Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphologic analyses of radical prostatectomy specimens after brachytherapy are rarities, as only few patients undergo radical prostatectomy due to prostate-specific antigen (PSA) progress after brachytherapy. In the literature, there are merely sporadic reports that do essentially correspond to findings after conventional radiotherapy with regressive changes in the tumor glands and, especially, in the surrounding stroma. From the presented cases, it can be concluded that the seed density must be very high in order to prevent tumor progression through undamaged parts of the carcinoma. The sequels of brachytherapy are compared with the reactions of prostatic carcinomas to various modes of therapy. It is demonstrated what the clinician can expect and which modes of control exist at present.
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PMID:Fundamentals on the pathology of prostatic carcinoma after brachytherapy. 1221 47

This paper is concerned with the development of a stochastic path of prostate-specific antigen (PSA) level after radiation treatment for prostate cancer. PSA is a biomarker for prostate cancer, higher levels of which indicate the seriousness of the cancer progression. Following the deterministic modeling of the data by the previous authors, Cox et al., this paper is concerned with the theoretical knowledge that could be gained by the stochastic modeling in discrete form of the PSA path over time. The expected value of the PSA level is computed and compared with the deterministic model and it is found that they are the same for about the first year after radiation therapy. The American Society for Therapeutic Radiology has set a consensus panel definition of biochemical failure following radiation therapy: the rise in three consecutive levels of PSA is considered to be a failure of the radiation therapy. Knowledge of the path of PSA presented in this paper would be useful in the management of the radiation treatment and in particular assessing quantitatively any clinically based policy for defining recurrence after radiation therapy. Application of the model is illustrated by fitting it to clinical data available in the University of Michigan cancer center.
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PMID:Prostate cancer: progression of prostate-specific antigen after external beam irradiation. 1259 20

Ca 15-3 is an aspecific tumor marker characteristic of cancer proliferation. Elevated serum levels seem to be closely correlated with cancer progression in non-urological tumors. This study assessed the role of Ca 15-3 as an aspecific tumor marker in patients with borderline prostate-specific antigen (PSA) biochemically suspected of prostate cancer (PCa) and with multiple negative prostate biopsies. The study is based on prospective analysis of 103 patients: (a) 33 patients (group A) presented lower urinary tract symptoms secondary to BPH with normal serum PSA values, DRE and TRUS negative for suspected PCa; (b) 31 patients (group B) with histologically diagnosed PCa; (c) 39 patients (group C) with borderline serum PSA values, DRE and TRUS normal, two ultrasound (US)-guided random prostate biopsies negative for PCa. Ca 15-3 was determined in the entire study series by the IRMA method, using as range the values proposed for the investigated non-urological tumors (38 UI/l).Ca 15-3 was within normal range in all group A patients (control), while the values were elevated in 27/31 of group B patients (PCa) and in 11/39 of group C (PCa suspected) patients. A third biopsy was performed in all 39 group C patients with borderline PSA and it was PCa-positive in 13 patients (33.3%, subgroup C3). In this series Ca 15-3 was increased in 9 of 13 patients (subgroup C3alpha), while the remaining four patients (subgroup C3beta) presented values within the normal range. On 26 group C patients who were negative for PCa to third biopsy (subgroup C4), 24 patients had Ca 15-3 levels within normal range (subgroup C4alpha) with histologic findings of BPH in 23 cases and granulomatous chronic prostatitis in one case, while two patients (subgroup C4beta) had elevated Ca 15-3 concentrations associated with lymphoplasmacytic chronic prostatitis. We hypothesize that Ca 15-3, as a specific tumor marker, could be an interesting and inexpensive second step diagnostic tool for PCa in patients with borderline PSA and multiple negative prostate biopsies, as it could indicate whether a repeated biopsy should be performed in a short time, having excluded other concomitant tumors. However, further prospective studies will be necessary to confirm this hypothesis.
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PMID:Role of Ca 15-3 in patients with biochemically suspected prostate cancer and multiple negative ultrasound-guided prostate biopsies. 1266 64

To better understand the clinical and pathologic features of end-stage, androgen-independent carcinoma of the prostate (CaP), we performed rapid autopsies on 14 men who died of progressive CaP and recorded relevant clinical data. The timing of tumor progression varied widely. The median time to androgen independence was 2 years (range, 4 months to 13.6 years). The median survival after androgen independence was 1 year (range, 1 month to 3.6 years). Because osseous metastases are prevalent in progressive CaP, up to 20 bone sites were systematically sampled in each patient. Bone metastases were widespread; tumor filled the marrow in an average of 14 bone sites. Tumor histology and expression of prostate-specific antigen (PSA) and chromogranin A (CGA) were examined in all metastases and were compared with the primary tumor. Five histological patterns of metastatic tumor were observed: solid (10 patients), macroacinar (1 patient), microacinar (1 patient), clear cell (1 patient), and comedocarcinoma (1 patient). Gleason grade of the primary tumor did not predict the histological pattern of the metastases. Although >70% of tumor cells expressed PSA, the fraction of PSA-positive cells varied widely in separate metastases in some patients (standard deviation >25). Likewise, the fraction of neuroendocrine (NE) (CGA-positive) tumor cells in different metastases varied widely. For example, between 0 and 95% of tumor cells in different metastases in 1 patient had a NE phenotype. The present study highlights the heterogeneity--histologically and immunophenotypically--of metastatic CaP. Consequently, therapy directed to the phenotype of 1 metastasis may have no effect on other metastases in the same patient because of phenotypic heterogeneity.
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PMID:Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. 1287 59

Androgen receptor (AR) activity is required for prostate growth, differentiation, and secretion. Deregulation of AR activity results in inappropriate mitogenic signaling and is thought to contribute both to the initiation and progression of prostate cancers. Cyclin D1 functions as a strong AR corepressor by directly interacting with and inhibiting receptor activity. However, the extent to which cyclin D1 functions to inhibit AR activity under conditions associated with cancer progression has not been determined. We now demonstrate that cyclin D1 action is conserved in multiple tumor cell backgrounds, inhibiting AR-dependent gene activation in breast, bladder, and androgen-independent prostatic adenocarcinoma cell lines. In androgen-dependent prostatic adenocarcinomas, cyclin D1 effectively muted androgen-stimulated target gene expression in a manner analogous to dominant negative ARs. The ability of cyclin D1 to inhibit AR activity was conserved with regard to target promoter, repressing transactivation from mouse mammary tumor virus, probasin, and prostate-specific antigen promoters. Inappropriate, nonligand AR activation, postulated to act through regulation of receptor phosphorylation, was also sensitive to cyclin D1 regulation. Moreover, we show that several phosphorylation site mutants of the AR were equally inhibited by cyclin D1 as compared with the wild-type receptor. Given these data establishing the potency of cyclin D1-mediated repression, we evaluated the ability of cyclin D1 to inhibit tumor-derived AR alleles and polymorphisms associated with tumor progression and increased prostate cancer risk. We demonstrate that the AR alleles and polymorphisms tested respond completely to cyclin D1 corepressor activity. In addition, activation of a common tumor-derived AR allele by 17 beta-estradiol and progesterone was inhibited through ectopic expression of cyclin D1. Taken together, these data establish the potency of cyclin D1 as an AR corepressor and provide support for additional studies examining the efficacy of developing novel prostate cancer therapies for both androgen-dependent and -independent tumors.
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PMID:Specificity of cyclin D1 for androgen receptor regulation. 1294 14

The class A macrophage scavenger receptor (SR-A) is expressed in antigen presenting cells and is involved in host immune responses. Germ-line mutation of this gene has been associated with increased risk of human prostate cancer. However, there is little known about its expression in normal or neoplastic human prostate tissues. Double immunofluorescent labeling with monoclonal antibodies to SR-A and specific macrophage and dendritic cell markers was used to identify cells expressing SR-A in human prostate tissues. SR-A immunohistochemical staining was performed on paraffin sections of normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and prostate cancers from radical prostatectomy specimens. SR-A was expressed in a subset of macrophages and dendritic cells that infiltrated prostatic tissues. The majority of SR-A-positive cells coexpressed CD68, and a relatively low percentage expressed S100 protein. The number of SR-A-positive cells was significantly increased in PIN as compared with normal prostatic tissue (P = 0.0176). In contrast, the number of SR-A-positive cells decreased with tumor progression. A lower SR-A-positive cell density was associated with higher clinical stage (rho = -0.26; P = 0.0234). Inverse associations were also found between SR-A density and positive lymph nodes (rho = -0.23; P = 0.0437), tumor size (rho = -0.31; P = 0.0100) and preoperative PSA levels (rho = -0.32; P = 0.0057). SR-A density is a significant predictor of disease-free survival after surgery univariately (P = 0.0003), as well as multivariately, adjusted for known clinical and pathological markers including preoperative prostate-specific antigen, clinical stage, Gleason score, surgical margin, extraprostatic extension, and seminal vesicle invasion, as well as lymph node metastasis (P = 0.0021). The preferential accumulation of SR-A-positive cells in PIN suggests a role for SR-A in the APC response to early malignancy. A reduction in the number of SR-A-positive cells demarcates tumor progression as indicated by clinical and pathological correlations. Our results additionally indicate that systematic measurement of SR-A density is a strong prognostic marker for clinical outcome after surgery.
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PMID:Reduced infiltration of class A scavenger receptor positive antigen-presenting cells is associated with prostate cancer progression. 1502 46

Increases in neuroendocrine (NE) cells and their secretory products are closely correlated with tumor progression and androgen-independent prostate cancer. However, the mechanisms by which NE cells influence prostate cancer growth and progression, especially after androgen ablation therapy, are poorly understood. To investigate the role of NE cells on prostate cancer growth, LNCaP xenograft tumors were implanted into nude mice. After the LNCaP tumors were established, the NE mouse prostate allograft (NE-10) was implanted on the opposite flank of these nude mice to test whether NE tumor-derived systemic factors can influence LNCaP growth. Mice bearing LNCaP tumors with or without NE allografts were castrated 2 weeks after NE tumor inoculation, and changes in LNCaP tumor growth rate and gene expression were investigated. After castration, LNCaP tumor growth decreased in mice bearing LNCaP tumors alone, and this was accompanied by a loss of nuclear androgen receptor (AR) localization. In contrast, in castrated mice bearing both LNCaP and NE-10 tumors, LNCaP tumors continued to grow, had increased levels of nuclear AR, and secreted prostate-specific antigen. Therefore, in the absence of testicular androgens, NE secretions were sufficient to maintain LNCaP cell growth and androgen-regulated gene expression in vivo. Furthermore, in vitro experiments showed that NE secretions combined with low levels of androgens activated the AR, an effect that was blocked by the antiandrogen bicalutamide. Because an increase in AR level has been reported to be sufficient to account for hormone refractory prostate cancers, the NE cell population ability to increase AR level/activity can be another mechanism that allows prostate cancer to escape androgen ablation therapy.
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PMID:NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice. 1528 59

Cell surface carbohydrates expressed on epithelial cells are thought to play an important role in tumor progression. Previously, we have shown that expression of core 2-branched O-glycans is closely correlated with vessel invasion and depth of invasion in colon and lung carcinomas. In this study, we found that expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1, Core2GnT, is positively correlated with the progression of prostate cancer in human patients. Statistical analysis demonstrated that Core2GnT is an independent predictor for progressed pathological stage (pT3) and for prostate-specific antigen (PSA) relapse. To determine directly the roles of Core2GnT in prostate cancer progression, we set up an experimental tumor model using the LNCaP prostate cancer cell line. Because this line does not express Core2GnT, we established an LNCaP line stably expressing Core2GnT, LNCap-Core2GnT, by transfecting cDNA encoding Core2GnT. When mock-transfected LNCaP cells and LNCaP-Core2GnT were inoculated in the prostate of nude mice, LNCaP-Core2GnT cells produced three times heavier prostate tumors than mock-transfected LNCaP cells. Furthermore, we found that LNCaP-Core2GnT cells adhered more strongly to prostate stromal cells, type IV collagen and laminin than did LNCaP-mock cells, but LNCaP and LNCaP-Core2GnT cells grew almost at the same rate on plates coated with type IV collagen or laminin. These results indicate that Core2GnT is an extremely useful prognostic marker for prostate cancer progression. The results also suggest that acquiring Core2GnT in prostate carcinoma cells facilitates adhesion to type IV collagen and laminin, and this increased adhesion may be a cause for aggressive tumor formation by prostate cancer cells expressing Core2GnT.
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PMID:Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression. 1593 19

Neuroendocrine (NE) tumor cells in prostatic carcinoma (PCa) may influence tumor proliferation by a paracrine stimulus. The role of NE tumor cells is discussed controversially. This study investigates the influence of NE tumor differentiation on proliferation in PCa. Neuroendocrine differentiation, Ki-67, and Polo-like kinase 1 were studied immunohistochemically in 73 consecutive prostatectomies. Polo-like kinase 1 (PLK1) expression was also studied by Western and Northern blot analysis. Tumors were classified as high NE (HNE) and low NE differentiated (LNE), and depending on the growth pattern, with solitary and clusters of NE tumor cells. Low NE differentiated tumors were defined as less than 30 and HNE as 30 or more NE tumor cells per hot spot. Patients were followed by serum prostate-specific antigen (PSA) analysis. Neuroendocrine differentiation was present at least focally in 70% of tumors; 57% were HNE and 43% LNE. Solitary NE tumor cells were more often found in low-grade PCa, whereas clusters of NE tumor cells were more frequent in high-grade PCa. PLK1 messenger RNA and protein as well as Ki-67 were overexpressed in tumor tissue compared with tumor-free tissue. A stronger proliferation as determined by Ki-67 and PLK1 expression was present in HNE tumors compared with LNE tumors and in tumors with clusters in contrast to tumors with solitary NE tumor cells. Analysis for PSA relapse-free survival showed an earlier progression in HNE than in LNE tumors and in PCa with clusters of NE tumor cells. A significant and clustered NE differentiation in PCa may lead to an increased proliferation and earlier tumor progression, whereas few and solitary NE tumor cells have no prognostic impact.
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PMID:Influence of neuroendocrine tumor cells on proliferation in prostatic carcinoma. 1594 24

Hepatocyte activator inhibitor-1 (HAI-1) is a transmembrane serine protease inhibitor that regulates the conversion of latent to active hepatocyte growth factor (HGF). Studies supporting a role for the HGF pathway in prostate carcinogenesis prompted an analysis of HAI-1 expression in the prostate. Here we analyze the regulation of HAI-1 expression by androgen, oncogenic transformation, and cancer progression. Immunohistochemical analysis revealed that HAI-1 expression was restricted to prostate epithelium, where staining occurred primarily in basal and atrophic luminal epithelial cells. Compared to normal glands, HAI-1 expression was significantly increased in localized prostate cancer and was present in most prostate cancer metastases. HAI-1 protein expression levels were sensitive to androgen in normal epithelium but not in cancer. Although androgen did not increase HAI-1 protein expression levels in LNCaP cells, it decreased HAI-1 surface expression, consistent with previous data from our group (Martin DB, Gifford DR, Wright ME, Keller A, Yi E, Goodlett DR, Aebersold R, Nelson PS: Quantitative proteomic analysis of proteins released by neoplastic prostate epithelium. Cancer Res 2004, 64:347-355). HAI-1 overexpression in cancer was predictive of prostate-specific antigen recurrence (relative risk, 1.24). These results suggest that HAI-1 regulates the HGF Met axis on prostate epithelial cells and influences HGF mediated tumor invasion and metastasis.
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PMID:Regulation of hepatocyte activator inhibitor-1 expression by androgen and oncogenic transformation in the prostate. 1597 69


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