Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to examine the outcome profiles of a large number of patients with locally advanced adenocarcinoma of the prostate following radical perineal prostatectomy (RPP) for clinically organ-confined disease. Of 1662 men who underwent RPP performed by a single surgeon between January 1972 and January 1999, 692 patients (41.6%) aged a median of 66.1 years were found to have extracapsular disease on pathological evaluation. The extent of disease was categorized as either specimen-confined (n = 355) or margin-positive (n = 337). The histological grade of the cancer was characterized using the Gleason score. Time to biochemical failure, defined as a prostate-specific antigen (PSA) level of > or = 0.5 ng/ml, and cancer-associated survival were the end points of our outcome analysis using the Kaplan-Meier product-limit method. The median time to cancer-associated death for patients with specimen-confined and margin-positive disease was 18.5 and 13.1 years, respectively. After 5 years, 37% and 54% of the patients with specimen-confined and margin-positive disease, respectively, had PSA failure. Prostate cancer patients with a Gleason score of 5-6, 7, and 8-10 experienced a median time to cancer-associated death of 19.9, 19.2, and 10.5 years, respectively. A subset of patients undergoing adjunctive radiation therapy (XRT) relapsed biochemically after a median period of approximately 18 months. RPP provides a substantial disease-control benefit in patients with specimen-confined cancer. The time to biochemical failure and the time to cancer-associated death are significantly influenced by the biology of the underlying disease, necessitating long-term follow-up in the outcome analysis of any modality of treatment for prostate cancer. A benefit of early adjunctive XRT for local failure remains to be determined.
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PMID:Outcome profiles of locoregional disease after radical prostatectomy and radiotherapy. 1092 80

Galectin-1, a member of the beta-galactoside-binding galectin family, is a pleiotropic dimeric protein participating in a variety of normal and pathological processes, including cancer progression. Modulation of the interactions with the basement membrane glycoprotein laminin and induction of apoptosis in activated T lymphocytes are well-known functions of this galectin. In this study, the expression of galectin-1 was examined in 148 human primary prostate carcinoma samples. Immunohistochemical staining of paraffin sections of prostate tissues revealed that galectin-1 was not detected in normal, PIN (prostatic intraepithelial neoplasia) or carcinoma cells, but accumulated in the stroma and associated fibroblasts. Galectin-1 expression was significantly increased in the tumour-associated stroma compared with the non-neoplastic gland-associated stroma in 21.3% of the cases (Mantel-Haenszel test, p=0.001; Wilcoxon signed rank test, p<0.0001). Increased galectin-1 expression in the cancer-associated stroma compared to the normal gland-associated stroma (p=0.03) was identified by multivariate analysis as a strong independent predictor of prostate-specific antigen (PSA) recurrence, just after the pathological stage (p<0.0001). The association between accumulation of galectin-1 in the stroma of the malignant tissue and aggressiveness of the tumour adds weight to the body of evidence that identifies a role for galectin-1 in the acquisition of the invasive phenotype. In addition to modulating cancer cell interactions with laminin, galectin-1 accumulated around the cancer cells may act as an immunological shield by inducing activated T-cell apoptosis. This exciting hypothesis warrants further investigation.
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PMID:Increased expression of galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients. 1116 19

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.
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PMID:Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy. 1504 96

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has limited specificity for distinguishing early prostate cancer(PCa) from benign disease since serum PSA can leak from both tumor and prostate tissues with benign disease. Molecular forms of free PSA have been identified that are associated with either benign or malignant prostate tissues. BPSA is a form of free PSA that is associated with benign prostatic hyperplasia(BPH), the predominant benign disease in men. The inactive precursor of PSA, proPSA, is associated with prostate tumors. We have developed research immunoassays with high sensitivity and specificity for BPSA and proPSA. Each of these PSA forms can range from 0-50% of the free PSA in individual serum samples in the total PSA range of 2-10 ng/ml. Typically, BPSA represents from 20-30% of the free PSA in serum, while proPSA ranges from 30-40% of the free PSA. ProPSA greatly improves the early detection of cancer in men with less than 4 ng/ml total PSA. More importantly, proPSA is more highly associated with aggressive cancers than other PSA forms such as PSA-ACT and free PSA. The BPH-associated BPSA and cancer-associated proPSA forms are complementary and provide improved detection of prostate cancer from benign disease.
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PMID:Tumor-associated forms of prostate specific antigen improve the discrimination of prostate cancer from benign disease. 1513 20

Activity-based protein profiling (ABPP) is a chemical method that utilizes active-site-directed probes to determine the functional state of enzymes in complex proteomes. Probe-labeled enzymes are typically detected by in-gel fluorescence scanning, a robust technique that nonetheless exhibits some key deficiencies, including limited sensitivity and resolution, as well as ambiguity regarding the molecular identity of the enzymes under investigation. Here, we report a microarray platform for ABPP that addresses these limitations. In this platform, proteomes are treated with ABPP probes in solution, after which labeled enzymes are captured and visualized on glass slides displaying an array of anti-enzyme antibodies. We show that ABPP microarrays exhibit superior sensitivity and resolution compared to gel-based methods, permitting the parallel analysis of several enzyme activities in proteomes, including cancer-associated proteases such as urokinase, matrix metalloproteinase-9, and prostate-specific antigen.
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PMID:Microarray platform for profiling enzyme activities in complex proteomes. 1557 75

This manuscript reviews the theories behind the propensity of prostate cancer to cause bone metastases and skeletal implications of the prostate cancer biology and treatment modalities. The escape of tumor cells from the primary tumor in the prostate to secondary tumor sites in the axial skeleton probably occurs before the primary tumor is detected. Several theories offer explanations for the observed proclivity of prostate tumors to selectively colonize the axial skeleton. The interaction between the tumor cells and cells that populate bone marrow, in particular osteoblasts and osteoclasts, is important for creating a 'fertile' environment where tumor cells can establish and grow. Prostate cancer cells are capable of producing growth factors that can affect both osteoblasts, resulting in osteoblastic bone formation, and osteoclasts, resulting in excessive bone resorption. In addition to the capability to progress from testosterone-dependent to testosterone-independent phenotype, the hallmark of metastatic prostate cancer is osteosclerosis similar to one induced experimentally in nude rats using CWR22 human prostate cancer cell line. Metastatic bone disease caused by excessive bone formation and bone resorption is the major cause of morbidity in patients with prostate cancer. The most common symptoms include pain, pathological fractures, spinal cord compression, cranial nerve palsies, bone marrow suppression and hypercalcemia. The introduction of prostate-specific antigen in clinical practice created a shift to where more prostate cancer patients with early disease receive androgen ablation treatment, which in return causes more bone loss and cancer-associated osteoporosis. Introduction of third generation bisphosphonates to treat skeletal consequences of malignancy further stressed the important interaction between the bone marrow stroma and cancer cells. Nevertheless, animal models and human prostate tumor cell lines that mimic all aspects of skeletal conditions in prostate cancer patients including osteoblastic bone response are needed to develop and screen for novel therapeutic and diagnostic modalities.
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PMID:Skeletal implications of prostate cancer. 1575 51

For prostate cancer patients with small, lower-grade tumors, expectant management with delayed surgical intervention (active surveillance) is a rarely used therapeutic option because the opportunity for cure may be lost. We compared outcomes of 38 patients with small, lower-grade prostate cancer in an expectant management program who underwent delayed surgical intervention at a median of 26.5 months (95% confidence interval [CI] = 17 to 32 months; range = 12.0-73.0 months) after diagnosis with 150 similar patients who underwent immediate surgical intervention at a median of 3.0 months (95% CI = 2 to 4 months; range = 1.0-9.0 months) after diagnosis. Noncurable cancer was defined as adverse pathology associated with a less than 75% chance of remaining disease-free for 10 years after surgery. Noncurable cancer was diagnosed in nine (23%) of the 38 patients in the delayed intervention cohort and in 24 (16%) of the 150 men in the immediate intervention group. After adjusting for age and prostate-specific antigen (PSA) density (i.e., PSA value divided by prostate volume) in a Mantel-Haenszel analysis, the risks of noncurable cancer associated with delayed and immediate intervention did not differ statistically significantly (relative risk = 1.08, 95% CI = 0.55 to 2.12; P = .819, two-sided Cochran-Mantel-Haenszel statistic). Age, PSA, and PSA density were all statistically significantly associated with the risk of noncurable cancer (P = .030, .013, and .008, respectively; two-sided chi-square test). Thus, delayed prostate cancer surgery for patients with small, lower-grade prostate cancers does not appear to compromise curability.
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PMID:Delayed versus immediate surgical intervention and prostate cancer outcome. 1650 32

Prostate-specific antigen (PSA) is usually detected in male adult urine and semen according to the Tanner stage development of males from birth to adolescence. To further study the pituitary-testicular axis in males, we determined urinary PSA levels in primates. Urinary PSA was detected with the use of anti-human PSA monoclonal antibody in male adult Japanese macaques (Macaca fuscaa fuscata) of seasonal breeding status. PSA activity in aseasonal animals (crab-eating macaques, Macaca fascisularis) did not change throughout the year; however, alterations in PSA activity were observed in Japanese macaques during breeding season, with the highest levels observed between October and January, the lowest levels between January and June, and a gradual increase in PSA activity observed from August until October. Although primate urinary PSA produces 2 polypeptide bands of approximately 55 and 33 kd, in addition to a band corresponding to human urinary PSA, the 33-kd polypeptide band was less pronounced during nonbreeding season in Japanese macaques. Urinary testosterone (T) levels in seasonally breeding animals (Japanese macaques) changed in parallel with urinary PSA levels. When urinary PSA and T levels were compared among animals during the breeding season (from October to February) and the nonbreeding season (from March to September), significantly increased PSA and T levels were observed during the breeding season. Furthermore, PSA and T levels in a monkey housed in a cage placed between 2 female cages were elevated compared with other monkeys. Increased PSA activity was observed concurrent with menstrual blood loss in females. These results suggest a link between PSA activity and testosterone levels, which could be influenced by changes in the female menstrual cycle.
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PMID:Seasonal changes in urinary prostate-specific antigenic activity in male Japanese macaques (Macaca fuscaa fuscata). 1760 99

Interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) facilitate the maturation and functioning of injected DC. We developed a method of in situ electroporation using IL-2 and GM-CSF genes (EGT/cytokines), followed by intra-tumoral (i.t.) immature DC to determine the immune response at the tumor site using prostate-specific antigen-transfected CT26 cells. Three cycles of EGT/cytokines and i.t. DC inhibited tumor growth most effectively, but not superior to EGT/cytokines alone. However, the role of i.t. DC became significant when radiation was given after immunotherapy, which may have clinical implications on achieving better local control and prevention of systemic relapse.
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PMID:Synergistic anti-tumor effect of combination radio- and immunotherapy by electro-gene therapy plus intra-tumor injection of dendritic cells. 1839 20

Prostate cancers that progress during androgen-deprivation therapy often overexpress the androgen receptor (AR) and depend on AR signaling for growth. In most cases, increased AR expression occurs without gene amplification and may be due to altered transcriptional regulation. The transcription factor nuclear factor (NF)-kappaB, which is implicated in tumorigenesis, functions as an important downstream substrate of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, AKT, and protein kinase C and plays a role in other cancer-associated signaling pathways. NF-kappaB is an important determinant of prostate cancer clinical biology, and therefore we investigated its role in the regulation of AR expression. We found that NF-kappaB expression in prostate cancer cells significantly increased AR mRNA and protein levels, AR transactivation activity, serum prostate-specific antigen levels, and cell proliferation. NF-kappaB inhibitors decrease AR expression levels, prostate-specific antigen secretion, and proliferation of prostate cancer cells in vitro. Furthermore, inhibitors of NF-kappaB demonstrated anti-tumor activity in androgen deprivation-resistant prostate cancer xenografts. In addition, levels of both NF-kappaB and AR were strongly correlated in human prostate cancer. Our data suggest that NF-kappaB can regulate AR expression in prostate cancer and that NF-kappaB inhibitors may have therapeutic potential.
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PMID:NF-kappaB regulates androgen receptor expression and prostate cancer growth. 1962 66


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