The present study was undertaken to investigate the antitumor effect of a combination of the antiestrogen tamoxifen (TAM) and either the antiprogestin onapristone (ON) or the progestogen megestrol acetate (MEG) in experimental mammary tumor models. Rats bearing DMBA- or NMU-induced mammary tumors were treated with ON or MEG either alone or in combination with TAM for four weeks. In the DMBA-tumor model, treatment with ON or TAM alone caused tumor remissions, whereas the combination of ON and TAM was almost as effective as ovariectomy (100% remission) and led to a remission of 86-100%. The combination of TAM and ON was distinctly more effective than that of TAM and MEG. A similar potentiation of the antitumor effect of TAM and ON was observed in the NMU-tumor model. In DMBA-tumors, the concentration of progesterone receptors was found to increase after treatment for three days with TAM and ON. In hosts bearing DMBA-tumors, treatment with the combination of TAM and ON caused a reduction in ovarian and uterine weights. In the same animals, the basal level of progesterone was decreased in spite of a slight increase in the LH level. These findings suggest that the high antitumor effect of the combination of TAM and ON compared to the corresponding monotherapies can be related not only to the interaction of antihormones and receptors, but also to the up-regulation of PR and to a decrease in progesterone production. These data clearly suggest the sense of a combination of TAM with an antiprogestin in breast cancer treatment.
2007-04-01·Investigative Radiology1区 · 医学
Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging
To investigate the potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for the differential diagnosis of nonalcoholic steatohepatitis (NASH) and fatty liver (FL).
Twenty-one male rats were divided into 3 groups. Seven rats in the NASH group were fed a choline-deficient diet for 10 weeks, and the 7 rats in the FL group were fed a standard diet also containing 1% (wt/wt) orotic acid for 4 weeks. As a control, 7 rats were fed a standard diet. After the feeding period, all rats were subjected to contrast-enhanced dynamic and delayed MRI with a 2D-FLASH technique. Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected into the tail vein at 24-hour intervals. Signal intensities of the liver were measured for each MR image and the relative enhancement (RE) was calculated. In addition, the time of maximum RE (Tmax) and the half-life of RE (T1/2) in liver were compared. After MRI, the liver was histologically analyzed to evaluate steatosis, hepatitis, and fibrosis.
Diffuse macrovesicular steatosis and severe fibrosis were observed in the NASH group, whereas diffuse microvesicular steatosis and rare fibrosis were observed in the FL group. Immediately after the Gd-DTPA injection, the RE in the liver of each group temporarily increased, and thereafter, rapid RE reduction was observed. However, a continuous increase and subsequent slow reduction of RE were induced after the Gd-EOB-DTPA injection. Although there was no difference between the Tmax and T1/2 of each group after the Gd-DTPA injection, Tmax and T1/2 of the NASH group were significantly prolonged in comparison with FL and control groups after the Gd-EOB-DTPA injection (P < 0.01).
It was possible to differentiate NASH and FL by evaluating the SI time course on Gd-EOB-DTPA enhanced MRI.
Current and future development of fludarabine phosphate (Fludara)
作者: Hayakawa, Masakane
A review, discussing the action mechanism and clin. pharmacol. of fludarabine phosphate (Fludara) injections for single and combination chemotherapy of chronic myelocytic leukemia and non-Hodgkin lymphoma.