Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is increasing evidence that neuropeptides, including bombesin, may influence growth, angiogenesis, invasiveness, and metastasis in prostate cancer. One of the molecules tightly involved in the regulation of neuropeptide activity is the integral membrane glycoprotein CD10, or neutral endopeptidase 24.11. The pattern of CD10 expression in hyperplastic and neoplastic conditions of the prostate gland has not been previously described. Immunohistochemical staining for CD10 and high-molecular-weight cytokeratin was performed on 92 cases of paraffin-embedded tissue from needle-core biopsy specimens and prostatectomy specimens. Normal and hyperplastic acini showed strong and distinct membrane (apical and intercellular) and cytoplasmic CD10 expression in basal and secretory cells. In contrast, no intercellular membrane or cytoplasmic staining of secretory cells was seen in any cases of adenocarcinoma with Gleason patterns 2 or 3. A subset of high-Gleason grade adenocarcinoma (patterns 4 and 5) displayed CD10 expression in the secretory cells; those cases shared a distinct morphological pattern. Prostatic intraepithelial neoplasia (PIN) showed consistent absence of intercellular membrane and cytoplasmic CD10 expression in the secretory cells, with preserved expression in basal cells. Interestingly, the basal cells in basal cell hyperplasia lacked CD10 expression, and no expression was noted in the secretory cells in all cases examined. Atrophic acini and those associated with acute and chronic inflammation retained CD10 expression. In conclusion, a consistent differential pattern of CD10 expression was seen in basal cell hyperplasia, PIN, and adenocarcinoma, suggesting a role for CD10 in the pathobiology of the prostate gland.
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PMID:The pattern of CD10 expression in selected pathologic entities of the prostate gland. 1279 18

The primary objective of this overview is to apprise clinical urologists and oncologists of the current state of fused multimodality imaging of prostate cancer, which can be applied to optimize treatment by ensuring that a patient's disease is characterized as well as current imaging technology permits. The focus of this study is the monoclonal antibody capromab pendetide, which targets prostate specific membrane antigen (PSMA), a type II membrane glycoprotein strongly associated with prostate cancer. Identifying where capromab pendetide uptake occurs can be done accurately if this functional imaging modality is combined with a modality that provides anatomic detail, such as computed tomography (CT) or magnetic resonance imaging (MRI). Image fusion, or coregistration, which is overlaying the functional images of capromab pendetide uptake on the anatomic CT or MRI images, provides a detailed map of cancer localization inside and outside the prostate gland. This same principle of fusing functional images on anatomic images is the basis for enormous growth of positron emission tomography with CT during the past 2 years. Positron emission tomography imaging has a different functionality base than does capromab pendetide, and thus the 2 modalities should be complementary. However, the key to both functional imaging modalities is accurate fusion with anatomic images, which is illustrated in our case reports. The cases cited demonstrate the need to optimize every phase of imaging from patient preparation to reading and reporting increased PSMA concentration seen on the fused images. Reference is also made to applying capromab pendetide/CT fused imaging to radiation therapy planning.
Clin Prostate Cancer 2005 Mar
PMID:Update on fused capromab pendetide imaging of prostate cancer. 1588 79

Prostate-specific membrane antigen (PSMA) is an integral membrane glycoprotein expressed in prostatic epithelia and is being evaluated as a therapeutic target in prostate cancer. It undergoes constitutive receptor-mediated endocytosis via clathrin-coated pits, which is enhanced in the presence of monoclonal antibodies directed against it. We describe distinct interactions of PSMA with clathrin and the clathrin adaptor protein-2 (AP-2) complex, two components of clathrin-coated pits. The intracellular N-terminal domain of PSMA interacts with the N-terminal globular domain of clathrin heavy chain. Deletion analysis revealed an important determinant of this interaction residing within the proximal portion of the clathrin heavy chain N-terminal domain (amino acids 1-85) distinct from the clathrin binding sites of other known clathrin-binding proteins. Furthermore, PSMA interacts with the ear domain of alpha-adaptin (an AP-2 subunit), and a glutamic acid residue at position 7 in the cytoplasmic tail of PSMA is essential for this interaction. These data indicate that PSMA exhibits a high affinity, specific association with the clathrin-based endocytic machinery by distinct interactions with both clathrin and AP-2. Thus, although PSMA is a new member of the dual AP and clathrin binding proteins, its alpha-adaptin and clathrin heavy chain binding determinants are distinct from those of other members.
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PMID:Interaction of prostate specific membrane antigen with clathrin and the adaptor protein complex-2. 1791 48

Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) is a multifunctional membrane glycoprotein overexpressed in many solid tumors, and involved in tumor invasion and angiogenesis. We investigated EMMPRIN expression in human prostate cancer (CaP) tissues and cells, and evaluated whether EMMPRIN expression is related to tumor progression and matrix metalloproteinase (MMPs) expression in human CaP. An immunohistochemical study using tissue microarrays of 120 primary CaPs of different grades and 20 matched lymph node metastases from untreated patients was performed. The association of EMMPRIN expression with clinicopathological parameters was evaluated. Co-immunolocalization for EMMPRIN and MMP-1, MMP-2 or MMP-9 in primary tumors was examined using confocal microscopy. Flow cytometry and immunoblotting were used to examine EMMPRIN expression in 11 metastatic CaP cell lines. Heterogeneous expression of EMMPRIN was found in 78/120 (65%) CaPs, correlated significantly with progression parameters including pre-treatment PSA level (P < 0.05) and increased with progression of CaP (Gleason score, P < 0.05; pathological stage, P < 0.01; nodal involvement, P < 0.05 and surgical margin, P < 0.05). Heterogeneous cytoplasmic MMP-1, MMP-2 and MMP-9 associated with EMMPRIN immunolabeling was observed, particularly in tumors with Gleason scores >3 + 4. Metastatic CaP cell lines, except DuCaP, expressed abundant EMMPRIN protein, indicating highly ( approximately 45 to approximately 65 kDa) and less ( approximately 30 kDa) glycosylated forms, although with no relationship to cells being either androgen responsive or nonresponsive. Our results suggest that EMMPRIN may regulate MMPs and be involved in CaP progression, and as such, could provide a target for treating metastatic CaP disease.
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PMID:The role of extracellular matrix metalloproteinase inducer protein in prostate cancer progression. 1827 14

Extracellular matrix metalloproteinase inducer (EMMPRIN, also named as CD147) is a multifunctional membrane glycoprotein over-expressed in many kinds of human solid tumors. It has been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological characteristics of the expression of CD147 in human prostate cancer (PCa), and to evaluate its clinical significance in the histologic classification and prognosis of PCa. CD147 protein expression in paraffin-embedded specimens gathered from 62 cases of PCa and 30 cases of benign prostatic hyperplasia (BPH) were detected by the method of immunohistochemistry. The association of CD147 protein expression with the clinicopathological characteristics and with the prognosis of PCa was subsequently assessed. CD147 expression were positively expressed in 51/62 (82.3%) of PCa and 4/30 (13.3%) of BPH cases, respectively. The positive expression rate of CD147 in PCa tissues was significantly higher than that in BPH. The positive expression of CD147 was dramatically associated with TNM grade (p < 0.001), the depth of the prostatic wall invasion (p = 0.008), GLEASON Score (p = 0.001) and Histologic grade (p = 0.001). The patients with CD147 expression were associated with a poor prognosis of PCa (p = 0.01) and the survival rate of the patients with a strong positive expression of CD147 was the lowest (p = 0.01). The results suggest that the expression of CD147 may be an important feature of PCa and the detection of its expression may benefit us in the prediction of the prognosis of PCa.
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PMID:CD147 expression indicates unfavourable prognosis in prostate cancer. 1904 97

Prostate-specific membrane antigen (PSMA) is a type II integral membrane glycoprotein, specifically expressed in prostatic epithelial cells and strongly upregulated in prostate cancer. PSMA is also present in the neovasculature of other solid tumors. These findings have spurred the development of PSMA-targeted therapies for prostate cancer, including immunotherapy, radioimmunotherapy, chemotherapy and gene therapy, and initiated the clinical trials of the first-generation products. However, general clinical application of these therapies still requires extensive clinical studies to test their clinical safety, stability and efficacy.
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PMID:[Advances in prostate-specific membrane antigen targeted therapies for prostate cancer]. 2060 62

Prostate-specific membrane antigen (PSMA) is a trans-membrane glycoprotein recognized by the murine monoclonal antibody (MAb) 7EII-C5.3 both in its native (CYT-351) and immunoconjugate form (CYT-356). Previous studies have shown that tissue expression of PSMA is highly restricted to prostate tissues. In this study, a definitive immunohistochemistry evaluation was performed to assess PSMA expression in prostate tissues. A stain index was established by multiplying the percentage of stained cells by the intensity of the stained cells to provide a quantitative measurement of PSMA expression in the various tissue types. The cellular location of PSMA, its correlation with clinical status, and its comparison with the expression of prostate-specific antigen (PSA) were evaluated. Prostate-specific membrane antigen was found to be highly expressed in most of the normal intraepithelial neoplasia, and the primary and metastatic prostate tumor specimens evaluated. In contrast to PSA, PSMA expression was often heterogeneous with variable staining patterns, ranging from a low-level diffuse cytoplasmic staining in normal prostate epithelium to very intense cytoplasmic and focal membrane staining in high-grade primary carcinomas and metastatic tissues. The predominant cytoplasmic staining was expected because the antigenic epitope of the PSMA transmembrane glycoprotein recognized by MAb 7EII-C5.3 is located in the cytoplasmic domain. Benign prostate tumors, ie, hypertrophy, showed the lowest expression of PSMA with a stain index of 52, compared with stain indexes of 146 and 258 for normal prostate and bone metastatic tissues, respectively. The reason for the apparent down-regulation of PSMA in benign prostate tissue is unknown but may be related to a splicing variant or post-translational modification of PSMA. Expression of PSMA was observed to increase with increasing pathologic grade, but not with clinical stage. Although PSMA was overexpressed in poorly differentiated and metastatic prostate tumors, expression in the primary tumor did not correlate with nodal status, extracapsular penetration, or seminal vesicle invasion. These results suggest that PSMA is not a useful biomarker of disease progression; however, high expression does appear to be associated with the more aggressive prostate carcinoma phenotype. The restricted specificity, differential prostate tissue expression, and overexpression of PSMA in metastatic tissues support the continued study of this unique prostate tumor-associated biomarker for developing new strategies for diagnostic and therapy of prostate cancer.
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PMID:Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. 2122 86

This study was designed to assess the condition of the basement membrane of archival prostate carcinoma tissue when adjacent to tumor cells of varying degrees of malignancy, using a simple staining technique. Tissue was obtained from 87 patients with untreated prostate cancer. Tissue was randomly selected from four patients from each of four Gleason grades of 2, 3, 4, and 5. Tissue was fixed in 10% formalin and routinely processed. Sections were freshly cut from paraffin blocks and slides were subjected to the periodic acid-Schiff (PAS) reaction. Gleason grades 2, 3, 4, and 5 were visualized. As the Gleason grade increased, the intensity of staining, density, and thickness of the gel-like basement membrane decreased. With the increasing Gleason grade, as seen by the PAS stain, the basement membrane glycoprotein decreased in its density and thickness with increased fragmentation, which suggested that the basement membrane would be so modified by the tumor cells to allow the tumor to spread locally. The breakdown of the basement membrane is probably a consequence of increased intratumor pressure, certain proteolytic enzymes, and increased cell motility associated with increased degree of malignancy.
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PMID:Extracellular matrix in prostate adenocarcinoma: Changes in the glycoprotein component of the basement membrane. 2122 15

Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, its high expression is associated with prostate cancer progression, and has been becoming an active target for imaging or therapeutic applications for prostate cancer. On the other hand, streptavidin-biotin system has been successfully employed in pretargeting therapy towards multiple cancers. Herein, we describe the synthesis of bifunctional ligands (biotin-CTT54, biotin-PEG(4)-CTT54, and biotin-PEG(12)-CTT54) possessing two functional motifs separated by a length-varied polyethylene glycol (PEG) spacer: one (CTT54) binds tumor-marker PSMA and the other (biotin) binds streptavidin or avidin. All three compounds exhibited high potencies (IC(50) values: 1.21, 2.53, and 10nM, respectively) and irreversibility; but only biotin-PEG(12)-CTT54 demonstrated specifically labeling PSMA-positive prostate cancer cells in a two-step pretargeting procedure. Additionally, the pre-formulated complex between biotin-PEG(12)-CTT54 and Cy5-streptavidin displayed the improved inhibitory potency (IC(50)=1.86 nM) and irreversibility against PSMA and rapid uptake of streptavidin conjugate into PSMA-positive prostate cancer cells through PSMA-associated internalization. Together, all these results supported a proof-concept that combination of streptavidin and PSMA's biotinylated inhibitor may lead to development of a novel strategy of tumor-targeting imaging or drug delivery towards prostate cancer.
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PMID:Targeting prostate cancer cells with a multivalent PSMA inhibitor-guided streptavidin conjugate. 2260 80

Prostate-specific membrane antigen (PSMA), a type II integral membrane glycoprotein, is highly overexpressed in all forms of prostate cancer tissues. It has also been demonstrated in a wide range of neovasculature of non-prostatic solid tumors, including bladder, pancreas, lung, kidney, colorectal, and gastric cancers. Given the unique expression of PSMA, it is considered an alluring target for antibody-based imaging and therapy of cancer. In the present study, the production and characterization of camel heavy chain antibodies (HCAbs) specific for the external domain of the PSMA are reported. Due to the absence of the CH1 domain, HCAbs are smaller than their counterparts in conventional antibodies. In this study, camel antibodies were generated through immunization of Camelus dromedarius with a synthetic 28 amino acid peptide corresponding to the external surface domain of antigen and PSMA-expressing cell lines. Different binding properties to protein A and protein G affinity columns were deployed to separate three subclasses of camel IgG. The affinity purified HCAbs bound selectively to the synthetic peptide in enzyme linked immunosorbent assay (ELISA) and reacted specifically with PSMA-expressing cell line through immunocytochemistry study. Currently, we are attempting to develop recombinant variable domain of these heavy chain antibodies (VHH or nanobody) for tumor imaging and cancer therapy.
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PMID:Camel heavy chain antibodies against prostate-specific membrane antigen. 2324 21


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