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A W Partin

Publications and source records attributed to A W Partin.

228 records · Page 13Linked to original sources
PubMed1989

The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia.

This study was designed to investigate the relationship of serum prostate-specific antigen to prostatic size and hormonal stimulation. Seven patients with benign prostatic hyperplasia were treated for six months with nafarelin acetate and then followed for an additional six months. Nafarelin acetate is a potent luteinizing-hormone-releasing hormone agonist which causes reversible testosterone deprivation resulting in involution of the prostate. During therapy and follow up, serum prostate-specific antigen correlated with: 1) serum testosterone (p less than 0.001); 2) quantity of prostatic epithelium (p less than 0.001); and 3) prostatic size (p less than 0.05). Before therapy, serum prostate-specific antigen (mean +/- SD) was 0.43 +/- 0.2 ng./ml. per gram of epithelium. This did not change significantly after six months of androgen deprivation (0.48 +/- 0.36), although the ratios of prostate-specific antigen to testosterone and to prostatic size each changed significantly. Despite testosterone levels in the castrate range at six months, five of seven patients had serum prostate-specific antigen concentrations above the female range and three of seven patients had prostatic biopsies containing columnar epithelium which stained positively for prostate-specific antigen. These results demonstrate that serum prostate-specific antigen is related to prostatic size, prostatic epithelial weight, and testosterone stimulation. However, prostatic size is not a good predictor of serum prostate-specific antigen because there is tremendous variation in the relative amount of epithelium in a prostate; in this study the ratio of prostatic size to epithelial weight varied threefold. Furthermore, although testosterone determines prostatic size and amount of prostatic epithelium, it may not totally control prostate-specific antigen production.

Aged↗
PubMed1989

Fourier analysis of cell motility: correlation of motility with metastatic potential.

We report the development of a computerized, mathematical system for quantitating the various types of cell motility. This Fourier analysis method simultaneously quantifies for individual cells (i) temporal changes in cell shape represented by cell ruffling, undulation, and pseudopodal extension, (ii) cell translation, and (iii) average cell size and shape. This spatial-temporal Fourier analysis was tested on a series of well-characterized animal tumor cell lines of rat prostatic cancer to study in a quantitative manner the correlation of cell motility with increasing in vivo metastatic potential. Fourier motility coefficients measuring pseudopodal extension correlated best with metastatic potential in the cell lines studied. This study demonstrated that Fourier analysis provides quantitative measurement of cell motility that may be applied to the study of biological processes. This analysis should aid in the study of the motility of individual cells in various areas of cellular and tumor biology.

Adenocarcinoma↗
PubMed1988

Early cell motility changes associated with an increase in metastatic ability in rat prostatic cancer cells transfected with the v-Harvey-ras oncogene.

The development of metastatic ability by cancer cells is a multifactorial process whose temporal events are complex and poorly understood. One step in the metastatic process may involve cell motility. Previous studies reported correlations between motility and metastatic ability. Whether this correlation, seen in cancer cells maintained for long periods of time, is an epiphenomenon developing late in the growth of the cancer as a selection artifact of continuous passage, or is critically required for the acquisition of metastatic ability is unknown. To investigate the relationship between cell motility and the acquisition of metastatic ability, advantage was taken of recently developed DNA transfection methods for inducing high metastatic ability in initially low metastatic cancer cells. The Dunning AT2.1 cell line, a clonal rat prostatic cancer cell line with low metastatic ability, was transfected with a plasmid containing the neomycin resistance gene alone or in combination with the v-Harvey-ras oncogene. A series of the transfected cells was isolated by limiting dilution. After the first in vitro passage following transfection, cells were inoculated into rats to characterize their metastatic ability. The same transfectants were simultaneously studied using our visual grading system of cell motility to study the early motility changes associated with newly acquired metastatic ability. The data demonstrate increased membrane ruffling, pseudopodal extension, and cell translation (translocation) in the v-H-ras-transfected cell lines with high metastatic potential.

Animals↗
PubMed1988

Metastatic potential prediction by a visual grading system of cell motility: prospective validation in the Dunning R-3327 prostatic adenocarcinoma model.

A method for accurate prediction of prognosis in individual patients with prostatic carcinoma does not exist. The limitations of pathological grading systems may result from the failure of standard pathological examination of fixed dead tissue to accurately assess the biological and metastatic behavior of live tumor cells. Many of the sublines of the Dunning R-3327 rat prostatic adenocarcinoma are histologically similar yet differ in metastatic potential. Cells from the Dunning model were grown in culture and filmed by time-lapse videomicroscopy. These cells exhibited characteristic membrane ruffling, pseudopodal extension, and cellular translation that could be graded with 80% reproducibility. Individual cells from sublines with high metastatic potential were separated from cells from sublines of low metastatic potential in 96% of cases. We have applied our cell motility grading system to prospectively classify the metastatic potential of neoplastic cells. The mean motility grades of sublines of high and low metastatic potential differed significantly (Mann-Whitney-Wilcoxon, P less than 0.0005). Among seven sublines in which the grading system was developed, individual cells were correctly classified as high or low metastatic in 71% of cases by ruffling or pseudopodal extension, 73% of cases by translation, and 75% of cases by motility index, an average of the three parameters of motility. Among four newly tested sublines, cells from a low metastatic and high metastatic sublines were perfectly classified. Cells from two other low metastatic sublines were misclassified. When all 88 cells from the 11 sublines were classified, high metastatic cells were detected with 94% sensitivity and 50% specificity. The predictive value of a determination of low metastatic was 93%, whereas the predictive value of an assignment of high metastatic was 52%. The ability to detect and accurately classify most highly metastatic cells while rarely erring in a classification of low metastatic potential suggests that a grading system of cancer cell motility should be evaluated in human prostatic carcinoma. The motility of live prostatic carcinoma cells may predict patient prognosis better than standard pathological grading systems.

Adenocarcinoma↗
PubMed1988

Nuclear roundness factor measurement for assessment of prognosis of patients with prostatic carcinoma. I. Testing of a digitization system.

Standard pathological grading systems for prostatic carcinoma based upon glandular architectural pattern or nuclear anaplasia have failed to predict the prognosis of individual patients. Quantitative morphometric analysis of nuclear shape has predicted the outcome of patients with prostatic carcinoma when evaluated by some but not all reported studies. Calculation of nuclear roundness factor by different investigators was complicated by equipment differences and lack of standardized methods for acquiring and reporting data. We have improved our system for nuclear contour digitization and determined its theoretical limitations by digitizing standardized objects. Measurement errors were independent of orientation or location of an object within a microscopic or digitizer tablet field, speed of digitization and introduction of a microscope extension tube and light emitting diode cursor. Perimeters and areas of circles and squares of actual or digitizer-projected diameter or sidelength greater than five mm. were measured with a reproducibility and accuracy of greater than or equal to 90%. When a microscopic circle of diameter similar to prostatic carcinoma nuclei was digitized at a magnification of 2580 X, perimeter and area measurements differed within or between observers by less than 5% and were more than 95% accurate. In order to calculate accurately and evaluate NRF for use in assessing the prognosis of patients with prostatic carcinoma investigators must precisely describe their digitization system, standardization method and observer reproducibility and accuracy when measuring circles that approximate the projected size of prostatic carcinoma nuclei.

Carcinoma↗
PubMed1988

Nuclear roundness factor measurement for assessment of prognosis of patients with prostatic carcinoma. II. Standardization of methodology for histologic sections.

A nuclear shape descriptor, nuclear roundness factor, predicted outcome in patients with prostatic carcinoma whereas standard pathological grading by Gleason's architectural pattern did not. The inability of others to duplicate those successes warranted a reevaluation of the technique for NRF measurement. We previously described our digitization system and measured the perimeter and area of a microscopic circle similar in size to prostatic carcinoma nuclei with a reproducibility and accuracy of greater than 95%. We have applied our improved system to nuclear contour digitization and standardized our method for NRF measurement. In order to calculate accurately the NRF for prostatic carcinoma, the histologic section must have been reviewed by a pathologist and 150 nuclei traced after random selection. NRF measurement reproducibility within and between observers exceeded 90%. This system for NRF measurement successfully predicted outcome in 13 of 15 patients with stages A2, B1, and B2 prostatic carcinoma. Our success with a carefully tested and improved system for NRF determination warrants further evaluation of NRF for assessment of prognosis of patients with prostatic carcinoma.

Carcinoma↗
PubMed1987

Prediction of metastatic potential by a new grading system of cell motility: validation in the Dunning R-3327 prostatic adenocarcinoma model.

Many grading systems for prostatic carcinoma exist; however, none allows pathologists to accurately predict the prognosis of individual patients. Examination of dead fixed histological sections of malignancies may not be the best way to predict the biological behavior of living dynamic tumors. We have developed a grading system that reproducibly characterized the motility of living cancer cells. In the Dunning R3327 rat prostatic adenocarcinoma model, three sublines of high metastatic potential (greater than 90%) were distinguished from four sublines of low metastatic potential (less than 10%). Individual cells from these sublines were correctly identified as high or low metastatic in 96% of cases by grading membrane ruffling, pseudopodal extension, and vectoral translation.

Adenocarcinoma↗
PubMed1987

Time lapse videomicroscopic identification of Dunning R-3327 adenocarcinoma and normal rat prostate cells.

A method for accurate prediction of prognosis in human prostatic cancer does not exist. The limitations of pathologic grading systems may result from the failure of standard pathological examination of fixed dead tissue to accurately assess the biological behavior of live tumor cells. Many of the sublines of the Dunning R-3327 rat adenocarcinoma are histologically similar yet differ widely in their metastatic potential. The nonmetastatic G, occasionally metastatic AT-1 and AT-2, and highly metastatic AT-3 and MAT-Lu Dunning sublines, and normal dorsal prostate were grown in culture and filmed by time-lapse videomicroscopy. Cell membrane ruffling, undulation and pseudopodal extension, vectoral translation, irregularity of pathway, and overall subjective motility (gestalt) were visually graded. Intra-assay, intra-observer, and inter-observer reproducibility were 75, 80 and 75% respectively. The combination of ruffling, pseudopodal extension and vectoral translation was most successful in identifying the six sublines. To validate this technique prospectively, five tumor sublines and two normal prostates were graded by 10 observers unfamiliar with the technique. Fifty-nine percent of unknowns were correctly identified when motility profiles were compared to previously developed standards by least sum of squares analysis. We devised a new technique for characterizing the motility of living prostate cells which was more accurate in identifying normal rat prostate and the Dunning sublines than standard pathological examination. Prostatic cancer cell motility may reflect biological behavior and metastatic potential and thus contribute to the assessment of an individual patient's prognosis.

Adenocarcinoma↗
PubMed1987

Correlation of prognosis to nuclear roundness and to flow cytometric light scatter.

The application of quantitative pathology to the study of malignant tumors is discussed, with emphasis on the correlation between nuclear roundness and prognosis in prostatic carcinoma. Stage A2 prostatic carcinoma patients with 4-year follow-ups and surgically treated stage B1 and B2 prostatic carcinoma patients with 15-year follow-ups were characterized by manual digitization of cancerous nuclei. A form factor that assessed nuclear shape produced an accurate separation of those patients who developed metastatic disease from those who did not. The digitized nuclear roundness correlated with the perpendicular light scatter measured by flow cytometry. When combined with forward light scatter, perpendicular light scatter separated four tumor cell lines of different metastatic potential in an animal model of prostatic cancer; a relative grading index based on these findings seemed capable of identifying human patients with more extensive disease in a preliminary study. The observation of freshly aspirated viable prostatic carcinoma cells led us to appreciate membrane ruffling, pseudopodal extension and translational movements that appear to distinguish these cells from their benign counterparts. Time-lapse cinematography, image digitization and Fourier analysis allow for the objective description of cell motion and should provide new and exciting tools for the pathologist.

Cell Movement↗
PubMedDate not supplied

Role of laparoscopy in the diagnosis and treatment of prostate cancer.

Laparoscopic surgical techniques were originally applied to the staging of prostate cancer in the form of laparoscopic pelvic lymph node dissection. The efficiency of laparoscopic pelvic lymph node dissection has proven to be comparable to open lymphadenectomy in tissue yield and also shows a considerable decrease in postoperative morbidity. Subsequently, laparoscopy has been used as an adjuvant to perineal prostatectomy for preliminary dissection of the seminal vesicles. Laparoscopic radical prostatectomy has been performed but the long-term efficacy of this treatment is unknown at this point. Future clinical applications of laparoscopic surgical techniques in the diagnosis and treatment of prostate cancer include harvesting of primary and metastatic prostatic tissue for adjuvant gene therapies for prostate cancer.

Combined Modality Therapy↗
PubMedDate not supplied

Prostatic growth rate determined from MRI data: age-related longitudinal changes.

Men with prostatic enlargement are at highest risk of developing symptomatic lower urinary tract symptoms (LUTS) and related outcomes, such as acute urinary retention. The study of prostatic growth rate can identify the age range at which prostate growth peaks. Evaluation of the natural course of prostate growth requires repeated intraindividual volume measurements at time intervals sufficient to document growth. Our objective was to examine age-stratified prostate growth rates from men taking part in a longitudinal study of aging using magnetic resonance imaging (MRI) of the prostate. Sixty-four men (ages 30-71 years) enrolled in the Baltimore Longitudinal Study of Aging (BLSA) who had T2 pelvic MRIs taken approximately every 2 years were studied. Men were age stratified into four groups: <45, 45-55, 56-65, and >65 years old. Whole prostate and central gland (anatomically referred to as the transition zone) volumes were determined from the MRI images by a semi-automated image analysis program. Peripheral gland volumes were calculated as the difference between whole prostate and central gland volumes. Growth rates (cc per year) were calculated as change in volume divided by the time interval. On the basis of measurements from the T2 images (n = 128), we observed a linear trend between prostate volume and age. The overall prostate growth rate was 2.36 +/- 3.52 cc per year. Age-stratified growth rates revealed that prostate growth increased with age, peaked at 4.15 +/- 4.98 cc/year for the 56-65-year-old age group and then declined rapidly for the older-aged men. The central gland growth rates followed a trend similar to total prostate volume. These data suggest that there is an age-related increase in prostate growth rate that peaks in men ages 56-65 and then declines. Identification of this trend in prostate growth may aid physicians in targeting men for early diagnosis of LUTS and for possible early intervention. Future studies with a larger sample size are necessary to substantiate these findings.

Adolescent↗