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Biomedical subjects

E Huland

Publications and source records attributed to E Huland.

At least 55 records · Page 3Linked to original sources
PubMed1995

In vivo system to detect long-term continuous release of bioactive interleukin-2 by immunopharmacological depot preparations in nude mice with human tumors.

For continuous release of cytokines for local application at tumor sites, we developed depot preparations consisting of a carrier substance (ethylene vinyl acetate copolymer) and either natural interleukin-2 (nIL-2) at 5 x 10(5) BRMP U or natural interferon-alpha (nIFN alpha) at 3 x 10(5) IU. We transplanted human tumors in nude mice and placed depot preparations next to the tumors to confirm the in vivo long-term biological activity of the depots according to the ability of IL-2 to inhibit growth of the tumors. Five different human tumors were used. Mice with each tumor were divided into groups of six to eight receiving different treatments: control (no treatment), human serum albumin, but no cytokine, IL-2 depot, IFN alpha depot and IFN alpha plus IL-2 depot. After proven in vivo tumor growth, these depot preparations were implanted subcutaneously directly at the tumor sites. Tumor growth was significantly reduced by IL-2 and IFN alpha plus IL-2 for 3 weeks after depot implantation. Complete tumor remission was not achieved. IFN alpha alone did not influence tumor growth. Our data show that the nude mouse is a valuable model for testing biological activity and release time of IL-2 depot preparations in vivo.

Animals↗
PubMed1995

Toxicity of local, continuous and cyclic, high-dose bladder perfusion with recombinant and natural interleukin-2 in advanced cancer of the urinary bladder.

We evaluated the toxicity of high-dose local interleukin-2 (IL-2) in 18 patients not eligible for standard treatment of advanced transitional cell bladder carcinoma. Seven received continuous high-dose local natural IL-2 via pump system in the bladder for up to 420 days. 11 received cyclic high-dose local natural IL-2 or recombinant IL-2 for up to 420 days. Treatment was well tolerated and, considering the low rate of toxicity, could be offered in an outpatient setting. Except for local contrast-media hypersensitivity, no serious side-effects were observed. This study provides a basis for the non-toxic use of local IL-2 in future studies to evaluate effectiveness of the treatment or prophylaxis of patients with superficial bladder cancer in order to prevent recurrences.

Administration, Intravesical↗
PubMed1995

Long-term monitoring of 486P 3/12 antigen pattern (quantitative immunocytology) before, during, and after mitomycin C prophylaxis in patients with superficial bladder cancer.

OBJECTIVES: Quantitative pattern of 486p 3/12 antigenicity in urine cytologies (Quic) of patients with superficial bladder carcinoma during operation and chemoprophylaxis was evaluated to determine the duration of prophylaxis on an individual patient-oriented basis. METHODS: Thirty-six patients with superficial bladder carcinoma during chemoprophylaxis (43 [range, 3 to 90] weeks of mitomycin C) have been evaluated monthly for 99 (range, 36 to 141) weeks. RESULTS: Only 6 of 36 patients (16.7%) had tumor recurrence after mean follow-up of 67.5 weeks. During mitomycin instillations, only 5 patients converted from positive to repeated negative Quic. None of them developed tumor. Thirty-one did not convert and only 6 of them developed recurrent tumor. CONCLUSIONS: Quic seems not to be a reliable marker during mitomycin prophylaxis. After mitomycin prophylaxis, a repeated positive Quic, however, was associated with a high risk of recurrence occurring in 3 of 8 Quic-positive patients. A repeated negative or alternating Quic identified a lower risk group, showing 3 recurrent tumors in 28 patients only. We conclude that Quic cannot be used during, but after, prophylaxis to identify risk patients requiring further treatment. During prophylaxis, its value is limited to a subgroup of patients developing negative Quic, for whom prophylaxis can be stopped individually.

Adult↗
PubMed1994

Inhaled interleukin-2 in combination with low-dose systemic interleukin-2 and interferon alpha in patients with pulmonary metastatic renal-cell carcinoma: effectiveness and toxicity of mainly local treatment.

We describe here a mainly topical interleukin-2 (IL-2) application in pulmonary metastatic renal-cell carcinoma: a high-dose long-term inhalation of IL-2 (90% of IL-2 dose) and low-dose systemic subcutaneous IL-2 (10% of IL-2 dose) and systemic subcutaneous interferon alpha (IFN alpha). The effectiveness of this treatment is remarkable. No pulmonary metastases progressed during treatment. One complete response, 8 partial responses, and 6 cases of stable disease were achieved in the lungs of the 15 patients. In addition, 3 of 7 patients had partial responses and 1 of 7 had stabilization of non-pulmonary metastases. Overall response according to WHO criteria was 1 complete response, 6 partial responses, 2 mixed responses, 5 stable diseases and 1 progressive disease. Toxicity was low. Only WHO grade I toxicity occurred, except for a single grade II event (bronchospasm). This allowed long-term ambulatory treatment (1-23 months) inclusion of high-risk patients, and inclusion of patients with advanced disease. The expected mean survival of patients was 9.9 months, the actual mean survival is now 19.1 months, and 11 of 15 patients are still alive. Quality of life during treatment was good. Inhalation of IL-2 serves as a clinical model for high effectiveness and low toxicity of long-term local IL-2 application. We conclude that mainly local treatment might be the key to successful nontoxic use of IL-2 in cancer patients.

Administration, Inhalation↗
PubMed1993

Virus-related serology and in situ hybridization for the detection of virus DNA among patients with testicular cancer.

Viral infections have been implicated in the pathogenesis of several malignancies. A high incidence of the Epstein-Barr virus (EBV) genome and increased EBV-specific antibody titers were frequently observed in Hodgkin's disease. Some epidemiologic and clinical similarities have been demonstrated between Hodgkin's disease and human testicular germ-cell carcinoma. However, we investigated testicular biopsies from 16 patients with testicular cancer and 16 noncancer controls for the presence of EBV, cytomegalovirus (CMV), and herpes simplex virus (HSV) genomes with in situ hybridization and evaluated serum antibodies against EBV, CMV, and mumps among 52 patients with testicular carcinoma and 54 age-matched controls without cancer. There were no statistically significant differences in increased virus titer between patients with testicular cancer and controls, and we detected no EBV or CMV DNA in tumor cells, although the HSV genome was found in 50% of the testicular-tumor patients and 37.5% of controls. The findings suggest that viral infections have no direct role in the etiology of testicular carcinoma. The detection of HSV DNA in both tumor patients and controls might be a sign of latent infection, rather than a risk factor for testicular cancer.

Antibodies, Viral↗
PubMed1992

Tumor-associated eosinophilia in interleukin-2-treated patients: evidence of toxic eosinophil degranulation on bladder cancer cells.

Blood eosinophilia in tumor patients treated with interleukin-2 (IL-2) is well known and is regarded as evidence of toxicity or as a side-effect [Lotze et al. (1986) Arch Surg 121:1373-1379; West et al. (1987) N Engl J Med 316:898-905]. We recently described a new local IL-2 approach to therapy for advanced bladder carcinoma that allows, for the first time, high-dose continuous administration of natural interleukin-2 (nIL-2) at the tumor site without side-effects [Huland and Huland (1989) Cancer Res 49:5469-5474]. Tumor-associated eosinophilia of up to 65% (i.e. eosinophils constituting 65% of leukocytes) was seen in four of five patients after treatment, but never before treatment or in untreated controls. Activated eosinophils were attached to bladder tumor cells. Local activation was seen only after natural IL-2 treatment and was determined by cytological criteria and by staining with monoclonal antibody (mAb) EG1 directed against all eosinophil granule proteins and mAb EG2 directed against the active secretory granule proteins of the eosinophils. Bladder cancer cells in urinary sediment also stained with these two mAbs, revealing active degranulation of eosinophils on bladder tumor cells. The number of eosinophils in blood increased, however, without signs of activation. These data constitute strong evidence that activated eosinophils in vivo are involved in the IL-2-induced antitumor response.

Administration, Intravesical↗
PubMed1992

Distribution of 486P 3/12 antigen, ABO(H) blood group antigen and T antigen in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder.

We used monoclonal antibody 486P 3/12, anti-ABO(H) antibodies and anti-T antigen lectins to detect malignant transformation in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder. We used an immunoperoxidase technique to do extensive chessboard-like mapping studies in 6 cystectomy bladders with stage T2 lesions and 1 normal bladder from a multiorgan donor as control to characterize antigen expression. Increased 486P 3/12 antigen expression, decreased ABO(H) expression and T antigen deletion were detectable not only in the tumor area but also in tumor-surrounding areas classified as benign. We believe that cells with abnormal antigen expression are a source of tumor recurrence and can be identified with our method of quantitative immunocytology.

ABO Blood-Group System↗
PubMed1992

Interleukin-2 by inhalation: local therapy for metastatic renal cell carcinoma.

We report the use of inhaled natural interleukin-2 in patients with metastatic disease. Six patients with metastatic renal cell carcinoma received 100,000 units natural interleukin-2, 5 times per day by inhalation in addition to a 4-day cycle of intravenous natural interleukin-2 every 2 weeks and subcutaneous interferon 5 days per week. Response was clearly correlated with metastatic site. Distinct tumor burden and the poor condition of the patient did not impair success. Pulmonary metastases responded in 5 of 5 patients. Metastases in the mediastinum, liver, abdomen and pelvis were stabilized in 4 patients. No response was noted in 3 solitary bone metastases, which were successfully removed surgically after several months of therapy, and a pleural metastasis progressed despite a clear response of the pulmonary disease in the same patient. New metastases did not develop in any of the patients during treatment (median followup 183 days of treatment, range 97 to 296 days). The over-all importance of the low toxicity of this novel route of administration (World Health Organization classification not exceeding grade 1) making long-term outpatient treatment possible must be emphasized because limitations of systemic interleukin-2 application are mainly caused by pulmonary side effects, for example pulmonary capillary leakage syndrome and edema. However, this new type of topical natural interleukin-2 application and combination with low dose intravenous interleukin-2 achieved considerable antitumor responses.

Administration, Inhalation↗
PubMed1991

Comparison of 15 monoclonal antibodies against tumor-associated antigens of transitional cell carcinoma of the human bladder.

Quantitative urinary immunocytology with our monoclonal antibody (mab) 486p 3/12 proved to be valuable for diagnostic use in bladder-cancer patients' urine, especially in the followup of patients with superficial bladder carcinoma. To evaluate the use of other monoclonal antibodies in bladder cancer, we compared 15 mabs directed against bladder-tumor-associated antigens from seven research groups in a broad panel of cellular and tissue specimens (bladder tumor, prostatic adenoma, and kidney stone). Quantitative evaluation was done in cytocentrifuged preparations and tissue specimens. None of the 15 mabs was bladder-tumor-specific. All 15 stained normal urothelium to some extent and six stained granulocytes. Each of the 15 seemed to identify a different cellular antigen, as can be clearly demonstrated by the staining pattern of different regions in the normal kidney. The sensitivity of quantitative urinary immunocytology in bladder-tumor patients can be improved by using a panel, rather than one mab in bladder-tumor patients, but specificity decreases simultaneously. A main reason for the poor specificity of quantitative urinary immunocytology with all 15 mabs is that false-positive results are obtained with all mabs in kidney-stone patients. Our quantitative urinary immunocytology method is a general tool for the diagnostic use of all mabs in bladder-tumor patients. Mabs that have a high sensitivity might be useful in the followup of patients with superficial bladder carcinoma. None of the 15 mabs (because of their poor specificity) seems to be helpful in quantitative urinary immunocytology for screening a population for bladder carcinoma.

Antibodies, Monoclonal↗
PubMed1991

Sensitivity of urinary quantitative immunocytology with monoclonal antibody 486 P3/12 in 241 unselected patients with bladder carcinoma.

We investigated the sensitivity of quantitative immunocytology with our monoclonal antibody 486 P3/12 in 241 unselected patients with transitional cell carcinoma. Immunocytology yielded a sensitivity of 91.8%, 89.4% and 92.9% for grade 1, 2 and 3 tumors, respectively. Standard cytology was positive in 59.2%, 63.8% and 84.7%, respectively. Deoxyribonucleic acid flow cytometry, used in the first 69 patients, was positive in only 27.7%, 48.6% and 57.1%, respectively.

Antibodies, Monoclonal↗
PubMed1990

Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final evaluation of a prospective multicenter study with 419 patients.

In a prospective multicenter study we compared the value of various protocols of mitomycin C and doxorubicin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (stages TA and T1) had been removed by transurethral resection. The 3-year and short-term instillation protocols were compared to each other and to a combination of 2 protocols. Evaluation after a mean followup of 28 months confirmed the value of cytostatic bladder instillation in preventing recurrence and progression of tumor in patients with superficial bladder carcinoma. There was no significant difference between the results of long-term and short-term prophylaxis; their combination achieved the best results. Doxorubicin and mitomycin yielded similar results; mitomycin was better tolerated.

Administration, Intravesical↗
PubMed1990

Quantitative immunocytology in the management of patients with superficial bladder carcinoma. I. A marker to identify patients who do not require prophylaxis.

We used monoclonal antibody 486P 3/12 to monitor 55 patients after transurethral resection of stages Ta and T1 transitional cell bladder carcinoma. The method has a high sensitivity (89%) in detecting grades 1 to 3 lesions. We examined voided urinary specimens taken every 4 weeks after transurethral resection for a mean of approximately 2 years. Of the 55 patients 22 remained negative for marker without prophylaxis and only 2 of them had another tumor. Only 6 of 33 patients who were positive for marker after transurethral resection were negative for marker at least once immediately after transurethral resection. Of the 33 patients 14 had a recurrent tumor. In all 14 patients a marker-positive urine specimen preceded visible tumor recurrence by several months. Monoclonal antibody 486P 3/12 is a safe marker to identify patients with superficial bladder carcinoma after transurethral resection who do not require prophylaxis. The 22 patients who remained negative for marker after transurethral resection had an almost equal distribution of stages Ta to T1 lesions (9 versus 13) and equal distribution of grades 1 and 2 lesions (11 versus 11).

Antibodies, Monoclonal↗
PubMed1989

Local continuous high dose interleukin 2: a new therapeutic model for the treatment of advanced bladder carcinoma.

Because efficient i.v. administration of interleukin 2 (IL-2) in tumor patients leads to severe cardiopulmonary side effects, we developed a new form of IL-2 application that allows activation of all IL-2-responsive immune cells directly at the tumor site. In five patients with T4N0M0 transitional cell carcinoma of the bladder, we used high-dose, continuous IL-2 perfusion of the bladder (1000 units/ml, 2 ml/min, 24 h/day), for 5 days after incomplete transurethral resection of the tumor. The total dose, 15 million units, was repeated after 4-12 weeks. None of our patients showed any evidence of side effects. In blood and especially in urine, the number of eosinophil leukocytes was remarkably increased. Eosinophils were attached to the tumor cells and degranulated on them. Before treatment, no cells positive for IL-2 receptors were found in urine, and only 0-3% of lymphocytes positive for IL-2 receptors were detected in blood. After the first cycle and especially after the second, a distinct increase in positive cells up to 17% occurred. One patient had a complete histologically confirmed remission and is free of tumor 6 months after therapy. Another patient died of a vertebral metastasis 8 weeks after the first (and only) therapeutic cycle. Local administration of a high dose of IL-2 induces local and systemic immunopotentiation diagnosed by activation marker analysis without any side effects and can be used in inoperable transitional cell carcinoma of the bladder. The optimal dosage still needs to be defined. Bladder carcinoma is an ideal model that offers a unique chance to use urine cytology to study the cooperation and activation of immune cells at the tumor site.

Administration, Intravesical↗
PubMed1989

[Quantitative immunocytology as a marker for indications and follow-up of recurrence prevention of superficial urinary bladder cancers].

In 1985, we initiated a prospective clinical trial to evaluate the risk of recurrence for superficial bladder cancer. Up to now, 41 patients subjected to TUR have subsequently been monitored by immunocytology with a monoclonal antibody (mab 486 p) recently developed in our laboratory. Of these patients, 15 (36.6%) remained marker-negative and received no prophylactic therapy. There was only one recurrence (6.7%) in this subset of patients, whereas 10 out of 26 (38.5%) marker-positive patients have so far developed recurrent malignancies. In all cases, the conversion of immunocytological characteristics preceded visible recurrence by 2-5 months. These preliminary results indicate that immunocytology might make it possible to identify patients at low risk of recurrence more accurately than has so far been feasible with standard cytology or flow-cytometry.

Administration, Intravesical↗
PubMed1988

Treatment of acute cellular rejection in renal transplantation patients on ciclosporin with antithymocyte globulin.

Our treatment of acute renal cellular rejection in patients on ciclosporin (cyclosporin A) involves the almost complete elimination of T cells (according to individual T cell monitoring in peripheral blood) through antithymocyte globulin (ATG) therapy. We present here the results of treatment of 44 histologically or cytologically proven acute rejection episodes in 33 of 62 consecutive renal transplantation patients. ATG therapy resulted in a 95.5% success rate when duration and dosage were individually adjusted according to T cell elimination in peripheral blood. Only two grafts were lost, both because of vascular occlusions. In neither case could it be clarified whether the loss was due to primary vascular lesions or the result of severe rejection or side effects of ATG. Our data show that the elimination of primed T cells with ATG permits the use of ciclosporin even in the presence of an established immune response.

Adolescent↗