Hormonal Therapy for Advanced Prostatic Carcinoma

Ad, Seftel; Jp, Spirnak; Mi, Resnick

doi:10.1002/jso.2930420505

Cited by 6 publications

(2 citation statements)

References 75 publications

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“…This was based on the finding that enzymes converting testosterone to DHT and dihydroepiandrostenedione to androstenedione were upregulated to a greater extent than the other enzymes in the synthesis pathway (32,33). However, it has also been demonstrated that an adrenalectomy paired with ADT does not limit CaP progression, suggesting limited involvement of adrenal precursors (34,35). Overall, it appears that adrenal precursors are not the only source of ligand for AR activation, and de novo androgen synthesis is likely required to provide sufficient ligand for maintaining this pathway in CRPC cells.…”

Section: De Novo Androgen Synthesis In Castration-resistant Prostate mentioning

confidence: 97%

Cholesterol as a Potential Target for Castration-Resistant Prostate Cancer

Twiddy

León

2010

Pharm Res

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Advanced prostate cancer (CaP) is often treated with androgen deprivation therapy (ADT). Despite high initial success rates of this therapy, recurrence of the cancer in a castration-resistant (CRPC) form is inevitable. It has been demonstrated that, despite the low levels of circulating androgens resulting from ADT, intratumoral androgen levels remain high and androgen receptor activation persists. Recently, it was discovered that de novo androgen synthesis is occurring within the tumor cells themselves, thus providing a potential mechanism for the high endogenous concentrations. A common upstream precursor in this steroidogenic pathway is cholesterol. For many decades, the breakdown of cholesterol homeostasis in cancer has been the focus of research, but this was largely to elucidate its involvement in maintaining membrane integrity and cell signaling. De novo steroidogenesis has provided a new avenue for cholesterol research and reinforces the importance of understanding the mechanisms that lead to the alterations in cholesterol regulation in the progression to CRPC. The findings to date suggest that cholesterol homeostasis is altered to support de novo androgen synthesis and appear to facilitate disease progression. We further propose that a better understanding of the link between cholesterol and de novo androgen synthesis in CaP progression may provide opportunities for novel therapeutic intervention, namely via eliminating sources of the precursor cholesterol. This review summarizes the implications of cholesterol dysregulation in CaP and particularly in the post-ADT castration-resistant state, as well as the potential implementation of novel therapies targeting these cholesterol sources.

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Section: De Novo Androgen Synthesis In Castration-resistant Prostate mentioning

confidence: 97%

Cholesterol as a Potential Target for Castration-Resistant Prostate Cancer

Twiddy

León

2010

Pharm Res

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“…Relative contra-indications to the procedure have included patients with bleeding diathesis, immunocompromise, and chronic infection. For many years, bilateral orchiectomy was held as the gold stand¬ ard for hormonal therapy of advanced prostate cancer (Herbst 1941, Seftel et al 1989). Nonsurgical forms of castration were also discovered during the 1940s with the introduction of estrogen therapy (Daneshgari & Crawford 1993).…”

Section: Introductionmentioning

confidence: 99%

Endocrine therapy of advanced carcinoma of the prostate

Waxman¹,

Crawford²

1996

Endocrine Related Cancer

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Fibrin formation on vessel walls in hyperplastic and malignant prostate tissue

Wojtukiewicz

Zacharski

Memoli

et al. 1991

Cancer

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To explore mechanisms of coagulation activation in adenocarcinoma of the prostate, the occurrence and distribution of components of coagulation and fibrinolysis pathways in situ were studied by means of immunohistochemical techniques applied to frozen sections of fresh malignant and benign hyperplastic prostatic tissue obtained at transurethral resection. Fibrinogen was distributed throughout the perivascular and tumor connective tissue in both malignant and benign disease but was not present in adjacent areas of normal prostate. Antibodies specific for fibrin and D-dimer crosslink sites stained vascular endothelium focally in both malignant and benign tissues. Both neoplastic cells and benign hyperplastic glandular epithelial cells stained weakly and in a patchy distribution for tissue factor and focally for low-molecular-weight urokinase-type plasminogen activator. Focal staining of vascular endothelium was also observed for tissue plasminogen activator and plasmin-antiplasmin complex neoantigen. By contrast, no tissue staining was observed for factor VII, factor X, factor XIII "a" subunit, high-molecular-weight urokinase-type plasminogen activator, plasminogen activator inhibitors 1 to 3, protein C, and protein S. Thus, the similarity in findings between benign hyperplastic and neoplastic prostate tissue, the lack of either an intact tumor cell-associated coagulation pathway or fibrin formation, and the presence of fibrin on vascular endothelium are consistent with the concept that coagulation activation in prostatic cancer may not be due to a direct effect of the tumor cells on the clotting mechanism. Rather, such activation may be induced by a soluble tumor product that activates procoagulant activity on certain host (for example, vascular endothelial) cells. These findings, together with the lack of effect of warfarin anticoagulation on the clinical course of patients with prostatic cancer, contrast with findings in certain other tumor types and suggest that coagulation activation may not contribute to progression of adenocarcinoma of the prostate.

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Hormonal Therapy for Advanced Prostatic Carcinoma

Cited by 6 publications

References 75 publications

Cholesterol as a Potential Target for Castration-Resistant Prostate Cancer

Cholesterol as a Potential Target for Castration-Resistant Prostate Cancer

Endocrine therapy of advanced carcinoma of the prostate

Fibrin formation on vessel walls in hyperplastic and malignant prostate tissue

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