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

Amplification of the MDM2 gene, which maps to chromosome band 12q13 and encodes a p53-binding protein, may result in functional inactivation of p53 and has been observed in various bone and soft tissue sarcomas. Published studies have included few cases of Ewing's sarcoma (ES) or peripheral neuroectodermal tumour (PNET), a tumour group in which alterations of the p53 pathway have so far not been extensively studied. We examined two ES cell lines, RD-ES and SK-ES-1, and 30 specimens from 27 patients (24 ES, 6 PNET; 19 primary, 4 local recurrence, 7 metastasis) for MDM2 gene amplification by Southern blot analysis. All 30 clinical specimens had been confirmed to contain sufficient ES/PNET DNA by the demonstration of a rearrangement of the t(11;22)-associated EWS gene using an EWS cDNA probe on the same blots. MDM2 gene amplification was detected in 3 of 30 specimens (10 per cent), including two ES and one PNET, but in neither of the cell lines. The three cases with amplification were morphologically typical primary tumours. Two of the three cases also showed co-amplification of the CDK4 gene, which encodes a cyclin-dependent kinase and also maps to band 12q13. Clinically, all three cases had metastatic disease at diagnosis, compared with only 1 of 15 MDM2-negative cases where the primary tumour was studied. The difference was statistically significant (P = 0.005), suggesting an association of MDM2 amplification with advanced stage.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:MDM2 and CDK4 gene amplification in Ewing's sarcoma. 773 17

p27kip1 (p27) protein is an inhibitor of cyclin and cyclin-dependent kinase complexes and prevents progression of cells from G1 to the S phase of the cell cycle. p27 might have tumor suppressor activity, and decreased p27 expression is associated with aggressive tumor behavior in several human malignancies. The object of this study was to evaluate p27 expression in prostatic adenocarcinoma treated by radical prostatectomy and to assess its association with numerous morphologic and clinical features. One hundred thirty-eight prostatic adenocarcinomas were evaluated for p27 expression by quantifying nuclear immunohistochemical staining. p27 expression was tested for association with patient age, family history of prostate cancer, preoperative serum prostate-specific antigen level, Gleason score, extraprostatic extension, seminal vesicle involvement, lymph node metastases, tumor-node-metastasis stage, DNA ploidy by flow cytometric analysis, and subclinical biochemical failure. p27 expression was analyzed as a continuous variable, and we also classified the tumors as low expressors (< 50% of cells p27 positive) or high expressors (> 50% of cells p27 positive) for comparison. Patients with adenocarcinomas that exhibited low p27 expression had higher mean Gleason scores than did high expressors (7 vs. 6.2, respectively; P = .002). Low p27 expression correlated with positive surgical margins (P = .05), seminal vesicle involvement (P = .007), lymph node metastasis (P = .03), and aneuploid cancers (P = .003), but it did not correlate with subclinical biochemical failure. p27 expression correlated with a number of prognostic morphologic features in prostatic adenocarcinoma, and the evaluation of p27 expression might provide additional prognostic information.
 ...
PMID:Expression of p27kip1 in prostatic adenocarcinoma. 957 81

In the USA, the incidence of kidney cancer has increased 43% since 1973. The risk of the disorder is higher in men than in women and increases with age. The von Hippel-Lindau tumour-suppressor gene is inactivated in over 75% of sporadic cases. Metastatic disease is present in 20-30% of patients at diagnosis. Early-stage kidney cancer is treated with a radical nephrectomy, but under certain circumstances a partial nephrectomy may be done. Tumour thrombus into the vena cava or right atrium requires thoracotomy and hypothermic circulatory arrest for successful removal of the tumour, but should not be done if extensive nodal or frank metastatic disease is present. Interleukin-2 is the systemic therapy of choice for metastatic disease at present, with long-term relapse-free survival of 5-8%. Several treatments including anti-angiogenesis drugs, cyclin-dependent kinase inhibitors, and differentiating agents are being actively investigated. Fluorouracil has a 10-15% response rate, and surgical excision of isolated metastases should always be considered. Therapy for metastatic renal cancer remains inadequate, but recent developments in basic and clinical research suggest future improvement.
 ...
PMID:Kidney cancer. 1002 13

Metastatic prostate cancer is a leading cause of cancer-related death in men. Although most patients will respond to androgen ablation as initial systemic therapy, nearly all patients will develop androgen-independent prostate cancer (AI CaP) and will succumb to the disease. Advances in molecular biology have demonstrated mutations in and persistent expression of the human androgen receptor in metastatic disease. Furthermore, recent evidence indicates that an apoptotic block through p53 mutations or bcl-2 overexpression may have a potential role in the poor responses seen with standard chemotherapy. Presently, the six general treatment options available for AI CaP are best supportive care, radiation therapy, radioisotopes, secondline hormonal therapy, chemotherapy (single agent or combination), and investigational therapies such as monoclonal antibodies, cyclin-dependent kinase inhibitors, matrix metalloproteinase inhibitors, and antiangiogenesis agents, among others. None of these modalities have produced durable remissions, although some have demonstrated palliative benefit. The next generation of clinical trials should not consist of futile hormonal manipulations or repetitive chemotherapy. Therapeutic strategies aimed at circumventing molecular blocks to cell death or targeting unique cancer molecules and genes will be more likely to improve quality of life and longevity. Furthermore, the aggressive use of palliative care will ensure effective caring for patients and the healing of families in the absence of cure.
 ...
PMID:Treatment options in androgen-independent prostate cancer. 1007 98

p27KIP1 is a member of the CIP/KIP family of cyclin-dependent kinase inhibitory proteins that negatively regulate cell proliferation. Recent studies reported decreased p27 expression in breast and colon carcinomas and found that the loss of p27 is associated with a poor prognosis. We report here the results of our immunohistochemical analysis of p27 in human prostate cancer. Formalin-fixed, paraffin-embedded, whole-mount sections of prostate cancer from 73 selected patients treated by radical retropubic prostatectomy were obtained from the Department of Pathology, The Methodist Hospital, Houston, Texas. Ten histologically normal and nine high-grade prostatic intraepithelia neoplasia foci were selected from these whole-mount sections, and nine cases of transplant donor prostates were chosen as controls. Also, 10 prostate cancer metastatic lymph nodes were used to compare with the primary cancer group. Sections were immunostained with a monoclonal antibody against p27 protein using the avidin-biotin complex immunohistochemical method. Immunoactivity was evaluated without knowledge of follow-up and recorded as the p27 labeling index (LI) (defined as the percentage of p27-positive cells among epithelia of the same category). The p27 (LI) in normal prostatic epithelia was 86.4+/-3.5% (the mean +/- the standard error of the mean). In contrast, the p27 immunoreactivity was significantly lower in cancers (LI: 43.5 +/-3.7%, P < .001) and in the high-grade prostatic intraepithelial neoplasia group (LI: 59.3 +/- 3.2%, P < .05). Expression of p27 in the metastatic lymph node group was significantly lower than in the other groups, including the prostate cancer cases and the cases of high-grade intraepithelial neoplasia (LI, 7.0%; P = .05). There was no association of the mean p27 LI with progression after radical prostatectomy. Nonrecurrent cases, with a mean follow-up time of greater than 5 years (n = 45), equalled 41.9%; recurrent cases, with a mean follow-up time of 18.3 months (n = 28), equalled 40.0%. The mean p27 LI was not associated with pathologic stage. Organ-confined specimens (n = 21) equalled 34.2%; cases of extraprostatic extension (n = 24) equalled 46.5%; and samples showing seminal vesicle involvement (n = 14) equalled 47.6%. In 14 cases with lymph node metastases, the mean p27 LI was 48.1% in the primary cancer (P = .2322). There was no association of the mean p27 LI with the Gleason score (P = .4747) nor with the clinical stage (P = .9914).
 ...
PMID:Levels of expression of p27KIP1 protein in human prostate and prostate cancer: an immunohistochemical analysis. 1046 75

Solid pseudopapillary tumor of the pancreas was studied in a 20-year-old woman and a 54-year-old woman. In the younger patient, the tumor had metastasized to the liver 8 years after distal pancreatectomy. In both neoplasms, the distinct histologic pattern of solid, pseudopapillary, and degenerative cystic areas was present. Analysis by means of immunohistochemistry revealed a diffuse expression for vimentin, neuron-specific enolase, and a focal positivity for al-antitrypsin, whereas epithelial markers were negative in the tumor of the older patient and only focally expressed in the tumor of the younger patient. Immunohistochemical analysis of cell cycle-associated proteins provided an overexpression of cyclin D1 and cyclin D3 in both tumors, although to varying degrees. In addition, the cyclin-dependent kinase inhibitors p21, and to a lesser extent p27, were up-regulated just as mdm2. There was no accumulation of p53 protein, and Ki67-positive cells were extremely scarce. Analysis of the liver metastases showed an immunoreactive profile similar to that of the primary tumor. The results show a deregulation of the cell cycle with overexpression of cell cycle-activating proteins D1 and D3 and a probably counterbalancing upregulation of the cyclin-dependent kinase inhibitors p21 and p27. The findings may explain the low pool of Ki67-reactive tumor cells and the generally good clinical outcome of these tumors. Whether a more profound dysbalance of the cell cycle regulation is responsible for the development of metastatic disease remains to be clarified.
 ...
PMID:Deregulated expression of cell cycle-associated proteins in solid pseudopapillary tumor of the pancreas. 1123 5

Progression through the mammalian cell cycle is facilitated by cyclin-cyclin-dependent kinase (cdk) complexes, which are activated at specific points during the cell cycle. Alteration in cyclin-cdk complexess may lead to altered cell cycle and tumorigenesis. In this study, we analyzed expression of cyclins A, D1, D3 and E in tumor tissue from 170 patients with primary invasive breast carcinomas. Immunohistochemical methods were used to detect protein expression of these cyclins. We detected positive immunoreactivity in 55 (32%), 22 (13%), 38 (22%) and 37 (21.8%) of the samples for cyclins A, D1, D3 and E, respectively. A highly statistically significant association was observed between expression of cyclin A and early relapse (p = 0.001 univariate analysis, p = 0.006 multivariate analysis) as well as cancer-specific death (p < 0.0001) during the follow-up time. No association was observed between cyclin D1 or cyclin E, respectively, and relapse of disease or survival, while cyclin D3 over-expression was associated with development of metastases during follow-up (p = 0.005 univariate analysis, p = 0.01 multivariate analysis). However, cyclin D3 did not show any statistically significant association when cancer-specific death was examined in a multivariate analysis (Cox regression for survival function).
 ...
PMID:Over-expression of cyclin A is highly associated with early relapse and reduced survival in patients with primary breast carcinomas. 1141 Aug 78

P21 (WAF1), P53 and cyclin D1 belong to the cell cycle-regulating family of proteins, and the loss of activity of proteins P53 and P21 (WAF1) seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer. The purpose of this study was to assess the relationship between P21 (WAF1), P53 and cyclin D1 immunoreactivity, and to evaluate the prognostic significance of their expression. Tissue sections from 122 paraffin-embedded colorectal carcinomas were immunostained with monoclonal antibodies. Positivity for P21 (WAF1) was found in 48 cases (39%), positivity for P53 in 96 cases (70%) and positivity for cyclin D1 in all the cases (100%). Statistical analyses revealed a statistically significant inverse correlation between P53 and P21 (WAF1)-immunopositivity and between P21 (WAF1)-immunopositivity and the degree of cyclin D1-immunopositivity, as well as an inverse correlation between P21 (WAF1) expression and clinical stage. In univariate analysis, down-regulation of P21 (WAFI) expression was associated with poor prognosis, but multivariate analysis did not confirm its independent prognostic significance. In Cox's analysis only regional lymph node invasion and hepatic metastases were proven as independent prognostic parameters. Our investigation results suggest that in colorectal cancer, the induction of P21 (WAF1) may occur mostly in a P53-dependent pathway. P21 (WAF1), as the main cyclin-dependent kinase (CDK)-inhibitor, may also inhibit the activity of cyclins such as cyclin D1.
 ...
PMID:P21 (WAF1) expression in colorectal cancer: correlation with P53 and cyclin D1 expression, clinicopathological parameters and prognosis. 1170 Aug 90

Although renal cell carcinoma accounts for only 3% of adult malignancies, it has been increasing in incidence by 2-4% per year since the 1970's. Cigarette smoking, obesity and end-stage renal disease are important risk factors. Genetic syndromes such as von Hippel-Lindau disease are also associated with an increased incidence of renal cell carcinoma. Localized disease should be treated with surgical resection. However, approximately 30% of patients present with metastatic disease. Complete resection of metastases can result in long-term survival in some individuals. Removal of the primary renal tumor in patients with unresectable disseminated disease has also been shown to improve survival in selected good performance status patients receiving systemic immunotherapy. While chemotherapy has been relatively ineffective in the treatment of renal cell carcinoma, biologic therapy with interleukin-2 or interferon does lead to responses in a minority of patients, with occasional long-term survivors. Recently, promising results have been reported with allogeneic stem cell transplantation using a non-myeloablative conditioning regimen. However, therapy for metastatic renal cell carcinoma remains inadequate. Ongoing trials with novel approaches such as anti-angiogenesis agents, cyclin-dependent kinase inhibitors, and tumor vaccines will hopefully lead to improved outcomes in this disease.
 ...
PMID:Renal cell carcinoma: current status and future directions. 1260 28

Transitional cell carcinoma (TCC) is reported to be the fifth most common solid malignancy in the U.S. Although radical cystectomy will cure a substantial number of patients with minimally invasive TCC, many patients with deeply muscle-invasive or extravesical disease who are treated with radical cystectomy alone die of metastatic TCC, as do patients with metastatic disease. The differing clinical course and the limited value of established prognosticators make analysis of new molecular parameters of interest in predicting the prognosis of patients with bladder cancer, particularly those in high-risk groups who are at risk of disease progression and recurrence. In the current review, a comprehensive MEDLINE/PubMed search of articles pertaining to the biology of TCC from 1965 to the present was performed, as well as a bibliographic review of cross references. TCC follow the general concept of multistep carcinogenesis and proceed through two distinct genetic pathways responsible for generating different TCC morphologies, namely the inactivation of cyclin-dependent kinase inhibitors in low-grade TCC and early p53-mediated abnormalities in high-grade TCC. TCC progression correlates with genetic instability and the accumulation of collaborative genetic lesions mainly involving p53, retinoblastoma, and growth factors. The bulk of these data are derived from cases of localized/locally advanced disease and none are ready yet for routine clinical application; however, the current knowledge has led to the clinical testing of novel biologic observations in several important trials. Understanding of the molecular biology of advanced bladder cancer continues to improve. It is likely that in the new millennium, real breakthroughs in the identification and therapy of high-risk, poor-prognosis patients will come from an integration of molecular modalities in the clinical application.
 ...
PMID:Current understanding of the biology of advanced bladder cancer. 1267 98


1 2 3 4 5 Next >>