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I.V., the maximal serum concentrations were 2.4 mg./mL, 1.7 mg./mL, and 0.52 mg./mL, respectively. As shown in FIG. No differences in lipid composition were noted (Holleran et al., 1986).The contribution of glycolipids may be important for the capacity of cells to survive a hostile environment (Furuya et al., 1995, Nakamura et al., 1996, Yan et al., 1995). Gangliosides are most abundant in the plasma membrane of neurons, where they constitute about 6% of the total lipid mass, though they are found in smaller quantities in most cell types. The immunizing composition is administered in a manner effective to stimulate antibody producing cells. The selective medium is generally one that contains an agent that blocks the de novo synthesis of nucleotides in the tissue culture media. 15B: Glycosylceramide levels in MDR Cells following drug treatment. Cancer Chemother. In regimens designed to cure testicular cancer, vinblastine is used in doses of 0.3 mg/kg every 3 weeks irrespective of blood cell counts or toxicity.The most important clinical use of vinblastine is with bleomycin and cisplatin in the curative therapy of metastatic testicular tumors. 65-66, 1986; Campbell, pp. For small-cell carcinoma of the lung, the intravenous dose (in combination therapy) is can be as much as 100 mg/m.sup.2 or as little as 2 mg/m.sup.2, routinely 35 mg/m.sup.2, daily for 4 days, to 50 mg/m.sup.2, daily for 5 days have also been used. A. Alternatively 0.02 mg/m.sup.2, 0.05 mg/m.sup.2, 0.06 mg/m.sup.2, 0.07 mg/m.sup.2, 0.08 mg/m.sup.2, 0.1 mg/m.sup.2, 0.12 mg/m.sup.2, 0.14 mg/m.sup.2, 0.15 mg/m.sup.2, 0.2 mg/m.sup.2, 0.25 mg/m.sup.2 can be given as a constant intravenous infusion. PPMP, alone, at the concentrations tested, had no effect on cell survival. Following the formation of specific immune complexes between the test sample and the originally bound material, and subsequent washing, the occurrence of even minute amounts of immune complexes may be determined.To provide a detecting means, the second or third antibody will have an associated label to allow detection. Elution occurs by changing the conditions to those in which binding will not occur (alter pH, ionic strength, temperature, etc.

Similar results have been obtained in KB-V-1 (vinblastine-resistant) epidermoid carcinoma cells, human melanoma, drug resistant ovarian carcinoma, cisplatin resistant breast cancer.The classical MDR reversing agents have wide diversity in effective potency. Using various solvent systems for TLC separation, the migration of commercial glycocerebroside (Gaucher's spleen) was compared with lipid-1 and -2 radioactivity and found that the compounds comigrated.Data thus indicate that lipids 1 and 2 are cerebrosides of the glycosylceramide type. 45 mg/m.sup.2 /day (30 mg/m.sup.2 for patients older than 60 yr.) for 1, 2 or 3 days every 3 or 4 wk or 0.8 mg/kg/day for 3 to 6 days every 3 or 4 wk; no more than 550 mg/m.sup.2 should be given in a lifetime, except only 450 mg/m.sup.2 if there has been chest irradiation; children, 25 mg/m.sup.2 once a week unless the age is less than 2 yr. or the body surface less than 0.5 m, in which case the weight-based adult schedule is used. The mass differences in glycosylceramide between the two cells was easily seen on TLC chars (FIG.

High levels of glycosylceramide have also been detected in other drug resistant cancer cells, showing that glycosylceramide accumulation is a general characteristic of MDR.A major challenge in cancer chemotherapy is to understand the molecular mechanisms by which the so-called chemosensitizing drugs circumvent MDR.

TNF can be quite toxic when used alone in effective doses, so that the optimal regimens probably will use it in lower doses in combination with other drugs. 7B. Previous work has reported an inhibition of acid sphingomyelinase activity of tamoxifen and other MDR circumventors (Jafferezou et al., 1995); however, these studies did not indicate whether sphingomyelin levels were altered.Further, the inventors have shown that synthesis of ceramide remained unchanged in the presence of tamoxifen, indicating that the tamoxifen site of action is distal to ceramide synthesis.

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