Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radioimmunoscintigraphy using a radio-labelled antibody to prostate-specific membrane antigen (PSMA) has growing applications as a means of tissue-specific imaging based on functional characteristics and complements traditional staging investigations. Clinical applications in men with carcinoma of the prostate are being refined, and this study reports outcomes with this technique in our practice. Prostatic immunoscintigraphy scans were performed with In-111 CYT 356 in 49 men with carcinoma of the prostate, obtaining sequential images in two and three dimensions at 10 min, 24 and 48 h. Of the 49 men, 36 had clinically localized cancer, 10 had recurrent disease after radical radiotherapy or radical prostatectomy and three had rising PSA after primary endocrine treatment. Scan findings are discussed in the context of clinical management. Of the 36 men with clinically localized cancer, seven had increased uptake in regional and distant lymph nodes. Of these seven, three were treated with hormone manipulation, two by radical prostatectomy and two by radical radiotherapy. Among 10 patients who had recurrence after radical treatment of the primary tumour, scans showed local recurrence alone in four, and six had regional or distant metastases. Three patients treated with primary hormone manipulation had scans for rising PSA, and of these one had a positive regional node and two had distant soft tissue and bone metastases. In conclusion, prostatic radio-immunoscintigraphy scans highlight tissues involved by prostate cancer, including the prostate, lymph nodes, soft tissues and bone metastases as well as pelvic recurrence. Results may contribute to the clinical management of individual patients, although histological confirmation may be appropriate when considering alternative treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 47-52
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PMID:Imaging with prostate-specific membrane antigen (PSMA) in prostate cancer. 1249 62

The objective of this study was to present two cases of adenosquamous cell carcinoma of the prostate following radiation therapy. Two patients with history of prostate cancer treated with radiation therapy presented with rectal bleeding and a large ulcerated rectal mass. The rectal biopsy revealed on both cases squamous cell carcinoma. The initial diagnosis was invasive squamous cell carcinoma from anal origin. Both patients underwent pelvic exenteration with continent urinary diversion. After extensive histological sampling and immuno-histochemisty, they were correctly diagnosed of adenosquamous cell carcinoma of the prostate with invasion of the rectum. The patients died 6 and 16 months after surgery with widespread metastases. A review of the literature is presented. Adenosquamous cell carcinoma of the prostate is an unusual histological variant of prostate cancer. To our knowledge, only three cases of adenosquamous cell carcinoma of the prostate following radiation therapy have been reported. The unusual clinical and histopathological features of the two cases reported here led to an initial mistaken diagnosis. Adenosquamous cell carcinoma of the prostate should be considered in the differential diagnosis when a patient with prostate cancer develops a rectal mass or rectal bleeding following radiation therapy and the rectal biopsy reveals squamous cell carcinoma. Prostate Cancer and Prostatic Diseases (2000) 3, 53-56
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PMID:Postradiation therapy adenosquamous cell carcinoma of the prostate. 1249 63

Recently, progress in the development of prostate-specific promoters and high resolution imaging techniques has made real-time monitoring of transgenic expression possible, opening a vista of potentially important in vivo models of prostate disease. Herein, we describe a novel prostate reporter model, called the EZC-prostate model that permits both ex vivo and in vivo imaging of the prostate using a sensitive charge-coupled device. Firefly luciferase and enhanced green fluorescent protein were targeted to the prostate epithelium using the composite human kallikrein 2 (hK2)-based promoter, hK2-E3/P. In EZC-prostate mice, the ventral and dorsal/lateral prostate lobes were brilliant green under fluorescence microscopy, with expression localized to the secretory epithelium. In contrast, enhanced green fluorescent protein was undetectable in the anterior lobes of prostate, seminal vesicles, testes, liver, lung, and brain. The kinetics of luciferase activity in intact and castrated living mice monitored with the IVIS charge-coupled device-based imaging system confirmed that firefly luciferase expression was largely prostate restricted, increased with age up to 24 wk, and was androgen dependent. Decreases in reporter expression after 24 wk may reflect well known, age-related decreases in androgen signaling with age in humans. Ex vivo imaging of microdissected animals further confirmed that the luminescence detected in living mice emanated predominately from the prostate, with minor signals originating from the testes and cecum. These data demonstrate that the hK2-E3/P promoter directs strong prostate-specific expression in a transgenic mouse model. Multigenic models, generated by crosses with various hyperplastic and neoplastic prostate disease models, could potentially provide powerful new tools in longitudinal monitoring of changes in prostate size, androgen signaling, metastases, or response to novel therapies without sacrificing large cohorts of animals.
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PMID:The EZC-prostate model: noninvasive prostate imaging in living mice. 1468 50

Prostate specific antigen (PSA) is the most successful and widely employed cancer serum marker in use today. There is growing evidence that the introduction of wide PSA screening and earlier detection can result in decreased cancer mortality associated with a decline in metastatic disease. PSA circulates in a number of distinct forms. Measurement of these in addition to total PSA significantly increases diagnostic utility. Diagnostic utility is likely to be further increased by adding kallikreins, cytokines, growth factors, receptors and cellular adhesion factors to the biomarker panel. The need for multiple markers reflects the multidimensional nature of prostate disease which ranges from metastatic cancer to indolent cancer to benign hyperplasia and inflammation, all of which require distinct treatments and medical interventions.
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PMID:Are multiple markers the future of prostate cancer diagnostics? 1523 33

Male breast cancer is uncommon, accounting for less than 1% of all breast cancers. Carcinoma metastatic to the male breast is also unusual, with metastatic prostatic carcinoma being among the most common primary sites from which such tumours derive. Metastatic prostatic cancer and primary breast cancer may be histologically indistinguishable without immunohistochemistry because both often infiltrate with a cribriform architecture. Distinguishing between primary and metastatic disease within the breast is important because the treatment options for each are radically different. Following a case in which metastatic prostatic disease was initially wrongly diagnosed as primary breast cancer, a small series of male breast cancers was examined for expression of prostate specific antigen (PSA) and prostatic acid phosphatase to assess the usefulness of these markers in making this distinction. Focal expression of PSA was found in one of 11 cases of male breast cancer. These results indicate that PSA should be used with caution in this context.
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PMID:Expression of prostate specific antigen in male breast cancer. 1562 86

Molecular markers that could stratify prostate cancer patients according to risk of disease progression would allow a significant improvement in the management of this clinically heterogeneous disease. In the present study, we analyzed the genetic profile of a consecutive series of 51 clinically confined prostate carcinomas and 27 benign prostatic hyperplasias using comparative genomic hybridization (CGH). We then added our findings to the existing literature data in order to perform a meta-analysis on a total of 294 prostate cancers with detailed CGH and clinicopathological information, using multivariate statistical methods that included principal component, hierarchical clustering, time of occurrence, and regression analyses. Whereas several genomic imbalances were shared by organ-confined, locally invasive, and metastatic prostate cancers, 6q and 10q losses and 7q and 8q gains were significantly more frequent in patients with extra-prostatic disease. Regression analysis indicated that 8q gain and 13q loss were the best predictors of locally invasive disease, whereas 8q gain and 6q and 10q losses were associated with metastatic disease. We propose a genetic pathway of prostate carcinogenesis with two distinct initiating events, namely, 8p and 13q losses. These primary imbalances are then preferentially followed by 8q gain and 6q, 16q, and 18q losses, which in turn are followed by a set of late events that make recurrent and metastatic prostate cancers genetically more complex. We conclude that significant differences exist in the genetic profile of organ-confined, locally invasive, and advanced prostate cancer and that genetic features may carry prognostic information independently of Gleason grade.
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PMID:Statistical dissection of genetic pathways involved in prostate carcinogenesis. 1623 41

The aim of this study was to prospectively evaluate the potential role of elevated urinary/serum human chorionic gonadotrophin-beta (hCGbeta) in prostate cancer prognosis. 104 patients with newly diagnosed prostate cancers were included; 68 patients had organ-confined, 18 had locally advanced and 18 had metastatic disease. A control group consisted of 115 patients presenting with benign prostatic disease. Serum and urinary total hCGbeta was measured prior to treatment and serum PSA was measured at diagnosis. The patients were treated along conventional lines and progression-free survival was assessed. Four patients had elevated serum and 10 had elevated urinary, total hCGbeta. There were no significant correlations between serum/urinary levels of hCGbeta and tumour stage, Gleason score or PSA. In contrast, serum PSA had significant linear correlations with both clinical tumour stage and Gleason score (p = 0.0001). At a median follow-up of 36 months, 22 (21.2%) patients had died while 17 (16.3%) others had progressed. Kaplan-Meier plots and log-rank test revealed no significant difference in progression-free survival between patients with elevated or normal levels of serum and/or urinary total hCGbeta. Clinical tumour stage, grade and PSA were statistically significant prognostic variables. Immunoassay measurement of serum or urinary hCGbeta has no significant role in the clinical management of prostate cancer.
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PMID:Detection of human chorionic gonadotrophin-beta in serum or urine of prostate cancer patients is of no clinical significance. 1665 52

Two randomized trials demonstrated an improvement in survival with docetaxel-based chemotherapy for patients with metastatic, androgen-independent prostate disease. However, the effect of current therapy is suboptimal in that it is complicated by toxicities and has no curative potential. Cilengitide (EMD121974; NSC 707544), is a potent selective alphavbeta3 and alphavbeta5 integrin antagonist. Integrins are cell surface receptors that mediate a variety of cell activities including endothelial cell proliferation and migration. Blocking the ligation of integrins by antagonists promotes apoptosis of proliferative angiogenic cells, thereby suspending new blood vessel formation, which is essential for the growth of malignant disease. In prostate cancer specifically, integrins are known to be involved in metastases with differential expression on tumor cells. Tumors and vascular endothelial cells produce factors, such as vascular endothelial growth factor and basic fibroblast growth factor, that promote neovascularization, which has been implicated in prostate cancer progression. Cilengitide has been shown to inhibit alphavbeta3- and alphavbeta5-mediated cell adhesion and block in vitro endothelial cell migration. In vivo experiments demonstrated that cilengitide inhibited cytokine-induced basic fibroblast growth factor- and vascular endothelial growth factor-mediated angiogenesis in a dose-dependent manner. Cilengitide also inhibited tumor growth in various in vivo systems. Two Cancer Therapy Evaluation Program-sponsored, multicenter, phase II trials are designed to evaluate the safety and efficacy of this agent in patients with androgen-independent prostate cancer. National Cancer Institute trial 6735 is evaluating cilengitide at 2000 mg in patients with nonmetastatic androgen-independent prostate cancer, and National Cancer Institute trial 6372 is evaluating 2 dose levels of cilengitide, 500 mg or 2000 mg, intravenously twice weekly in patients with metastatic prostate cancer.
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PMID:Phase II evaluations of cilengitide in asymptomatic patients with androgen-independent prostate cancer: scientific rationale and study design. 1672 16

Prostate cancer is a major health problem, and the exploration of noninvasive imaging methods that have the potential to improve specificity while maintaining high sensitivity is still critically needed. Tissue changes induced by tumor growth can be visualized by magnetic resonance imaging (MRI) methods. Current MRI methods include conventional T2-weighted imaging, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping and magnetic resonance spectroscopy (MRS). Techniques such as DWI/ADC provide functional information about the behavior of water molecules in tissue; MRS can provide biochemical information about the presence or absence of certain metabolites, such as choline, creatine, and citrate. Finally, vascular parameters can be investigated using dynamic contrast-enhanced MRI. Moreover, with whole-body MRI and DWI, metastatic disease can be evaluated in 1 session and may provide a way to monitor treatment. Therefore, when combining these various methods, a multiparametric data set can be built to assist in the detection, localization, assessment of prostate cancer aggressiveness, and tumor staging. Such a comprehensive approach offers more power to evaluate prostate disease than any single measure alone. In this article, we focus on the role of DWI/ADC and MRS in the detection and characterization using both in vivo and ex vivo imaging of prostate pathology.
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PMID:Diffusion-weighted imaging with apparent diffusion coefficient mapping and spectroscopy in prostate cancer. 1951 48

The matrix metalloproteinase family of enzymes is comprised of critically important extracellular proteases whose activity has been implicated in a number of key normal and pathological processes. The latter include growth, progression and metastasis as well as dysregulated angiogenesis that is associated with these events. The MMPs are secreted by all types of cells, and they also carve through the extracellular matrix, allowing cancer cells to take root and metastasize. Endogenous inhibitors typically hold MMPs in check but in cancer, the balance shifts against the inhibitors and in favor of MMPs, which ultimately spill over from blood into urine. By gelatin zymography we verified MMP activity in concentrated urine of patients with prostate disease. Of these patients, 30 had cancer, consisting of 13 with Gleason score 6, 12 with Gleason 7, 2 with Gleason 8, 3 with Gleason 9 and 8 had benign prostate hyperplasia. Zymography showed 4 dominant gelatinolityc bands of 240, 130, 92 and 72 kDa in prostate disease. The most abundant lytic activity is at 92 kDa (MMP-9), whereas MMP-2 is present in lesser quantities. Moreover, MMP-9 activity is enhanced in the urine from patients with benign prostate hyperplasia compared with cancer patients. No correlation between gelatinolytic activity and Gleason score or pathological findings was found.
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PMID:Matrix metalloproteinase-2 and -9 in the urine of prostate cancer patients. 2051 37


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