Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.17.21 (prostate-specific membrane antigen)
 1,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MLN2704 is an antibody-chemotherapeutic conjugate designed to target prostate-specific membrane antigen (PSMA). PSMA is a transmembrane receptor whose expression is largely restricted to prostatic epithelium and prostate cancer cells with its expression level increasing during the progression of malignancy. MLN2704 consists of a de-immunized, monoclonal antibody that is specific for PSMA conjugated to drug maytansinoid 1 (DM1), a microtubule-depolymerizing compound. After antibody binding to PSMA and the subsequent cellular internalization of this complex, DM1 is released leading to cell death. MLN2704 has an approximate half-life of 39 hours in scid mice bearing CWR22 tumor tissue, and the antibody effectively penetrates xenograft tumor tissue. Optimization of dosage and schedule of MLN2704 administration defined interdependency between these conditions that maximized efficacy with no apparent toxicity. Tumor growth delays of approximately 100 days could be achieved on the optimized schedule of one dose of 60 mg/kg MLN2704 every 14 days for five doses (q14dx5). The unconjugated antibody (MLN591) demonstrated essentially no antitumor activity and DM1 alone or a non-PSMA targeted antibody-DM1 conjugate was only weakly active. Furthermore, we show that MLN2704 is active in a novel model of osteoblastic prostate cancer metastasis.
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PMID:A prostate-specific membrane antigen-targeted monoclonal antibody-chemotherapeutic conjugate designed for the treatment of prostate cancer. 1552 Feb 7

Folate hydrolase (prostate-specific antigen) 1 (FH(PSA)1), also known as prostate-specific membrane antigen (PSMA), is a transmembrane receptor expressed on prostate cancer cells that correlates with a more aggressive phenotype. Recent studies have demonstrated FH(PSA)1 expression in numerous benign and malignant tissue types, as well as the malignant neovasculature. As FH(PSA)1 represents a diagnostic immunomarker for prostate cancer, we explored its expression pattern in various subtypes of bladder cancer. Immunohistochemical analysis (IHC) of FH(PSA)1 was performed using tissue microarrays constructed from 167 bladder cancers, including 96 urothelial carcinomas (UCCs), 37 squamous cell carcinomas, 17 adenocarcinomas and 17 small cell carcinomas. We used a FH(PSA)1 monoclonal antibody obtained from Dako (clone 3E6, dilution 1:100), which recognizes the epitope present in the 57-134 amino acid region of the extracellular portion of the PSMA molecule. Intensity of IHC staining was scored as 0 (no expression) to 3+ (strong expression), with 2-3+ IHC considered a positive result. FH(PSA)1 demonstrated expression in a subset of bladder cancers and was most common in small cell carcinoma (3/17; 18%), with concurrent expression in non-small cell components in a subset of cases (2/6). FH(PSA)1 expression was less frequent in UCC (3/96; 3%) and adenocarcinoma (2/17; 12%). None of the squamous cell carcinomas demonstrated tumor cell expression of FH(PSA)1. However, all bladder cancers examined expressed FH(PSA)1 in the tumor vasculature, suggesting a potential role for this molecule in mediating new vessel ingrowth. FH(PSA)1 may occasionally be expressed in various subtypes of bladder cancer. These findings suggest cautious use of FH(PSA)1 as a diagnostic marker for prostatic tissue invading the bladder. The finding of FH(PSA)1 in the bladder cancer neovasculature suggests that this molecule may promote tumor growth and may represent a potential new vascular target in this disease.
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PMID:Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature. 2172 90

Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative, soft tissue tumor. It has a propensity for deep invasion but a low risk for distant metastasis. The classic presentation is a slowly progressive, painless, and erythematous to purpuric patch on the trunk or arms. A deep, subcutaneous punch biopsy or incisional biopsy should be performed for diagnosis in all suspected cases; wide undermining of the skin is to be avoided for minimizing the risk of tumor seeding and for retaining the feasibility of histopathologic examination of re-excisions. Histopathologic distinction of DFSP from dermatofibroma requires immunohistochemical assessment for CD34, factor XIIIa, nestin, apolipoprotein D, and cathepsin K. Management of this cutaneous sarcoma involves a multidisciplinary oncologic approach. Surgical excision is usually the first step in management. DFSP has a high propensity for local recurrence, even when surgical margins are negative; therefore, radiation therapy or rarely systemic therapy is recommended, especially for locally advanced or metastatic cases. The indolent nature of DFSP requires lifelong surveillance for recurrence; however, most recurrences occur within 3 years of the primary excision. The median time for the development of a local recurrence is estimated to be 32 months. An emerging theragnostic transmembrane receptor target, folate hydrolase-1 (FOLH1; prostate-specific membrane antigen), has been expressed in benign dermatofibromas and in high-grade sarcomatous phenotypes. These findings suggest that DFSP may also express FOLH1, which could allow for surveillance with FOLH1 PET/CT and antibody-mediated brachytherapy.
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PMID:Dermatofibrosarcoma Protuberans: The Current State of Multidisciplinary Management. 3316 Apr 38