Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre- and post-treatment specimens from 47 patients with hormone resistant prostatic carcinoma were compared with each other regarding histological grade and immunoreactivity for p53 protein, neuron specific enolase and c-erbB-2 protein. Significantly more specimens expressed a high malignancy grade when the tumour had become hormone resistant than at the time of initial diagnosis (Gleason P: < 0.0001, WHO P:0.0003). p53 protein immunoreactivity increased significantly with disease progression (P:0.006), while tissue PSA immunoreactivity was reduced in post-treatment specimens (P:0.011). p53 protein expression did not correlate with histological grade or PSA expression and seems to be an independent parameter which participates late in the neoplastic transformation. Thirty-two percent of the tumours were neuron specific enolase positive, but this parameter did not correlate with development of hormone resistance. c-erbB-2 protein reactivity was not recognised.
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PMID:Hormone resistant prostatic adenocarcinoma. An evaluation of prognostic factors in pre- and post-treatment specimens. 768 48

The state of the art concerning major biological phenomenons of importance for current research on urological cancers is first briefly presented, followed by notes on the more outstanding presentations in this field. These notes are organized in a synthetic fashion, in order to point to the meaning of the hypotheses and findings presented, when taken together, as they pertain to the understanding of the mechanisms at play in urological cancers, as we see them in 1995. Some concepts seem to have now reached a point where we can expect to see some applications in a not so distant future: in prostate cancer, it is confirmed that the machinery of apoptosis is functional even in the hormone-insensitive cells, suggesting that its enhancement might be useful in these often difficult situations; techniques to detect circulating malignant cells, which have been greatly refined (RT-PCR of PSA and PSM), are now extremely sensitive and may prove unvaluable in providing intermediate end points to compare the relative efficacy of treatment regimens in clinical trials; the symposium on prostate cancer screening by PSA dosage was an excellent opportunity to review extensively the data available on this topic, but -as expected- it could not decide on some essential issues; in bladder tumors, data on the expression of adhesion molecules (CD44 variant) are still preliminary, but some provocative observations have been reported (presence on mature ARN, only in bladder cancer cells, of intronic sequences that have not been excised); in renal cell cancer, a considerable amount of knowledge has accumulated on the von Hippel-Lindau gene, a putative anti-oncogene, and work is in progress to define the function of its protein; finally, pathways essential to understanding and treating cancer have been dissected, particularly the apoptosis-proliferation network, and the involvement in it of p53, Waf-1 and the bcl-2 gene family cascade.
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PMID:[The annual meeting of the American Association for Cancer Research (AACR), Toronto (Ontario), 18-22 May 1995]. 867 62

New human prostate cell lines were developed from prostatic carcinoma (BRF-41T) and BPH (BRF-55T). Primary cultures were initiated from cellular outgrowths of explanted tissues. A serum-free medium, BRFF-HPC1, was developed for growing human prostatic cancer cells. Cell strains were immortalized with pRSV-T plasmid to generate permanent cell lines that exhibited an epithelial morphology. Both cell lines expressed the epithelial cell markers, cytokeratins 8 and 18 as well as the prostatic marker, PSA, and the androgen receptor gene. They possess the H-ras, K-ras, and p53 genes. We hope that these new human prostatic cell lines will be useful as in vitro models for cancer research.
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PMID:Establishment and characterization of immortalized human cell lines from prostatic carcinoma and benign prostatic hyperplasia. 945 47

Recently, using an ultrasensitive time-resolved immuno-fluorometric assay, PSA immunoreactivity (IR-PSA) was found in breast tumor cytosols. We retrospectively studied 219 breast cancer patients, measuring IR-PSA in the tumor cytosols, and classified the breast cancers as either PSA positive or PSA negative based on an IR-PSA cut off level of 1 pg/mg. Multivariated analysis showed that IR-PSA is an independent favourable prognostic indicator for postmenopausal, node positive breast cancer patients. Additionally, IR-PSA correlates with reduced risk of relapse in ER+ve tumors and is negatively correlated with mutated p53, which increases the risk of relapse.
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PMID:Correlation of prostate specific antigen immunoactivity (IR-PSA) to other prognostic factors in female breast cancer. 958 52

The present study evaluated three human prostate xenograft tumors (CWR22, CWR22R, and CWR91) as models for drug activity evaluation. The chemosensitivity and the expression of several proteins (i.e., p-glycoprotein or Pgp, prostate specific antigen or PSA, p53, and Bcl-2) in xenograft tumors were compared with those in patient tumors obtained through radical prostatectomy (n = 26). CWR22 is androgen-dependent, CWR22R is the androgen-independent subline of CWR22, and CWR91 is a separately derived androgen-independent tumor. The results of immunohistochemical and/or Western blot analysis indicate that the expression of PSA, Pgp, p53, and Bcl-2 in the three CWR xenograft tumors are representative of their expression in 100, 85, 90, and 60%, respectively, of patient tumors. The responses of histocultures of xenograft tumors to doxorubicin and paclitaxel, including inhibition of DNA precursor incorporation and cell death induction, were qualitatively similar to the responses of patient tumors. For example, in all three xenograft and patient tumors, doxorubicin produced complete antiproliferation and cytotoxicity (ie., cell kill) whereas paclitaxel produced incomplete effects. A comparison of the concentration-effect relationships in xenograft and patient tumors (population median values) indicates that the chemosensitivity observed in patient tumors is represented by the chemosensitivity of one or more of the three xenograft tumors, as follows: (a) the three xenograft tumors and patient tumors responded equally to doxorubicin-induced antiproliferation; (b) CWR22R, CWR91 and patient tumors responded equally to doxorubicin-induced cytotoxicity, whereas CWR22 was 2-3-fold less sensitive; (c) CWR22 and CWR22R tumors were less sensitive to paclitaxel-induced antiproliferation compared with patient tumors, whereas CWR91 was several-fold more sensitive; and (d) CWR22, CWR22R and patient tumors responded equally to paclitaxel-induced cytotoxicity, whereas CWR91 was 2-3-fold more sensitive. The results of this study indicate that the three xenograft tumors, which show chemosensitivity comparable with the results of > or =50% patient tumors and encompass the majority of the heterogeneous patient prostate tumors in the expression of Pgp, PSA, p53 and Bcl-2 proteins, are useful models for drug activity evaluation.
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PMID:Androgen-dependent and -independent human prostate xenograft tumors as models for drug activity evaluation. 966 91

Prostate cancer is the second most common malignancy in men in the UK. The disease is unpredictable in its behaviour and, at present, no single investigative method allows clinicians to differentiate between tumours that will progress and those that will remain quiescent. There is an increasing need for novel means to predict prognosis and outcome of the disease. The aim of this study was to assess the value of artificial neural networks in predicting outcome in prostate cancer in comparison with statistical methods, using a combination of conventional and experimental biological markers. Forty-one patients with different stages and grades of prostate cancer undergoing a variety of treatments were analysed. Artificial neural networks were used as follows: eight input neurons consisting of six conventional factors (age, stage, bone scan findings, grade, serum PSA, treatment) and two experimental markers (immunostaining for bcl-2 and p53, which are both apoptosis-regulating genes). Twenty-one patients were used for training and 20 for testing. A total of 80% of the patients were correctly classified regarding outcome using the combination of factors. When both bcl-2 and p53 immunoreactivity were excluded from the analysis, correct prediction of the outcome was achieved in only 60% of the patients (P = 0.0032). This study was able to demonstrate the value of artificial neural networks in the analysis of prognostic markers in prostate cancer. In addition, the potential for using this technology to evaluate novel markers is highlighted. Further large-scale analyses are required to incorporate this methodology into routine clinical practice.
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PMID:Neural network analysis of combined conventional and experimental prognostic markers in prostate cancer: a pilot study. 968 1

The prognostic value of immunohistochemical staining of P53, BCL-2, p27kip1, PSA, AR and MIB-1 was compared with that of established prognostic variables (Gleason score, surgical margins, tumour volume) following radical prostatectomy. Five groups were selected: negative margins with stable serum PSA (n=11), negative margins with rising serum PSA (n=7), positive margins with stable serum PSA (n=7), positive margins with rising serum PSA (6) and patients with micrometastatic disease diagnosed in lymph nodes removed during radical prostatectomy (n=8). Gleason score and tumour volume were of prognostic significance and immunohistochemical staining for MIB-1 and BCL-2 showed added independent prognostic significance in multivariate analysis.
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PMID:Prognostic markers in clinically localised prostate cancer. 1008 30

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

To determine the potential role of p53 inactivation in prostate cancer, we studied a well characterized cohort of 86 patients treated with radical prostatectomy. We analyzed patterns of p53, mdm2, and p21/WAF1 expression by immunohistochemistry. Results were then correlated with clinicopathological parameters of poor outcome, including time to PSA relapse. In addition, data were also correlated with proliferative index, as assessed by Ki67 antigen detection. p53-positive phenotype, defined as identification of nuclear immunoreactivity in > 20% of tumor cells, was observed in 6 of 86 cases (7%). An association was observed between p53-positive phenotype and decreased time to PSA relapse (P < 0.01). mdm2-positive phenotype, defined as > or = 20% of tumor cells displaying nuclear immunoreactivity, was observed in 28 of 86 cases (32.5%). mdm-2-positive phenotype was found to be associated with advanced stage (P = 0.009). p21-positive phenotype, defined as > 5% of tumor cells with nuclear immunoreactivity, was observed in 28 of 86 cases (32.5%). An association was observed between p21-positive phenotype and high Ki67 proliferative index (P = 0.002). Patients with p21-positive phenotype had a significant association with decreased time to PSA relapse (P = 0.0165). In addition, a significant association was found between p21-positive phenotype and coexpression of mdm2 (P < 0.01). Forty-three of 86 cases (50%) were found to have one or more alterations, and patients with any alteration were found to have a higher rate of PSA relapse (P < 0.01). It is our hypothesis that a pathway of prostate cancer progression involves p53 inactivation caused by mdm2 overexpression and that p21 transactivation in this setting is due to an alternative signaling system, rather than through a p53-dependent mechanism.
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PMID:Inactivation of the p53 pathway in prostate cancer: impact on tumor progression. 1047 90

A prospective study on 16 patients with advanced (stage III and IV) prostate cancer was carried out. TNM stage, general clinical status, serum PSA level, the histological type and Gleason's grade of the tumor were registered. Total androgen blockade or single-drug therapy (flutamide) was performed. On average, 4.81 months after the start of therapy rebiopsy, serum PSA determination and general clinical examination were performed. Histologic examination before and after treatment of HE-stained slides, as well as apop-tag reaction to show apoptotic cells, p53, bcl(2), and Ki-67 immunostaining. Clinical improvement manifested by regression or lack of progression was observed in 10 patients. Increase of the apoptotic index and decrease of the mitotic index was detected in these cases. Serum PSA level decreased in all patients except in 3 fatal cases. The 6 clinically nonresponders who died after the second biopsy did not show an increased apoptotic or decreased mitotic index. Ki-67 positivity correlated well with the mitotic activity. Mutant p53 expression was higher in patients in whom antiandrogen therapy was ineffective. The bcl(2) expression was a characteristic of the tumors of patients who later died. These results show that the degree of induction of apoptosis in prostate carcinoma by hormonal therapy varies from case to case. A given prostate cancer patient's response to therapy may be predicted by following apoptotic and mitotic activity, as well as Ki-67 and p53 expression in repeated biopsies.
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PMID:Apoptosis, mitosis, p53, bcl(2), Ki-67 and clinical outcome in prostate carcinoma treated by androgen ablation. 1059


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