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SummaryExpression of carbonic anhydrase IX (CA9) was shown to be strongly involved in high incidences of metastasis and poor prognosis in various human tumors. In this study, we investigated the possible role for CA9 in tumor metastases in vitro, using a gene transfection tool in the human cervical carcinoma cell line C33A. Gene expression profiling of CA9-transfected cells (C33A/CA9) and vectortransfected cells (C33A/Mock) was investigated by DNA microarray. The biological functions of differentially expressed genes between the C33A/CA9 and C33A/Mock cells included cell growth, regulation of cell-cell and cell-extracellular matrix adhesion and cytoskeletal organization. Immunofluorescent stain and Matrigel culture showed cytoskeletal remodeling, disassembled focal adhesion, weakened cell-cell adhesion and increased motility in C33A/CA9 cells. These invasive and metastatic phenotypes were associated with Rho-GTPase-related epithelial-mesenchymal transition. Inhibition of the Rho/Rho kinase pathway by a ROCK inhibitor (Y27632) and si-Rho (short interference RNA against RhoA) showed that Rho-GTPase signaling was involved in cellular morphologic and migratory changes. The effect of CA9 on Rho-GTPase signaling was also confirmed by silencing CA9 expression. Our results suggest that CA9 overexpression induces weakening of cell adhesions and augmented cell motility by aberrant Rho-GTPase signal transduction. Our study shows an underlying mechanism of CA9-related enhanced metastatic potential of tumor cells.

Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.

Cubic shaped Magnesium oxide nanoparticles were successfully synthesized by sol-gel method using magnesium nitrate and sodium hydroxide at room temperature. Hydrated Magnesium oxide nanoparticles were annealed in air at 300 and 500°C. X-ray diffraction patterns indicate that the obtain nanoparticles are in good crystallinity, pure magnesium oxide periclase phase with (200) orientation. Morphological investigation by FESEM reveals that the typical sizes of the grown nanoparticles are in the range of 50-70nm. Powder composition was analyzed by the FTIR spectroscopy and the results confirms that the conversion of brucite phase magnesium hydroxide in to magnesium oxide periclase phase was achieved at 300°C.The Thermo-gravimetric analysis showed the phase transition of the synthesized magnesium oxide nanoparticles occurs at 280-300°C.

Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low-oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease-free survival (relative risk, 6.1; 95% confidence interval, 1.3 -28. H ypoxia is known to cause treatment resistance and promote the selective survival of metastatic phenotype.(1) Carbonic anhydrase (CA) 9 is the most specific and strongly overexpressed gene in response to hypoxia in human cancer cells, suggesting it may be a surrogate marker of hypoxia in various human cancers.(1-5) IGFBP-5, another hypoxia-overexpressed gene, has been found to show a four-fold increase under 1.5% hypoxia, and is related to axillary lymph node (LN) metastases in patients with breast cancer.(6) We previously reported that expression of CA9 mRNA in uterine cervical cancer (UCC) is a strong predictor for poorer metastasis-free survival.(7) To further examine whether expression of CA9 and CA12 is associated with LN metastases in UCC, we assayed their expression patterns in tumor tissues by immunohistochemical staining. Because we found that CA9 expression was associated with LN metastases, we assayed CA9 expression in primary cervical cancer and matching metastatic LN specimens from the same individuals. To understand the different patterns of expression of these two isoenzymes, we assayed expression in a series of archived paraffin-embedded cervical tissues comprising various stages of preinvasive epithelial lesions.

The strong correlation between CA9 expression and metastasis suggests that CA9 expression might be an important indicator for identifying patients who require more aggressive systemic therapy.

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Anterior communicating artery aneurysm can cause visual symptoms by compressing the optic nerve or direct rupture to the optic nerve with focal hematoma formation. We emphasize that cerebral vascular study is highly recommended to detect intracranial aneurysm before its rupture in the case of normal CT findings with visual symptoms and frequent headache.