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 × 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.
Studies on intraabdominal infections have been difficult to compare in the past due to a missing system of classification for peritonitis. According to a recently developed classification system, secondary peritonitis, including spontaneous acute peritonitis, postoperative peritonitis and posttraumatic peritonitis, is the most common complication of severe intraabdominal infections. In several studies the mortality rate of postoperative peritonitis was still between 60% and 79%. Scoring systems were developed, some of them with the idea to predict mortality in peritonitis. Although the APACHE II score cannot predict the outcome of peritonitis in an individual patient, it is a reliable, valid and objective system for risk stratification in intraabdominal infections. Local trauma or bacterial contamination is responsible for an acute phase reaction, which involves the release of certain cytokines such as TNF-alpha, interleukin-1 (IL-1) and interleukin-6 (IL-6). The IL-6 seems to play an important role in the mechanism of the acute phase reaction, acting on hepatocytes to release acute phase proteins (e.g. CRP). Preliminary results of investigations of IL-6 levels in peritonitis indicate a possible role for IL-6 as a predictor of the outcome of peritonitis.
In a phase I trial 34 patients w i t h 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 t o 14 days (highest single dose 100 mg, highest cumulative dose 490 mg). During this treatment serum levels of murine IgG increased t o 43.4 pg/ml. The serum half life of murine IgG ranged from 2 t o 3 days. Repeated injections of M A b BW 494 were normally well-tolerated when given within the f i r s t I 5 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 f i r s t application of MAb BW 494, 17/18 patients presented with H A M A (IgG). It could be demonstrated that the anti-murine response was in part anti-idiotypic. A t 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 t o 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 t o 40 weeks). Nine patients had progressive tumor disease in spite of MAb treatment.Antigenic determinants or epitopes on pancreatic cancer recognized by MAbs can be associated with glycolipids (Magnani et al., 1982) and/or glycoproteins (Magnani et al., 1983), and can be carbohydrate or protein in nature (Imai et al., 1984). The murine MAb BW 494 (BI 51.011) defines a carbohydrate epitope located on a more than 200 kDa glycoprotein which is mainly expressed on the majority of well-differentiated adenocarcinomas of the pancreas (Bosslet et al., 1986).This antibody was selected for an immunotherapy phase I trial because of several functions: 1) Strong reactivity in vitro and in vivo with pancreatic cancer of histological grading I and I1 (Bosslet et al., 1986;Montz et al., 1986). In radio-imaging studies the antibody conjugated to 1311 or ll1I specifically localized human tumor xenografts in nude mice as well as primary tumors and metastases in patients Klapdor et al., 1986). 2) The MAb BW 494 mediates antibody-dependent-cellular-cytotoxicity (ADCC) with human mononuclear cells against "Crlabelled pancreatic cancer target cells in vitro (Bosslet et al., 1986). 3) In addition, this antibody inhibits endocytosis, superoxide anion generation and release of lysosomal enzymes of these cancer cells (Schorlemmer et al., 1987). 4) Finally, single regional injection of radiolabelled MAb BW 494 in nude mice caused suppression of tumor growth (Klapdor el al., 1986).Murine MAbs, which are able to initiate inflammatory reactions in tumor tissues, successfully induced long-term remissions in patients with advanced melanomas (Hou...
Native Fluorescence, Tumor, Lung Illumination of unstained 9 |am cryosections of lung tissue with 365 nm results in visible fluorescence light with a maximum intensity at about 460 nm. These fluorescence tomographical studies can be used for detecting carcinoma of the lung. The fluorescence pattern obtained can be matched nicely with histological findings. Since it takes less than 5 min for getting the fluorescence images, the fluorescence tomographical technique might be used in addition to established methods for determining the histology of a biopsy sample.
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