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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review is concerned with computer-based image analysis (CBIA) in prostate cancer. The emphasis is placed on evaluating extent and grade of prostate cancer. The quest for reproducibility in these evaluations has provided an important area of possible application for CBIA studies. Commercially available CBIA systems allow an opportunity for increased efforts in studying the merits of CBIA in prostate cancer. Many CBIA systems with various capabilities are currently on the market. They can be described as either "general" or "dedicated" CBIA systems and are exemplified by two systems: the Werner Frei Imlab/Imtool (Werner Frei Associates, Venice, CA) and the CAS 200 (Cell Analysis Systems, Inc, Lombard, IL), respectively. "General" systems are composed of individual components with data being stored and analyzed using a personal computer (Werner Frei Imlab/Imtool). "Dedicated" systems are integrated systems, usually with little variability of either software or hardware specifications (CAS 200). It is helpful to be cognizant of the contrasting abilities provided by these two systems when evaluating which CBIA system would be most appropriate for a particular application in the study of prostate cancer.
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PMID:Computer-based image analysis of prostate cancer: comments with emphasis on use of commercially available systems. 155 39

We compared mean nuclear size and mean nuclear shape (nuclear roundness) on Feulgen-stained smears from 113 cases of prostatic carcinoma analyzed by DynaCELL system at x 100 magnification versus CAS system at x 40 where DNA can be assessed simultaneously. Correlation coefficients were 0.67 for size and -0.07 for shape. A subgroup of cases were compared at x 40 versus x 100 on the CAS system by two observers: The correlation for size ranged 0.47 to 0.49, with correlations for shape ranging from -0.19 to 0.54. In this subgroup at x 100 magnification, the correlation between CAS and DynaCELL was 0.32 for size and 0.07 for shape. At x 100 magnification on the CAS system, intraobserver correlation was 0.58 for size and 0.37 for shape with interobserver correlations of 0.36 for size and -0.05 for shape. At x 40 on the CAS system, intraobserver correlation was 0.42 for size and 0.72 for shape, with interobserver correlations of 0.06 for size and 0.45 for shape. This study shows that in comparison to video planimetry of prostatic cancer nuclei, which has been shown to have a high inter- and intraobserver correlation, the CAS 200 system provided accurate measurements of size yet not shape. Intra- and interobserver correlations were suboptimal with CAS, showing better results at x 100 for size and x 40 for shape. These results in part reflect the relative narrow range of size and shape in prostate cancer in comparison to other tumors, and the use of Feulgen smears where nuclear RNA is not stained or measured by the CAS system, potentially leading to artifactually irregular shapes.
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PMID:Nuclear morphology of prostatic carcinoma: comparison of computerized image analysis (CAS 200) versus video planimetry (DynaCELL). 178 68

More than 50% of Lobund-Wistar (L-W) strain rats developed large, palpable prostate adenocarcinomas (PAs) following treatments with N-nitroso-N-methylurea (CAS: 684-93-5) and testosterone propionate [(TP) CAS: 57-85-2], and most of the tumor-bearing rats manifested metastatic lesions. The incubation periods averaged 10.6 months. Within the same timeframe, no L-W rat developed a similar palpable PA when treated only with TP. In L-W rats, TP acted as a tumor enhancement agent, with primary emphasis on the development of prostate cancer.
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PMID:Production of autochthonous prostate cancer in Lobund-Wistar rats by treatments with N-nitroso-N-methylurea and testosterone. 346 Dec 17

A retrospective cohort mortality study of 1,008 male oil refinery workers who ever worked on the lubricating-dewaxing process of the lube oil department and who have been followed for a period of 43 years is presented. These workers were exposed to a number of solvents, primarily methyl ethyl ketone [(MEK) CAS: 78-93-3] and toluene (CAS: 108-88-3), but at levels far below the current Occupational Safety and Health Administration's standard. The standardized mortality ratio (SMR) for all causes (0.70) and the SMR for cancer (0.86) are much lower than unity when they are compared to the mortality experience of the U.S. population. Also observed in this study were 8 prostate cancer deaths (4.4 expected) with an SMR of 1.82, which was not statistically significant (P = .16). Seven of these 8 prostate cancer deaths occurred among nonwhite males, who showed an SMR of 2.47 (P = 0.53). However, only 1 prostate cancer death was seen among workers specifically assigned to the MEK units. The remaining deaths occurred among maintenance workers who had lube oil department-wide assignments. This cancer risk increased with increasing duration of employment in the lube oil department. A latency of 20 years or more was also observed for these prostate cancer deaths. In this study the processing of lubricating oils was found to be at least as important as the MEK solvents, and department-wide maintenance workers were as much at risk as the MEK unit workers. In view of this finding and findings obtained by others, it seems prudent to continue to study lubricating-dewaxing process workers, including the medical monitoring of all such workers for prostate cancer.
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PMID:Long-term mortality study of oil refinery workers. IV. Exposure to the lubricating-dewaxing process. 385 71

One hundred and twenty-four localized prostate cancer patients operated on at Johns Hopkins Hospital (JHH) since 1975 were identified. The sample was optimized for evaluation of prostate cancer progression. Based upon accurate clinical histories, these radical prostatectomy patients included 50 progressors and 74 non-progressors using appearance of serum PSA as an indication of recurrence (mean follow-up = 8.6 +/- 1.8 years, range 7-15 years). All patients included in the study had no involvement of their seminal vesicles or lymph nodes at the time of prostatectomy. Average time to progression was 3.6 +/- 2 years, range of 1-8 years. Using paraffin-embedded specimens, several five micron sections were cut and placed on Probe-On slides; one slide was H&E-stained and the other was Feulgen-stained. The H&E and Feulgen-stained slides were screened and "dotted" by pathologists at JHH and CytoDynostics, Inc. A CAS-200 Image analysis system (Cell Image Systems, Elmhurst, IL) equipped with a Cell Measurement Program version 1.2 beta, was used to capture the Feulgen-stained images and to perform the calculations. From the "dotted" areas, 150 cancer cells were selected for measurement of DNA content and 27 nuclear morphometric shape and size factors, including 21 Markovian chromatin texture variables. Additional sections were used for immunochemistry staining with an alkaline phosphatase streptavidin-biotin complex stain to detect and quantitate cancer cells binding monoclonal antibodies directed against proliferating cell nuclear antigen (PCNA) and HER-2/neu antigen. All data were entered into a statistical program (STATA) for further analysis and univariate and multivariate statistical analysis was performed using logistic regression and its stepwise variant. The biomarkers of greatest utility to detect progressors when analyzed univariately included post-operative Gleason score (p = < 0.0001), HER-2/neu antigenicity (p = 0.0147), CAS-200 DNA ploidy (p = 0.008), and twelve Markovian nuclear texture and shape features (p = < 0.0001), whereas PCNA (p = 0.160) failed. The optimal set of nuclear morphometry progression tumor features were selected using backward stepwise logistic regression estimate analysis which drops variables due to collinearity. Although post-operative Gleason score is a strong univariate predictor of progression, DNA ploidy and HER-2/neu contributed significantly to further stratification of higher risk groups within the low Gleason score subpopulation. The best Markovian features combined with post-operative Gleason score generated sensitivity = 90%, specificity = 96%, positive predictive value = 94%, negative predictive value = 93% and the area under the receiver operator curve was 0.975.
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PMID:Quantitative nuclear morphometry, Markovian texture descriptors, and DNA content captured on a CAS-200 Image analysis system, combined with PCNA and HER-2/neu immunohistochemistry for prediction of prostate cancer progression. 752 56

The biological behavior of a prostate cancer can be predicted to some degree by the volume and extent (stage) of the tumor, and its histological grade. The deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another independent prognostic factor for localized prostate cancer. We determined the DNA ploidy value of each individual focus of cancer in radical prostatectomy specimens using nuclear image analysis (CAS 200 system). Ploidy results were correlated with the volume, Gleason grade and zone of origin (transition zone or peripheral zone) of each tumor, and with the presence of extracapsular extension or seminal vesicle invasion. There were 141 separate cancers in 68 patients (mean 2.1 per prostate): 9 clinical stage A1, 22 stage A2, 23 stage B1 and 14 stage B2. DNA ploidy correlated significantly (p < 0.0001) with volume, grade, extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to 0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers confined to the prostate 76% were diploid, compared to only 13% of those with extraprostatic spread. Most cancers of transition zone origin (86%) were diploid, compared to only 49% of peripheral zone cancers, and ploidy and volume relationships were significantly different for peripheral zone cancers compared to transition zone cancers. All small nondiploid cancers arose in the peripheral zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc. We conclude that prostate cancers that are nondiploid are highly likely to have adverse pathological features. Some small prostate cancers contain a nondiploid cell population and these cancers arise predominantly within the peripheral zone of the prostate. Ploidy and volume relationships provide further support for the hypothesis that there is a difference in malignant potential between cancers of peripheral zone and transition zone origin.
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PMID:Some small prostate cancers are nondiploid by nuclear image analysis: correlation of deoxyribonucleic acid ploidy status and pathological features. 815 76

Ultrasonography of the prostate detects some cancers that are not palpable, but the pathologic features of such cancers have not been well described. Since screening trials consistently find sonography more sensitive (though less specific) than digital rectal examination, nonpalpable cancers that are visible as hypoechoic lesions on ultrasound have been postulated to be early cancers of limited malignant potential and may not require aggressive treatment. To test this hypothesis, we determined the pathologic features and DNA ploidy value of prostate cancers in 63 radical prostatectomy specimens taken from patients with clinical stage T1 (n = 28) and T2 (n = 35) prostate cancer. In 40 patients (63%), the cancer appeared hypoechoic on ultrasound. The median volume of these cancers was 4.19 cm3 (range 0.45-19.22); 80% exhibited extra-capsular extension (ECE); 30% had seminal vesicle invasion (SVI); and 95% were nondiploid by nuclear image analysis (CAS 200 system). In patients with isoechoic cancer, tumor volume was significantly less (median 0.38 cm3) and ECE and SVI occurred less frequently (13% and 0%, respectively). Only seven (30%) had nondiploid tumors. In 35 patients, the tumor was palpable, and the pathologic features and DNA ploidy values (94% nondiploid) of these cancers were similar to those of the tumors that were visible on ultrasound. In seven patients, the cancer was visible by ultrasound but not palpable by digital rectal examination. Median tumor volume was 1.72 cm3 (range 0.45-18.98); four patients (57%) had ECE; one (14%) had SVI, and six (86%) had nondiploid cancers. We conclude that most cancers that appear hypoechoic on ultrasound are clinically important and exhibit aggressive pathologic features. Palpable cancers and sonographically visible cancers are similar and should be staged and treated similarly.
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PMID:Comparison of the pathologic features and DNA ploidy value of prostate cancers detectable by sonography and by palpation. 825 41

CGP 48664A (2-(4-aminoiminomethyl)-2,3-dihydro-1H-inden-1-ylidene dihydrochloride, CAS 149400-88-4) is a new potent inhibitor of S-adenosylmethionine decarboxylase with antitumor properties. In view of the eminent clinical problems in the treatment of non hormone dependent prostatic cancer, the antiproliferative potency of this compound was tested in Dunning MAT-LyLu rat prostatic adenocarcinoma. The compound proved inefficient in preventing the growth of this tumor, even at a near toxic dose. A reason for the lacking effect is presumably the inadequate accumulation of the drug in the tumor cells due to the excessive growth rate of the MAT-LyLu xenografts. Tumor growth seems not to be accompanied by a proportionally rapid vascularization of the tumor mass. CGP 48664A was found to be a potent inhibitor of polyamine oxidase. This property of the drug may have contributed to the activation of the phagocytic capacity of peritoneal macrophages from tumor-bearing rats.
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PMID:Observations with an S-adenosylmethionine decarboxylase inhibitor in rats with prostatic adenocarcinoma. 890 Nov 56

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.
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PMID:Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer. 1007 20

Src family kinases (SFK) are currently being investigated as targets for treatment strategies in various cancers. The novel SFK/Abl inhibitor, dasatinib (BMS-354825), is a promising therapeutic agent with oral bioavailability. Dasatinib has been shown to inhibit growth of Bcr-Abl-dependent chronic myeloid leukemia xenografts in nude mice. Dasatinib also has been shown to have activity against cultured human prostate and breast cancer cells. However, the molecular mechanism by which dasatinib acts on epithelial tumor cells remains unknown. In this study, we show that dasatinib blocks the kinase activities of the SFKs, Lyn, and Src, in human prostate cancer cells at low nanomolar concentrations. Moreover, focal adhesion kinase and Crk-associated substrate (p130(CAS)) signaling downstream of SFKs are also inhibited at similar concentrations of dasatinib. Consistent with inhibition of these signaling pathways, dasatinib suppresses cell adhesion, migration, and invasion of prostate cancer cells at low nanomolar concentrations. Therefore, dasatinib has potential as a therapeutic agent for metastatic prostate cancers harboring activated SFK and focal adhesion kinase signaling.
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PMID:Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. 1623 Mar 77


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