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)

Within the past 5 years, research has increasingly addressed molecular alterations in prostate cancer (CaP). Mutations of tumor suppressor gene p53 have been found in a variety of cancers, including urologic neoplasms. Several studies have been conducted on CaP specimens, citing frequencies of p53 alterations in localized cancers ranging from 4 to 60% and with more advanced hormone refractory disease, as high as 94%. The majority of studies have revealed a low percentage of p53 abnormalities in early-stage (clinically organ-confined) CaP. The overwhelming bulk of evidence suggests that the frequency of p53 abnormalities does increase with disease progression and is highest in tissues from patients with hormone-refractory prostate cancer. More recently, our group and others have found that focal p53 expression in the primary tumor by immunohistochemistry is predictive of cancer recurrence after radical prostatectomy. bcl-2 is an oncogene critically involved in the apoptosis, or programmed cell death. Overexpression of bcl-2 protein by immunohistochemistry has been commonly detected in advanced hormone refractory CaP. Our group recently has also shown that bcl-2 protein expression in primary CaP is a predictor of cancer recurrence after radical prostatectomy. Furthermore, the combination of p53 and bcl-2 protein expression were both independent predictors of recurrence after surgery. Most recently, we have shown that even though p53 and bcl-2 are predictive biomarkers when sampling the radical prostatectomy specimen, they are not useful to predict postoperative recurrence when sampling the pretreatment needle biopsy. Ki-67 is an antigen of cellular proliferation. Immunohistochemical staining for Ki-67 in archival material can be performed using the MIB-1 antibody. Unlike our results with p53 and bcl-2, Ki-67 protein expression by immunohistochemistry using MIB-1 was not an independent prognostic marker for cancer recurrence after radical prostatectomy although it may have clinical utility in subsets of patients. Assessment of MIB-1 staining in CaP needle biopsy samples is underway. Tumor neovascularity, or angiogenesis, is necessary for cancers to grow and metastasize. Angiogenesis in CaP as a prognostic marker has received recent attention. Most studies have used factor VIII immunohistochemical staining and increased angiogenesis has been suggested as a staging and prognostic marker. Our group has recently conducted a large study of radical prostatectomy patients and used CD34 antigen immunohistochemistry to assess neovascularity. We did not find that this biomarker assessment was an independent prognostic marker of cancer recurrence after radical prostatectomy. Further work is being conducted in needle biopsy samples. More research is needed to assess new biomarkers and, most importantly, to standardize the methodology for sampling and assaying biomarkers in heterogeneous and multifocal prostate cancer.
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PMID:Angiogenesis, p53, bcl-2 and Ki-67 in the progression of prostate cancer after radical prostatectomy. 1032 96

Molecular genetic analyses of human prostate cancer (CaP) has revealed frequent loss of specific chromosome regions suggesting the presence of putative tumor suppressor gene(s) (TSG) on these chromosome loci whose inactivation may play a role in prostate tumorigenesis. To understand the role of 6q alterations in CaP, we have undertaken a comprehensive analysis of proximal 6q. Genomic DNA from tumor and normal prostate tissues from radical prostatectomy specimens of 38 patients were analyzed by polymerase chain reaction (PCR) for 13 polymorphic microsatellite loci on 6q. Allelic losses of 1 or more polymorphic loci were detected in 11 of 38 patients (29%). Six of 11 tumors showing any 6q deletion were found to have allelic losses at D6S1056 and D6S300 loci. Our results revealed a 1.5 megabase interval between D6S1056 and D6S300 at 6q16.3-21 as the minimal region of deletion, which may contain the putative TSG involved in prostate tumorigenesis. One of the tumor samples demonstrated homozygous deletion at a distal location D6S314 (6q23-24), suggesting another locus potentially associated with CaP. Although the relationship of 6q loss of heterozygosity (LOH) with various clinico-pathologic variables, i.e., cancer recurrence or pathologic stage, did not reveal a statistically significant association, the risk for 6q LOH to non-organ confined (pT3) disease was 5-fold higher than for organ confined disease.
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PMID:Allelic loss on chromosome 6Q in primary prostate cancer. 1037 56

One of the single most important considerations in clinical management of the patient with prostate cancer is whether or not metastatic disease is present. The identification of metastatic disease in a patient with newly diagnosed prostate cancer represents an absolute contraindication to definitive local therapies such as radial prostatectomy or radiation therapy. Similarly, the identification of metastatic disease in a patient with disease recurrence after definitive local therapy represents an absolute contraindication to salvage radiotherapy or cryosurgery. Patients with metastatic disease do not benefit from definitive therapy, and the cost and morbidity associated with such treatment should therefore be avoided in these patients. Because of the significance of metastatic disease to clinical management, it is important for the diagnostic radiologist to be aware of important considerations in the metastatic work-up of patients with newly diagnosed prostate cancer and patients with suspected cancer recurrence after definitive local therapy.
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PMID:The prostate: diagnostic evaluation of metastatic disease. 1066 70

To evaluate the potential application of somatostatin (SST) analogs as an adjuvant treatment for prostate cancer, we characterized the binding sites for SST octapeptide analogs on prostate cancers in patients treated with radical prostatectomy. The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class of specific binding sites for RC-160 with a mean dissociation constant (K(d)) of 9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason score of 8-10), the incidence of RC-160 binding (65.7%) was similar to that observed in the low risk group (64.3%). The demonstration of the high incidence of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate cancers supports the merit of further investigations of the application of SST analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment of patients at high risk of cancer recurrence after radical prostatectomy. Such approaches could be also considered for patients with advanced prostate cancer at the time of relapse.
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PMID:High expression of somatostatin receptors and messenger ribonucleic acid for its receptor subtypes in organ-confined and locally advanced human prostate cancers. 1090 9

Nerve-sparing radical prostatectomy can be performed safely in most men undergoing radical prostatectomy. As is true in many aspects of prostate cancer diagnosis and therapy, the key element is patient selection. With many prostate tumors diagnosed at an earlier stage, the authors have seen a shift toward more favorable pathologic findings at the time of surgery. Concomitant with the success of early detection of prostate cancer is the realization that men are younger at the time of diagnosis and more interested in preserving sexual function. This article has described factors associated with an increased risk for extraprostatic tumor and, subsequently, an increased possibility of postprostatectomy cancer recurrence. Except for the previously mentioned absolute contraindications, none of these factors, by themselves, should be used to exclude a patient from nerve-sparing prostatectomy. Instead, meticulous attention must be given to the surgical dissection. If any doubt remains regarding residual tumor, the surgeon should err on the side of caution and remove the neurovascular bundle. The use of standardized intraoperative frozen-section analysis can help guide these decisions. The patient must be informed before surgery regarding the risks of nerve-sparing surgery, the potency rates of the surgeon, and the possibility that, to ensure adequate cancer control, the nerves may be sacrificed despite any preoperative optimism favoring the potential for their salvage.
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PMID:Indications and contraindications for nerve-sparing radical prostatectomy. 1159 Aug 12

An increasing number of studies are being published on the impact of localized prostate cancer on patient quality of life. Research suggests that the majority of patients diagnosed with prostate cancer return to pretreatment levels of general quality of life within 1 year after treatment. However, sexual, urinary, and bowel symptoms continue to be an issue for many patients beyond 1 year post-treatment. Focusing on psychologic impacts and social functioning, in addition to physical symptoms, may provide useful avenues for improving patient quality of life. We also discuss emerging evidence of racial and/or ethnic disparities in prostate cancer-related quality of life, the role of social networks and support in recovery and adjustment, as well as the impact of cancer recurrence.
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PMID:Quality-of-life differences among various populations of localized prostate cancer patients: 2001. 1208 95

Clinical oncologists have always shown great interest in circulating tumor markers. There are several markers that in the clinical routine are a signal of particular tumor types; some of them are strictly tissue-specific such as prostatic specific antigen (PSA) for prostatic cancer, AFP and HCG for germ cell tumors of the testis and ovary, others such as CA 15.3, CA125, CEA or cytokeratins are less specific since their elevations can be found in different varieties of cancers even if they are preferentially associated to a certain tumor type, thus are considered markers for breast, ovarian cancer and colon adenocarcinoma. The most useful clinical applications of these parameters is their determination during the follow-up of the treated patients, in order to detect the tumor recurrence early, and also to evaluate the evolution of the disease by monitoring the treatment responses. During follow-up, increasing levels of tumor markers can be observed even several months before the clinical demonstration of cancer recurrence. The association of tumor marker tests with imaging modalities can lead to several advantages: the first is to confirm the diagnosis of relapses, possibly before the appearence of the related clinical symptoms due to tumor growth; the second is to localize the sites of lesions, while tumor markers provide only a general indication of the existence of metastases; the third is to make possible a correct whole body restaging. In the assessment of cancer response tumor markers are often very reliable and their changes are faster than the morphological ones. Among all the imaging modalities, nuclear medicine plays an important role in detecting recurrences and metastatic localizations as it is able to investigate functional rather than morphological aspects of tumors, and provide different information in comparison to morphologic imaging. In addition, the scintigraphic techniques offer the possibility to evaluate treatment responses, confirming or not the information from biochemical changes. This review aims to show some examples (breast, prostate and ovarian cancer) in which the combination of nuclear medicine imaging modalities and tumor marker tests is proposed for clinical practice. The advantages and some critical aspects are discussed on the basis of the clinical findings and the most important clinical indications are described.
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PMID:Circulating tumor markers and nuclear medicine imaging modalities: breast, prostate and ovarian cancer. 1211 72

A comparative analysis of cancer prevalence in France, Spain and Italy is presented as part of the EUROPREVAL project. The three countries are culturally and sociologically relatively homogeneous compared with Europe as a whole. However, in all three countries, the cancer registries (CRs) providing the data for prevalence calculation cover only small fractions of the populations, and have been operating for relatively short periods. This leads to problems of representativity and to prevalence underestimates as surviving cases diagnosed before operation of the CR are not recorded. Partial prevalences obtained directly from CR data were therefore corrected using a completeness index obtained by modelling to provide estimates of the complete prevalence. For CRs operating for only 5 years, only approximately half the prevalence was observed. Thus, due to the rather recent start of most of southern European CRs, the role of correction is very important. The prevalence of all cancers was highest in Italy for women and in France for men, while lowest in Spain. Differences in the age structures of the populations were the major cause of these discrepancies and after age adjustment only the prevalence of stomach cancer remained highest in Italy, although differences in incidence also contributed to the prevalence differences. Survival varied little between the three countries and differences in incidence are more important determinants of prevalence. Prevalence of cancer in the elderly represents an increasing load for the community, particularly for France, Italy and Spain due to the ageing population in these countries. Elderly patients with cancer frequently suffer from problems of co-morbidity and disability factors, thus placing a burden on the local medical system where this proportion is high. Prevalent cases diagnosed 1-5 years before the prevalence date formed approximately one-third of the total prevalence, with higher proportions for melanoma, and prostate cancer in males and breast and colorectal cancer in females, and lower proportions for uterine cancer. This subset of the prevalent population consists of those probably on intensive follow-up, or being treated for cancer recurrence or sequelae to primary therapy.
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PMID:A comparative analysis of cancer prevalence in cancer registry areas of France, Italy and Spain. 1217 94

Biological markers that are both sensitive and specific for tumour regrowth or metastasis are increasingly becoming available and routinely monitored during the regular follow-up of patients treated for cancer. Obtained by a simple blood test, these markers provide an inexpensive non-invasive means for the early detection of recurrence (or progression). Currently, the longitudinal behaviour of the marker is viewed as an indicator of early disease progression, and is applied by a physician in making clinical decisions. One marker that has been studied for use in both population screening for early disease and for detection of recurrence in prostate cancer patients is PSA. The elevation of PSA levels is known to precede clinically detectable recurrence by 2 to 5 years, and current clinical practice often relies partially on multiple recent rises in PSA to trigger a change in treatment. However, the longitudinal trajectory for individual markers is often non-linear; in many cases there is a decline immediately following radiation therapy or surgery, a plateau during remission, followed by an exponential rise following the recurrence of the cancer. The aim of this article is to determine the multiple aspects of the longitudinal PSA biomarker trajectory that can be most sensitive for predicting time to clinical recurrence. Joint Bayesian models for the longitudinal measures and event times are utilized based on non-linear hierarchical models, implied by unknown change-points, for the longitudinal trajectories, and a Cox proportional hazard model for progression times, with functionals of the longitudinal parameters as covariates in the Cox model. Using Markov chain Monte Carlo sampling schemes, the joint model is fit to longitudinal PSA measures from 676 patients treated at Massachusetts General Hospital between the years 1988 and 1995 with follow-up to 1999. Based on these data, predictive schemes for detecting cancer recurrence in new patients based on their longitudinal trajectory are derived.
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PMID:Predicting time to prostate cancer recurrence based on joint models for non-linear longitudinal biomarkers and event time outcomes. 1248 74

Carcinoma of the prostate is the second leading cause of male cancer-related death in the United States. Better indicators of prostate cancer presence and progression are needed to avoid unnecessary treatment, predict disease course, and develop more effective therapy. Numerous molecular markers have been described in human serum, urine, seminal fluid, and histological specimens that exhibit varying capacities to detect prostate cancer and predict disease course. However, to date, few of these markers have been adequately validated for clinical use. The purpose of this review is to examine the current status of these markers in prostate cancer and to assess the diagnostic potential for future markers from identified genes and molecules that display loss, mutation, or alteration in expression between tumor and normal prostate tissues. In this review we cite 91 molecular markers that display some level of correlation with prostate cancer presence, disease progression, cancer recurrence, prediction of response to therapy, and/or disease-free survival. We suggest criteria to consider when selecting a marker for further development as a clinical tool and discuss five examples of markers (chromogranin A, glutathione S-transferase pi 1, prostate stem cell antigen, prostate-specific membrane antigen, and telomerase reverse transcriptase) that fulfill some of these criteria. Finally, we discuss how to conduct evaluations of candidate prostate cancer markers and some of the issues involved in the validation process.
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PMID:Detection of prostate cancer and predicting progression: current and future diagnostic markers. 1521 24


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