Experimental studies on the heterogeneity of bladder carcinoma.
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Animals↗
Biomedical subjects
E Huland
Publications and source records attributed to E Huland.
Monoclonal antibody 486 P 3/12: a valuable bladder carcinoma marker for immunocytology.
Monoclonal antibodies directed against tumor-associated antigens of bladder carcinoma were used to identify tumor cells in bladder washout specimens of 40 patients with bladder carcinoma (group 1), 41 with no bladder disease or with urinary tract infections (group 2), 41 who received long-term mitomycin C instillation therapy after excision of the tumors (group 3) and 39 who received no prophylaxis after excision of the tumors (group 4). In all groups the same bladder washout specimen was used for standard urinary cytological and immunocytological tests. True positive results were obtained in 90 per cent of the patients in group 1 according to our immunocytological criteria and in 43 per cent according to standard cytology studies. No urine specimens in group 2 (controls) were immunocytologically positive, while 16 of 41 in group 3 and 17 of 39 in group 4 were positive immunocytologically but only 4 and 5, respectively, were positive according to standard cytology studies. Further followup of these patients will show whether cells positive for monoclonal antibody 486 P 3/12 will permit early detection of recurrent bladder cancer and whether one can identify patients who require prophylaxis after removal of the superficial bladder tumors.
Antibodies, Monoclonal↗
Human transitional cell carcinoma in the NMRI-nu/nu mouse bladder: a new animal model for the in vivo use of monoclonal antibodies and cytotoxic agents.
Human transitional cell carcinoma of the bladder was successfully transplanted into the bladder of the NMRI-nu/nu mouse. Transplantation of a single-cell suspension from a human Grade II transitional cell carcinoma had an acceptance rate of 33%. The tumors showed invasive growth and could be identified by an anti-human monoclonal antibody. This tumor model can be valuable as an in vivo test system for the local use of cytotoxic agents and monoclonal antibodies in diagnosis of and therapy for human bladder carcinoma.
Animals↗
Kinetic studies of D-glucose transport in renal brush-border membrane vesicles of streptozotocin-induced diabetic rats.
Renal brush-border membrane vesicles prepared from streptozotocin-induced 4-day-diabetic rats possessed a Na+-dependent D-glucose transport system that exhibited apparent Kt and Vmax values about 2-fold greater than normal. Apparently, hyperglycemia and probably other stimuli cause the induction and membrane incorporation of a low-affinity transporter in these membranes; this increased sugar-transport capacity is retained for at least 4 weeks so long as the animals maintained or increased their body weight. Membranes prepared from 28-day-diabetic, severely ill ketoacidotic animals lose this enhanced transport ability and the decrease in Vmax was found to correlate directly with the weight loss. Furthermore, the transporter in brush-border membranes prepared from these cachectic animals had an even lower affinity for glucose than those from the acute hyperglycemic animals. That these changes in the diabetic animals represent major alterations in renal brush-border membrane construction is further supported by our observation that the specific activity of the marker enzymes, alkaline phosphatase and neutral alpha-glucosidase, are profoundly increased and decreased, respectively, in this condition.
Alkaline Phosphatase↗
Supersensitive PSA-analysis after radical prostatectomy: a powerful tool to reduce the time gap between surgery and evidence of biochemical failure.
BACKGROUND: Using three commercially available, unmodified PSA assays, 917 sera of 355 patients after radical prostatectomy underwent native and lyophilisation-concentrated PSA-detection to evaluate the benefit of serum concentration as a tool to increase sensitivity for earlier detection of recurrent prostate cancer after RP. MATERIALS AND METHODS: We evaluated Abbott IMX, Tosoh ALA-600 and DPC-Immulite Assay in the follow-up of 355 patients. Mean follow-up time is 374 days (43-2057). All sera underwent native analysis and 4 fold- lyoconcentration and subsequent triplicate standard analysis on each assay. Evaluation of native and concentrated sera: A PSA-value of > or = 0.10 ng/ml was positive. Sera reading < 0.10 ng/ml were considered negative. In 4-fold concentrated sera this means a calculated increase of sensitivity to > or = 0.025 ng/ml. The average day of detection of a first positive signal either in native or concentrated sera for each assay was calculated as well as the time showing the average day difference of earlier detection in the lyoconcentrated sera for each assay. 20 Female sera were run and consistently read zero values in native and concentrated sera. RESULTS: In 355 patients, the number of PSA-positive patients were 58, 65 and 62 on Abbott, Tosoh and Immulite, respectively. 17/58 (29.3%), 19/65 (29.2%) and 20/62 (31.7%) patients could be identified earlier in lyoconcentrated than in native sera. A mean time advantage of 308-336 days was found. No patient who was positive according to supersensitive criteria had a negative supersensitive result, in his later follow-up. 17/19 (89.4%) patients in the Tosoh, 17/20 (85%) in the Immulite and 10/17 (58.8%) in the Abbott were identified as PSA-positive within one year after RP. CONCLUSION: PSA was positive in lyoconcentrated sera a mean of one year earlier than in native sera The maximum time advantage of lyoconcentration was 862 days, indicating PSA-recurrence 2.3 years earlier than standard analysis. 58.8-89.4% of patients with biochemical evidence of PSA-recurrence in supersensitive analysis were found within one year after RP. Lyoconcentration increases PSA-signals reliably in different assays. It can be performed as a quick routine procedure.
Female↗
Local intratumor immunotherapy of prostate cancer with interleukin-2 reduces tumor growth.
BACKGROUND: This study was designed to determine the effectiveness and toxicity of local continuous immunotherapy for prostatic cancer. METHODS: 60 juvenile male Copenhagen rats with Dunning adenocarcinoma of the prostate, implanted subcutaneously into both flanks after proven tumor growth, were treated with either human interleukin-2 (IL-2) depot preparations (n = 30) or albumin (placebo) depot preparations (n = 30) implanted directly next to tumor site. IL-2 depots released IL-2 reliably for more than 24 days. Rat serum was tested during treatment for human IL-2, possibly absorbed from depots, and for rat interferon gamma. RESULTS: IL-2 treatment reduced tumor growth significantly (p < 0.001) compared with albumin treated sites or untreated contralateral sites. No toxicity was observed during treatment. That neither human IL-2 nor rat interferon gamma was detected in serum indicates an exclusively local IL-2 effect. CONCLUSIONS: IL-2 depot preparations reduce tumor growth in Dunning adenocarcinoma of the prostate significantly without toxicity.
Adenocarcinoma↗
Treatment of pulmonary metastatic renal-cell carcinoma in 116 patients using inhaled interleukin-2 (IL-2).
BACKGROUND: We report 6 years of experience in 116 patients who used inhaled interleukin-2 (IL-2) and were treated in different protocols with natural, recombinant glycosylated and recombinant nonglycosylated IL-2. MATERIALS AND METHODS: All protocols had in common high-dose inhalation of IL-2, either exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treatment time (median treatment time, 7.2 months) was mild and at a low incidence (16%) of WHO grade 3 toxicity. Treatment was allowed in patients for whom systemic IL-2 was not suitable. RESULTS: Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range 4.1-33) and were stabilized in 55% for a median of 6.6 months (range, 3-51.7). Overall response rate was 16%, 49%, and 35%, respectively. Median overall response duration was 9.6 mo. Median achieved survival was 11.8 months (range 1.7-68.8). CONCLUSIONS: Inhaled IL-2 prevents progress of pulmonary metastases effectively in 70% of patients. Local use of IL-2 allows the use of the full potential of cytokines with little or no toxicity.
Administration, Inhalation↗
Super-sensitive prostate-specific antigen (PSA) in serum of women with benign breast disease or breast cancer.
BACKGROUND: Serum prostate-specific antigen (PSA) can be discovered in patients with breast cancer. We used ultrasensitive methods of PSA detection, successfully developed for early detection of PSA recurrence in prostatic-cancer patients, to study PSA in women with breast cancer and benign breast lesions before and after surgery. MATERIALS AND METHODS: Blood samples of 45 women with suspect breast findings were prospectively analyzed for PSA before and after breast surgery. Supersensitive 2nd and 3rd generation DPC assays were used to measure PSA (clinical detection limit of > 0.1 and > 0.02 ng/mL, respectively) and combined with concentration of serum to improve the clinical detection limit to > 0.025 and > 0.005 ng/mL, respectively. PSA concentrations were correlated with histological findings. RESULTS: The most sensitive detection was required to detect PSA preoperatively in 12 out of 45 patients, 8 (31%) out of 26 breast-cancer patients and 4 (25%) out of 16 patients with benign breast lesions. Postoperatively, 13 out of 45 patients were positive for PSA, 7 (27%) breast-cancer patients and 6 (23%) patients with benign breast lesions. CONCLUSIONS: Cancer patients showed the highest concentrations of PSA measured preoperatively and a decrease after surgery that was however not significant. Women with breast lesions expressed serum PSA in one third of the cases studied. PSA expression in serum does not distinguish benign from malignant breast diseases, but it might be valuable for follow-up to analyze whether recurrent disease can be detected with quantitative ultrasensitive PSA measurement.
Adult↗
Treatment of metastatic hormone-refractory prostate adenocarcinoma (MatLyLu) in Copenhagen rats with micro-osmotic interleukin-2 pumps.
BACKGROUND: We studied the influence of interleukin-2 (IL-2) therapy on tumor growth and prevention of metastasis in metastatic, hormone-refractory prostatic carcinoma (PCa) in an animal model orthotopically (ortho) and subcutaneously (s.c.). MATERIALS AND METHODS: 75 juvenile male Copenhagen rats were divided into five groups of 15 rats each. MatLyLu-PCa (MLL) was implanted ortho (n = 30) in 2 groups or s.c. (n = 30) in 2 groups and were treated locally at the tumor site with micro-osmotic pumps. The rats in 2 groups received IL-2 pumps with 36 x 10(6) IU of IL-2 and the rats in 2 other groups were treated with pumps delivering albumin only as a control. The rats in the last group received ortho MLL and s.c. IL-2 (n = 15). Survival time was then monitored. RESULTS: Prostatic tumor was found in all ortho animals. Additionally lymphogenic and pulmonary metastasis was found in all animals. The orthotopic and s.c. IL-2-treated groups showed a statistically significantly increased survival compared with the orthotopic and s.c. albumin-treated groups. When treating the ortho MLL with s.c. IL-2 there was still a statistically significant longer survival than in the control groups. CONCLUSION: IL-2 therapy significantly reduces tumor growth of rats with metastatic, hormone-refractory prostatic cancer MatLyLu.
Adenocarcinoma↗
Analysis of molecular isoforms of PSA and their ratios in men with PSA-relapse after radical prostatectomy.
BACKGROUND: The aim of this study was the longitudinal comparison of % f-PSA in patients before radical prostatectomy and after PSA relapse. Is % f-PSA a consistent tumor specific parameter or does this ratio change during untreated tumor progression? MATERIALS AND METHODS: In this study 41 out of 420 patients with untreated increasing PSA-progression (> 0.5 ng/ml) were analysed. Patients with neoadjuvant or adjuvant hormonal therapy were excluded. T-PSA were f-PSA were analyzed by Immulite DPC (Diagnostic Products Coop., CA) and Abbott Axsym (Abbott Park, Il, USA). RESULTS: Pre-operative % f-PSA ratio was 10.6% (range 4.6-22%; Std. dev.: 4.9); T-PSA concentration was 26.4 ng/ml (range 5.5-10.2 ng/ml Std. dev.: 20.3). In men with PSA relapse after radical prostatectomy % f-PSA ratio was 14.73% (range 2.2-4.5% Std. dev.: 9.7). Repeated post-operative % f-PSA measurements resulted in 12.94% f-PSA (range 2.7-3.8% Std. dev.: 9.9%) with a regression of R = 0.57. All men with pre-operative elevated % f-PSA (> 15%) had post-operative elevated % f-PSA. CONCLUSIONS: The data indicates that post-operative % f-PSA is a constant tumor specific parameter in men with untreated PSA relapse after radical prostatectomy. Post-operative % f-PSA was higher compared with pre-operative % f-PSA concentrations. No correlation with Gleason score or pathological stage was found.
Humans↗