Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer

The Prostate ◽  
2007 ◽  
Vol 67 (10) ◽  
pp. 1029-1037 ◽  
Author(s):  
Jinpei Kumagai ◽  
Tetsuya Fujimura ◽  
Satoru Takahashi ◽  
Tomohiko Urano ◽  
Tetsuo Ogushi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cytochrome P450 ◽  
Prognostic Factor ◽  
Cytochrome P450 2B6 ◽  
Growth Inhibitory

Cytochrome P450 2B6 is aGrowth-Inhibitory and Prognostic Factor for ProstateCancer.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Prostate Cancer ◽  
Cytochrome P450 ◽  
Androgen Receptor ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Standard Treatment ◽  
Beneficial Effects ◽  
Cytochrome P450 2B6 ◽  
The World ◽  
Abundant Evidence

Prostate cancer is one of the most common malignanciesin the world. There is abundant evidence thatandrogens influence the development and progressionof prostate cancer [1–3]. Since most of prostate cancer isandrogen-dependent, standard treatment for metastaticprostate cancer patients is androgen deprivationtherapy (ADT). However the beneficial effects of ADTare transient and prostate cancer progresses to recurrentcancer. Recent reports showed that levels oftestosterone and its metabolites, dihydrotestosterone(DHT) and androstenediol, were still sufficiently highto activate the androgen receptor in recurrent prostate

Polymorphism of cytochrome P450 2B6 and prostate cancer risk: A significant association in a Japanese population

2009 ◽  
Vol 16 (4) ◽  
pp. 364-368 ◽  
Author(s):  
Takayuki Kurosaki ◽  
Motofumi Suzuki ◽  
Yutaka Enomoto ◽  
Tomio Arai ◽  
Motoji Sawabe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cytochrome P450 ◽  
Cancer Risk ◽  
Japanese Population ◽  
Prostate Cancer Risk ◽  
Cytochrome P450 2B6

664: PSA Decline from Baseline is not a Prognostic Factor for Outcome in Hormonally Treated Patients with T0-4N0M0 Prostate Cancer not Suitable for Local Treatment with Curative Intent Treated in Eortc 30891

2006 ◽  
Vol 175 (4S) ◽  
pp. 214-214
Author(s):  
Urs E. Studer ◽  
Laurence Collette ◽  
Peter Whelan ◽  
Walter Albrecht ◽  
Jacques Casselman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Local Treatment ◽  
Curative Intent

Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Hazard Analysis ◽  
Critical Role ◽  
Immunohistochemical Analysis ◽  
Lncap Cells ◽  
Cancer Specific Survival ◽  
High Gleason Score ◽  
Castrate Resistant ◽  
Transcription Factor 1

The androgen receptor (AR) plays a critical role in the development and the progression of prostate cancer. Alterations in theexpression of AR coregulators lead to AR hypersensitivity, which is one of the mechanisms underlying the progression ofprostate cancer into a castrate-resistant state. Octamer transcription factor 1 (Oct1) is a ubiquitous member of the POUhomeodomainfamily that functions as a coregulator of AR. In our study, the contribution of Oct1 to prostate cancerdevelopment was examined. Immunocytochemistry analysis showed that Oct1 is expressed in the nuclei of LNCaP cells.siRNA-mediated silencing of Oct1 expression inhibited LNCaP cell proliferation. Immunohistochemical analysis of Oct1expression in tumor specimens obtained from 102 patients with prostate cancer showed a positive correlation of Oct1immunoreactivity with a high Gleason score and AR immunoreactivity (p 5 0.0042 and p < 0.0001, respectively). Moreover,patients with high immunoreactivity of Oct1 showed a low cancer-specific survival rate, and those patients with highimmunoreactivities of both Oct1 and AR exhibited poorer cancer-specific prognosis. Multivariate hazard analysis revealed asignificant correlation between high Oct1 immunoreactivity and poor cancer-specific survival (p 5 0.012). These resultsdemonstrate that Oct1 can be a prognostic factor in prostate cancer as a coregulator of AR and may lead to the developmentof a new therapeutic intervention for prostate cancer.

Role of Cytochrome P450 in Prostate Cancer and its Therapy

2020 ◽  
Vol 16 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Rishabh Kaushik ◽  
Sheeza Khan ◽  
Meesha Sharma ◽  
Srinivasan Hemalatha ◽  
Zeba Mueed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cytochrome P450 ◽  
Drug Discovery ◽  
Cholesterol Metabolism ◽  
Molecular Targets ◽  
Health Concern ◽  
Metabolic Functions ◽  
Novel Drugs ◽  
Genes Encoding ◽  
Causes Of Mortality

Prostate cancer has become a global health concern as it is one of the leading causes of mortality in males. With the emerging drug resistance to conventional therapies, it is imperative to unravel new molecular targets for disease prevention. Cytochrome P450 (P450s or CYPs) represents a unique class of mixed-function oxidases which catalyses a wide array of biosynthetic and metabolic functions including steroidogenesis and cholesterol metabolism. Several studies have reported the overexpression of the genes encoding CYPs in prostate cancer cells and how they can be used as molecular targets for drug discovery. But due to functional redundancy and overlapping expression of CYPs in several other metabolic pathways there are several impediments in the clinical efficacy of the novel drugs reported till now. Here we review the most crucial P450 enzymes which are involved in prostate cancer and how they can be used as molecular targets for drug discovery along with the clinical limitations of the currently existing CYP inhibitors.

Effect of Commonly Used Organic Solvents on the Kinetics of Cytochrome P450 2B6- and 2C8-Dependent Activity in Human Liver Microsomes

2007 ◽  
Vol 35 (11) ◽  
pp. 1990-1995 ◽  
Author(s):  
Ragini Vuppugalla ◽  
Shu-Ying Chang ◽  
Hongjian Zhang ◽  
Punit H. Marathe ◽  
David A. Rodrigues
Keyword(s):  
Cytochrome P450 ◽  
Organic Solvents ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cytochrome P450 2B6 ◽  
Dependent Activity ◽  
Kinetics Of

scholarly journals Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Teppei Okamoto ◽  
Daisuke Noro ◽  
Shingo Hatakeyama ◽  
Shintaro Narita ◽  
Koji Mitsuzuka ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Abiraterone Acetate ◽  
Tumor Burden ◽  
Hazard Ratio ◽  
Historical Cohort ◽  
High Tumor Burden ◽  
Significant Difference ◽  
Hormone Sensitive ◽  
The Impact

Abstract Background Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. Methods We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). Results We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. Conclusion Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

scholarly journals Expression of AR-V7 (Androgen Receptor Variant 7) Protein in Granular Cytoplasmic Structures Is an Independent Prognostic Factor in Prostate Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2639
Author(s):  
Paul König ◽  
Markus Eckstein ◽  
Rudolf Jung ◽  
Amer Abdulrahman ◽  
Juan Guzman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Androgen Receptor ◽  
Prognostic Factor ◽  
Cancer Biology ◽  
Splice Variants ◽  
Independent Prognostic Factor ◽  
Cytoplasmic Granules ◽  
Cox's Regression ◽  
Cytoplasmic Structures

Prostate cancer (PCa) is the second most common cancer, causing morbidity and mortality among men world-wide. The expression of the androgen receptor (AR) and its splice variants is a crucial factor of prostate cancer biology that has not been comprehensively studied in PCa tumors. The aim of this study was to characterize the protein expression of the AR and its splice variant, AR-V7, and their subcellular distributions in PCa by immunohistochemistry and to correlate the results to the clinicopathological data and prognosis. Immunohistochemical staining for AR and AR-V7 was performed on a tissue microarray (TMA) with specimens from 410 PCa patients using an immunoreactive score (IRS) or only the percentage of AR-V7 staining in cytoplasmic granules. Nuclear or cytoplasmic AR staining was not associated with prognosis. AR-V7 staining was only occasionally observed in the nucleus. However, AR-V7 staining in the cytoplasm or in cytoplasmic granules was associated with relapse-free survival (RFS). AR-V7 staining of the cytoplasm was associated with a shorter RFS, whereas AR-V7 staining of cytoplasmic granules was associated with a longer RFS. In a multivariate Cox’s regression analysis, only negative (<5%) AR-V7 staining of cytoplasmic granules remained an independent prognostic factor for RFS (HR = 5.3; p = 0.006). In a further subgroup analysis by multivariate Cox’s regression analysis, AR-V7 was an independent prognostic factor in the following groups: age ≤ 65 (HR = 9.7; p = 0.029), negative CK20 staining (HR = 7.0; p = 0.008), and positive perineural invasion (HR = 3.7; p = 0.034). Altogether, AR-V7 protein in granular cytoplasmic structures is an independent prognostic factor for RFS in PCa patients.

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