Background A role for theTP53 (alias p53) tumor-suppressor gene in chemoresistance has recently been discussed, but little is known about the clinical
relevance of theTP53 gene to chemoresistance. To elucidate the relevance ofTP53 status to chemoresistance, we investigated theTP53 gene and TP53 protein expression in tumors from the same patients, before and after chemotherapy.
Methods Twenty-one patients with ovarian cancer, who had residual disease after primary surgery, were studied. These patients received
chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide, and then underwent a second surgery. Polymerase chain
reaction-single strand conformation polymorphism analysis and cycle sequencing were performed to determineTP53 mutation. TP53 protein was detected by Western blot analysis.
Results Of the 21 patients studied, 9 responded to chemotherapy. Mutation of theTP53 gene was seen in 7 patients (2 responders and 5 nonresponders) before chemotherapy. After chemotherapy, another mutation
of the gene was observed in 5 patients, all of whom were nonresponders. TP53 protein was detected in 10 patients (3 responders
and 7 nonresponders) before chemotherapy. After chemotherapy, the expression of TP53 protein increased in these 3 nonresponders,
and became positive in 2 other nonresponders.
Conclusions This study showed for the first time in clinical investigation that alterations toTP53 could develop in association with chemotherapy, and thatTP53 status may relate to the mechanisms of chemoresistance in patients with epithelial ovarian cancer. 相似文献
To investigate the effects of musk-1, a glucoprotein component isolated from the water extract of musk, on some functions of rat polymorphonuclear leukocytes activated by LTB4, an in vitro incubation system with rat polymorphonuclear leukocytes was used. The superoxide anion production was determined by cytochrome C reduction, and the beta-glucuronidase and lysozyme release was quantitated by enzyme reactions in which phenolphthaleinglucuronic acid and micrococcus lysodeikticus were used as the substrates. In comparison with the control, musk-1 at final concentrations of 1 microgram/ml-100 micrograms/ml can increase the superoxide anion production by 28.7%-202.1% and decrease the beta-glucuronidase and lysozyme release by 3%-46% and 6%-32% respectively in rat polymorphonuclear leukocytes. It is concluded that musk-1 can significantly affect the functions of rat polymorphonuclear leukocytes activated by LTB4. One of the mechanisms of this anti-inflammatory action of musk may consist in the inhibition of lysosomal enzyme release. 相似文献
Objective: To characterize the pattern of endothelial nitric oxide synthase (eNOS) expression on human spermatozoa and to determine whether sperm eNOS expression correlates with sperm function.
Design: Prospective, observational study.
Setting: University infertility clinic.
Patient(s): Twelve nonazoospermic infertile men.
Intervention(s): Semen samples (n = 12) obtained from nonazoospermic infertile men were fractionated on discontinuous Percoll gradients. Endothelial nitric oxide synthase staining on spermatozoa was correlated with sperm motility in Percoll gradient–fractionated spermatozoa. Endothelial nitric oxide synthase protein was detected with the use of a previously characterized monoclonal antibody. Control slides were incubated with preabsorbed antibody or mouse immunoglobulin G.
Main Outcome Measure(s): Localization of eNOS on human spermatozoa and correlation between the pattern of sperm eNOS expression and sperm motility.
Result(s): Morphologically normal spermatozoa exhibited postacrosomal and equatorial eNOS immunostaining. However, abnormally shaped spermatozoa often exhibited aberrant staining (in the midpiece and/or head region). A significant negative correlation was observed between the percentage of sperm with aberrant eNOS immunostaining and the percentage of motile sperm (r = −.46).
Conclusion(s): The specific localization of eNOS to human spermatozoa suggests that nitric oxide may be involved in normal sperm physiology. However, aberrant patterns of sperm eNOS expression are associated with decreased sperm motility, possibly through the generation of excessive cytotoxic oxidants. 相似文献