Background We studied the relationship between the augmentative effects of leucovorin (LV) on 5-fluorouracil (5-FU) and the inhibition
rate of thymidylate synthase (TS) activity in Colon 26 murine colon carcinoma cells and L1210 murine leukemia cells.
Methods In cytotoxic and TS inhibition studies, cells were exposed for 24 hours to varied concentrations of 5-FU alone or in combination
with 1 or 10 μmol/L LV. Cytotoxicity was determined by colony forming efficiency or trypan blue dye exclusion, and TS inhibition
rate was determined by [6-3H]-5-FdUMP binding assay. A growth inhibition curve was constructed for longer exposures.
Results For tumor cell growth inhibition and cytotoxicity, the augmentative effect was observed when the lower 5-FU concentrations
(0.1 μg/mL) were used. There was no difference in the effects between the low (1 μmol/L) and high (10 μmol/L) LV doses. Normally,
TS enzyme levels rise acutely when cells are exposed to 5-FU. Both cell lines displayed an increase in TS after exposure to
5-FU. This exposure to 5-FU resulted in the maintenance of free enzyme. LV was able to increase the ternary complex and TS
inhibition rate with little induction of TS, however, the inhibition rate was not dependent on doses of LV.
Conclusions It was concluded that the augmentative effect of LV at a concentration of 0.1 μg/mL 5-FU occurred at the clinically achievable
levels of 1 μmol/L of LV, and there was no difference in the effect between the low and high doses. TS was inhibited effectively
by 5-FU and the addition of LV, without a marked induction of TS. 相似文献
Background The purpose of this study was to assess the accuracy of contrast-enhanced magnetic resonance imaging (dynamic MR imaging)
in the evaluation of preinvasive and early invasive cancer of the cervix.
Methods Twenty-nine women with untreated squamous cell carcinoma of the cervix with either no stromal invasion or early stromal invasion
underwent pretreatment MR imaging and dynamic MR imaging within 4 weeks of surgical evaluation. The images were evaluated
for tumor detection and compared with results of histologic examination of the surgical specimens.
Results The lesions in 17 cases with histologically proven stromal invasion of 4 mm or greater were detected with dynamic MR imaging,
whereas lesions in only 8 of these cases were detected with T2 imaging. In 9 cases with stromal invasion between 4.0 mm and
5.0 mm, lesions were represented as early phase focal enhancement on dynamic MR images, but not detected on T2-weighted images.
In the 12 cases with less than 4 mm stromal invasion, no lesions were visualized on either T2-weighted images or dynamic MR
images, except in 1 case of glandular involvement without stromal invasion that appeared as enhancement on early-phase dynamic
MR imaging.
Conclusion Dynamic MR imaging detected more lesions of early stromal invasion in pretreatment imaging for cervical cancer than nonenhanced
MR imaging. 相似文献
Paclitaxel and irinotecan are important new anticancer agents. The combination of these two agents has been considered for
use against a variety of advanced solid tumors. Since the schedule-dependent effects of this combination may be crucial to
its use, we studied the interaction of paclitaxel and SN-38 (the active metabolite of irinotecan) in various schedules in
four human cancer cell lines in culture. Cell growth inhibition after 5 days was determined using an MTT assay. The effects
of drug combinations at the IC80 level were analyzed by the isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h produced antagonistic
(subadditive and protective) effects in the human lung cancer cell line A549, the breast cancer cell line MCF7, and the colon
cancer cell line WiDr, and produced additive effects in the ovarian cancer cell line PA1. Sequential exposure to paclitaxel
for 24 h followed by SN-38 for 24 h, and the reverse sequence, produced additive effects in all four cell lines. These findings
suggest that sequential administration, not simultaneous administration, may be the appropriate schedule for the therapeutic
combination of paclitaxel and irinotecan. Continued preclinical and clinical studies should provide further insights and assist
in determining the optimal schedule for this combination in clinical use.
Received: 25 February 1997 / Accepted: 6 November 1997 相似文献
Objective: To evaluate the effect of prednisolone plus low-dose aspirin (PSL/LDA) in women with autoimmune conditions who were enrolled in an IVF-ET program.
Design: A retrospective clinical study.
Setting: In vitro fertilization unit, Niigata University Hospital, Niigata, Japan.
Patient(s): Three hundred seven women who underwent IVF-ET between January 1996 and December 1997.
Intervention(s): Prednisolone (10 mg/d) and aspirin (81 mg/d) were administered to the women with autoantibodies who chose to participate.
Main Outcome Measure(s): Pregnancy and implantation rates with IVF-ET.
Result(s): Women undergoing IVF who had positive antinuclear antibodies, with or without antiphospholipid antibodies, had significantly lower pregnancy and implantation rates than did women without autoantibodies (14.8% versus 21.7% and 6.8% versus 10.4%, respectively). The administration of PSL/LDA to women with antinuclear antibodies significantly improved the outcome of IVF-ET (40.6% pregnancy rate and 20.3% implantation rate).
Conclusion(s): A high proportion of women who are undergoing IVF-ET have autoantibodies, which are associated with poor IVF outcomes. The administration of PSL/LDA to these women may improve their implantation rate. 相似文献
The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially characterized. It now appears that Kupffer cell derived TNF-alpha participates in several aspects of alcoholic liver injury. On the other hand, protease inhibitors have been used successfully for treatment of intractable diseases in which TNF-alpha is involved in the pathogenesis, including ulcerative colitis and Crohn's disease. Here, we will review new evidence for the proposal that serine protease inhibitors prevents alcoholic liver injury via mechanisms dependent on Kupffer cell derived TNF-alpha. 相似文献
Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy. 相似文献
Gender differences of alcoholic liver injury have been described previously, but mechanisms have only partially characterized. For example, it is known that females develop alcoholic liver injury more rapidly and to a greater extent than males. It now appears that estrogen participates in several aspects of this phenomenon. On the other hand, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cell and alcohol-induced liver injury. 相似文献
Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation. 相似文献