Intra-arterial chemotherapy of malignant gliomas.
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Biomedical subjects
Publications and source records attributed to D Dormont.
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Long term cultures of Reed-Sternberg like cells were obtained from lymph node biopsies of two patients suffering from Hodgkin's disease. As soon as the 15th day of culture, a weak magnesium-dependent reverse transcriptase activity was observed in the cell culture supernatants. Retroviral-like particles were observed in cell cultures as well as in their supernatants.
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20 patients with F.I.G.O. stages III ovarian cancer were entered into a randomised trial between January 1980 and March 1984. After a surgical resection as complete as possible, 10 of these patients received an intravenous chemotherapy with Adriamycin, Vincaleucoblastin Bleomycin, Fluorouracil and Ifosfamid monthly for 10 months. The other 10 patients received the same combined chemotherapy but by a double route: Intravenously and intraperitoneally. The results were judged at "second look surgery". 1 Of the 10 patients who were treated intravenously, 2 who had had a complete surgical resection had no recurrence. Of the remaining 8 patients who had had an incomplete resection, 4 still had residual lesions that could not be removed completely.
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Lymphadenopathy associated virus is inactivated by heating at 56 degrees C for 30 min, and is not inactivated by 2 X 10(5) rad gamma irradiation or 5 X 10(3) J/m2 ultraviolet irradiation.
Anergy associated with an increase in suppressor helper T cell (Tc) ratio and a decrease in natural killer (NK) is one main cause of death following thermal injury (Tl). Recently, in vitro studies have shown that LTB4 can induce human Tc to exert suppressor cell activity, and incubation of lymphocytes with LTB4 for 24 hours significantly suppressed NK cell activity. Thus, we undertook an investigation of both AA metabolism and immunologic response in 20 patients who suffered 40-90% total body surface area (TBSA) burns. Cyclooxygenase (CO:RIA) and lipoxygenase (LO;HPLC det.) metabolites and superoxide (O2 X-) production were measured in stimulated polymorphonuclear cells (PMNL) (A 23187 +/- AA for icosanoid release; phorbol myristate acetate for O2 X-production). Lyso-paf-acether (P-LPA) was measured in plasma samples. Ca2+-dependent K+permeability in PMNL was measured by the cell K+ release induced by A 23187. Tc and Tc subsets were determined using monoclonal antibodies (OKT3+, OKT4+ and OKT8+). A biphasic sequential release of the different substances (leukocytic icosanoids and O2 X-) was monitored: increase (approximately 36-48 h after Tl) and decrease (greater than or equal to 72 h after Tl). The increase in AA stimulation was more transient than that of O2 X -. The decline in the release of AA metabolites and O2 X-production was associated with the anergic phase (decrease OKT4+/OKT8+ ratio) and with the clinical outcome of the patients. The decrease in LTB4 and other LO metabolites could explain the impairment of neutrophil chemotaxis. Ca2+-dependent K+ permeability increased early up to 2 or 3 times normal. In order to go further with the mechanism of inhibition of LTB4 and O X-release, the effect of Tl plasma was assayed on normal leukocytes: a 10 min incubation with such plasma was sufficient to abolish LTB4 secretion. A less important inhibition was observed with O2 X-release (-32%) and Ca2+-dependent K+ permeability (-30%). Plasma inhibition seems to be due to a thermolabile factor(s) [protein(s): "suppressive factor(s) of membrane activation "SFMA] which is (are) under active investigation using gel-filtration chromatography and fast protein liquid chromatography (FPLC). Among the SFMAs, certain acute phase proteins could play a key role: i.e., incubation (10 min) of normal PMNL with ceruloplasmin (1 mg/ml) abolished LO products and O X 2-release.
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Sixteen patients with clinical primary inflammatory carcinoma of the breast were treated with initial immunochemotherapy from September 1974 to May 1977. This chemotherapy was an association of adriamycin, vincristine, fluorouracil, methotrexate, and melphalan. Thermographic cooling was taken as the criterion of operability. Chemotherapy was resumed after surgery up to a total of ten periods, and followed by a minimum one year chemotherapy. I-BCG-F Pasteur was used as immunotherapy and associated with the chemotherapy regimen. Five patients have died, four are alive with disease, and seven are free of disease at time of reporting. Median survival exceeds 90 months. Our data supports the conclusion that mastectomy combined with preoperative and postoperative immunochemotherapy may permit a better prognosis for inflammatory carcinoma of the breast: this benefit seems to be the consequence of adapting the length of initial chemotherapy to the data given by plate-thermography.
Mouse glial and neuroblastoma cells were infected with the mouse adapted strains C506 and 139A of scrapie agent. Lysates of the in vitro infected cells (from the 3rd to the 16th passage) intracerebrally inoculated into CD-1 mice, caused the development of a neurological disease, with characteristic signs of scrapie. Morphological changes in scrapie-infected neural cells were observed after about fifteen in vitro passages. In liquid medium, the cloning efficiency of these cells increased. They acquired the capacity to form large tridimensional colonies in agar. Heating the infectious brain extracts at 60 and 80 degrees C for 30 minutes did not inhibit these changes thus showing the involvement of the thermoresistant scrapie agent. Supernatants of scrapie-infected glial cells promoted colony formation in liquid medium with different types of normal cells. Analysis of supernatants of scrapie-infected mouse neuroblastoma cells showed a profound modification of neurotransmitter metabolism.
Between the years 1972 and 1978, 55 women who were less than 40 years of age at the time of the diagnosis of the condition and of the original treatment were studied. 32 of these had local and regional treatment, which was surgery with or without radiotherapy. The remaining 23 had chemotherapy as well. Their prognosis was compared with those of 288 women who were more than 40 years of age and treated during the same period of time. Various comparisons were carried out between the two groups according to their treatment, the size of the tumour and the degree of lymph node invasion. This showed, on the one hand, that chemotherapy was beneficial in all groups whether they were less or more than 40 years of age, and on the other hand, that being young when the condition was first diagnosed made the prognosis poorer.