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.
The delivery of cytotoxic drugs in cancer treatment is often accompanied by posttreatment side effects (e.g., nausea). Moreover, there is evidence that cancer patients are at risk to develop these side effects in anticipation of chemotherapy (i.e., anticipatory nausea [AN]). AN can be explained as the result of a classical conditioning process with the cytotoxic drug as the unconditioned stimulus (US). Stimuli paired with the US (e.g., smells, tastes) can become conditioned stimuli (CSs) eliciting AN as the conditioned response (CR). The present study was conducted to test whether AN shows characteristics of a CR. Fifty-five ambulatory cancer patients were asked to record nine kinds of physical symptoms (e.g., nausea, vomiting, sweating) on time-scheduled symptom lists: after an infusion (indicating posttreatment symptoms) and prior to their next infusion (indicating anticipatory symptoms). Each measurement period covered a maximum of 48 hours. AN was reported by ten patients (18.08%). Data revealed (a) a statistically significant association between posttreatment nausea and vomiting, respectively, and AN; (b) the occurrence of AN increased with drug emetogenity (i.e., US-intensity); and (c) the duration of AN increased with temporal proximity to the infusion. The results support the conditioning model. Thus, it is proposed to prevent AN by classical conditioning techniques (e.g., overshadowing).
Polyploidy--the doubling of chromosome sets of cells caused by a stop of mitosis at different levels of the mitotic cycle--is a phenomenon widely observed in plants, protozoa, metazoa, and animals. In man obligate polyploid tissues are found in liver parenchyma, heart muscle cells, and bone marrow megakaryocytes. Polyploidy occurs mostly in stable and highly differentiated cells and tissues. Besides age, stimulation of proliferation and increased metabolic function lead to polyploidization in these organs. Aneuploidy, however, is exclusively found in tumor cells. Megakaryocyte differentiation and polyploidy are controlled by thrombopoietin-like activities, of which the loci of production are still unknown. Megakaryocytes are unique among polyploid mammal cells. On the precursor level they maintain their proliferative activity independently of the mammal's age. Once having entered the incomplete mitotic cycle they stop cytokinesis and develop into highly polyploid cells. Polyploidization of megakaryocytes is the basic requirement for establishing highly effective hemostasis in mammals, which exhibit blood circulation based on high blood pressures. Every polyploidization results in increased production of membrane materials with which the platelet becomes endowed. By shedding cytoplasmic fragments approximately 3000 platelets are set free from a 32c megakaryocyte, compared with only 16 nucleated thrombocytes by mitotic division. There is further evidence that the heterogeneity of platelets mostly depends on the different polyploidy classes of the megakaryocytes from which they are derived. Changes in the polyploidy pattern of megakaryocytes could therefore have consequences for hemostatic disorders in several human diseases, particularly in malignancy.
It has been shown that fatal "poisoning" with the mushroom species Paxillus involutus is caused by antibodies against the fungus in sensitized patients. Because circulating immune complexes play an important role, therapeutic procedures which can eliminate those complexes could stop immune hemolysis. A 37-year-old patient became severely ill after repeated ingestion of sufficiently cooked Paxillus involutus. As a result of hemolysis with reversible shock symptoms, acute renal failure developed. Plasma exchange with 3,000 ml albumin 5% was carried out daily during the first 3 days after admission. Each plasma exchange lowered free hemoglobin and immune complex levels by 60%-75%. Acute renal failure was successfully treated with hemodialysis. Specific IgG-antibodies against membrane particles of Paxillus involutus were detected by hemagglutination tests in the serum of the patient. The sequence of reactions resulting from the testing procedures strongly suggests the formation of immune complexes. These complexes are likely to bind to erythrocytes acting as innocent bystanders. Activation of the complement system finally results in hemolysis and shock. In addition to adequate shock treatment elimination of these immune complexes by plasma separation seems to be the therapy of choice.
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