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

TRAF-4 was discovered because of its expression in breast cancers and is a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of putative signal-transducing proteins. In vitro binding assays demonstrated that TRAF-4 interacts with the cytosolic domain of the lymphotoxin-beta receptor (LT beta R) and weakly with the p75 nerve growth factor receptor (NGFR) but not with TNFR1, TNFR2, Fas, or CD40. Immunofluorescence analysis of TRAF-4 in transfected cells demonstrated localization to cytosol but not nucleus. Immunohistochemical assays of normal human adult tissues revealed prominent cytosolic immunostaining in thymic epithelial cells and lymph node dendritic cells but not in lymphocytes or thymocytes, paralleling the reported patterns of LT beta R expression. The basal cell layer of most epithelia in the body was very strongly TRAF-4 immunopositive, including epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus. Similar findings were obtained in 12- to 18-week human fetal tissue, indicating a highly restricted pattern of expression even during development in the mammary gland, epithelial cells of the terminal ducts were strongly TRAF-4 immunopositive whereas myoepithelial cells and most of the mammary epithelial cells lining the extralobular ducts were TRAF-4 immunonegative. Of 84 primary breast cancers evaluated, only 7 expressed TRAF-4. Ductal carcinoma in situ (DCIS) lesions were uniformly TRAF-4 immunonegative (n = 21). In the prostate, the basal cells were strongly immunostained for TRAF-4, whereas the secretory epithelial cells were TRAF-4 negative. Basal cells in prostate hypertrophy (n = 6) and prostatic intraepithelial neoplasia (PIN; n = 6) were strongly TRAF-4 positive, but none of the 32 primary and 16 metastatic prostate cancer specimens examined contained TRAF-4-positive malignant cells. Although also expressed in some types of mesenchymal cells, these findings suggest that TRAF-4 is a marker of normal epithelial stem cells, the expression of which often ceases on differentiation and malignant transformation.
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PMID:TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues. 984 90

Prostatic intraepithelial neoplasia (PIN) has been considered as a precursor of prostatic cancer. Few reports have dealt with the long-term follow-up of PIN lesions, and there is still a lack of proof that PIN is a true premalignant lesion. The objective of this study was to evaluate PIN in the transition/central zone as a marker for subsequent development of prostatic cancer. The PIN status of tissue specimens from 789 men without prostate cancer was determined in 508 transurethral resections and 281 transvesical prostatic enucleations. All slides were reviewed blind and independently by two pathologists. The patients were followed for an average of 11 years, and the incidence of subsequent cancer and cause-specific survival were analysed. Thirty-six cases of clinical prostatic cancer occurred among the cohort of 789 men through follow-up. No association between the presence of PIN in the transition/central zone and subsequent cancer development was found. There was also no difference in survival related to PIN status among the subsequent cancer patients.
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PMID:Is prostatic intraepithelial neoplasia in the transition/central zone a true precursor of cancer? A long-term retrospective study in Norway. 966 49

We have previously identified (M. Wang et al., Oncol. Res., in press, 1998) an enhancer element [human tissue inhibitor of metalloproteinase-1 enhancer-1 (HTE)] for the human tissue inhibitor of metalloproteinase-1 promoter that binds a novel zinc finger, cysteine-rich transcription factor (CRTF). In this study, we have used electrophoretic mobility shift assays to examine the relative level of expression of CRTF, jun/fos, and IFN-gamma responsive signal transducer activators of transcription (STATs) that bind specific HTE, activator protein, and IFN-gamma (Fcy and interferon regulatory factor) response motifs in tumor lines and human prostate tissue [i.e., normal (n = 3); benign prostatic hyperplasia (BPH; n = 12); high grade prostate intraepithelial neoplasia (PIN; n = 10); and prostate cancer adenocarcinoma (PCA; n = 61) plus seminal vesicle (n = 10) tissues]. The data showed that CRTF was overexpressed in PCA (Gleason's score, 10>8>6>5>4) compared with BPH, PIN, seminal vesicle, and normal tissues. To a much lesser degree, jun/fos and STAT 1 were also elevated in PCA compared to BPH, PIN, and normal tissues. In addition, blinded studies showed that CRTF and jun/fos were present at low levels in organ-confined specimens but at significantly elevated levels (P < 0.001) in samples exhibiting capsular penetration and localized spread, which indicated that CRTF and perhaps jun/fos were markers for cancer progression.
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PMID:Specific transcription factors prognostic for prostate cancer progression. 974 34

Chemoprevention is the administration of agents to prevent induction and inhibit or delay progression of cancers. For prostate, as for other cancer targets, successful chemopreventive strategies require well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer for evaluating chemopreventive efficacy. Agent requirements are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the observed chemopreventive activity. On this basis, promising chemopreventive drugs in prostate include retinoids, antiandrogens, antiestrogens, steroid aromatase inhibitors, 5alpha-reductase inhibitors, vitamins D and E, selenium, lycopene, and 2-difluoromethylornithine. Phase II trials are critical for evaluating chemopreventive efficacy. Cohorts in these trials should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen as endpoints. Many cohorts proposed for phase II trials are patients with previous cancers or premalignant lesions. For such patients, trials should be conducted within the context of standard treatment. Two cohorts currently used in phase II prostate cancer chemoprevention trials are patients with PIN and patients scheduled for prostate cancer surgery. Biomarkers should fit expected biological mechanisms, be assayed reliably and quantitatively, measured easily, and correlate to decreased cancer incidence. Protocols for adequately sampling tissue are essential. Changes in PIN provide prostate biomarkers with the ability to be quantified and a high correlation to cancer. PIN measurements include nuclear polymorphism, nucleolar size and number of nucleoli/nuclei, and DNA ploidy. Other potentially useful biomarkers are associated with cellular proliferation kinetics (e.g. PCNA and apoptosis), differentiation (e.g. blood group antigens, vimentin), genetic damage (e.g. LOH on chromosome 8), signal transduction (e.g. TGFalpha, TGFbeta, IGF-I, c-erbB-2 expression), angiogenesis, and biochemical changes (e.g. PSA levels).
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PMID:Chemoprevention of prostate cancer: concepts and strategies. 1032 87

The identification of 2 or 3 different grades of prostate intraepithelial neoplasia has led to a number of difficult concepts and treatment possibilities. Postmortem examination of the prostates of men over the age of 20, who have died of other causes, mainly road traffic accidents, have been examined and the earliest signs of intraepithelial neoplasia can be seen in some of them. The most common age for prostate cancer to present clinically is between 60 and 65 years and because the majority of men do not develop clinical prostate cancer, there must be a very large number who never progress further than PIN I or II. It is very rare for the early stages of intraepithelial neoplasia to be associated with frank carcinoma. However, it is known that PIN III is frequently found in the presence of carcinoma elsewhere in the gland and this stage is seen as a premalignant development. PIN III in the presence of prostate carcinoma is treated by whatever modality is used to treat the carcinoma. In the absence of carcinoma, there are urologists who consider that it should be regarded as a T1 tumor and radical prostatectomy or radiotherapy with delayed hormonal therapy are definite alternatives. From a certain amount of anecdotal evidence, it seems that the transition from PIN III to a focal carcinoma may take in the order of 2-3 years. Whether this transition can be definitely postponed by the early use of hormonal therapy is not known. Prostate intraepithelial neoplasia may also be treated by other modalities such as anti-angiogenesis agents, gene therapy, anti-metastatic agents, or metalloproteinase inhibitors. The effects of these treatments can be examined histologically by repeated biopsies to ensure that the process remains arrested. If the process of intraepithelial neoplasia can be identified at early stages, dietary modifications may well reduce mitogenic influences and slow down the process or even halt it altogether.
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PMID:PIN I-III: when should we interfere? 1032 14

Prostatic intraepithelial neoplasia (PIN) is the most common precursor lesion of prostatic adenocarcinoma. In 50- to 70-year-old participants of a randomized screening program for prostate cancer (Rotterdam section of the ERSPC) the frequency of high-grade PIN as an isolated finding in sextant prostatic needle biopsies was estimated to be about 1%. As yet, data in literature on the impact of androgen deprivation on PIN lesions are limited, showing discrepant outcomes. In part this may be the consequence of the application of different criteria for the identification of PIN under conditions of androgen deprivation. Foci of PIN could be distinguished in the majority of radical prostatectomy specimens of men treated for 3 or 6 months with combined endocrine therapy. Endocrine manipulation led to architectural changes (remodelling) in residual PIN which were more pronounced at 6 months of endocrine therapy. This is consistent with a prolonged effect of androgen deprivation on this precursor lesion. The presence of MIB-1 immunopositive nuclei in PIN lesions suggests that they still have the potential to expand after cessation of therapy.
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PMID:Prostatic intraepithelial neoplasia and endocrine manipulation. 1032 15

Based on autopsy and epidemiologic data the lifetime risk of developing prostate cancer for a 50-year-old man is 42%, but only 9.5% will develop a clinically manifest disease and only 2.9% will die from this disease. The actual rate of carcinoma detection using PSA, digital rectal examination and transrectal ultrasound is 1%-3%. The majority of prostate carcinoma never progress to clinically significant disease, a minor portion remains confined to the prostate for many years and other carcinomas progress rapidly to a life threatening disease. The dilemma for clinicians and pathologists dealing with this tumor is how to distinguish these three biologically different types. Pathologists play an important role in preoperative diagnosis and in the postoperative prognosis oriented evaluation of the prostatectomy material. Volunteer PSA screening trials have led to an enormous increase in core-needle biopsies of the prostate. Since biopsies are often performed in men without palpable or ultrasound-visible nodules, are now faced with an increasing number of equivocal morphological features which can not be clearly defined, even with standardized criteria. Further investigations are also required to elucidate the clinical importance of PIN detection in biopsies. The heterogeneous histomorphology of prostate carcinoma can not be used as a prognostic factor. Therefore the histological grading is a very important factor for the assessment of prognosis. Carcinoma grading in biopsies is also of limited value in predicting tumor stage. Currently, several different grading systems are in use. Gleason's grading is the most favored, although its reproducibility is very low. The stage of the prostate carcinoma is still the best prognostic factor. In order to accurately assess the pTNM stage, TUR or prostatectomy material must be subject to extensive and standardized processing. Additionally, the volume of the tumor, the vascular invasion, the amount of extension of the tumor through the prostate capsule and perhaps the neoangiogenesis might be valid prognostic factors for disease progress and for survival. The value of novel methods (p53, bcl-2, apoptosis, microvessel density, interphase cytogenetics, androgen receptor mutation, neuroendocrine cells, E-Cadherin) remains to be proved. DNA ploidy is a good prognostic factor after prostatectomy and can be used to plan adjuvant hormone therapy.
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PMID:Pathology of prostate cancer. Old problems and new facts. 1035 66

For urologists and pathologists one of the two main issues in prostate pathology is the identification of those prognostic factors that could predict the exact outcome of individual patients with prostate cancer (PC). Therefore, the goal is to tailor the therapeutic approach to the clinical, morphological and biological features of each patient. The other issue involves the early detection of PC, preferably in the preinvasive phase, in order to treat the patient efficaciously. For this reason, understanding the biology of preinvasive or precursors lesions has become increasingly important. Prostatic intraepithelial neoplasia is only one of these lesions, and the best known to date. The role of others, such as atypical adenomatous hyperplasia, is considered as worth exploring. Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered the direct precursor of invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterised by basal cell layer disruption, basement membrane disruption, progressive loss of markers of secretory differentiation, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognising PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. The issue of precursors of prostate cancer has several facets which reflect the multiplicity of patterns and variants of PC. A big step forward in understanding some basic aspects has already been made, especially in relation to PIN. More will be available soon. A large contribution to the management of isolated PiN lesions found in prostate biopsies is expected from molecular pathology and quantitation analysis.
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PMID:Preneoplastic lesions of the prostate. 1035 67

For urologists and pathologists one of the two main issues in prostate pathology is the identification of those prognostic factors that could predict the exact outcome of individual patients with prostate cancer (PC). Therefore, the goal is to tailor the therapeutic approach to the clinical, morphological and biological features of each patient. The other issue involves the early detection of PC, preferably in the preinvasive phase, in order to treat the patient efficaciously. For this reason, understanding the biology of preinvasive or precursors lesions has become increasingly important. Prostatic intraepithelial neoplasia is only one of these lesions, and the best known to date. The role of others, such as atypical adenomatous hyperplasia, is considered as worth exploring. Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered the direct precursor of invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterised by basal cell layer disruption, basement membrane disruption, progressive loss of markers of secretory differentiation, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognising PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. The issue of precursors of prostate cancer has several facets which reflect the multiplicity of patterns and variants of PC. A big step forward in understanding some basic aspects has already been made, especially in relation to PIN. More will be available soon. A large contribution to the management of isolated PiN lesions found in prostate biopsies is expected from molecular pathology and quantitation analysis.
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PMID:Prostatic intraepithelial neoplasia and prostate cancer: analytical evaluation. 1035 69

The presence and morphology of high-grade prostatic intraepithelial neoplasia (H-PIN) was blindly evaluated in 40 totally embedded radical prostatectomy specimens of patients with prostate cancer randomized to either a 3 (n = 18) or 6 months (n = 22) combined androgen blockade regimen before surgery. In 5 cases, neo-adjuvant therapy was abrogated some time before surgery. In the remaining cases, foci of H-PIN were identified in 72% and 59% of prostates from patients treated for 3 and 6 months, respectively. Cellular features used to distinguish H-PIN from normal glands were increased nuclear size, nuclear crowding, anisonucleosis, and disordered nuclear arrangement. In some cases, density of cytoplasm was an additional feature. Unfortunately, the molecular marker erbB2 proved unhelpful for identification of H-PIN. The median number of prostatic glands involved by H-PIN was 19 +/- 21 (SD) glands in 3 months treated prostatectomies (n = 18) and 7 +/- 12 (SD) glands in 6 months treated prostatectomies (n = 17), a nonsignificant difference (P = .17). H-PIN was localized within areas of residual carcinoma in 62% and 20%, respectively of prostatectomies of patients treated for 3 and 6 months, respectively. Architectural patterns of H-PIN differed at 3 and 6 months of endocrine pretreatment: The predominant tufted pattern at 3 months was replaced by flat H-PIN at 6 months. The continued expression of androgen receptors and the cell cycle marker MIB-1 in persistent H-PIN suggests that recovery of androgen levels after cessation of androgen blockade therapy will lead to its further expansion.
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PMID:Persistence of high-grade prostatic intra-epithelial neoplasia under combined androgen blockade therapy. 1066 30


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