Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.
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PMID:Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines. 138 43

Histologic grade, DNA ploidy, and percentage tumor area were assessed in prostatectomy specimens from 73 patients with clinical stage B adenocarcinoma of the prostate and analyzed for their value as predictors of tumor progression. Further, the relationship between percentage tumor area and DNA ploidy was studied. Percentage tumor area was the indicator most strongly associated with the likelihood of tumor extension beyond the capsule of the prostate and of tumor progression as assessed in a logistic regression model. Grade was slightly superior to percentage area in predicting time to progression in a Cox model analysis. Increasing percentage tumor area was associated with an increased likelihood of aneuploidy. Little additional predictive ability was obtained with the concurrent use of two indicators in multivariate analysis, suggesting a high degree of interrelatedness of percentage tumor area, histologic grade, and DNA ploidy. DNA ploidy was not an independent predictive factor, and from a practical standpoint histologic grade and percentage tumor area were more important predictors of tumor progression than DNA ploidy.
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PMID:Histologic grade, DNA ploidy, and intraglandular tumor extent as indicators of tumor progression of clinical stage B prostatic carcinoma. A direct comparison. 174 83

Over a 16-year period (1966 to 1981), 349 patients underwent radical retropubic prostatectomy for pathologic stage B adenocarcinoma of the prostate. Nuclear DNA content was measured by flow cytometry on available archival material of 283 patients. Two hundred sixty-one patients (92%) had high-quality histograms. The ploidy distribution was as follows: DNA diploid, 177 (68%); DNA tetraploid, 74 (28%); and DNA aneuploid, 10 (4%). The average follow-up was 9.4 years. At the time of follow-up, 53 patients (20%) within the study group had developed tumor progression: 22 local, 23 systemic, and 8 both. The ploidy distribution of the population that developed tumor progression was 27 DNA diploid (51%), 16 DNA tetraploid (30%), and 10 DNA aneuploid (19%). This ploidy distribution is significantly different from that found for the nonprogression group with stage B disease. Overall, 31% of patients with DNA nondiploid tumors had tumors that progressed compared with 15% of patients with DNA diploid tumors. All (100%) DNA aneuploid tumors progressed. The DNA ploidy distribution of all pathologic stage B prostate cancers differs significantly from that found in more advanced stages (C and D1) previously reported for the same time interval. However, the ploidy distribution of stage B tumors that progressed closely resembles that of the stage C and D1 tumors. These results further support the working hypothesis that nuclear DNA content has marked prognostic significance for patients with adenocarcinoma of the prostate. It seems to us that analysis of ploidy by flow or static cytometry will become an essential tool for treating patients with localized prostate cancer.
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PMID:Stage B prostate adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis. 230 81

The role of staging transurethral resection of the prostate in the management of stage A prostate cancer is controversial. The accuracy of staging transurethral resection, A1/A2 substaging and probability of progression tables for predicting cancer progression was evaluated in untreated patients with stage A adenocarcinoma of the prostate who were followed for at least 5 years. Survival free of disease was predicted correctly in 93% of 52 patients who underwent staging transurethral resection of the prostate, 92% of 96 with the probability tables and in 85% of 96 using a common criteria for A1 and A2 substaging. Staging transurethral resection of the prostate upgraded patient risk in 7% of the low risk patients predicted by the probability tables and 14% of the stage A1 cancer patients. Staging transurethral prostatectomy and the probability of progression tables were more accurate in predicting survival free of disease than the A1/A2 substaging system. Comparison of the predictive accuracy of staging transurethral prostatectomy to that of the probability of progression tables showed no significant difference. There was no additional benefit from combining the 2 methods. When the probability of progression tables are used to predict cancer progression it may be unnecessary to use staging transurethral resection of the prostate in the patient with stage A prostate cancer.
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PMID:The predictive accuracy of staging transurethral resection of the prostate in the management of stage A cancer of the prostate: a comparative evaluation. 234 75

DNA content of prostatic adenocarcinoma was determined by flow cytometry on formalin-fixed, paraffin-embedded tissue from 57 radical prostatectomies. This was done to define the relationship of aneuploidy to prostatic adenocarcinoma grade, volume, and pathologic stage and to examine its utility in candidates for surgical treatment. Aneuploidy was found in 26 (46%) cases. With one exception, all of the aneuploid cases were found in tumors larger than 4 cc. The percentage of aneuploid cases increased with advancing pathologic stage, and it was highest in those cases with lymph node metastases. This percentage was also higher among more poorly differentiated tumors. However, diploid tumors were also found among these groups, and the relationship between aneuploidy versus pathologic stage and grade did not achieve statistical significance. Except for a 91% specificity for tumor volume greater than 4 cc, the sensitivity and specificity of DNA content analysis to predict these groups was low (50% to 72%). It is concluded that aneuploidy is a later event linked to tumor progression, but it is not a requirement for progression to occur. The overlap in aneuploid and diploid tumor behavior precludes the use of DNA content analysis as an independent predictor to direct preoperative treatment of prostatic carcinoma.
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PMID:DNA content in prostatic adenocarcinoma. A flow cytometry study of the predictive value of aneuploidy for tumor volume, percentage Gleason grade 4 and 5, and lymph node metastases. 238 3

The extent of tumor in prostatectomy specimens was determined by a grid method in 117 patients with prostatic adenocarcinoma. A plastic strip or ruler with squares of 3.0 mm was used, and the ratio of squares overlying carcinoma to the total number of squares overlying prostate tissue was calculated. This grid ratio, which represents an estimate of the percentage of the prostate involved by tumor, was a significant prognosticator closely tied to the likelihood of tumor progression and to survival time, as assessed by logistic regression analysis and a proportional hazard model. The grid ratio was better than histologic grade in predicting tumor progression and patient survival; also, the ratio was more objective than histologic grade as judged by interobserver agreement values. Only slight improvement in prognostication was obtained with concurrent use of both extent and grade. The grid ratio method was slightly better in predicting tumor progression and patient survival than a second method of assessing the percentage of prostatic tissue involved by tumor, the pathologist's percentage estimate. These results indicate that it is important to quantitate tumor extent within prostatectomy specimens; such quantitation need not require step-sectioning of the entire prostate and an expensive and time-consuming method such as computerized morphometrics but rather may be performed by a simple estimate of the percentage of the prostate involved by tumor. Reporting of histologic grade and tumor extent in the prostate gland is recommended as both appear to be important in identifying those patients at risk for a poor outcome after prostatectomy for prostatic carcinoma.
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PMID:Intraglandular tumor extent and prognosis in prostatic carcinoma: application of a grid method to prostatectomy specimens. 238 73

The Dunning R-3327 rat prostatic adenocarcinoma and its sublines have been developed as a model system to study prostate tumor progression. We have used this system to study the changes in androgen receptor (AR) and AR mRNA expression which occur during tumor progression from androgen dependent to androgen independent growth. Dorsal prostate and all tumor sublines contained a 10-kilobase AR mRNA on Northern blot analysis. The levels of AR mRNA in each subline compared to dorsal prostate (100%) were: H (75%) greater than G (48%) greater than HI (25%) greater than HI-F = AT-1 = AT-3 = MAT-Lu = MAT-Ly-Lu = less than 5%. Immunocytochemistry showed AR predominantly in acinar epithelial cells of dorsal prostate and the androgen sensitive H subline. In the H subline, both acinar epithelial cells and locally invasive adenocarcinoma cells within the stroma showed positive immunostaining. The androgen responsive, anaplastic G subline also showed strong positive immunostaining. The androgen resistant AT-1 and MAT-Lu sublines lacked immunostaining for the AR. Steroid autoradiography revealed a similar cellular distribution of AR. These data suggest that in the Dunning system the loss of androgen binding and responsiveness is primarily due to selective changes in gene expression and not to gene rearrangements or posttranscriptional or translational modification of the AR mRNA or protein.
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PMID:Expression and localization of androgen receptor in the R-3327 Dunning rat prostatic adenocarcinoma. 240 76

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels were measured in 117 patients with prostatic adenocarcinoma, in 9 patients with prostatic hyperplasia and in 14 patients with other malignancies to compare the clinical usefulness of the PSA and PAP levels. PSA was elevated (PSA+) in 14 of 18 untreated patients (78%) with prostatic cancer. PAP was elevated (PAP+) only in 3 of these untreated cases (17%). Also in previously treated patients PSA was more often positive than PAP. PSA was positive in 40 of the 99 treated patients (40%), PAP was elevated only in 21 cases (21%). There was a significantly (P less than 0.001) higher tendency towards elevated PSA in the prostatic cancer patients: 32 (27%) patients with PSA+ and PAP- compared with only 2 cases (2%) with PAP+ and PSA-. The PSA+/PAP- patients were analyzed further. In seven of them the PSA level also returned to its normal level after orchiectomy or/and radiotherapy. In two patients the PSA levels indicated tumor progression earlier than PAP, their PAP levels did not rise until bone metastasizing was evident. There were also progressive disease in some patients evidenced only by increased PSA levels. In addition to cancer patients the PSA level was increased in three (30%) of the prostatic hyperplasia patients. It was also elevated in three patients with other malignancies. However, these three patients also had prostatic hyperplasia and the increase in the PSA level is considered more likely to be due to that.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostate-specific antigen as a marker of adenocarcinoma of prostate. 247 59

Steady-state levels of c-Ha-ras mRNA were measured in eight sublines of the Dunning R3327 rat prostatic adenocarcinoma. As a control, normal dorsal prostate tissue was studied. Increased expression of c-Ha-ras is associated with tumor progression in one lineage of the Dunning R3327 system (H to AT1 to MAT-Lu and MAT-Ly-Lu). Here ras mRNA increases as the tumor advances from androgen dependence and a high degree of differentiation to an anaplastic aneuploid phenotype with high metastatic potential. However, in the other Dunning lineage (H to HI to HI-F to AT3), expression of c-Ha-ras is variable and does not correlate with tumor progression. Immunocytochemistry showed that levels of the c-Ha-ras p21 protein paralleled steady-state mRNA levels in variants. Transfection assays, using NIH/3T3 cells, suggested that the ras loci were not activated in the R3327 tumors. Levels of c-Ki-ras mRNA were also measured in the Dunning tumors; these did not correlate with tumor progression in either lineage. Expression of N-ras mRNA was not detected in the Dunning tumors.
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PMID:Expression of ras proto-oncogenes in the Dunning R3327 rat prostatic adenocarcinoma system. 306 50

Prostate cells of human and rat origin produce polyamines in high content, whose apparent functions relate to cellular proliferation and secretory activities. Formation is dependent on the enzyme ornithine decarboxylase (ODC) which is irreversibly inhibited by alpha-difluoromethylornithine (DFMO). It has been postulated that pretreatment with DFMO may render cells more susceptible to subsequent chemotherapy. Copenhagen X Fischer F1 rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were given DFMO or adriamycin (ADR), alone or in combination. Those receiving DFMO were continuously provided the drug ad libitum, in water (2.5%), for the duration of the experiment, beginning 2 days prior to ADR administration. At intervals, tumor sizes were measured, animal survivals noted and comparisons made to nontreated, tumor-bearing controls. The results indicate that ADR alone or in combination with DFMO significantly reduced tumor progression, but that only combination therapy significantly prolonged survivals. Decreased tumor progression produced by DFMO alone was not statistically significant. Differences produced with combined use were additive and suggest that DFMO may augment ADR chemotherapy.
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PMID:Combination therapy using polyamine synthesis inhibitor alpha-difluoromethylornithine and adriamycin in treatment of rats carrying the Dunning R3327 MAT-LyLu prostatic adenocarcinoma. 311 12


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