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Influence of pulse angle variations on stimulated echo acquisition mode proton nuclear magnetic resonance spectra of AB spin systems: theory and experiments with citrate.

The influence of pulse angle variations in the localization sequence stimulated echo acquisition mode (STEAM) on the signal of strongly coupled AB spin systems has been examined. Experimental 1H nuclear magnetic resonance (NMR) spectra of citrate were recorded on a 1.5 T whole-body imager. Theoretically calculated spectra were generated, with good correlation to experimental results. The dependence of the signal intensity on sequence timing and pulse angles was calculated analytically. For longer sequence timings, the ratio of the signal intensity from citrate to the signal intensity from uncoupled nuclei depends strongly on the applied flip angles. The shape of spectra also changes with varying flip angles. These effects are clearly less pronounced for STEAM than for point resolved spectroscopy (PRESS). The results have to be considered for quantitative measurements of citrate in spectroscopic investigations as, e.g. of prostate neoplasms.

Acetic Acid↗

Hereditary aspects of prostate cancer.

OBJECTIVE: To review current literature on the hereditary aspects of prostate cancer and to evaluate the importance of family history in history taking and screening for prostate cancer. DATA SOURCES: MEDLINE was searched for articles in English or French published between Jan. 1, 1956, and Oct. 31, 1994, with the use of MeSH headings "prostatic neoplasms," "genetics" and "chromosomes." Additional references were selected from the bibliographies of articles found during the search. STUDY SELECTION: Case-control studies involving the incidence of prostate cancer and relative risk (RR) of such cancer in the families of men with this disease, compared with a control group, were included. Only studies in which prostate cancer was diagnosed on the basis of histologic tests were included. Animal investigations were excluded. DATA EXTRACTION: Ten case-control studies were evaluated critically in terms of design, case and control groups, the size of the samples and statistical results. The incidence of prostate cancer in the families of cases, compared with that in the families of controls, and differences in RR were reviewed. DATA SYNTHESIS: The lifetime risk of prostate cancer is 9.5% and of death from prostate cancer is 2.9% for a man 50 years of age. For first-degree male relatives of men with prostate cancer, the calculated RR ranges from 1.7 to 8.73. "Hereditary" prostate cancer is a term applied to a specific subset of patients with prostate cancer. This form of prostate cancer is transmitted by a rare, autosomal, dominant allele with high penetrance; it accounts for an estimated 43% of early-onset disease (affecting men less than 55 years of age) but only 9% of all prostate cancer in men up to 85 years of age. A greater number of affected family members and early onset among family members are the most significant predictors of risk. CONCLUSIONS: Recent confirmation of the familial clustering and Mendelian inheritance patterns of some prostate cancer has important implications. It increases the potential for directed research into the causes of prostate cancer and for refinements in the current screening practices to detect this common disease. Manoeuvres to detect prostate cancer should be started earlier among men with one or more first-degree relatives with the disease than among other men.

Age Factors↗

Urinary polyamine levels in the diagnosis of carcinoma of the prostate.

Urinary excretion of the basic polyamine, spermidine, was significantly elevated in patients with prostatic carcinoma as compared to a control group of patients, Of 44 urine specimens from patients with prostatic malignancy 31 had spermidine levels more than 2 mg. per 24 hours, while only 3 of 13 urine specimens from the control groups had levels in excess of this value. The increase in spermidine appeared to be correlated with the histologic grading of the tumor, that is 30 of 34 specimens from patients with grade II, III or IV carcinoma had excessive spermidine excretion and only 1 of 10 urine specimens from patients with grade I tumors had similiar spermidine elevations. High spermidine levles were found in tumors localized to the prostate and in 7 of 8 patients with negative pelvic and para-aortic lymph node biopsies. This study raises the possibility that urinary spermidine determinations may aid in the development of a biochemical screening test for prostatic neoplasms.

Aged↗

[Transrectal ultrasound-guided biopsy of the prostate].

The early detection of prostatic neoplasm is nowadays a primary need in the urological field. The availability of transrectal ultrasound equipment alongside with bioptic tools made possible that transrectal ultrasound-guided biopsy of the prostate became the standard procedure to achieve this goal. With this work we would like to confirm the efficacy of this method which is also associated with a good tolerance and low complications rate. 82 patients that came to our Department between 1997 and 1999 were submitted to this procedure, 25 resulted positive for prostatic adenocarcinoma. Only 2 of them did not tolerate the procedure while all the others referred only mild discomfort at the moment of the puncture; 9 patients afterwards had to be admitted to the hospital due to fever (1 patient), acute retention of urine (3 patients) and persistent macroscopic hematuria (5 patients). Transrectal ultrasound-guided biopsy of the prostate reveals to be a safe and accurate method to obtain tissue samples of the prostate along with high tolerance and low incidence of serious complications.

Biopsy, Needle↗

[Analysis of loss of heterozygosity on chromosome 8 in human prostate carcinoma and high grade prostatic intraepithelial neoplasia].

OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 8 in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN). METHODS: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. LOH on chromosome 8 was detected by PCR based microsatellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade PIN. RESULTS: There were different frequencies of LOH on chromosome 8 in 10 samples of prostate carcinoma. 8p23.1-p23.2 and 8p21-p22 were two high-frequency LOH regions. LOH on chromosome 8 was detected in 3 samples of high grade PIN. CONCLUSIONS: There were high-frequency LOH regions on chromosome 8 of prostate carcinoma, located on 8p23.1-p23.2 and 8p21-p22. High grade PIN and prostate carcinoma share the same allelic loss on 8p. Tumor suppressor genes located at these two regions may be potentially involved in the initiation and progression of prostate carcinoma.

Aged↗

[Analysis of loss of heterozygosity on chromosome 10 in human prostate carcinoma and high grade prostatic intraepithelial neoplasia].

OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 10 in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN). METHODS: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. LOH of chromosome 10 was detected by PCR based microsatellite polymorphism analysis technique using 20 pairs of microsatellite primers in 16 samples of prostate carcinoma and 14 samples of high grade PIN. RESULTS: There were different frequencies of LOH in different loci on chromosome 10, varying from 0 to 46.2%, mainly located at 10q23 and 10q24-q25 regions. Seven samples of high grade PIN had LOH detected on chromosome 10. CONCLUSION: There were high frequency of LOH regions on chromosome 10 of prostate carcinoma. The rate of LOH in high grade PIN was much lower than that in prostate carcinoma. PTEN and MXI1 were two candidate tumor suppressor genes on 10q23 and 10q24-q25. They may be potentially involved in the initiation and progression of prostate carcinoma.

Aged↗

Histological characteristics of prostatic biopsies after 125iodine implantation.

There were 39 prostatic needle biopsies obtained from 33 patients with carcinoma of the prostate 1 to 3 years after definitive treatment with interstitial implantation using 125iodine radioactive sources. Of these biopsies 57 per cent obtained at 12 to 18 months and 73 per cent obtained at 19 to 36 months after implantation were negative for malignancy. All biopsies revealed histologic evidence of significant radiation injury. Neither the presence or absence of malignancy on biopsy nor the degree of radiation injury could be related to the initial stage and grade of the prostatic neoplasm.

Aged↗

[Small cell carcinoma of the prostate].

Pure small cell carcinoma of the prostate is rare (less than 1% of all prostatic neoplasm). As a result there are few reports in the literature that describe the salient features and appropriate management of this cancer (less than 200 cases reported). Small cell carcinomas of the prostate are a heterogeneous group of tumors, a number of them have neuroendocrine differentiation and are highly aggressive, commonly with visceral metastases at time of diagnosis. Complete temporary remission has been reported with chemotherapy but this tumor has a poor prognosis. The median overall survival from the time of diagnosis is between 5-17.5 months. We report 2 new cases of small cell carcinoma of the prostate and a review of the literature.

Aged↗

Proliferation, apoptosis and cell cycle regulation in prostatic carcinogenesis.

Cancer progression occurs because of imbalance in the processes of proliferation, differentiation and programmed cell death. In prostate cells, these processes are regulated at least in part by androgens. Structural alterations occur in a variety of genes regulating such processes. In order to obtain meaningful information on the biologic behavior of prostate cancers, it is important to assess androgen dependence and alterations in key genes regulating cell cycle kinetics as well as the aberrant response in cellular proliferation and death that such genetic events bring about. Most genetic alterations resulting in cancer progression alter normal cell cycle progression. Assessment of cell division cycle alterations by means of quantitative methods may have prognostic value, while interference with cell cycle regulatory proteins may result in powerful therapeutic tools. Here we review the methodologies utilized in the assessment of cell cycle kinetics and the abnormalities in proliferation and apoptosis encountered in prostate cancer. In addition, alterations in novel, important genes likely to have an impact on the behavior of prostate cancer and its precursor lesions are discussed. Molecular assessment of genetic alterations in genes that play a pivotal role in prostate cancer coupled with quantitative cytometry of cell kinetics may be utilized for a more precise evaluation of biologic behavior of prostate neoplasms.

Animals↗

Transforming growth factor-beta expression in prostate neoplasia.

OBJECTIVE: To understand the role of transforming growth factor (TGF) -beta 1, -beta 2 and -beta 3 proteins and TGF-beta type I and II receptors in prostate neoplasia; to determine the correlation between expression of TGF-beta s and their relative receptors in the epithelial and stromal compartments of benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostate carcinoma; and to determine whether TGF-beta and TGF-beta receptor expression is associated with the grade of tumor differentiation. STUDY DESIGN: Sixty prostate neoplasms were analyzed by immunohistochemistry using anti-TGF-beta 1, -beta 2, -beta 3, -beta RI and -beta RII antibodies. RESULTS: TGF-beta and TGF-beta receptor immunoreactivity was more strongly expressed in prostate carcinoma than in PIN and BPH, and TGF-beta type I and type II receptors were less strongly expressed than TGF-beta 1-3 proteins. The difference between epithelial and stromal compartments reached significance (P < .05) for all TGF-beta isoforms and related receptors only in BPH, whereas a significant difference was found for TGF-beta protein in all grades of PIN but not for prostate carcinoma tissue. Luminal epithelial cells of BPH and PIN coexpressed all three TGF-beta isoforms and preferentially TGF-beta RII. Conversely, basal epithelial cells stained strongly for TGF-beta 1, -beta 3 and -beta RI but not for TGF-beta 2 and more strongly for TGF-beta RI than -beta RII. Linear regression showed a positive correlation between TGF-beta 1 and -beta 2, between TGF-beta 2 and -beta 3 and between TGF-beta RI and -beta RII proteins in all areas. The epithelium of Gleason score 7 tumors contained significantly higher TGF-beta 2 protein levels than Gleason score 3 and 4, and 5 and 6 tumors (P < .05). CONCLUSION: Stromal and epithelial cells of malignant and nonmalignant prostatic tumors express all three TGF-beta isoforms and their related receptors. These may act as both paracrine and autocrine factors to influence prostate function and the stromal-epithelial cell interaction. TGF-beta and -beta R immunoreactivity noted in basal cells indicates that in BPH and PIN, TGF-beta Rs and signaling pathways remain intact. The overexpression of TGF-beta proteins and underexpression of TGF-beta receptors in prostate cancer could suggest a mechanism for prostate cancer cells to escape the growth inhibitory effect of TGF-beta, thus leading to a more malignant phenotype.

Activin Receptors, Type I↗

Concepts of citrate production and secretion by prostate: 2. Hormonal relationships in normal and neoplastic prostate.

A unique and major function of prostate secretory epithelial cells is to synthesize, accumulate, and secrete extraordinarily high levels of citrate. This function is regulated by testosterone and by prolactin. Concepts of the mechanisms of hormonal regulation are presented. The relationship of testosterone and prolactin to the origin and homologies of different prostate cell lines is described. The metabolic differentiation of citrate and non-citrate producing prostate secretory epithelial cells is discussed. Concepts of the pathogenesis of prostatic neoplasms are presented based on hormonal, metabolic, and homologous relationships associated with citrate production. Characterization of normal and neoplastic secretory epithelial cells by their citrate function is emphasized. The urgency and necessity for research relating to all aspects of prostate citrate production in normal and pathological prostate are emphasized.

Animals↗

A review of genetic polymorphisms and prostate cancer risk.

In this study, we review a variety of genetic polymorphisms that may have an etiologic role in prostate cancer. We include associations identified in molecular epidemiology studies and the consistency of findings reported to date. Suggestions for further research are also offered. For the purposes of this review, we identified relevant articles through a MEDLINE search for the period of January 1987 through March 2001. The searches were limited to articles published in English. Medical subject headings were used to scan titles, abstracts, and subject headings in the databases using the keywords "prostate neoplasms," "genetics," and "polymorphisms."

Genetic Linkage↗

Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells.

BACKGROUND: Diethylstillbestrol (DES) and diethylstilbestrol diphosphate (DESdP) are effective agents for the treatment of advanced prostate cancers. Tumor-inhibiting effects of DES and DESdP are presumed secondary to suppression of androgen production in vivo. Little is known, however, about the direct cellular mechanisms of the tumor inhibition. Estrogens have been reported not only to stimulate growth but also to disrupt microtubule formation in prostate cancer cells. PURPOSE: The study was designed to examine and compare mechanisms of in vitro growth inhibition of DES and DESdP in human androgen-insensitive prostate cancer cells (DU145, 1-LN, and PC-3) and human androgen-sensitive prostate cancer cells (LNCaP) and to examine estrogen receptor modulation of such effects. METHODS: The cytotoxic effects of DES and DESdP were examined in vitro by use of a standard microculture tetrazolium assay to quantitate numbers of viable cells. Immunofluorescence microscopy, DNA fragmentation analysis, and fluorescence flow cytometry were used to investigate microtubules, the induction of apoptosis, and changes in cell cycle distribution. The degree of estrogen receptor positivity of untreated and treated cells was determined by immunohistochemistry and quantitative image analysis. RESULTS: LD50 levels (the dose at which 50% of cells are no longer viable) in the concentration range of 19-25 microM were observed for both DES and DESdP in all cell lines examined. DESdP-induced growth inhibition was found to be dependent on heat-labile phosphatases present in fetal calf serum. DES-induced cytotoxicity was not affected by the presence of 17 beta-estradiol, and it was not dependent on the presence of estrogen receptor. Estrogen receptor-positive cells and estrogen receptor-negative cells were equally responsive to DES. PC-3 cells stained with fluorescent anti-tubulin, phalloidin (actin stain), and 4',6-diamidino-2-phenylindole (DNA stain) showed no inhibition of microtubules or actin filaments but revealed the presence of apoptotic bodies in the nuclei. Fluorescence flow cytometry of nuclear DNA content of propidium iodide-stained nuclei from androgen-insensitive prostate cancer cells treated with 15 or 30 microM DES or DESdP revealed an increase in relative numbers of hypodiploid (apoptotic) nuclei, a depletion of G1- and S-phase cells, and an accumulation of cells in G2/M phase. Conversely, androgen-sensitive cells contained a lower percentage of hypodiploid nuclei but no accumulation of cells in G2/M phase. CONCLUSIONS: Direct cytotoxic effects of DES in prostate cancer cells are estrogen receptor independent and do not involve disruption of microtubule architecture but do involve the promotion of cell cycle arrest and apoptosis. These are the first data confirming direct cytotoxic effects of DES and DESdP in prostate cancer cells via an apoptotic mechanism. IMPLICATIONS. These results suggest that DES and DESdP have potential value as agents against androgen-insensitive prostate neoplasms through induction of an apoptotic cascade.

Antineoplastic Agents, Hormonal↗

Progression-linked overexpression of c-Met in prostatic intraepithelial neoplasia and latent as well as clinical prostate cancers.

The c-met proto-oncogene encoding the receptor for the hepatocyte growth factor is expressed in several cancers. In the present study, c-met protein (c-Met) was detected in eight of 22 (36%) cases of prostatic intraepithelial neoplasia (PIN), five of 15 (33%) latent and 17 of 21 (81%) clinical prostate cancers, including seven metastatic lesions, using an immunohistochemical method. All seven (100%) metastatic lesions investigated demonstrated strong staining, and a correlation between c-Met expression and histology was observed. These results suggest a significant relationship between c-Met expression and progression of prostate neoplasms, including latent cancers.

Adenocarcinoma↗

Prostate brachytherapy. An overview.

BACKGROUND: Prostate brachytherapy represents one of the oldest techniques of using radiation therapy to treat prostate cancer. Over the past 10 years, there have been major changes in the types of prostate brachytherapy that can be performed with the introduction of new radioactive isotopes, new afterloading techniques, and an improved understanding of the radiobiology associated with differing dose rates. METHODS: Prostate brachytherapy can be divided into temporary implantation using high activity sources such as iridium-192, or permanent brachytherapy using the interstitial implantation of iodine-125 or palladium-103 sources. There are various techniques that can be used to actually insert the radioactive material into the prostate. This can be done as an open or closed procedure and can be performed via a suprapubic or a perineal retropubic approach. The use of remote afterloading has substantially reduced the radiation protection problems associated with manually loaded radioactive sources. RESULTS: Results using brachytherapeutic isotopes in the treatment of prostate cancer have been variable, but it appears that using the higher dose rate sources and delivering a high relative integral dose to the prostate can result in improved histologic control of prostate cancer. In patients with aggressive prostate cancer, the use of iodine-125 permanent implantation has not been successful. CONCLUSIONS: The role of brachytherapy in the treatment of prostate cancer remains an exciting alternative in the management of prostate cancer. Its role is becoming more defined in the treatment of large, bulky prostatic neoplasms as a way of improving the dose distribution achieved between normal and tumor tissue.

Brachytherapy↗

Determination of a minimal deletion interval on chromosome band 8p21 in sporadic prostate cancer.

Loss of the short arm of chromosome 8 is a common event in prostatic neoplasms. Previous studies indicate that there may be up to three separate tumor suppressor genes on chromosome arm 8p, based on patterns of allelic loss. The responsible gene or genes have yet to be identified. In the present study, we used laser-capture microdissection of primary human prostate tumors and 17 microsatellite markers across chromosome band 8p21 to determine a minimal deletion interval. From an initial set of 120 cases, three tumors contained overlapping interstitial deletions on chromosome band 8p21. The three cases define an internally consistent minimal candidate tumor suppressor gene interval of approximately two megabases.

Chromosome Banding↗

Metabolic profile in patients with benign prostate hyperplasia or prostate cancer and normal glucose tolerance.

Familial predisposition together with several environmental factors may be involved in the pathogenesis of common prostate disease such as benign hypertrophy or prostate neoplasm. A higher incidence of both these conditions has been described in some insulin-resistant states such as obesity, but not much information is available on the effect of metabolic profile on gland morphology. The aim of this study was to evaluate the relation between glucose and lipid pattern and prostate diameters in two groups of non-diabetic individuals with benign prostate hypertrophy or cancer. 109 patients were recruited; plasma glucose, lipids and hormonal profile as well as an ultrasonographic evaluation of the gland volume and diameters were determined. Patients with prostate cancer had significantly higher levels of insulin and were more insulin resistant; in contrast, in subjects with prostate hypertrophy, fasting plasma glucose and--to a lesser extent--serum triglycerides emerged as the main determinants of gland volume. These observations may indicate that an improvement of insulin sensitivity and strategies to maintain a strict glucose and lipid control even in non-diabetic subjects are useful objectives in the prevention of prostate diseases.

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