Responsiveness of experimental chemotherapy on human cancer xenografts in nude mice was directly compared with clinical response to the same chemotherapy in their donor patients. These xenografts were 1 line of rectal cancer (H-26), two lines of gastric cancer (H-08 and H-22), and 1 line of breast cancer (H-62). Experimental chemotherapies studied were single-drug FT-207 to four lines of xenografts and a combination of mitomycin C, 5-FU, and cytosine arabinoside (MFC) to a line of gastric cancer H-08. Single-drug treatment with FT-207 to H-26 resulted in remarkable retardation of the tumor growth. The comparative treatment with FT-207 suppository to the donor patient of H-26 showed appreciable response. All the other chemotherapies to three other lines (H-08, H-22, and H-62) induced no significant response, which was parallel to the corresponding clinical response in each donor patient. The sensitivity to chemotherapeutic drugs was thought to be still preserved in human cancer xenografts in nude mice.
Abrupt disease onset and severe metabolic disorders are main characteristics of fulminant type 1 diabetes. Diffusionweighted magnetic resonance imaging (DWI) is an imaging technique that reflects restricted diffusion in organs and can detect mononuclear cell infiltration into the pancreas at the onset of the disease. Fourteen patients with fulminant type 1 diabetes who underwent abdominal magnetic resonance imaging were recruited for the measurement of apparent diffusion coefficient (ADC) values of the pancreas that were compared with those of 21 non-diabetic controls. The ADC values of all parts of the pancreas were significantly lower in fulminant type 1 diabetes than in controls (head, 1.424 ± 0.382 × 10 −3
High-dose methotrexate(H-D MTX) therapy followed by citrovorum factor rescue is now widely used for the treatment of childhood malignant tumors. To understand pharmacokinetics and toxicity of H-D MTX (50-300 mg/ kg), we measured plasma and urine levels of the subject after a total of 170 infusions to 16 children. The samples were obtained 12, 24 and 48hr after the beginning of 6 hr infusion. Two phases of plasma MTX disappearance were seen after infusion: the first phase (12-24 hr) had a half-life 2.28-3.27 hr and the second phase (24-48 hr) 6.96-8.74 hr. Significant correlation was obtained between dosage and plasma levels on concentration curve. With the same dose, the younger patients (under 8 years) had low plasma MTX levels, as compared with the older patients (over 13 years). After H-D MTX infusion, severe toxicities such as myelosuppression, abnormal kidney function and stomatitis were observed in 2 cases. We consider that the maximum allowable plasma MTX levels be 10-5M at 24hr and 10-6M at 48hr, on the basis of the finding that the plasma MTX levels in these cases exceeded those levels, respectively, at the same hours. From the beginning of H-D MTX infusion, cumulative urinary excretion in the first 12hr was greater than 50% of the administered dose. Our data suggest that in view of the safety of H-D MTX therapy, monitoring of plasma MTX levels and adequate hydration be important, especially for the older patients.
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