Vitamin A, Cancer Treatment and Prevention: The New Role of Cellular Retinol Binding Proteins

Doldo, Elena; Costanza, Gaetana; Agostinelli, Sara; Tarquini, Chiara; Ferlosio, Amedeo; Arcuri, Gaetano; Passeri, Daniela; Scioli, Maria Giovanna; Orlandi, Augusto

doi:10.1155/2015/624627

Cited by 135 publications

(99 citation statements)

References 124 publications

(143 reference statements)

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“…In addition, the RA pathway is defective in many cancers, including EOC [49]. To test whether PRAME expression is associated with altered RA signaling in EOC and HGSC, we used Gene Set Enrichment Analysis (GSEA) to test the relationship between PRAME mRNA expression and RA-mediated gene expression in a large set of published EOC ( N = 285) and HGSC ( N = 218) expression data [50].…”

Section: Resultsmentioning

confidence: 99%

PRAME expression and promoter hypomethylation in epithelial ovarian cancer

et al. 2016

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PRAME is a cancer-testis antigen (CTA) and potential immuno-therapeutic target, but has not been well-studied in epithelial ovarian cancer (EOC) or its high grade serous (HGSC) subtype. Compared to normal ovary, PRAME expression was significantly increased most EOC, regardless of stage and grade. Interestingly, PRAME mRNA expression was associated with improved survival in the HGSC subtype. The PRAME locus was a frequent target for copy number alterations (CNA) in HGSC but most changes were heterozygous losses, indicating that elevated PRAME expression is not typically due to CNA. In contrast, PRAME promoter DNA hypomethylation was very common in EOC and HGSC and correlated with increased PRAME expression. PRAME expression and promoter hypomethylation both correlated with LINE-1 hypomethylation, a biomarker of global DNA hypomethylation. Pharmacologic or genetic disruption of DNA methyltransferase (DNMT) enzymes activated PRAME expression in EOC cells. Immunohistochemistry (IHC) of PRAME in EOC revealed frequent, but low level, protein expression, and expression was confined to epithelial cells and localized to the cytoplasm. Cytoplasmic PRAME expression was positively associated with PRAME mRNA expression and negatively associated with promoter methylation, but the latter correlation was not statistically significant. PRAME protein expression did not correlate with EOC clinicopathology or survival. In summary, PRAME is frequently expressed in EOC at the mRNA and protein levels, and DNA methylation is a key mechanism regulating its expression. These data support PRAME as an immunotherapy target in EOC, and suggest treatment with DNMT inhibitors as a means to augment PRAME immunotherapy.

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Section: Resultsmentioning

confidence: 99%

PRAME expression and promoter hypomethylation in epithelial ovarian cancer

et al. 2016

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“…However, they cannot be synthesized de novo by animals (including human) and must be obtained from the diets11. Recently, a myriad of epidemiological studies have demonstrated an inverse relationship between dietary vitamin A consumption and cancer development12. For instance, vitamin A has been proved to play a protective role in breast cancer13 and lung cancer14.…”

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confidence: 99%

Association between vitamin A, retinol and carotenoid intake and pancreatic cancer risk: Evidence from epidemiologic studies

Huang

Yuan-fu

Zhi

et al. 2016

Sci Rep

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Pancreatic cancer is a devastating disease with poor prognosis. The association between vitamin A, retinol and carotenoid intake and the risk of pancreatic cancer occurrence remains controversial, and therefore it is necessary to make a meta-analysis to clarify the association between vitamin A, retinol and carotenoid intake and pancreatic cancer risk. In the present study, PubMed and EMBASE databases were used to identify qualified studies. The association between dietary vitamin A, retinol and carotenoids was estimated by pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). It was found that there was an inverse correlation between vitamin A, beta-carotene and lycopene intake and the risk of pancreatic cancer (for vitamin A, pooled OR = 0.85, 95%CI = 0.74–0.97, P = 0.015; for beta-carotene, pooled OR = 0.78, 95%CI = 0.66–0.92, P = 0.003; for lycopene, pooled OR = 0.84, 95%CI = 0.73–0.97, P = 0.020), which was more prominent in case-control study subgroup. In conclusion, dietary vitamin A, beta-carotene and lycopene might inversely correlate with pancreatic cancer.

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“…CRBP-1 suppression is associated with a more aggressive phenotype in breast, ovary, and nasopharyngeal cancer. Overexpression of CRBP-1 increases the sensitivity to retinol and reduces the viability of ovarian cancer cells in vitro [51].…”

Section: Discussionmentioning

confidence: 99%

Model of Long-Term Vitamin A Deficiency in the Mammary Gland of Virgin Rats

Gomez¹,

Varas²,

Giménez³

2017

OALib

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Deficiency in vitamin A is an evil in underdeveloped countries where the minimum recommended intake is not achieved. This may have long-term implications on the health of the population. For this reason, it would be very useful to achieve an animal model where the different implications of this deficiency can be observed. This could lead to the formulation of future nutrition politics. The levels of retinoic acid and intermediary of the vitamin A pathway were studied; The levels of retinoic acid and intermediary of the vitamin A pathway (CRBP-1 and RARα) were studied. There was a decrease in the values of retinoic acid main indicator of deficiency of this vitamin in serum, liver and mammary gland and variation in expression of CRBP-1 and RARα mRNA in mammary gland. This model provides a tool for the study of the metabolism of vitamin A and its effects in different organs and especially in virgin mammary gland, where a deficiency is achieved despite being in a state of latency.

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Vitamin A, Cancer Treatment and Prevention: The New Role of Cellular Retinol Binding Proteins

Cited by 135 publications

References 124 publications

PRAME expression and promoter hypomethylation in epithelial ovarian cancer

PRAME expression and promoter hypomethylation in epithelial ovarian cancer

Association between vitamin A, retinol and carotenoid intake and pancreatic cancer risk: Evidence from epidemiologic studies

Model of Long-Term Vitamin A Deficiency in the Mammary Gland of Virgin Rats

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