Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult and prognosis is poor. Objective: In this study we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6-overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells established from cisplatin-resistant cells were generated, and the sensitivity of cisplatin was examined. Results: The sensitivity of the UBE2L6- overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.

Cervical cancer commonly metastasizes first to the pelvic lymph nodes and then subsequently spreads to distant organs, making lymph node metastases the most significant prognostic factor in cervical cancer, and the strategy for its treatment directly influences prognosis. This review focuses on the treatment strategies for cases of cervical cancer with bulky pelvic lymph nodes. Concurrent chemoradiotherapy is the standard treatment modality for patients with pelvic lymph node metastases, but it is inadequate for bulky pelvic lymph nodes. Accordingly, surgical resection of the bulky lymph nodes has been attempted, and its therapeutic significance has been reported. If the bulky lymph nodes are unresectable, definitive concurrent chemoradiotherapy is performed. If it yields an inadequate degree of lymph node shrinkage, boosted radiation should be considered. The addition of chemotherapy after concurrent chemoradiotherapy has also been reported to be effective in patients with lymph node metastases and is currently being evaluated in clinical trials.

It was reported that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used to prevent hypercholesterolemia, have antitumor activity in several cancers. In this study, we investigated the cell viability of statins in Cisplatin-resistant HCP4 and PCDP5 cells compared with their parent Hela and PC3 cells, respectively, and found that HCP4 and PCDP5 cells were 37-fold and 18-fold more resistant to Cisplatin but 13-fold and 7-fold more sensitive to Lovastatin by cell proliferation assay. Lovastatin induced the apoptosis of HCP4 cells more rapidly and to greater extent than in Hela cells as assessed by flow cytometry and western blotting analyses. The MVA pathway was not involved in this acquired Cisplatin resistance. To elucidate the mechanism underlying the reduced viability to Lovastatin, we performed cDNA microarray analysis and identified 65 and 54 genes that were induced more than 2-fold by Lovastatin in HCP4 and PCDP5 cells, respectively. Of these, only three genes, KLF2, KLF6, and RHOB, were commonly induced between HCP4 and PCDP5 cells. These mRNAs were strongly induced by Lovastatin with transcriptional regulation in HCP4 cells. Consistent with transcription, the protein expression of RHOB also was induced by Lovastatin. The induction of these genes was associated with cell cycle arrest and apoptosis. Combination treatment with Cisplatin and Lovastatin resulted in an agonistic effect in Hela and PC3 cells and an antagonistic effect in HCP4 and PCDP5 cells. These results suggest that statins might have the potential to overcome Cisplatin resistance as single-agent therapy.

We report a case of microcystic stromal tumor (MCST) resected by laparoscopy. MCST is a very rare ovarian tumor with distinctive microcystic features and a characteristic stromal tumor immunopheno-type. The present case was a 26-year-oId woman who underwent laparoscopic surgery for suspected endometrial cyst of the left ovary. The mass was 8 cm in size and contained bloody fluid, and after attempting cystectomy, we eventually performed left salpingo-oophorectomy with a final postoperative pathological diagnosis of MCST. Although MCST has not yet been associated with malignancy, there are reported links to mutations in the β-catenin gene, and long-term prognosis is still unknown. As MCST resection by laparoscopy has not yet been fully described in the literature, the current case provides an example of when an unexpected, potentially malignant mass is encountered during routine cystectomy and details its subsequent management laparoscopically.

GalNAc-T6 might be related to cell-cell adhesion in the early phase of cancer invasion in endometrial carcinoma.