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A Pollack

Publications and source records attributed to A Pollack.

At least 163 records · Page 9Linked to original sources
PubMed1994

Serum prostate-specific antigen, clinical stage, pathologic grade, and the incidence of nodal metastases in prostate cancer.

OBJECTIVES: To evaluate the potential gains in using serum prostate-specific antigen (PSA) levels for predicting the incidence of pelvic nodal metastases in patients with otherwise localized prostate cancer. METHODS: We reviewed 569 patients undergoing staging lymphadenectomy, and evaluated the correlation between clinical stage, tumor grade, presurgical PSA level, and the incidence of nodal metastatic disease using univariate and multivariate regression. RESULTS: In univariate analysis stage, grade, and PSA level were highly significant covariates with nodal metastasis. Nodal metastatic rates increased as stage increased: Stage T1 (A2), 6 of 127 (5%); Stage T2 (B), 41 of 243 (17%); Stage T3 (C), 95 of 199 (48%), (p < 0.0001). Likewise metastatic rates increased as grade increased: Gleason grades 2 to 4, 6 of 124 (5%); Gleason grades 5 and 6, 52 of 238 (22%); Gleason grade 7, 41 of 122 (34%); Gleason grades 8 to 10, 43 of 84 (51%) (p < 0.0001). The relationship between PSA level and nodal metastases was not linear and we selected the following groupings that correlated with nodal disease: 4 or less ng/mL, 4 of 104 (4%); more than 4 to 20 or less ng/mL, 73 of 335 (22%); more than 20 to 40 or less ng/mL, 35 of 85 (41%); more than 40 ng/mL, 30 of 45 (67%) (p < 0.0001). Using multivariate logistic regression, stage, grade, and PSA were independently predictive of nodal status. CONCLUSIONS: The gains in predictive accuracy from PSA beyond that obtained from stage and grade were small and in practice would benefit fewer than 15% of our patients. Staging pelvic lymphadenectomy remains the only satisfactory method for elucidating nodal status in the majority of patients with prostate cancer.

Adult↗
PubMed1994

Significance of tumor angiogenesis in clinically localized prostate carcinoma treated with external beam radiotherapy.

OBJECTIVES: To determine the prognostic significance of microvessel density (a measure of tumor angiogenesis) in comparison with other prognostic factors for patients with clinically localized prostatic carcinoma treated with external beam radiotherapy. METHODS: Microvessel density was quantified within the initial invasive carcinoma from the diagnostic transurethral resection specimen of 25 patients with a mean follow-up of 44 months. Microvessels were identified by immunohistochemical staining of endothelial cells for factor VIII-related antigen in formalin-fixed, paraffin-embedded tissue. Microvessels were counted in a x200 field (0.754 mm2) in the area of maximal angiogenesis. RESULTS: Microvessel density correlated with several pretreatment prognostic factors, including prostate-specific antigen (PSA) (p < 0.0001), tumor grade (p = 0.006), and ploidy (p = 0.016). The degree of tumor angiogenesis also correlated with outcome following external beam radiotherapy. The mean microvessel count in the nine tumors from patients who failed radiotherapy (ie, had rising PSA and/or clinical relapse) was 97.0 +/- 33.6 (+/- SD) per x200 field compared with 46.1 +/- 17.1 for the 16 patients with no evidence of failure (p < 0.0001). Increased microvessel density was also associated with a significantly worse actuarial outcome at 4 years using either biochemical relapse (rising PSA) or a composite endpoint of rising PSA or clinical relapse (p = 0.0003). CONCLUSIONS: The intratumoral quantification of tumor angiogenesis may prove valuable as a prognostic indicator in patients with clinically localized prostate cancer treated with radiotherapy.

Aged↗
PubMed1994

Relationship of tumor DNA-ploidy to serum prostate-specific antigen doubling time after radiotherapy for prostate cancer.

OBJECTIVES: DNA-ploidy is a strong prognostic factor for prostate cancer patients treated with definitive external beam radiotherapy. Using DNA/nuclear protein flow cytometry, three prognostic groups based on DNA-ploidy were identified: from good to poor, these are diploid, near-diploid, and nondiploid tumors. Since recent evidence indicates that the rate at which prostate-specific antigen (PSA) increases in the presence of biochemical failure is predictive of the time to clinical relapse, we examined the relationship between DNA-ploidy and PSA doubling time (PSA-DT). METHODS: Formalin-fixed paraffin-embedded tissues from 76 patients treated at M.D. Anderson Cancer Center with definitive radiotherapy alone were analyzed for ploidy using DNA/nuclear protein flow cytometry. Of these, 24 of the 27 patients with a rising PSA profile had three or more post-treatment PSA values from which the PSA-DTs were calculated. PSA-DTs were estimated using nonlinear regression techniques. RESULTS: The average PSA-DT for the 24 patients in this cohort was 11.3 +/- 10.5 months (+/- SD) with a median of 8.4 months. Diploidy (n = 3) was associated with a PSA-DT of 27.0 +/- 22.8 months, near-diploidy (n = 7) with a PSA-DT of 12.2 +/- 5.7 months, and non-diploidy (n = 14) with a PSA-DT of 7.5 +/- 5.7 months (p = 0.004, Spearman rank test). Stage, grade, and pretreatment PSA, as well as the endpoints of local control, freedom from metastases, and freedom from any relapse, did not correlate significantly with PSA-DT values. However, when patients were subdivided by PSA-DT into those with values 10 months or less (n = 14) and those more than 10 months (n = 10), there was a correlation with 3-year actuarial freedom from relapse: 28% and 74%, respectively (p < 0.01, log-rank). This subdivision of PSA-DT also correlated with DNA-ploidy (p = 0.03, chi-square) and stage (p = 0.04). CONCLUSIONS: The results show that there is a significant correlation of DNA-ploidy with PSA-DT. Diploidy was associated with the longest PSA-DTs, near-diploidy with intermediate PSA-DTs, and nondiploidy with short PSA-DTs. Patients with short PSA-DTs also had significantly higher actuarial rates of disease relapse at 3 years. These data confirm that PSA-DT is a strong predictor of tumor behavior and that patients who have nondiploid tumors probably require more aggressive, combined modality, treatment.

Actuarial Analysis↗
PubMed1994

Beneficial effects of acarbose on daily plasma glucose profile and cataract development in sand rats.

Sand rats were used as a model for nutritionally induced type II (non-insulin-dependent) diabetes in an effort to evaluate the effect of acarbose on carbohydrate digestion. Daily plasma glucose profiles, insulin levels and weekly cararact development were determined following long-term feeding with a diet containing acarbose (20 or 40 mg/100 g diet). Acarbose not only dramatically decreased daily plasma glucose and insulin levels (p < 0.05) but also delayed, and possibly prevented, cataract formation in sand rats. The effect of acarbose persisted for 150 days. The control of daily plasma glucose levels and reduction of insulin levels obtained with acarbose may lead to the delay of cataract formation in sand rats. These results could have potential applications to diabetic patients as an adjunct treatment.

Acarbose↗
PubMed1994

Circumferential argon laser photocoagulation for prevention of retinal detachment.

Circumferential argon laser photocoagulation was administered as preventive treatment for retinal detachment in 53 eyes with extensive areas of lattice degeneration and/or retinal breaks and at least one additional high-risk factor for retinal detachment. Laser burns were applied in several continuous rows 360 degrees around the peripheral retina at the junction between the posterior border of the lesions and the unaffected retina. The retina posterior to the treated areas remained attached in 51 eyes (96.2%) during a mean follow-up period of 85.8 months (range 6 months to 18 years). The treatment did not affect visual acuity. The only complication was the appearance in 2 eyes (3.8%) of a delicate epiretinal membrane which, however, did not require surgical intervention.

Adolescent↗
PubMed1994

Double labelling to obtain S phase subpopulations: application to determine cell kinetics of diploid cells in an aneuploid tumour.

We studied the cell kinetics of the murine mammary carcinoma MCa-K using iododeoxyuridine (IdUrd) and chlorodeoxyuridine (CldUrd) given at different times as independently detectable labels of S phase cells. The presence of IdUrd and CldUrd, and the amount of DNA were measured by three-colour flow cytometry making it possible to define three subpopulations within S phase and to measure the progression through the cell cycle during the time following labelling. In DNA histograms of these subpopulations, the diploid and aneuploid cells (which had a DNA index of 1.7) are essentially completely separated. From appropriate combinations of cells labelled with IdUrd only, CldUrd only, or both, it was possible to construct separate DNA distributions for the labelled diploid and aneuploid cells at the times of administration of each label. The kinetics of the diploid and aneuploid cells could be calculated for individual tumours from these two time points without having to make corrections for the presence of the second population. The diploid and aneuploid populations had indistinguishable S and G2 + M phase durations, T(S) and T(G2 + M), of about 9 and 2 h; however, the potential doubling time values for the aneuploid and diploid populations were 30.2 and 101.2 h respectively.

Aneuploidy↗
PubMed1994

Biomarkers associated with prostate cancer progression.

In search of biomarkers that predict of human prostate cancer progression, we hypothesized that these markers must be expressed in prostatic epithelial cells during multi-step prostate carcinogenesis. Since both genetic and epigenetic factors have been implicated in human prostate cancer development, two osseous-metastatic experimental models were developed in our laboratory, one based on gene transfection and the other on stromal-epithelial interaction studies. In the genetic model, PC-3 cells transfected with point-mutated c-erbB-2/neu oncogene subsequently acquired the potential to metastasize from the prostate to soft tissues and the skeleton. In the epigenetic model, sublines derived from the parental androgen-dependent LNCaP cell line metastasized from the primary tumor to the lymph node and bone. Cells with known lineage relationships were cloned from both the primary and the metastatic tumors and were characterized extensively using cellular, biochemical, immunohistochemical, and molecular techniques. Relevant stage-specific biomarkers associated with prostate cancer progression in these two models were defined and used to evaluate human prostate tissues obtained from the clinic. In this communication, we focused our discussion on the potential importance of c-erbB-2/neu oncogene, vimentin, hepatocyte growth factor/scatter factor and its receptor, c-met oncogene, tumor angiogenesis and neuroendocrine factors as biomarkers for human prostate cancer progression.

Animals↗
PubMed1993

Calculating potential doubling time using monoclonal antibodies specific for two halogenated thymidine analogues.

PURPOSE: A new flow cytometric technique that allows for two-incorporated thymidine analogues to be measured simultaneously and independently has been used to improve the accuracy of in vivo cell kinetic estimates, i.e., the length of S-phase (TS) and potential doubling time (Tpot). METHODS AND MATERIALS: The analogues chlorodeoxyuridine and iododeoxyuridine were injected at different times into mice bearing the mouse mammary tumor MCaK. At different times after labeling, the tumors were harvested and prepared for three color flow cytometric analysis of DNA, chlorodeoxyuridine, and iododeoxyuridine. Control experiments showed that similar estimates of Tpot were obtained from each label when administered singly, or as staggered pulses. Comparisons were made between TS and Tpot calculated from a single label (single point), from the averaged result of the two labels from the same tumor (two point-ave), and from the simultaneous nonlinear fitting of the measured parameters from the two labels, from the same tumor (two point-fit). These estimates of TS and Tpot were then compared to reference values obtained by fitting the pooled measured parameters from all the tumors, that were labeled for different periods of time. RESULTS: While all of the methods resulted in similar mean estimates of TS and Tpot that were close to the reference values, the fewest assumptions, and the least variability in the results, were obtained using the two point-fit data. CONCLUSION: The estimation of Tpot using two thymidine analogues is more accurate than that obtained from a single label.

Animals↗
PubMed1993

The fall and rise of prostate-specific antigen. Kinetics of serum prostate-specific antigen levels after radiation therapy for prostate cancer.

BACKGROUND: The serum kinetics of prostate-specific antigen (PSA) after radiation therapy for prostate cancer are not well characterized, and the potential prognostic significance of serum half-lives and of serum doubling times is unclear. This study was designed to address those issues. METHODS: One hundred fifty-four patients with at least four serial PSA determinations who received external-beam radiation therapy alone were analyzed to determine PSA kinetics and to correlate kinetic parameters with outcome. Nonlinear regression techniques were used to estimate PSA half-lives and doubling times. RESULTS: The PSA data fitted well to exponential models consistent with the hypothesis that PSA kinetics after radiation follow first-order (exponential) kinetics. The mean PSA half-life was 1.9 months (range, 0.5 to 9.2 months). No significant correlation existed between half-life and grade, stage, acid phosphatase level, serum testosterone level, or patient age. A weak correlation between half-life and pretreatment PSA level was observed: patients with low PSA levels tended to have longer half-lives. Half-life did not correlate with disease relapse or with the likelihood of developing a rising PSA profile. PSA doubling time in 37 patients with rising values ranged from 1.6 to 53 months (mean, 12.5 months). Doubling times were significantly longer than half-lives by an average factor of 6.5 and there was no correlation between half-life and subsequent doubling time. Doubling times were longer in low-grade tumors. CONCLUSIONS: Serum kinetics of PSA in particular its rate of fall after radiation provide little, if any, useful clinical information. It is possible that serum kinetics of PSA are related to tumor cell kinetics but such relationships remain speculative. Correlative cell kinetic--PSA kinetic studies are needed to elucidate the mechanisms underlying the changes in PSA level after radiation therapy.

Actuarial Analysis↗
PubMed1993

Flow cytometric analysis of two incorporated halogenated thymidine analogues and DNA in a mouse mammary tumor grown in vivo.

A technique was developed for the staining of nuclei for DNA using propidium iodide, and incorporated chlorodeoxyuridine (CldUrd) and iododeoxyuridine (IdUrd) using two monoclonal antibodies that showed negligible cross-reactivity. The mouse mammary solid tumor MCaK was labeled in vivo by intraperitoneal injection of the nucleosides. Tumor cell nuclei were stained after isolation from ethanol-fixed solid tumor tissue and acid denaturation. The Br3 antibody, which specifically recognizes CldUrd, was applied first, followed by indirect staining with goat anti-mouse phycoerythrin. The direct fluorescein isothiocyanate conjugate of the B44 antibody, which specifically recognizes IdUrd, was then applied. In the direct conjugate form this antibody reacted only minimally with CldUrd. The nuclei were then stained with propidium iodide. With this dye combination the coefficients of variations of the DNA histograms were consistently in the 2-4% range. Two other dye combinations were compared. The propidium iodide/phycoerythrin/fluorescein isothiocyanate dye combination was the simplest because of the compatibility with single laser flow cytometry.

Animals↗
PubMed1993

Flow cytometric analysis of DNA and nuclear protein in paraffin-embedded tissue.

Previously we described the simultaneous quantification of DNA and nuclear protein in unfixed tissue from solid tumors. The resultant 2 parameter flow cytometric analysis has several advantages over that of DNA alone. In this report, we describe a modification of the technique for the analysis of formalin-fixed paraffin-embedded tissue. Paraffin-embedded material was prepared by hydrating sections, incubating in 0.5% pepsin solution, washing, and resuspending in buffer containing nonionic detergent. The nuclei were then stained with fluorescein isothiocyanate and propidium iodide in the presence of ribonuclease. Several solid tumor tissue types have been analyzed, including breast, colon, kidney, and thymus. The best results were obtained when the initial pepsin treatment was for 1.5 h, instead of 0.5 h. Pepsin treatment for 1.5 h improved the CVs of both the DNA and nuclear protein parameters, and did not appear to reduce nuclear protein levels or to cause significant disintegration of nuclei. The DNA/nuclear protein histograms of unfixed and fixed, paraffin-embedded tissue were similar. Since tumor nuclei typically have higher protein levels than DNA-diploid nuclei, the technique reduces population overlapping and permits less subjective identification of DNA aneuploidy.

Aneuploidy↗
PubMed1993

Recognition and reduction of artifacts from autolysis in paraffin-embedded tissue using DNA/nuclear protein flow cytometry.

Artifacts from autolysis can be a problem in retrospective flow-cytometric analyses of DNA content in paraffin-embedded tissues. Autolyzed tissue from rat liver, human liver, and rat spleen were stained for DNA and nuclear protein to determine if this technique would be useful in identifying partially degraded cells. After the tissue was deparaffinized and rehydrated, the nuclei were isolated using 0.5% pepsin. Propidium iodide (PI) and fluorescein isothiocyanate (FITC) were used to stain DNA and nuclear protein. When unfixed rat liver tissue was allowed to undergo autolysis at 4 degrees C for 24-48 h before fixation, there was a progressive broadening of the G1 and G2M DNA peaks and a slight increase in the average DNA contents of these peaks. Nuclei that stained more intensely with PI also stained more intensely with FITC. Similar results were obtained using human liver and rat spleen. Sometimes the increased PI staining resulted in a false aneuploid peak. The distinctive skewing of the DNA/nuclear protein histograms from autolysis was reduced by increasing the incubation of the tissue in 0.5% pepsin from 0.5 h to 1.5 h during the nuclei-isolation step. The DNA/nuclear protein method provides a means for identifying artifacts from autolysis, whereas the extended pepsin treatment provides a means for reducing these artifacts.

Animals↗
PubMed1993

Restoration of the outer blood-retinal barrier after krypton laser photocoagulation.

The restoration of the outer blood-retinal barrier following krypton laser injury to the rat retina was studied at small and large laser lesions using intravenously injected sodium fluorescein, horseradish peroxidase, and catalase. The regenerated choriocapillaris and new blood vessels were permeable to fluorescein and peroxidase, but not to catalase. The regenerating retinal pigment epithelium gradually reformed a continuous sheet of cells covering all small laser sites and the periphery of large lesions. Zonulae occludens between the regenerated cells restored the outer retinal barrier and prevented diffusion of peroxidase into the retina. This occurred along Bruch's membrane and the new blood vessels that were covered by the regenerated pigment epithelial cells, but not in the center of the large lesion that was not relined by regenerated cells.

Animals↗
PubMed1992

Thymoma. The prognostic significance of flow cytometric DNA analysis.

The clinical course of patients with thymoma varies widely despite its histologically benign appearance. Treatment decisions are based on local invasion and the extent of resection. Because some patients have more aggressive tumors, the prognostic significance of flow cytometric (FCM) analysis of nuclear DNA content was examined. Adequate tissue from paraffin-embedded blocks was available for 25 patients. Using FCM, the percentage of cells in S-phase (%S) and the ploidy, based on the DNA index (DI), were determined. The mean patient age was 52 years, with a female-to-male ratio of 1.3:1 and a median follow-up of 64 months. Seventeen patients underwent total tumor resections, and 12 also received radiation therapy. Eight patients underwent subtotal resections, with five receiving radiation therapy (with or without chemotherapy) and three receiving chemotherapy alone. Based on invasion and intrathoracic dissemination, the tumors were classified into four stages. The mean %S was 5.6. There was no relationship observed between %S and patient outcome. The 5-year disease-free survival rate was 85% for the 16 patients with diploid (DI = 1) tumors and 33% for the 9 patients with aneuploid (DI more than 1) tumors (P less than 0.002). Similar significant differences were observed by stage and extent of surgery. For those who had total resection (n = 17), the disease-free survival rate was 89% when DI equaled 1 and 50% when DI was more than 1 (P = 0.01). Although the numbers studied were small, when stage, histologic findings, and type of surgery were subdivided by DI, a higher incidence of relapse was associated consistently with aneuploidy. The DI appears to be a useful prognostic parameter for identifying patients at high risk of relapse.

Adolescent↗
PubMed1992

Choroidal vascular repair: scanning and transmission electron microscopy.

Repair of the choroidal vasculature following laser photocoagulation in the rat was examined with vascular casts and correlated with observations on thin-sections. The regenerative process began at the periphery of the damaged area, starting from the surviving choriocapillaris and venules, and proceeding towards the center by means of recanalization of damaged vessels and growth of new ones. In small healed lesions the capillary bed was re-formed. It resembled the adjacent undamaged choriocapillaris morphologically but appeared to be less dense than the intact choriocapillaris when examined by scanning microscopy. In large lesions the capillary bed was re-formed at the periphery but not at the center. Also present at the edges of the large lesions were groups of new vessels which, when observed by scanning microscopy, appeared to extend in two directions; towards the subretinal space and towards the choroidal network. Another aspect of the repair process was the simultaneous occurrence of new vessel growth and capillary regression, which was observed both at the level of the choriocapillaris and at the foci of new vessels.

Animals↗
PubMed1992

Autodecremental pacing for the interruption of ventricular tachycardia and atrial flutter.

The efficacy and safety of autodecremental pacing (ADP) to interrupt ventricular tachycardia (VT) and atrial flutter was examined. Once tachycardia was recognized, ADP was initiated using a short train of stimuli with gradual shortening (3%) of the interstimulus interval. ADP was applied to 13 consecutive patients during 75 episodes of VT (mostly following induction by ventricular stimulation). Successful interruption of VT occurred in 88% of the episodes. In 6 episodes (8%), ADP resulted in ventricular fibrillation and in 3 episodes VT was unaffected by ADP. The only significant discriminator between the failure or success of ADP was the rate of VT. ADP was also applied to 17 consecutive patients with an atrial flutter that was resistant to conventional antiarrhythmic agents. Successful conversion of atrial flutter to sinus was seen in only 8 patients (47%). A temporary acceleration to atrial fibrillation appeared in 3 patients (18%), and in 6 patients atrial flutter was unaffected by ADP. ADP was successful in 70% (7/10) of patients with type 1 (< 300 beats/min) atrial flutter. The authors conclude that ADP is beneficial in the interruption of VT and atrial flutter in a selected group of patients, especially with a slower rate of tachyarrhythmia (atrial rate during atrial flutter < 300 beats/min and ventricular tachycardia < 180 beats/min).

Adult↗