Prostate-Specific Membrane Antigen-Based Therapeutics

Akhtar, Naveed; Pail, Orrin; Saran, Ankeeta; Tyrell, Lauren; Tagawa, Scott T.

doi:10.1155/2012/973820

Cited by 74 publications

(54 citation statements)

References 78 publications

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“…PSMA, as an integral membrane protein highly specific for prostate, may prove to be effective as a target for imaging and cytotoxic targeting modalities [23,40]. Monoclonal antibodies may be internalized by PC cells [21].…”

Section: Discussionmentioning

confidence: 99%

“…Monoclonal antibodies may be internalized by PC cells [21]. The availability of prostate-specific internalizing antibodies should aid the development of novel therapeutic methods to target the delivery of toxins, drugs, or short-range isotopes specifically to the interior of prostate cancer cells [22,23,40]. The high expression in metastatic tissues strongly suggests that PSMA may be a clinically useful target for antibody and genetic-directed therapy of PC that recurs after androgen deprivation [36].…”

Section: Discussionmentioning

confidence: 99%

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Differences in the expression of telomerase and prostate-specific membrane antigen in non-advanced prostatic cancer

Gasińska

Łuczyńska

Wilk

et al. 2013

Folia Histochem Cytobiol.

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Early recognition of prostate cancer (PC) based on biological markers could be helpful in identification of differences in benign and malignant lesions and facilitate further precise indication for more aggressive treatment. Therefore, the aim of our study was to assess expression of hTERT (human telomerase reverse transcriptase, a catalytic subunit of telomerase) and prostate-specific membrane antigen (PSMA), both considered to be markers of tumor aggressiveness. 140 low advanced PC specimens from patients who underwent radical prostatectomy were studied. Protein expression was assessed immunohistochemically on tumor sections and expressed as labeling index (LI), i.e. the percentage of positively stained cells. In case of telomerase, only nuclear staining and in case of PSMA, membrane and cytoplasmic staining, were considered as positive. The mean age of the patients was 62.9 ± 6.2 years. There were 75 (53.6%) well differentiated tumors (Gleason score 6), 52 (37.1%) moderately differentiated tumors (Gleason score of 7) and 13 (9.3%) poorly differentiated tumors (Gleason score 8-10). The mean pre-operative serum PSA was 9.9 ± SE 5.5 ng/mL, and the mean LI were 18.0 ± 1.5% and 44.1 ± 1.9%, for hTERT and PSMA, respectively. With increase of pathological tumor stage and tumor grade statistically significant increase of PSA serum concentration (P < 0.011) and PSMA (P < 0.004) expression was noticed, however, for expression of telomerase the relation was opposite one. The observed in higher pTNM stages and tumor grades decrease in nuclear expression of hTERT was caused by translocation of the subunit to the cytoplasm, what may indicate extranuclear telomerase activity independent of telomere lengthening, hence, it cannot be considered as a marker of malignancy. Higher PSMA expression in higher pTNM stages and tumor grades suggest that PSMA may be a good marker of biological aggressiveness suitable for patients' selection for more aggressive treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differences in the expression of telomerase and prostate-specific membrane antigen in non-advanced prostatic cancer

Gasińska

Łuczyńska

Wilk

et al. 2013

Folia Histochem Cytobiol.

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“…[44][45][46][47][48][49] Our data show that J591 conjugated to paclitaxel-loaded micelles specifically target the micelles to human prostate cancer cells and prevent tumor growth in a PSMA-dependent manner. PSMA is highly expressed in almost all primary and metastatic prostate cancer tumors.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner

Taylor¹,

Sillerud²

2012

IJN

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Background and methods:Problems with the clinical management of prostate cancer include the lack of both specific detection and efficient therapeutic intervention. We report the encapsulation of superparamagnetic iron platinum nanoparticles (SIPPs) and paclitaxel in a mixture of polyethyleneglycolated, fluorescent, and biotin-functionalized phospholipids to create multifunctional SIPP-PTX micelles (SPMs) that were conjugated to an antibody against prostate-specific membrane antigen (PSMA) for the specific targeting, magnetic resonance imaging (MRI), and treatment of human prostate cancer xenografts in mice. Results: SPMs were 45.4 ± 24.9 nm in diameter and composed of 160.7 ± 22.9 µg/mL iron, 247.0 ± 33.4 µg/mL platinum, and 702.6 ± 206.0 µg/mL paclitaxel. Drug release measurements showed that, at 37°C, half of the paclitaxel was released in 30.2 hours in serum and two times faster in saline. Binding assays suggested that PSMA-targeted SPMs specifically bound to C4-2 human prostate cancer cells in vitro and released paclitaxel into the cells. In vitro, paclitaxel was 2.2 and 1.6 times more cytotoxic than SPMs to C4-2 cells at 24 and 48 hours of incubation, respectively. After 72 hours of incubation, paclitaxel and SPMs were equally cytotoxic. SPMs had MRI transverse relaxivities of 389 ± 15.5 Hz/mM iron, and SIPP micelles with and without drug caused MRI contrast enhancement in vivo. Conclusion: Only PSMA-targeted SPMs and paclitaxel significantly prevented growth of C4-2 prostate cancer xenografts in nude mice. Furthermore, mice injected with PSMA-targeted SPMs showed significantly more paclitaxel and platinum in tumors, compared with nontargeted SPM-injected and paclitaxel-injected mice.

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“…PSMA is overexpressed at levels of up to 1000-fold at all Gleason scores [15,16], while overexpression increases with tumor progression [17,18]. Despite the heterogeneous nature of the disease, primary tumors or metastases that are completely PSMA-negative are rare [19].…”

Section: Priority Research Papermentioning

confidence: 99%

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2017

Oncotarget

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Prostate-Specific Membrane Antigen-Based Therapeutics

Cited by 74 publications

References 78 publications

Differences in the expression of telomerase and prostate-specific membrane antigen in non-advanced prostatic cancer

Differences in the expression of telomerase and prostate-specific membrane antigen in non-advanced prostatic cancer

Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner

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