Prostate‐Specific antigen expression by various tumors

Levesque, Michael A.; Hu, He Ping; Diamandis, Eleftherios P.; D’Costa, Mario

doi:10.1002/jcla.1860090209

Cited by 108 publications

(45 citation statements)

References 31 publications

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“…although it is also expressed at low concentrations in the para- 10 1997 British Journal of Urology urethral glands [2] and normal breast tissue. as well as in breast and some other cancers [3]. PSA is expressed both by normal and by malignant prostatic cells.…”

Section: Expression Oj Psamentioning

confidence: 99%

Prostate‐specific antigen, clinical use and staging: an overview

Stenman

1997

British Journal of Urology

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Section: Expression Oj Psamentioning

confidence: 99%

Prostate‐specific antigen, clinical use and staging: an overview

Stenman

1997

British Journal of Urology

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“…2,3 Over-expression of PSA has primarily been demonstrated in prostate carcinoma and at low levels in breast cancer. [4][5][6][7][8] We have recently developed an albumin-binding prodrug of doxorubicin that is cleaved by PSA, i.e., EMC-Arg-Arg-Ser-SerTyr-Tyr-Ser-Gly-DOXO (EMC 5 6-maleimidocaproic acid; DOXO 5 doxorubicin. 9 Our drug targeting strategy is based on 2 features [10][11][12] : (i) in situ binding of a thiol-binding prodrug to the cysteine-34 position of circulating albumin after intravenous administration with subsequent accumulation of the drug albumin conjugate in the tumor because of passive targeting; (ii) release of the albumin-bound drug at the tumor site because of the incorporation of a cleavable bond between the drug and the carrier.…”

mentioning

confidence: 99%

Synthesis and biological evaluation of an albumin‐binding prodrug of doxorubicin that is cleaved by prostate‐specific antigen (PSA) in a PSA‐positive orthotopic prostate carcinoma model (LNCaP)

Graeser¹,

Chung

Esser³

et al. 2007

Intl Journal of Cancer

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The prostate-specific antigen (PSA) is a serine protease that is over-expressed in prostate carcinoma and represents a molecular target for selectively releasing an anticancer agent from a prodrug formulation. We have recently investigated a macromolecular prodrug strategy for improved cancer chemotherapy based on 2 features: (i) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration, and (ii) enzymatic release of the albuminbound drug at the tumor site (Mansour et al., Cancer Res 2003, 63, 4062-4066). In this work, we describe an albumin-binding prodrug, EMC-Arg-Ser-Ser-Tyr-Tyr-Ser-Arg-DOXO [EMC: e-Maleimidocaproic acid; DOXO 5 doxorubicin; X 5 amino acid] that is cleaved by PSA. Because of the incorporation of 2 arginine residues, the prodrug exhibited excellent water-solubility and was rapidly and selectively bound to endogenous albumin. Incubation studies with PSA and tumor homogenates from PSA-positive tumors (LNCaP) demonstrated that the albumin-bound form of the prodrug was efficiently cleaved by PSA at the P 1 -P 0 1 scissile bond releasing the doxorubicin dipeptide H-Ser-Arg-DOXO, which was further degraded to doxorubicin as the final cleavage product. In cell culture experiments, the prodrug was 100-fold less active against LNCaP cells than the free drug. In contrast, in a mouse model of human prostate cancer using luciferase transduced LNCaP cells orthotopically implanted in SCID mice, the prodrug showed enhanced antitumor efficacy when compared to doxorubicin. Doxorubicin treatment at a dose of 2 3 4 mg/kg caused significant weight loss and mortality (225%), and did not result in a significant antitumor response at the end of the experiment. The prodrug at 3 3 12 mg/kg doxorubicin equivalents, however, was well tolerated and induced a significant reduction in tumor size of 62% (625%, **p 5 0.003) as well as a decrease of the metastatic burden in the lungs as detected in luciferase assays (250%, SD 6 115%, *p 5 0.038). ' 2007 Wiley-Liss, Inc.Key words: doxorubicin; macromolecular prodrug; human serum albumin; PSA; orthotopic animal model; LNCaP; luciferase; in vivo bioluminescence Hormone refractory prostate cancer responds unfavorably to chemotherapy. The best results to date are achieved with Taxotere. 1 To improve prostate cancer therapy, tumor-specific delivery of anticancer agents to the primary tumor and metastases is a goal worth pursuing.For selectively releasing anticancer agents, the prostate-specific antigen (PSA) is especially attractive as a target protease because it is solely expressed in prostate tissue and prostate carcinoma in prostate cancer patients with high levels up to mg/g present in human prostate carcinoma. 2,3 PSA is a serine protease that belongs to the kallikrein gene family with chymotrypsin-like activity that is involved in the hydrolytic processing of semenogelins (cleavage of the semenal fluid proteins semenogelin I and II), which is required for liquefaction of seminal fluids. 2,3 Over...

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“…It is now widely accepted that prostate-specific antigen (PSA) is present in many non-prostatic tissues and especially in the female breast (Yu et al, 1994a(Yu et al, , 1995a; Levesque et al, 1995;Ferguson et al, 1996. PSA has also been found in breast cancer cell lines after hormone stimulation (Yu et al, 1994b(Yu et al, , 1995b, in female serum Giai et al, 1995;Melegos and Diamandis, 1996) in milk from lactating women (Yu and Diamandis, 1995a), in breast cyst fluid and in amniotic fluid (Yu and Diamandis, 1995b).…”

mentioning

confidence: 99%

Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases

Borchert

Melegos²,

Tomlinson³

et al. 1997

Br J Cancer

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Summary Using a highly sensitive immunofluorometric procedure, we measured the total prostate-specific antigen (PSA) concentration in 632 sera obtained from female blood donors and women with idiopathic hirsutism, breast cancer or benign breast diseases. A total of 50 sera with total PSA> 15 ng 1-' were fractionated by high-performance liquid chromatography (HPLC) in order to resolve the two immunoreactive molecular forms, i.e. free PSA (approximately 30 kDa) and PSA bound to a1-antichymotrypsin (PSA-ACT, 100 kDa). We found that breast cancer patients have presurgical serum total PSA levels similar to those of blood donors. Total serum PSA concentration decreases with age in women with idiopathic hirsutism, in cancer patients and in patients with benign breast diseases. The major molecular form of PSA in the serum of all normal and hirsute women (n = 15) is PSA bound to the proteinase inhibitor a,-antichymotrypsin. The major molecular form in 44% of presurgical cancer patient sera-is free PSA. A total of 58% of benign breast disease patients also have in their serum mainly free PSA. We conclude that about half the patients with breast cancer or benign breast diseases have free PSA as the major molecular form in their serum, whereas patients without breast pathologies (normal blood donors, idiopathic hirsutism) have PSA bound to a1-antichymotrypsin as the major molecular form. The ratio of PSA/PSA-ACT may have value as a simple biochemical test for diagnosis of breast pathologies including breast cancer.

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Prostate‐Specific antigen expression by various tumors

Cited by 108 publications

References 31 publications

Prostate‐specific antigen, clinical use and staging: an overview

Prostate‐specific antigen, clinical use and staging: an overview

Synthesis and biological evaluation of an albumin‐binding prodrug of doxorubicin that is cleaved by prostate‐specific antigen (PSA) in a PSA‐positive orthotopic prostate carcinoma model (LNCaP)

Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases

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