PubMed Health⌕ Search

Biomedical subjects

R Klapdor

Publications and source records attributed to R Klapdor.

At least 19 recordsLinked to original sources
PubMed1992

Detection of colorectal carcinomas by intraoperative RIS in addition to preoperative RIS: surgical and immunohistochemical findings.

The immunoscintigraphic detection of tumour foci less than 1 cm in diameter fails even with single photon emission tomography (SPET) owing to low contrast against background activity. In an attempt to improve detection of macroscopically invisible tumour spread, intraoperative scintimetry (IOSM) with a hand-held gamma-probe was performed in addition to SPET 24-30 and 41-48 h after injection of the technetium-99m carcinoembryonic antigen (CEA MoA) on 12 patients with colorectal carcinoma and 3 patients with different neoplastic and inflammatory diseases. Tumour specimens were measured in vitro in a gamma well counter. For comparison, the presence and amount of CEA in the tumour cells were evaluated immunohistochemically. After modification, the gamma-probe originally designed for iodine-131 was 20 times more sensitive; activities of 99mTc located close to the collimator hole were measured with absolute sensitivity of 100 cps = 2.5 kBq 99mTc. The unfavourably high background activity affected both the in vitro and in vivo analysis: SPET results had been considered positive in 8 of 15 cases. In vitro tumour/non-tumour (t/nt) ratios greater than 2.0 were found in 4 cases. In vivo IOSM resulted in t/nt ratios greater than 2.0 in only 3 patients. In most cases, there was no coincidence of elevated t/nt ratios from the different methods. A correlation was derived between positive immunoscintimetric in vitro findings and immunohistochemically proven interstitial localization of CEA in tumor cells. In conclusion, the measurement technique of IOSM seems adequate, but clinical success will depend on a more specific enrichment of MoA in tumour tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A randomized controlled trial of adjuvant immunotherapy (murine monoclonal antibody 494/32) in resectable pancreatic cancer.

In a prospective randomized multicentric trial, 61 patients from six hospitals with resectable pancreatic cancer were recruited between 1987 and 1989. All patients underwent a Whipple resection. Two weeks after surgery, the patients were randomized to be given either intravenous (IV) treatment with 370 mg (100 mg loading dose, 9 x 30 mg continuing within 10 days) of monoclonal antibody (MoAb) 494/32 (Behringwerke AG, Marsburg, Germany) or no additional anti-cancer treatment. This murine immunoglobulin (Ig) G1 antibody has been shown to strongly bind to human pancreatic cancer cells and to induce an antibody-dependent cellular cytotoxicity (ADCC). Both study groups were well matched with respect to age, sex, tumor staging, and grading. Six patients suffered from minor toxicity (vomiting and abdominal pain) after immunotherapy. Ten months after the end of the recruitment period, 65% and 53% of the patients in the treatment and control groups, respectively, had died. Of the living patients, 60% and 53% are alive with recurrent or progressive cancer disease. Median survival time was 428 days (range, 248 to 510 days) and 386 days (range, 296 to 509 days) in the treatment and control groups, respectively. The authors concluded that repeated IV treatment with the antibody 494/32 is not helpful in resectable pancreatic cancer. This study provides the first controlled data on passive immunotherapy in solid cancer.

Adult↗
PubMed1991

Radioimmunodiagnosis of pancreatic cancer disease.

From a theoretical point of view, immunoscintigraphy of exocrine pancreatic cancer offers itself as a promising diagnostic method. However, the actually available clinical and experimental data point out that the indication for diagnostic application in patients with pancreatic carcinoma has to be viewed more critically than in the case of, e.g., colorectal cancer disease. The quality of imaging depends on a lot of factors, such as the cellular antigen expression, the affinity of the MAbs to the corresponding antigens expressed by the cells, tumor vascularization, tumor size, and unspecific background activity as well as on labeling techniques, the kind of antibodies used, and the technical equipment. All these factors may vary from one patient to the other and from one center to the other. In summarizing the available clinical data, we have to state that immunoscintigraphy does not allow early detection of pancreatic cancer and, consequently, does not allow screening for early stages in asymptomatic patients. Even nowadays primary diagnosis and staging should be based on the imaging methods of ultrasound, CT and/or ERCP, and angiography. With respect to detection of local recurrence and especially peritoneal carcinosis, immunoscintigraphy, however, may be superior when compared to the other imaging methods. The potential clinical value for followup and as a preinvestigation to assess the probability of effective MAb treatment has still to be evaluated in prospective clinical studies. Altogether, a lot of experimental and clinical work remains to be done to introduce immunoscintigraphy of pancreatic cancer into clinical practice as a routine method.

Animals↗
PubMed1990

[Is there an advantage to neo- or adjuvant chemotherapy in pancreatic cancer?].

In view of the lack of representative clinical studies indication and potential value of neo-/adjuvant chemotherapy of pancreatic cancer has still to be discussed on the basis of palliative treatment results, prognostic and pathohistological data, theoretical considerations and experimental data. A critical analysis, however, indicates that the widespread therapeutical nihilism at least with regard to adjuvant trials should be obsolete today. On the contrary, adjuvant chemotherapeutic trials should be recommended, alone or in combination with radiation or immunotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Individualization of chemotherapy through in vitro predictive determination of the cytostatic sensitivity of malignant tumors].

An in-vitro test was developed for predicting the efficacy of anti-tumour chemotherapy. Cell cultures were grown from freshly removed tumours and it was then demonstrated by DNA cytophotometry and immuno-cyto-chemistry whether the growing tumour cells corresponded to those of the original tumour cells. Several cytostatic agents were then tested for their efficacy of inhibiting growth at clinically customary dosage. Growing cell cultures were established in 306 of 413 submitted tumours (74%). They responded quite differently to the various drugs that were tried. The clinical course in 94 cases was observed for minimally four and a mean of eight months to obtain an in-vitro to in-vivo correlation of response, with 178 individual correlations. A discrepancy was recorded in 16% of cases, a false-positive in-vitro sensitivity result was 3.6 times more frequently associated with an in vivo resistance than the reverse. Concordance between test results and clinical tumour response occurred in 84%. The monolayer proliferation assay correctly indicated resistance in 93.8%, sensitivity in 72.8%.

Antineoplastic Agents↗
PubMed1989

[Insulin reserve and morphology of the tail of the pancreas following resection of the head of the pancreas using various surgical methods].

Four modifications of dealing surgically with the remaining pancreas after resection of the pancreatic head were compared to each other in dogs. Insulin response and corresponding blood sugar levels were controlled, the remaining pancreas was examined histologically. The obstruction of the pancreatic ducts by prolamine showed mainly sclerosis of the exocrine tissue whereas the duct ligation was followed by atrophy. The free intraperitoneal draining of the duct system showed both alterations, the pancreatojejunostomy did hardly impair the exocrine pancreas. According to the grade of sclerosis of the exocrine tissue, the insulin response was delayed followed by a pathologic glucose tolerance. This was shown particularly for the obstruction of the ducts by prolamine.

Amylases↗
PubMed1989

Increase in B-cells in the pancreatic remnant after partial pancreatectomy in pigs. An immunocytochemical and functional study.

The regenerative and functional capacity of B-cells in the remaining pancreatic tissue after surgical removal of 40%, 60% and 80% of the pancreas was examined in 7 month old pigs (three animals in each group). Prior to resection and 1, 3 and 6 weeks after surgery, basal and glucose-stimulated levels of insulin and blood glucose were determined and compared with the preoperative data and that of sham-operated controls. For quantitative morphology, the volume of the resected specimen and the residual pancreatic tissue, 6 weeks after surgery, was determined and sections evaluated by immunocytochemistry (insulin, glucagon, somatostatin, pancreatic polypeptide) combined with morphometry. In the remaining pancreas, the volume density of the B-cells was increased by 19% (1.57-1.92 after 60% resection; p less than 0.02) and 56% (1.57-2.38 after 80% resection; p less than 0.02) 6 weeks after surgery, compared with the respective resected portion of the pancreas and the controls (n = 12). The non-B-cells gained between 0-10% (PP-cells), 10-20% (D-cells) and 30-40% (A-cells) in the different resection groups. As the number of B-cells per given islet area remained unchanged (mean 4.12 cells/0.25 mm2), the increased volume density was due to an increase in cell number rather than cell size. Insulin secretion (integrated values, 0-120 min), was not significantly impaired after 40% and 60% resection (2711 +/- 250 all preoperative samples; 3215 +/- 474 40% at 6 week intravenous glucose tolerance test (IV-GTT); 1677 +/- 109 60% at 6 week IV-GTT), although the glucose levels (integrated values) were increased during the IV-GTT. The 80% resected animals showed a significant decrease in the insulin response only 1 week after surgery (integrated values: 2711 +/- 250 all preoperative samples, compared with 1250 +/- 508 1 week IV-GTT; p less than 0.05), while the integrated glucose values during IV-GTT (0-120 min) were significantly elevated throughout the observation period. These results suggest a B-cell hyperplasia in the residual pancreas after resection, which may cope with a normal functional demand, but disclose functional abnormalities when challenged with an increased glucose load.

Animals↗
PubMed1989

Cytokines and pancreatic cancer. The effect of rIFN-gamma, HuLeIFN, rTNF-alpha, and LAK-cells on pancreatic and other gastrointestinal tumors in vitro.

A panel of 10 digestive tract carcinoma cell lines (6 pancreatic carcinomas) was assayed for their sensitivity to HuLeIFN, human rIFN-gamma, rTNF-alpha and allogeneic human LAK-cells in vitro. In addition, a combination of rIFN-gamma + rTNF-alpha was tested on 3 pancreatic carcinoma cell lines. Whereas 6/7 cell lines were completely resistant to HuLeIFN, rIFN-gamma and rTNF-alpha did inhibit growth of some carcinomas tested. The individual sensitivity was heterogenous as is already known from cytostatics. Response to rIFN-gamma tended to increase with increment of cell doubling time. Only high concentrations (greater than 1000 U/ml) of rIFN-gamma displayed cytotoxicity on sensitive tumors. The antitumoral effect of rIFN-gamma was stimulated by rTNF-alpha. As revealed by isobole analysis this interaction was synergistic in all pancreatic carcinomas tested. In comparison to rIFN-gamma or rTNF-alpha the response to LAK-cells was slightly superior at high effector target ratios, even though heterogenous.

Biological Factors↗
PubMed1989

Combined therapy of xenografts of human pancreatic carcinomas with rTNF-alpha and mitomycin C.

Based on previously published experimental studies in nude mice indicating that rTNF-alpha as well as mitomycin C are able to induce significant growth inhibition of xenotransplants of gastrointestinal and pancreatic carcinomas we have investigated the antitumor effects of rTNF-alpha (0.8 mg/kg daily for 21 days) and mitomycin C (2.4 mg/kg once weekly, day 1, 7, 14) as single drugs and in combination (0.8 + 2.4) in nude mice bearing xenografts of 4 human pancreatic carcinomas and 1 colorectal cancer. Serum CA 19-9 was measured additionally to tumor growth rate. The results demonstrate that combined treatment is more effective compared to rTNF-alpha and mitomycin C alone. Combined therapy resulted in a significant inhibition of tumor growth in 3 of 5 xenografts and in decrease of tumor volume to less than 50% of the initial values in 2 of 5 tumors. The results support the concept that combinations of cytokines with cytostatics might be of value for treatment of gastrointestinal and pancreatic cancer in vivo.

Animals↗
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↗