Biomedical subjects

A Semjonow

Publications and source records attributed to A Semjonow.

48 records · Page 3Linked to original sources

PubMed1992

Half-life of prostate-specific antigen after radical prostatectomy: the decisive predictor of curative treatment?

Prostate-specific antigen (PSA) half-life calculated in 51 patients subsequent to radical prostatectomy was found to identify patients with residual disease earlier and more reliably than the criterion of not achieving undetectable PSA levels postoperatively. It is proposed that residual tumor affects the half-life by contributing to the serum level of PSA. When PSA half-life was calculated solely in potentially cured patients, we found a half-life of 1.5 days being considerably shorter than in the previous reports based on patient populations regardless of the outcome of disease in the follow-up.

Adenocarcinoma↗

PubMed1985

Generalization of the discriminative stimulus properties of delta 9-THC to delta 9(11)-THC in rats.

Rats were trained in a water maze to discriminate between IP injections of 3 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) and its vehicle. Both delta 8- and delta 9(11)-THC were generalized to the training drug. In contrast to our observations in rhesus monkeys, where delta 9(11)-THC is at least 100 times less potent than delta 9-THC, delta 9(11)-THC was found to be only seven times less potent in the rat. Relative potencies, expressed as the dosage at which 50% of the animals gave drug responses (ED50) were 1.8 mg/kg and 12.2 mg/kg for delta 9- and delta 9(11)-THC respectively. Twenty-four hours after receiving 7 X ED50 = 12 mg/kg delta 9-THC the tests showed intermediate results when conducted with the training dosage; 4 X ED50 = 50 mg/kg delta 9(11)-THC 48 h prior to the training dosage of 3 mg/kg delta 9-THC completely blocked drug-appropriate responses. Coinjection of ED50 dosages of delta 9- and delta 9(11)-THC led to 90% drug responses, demonstrating the additivity of the cannabis-like effect of both cannabinoids. Differences in the individual sensitivity of the rats to the tested cannabinoids were observed. Findings are interpreted in terms of the receptor mechanism for cannabis-like activity.

Animals↗

PubMedDate not supplied

Blood-borne cancer cells--quo vadis?

The detection of blood-borne cancer cells may help in clinical staging and further understanding of cancer metastasis. We developed a cytokeratin-based immunomagnetic method to isolate epithelium-derived cells from the circulating blood of patients. The number of cell clusters positive for cytokeratin/prostate-specific antigen (PSA) from the peripheral blood of prostate cancer patients and cytokeratin/p185c-erbB-2 from the peripheral blood of breast cancer patients has been related to stage of the disease. Breast cancer patients who presented cytokeratin/p185c-erbB-2-positive cell clusters showed a decrease in such cells under adriamycin adjuvant therapy with Further molecular characterization by a highly sensitive microsatellite multiplex-PCR enabled reproducible detection of microsatellite alterations. The impact of these individually targeted results may contribute to an individual diagnostic and therapeutic strategy.

Biomarkers↗

PubMedDate not supplied

The impact of intraoperative manipulation of the prostate on total and free prostate-specific antigen.

OBJECTIVES: It is well documented that mechanical manipulation of the prostate can elevate total PSA (t-PSA) levels in serum. However, less is known about its effects on free PSA (f-PSA) and the free-to-total PSA ratio (f/t-PSA). We therefore examined the impact of prostate manipulation on t-PSA and f-PSA during surgical procedures involving the prostate. METHODS: Intraoperative blood samples for t-PSA and f-PSA measurement (Hybritech) were collected every 15 min during 14 radical retropubic prostatectomies (RRP) and 10 radical cystoprostatectomies (RCP). RESULTS: Prostatic manipulation induced significant elevations in t-PSA and f-PSA during RRP and RCP. Postmanipulatory peaks were markedly higher for f-PSA than for t-PSA. The mean maximum f-PSA levels showed a 4.3- (RRP) and 7.9-fold (RCP) increase, followed by a rapid decline after prostate removal. t-PSA increased 1.2- (RRP) and 1.3-fold (RCP), and declined more slowly. Postmanipulatory f/t-PSA ratios also increased significantly, reaching mean elevations of +0.29 and +0.28 over preoperative ratios during RRP and RCP, respectively. CONCLUSIONS: Prostate manipulation can induce transient increases in t-PSA, f-PSA and f/t-PSA in benign and malignant prostates. The extent of these alterations and their course over time must be taken into account when postmanipulatory changes in PSA forms are investigated. Timing of postmanipulatory venipunctures and the molar response ratio of t-PSA assays used (equimolar versus nonequimolar) seem to have substantial impact on the results of such studies.

Adult↗

PubMedDate not supplied

Frequent detection and immunophenotyping of prostate-derived cell clusters in the peripheral blood of prostate cancer patients.

BACKGROUND: Recent scientific studies have failed to determine parameters for the assessment of prostate cancer aggressiveness. The present study deals with the detection of blood-borne cancer cells based on polymerase chain reaction (PCR) and cell enrichment methods. The contradictory results reported in the literature have called into question the clinical usefulness of this diagnostic method in the preoperative staging of clinically localized prostate cancer. METHODS: We established a combined method of density gradient centrifugation and immunomagnetic separation using epithelium-specific antibodies, i.e. cytokeratins, to isolate prostate-derived circulating cells from the peripheral blood of patients with prostate cancer. Isolated cells were characterized by DNA staining and immunocytochemistry using antibodies for the detection of prostate-specific antigen (PSA), proliferation-associated proteins (MIB-1, H1 and H3) and apoptosis-associated proteins (M30, c-FasR). RESULTS: We applied these methods to 68 prostate cancer patients and were able to isolate cell clusters in 98%. Immunophenotypic and morphological characterization of PSA-positive prostate-derived cell clusters found in the peripheral blood of prostate cancer patients showed two main populations: 1) in 35% of the investigated prostate cancer patients we detected rounded cell aggregates of probable cancer cells expressing proliferation-associated proteins and lacking apoptosis-associated protein expression; 2) in all cases there was a high frequency of circulating dysmorphic cell clusters positive for apoptosis-associated protein expression. CONCLUSION: Our results demonstrate the existence of at least two different types of blood-borne prostate-derived circulating cell clusters. Of these, only the less frequent, round, small cell clusters harbor features that are probably necessary for the cells to survive for metastatic spread.

Biomarkers, Tumor↗

PubMedDate not supplied

[Thermal knot fixation].

Knots represent the weakest point in suture material. As a result of bending and tension, forces develop within the knot that exceed the strength of the suture material and lead to rupture. Furthermore, because of their relatively large surface area, the most pronounced reactions occur in the vicinity of knots. The results of in vitro experiments conducted with the aim of improving the strength of knots are reported. The knot holding capacity of polypropylene filaments (EP 5/USP 2) was determined at room temperature (22 degrees C) after exposure to temperatures of 63, 98 and 150 degrees C. Knots that were exposed to a temperature of 98 degrees C for 10 seconds had a 50% higher holding capacity than untreated knots. With a higher knot holding capacity, secure fixation can be achieved with fewer knots. Since fewer knots have a smaller surface area, a reduction in tissue reaction may be expected.

Heating↗

PubMedDate not supplied

[Suture surface and suture strength of polypropylene monofilaments].

Knots form the weakest sections in suture materials. The addition of forces in the knot caused by bend and tension exceed the strength of the suture material and lead to rupture in the knot. Furthermore the most pronounced tissue reactions occur in the surrounding of knots because of their relatively large surface as compared to the linear filament. With a higher knot holding capacity a secure fixation can be achieved with less knots. As a reduced number of knots leads to a smaller surface a reduced tissue reaction can be expected. Because of high rigidity and a low coefficient of friction synthetic monofilaments achieve only a low knot holding capacity. To improve the knot holding capacity a usually large number of knots is being used. With increasing surface of exogenous materials the extent of foreign-body reactions increases, e.g. formation of granuloma. Results of in-vitro experiments are reported that were conducted to identify the smallest secure knot in polypropylene filaments of various diameters.

Humans↗

PubMedDate not supplied

The biologic lower detection limit of six ultrasensitive PSA assays.

BACKGROUND: The benefit of monitoring patients with prostate cancer (PCA) by ultrasensitive measurement of prostate specific antigen (PSA) is frequently discussed. Usually, the analytic lower detection limit of an ultrasensitive assay is determined by the manufacturer. As the analytic lower detection limit does not take into account interfering factors of human serum, the biologic lower detection limit, which is defined as PSA concentration detected in PSA-free human serum, plus 3 standard deviations, is of greater interest. MATERIALS AND METHODS: We investigated the biologic lower detection limit of six ultrasensitive PSA assays. Sera from 15 men with bladder cancer after radical cystoprostatectomy and from 30 healthy women were applied. Hence, we expected no PSA of prostatic origin. RESULTS: The biologic lower detection limit obtained using these sera was up to 30 fold higher (men, 0.29-0.63 ng/ml; women, 0.03-0.69 ng/ml) than the analytic lower detection limit (0.01-0.09 ng/ml). CONCLUSIONS: PSA measurement in sera obtained from men without prostate and women results in PSA values above the ultrasensitive range. Therefore, advantages provided by ultrasensitive PSA measurement in monitoring PCA patients after radical prostatectomy are limited.

Environmental Monitoring↗

PubMedDate not supplied

Estradiol and high-dose dihydrotestosterone treatment causes changes in cynomolgus monkey prostate volume and histology identical to those caused by testosterone alone.

To evaluate the effects of testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) on the regulation of prostate growth and tissue composition, the following study was conducted in a nonhuman primate model. Fifteen adult, long-term castrated cynomolgus monkeys were randomly assigned to receive implants filled with T (0.19 +/- 0.01 g), DHT alone (0.21 +/- 0.01 g), or (99%) DHT + (1%) E2 (0.21 +/- 0.01 g). Prior to and at 4-week intervals during the treatment phase of 252 days, prostate volumes (PV), body weight, ejaculate weight, hormone levels (of T, DHT, and E2), and red blood cell count were measured. Five adult, intact monkeys served as controls for prostate volume and histology. At the end of the study, histological analysis of an ultrasound-guided prostate biopsy was performed. T levels increased significantly in the T group compared with baseline (P < 0.01) and with the DHT and DHT + E2 groups (P < 0.05). Both groups receiving DHT showed higher DHT levels than did animals in the T group (P < 0.001). E2 levels in all groups increased over time (P < 0.05), although significant differences (P < 0.01) could only be detected between the DHT + E2 and the DHT group. Prostate volume in all groups increased (at baseline: T = 1.03 +/- 0.12 ml, DHT = 1.08 +/- 0.15 ml, DHT + E2 = 1.13 +/- 0.09; at day 252: T = 5.83 +/- 1.00, DHT = 4.72 +/- 0.9, DHT + E2 = 5.05 +/- 0.62) over time (P < 0.001), whereas no differences could be detected between the groups. Prostate biopsy could be performed successfully in 15 out of 20 monkeys. Prostate tissue evaluation between the treatment groups and the evaluated intact monkeys revealed no differences in the status of secretory epithelia, nuclear chromatin, excretory vacuoles, interstitial stroma, smooth muscles, and total functional status, whereas the prostate of a long-term castrated monkey showed severe atrophy. Thus, both androgens fully restored prostate volume and ejaculatory function. Highly supraphysiological DHT serum levels are not associated with abnormal volumetric or histological changes of the prostate. Comparing the DHT group with the DHT + E2 group, an additional stimulatory effect of normal or slightly elevated estrogens on the prostate cannot be found in the presence of highly supraphysiological DHT levels.

Animals↗

PubMedDate not supplied

Radical prostatectomy: survival outcome and correlation to prostate-specific antigen levels.

BACKGROUND: This paper reviews a 10-year experience with radical retropubic prostatectomy (RP) focussing on survival outcome related to pre- and postoperative levels of prostate-specific antigen (PSA). PATIENTS AND METHODS: 739 patients who underwent RP between 1987 and 1998 were prospectively investigated. Kaplan-Meier analyses were performed and correlated to pre- and postoperative PSA concentrations. RESULTS: In a follow up period of 11 years duration, (mean 3 yrs.) 57 of 739 patients died (20 from prostate disease progression, 37 from other causes). Correlation between low pre-operative PSA and pathological organ-confinement was significant (p < 0.001). Of 175 patients with PSA progression, 53 (30%) had never reached undetectable levels of PSA. 57% of PSA relapses were detected during the first year, and 3% later than 5 years post-operatively. Kaplan-Meier analysis yielded an average 3 years advantage in estimated prostate-cancer-specific survival when pre-operative PSA levels were below 50 ng/ml. Overall, prostate-cancer-specific and PSA-free 5-year survival-rates were 88%, 96% and 67% respectively. CONCLUSIONS: Survival-rates after RP are high even in conjunction with unfavourable PSA outcome. Merely one third of deaths resulted from prostate cancer, since men at risk frequently suffer from concomitant diseases that affect survival.

Aged↗

PubMedDate not supplied

Prostate specific antigen in as a dynamic model in advanced prostate cancer.

BACKGROUND: Prostate specific antigen doubling time (PSADT) is a prognostic factor after radical prostatectomy, radiation therapy, and hormonal therapy respectively for prostate cancer. However, its role in patients receiving chemotherapy has not been evaluated to date. PATIENTS AND METHODS: Thirty patients (pts.) with hormone resistant prostate cancer were enrolled in a prospective phase II study to receive oral Idarubicin. The drug was administered at a dose of 35 mg on day 1 and 8 of each cycle, and treatment was repeated every 3 weeks. RESULTS: Fully evaluable for response were 26 pts. 13 of these 26 had measurable disease and 3 out of 13 had no change (NC) after therapy. Ten pts. had progression. All 13 pts. with non-measurable disease showed no response. PSA values increased exponentially over time in all pts., except for the 3 pts. with NC, in whom PSA values remained stable. Median PSADT of pts. with a rising PSA was 2.1 months (mean 2.6; range 0.7-6.1). CONCLUSIONS: PSA levels in pts. not responding to treatment with Idarubicin rose in an exponential fashion similar to pts. who were only on hormonal therapy. PSADT should be evaluated in a larger number of hormone resistant prostate cancer pts. as a possible surrogate endpoint.

Aged↗

PubMedDate not supplied

The use of prostate-specific antigen (PSA) for the monitoring of radiation therapy in prostate cancer.

BACKGROUND: The classic methods for surveilling the efficacy of radiotherapy in prostate cancer are not accurate enough. The objective of this analysis was to determine whether prostate-specific antigen could perform this task. MATERIALS AND METHODS: From 1/95 to 10/95, 16 patients were treated at our clinic. 7 of these underwent primary irradiation, 4 treatment for local recurrence, and 5 had adjuvant radiotherapy. Radiotherapy was carried out with a total dose of 60 Gy in 30 fractions, 10 fractions per week, to the prostate bed plus 2 cm safety margin. RESULTS: PSA levels usually start to decline between the 3rd and the 4th week of radiotherapy with a half-life of 2.5 months. Five patients had equal or rising PSA levels, including all three patients with recurrent tumor. DISCUSSION: In most cases, PSA declined continuously from the 3rd week of therapy. Our median half-life was similar to other reported results. Persisting or rising PSA levels are an indicator for local or distant recurrence; all our patients who developed a recurrence showed a corresponding PSA increase.

Humans↗