Prognostic outcome of patients with clinical stage I-II endometrial cancer according to bilateral salpino-oophorectomy / 대한산부인과학회지

OBJECTIVE: The aim of this study is to verify the clinical outcome of staging surgery with and (or) without bilateral salpingo-oophorectomy (BSO) in clinical stage I-II endometrial cancer patients. METHODS: We reviewed the medical records of 178 surgically treated patients in clinical stage I-II endometrial cancer between January 1994 and December 2004. Overall survival (OS) and disease free survival (DFS) were analyzed by using data gathered from the National Statistics Office. The clinical outcome was compared between patients who underwent hysterectomy with and without BSO. RESULTS: One hundred sixty patients were in clinical stage I, and 18 patients were in clinical stage II. Most of the cases showed endometrioid (93.8%) in histology and G1 (56.1%) in differentiation. BSO was performed in 142 patients. Surgico-pathological features of two group are not different but the group without BSO were younger (40.7 vs. 55.8 years old) and less myometrial invasion than the group with BSO. After mean 39.27 months follow up, we found no difference in OS and DFS between the two groups with BSO and without BSO. No factors except stage were significantly related with OS and DFS by multivariate Cox regression analysis. The rate of pelvic and paraaortic lymph node metastasis was not different between two groups. CONCLUSION: The retrospective data in the study reveals that staging surgery with and without BSO does not affect OS and DFS in clinical stage I-II endometrial cancer patients. In limited cases, such as young women, omitting BSO can be considered carefully.

Co-operative effect of glutathione depletion and selenium induced oxidative stress on API and NFkB expression in testicular cells in vitro: insights to regulation of spermatogenesis

Previous studies have shown that transcription factors, API and NFkB exert important roles in the process by which selenium regulates spermatogenesis. Glutathione, an intracellular thiol, acts as a source of reducing power and aids in maintenance of the cellular redox status. The activities of selenium are closely related to the availability of glutathione. Presently, mouse testicular cells were cultured in the presence of BSO, a known glutathione depletor, to generate oxidative stress. Selenium (Se) was added as sodium selenite to these cells at concentrations of 0.5 µM and 1.5 µM. It was observed that at 1.5 µM, Se acted as a pro-oxidant and significantly decreased the redox ratio. RT PCR analysis revealed that cjun, cfos expression increased in testicular cells cultured with Se compared to control. However, the major outcome was that the combined effect of Se supplementation and GSH depletion resulted in reduced expression of cjun and cfos while p65 expression increased. This suggests that selenium affects both these transcription factors differently. Our study indicates that though low levels of oxidative stress generated by moderate doses of selenium augments the expression of cjun and cfos, a robust increase in the ROS generation caused by the dual effect high levels of selenium and glutathione depletion leads to decrease in the expression of these genes. The present work substantiates our in vivo experiments and indicates the detrimental effect of excess selenium supplementation on male fertility.

BSO up-regulating cisplatin sensitivity of a MRP-overexpression lung cell line SPC-A-1 by changing the activity of GSH detoxification system / 中国癌症杂志

Purpose:To evaluate the feasibility and study the mechanism of buthionine sulfoximine (B SO) as an effective sensitizer to overcome cisplatin resistance caused by overex pressing multidrug resistance associated protein(MRP).Methods:T he vector pcDNA3.1(-)-MRP, which included the complete cDNA of mrp, was transf ected into human lung cancer cell line SPC-A-1 and the positive clone(SPC-A- 1/MRP) was screened by G418,MRP expression comfirmed by Werstern blot and immuno histochemistry. The cell line SPC-A-1/MRP(-) was constructed by transfected p lasmid pcDNA3.1(-) as control. Comparing the sensitivities of SPC-A-1/MRP and control cells to anticancer drug- cisplatin(CDDP) with or without 1mg/mL BSO w as done by MTT assay. At the same time, the changes of glutathione detoxifcation system (glutathione,glutathione S-transferase , glutathione peroxidase) by RT -PCR and biochemistry methods under treated with CDDP and/or BSO were determine d.Results:SPC-A-1/MRP cells showed 2 fold resistance to CDDP as compared to the parent S PC-A-1/MRP(-) cell line and the cytotoxicity was markedly enhanced by 1mg/m B SO at low cisplatin concentration. When treated with CDDP , accompanied by a hig her transscript of MRP, it was found there was greater GSH content and lower tot al GSH-Px activity in the resistant SPC-A-1/MRP cells. Combined with BSO, the GSH content decreased greatly ,the MRP mRNA was reduced and the transscript of GST and GSH-Px were increased although the activities of both GST and GSH-Px were all decreased.Conclusions:Cisplatin resistance can be caused by over-expression MRP, glutation detoxifcat ion system played an important role in MRP-mediated resistance which can be ove rcomed by BSO.

Effect of Buthionine Sulfoximine on DAAO/D-Ala System Killing K562e Cells / 中国肿瘤生物治疗杂志

Objective: To investigate the effect of BSO on DAAO/D-Ala system killing K562e cells. Methods: KDFGC cell stably expressing DAAO was obtained by retrovirus transfection. The integration and expression of DAAO gene in KDFGC cells were identified by PCR and in situ hybridization. The killing effects of D-Ala on KDfGC cells treating with Immol/L BSO were observed. Results: PCR and in situ hybridization analysis confirmed integration of DAAO gene in positive clone and expression of it at mRNA level. The IC50 of KDFGC and KDFGC + BSO treating with D-Ala for 24 hours were 10.21 mmol/L and 7.92 mmol/L, respectively. The 95% confidence limits of them were different. Conclusion: BSO can enhance the killing effect of DAAO/D-Ala system on K652e cells.