Limited effectiveness of in vitro high-dose methotrexate and leucovorin to overcome resistance in L1210 leukemia cells with elevations of dihydrofolate reductase.
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Biomedical subjects
Publications and source records attributed to H Bruckner.
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Forty-six patients with recurrent disseminated ovarian carcinoma were treated with a combination of cis-dichlorodiammine platinum II (DDP) 50 mg/m2 and adriamycin 50 mg/m2 given intravenously every 3 weeks. All patients had failed prior chemotherapy. The combination of adriamycin and DDP produced objective responses in 14 of 46 patients. Severe side effects were frequent, but no patient died as a result of treatment. Disease in 4 of 7 complete responders is currently in remission up to 4 years.
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The chemotherapeutic agent methotrexate is metabolized by the intestinal flora of normal mice. This metabolism is reduced either by treatment of mice with the antibiotics neomycin and sulfathiazole, or in germ-free mice. In addition to affecting metabolism, these antibiotics alter physiological distribution of methotrexate so that excretion by the intestinal route is significantly enhanced.
Endoscopic ultrasonography was used to examine 38 patients with a pancreatic neoplasm (mean size, 2.8 cm; range, 1 to 5 cm). Three EUS signs appear to be reliable criteria for the identification of tumor invasion of major veins forming the portal confluence: (1) peri-pancreatic venous collaterals in the area of a mass that obliterates the normal anatomic location of a major portal confluence vessel; (2) tumor within the vessel lumen; and (3) abnormal vessel contour with loss of the vessel-parenchymal sonographic interface. At least one of these signs was present in each of the 21 patients with vascular invasion; none of them was present in the 17 patients without vascular invasion. Findings were confirmed by laparotomy plus biopsy (33 patients), autopsy (1 patient), or angiography plus biopsy (4 patients). Arterial involvement was identified by alteration of vessel course and caliber. All 7 patients with arterial involvement also had venous involvement. These signs provide reliable criteria for endoscopic ultrasonographic definition of unresectable tumors in patients with a pancreatic neoplasm that appears to be resectable on standard radiologic tests.