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121.
The ability of lonidamine (LND), an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxic activity of cisplatin (CDDP) and epidoxorubicin (EPI), singly or in combination, was investigated in two human breast cancer cell lines (MCF7 and T47D). A 72-hr post-incubation with a non-cytotoxic concentration of LND (75 microM) increased the activity of a 1-hr CDDP treatment as well as that of a 1 to 16-hr EPI treatment. A different pattern of interaction among the drugs and modulator was observed as a function of the sequence of drug treatment. Specifically, supra-additive or additive effects of the combination were obtained in the two cell lines according to the different treatment schemes. In particular, the maximum potentiation was observed in MCF7 cells simultaneously exposed to CDDP, EPI and LND for 1 hr and then post-incubated with LND for 72 hr, and in T47 first exposed to EPI and LND, then to CDDP and LND, and finally post-incubated with LND. Flow cytometric analysis of MCF7 cell distribution in the different cycle phases showed that combined treatment with EPI/CDDP/LND was able to stabilize cell cycle perturbations (mainly G2M accumulation) induced by individual agents. The ability of LND to potentiate CDDP and EPI cytotoxicity, and the consideration that LND causes side effects different from those caused by alkylating agents and anthracyclines, make this compound an attractive candidate for multidrug combination therapy in breast cancer.  相似文献   
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Two laboratories equipped with CAS 200 (Becton Dickinson Image Cytometry Systems, San Jose, CA) instruments participated in this study of variability of DNA analysis of bladder tumor specimens. Formalin fixed paraffin embedded specimens were disaggregated and centrifuged onto microscope slides from ten bladder tumor specimens and two specimens of normal urothelium. Sources of variability considered were Specimen, Slide, Run, Laboratory, and Error. Slides were systematically scanned and 200 cells measured followed by the operator selecting 100 nuclei with abnormal morphology. DNA index (DI) and hyperdiploid fraction (HDF) were calculated from the DNA frequency distributions. For systematic sampling, 92% of the variability was due to Specimen indicating that differences in HDF values between specimens reflect biological differences. With selective sampling, only 67% of the variability in HDF is due to Specimen differences. Other factors, Laboratory, Error, and Laboratory x Specimen interaction each accounted for approximately 10% of the variability. Similarly variability of DI with selective sampling was also higher, and less specimen dependent than systematic sampling. It is important that sampling schemes and selection criteria be carefully documented in order to control variability. Enriched (or selective) sampling for abnormal cells has the potential to increase sensitivity but specimen classification based on these measurements must depend on determination of the frequency of such cells in the total population.  相似文献   
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Cholesterol synthesis (HMG-CoA reductase) inhibitors have proven their value in preventing cardiovascular events, especially in patients with manifest coronary heart disease. Besides cholesterol lowering a number of effects have been described which may contribute to the beneficial influence of these agents on the process of atherosclerosis. Measurement of serum lipids is still necessary for various reasons, namely, to know the degree of elevation in serum cholesterol and specific disturbances in lipid metabolism, the extent to which serum lipids must be lowered and the compliance with cholesterol lowering therapy.  相似文献   
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Gain adaptation of eye and head movement components of simian gaze shifts. J. Neurophysiol. 78: 2817-2821, 1997. To investigate the site of gaze adaptation in primates, we reduced the gain of large head-restrained gaze shifts made to 50 degrees target steps by jumping the target 40% backwards during a targeting saccade and then tested gain transfer to the eye- and head-movement components of head-unrestrained gaze shifts. After several hundred backstep trials, saccadic gain decreased by at least 10% in 8 of 13 experiments, which were then selected for further study. The minimum saccadic gain decrease in these eight experiments was 12.8% (mean = 18.4%). Head-unrestrained gaze shifts to ordinary 50 degrees target steps experienced a gain reduction of at least 9.3% (mean = 14.9%), a mean gain transfer of 81%. Both the eye and head components of the gaze shift also decreased. However, average head movement gain decreased much more (22.1%) than eye movement gain (9.2%). Also, peak head velocity generally decreased significantly (20%), but peak eye velocity either increased or remained constant (average increase of 5.6%). However, the adapted peak eye and head velocities were appropriate for the adapted, smaller gaze amplitudes. Similar dissociations in eye and head metrics occurred when head-unrestrained gaze shifts were adapted directly (n = 2). These results indicated that head-restrained saccadic gain adaptation did not produce adaptation of eye movement alone. Nor did it produce a proportional gain change in both eye and head movement. Rather, normal eye and head amplitude and velocity relations for a given gaze amplitude were preserved. Such a result could be explained most easily if head-restrained adaptation were realized before the eye and head commands had been individualized. Therefore, gaze adaptation is most likely to occur upstream of the creation of separate eye and head movement commands.  相似文献   
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