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R Klapdor

Publications and source records attributed to R Klapdor.

At least 37 records · Page 2Linked to original sources
PubMed1989

Cytokines and pancreatic cancer. Sensitivity of xenotransplants of predominantly pancreatic carcinomas to rIFN-gamma and rTFN-alpha in nude mice.

Ten xenotransplants of human gastrointestinal carcinomas (eight human pancreatic carcinomas) were assayed for their sensitivity to human rIFN-gamma and human rTNF-alpha in nude mice. Both substances demonstrated a dose and route dependent antitumoral activity in principle. However, the extent of response varied distinctly between the tested xenografts. rTNF-alpha was clearly superior to rIFN-gamma at systemic application of comparable doses (0.8 mg/kg/d). Intramural administration of both cytokines could cause cytotoxic effects and was significantly more effective than systemic administration that predominantly resulted in antiproliferation. Growth inhibition of rIFN-gamma or rTNF-alpha alone could be clearly enhanced by combining both cytokines. In addition, the results suggest: the possibility to enhance the effects of rIFN-gamma alone also by combination with nIL 2, as well as a decrease of the effects of rTNF-alpha with time of therapy.

Animals↗
PubMed1988

Immunotherapy of pancreatic cancer with monoclonal antibody BW 494.

In a phase I trial 34 patients with pancreatic cancer were treated with the murine monoclonal antibody (MAb) BW 494 (BI 51.011) directed against a glycoprotein antigen. The patients received repeated doses of MAb over a time period from 5 to 14 days (highest single dose 100 mg, highest cumulative dose 490 mg). During this treatment serum levels of murine IgG increased to 43.4 micrograms/ml. The serum half life of murine IgG ranged from 2 to 3 days. Repeated injections of MAb BW 494 were normally well-tolerated when given within the first 15 days. Two patients presented with fatigue and a neuritis-like syndrome 2 weeks after the last IgG infusion which had resolved spontaneously by the next day. Severe allergic reactions were observed in 3 patients after repeated injections of the MAb. These 3 patients had high levels of human anti-murine antibodies (HAMA). Four weeks after the first application of MAb BW 494, 17/18 patients presented with HAMA (IgG). It could be demonstrated that the anti-murine response was in part anti-idiotypic. At the moment 16/34 patients are eligible for evaluation of tumor response. There was no complete or partial remission; however, 2 patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in CAT scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). Nine patients had progressive tumor disease in spite of MAb treatment.

Adult↗
PubMed1988

[Intravenously stimulated insulin reserve of the pancreas following experimental pancreatic duct ligation in the swine--studies 2, 4 and about 60 days following ligation].

After pancreatic duct ligation (PDL) intravenous glucose tolerance tests (i.v. GTT) were performed in 12 pigs. The release of insulin and the corresponding blood sugar levels were controlled, the pancreata were examined histologically and immunohistochemically. In spite of a reduced number of beta-cells no reduction of glucose tolerance could be shown 60 days after PDL. Two days after the i.v. GTT showed an increased release of insulin corresponding with lowered blood sugar levels. This phenomenon is explained as a stimulated state of the beta-cell in the phase of interstitial edema.

Animals↗
PubMed1988

Immunoscintigraphy with combinations of various monoclonal antibodies--studies on xenografts of human gastrointestinal carcinomas.

In order to investigate whether combinations of monoclonal antibodies (MAbs) allow a more sensitive and valid localisation of tumors by immunoscintigraphy compared to the application of single MAbs we injected 3.7 MBq/animal of various 131I-labelled MAbs (anti-CA 19-9, -CA 125, -CEA, BW 494/32, 431/31) or equivalent combinations thereof into NuNu-Balb-C mice bearing xenografts of human gastrointestinal tumors. In addition, "dose response curves" were calculated in order to evaluate the results for different total doses. As parameters we mainly used quality of the scans, fractional uptake of injected dose and tumor/blood or tumor/organ ratios. The results do not support the concept that "cocktails" of MAbs improve the results of immunoscintigraphy. In contrast, a single MAb should be used for clinical immunoscintigraphy, preferably the most appropriate one according to the results of serum determinations of the corresponding tumor-associated antigens or of immunohistochemistry. Cocktails or consecutive applications of different MAbs for immunoscintigraphy should be restricted to cases without dominant tumor-associated antigen and corresponding MAb, respectively, and to patients in whom a first trial with a first single MAb failed.

Animals↗
PubMed1988

[Radioimmunotherapy of solitary liver metastases using intratumor instillation of 131I-labeled monoclonal antibodies--initial results of a clinical study].

Solitary liver metastases (carcinoembryogenic antigen positive) in two patients suffering from colon carcinoma were multifocally injected with 131I-labelled monoclonal antibodies (131I-MAb) against the carcinoembryogenic antigen (CEA). The 131I activity in the metastases decreased biexponentially. The 131I serum concentration declined triexponentially in patient 1 and monoexponentially in patient 2. The radiation dose to the whole tumor volume amounted to 358 Sv and 762 Sv, respectively; the whole-body radiation dose was 87.5 mSv for patient 1 and 39.0 mSv for patient 2. Complications did not occur. Before treatment there had been a volume doubling time of the metastases of 1.5 and 0.9 months, respectively; this contrasts with a constant tumor volume after treatment as observed over the follow-up period of 3.5 and 2 months, respectively. The CEA serum concentration decreased after 131I-MAb instillation within 1.5 and 2.5 months to 66% and 58%, respectively, when compared with values immediately before treatment. On the basis of these results the intratumoral application of 131I-MAb appears in selected cases to be a suitable method of slowing down growth of liver metastases from gastrointestinal tumors.

Antibodies, Monoclonal↗
PubMed1988

Human monoclonal anti-idiotypic antibodies as an epitope vaccine against pancreatic carcinoma.

During therapeutic repetitive application of MAb BW 494 in pancreatic carcinoma patients, a human IgG anti MAb BW 494 response arose, which was analyzed on the B cell clonal level as well as in the serum of these patients 2-4 months after treatment. From 5 investigated patients 3 developed a polyclonal human IgG anti-idiotypic response in the serum and had B cells with the same specificity which could be immortalized by EBV transformation. Two out of 5 patients showed an anti-idiotypic and anti-isotypic polyclonal response which could be found on the B cell clonal level as well. The data indicated that the human IgG anti MAb BW 494 response was mainly anti-idiotypic.

Antibodies, Monoclonal↗
PubMed1988

[Monoclonal antibodies in the therapy of non-resectable pancreatic cancers. Initial experiences].

In this study 34 patients with pancreatic cancer were treated postoperatively with monoclonal antibodies (MABs). The antibody BW 494/32 is directed against a membrane antigen of differentiated adenocarcinomas of the pancreas and mediates cellular cytotoxicity. The patients suffered from non resectable tumors, mostly with lymph-node or liver metastases. The patients received repeated doses of MABs over a time period from 5 to 14 days. The highest single dose was 100 mg, the highest cumulative dose 490 mg. At the moment 16 out of 34 patients are eligible for evaluation of tumor response. There was no complete or partial remission (reduction more than 50% of tumor volume). However, two patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in cat scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). 9 patients had progressive tumor disease in spite of MAB-treatment. Two to three weeks after antibody infusion most patients produce human anti-murine-antibodies, so that severe allergic reactions may occur, if the application is repeated.

Adenocarcinoma↗
PubMed1986

Antigen detection by the monoclonal antibodies CA 19-9 and CA 125 in normal and tumor tissue and patients' sera.

The tumor markers CA 19-9 and CA 125 defined by the monoclonal antibodies 19-9 and OC 125 were investigated with respect to organ specificity and tumor sensitivity. Normal and tumor tissue specimens, and blood samples from 34 patients with pancreatic carcinomas, 40 with ovarian carcinomas and 39 with miscellaneous tumors were examined. CA 19-9 and CA 125 were determined by immunohistochemistry (IH) applied to sections of the tumors and adjacent normal tissues. In parallel, the antigens were measured in the patients' sera by radioimmunoassay (RIA). By means of IH CA 19-9 and CA 125 were detected in normal surface cells from many different organs. Both antigens were also found in tissue sections of various types of tumors and in the sera of the corresponding patients. Thus, organ specificity could not be demonstrated. Sensitivity of CA 19-9 was found to be high for pancreatic carcinomas, i.e., 88% of the tumors expressed the antigen shown by IH and 85% of the sera revealed concentrations above the cut-off value (greater than 37 units/ml). Evidence for CA 125 was high in ovarian carcinomas with a tissue positivity in 83% and elevated (greater than 35 units/ml) serum levels in 70% of patients. Comparing IH and RIA case by case a discrepancy was found in 14% of cases with positive IH and low serum values a vice versa. Reasons for this finding are small tumor mass not producing elevated serum levels, retention of the antigen inside the tumor cells because of defective release mechanisms demonstrable only by IH, or heterogeneity of tumors with only focal antigen expression not present in the tissue sections investigated and thus disclosable only by RIA. The relevance of immunohistochemical detection of the antigens for therapeutic planning is discussed.

Antibodies, Monoclonal↗
PubMed1986

Inhibition of gastric acid secretion by brain peptides in the dog. Role of the autonomic nervous system and gastrin.

We have studied the effects of 30 peptides administered intracerebroventricularly on basal and pentagastrin-stimulated (8 micrograms/kg s.c.) gastric acid secretion in conscious dogs. None of the peptides significantly increased basal gastric acid secretion. Twelve peptides (2 nmol/kg) significantly (p less than 0.01) decreased the pentagastrin-stimulated 2-h acid output (percentage inhibition in parentheses): human calcitonin (CT) (36%), neurotensin (NT) (52%), rat corticotropin-releasing factor (CRF) (59%), human calcitonin gene-related peptide (CGRP) (59%), ovine CRF (66%), beta-endorphin (beta-End) (80%), urotensin-I (81%), rat CT (81%), porcine gastrin-releasing peptide (GRP) (83%), sauvagine (Svg) (85%), rat CGRP (87%), and bombesin (Bom) (95%). Blockade of the autonomic nervous system with chlorisondamine abolished the gastric inhibitory action induced by CRF, beta-End, CT, and NT, but not by CGRP and Bom (1 nmol/kg each). Corticotropin-releasing factor, beta-End, CT, NT, CGRP, and Bom significantly inhibited gastric acid secretion stimulated by an intragastric 8% peptone meal for 2 h. None of these six peptides significantly altered plasma gastrin concentrations in response to the peptone meal as compared with control experiments. A rise of plasma concentrations of gastrin, CT, CRF, and CGRP could not be detected by radioimmunoassay in animals after intracerebroventricular administration of these four peptides. The results of this study indicate that CT, CGRP, NT, beta-End, and peptides of the CRF and Bom families act within the brain to inhibit pentagastrin- and meal-stimulated gastric acid secretion in conscious dogs. None of the 30 peptides administered intracerebroventricularly increased basal gastric acid secretion in the dog. Inhibition of gastric acid secretion induced by CRF, beta-End, CT, and NT, but not by CGRP and Bom is mediated by the autonomic nervous system. Gastrin does not appear to play a role in gastric acid inhibition induced by the six brain peptides studied.

Animals↗
PubMed1986

Immunoscintigraphy and radioimmunotherapy in patients with pancreatic carcinoma.

A new monoclonal antibody (BW 494/32) labeled with 131I or 111In was used for planar and tomographic immunoscintigraphy (IS) in patients with pancreatic carcinoma. It appears that IS for pancreatic carcinoma and its metastases remains a hopeful but still difficult procedure and labeling with 111In is of advantage and results in more convincing images in the case of tumor lesions distant from liver and spleen. Attempts at radioimmunotherapy with 131I-anti-CA 19-9 and with 131I-494/32 in a patient with local recurrence of a pancreatic cancer and with large liver metastases were without success because of extremely poor blood supply to the metastatic tumor masses. Intraarterial infusion of the tracer without or with blockade and perfusion of the common hepatic artery with saline solution could not enhance the tracer uptake compared to that after intravenous infusion. High intratumoral concentrations, however, as achieved e.g. by intratumoral instillation in animal studies, represent a necessary precondition for effective beta-irradiation of tumor lesions.

Adult↗