Interactions of SNPs in Folate Metabolism Related Genes on Prostate Cancer Aggressiveness in European Americans and African Americans
Hui-Yi LinSusan E. SteckIndrani SarkarElizabeth T. H. FonthamAlan B. DiekmanLora J. RogersCalvin T. RatliffJeannette T. BensenJames L. MohlerL. Joseph Su
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Prostate cancer is a malignancy commonly occuring in male genitourinary system.Androgen receptor promotes gene transcription in prostate cell growth and carcinogenesis of prostate cancer,which makes it to become an important target in prostate cancer treatment possibly.Prostate cancer may be deteriorated into be castration-resistant prostate cancer easily after androgen deprivation therapy,so it is popular to seek the effective androgen receptor antagonists for treating of castration-resistant prostate cancer.This review focuses on the action mechanism and the development of androgen receptor antagonists for the treatment of prostate cancer.
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Objective:To detect single nucleotide polymorphisms(SNPs) existing in 5′-regulatory region of β2-adrenoceptor(β2-AR) gene and to investigate association of the identified SNPs with essential hypertension in Uighur of Xinjiang.Methods:Single nucleotide polymorphisms(SNPs)in the position-654G/A and-1429T/A of β2-AR gene were tested with MALDI-TOF-MS and Genotypes of the SNP were typed by MassARRAY iPLEXTMmethod.Results:Two SNPs were identified at position-654 with G→A substitution and-1429 with T→A substitution.The frequency of genotype of the two SNPs complied well with the Hardy-Weinberg equilibrium in normal group Distribution of genotype AA,GA,GG of the SNPs at locus-654 in hypertension group was no significantly different from that in normal group(P0.05),No significant difference was observed in distribution of geno-types of the SNPs at locus-1429 between the two groups(P0.05).Conclusion:These results indicate that the SNPs at locus-654 and-1429 of β2-AR gene were the SNPs position but not linked to hypertension.
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Prostate cancer is a common malignancy that affects men's health in the Western countries. Single nucleotide polymorphisms (SNPs), as the third generation of genetic markers, can influence the development, progression, and prognosis of prostate cancer. The same SNP may be related differently with prostate cancer among different races. This paper describes the relationship between SNPs and prostate cancer according to their related genes. SNPs can predict the risk of prostate cancer as well as the possible adverse reactions in its treatment, but at present they do have some limitations.
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Androgen deprivation therapy has been the standard treatment for the patients with advanced prostate cancer. Androgen deprivation therapy initially suppresses the growth of prostate cancer. However, most patients eventually progress to castration-resistant prostate cancer. Novel drugs, including enzalutamide and abiraterone acetate, are recently able to be used for the patients with castration-resistant prostate cancer. Even so, the therapeutic options for castration-resistant prostate cancer are not enough. Interestingly, androgen receptor degradation enhancer ASC-J9 is reported to degrade the androgen receptor, resulting in the suppression of the growth in castration-resistant prostate cancer cells. In this chapter, ASC-J9 for prostate cancer is reviewed.
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Prostate cancer is one of the most common and socially significant cancers among men. The aim of this study was to identify significant changes in the expression of exosomal miRNAs associated with an increase in the level of prostate specific antigen in castration-resistant prostate cancer during therapy and to evaluate them as potential prognostic markers for this category of disease. High-throughput miRNA sequencing was performed on 49 blood plasma samples taken from 11 Russian patients with castration-resistant cancer during therapy. Bioinformatic analysis of the obtained miRNA-seq data was carried out. Additionally, miRNA-seq data from the PRJNA562276 project were analyzed to identify exosomal miRNAs associated with castration-resistant prostate cancer. We found 34 differentially expressed miRNAs associated with the progression of castration-resistant prostate cancer during therapy in Russian patients. It was also shown that hsa-miRNA-148a-3p expression can serve as a potential prognostic marker. We found the exosomal miRNA expression signature associated with castration-resistant prostate cancer progression, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.
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Abstract : Prostate cancer cells have a remarkable affinity to develop metastases in bone. Clinical data and laboratory observations both suggest that bone-malignant epithelium interactions play a central role in prostate cancer progression. We have developed an in vitro model system that reflects the most common cellular features of prostate cancer bone metastases. The model consists of the prostate cancer cell lines: MDA PCa 2a or MDA PCa 2b (the TabBO cells) co-cultured with primary mouse osteoblasts (PMO). The two cell types share medium but are not in physical contact because the prostate cancer cells are plated in cell-culture inserts. We have established the optimal conditions for growing prostate cancer cells in co-culture with PMO. Using those conditions, we defined the effect that prostate cancer cells have in PMO in our model system. This effect reflects the interaction between prostate cancer cells and osteoblasts in prostate cancer bone metastases. Therefore we conclude that our model system may be suitable to study the molecular and cellular events involved in the new bone formation observed in prostate cancer bone metastases.
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Recurrence of localized prostate cancer following treatment can lead to lethal metastatic castration-resistant prostate cancer. Although numerous studies aimed at developing biomarkers for predicting recurrence of localized prostate cancer are promising, they have not yet led to useful applications. Dysregulation of exportins (XPOs, nucleocytoplasmic transporters) associated with subcellular mislocalization of proteins has been reported for various human cancers. However, most of the XPOs have not been studied in prostate cancer. In this study, we are the first to examine whether changes in expression of XPOs could be used as potential biomarkers for recurrence of localized prostate cancer. Using the oncomine database, gene expressions of 7 known XPOs by 1128 patient samples, obtained from 16 independent prostate cancer patient cohorts, were analyzed. Relatively highly elevated expression of XPO6 (compared to prostate cancer tissue) was found to be significantly associated with poor patient prognosis, in particular, with rapid recurrence in a clinical low risk group. As such, expression of XPO6 may be a potential prognostic biomarker for predicting prostate cancer recurrence.
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ポストシークエンスの時代に入り, 複数の遺伝子と環境因子が関与して発症する多因子性疾患の危険因子の探求が注目されるようになってきた。'ありふれた病気'の一つである歯周炎の発症および進行には, 口腔内環境や生体の免疫応答が関与していると考えられ, 歯周炎についての遺伝子学的検索が求められている。本研究では, 一塩基多型 (SNPs) 解析により歯周炎の関連因子の検討を行った。SNPsは, DNA配列中に見られる多型のうちもっともよく見られる多型で, SNPs解析は多くの遺伝子の解析が可能である。被検者は, 早期発症型歯周炎患者 (EOP) 13人, 成人性歯周炎患者 (AP) 9人, 健常者19人とした。本研究は, インターロイキン1 (IL1), 腫瘍壊死因子α (TNFα) 等の歯周炎候補遺伝子の一塩基多型 (Single Nucleotide Polymorphisms: SNPs) 計59について, TaqMan PCR法により, 歯周炎との関連について検討すること目的とした。また, SNPsの選択には, 連鎖不平衡を考慮した。その結果, 早期発症型歯周炎群とコントロール群では, カテプシンG (CTSG) と腫瘍壊死因子レセプター関連因子1 (TRAF1) において有意差 (P<0.05) が認められた。成人性歯周炎群とコントロール群では, インターロイキン10レセプターβ (IL10RB) とマトリックスメタロプロテアーゼ9 (MMP9) において有意差が認められた。また, 早期発症型歯周炎群と成人性歯周炎群では, インターフェロンγ (IFNG) において有意差が認められた。以上のことから, 早期発症型歯周炎においては, CTSGの関与が推測された。成人性歯周炎においては, IL10RBとMMP9の関与が推測された。さらに, 早期発症型歯周炎と成人性歯周炎においては, IFNGの関与に相違があるものと推測された。本研究より, 今後日本人の標準SNPsのデータベースであるJSNPに登録されているSNPsのさらなる解析により, 日本人における歯周炎の遺伝子学的な関連因子の解明につながる可能性が示唆された。
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