Browsing by Subject "PSMA"

Now showing 1 - 4 of 4
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    AB025. Evaluation of potential therapeutic immunohistochemical targets with experimental or FDA-approved therapies in thymic epithelial tumor microarrays
    (AME, 2023-12-30) Ardeshir-Larijani, Fatemeh; Loehrer, Patrick J.; Maniar, Rohan; Hou, Tieying; DeBrock, Victoria; Mesa, Hector; Pathology and Laboratory Medicine, School of Medicine
    Background: Thymus epithelial tumors (TETs) are rare malignancies of the anterior mediastinum. The current standard of care for metastatic TETs is a combination of platinum-based chemotherapy. Here, we have evaluated the experimental and FDA-approved makers in a large TET tissue array with the hope of identifying a new therapeutic option. Methods: A tissue microarray (TMA) containing ninety malignant thymic tumors (A, AB, B1 and B2, n=62, B2/B3 and B3, n=16, and thymic carcinoma, n=12) and seven normal adult thymus were assembled. The protein expressions of GLUT1, TROP2, PSMA, ROS1, ALK, HER2, and PDL-1 were tested with immunohistochemical assays. Expression was quantified using a “staining score (SS)”, which is a 0–3 numerical score that results from the product of the intensity of expression: 0= negative, 1= weak, 2= moderate, 3= strong, and the area of expression in fractions of a percent (0= no expression, 1= 100% area). Expression of HER2 and PDL-1 was quantified according to existing guidelines [HER2 score and combined positive score (CPS)]. Results: Trop-2 had the highest expression in thymic carcinoma (TC) (100%, SS 2.6±0.6) followed by thymoma B2/B3 (78%, SS 1.3±1.3), types A/AB/B1 (54%, SS 1.1±1.1) (P=0.01). In TC, all patients with squamous histology had immunohistochemistry (IHC) SS of 3. Patients with thymoma who had Trop-2 expression experienced significantly worse survival [hazard ratio (HR): 3.3, P=0.008]. GLUT1 was highly expressed in TC (81.8%, SS: 2.1±1, TC vs. normal thymus, P=0.0003). PDL-1 was expressed in all TET tissues (mean, 2.5–52 CPS). No significant expression of ALK, ROS1, or HER2 observed in normal thymus or TETs. Conclusions: Trop-2 expression is a prognostic marker in TETs. High expression of Trop-2 protein in thymoma and TC appears a promising therapeutic target for Trop-2 antibody-drug conjugates.
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    Editorial: Emerging Biomarkers in Genitourinary Tumors
    (Frontiers, 2019-04-26) Montironi, Rodolfo; Santoni, Matteo; Cimadamore, Alessia; Lopez-Beltran, Antonio; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
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    New Prostate Cancer Targets for Diagnosis, Imaging, and Therapy: Focus on Prostate-Specific Membrane Antigen
    (Frontiers, 2018-12-21) Cimadamore, Alessia; Cheng, Monica; Santoni, Matteo; Lopez-Beltran, Antonio; Battelli, Nicola; Massari, Francesco; Galosi, Andrea B.; Scarpelli, Marina; Montironi, Rodolfo; Radiology and Imaging Sciences, School of Medicine
    The rising incidence rate of the cancer in the prostate gland has increased the demand for improved diagnostic, imaging, and therapeutic approaches. Prostate-specific membrane antigen (PSMA), with folate hydrolase and carboxypeptidase and, internalization activities, is highly expressed in the epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with, metastasis, progression, and androgen independence. Recently, PSMA has been an active target of investigation by several approaches, including the successful utilization of small molecule inhibitors, RNA aptamer conjugates, PSMA-based immunotherapy, and PSMA-targeted prodrug therapy. Future investigations of PSMA in prostate cancer (PCa) should focus in particular on its intracellular activities and functions. The objective of this contribution is to review the current role of PSMA as a marker for PCa diagnosis, imaging, and therapy.
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    Novel Prostate-Specific Promoter Derived from PSA and PSMA Enhancers
    (Elsevier, 2002-09) Lee, Sang-Jin; Kim, Hong-Sup; Yu, Rong; Lee, KangRyul; Gardner, Thomas A.; Jung, Chaeyong; Jeng, Meei-Huey; Yeung, Fan; Cheng, Liang; Kao, Chinghai; Pathology and Laboratory Medicine, School of Medicine
    The expression of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA), two well characterized marker proteins, remains highly active in the hormone refractory stage of prostate cancer. In this study, an artificial chimeric enhancer (PSES) composed of two modified regulatory elements controlling the expression of PSA and PSMA genes was tested for its promoter activity and tissue specificity using the reporter system. As a result, this novel PSES promoter remained silent in PSA- and PSMA-negative prostate and non-prostate cancer cell lines, but mediated high levels of luciferase in PSA- and PSMA-expressing prostate cancer cell lines in the presence and absence of androgen. To determine whether PSES could be used for in vivo gene therapy of prostate cancer, a recombinant adenovirus, Ad-PSES-luc, was constructed. Luciferase activity in prostate cancer cell lines mediated by Ad-PSES-luc was 400- to 1000-fold higher than in several other non-prostate cell lines, suggesting the high tissue-specificity of the PSES promoter in an adenoviral vector. Finally, recombinant virus Ad-PSES-luc was injected into mice to evaluate the tissue-discriminatory promoter activity in an experimental animal. Unlike Ad-CMV-luc, the luciferase activity from systemic injection of Ad-PSES-luc was fairly low in all major organs. However, when injected into prostate, Ad-PSES-luc drove high luciferase activity almost exclusively in prostate and not in other tissues. Our results demonstrated the potential use of PSES for the treatment of androgen-independent prostate cancer patients.