Cervical intraepithelial neoplasia based on array comparative genomic hybridization.

Uterine cervical cancer is one of the most frequently observed malignant gynaecologic tumors. Carcinoma in situ or invasive cervical carcinoma develops from a low-grade intraepithelial lesion of the cervix over time. Human papillomavirus (HPV) is known to be a major contributing factor. With improvements in molecular genetic technologies, the authors attempted to identify the genomic changes associated with cervical precancerous lesions. In this study, changes in gene copy numbers were evaluated in five cases of severe uterine cervical dysplasia (HPV negative, two cases; HPV 16 and 18 positive only, three cases) by array comparative genomic hybridization (array CGH), and genes with copy number changes were compared between the two groups. Between the HPV positive and negative groups, only one gene was found to be upregulated more than 1.5 fold (3q23-q24), and no downregulated genes were identified. In conclusion, it is useful to evaluate genomic aberrations in cervical cancer using array CGH.

Epigallocatechin gallate with photodynamic therapy enhances anti-tumor effects in vivo and in vitro.

OBJECTIVES: To evaluate anti-tumor effects of combined photodynamic therapy and epigallocatechin-3-gallate (EGCG). MATERIALS AND METHODS: TC-1 cells were injected into C57BL/6 mice. Mice were grouped by 7 into 4 groups as PDT, EGCG, combined PDT with EGCG, and control group. The photosensitizer Radachlorin was used. The light source was a diode laser with 662 nm wavelength. In vitro TC-1 cells were treated with Radachlorin and irradiated. In vivo, when tumors were 8-10mm, Radachlorin was injected into mice and irradiated. For in vitro, different doses of EGCG were added to culture dishes. For combination, EGCG was added to the cells. 2.5 or 5 µg/ml of Radachlorin was added to the cells. Cells were incubated with EGCG and/or Radachlorin and laser irradiated. In vivo, EGCG were given for 20 days, alone or after PDT treatment. Cell growth inhibition was determined using MTT assay. Tumor growth inhibition assays were done in each group. Tumor growth was measured using caliper. Western blottings were performed with primary antibodies as COX-2, p21, p53, PARP, Bax, P-p38, VEGF, HIF-1α, MMP9 and actin. RESULTS: The cell growth and the tumor volume in PDT combined with EGCG treatment group was significantly suppressed, compared with control and PDT or EGCG alone treated groups. We have shown that PDT combined with EGCG in vivo increase levels of both p21 and p53. Both Bax and activated PARP genes were significantly expressed. CONCLUSIONS: It is suggested that high anti-cancer activity of combined photodynamic therapy with EGCG may be useful for effective cancer therapy.

Multicystic benign mesothelioma of the pelvic peritoneum presenting as acute abdominal pain in a young woman.

Multicystic benign mesothelioma (MBM) of the peritoneum is a very rare condition. Since the first description of MBM in 1979, approximately 100 cases have been reported. This is a case report of MBM of the pelvic peritoneum presenting as acute abdominal pain in a young woman. Laparoscopy confirmed multiple grapelike clusters of cysts that originated in the peritoneum of the rectouterine pouch and histopathologic diagnosis was confirmed as MBM of the pelvic peritoneum. We hope to alert gynaecologists of the diagnostic and therapeutic approaches to MBM which can be accomplished by laparoscopy.

Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma.

BACKGROUND: Most patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis. METHODS: The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups. RESULTS: A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such as RNase K, FOXP1, LAMB2 and MRVI1 were up-regulated. CONCLUSION: The DEGs in patients with stage III serous ovarian cancer were successfully and reliably identified by the ACP-based RT PCR technique. The DEGs identified in this study might help predict the prognosis of patients with stage III serous ovarian cancer as well as suggest targets for the development of new treatment regimens.

Risk factors for complications in patients undergoing myomectomy at the time of cesarean section.

AIM: The aim of this study was to evaluate the risk factors for complications of myomectomy at cesarean section (CS). METHODS: The subjects were a non-complicated group (n = 100) and a complicated group (n = 10) of patients aged between 20 and 43 years who underwent CS and simultaneous myomectomy at our institution from January 2006 until December 2008. Complications were defined as blood transfusion greater than three packed red blood cells, postoperative ileus, and two days longer than average hospitalization. RESULTS: The complicated group (n = 10) had (i) a myoma larger than 10 cm and no secondary change; and (ii) intramural myoma type. CONCLUSION: Myomectomy during CS can be performed in selected cases, but some patients had significant complications like ileus and postoperative atonic bleeding.

The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma.

BACKGROUND: Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of KLOTHO in human cervical carcinoma. RESULTS: Loss of KLOTHO mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. KLOTHO mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of KLOTHO revealed CpG hypermethylation in non-KLOTHO-expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for KLOTHO in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active beta-catenin levels, suppression of T-cell factor/beta-catenin target genes, such as c-MYC and CCND1, and inhibition of colony growth. CONCLUSIONS: Epigenetic silencing of KLOTHO may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.