Effects of Paclitaxel, Irinotecan, and Mitomycin C on a Highly Malignant Xeno-Transplanted Neuroblastoma

BACKGROUND: The purpose of this study was to assess the efficacy of three chemotherapeutic agents both new and old, on a human neuroblastoma xenograft, designated TNB9, according to the standard Battelle Columbus Laboratories protocol. Cytogenetic and phenotypic analyses showed that TNB9 was one of the most malignant strains among human neuroblastoma xenografts. METHODS: When the estimated TNB9 tumor weight reached 100 to 200 mg, 28 nu/nu BALB/c tumor- bearing mice were randomly divided into 4 groups. One of three drugs was administered intraperitoneally in a total of three doses at four-day intervals to the mice in each experimental group while the control group received injections of normal saline. The doses of these agents at each injection were equivalent to one-third of the LD50. The results were evaluated on the basis of the maximum inhibition rate and also by the degree of tumor regression. RESULTS: Maximum inhibition rates were as follows: mitomycin C, 95.6%; irinotecan (CPT-11), 72.5%; paclitaxel, 46.4%. Mitomycin C was graded as having effects, representing tumor regression. Irinotecan was also effective against TNB9, and none of the irinotecan treated mice lost weight, suggesting minimal toxicity. CONCLUSIONS: Assessment of the chemotherapeutic sensitivity in vivo showed that irinotecan, mitomycin C were active agents whereas paclitaxel had minimal or marginal activity in the treatment of neuroblastoma.

Alteration of Coagulation and Fibrinolysis in Multiple Trauma

BACKGROUND: After multiple trauma, blood coagulation activity is enhanced and fibrinolytic activity is suppressed. Due to high tissue thromboplastin concentration in cerebral tissue, more serious coagulation and fibrinolytic abnormalities may occur when concomitant head trauma is present. The aim of this study was to determine the changes in coagulation and fibrinolysis after trauma and the effects of head trauma on coagulation and fibrinolysis. METHODS: This study includes 35 trauma patients: 16 patients with head trauma (group A) and 19 patients without head trauma (group B). We measured the plasma levels of functional protein C, antithrombin III (AT III), thrombin antithrombin III complex (TAT), plasmin alpha 2 plasmin inhibitor complex (PIC), tissue plasminogen activator antigen (t-PA), and plasminogen activator inhibitor-1 antigen (PAI-1) on admission and on days 1, 2, 4, and 6 after the trauma. RESULTS: The TAT and the TAT/PIC were significantly higher in group A than in group B on all days. PIC was significantly lower in group A than in group B on all days except the day of admission. Over the course of time, the TAT and the TAT/PIC decreased in both groups and PIC increased. On admission, the PAI-1 of both groups was increased, but it decreased over the course of time. The t-PA was increased on admission, was suppressed on the 1st day, and then increased again. The PAI-1 and the t-PA showed no significant difference between the two groups. CONCLUSIONS: After multiple trauma, coagulation was enhanced and fibrinolysis was suppressed. Enhanced coagulation and suppressed fibrinolysis were significantly greater in group A than in group B.