An in vitro study of the cytogenetic and cytotoxic effects of imatinib mesylate, STI571 on murine erythroleukemia GM-86 cells.

Imatinib mesylate, STI571, is a novel anticancer drug used to treat Philadelphia chromosome positive (Ph+) chronic myeloid leukemia. Studies have demonstrated the efficacy of imatinib mesylate in human cancers; however, its effects in murine cancer cell lines are not well documented. This study investigated the cytogenetic and cytotoxic effects of imatinib mesylate in vitro on virus-induced mouse erythroleukemia GM-86 cells. Cytogenetic studies revealed a noticeable increase in chromosomal abnormalities and multinucleation, as well as micro and macronuclei formation in treated cells. An increase in abnormalities such as condensed nuclei and nuclear and cytoplasmic degradations were also detected in cells treated with imatinib mesylate. It is suggested that the reduction in cell proliferation, mitotic index, and increase in cell damaging effects observed in imatinib mesylate-treated GM-86 cells were a result of the induced chromosomal and nuclear abnormalities.

Enhanced spermatogonial stem cell killing and reduced translocation yield from X-irradiated 101/H mice.

The spermatogonial stem cells of 101/H mice have been found to be more sensitive to killing by acute X-ray doses than those of the "standard" C3H/HeH X 101/H F1 hybrid. Duration of the sterile period was longer throughout the 0.5-8.0-Gy dose range tested and "recovered" testis weights, taken after recovery of fertility, were more severely reduced. The shapes of the sterile period dose-response curves were similar, but with the 101/H mice the plateau occurred at 3-5 Gy, rather than at 6 Gy. An equivalent observation was made with the testis weight data. The translocation dose-response curve was bell-shaped, as previously found with the hybrid, but yields were lower at all but the lowest doses. Notably, peak yields occurred at 3-5 Gy, rather than at 6 Gy. The altered stem cell killing and genetic responses may be explained either by a higher proportion of radiosensitive cells in the heterogeneous stem cell population or by a higher ratio of cell killing to recoverable chromosome damage which might imply a reduced repair capacity. The latter finds some support in other data. The pattern of genetic response obtained when an X-ray dose was given in two fractions at various intervals was similar in 101/H and the hybrid mice, suggesting that their kinetics of stem cell repopulation following depletion differ little.

Non-patient related variables affecting levels of vascular endothelial growth factor in urine biospecimens.

Vascular endothelial growth factor (VEGF) is an angiogenic protein proposed to be an important biomarker for the prediction of tumour growth and disease progression. Recent studies suggest that VEGF measurements in biospecimens, including urine, may have predictive value across a range of cancers. However, the reproducibility and reliability of urinary VEGF measurements have not been determined. We collected urine samples from patients receiving radiation treatment for glioblastoma multiforme (GBM) and examined the effects of five variables on measured VEGF levels using an ELISA assay. To quantify the factors affecting the precision of the assay, two variables were examined: the variation between ELISA kits with different lot numbers and the variation between different technicians. Three variables were tested for their effects on measured VEGF concentration: the time the specimen spent at room temperature prior to assay, the addition of protease inhibitors prior to specimen storage and the alteration of urinary pH. This study found that VEGF levels were consistent across three different ELISA kit lot numbers. However, significant variation was observed between results obtained by different technicians. VEGF concentrations were dependent on time at room temperature before measurement, with higher values observed 3-7 hrs after removal from the freezer. No significant difference was observed in VEGF levels with the addition of protease inhibitors, and alteration of urinary pH did not significantly affect VEGF measurements. In conclusion, this determination of the conditions necessary to reliably measure urinary VEGF levels will be useful for future studies related to protein biomarkers and disease progression.

Elevated serum progesterone values at the time of ovulation induction in luteal leuprolide acetate-down-regulated GIFT cycles are associated with decreased clinical pregnancy rates.

PURPOSE: The effects of premature luteinization of ovarian follicles as detected by elevated progesterone values on the day of human chorionic gonadotropin induction of ovulation were evaluated in 38 consecutive gamete intrafallopian transfer (GIFT) retrieval cycles. MATERIALS AND METHODS: All patients received leuprolide acetate beginning in the midluteal phase of their prior menstrual cycle, followed by gonadotropin stimulation of folliculogenesis. At least four oocytes were transferred in each cycle. RESULTS: No significant differences in gonadotropin dosage, total number of days of gonadotropins, age, number of prior pregnancies, years of infertility since last pregnancy, total number of eggs retrieved, mature residual oocytes, fertilization of mature residual oocytes, or primary etiology of infertility were observed between groups; however, estradiol concentrations were significantly higher in the group with elevated progesterone values (2573 +/- 216 pg/ml) compared to the lower progesterone group (1925 +/- 202 pg/ml, P = 0.035) and the total number of oocytes transferred was greater in the high progesterone group (7.5 +/- 0.5) vs the low progesterone group (6.3 +/- 0.3, P < 0.038). P4 concentrations < or = 0.8 ng/ml were associated with significantly higher pregnancy rates (11/19; 57.9%) compared to progesterone concentrations > 0.8 ng/ml (5/19, 26.3%; P = 0.050). CONCLUSIONS: Premature luteinization may occur in luteal leuprolide acetate-down-regulated patients and progesterone values > 0.8 ng/ml are associated with significantly lower pregnancy rates in GIFT cycles.