,Mice ,Prostate cancer ,chemistry.chemical_compound ,Lycopene ,Solanum lycopersicum ,Internal medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,medicine ,Animals ,Anticarcinogenic Agents ,Humans ,RNA, Messenger ,Testosterone ,Oligonucleotide Array Sequence Analysis ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Prostatic Neoplasms ,Androgen ,medicine.disease ,Carotenoids ,Diet ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,Endocrinology ,SRD5A1 ,Castration ,Oncology ,chemistry ,SRD5A2 ,Androgens ,Signal Transduction ,Tramp - Abstract
Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer–related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P < 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P < 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation–related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. Cancer Prev Res; 7(12); 1228–39. ©2014 AACR.
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- 2014
25. β-Carotene-9′,10′-Oxygenase Status Modulates the Impact of Dietary Tomato and Lycopene on Hepatic Nuclear Receptor–, Stress-, and Metabolism-Related Gene Expression in Mice
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Steven J. Schwartz, Steven K. Clinton, Nancy E. Moran, Ken M. Riedl, Jennifer M. Thomas-Ahner, Dennis K. Pearl, John W. Erdman, Morgan J. Cichon, and Hsueh Li Tan
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Male ,medicine.medical_specialty ,Nuclear Receptor Coactivators ,Down-Regulation ,Receptors, Cytoplasmic and Nuclear ,Medicine (miscellaneous) ,Peroxisome proliferator-activated receptor ,Biology ,Retinoid X receptor ,Dioxygenases ,Mice ,Random Allocation ,chemistry.chemical_compound ,Lycopene ,Glucocorticoid receptor ,Solanum lycopersicum ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Gene expression ,medicine ,Animals ,Genomics, Proteomics, and Metabolomics ,Triglycerides ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,Regulation of gene expression ,chemistry.chemical_classification ,Nutrition and Dietetics ,Gene Expression Profiling ,DNA ,Aryl hydrocarbon receptor ,Carotenoids ,Fatty Liver ,Endocrinology ,Gene Expression Regulation ,Liver ,Nuclear receptor ,chemistry ,Fruit ,Dietary Supplements ,biology.protein - Abstract
Tomato and lycopene (c, c-carotene) consumption is hypothesized to protect against nonalcoholic steatohepatitis and hepatocarcinogenesis, processes that may depend upon diet and gene interactions. To investigate the interaction of tomato or lycopene feeding with b-carotene-9#,10#-monooxygenase (Bco2) on hepatic metabolic and signaling pathways, male wild-type (WT) and Bco2 2/2 mice (3-wk-old; n = 36) were fed semi-purified control, 10% tomato powder‐containing, or 0.25% lycopene beadlet‐containing diets for 3 wk. Serum lycopene concentrations were higher in lycopene- and tomato-fed Bco2 2/2 mice compared with WT (P = 0.03). Tomato- and lycopene-fed mice had detectable hepatic apo-6#-, apo-8#-, and apo-12#-lycopenal concentrations. Hepatic expression of b-carotene-15,15-monooxygenase was increased in Bco2 2/2 mice compared with WT (P = 0.02), but not affected by diet. Evaluation of hepatic gene expression by focused quantitative reverse transcriptase-polymerase chain reaction arrays for nuclear receptors and coregulators (84 genes) and stress and metabolism (82 genes) genes indicates that tomato feeding affected 31 genes ($1.5-fold, P < 0.05) and lycopene feeding affected 19 genes, 16 of which were affected by both diets. Lycopene down-regulation of 7 nuclear receptors and coregulators, estrogen-related receptor-a, histone deacetylase 3, nuclear receptor coactivator 4, RevErbAb, glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)-a, and PPAR-g, coactivator 1 b was dependent upon interaction with Bco2 status. Lycopene and tomato feeding induced gene expression patterns consistent with decreased lipid uptake, decreased cell proliferation and mitosis, down-regulated aryl hydrocarbon receptor signaling, and decreased expression of genes involved in retinoid X receptor heterodimer activation. Tomato feeding also caused expression changes consistent with down-regulation of DNA synthesis and terpenoid metabolism. These data suggest tomato components, particularly lycopene, affect hepatic gene expression, potentially affecting hepatic responses to metabolic, infectious, or chemical stress. J. Nutr. doi: 10.3945/jn.113.186676.
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- 2014
26. β-carotene 9’,10’ oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model
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Steven K. Clinton, John W. Erdman, Gregory S. Young, Nancy E. Moran, Jessica L. Cooperstone, Jennifer M. Thomas-Ahner, and Hsueh Li Tan
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Oxygenase ,Carcinogenesis ,medicine.medical_treatment ,Biology ,medicine.disease_cause ,Article ,Dioxygenases ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Lycopene ,Solanum lycopersicum ,medicine ,Animals ,Anticarcinogenic Agents ,Carotenoid ,chemistry.chemical_classification ,Mice, Knockout ,Carotene ,food and beverages ,Prostatic Neoplasms ,medicine.disease ,Carotenoids ,In vitro ,Diet ,030104 developmental biology ,Oncology ,Biochemistry ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Tramp - Abstract
The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9′,10′-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at 3 weeks of age, TRAMP:Bco2+/+ and TRAMP:Bco2−/− mice were fed either AIN-93G control, or semipurified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2−/− mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2+/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared with the control-fed mice. Although Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (Pinteraction = 0.0004 and 0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anticancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis. Cancer Prev Res; 10(2); 161–9. ©2016 AACR.
- Published
- 2016
27. Assessing the order of critical alterations in prostate cancer development and progression by IHC: further evidence that PTEN loss occurs subsequent to ERG gene fusion
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Christopher Weier, Jessica L. Hicks, Tamara L. Lotan, Bora Gurel, Hsueh Li Tan, Berrak Gumuskaya, A. M. De Marzo, Michael C. Haffner, and Helen L. Fedor
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Adult ,Male ,PTEN ,Cancer Research ,Oncogene Proteins, Fusion ,genetic structures ,Carcinogenesis ,Urology ,Loss of Heterozygosity ,Adenocarcinoma ,Biology ,Article ,Loss of heterozygosity ,Fusion gene ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Transcriptional Regulator ERG ,FISH ,medicine ,Humans ,Tensin ,Oncogene Fusion ,Aged ,Neoplasm Staging ,030304 developmental biology ,0303 health sciences ,Homozygote ,PTEN Phosphohydrolase ,Prostatic Neoplasms ,Middle Aged ,prostate cancer ,medicine.disease ,Immunohistochemistry ,3. Good health ,Oncology ,ERG ,030220 oncology & carcinogenesis ,Disease Progression ,Trans-Activators ,Cancer research ,biology.protein ,sense organs ,Neoplasm Grading ,Erg ,Gene Deletion - Abstract
ERG rearrangements and PTEN (phosphatase and tensin homolog deleted on chromosome 10) loss are two of the most common genetic alterations in prostate cancer. However, there is still significant controversy regarding the order of events of these two changes during the carcinogenic process. We used immunohistochemistry (IHC) to determine ERG and PTEN status, and calculated the fraction of cases with homogeneous/heterogeneous ERG and PTEN staining in a given tumor. Using a single standard tissue section from the index tumor from radical prostatectomies (N=77), enriched for relatively high grade and stage tumors, we examined ERG and PTEN status by IHC. We determined whether ERG or PTEN staining was homogeneous (all tumor cells staining positive) or heterogeneous (focal tumor cell staining) in a given tumor focus. Fifty-seven percent (N=44/77) of tumor foci showed ERG positivity, with 93% of these (N=41/44) cases showing homogeneous ERG staining in which all tumor cells stained positively. Fifty-three percent (N=41/77) of tumor foci showed PTEN loss, and of these 66% (N=27/41) showed heterogeneous PTEN loss. In ERG homogeneously positive cases, any PTEN loss occurred in 56% (N=23/41) of cases, and of these 65% (N=15/23) showed heterogeneous loss. In ERG-negative tumors, 51.5% (N=17/33) showed PTEN loss, and of these 64.7% (N=11/17) showed heterogeneous PTEN loss. In a subset of cases, genomic deletions of PTEN were verified by fluorescence in situ hybridization in regions with PTEN protein loss as compared with regions with intact PTEN protein, which did not show PTEN genomic loss. These results support the concept that PTEN loss tends to occur as a subclonal event within a given established prostatic carcinoma clone after ERG gene fusion. The combination of ERG and PTEN IHC staining can be used as a simple test to ascertain PTEN and ERG gene rearrangement status within a given prostate cancer in either a research or clinical setting.
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- 2013
28. Tomato-based food products for prostate cancer prevention: what have we learned?
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David M. Francis, Hsueh Li Tan, Elizabeth Grainger, Steven K. Clinton, Jennifer M. Thomas-Ahner, Lei Wan, John W. Erdman, and Steven J. Schwartz
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Male ,Clinical Trials as Topic ,Cancer Research ,Cancer prevention ,business.industry ,Prostatic Neoplasms ,Cancer ,medicine.disease ,Article ,Biotechnology ,Clinical trial ,Prostate cancer ,Solanum lycopersicum ,Oncology ,Phytochemical ,Food products ,medicine ,Food processing ,Humans ,business ,Prostate Cancer Prevention ,Phytotherapy - Abstract
Evidence derived from a vast array of laboratory studies and epidemiological investigations have implicated diets rich in fruits and vegetables with a reduced risk of certain cancers. However, these approaches cannot demonstrate causal relationships and there is a paucity of randomized, controlled trials due to the difficulties involved with executing studies of food and behavioral change. Rather than pursuing the definitive intervention trials that are necessary, the thrust of research in recent decades has been driven by a reductionist approach focusing upon the identification of bioactive components in fruits and vegetables with the subsequent development of single agents using a pharmacologic approach. At this point in time, there are no chemopreventive strategies that are standard of care in medical practice that have resulted from this approach. This review describes an alternative approach focusing upon development of tomato-based food products for human clinical trials targeting cancer prevention and as an adjunct to therapy. Tomatoes are a source of bioactive phytochemicals and are widely consumed. The phytochemical pattern of tomato products can be manipulated to optimize anticancer activity through genetics, horticultural techniques, and food processing. The opportunity to develop a highly consistent tomato-based food product rich in anticancer phytochemicals for clinical trials targeting specific cancers, particularly the prostate, necessitates the interactive transdisciplinary research efforts of horticulturalists, food technologists, cancer biologists, and clinical translational investigators.
- Published
- 2010
29. Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization
- Author
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Angelo M. De Marzo, William G. Nelson, Ibrahim Kulac, Srinivasan Yegnasubramanian, Hsueh Li Tan, Berrak Gumuskaya, Meng Meng Xu, Christopher Weier, Helen Fedor, Bora Gurel, Jessica Hicks, David M. Esopi, William B. Isaacs, Tamara L. Lotan, Ajay Vaghasia, and Michael C. Haffner
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Oncogene Proteins, Fusion ,Adenocarcinoma ,Article ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Transcriptional Regulator ERG ,Cell Line, Tumor ,medicine ,Carcinoma ,PTEN ,Humans ,Neoplasm Invasiveness ,In Situ Hybridization, Fluorescence ,Prostatic Intraepithelial Neoplasia ,Intraepithelial neoplasia ,biology ,PTEN Phosphohydrolase ,Prostatic Neoplasms ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,Carcinoma, Intraductal, Noninfiltrating ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Trans-Activators ,Differential diagnosis - Abstract
Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for intraductal carcinoma adjacent to invasive adenocarcinoma. These findings represent a potentially undervalued indicator of pre-existing invasive prostate cancer and have significant implications for prostate cancer diagnosis and risk stratification.
- Published
- 2015
30. Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
- Author
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R. Jeffrey Karnes, Nilesh S. Gupta, Jonathan I. Epstein, George J. Netto, Hsueh-Li Tan, Tamara L. Lotan, Mohammed Alshalalfa, Zaid Haddad, Elai Davicioni, Edward M. Schaeffer, Carlos L. Morais, Robert L. Vessella, Jun Luo, William B. Isaacs, Angelo M. De Marzo, Harrison Tsai, Jessica Hicks, and Rohit Mehra
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Gene Expression ,Kaplan-Meier Estimate ,Biology ,Adenocarcinoma ,Neuroendocrine differentiation ,Small-cell carcinoma ,Retinoblastoma Protein ,Article ,Metastasis ,Androgen deprivation therapy ,Mice ,Cyclin D1 ,Carcinoma ,medicine ,Biomarkers, Tumor ,Animals ,Humans ,Carcinoma, Small Cell ,Neoplasm Metastasis ,Cyclin-Dependent Kinase Inhibitor p16 ,Gene Expression Profiling ,Retinoblastoma protein ,Prostatic Neoplasms ,medicine.disease ,Prognosis ,Immunohistochemistry ,Disease Models, Animal ,Oncology ,Cancer research ,biology.protein ,Heterografts ,Neoplasm Grading - Abstract
Purpose:Small cell neuroendocrine differentiation in prostatic carcinoma is an increasingly common resistance mechanism to potent androgen deprivation therapy (ADT), but can be difficult to identify morphologically. We investigated whether cyclin D1 and p16 expression can inform on Rb functional status and distinguish small cell carcinoma from adenocarcinoma. Experimental Design:We used gene expression data and immunohistochemistry to examine cyclin D1 and p16 levels in patient-derived xenografts (PDX), and prostatic small cell carcinoma and adenocarcinoma specimens. Results:Using PDX, we show proof-of-concept that a high ratio of p16 to cyclin D1 gene expression reflects underlying Rb functional loss and distinguishes morphologically identified small cell carcinoma from prostatic adenocarcinoma in patient specimens (n=13 and 9, respectively). At the protein level cyclin D1, but not p16, was useful to distinguish small cell carcinoma from adenocarcinoma. Overall, 88% (36/41) of small cell carcinomas showed cyclin D1 loss by immunostaining compared to 2% (2/94) of Gleason score 7-10 primary adenocarcinomas at radical prostatectomy, 9% (4/44) of Gleason score 9-10 primary adenocarcinomas at needle biopsy, and 7% (8/115) of individual metastases from 39 patients at autopsy. Though rare adenocarcinomas showed cyclin D1 loss, many of these were associated with clinical features of small cell carcinoma, and in a cohort of men treated with adjuvant ADT who developed metastasis, lower cyclin D1 gene expression was associated with more rapid onset of metastasis and death. Conclusions: Cyclin D1 loss identifies prostate tumors with small cell differentiation and may identify a small subset of adenocarcinomas with poor prognosis.
- Published
- 2015
31. Prostate adenocarcinomas aberrantly expressing p63 are molecularly distinct from usual-type prostatic adenocarcinomas
- Author
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Hillary M. Ross, Jessica Hicks, David M. Esopi, Hsueh Li Tan, Angelo M. De Marzo, Michael C. Haffner, Giovanna A. Giannico, Ankur R. Sangoi, Tamara L. Lotan, Srinivasan Yegnasubramanian, Jonathan I. Epstein, Adeboye O. Osunkoya, Qizhi Zheng, Susmita Ghosh, and Ajay Vaghasia
- Subjects
Male ,Pathology ,medicine.medical_specialty ,medicine.drug_class ,Chromogenic in situ hybridization ,Fluorescent Antibody Technique ,Biology ,Adenocarcinoma ,Polymerase Chain Reaction ,Article ,Pathology and Forensic Medicine ,Prostate cancer ,Cytokeratin ,Prostate ,medicine ,Humans ,Protein Isoforms ,prostatic adenocarcinoma ,GSTP1 ,In Situ Hybridization ,p63 ,medicine.diagnostic_test ,Membrane Proteins ,Prostatic Neoplasms ,medicine.disease ,Androgen ,3. Good health ,Androgen receptor ,medicine.anatomical_structure ,ERG ,aberrant ,Fluorescence in situ hybridization - Abstract
We have described a rare group of prostate adenocarcinomas that show aberrant expression of p63, a protein strongly expressed in prostatic basal cells and absent from usual-type acinar prostate cancers. The partial basal-like immunophenotype of these tumors is intriguing in light of the persistent debate surrounding the cell-of-origin for prostate cancer; however, their molecular phenotype is unknown. We collected 37 of these tumors on radical prostatectomy and biopsy and assessed subsets for a diverse panel of molecular markers. The majority of p63-expressing tumors were positive for the ΔNp63 isoform (6/7) by immunofluorescence and p63 mRNA (7/8) by chromogenic in situ hybridization. Despite p63 positivity, these tumors uniformly expressed luminal-type cytokeratin proteins such as CK18 (13/13), CK8 (8/8), and markers of androgen axis signaling commonly seen in luminal cells, including androgen receptor (10/11), NKX3.1 (8/8), and prostein (12/13). Conversely, basal cytokeratins such as CK14 and CK15 were negative in all cases (0/8) and CK5/6 was weakly and focally positive in 36% (4/11) of cases. Pluripotency markers including β-catenin, Oct4, and c-kit were negative in p63-expressing tumors (0/11). Despite nearly universal expression of androgen receptor and downstream androgen signaling targets, p63-expressing tumors lacked ERG rearrangements by fluorescence in situ hybridization (0/14) and ERG protein expression (0/37). No tumors expressed SPINK1 or showed PTEN protein loss (0/19). Surprisingly, 74% (14/19) of p63-expressing tumors expressed GSTP1 protein at least focally, and 33% (2/6) entirely lacked GSTP1 CpG island hypermethylation by bisulfite sequencing. In contrast to usual prostatic adenocarcinomas, prostate tumors with p63 expression show a mixed luminal/basal immunophenotype, uniformly lack ERG gene rearrangement, and frequently express GSTP1. These data strongly suggest that p63-expressing prostate tumors represent a molecularly distinct subclass and further study of this rare tumor type may yield important insights into the role of p63 in prostatic biology and the prostate cancer cell-of-origin.
- Published
- 2014
32. Bioactive tomato components inhibit cancer promoting activity of testosterone in the mouse prostate epithelium
- Author
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John W. Erdman, Jennifer M. Thomas-Ahner, Amy C. Elsen, Steven K. Clinton, and Hsueh-Li Tan
- Subjects
business.industry ,Cancer ,Testosterone (patch) ,medicine.disease ,Biochemistry ,Epithelium ,medicine.anatomical_structure ,Genetics ,Cancer research ,Medicine ,Mouse Prostate ,business ,Molecular Biology ,Biotechnology - Published
- 2012
33. Abstract A59: Dietary tomato and lycopene inhibition of prostate carcinogenesis in the TRAMP Model is β,β-carotene 9',10'-oxygenase (BCO2)-dependent
- Author
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Jennifer M. Thomas-Ahner, Steven K. Clinton, John W. Erdman, Nancy E. Moran, Hsueh-Li Tan, and Gregory S. Young
- Subjects
chemistry.chemical_classification ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Carotene ,food and beverages ,Cancer ,medicine.disease ,Phytofluene ,Lycopene ,chemistry.chemical_compound ,Prostate cancer ,Phytoene ,Endocrinology ,Oncology ,chemistry ,Biochemistry ,Internal medicine ,medicine ,Carotenoid ,Tramp - Abstract
Background: Epidemiology and laboratory studies have implicated diets rich in tomatoes and the carotenoid lycopene in prostate cancer risk reduction. However, the specific roles of lycopene, lycopene metabolites, or other tomato phytochemicals are uncertain. The discovery of carotenoid metabolizing enzymes has opened the door to mechanistic studies. The enzyme β,β-carotene 9',10'-oxygenase (BCO2) has been shown to asymmetrically cleave lycopene and other carotenoids, yielding metabolites. We hypothesize that these cleavage products may be more biologically active and convey anti-cancer activity. Therefore, we defined the impact of BCO2 ablation on the efficacy of dietary tomato and lycopene to inhibit cancer progression in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model of prostate carcinogenesis. Methods: BCO2-/- (B6; 129S6-Bcdo2tm1Dnp) mice were crossed with TRAMP+/- (C57BL/6-Tg(TRAMP)8247Ng/J) transgenic mice leading to the generation of TRAMP+/-:BCO2+/+ and TRAMP+/-:BCO2-/-. Male TRAMP:BCO2+/+ and TRAMP:BCO2-/- mice were randomized to three dietary treatments: AIN-93G control diet, 10% tomato powder diet, or 0.25% lycopene beadlet-containing diet from 3 until 18 weeks of age. Serum was collected for carotenoid analysis by HPLC, and prostate tissues were processed for histopathologic assessment of prostate carcinogenesis. Results: TRAMP:BCO2 +/+ mice fed tomato powder and lycopene attained similar serum lycopene concentrations (0.141μM +/- 0.007μM vs. 0.139μM +/- 0.007μM, respectively). The presence of the tomato carotenoids phytofluene (0.13μM +/- 0.002μM) and phytoene (0.025μM +/- 0.003μM) in serum was only observed with tomato feeding as anticipated. Loss of BCO2 enzyme resulted in significantly increased serum concentrations of total, total cis, 5-cis, and all-trans lycopene in both tomato and lycopene fed mice, and the accumulation of phytoene, phytofluene, and zeta-carotene in the tomato fed mice compared to the BCO2+/+ counterparts. For example, total serum lycopene levels were 0.229μM +/- 0.029μM and 0.223μM +/- 0.030μM in tomato- and lycopene-fed TRAMP:BCO2-/- mice, respectively. Dietary tomato powder and lycopene inhibited cancer progression. Incidence of cancer was 80% in control diet-fed TRAMP:BCO2+/+ mice, while tomato and lycopene feeding decreased incidence to 15% and 11%, respectively. Ablation of BCO2 (TRAMP:BCO2-/-) partially attenuated the anti-cancer efficacy of tomato and lycopene observed in TRAMP:BCO2+/+ mice as the incidence was 24% for tomato-fed and 46% for lycopene-fed mice. Conclusions: Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a BCO2-dependent manner. Future human studies to examine the role of lycopene metabolism and BCO2 genotype in cancer risk reduction are warranted. Citation Format: Hsueh-Li Tan, Jennifer M. Thomas-Ahner, Nancy E. Moran, Gregory S. Young, John W. Erdman, Jr., Steven K. Clinton. Dietary tomato and lycopene inhibition of prostate carcinogenesis in the TRAMP Model is β,β-carotene 9',10'-oxygenase (BCO2)-dependent. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A59.
- Published
- 2015
34. Abstract 3701: Tomato carotenoids and testosterone modulate mRNA and miRNA profiles during prostate carcinogenesis
- Author
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Steven K. Clinton, Nancy E. Moran, Jennifer M. Thomas-Ahner, John W. Erdman, Lei Wan, Dennis K. Pearl, Hsueh-Li Tan, and Amy C. Elsen
- Subjects
Cancer Research ,medicine.medical_specialty ,Biology ,TMPRSS2 ,Lycopene ,chemistry.chemical_compound ,HIF1A ,Cyclin E2 ,medicine.anatomical_structure ,Cyclin D1 ,Endocrinology ,Oncology ,chemistry ,Prostate ,Internal medicine ,medicine ,Testosterone ,Tramp - Abstract
There is considerable evidence supporting the hypothesis that tomato carotenoids may contribute to prostate cancer prevention however the mechanisms remain uncertain. We propose that bioactive tomato components, such as lycopene, may impact testosterone signaling to inhibit prostate carcinogenesis. Four week-old C57/BL6 WT and TRAMP male mice were fed either control (AIN93G), 10% tomato powder or 0.25% lycopene beadlets. At eight weeks of age, mice were randomized among treatments: intact, castration, or castration + 2.5mg/kg testosterone repletion and animals sacrificed at 10 weeks of age. Prostate gene expression was quantified by Nanostring nCounter was used to quantify prostate gene expression with a 200 gene murine prostate carcinogenesis custom codeset and miRNA with codeset v1.1. Carotenoid analysis is by HPLC and proliferation (Ki67) by immunohistochemical evaluation. Feeding dietary tomato or lycopene increased serum lycopene, for example, in WT mice concentrations reached 335 +/- 33 nmol/L and 337 +/- 34 nmol/L in tomato and lycopene fed animals, respectively. As expected, the TRAMP genotype and testosterone stimulate proliferation with diet as a modulating factor. In the WT intact prostate, the tomato powder and lycopene diet decreased proliferation (p Citation Format: Jennifer M. Thomas-Ahner, Lei Wan, Hsueh-Li Tan, Nancy E. Moran, Amy C. Elsen, Dennis K. Pearl, John W. Erdman, Steven K. Clinton. Tomato carotenoids and testosterone modulate mRNA and miRNA profiles during prostate carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3701. doi:10.1158/1538-7445.AM2013-3701
- Published
- 2013
35. Abstract 963: Bioactive tomato components antagonize the androgen regulation of epithelial cell turnover in the mouse prostate
- Author
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Steven K. Clinton, Robert C. Rengel, John W. Erdman, Amy C. Elsen, and Hsueh-Li Tan
- Subjects
Testosterone propionate ,Cancer Research ,medicine.medical_specialty ,Proliferation index ,medicine.drug_class ,Cancer ,Biology ,Androgen ,medicine.disease ,chemistry.chemical_compound ,Castration ,Endocrinology ,medicine.anatomical_structure ,Oncology ,chemistry ,Prostate ,Apoptosis ,Internal medicine ,medicine ,Testosterone - Abstract
Introduction: Testosterone is a critical regulator of prostate function and carcinogenesis. Inhibition of testosterone action is an approach for prostate cancer prevention. We hypothesize that consumption of tomato phytochemicals may have a protective impact during prostate carcinogenesis via inhibition of androgen signaling in the prostate epithelium. Methods: Four week-old C57/BL6 male mice (n=84) were fed either: AIN93-G diet as a control, AIN93-G with10% tomato powder (0.02 g LYC/Kg diet) or AIN93-G with 10% LYC beadlets (0.40 g LYC/Kg diet). At eight weeks of age, mice were randomized among three endocrine treatments: intact control, castration, or castration + testosterone repletion (2.5 mg testosterone propionate/Kg body weight/mouse/day by subcutaneous osmotic minipumps starting 7 days after castration). At 10 weeks of age, blood was collected for carotenoid analysis by HPLC and tissues were collected for evaluating prostate epithelial cell proliferation index (Ki67), apoptosis index (ApopTag), and other biomarkers. Results: Dietary intakes did not differ among groups. However, the estimated LYC consumption was 0.00 mg/d for controls, 1.13 mg/d in LYC fed mice, and 0.06 mg/d in tomato fed mice (P< 0.001). Interestingly, serum LYC levels did not differ between mice fed the tomato and LYC diets (366 and 371 nmol/L, respectively). As anticipated, castration decreased proliferative indices in control mice (1.8% vs. 4.7%) and testosterone repletion restored and further enhanced the proliferative index (15.8%) (P Conclusion: LYC absorption in mice is limited and similar blood concentrations are achieved over a wide range of dietary intake from either pure LYC or tomato components. Mice consuming tomato powder or LYC show reduced prostate epithelial proliferation in response to testosterone. Tomato powder is a more potent enhancer of apoptotic cascades in response to androgen deprivation. Bioactive components in tomatoes in addition to LYC may influence prostate biology and participate in the inhibition of prostate carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 963.
- Published
- 2010
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