Papillary ependymoma is a rare variant of ependymoma and often gives rise to confusion with choroid plexus papilloma because of topographic, light microscopic and ultrastructural similarities. Here, we report two cases of papillary ependymomas regarding their unique clinicopathologic features and differential points from choroid plexus papilloma. Brain MRI revealed a large mass in the left lateral ventricle in one case and a 3cm sized mass in the pineal area and the 3rd ventricle in the other. Microscopically, the tumor was characterized by papillary and tubular structures. Immunohistochemically, the tumor cells in both cases expressed cytokeratins(CK22 and CAM 5.2) but did not express glial fibrillary acidic protein(GFAP), vimentin, epithelial membrane antigen, and S100 protein. This is a very unusual immunohistochemical feature for papillary ependymoma. Ultrastructurally, the tumor showed a mosaic pattern of tumor cells with frequent intercellular microrosettes having a few stubby microvilli, a few cilia and zonulae adherentes. The cytoplasmic processes were markedly reduced compared to conventional ependymoma. The cytoplasm did not contain intermediate filaments. Interestingly, the mitochondria showed abnormal features with a pleomorphic shape and abnormal cristae in both cases. These ultrastructural features enabled differentiation between papillary ependymoma and choroid plexus papilloma in addition to the light microscopic findings.
Adult ; Carcinoma, Papillary/*pathology/surgery ; Case Report ; Diagnosis, Differential ; Ependymoma/*pathology/surgery ; Fatal Outcome ; Female ; Follow-Up Studies ; Glioma/*pathology ; Human ; Magnetic Resonance Imaging ; Middle Age

OBJECTIVE: Vascular Endothelial Growth Factor (VEGF) is a potent stimulator of angiogenesis in solid tumors. Thrombospondin-1 (TSP-1) has inhibitory role in cancer cell proliferation and metastasis. To analyze the correlation with expression of VEGF and TSP-1 including microvessel density (MVD), the levels of VEGF/TSP-1 mRNA expression and microvessel count (MVC) were estimated in patients with invasive cervical carcinomas. METHODS: From 1996 to 1999, 37 carcinomas and 7 normal cervical tissues were collected, frozen and stored at -70 degrees C until used. The levels of VEGF and TSP-1 mRNAs were determined by quantitative RT-PCR. MVD was assessed by immunostaining for factor VIII-related antigen. The results are expressed as the largest number of microvessels present within a single x 40 field, and counted at x 100 field. RESULTS: Quantitative RT-PCR analysis demonstrated abnormally increased VEGF mRNA expression levels (>0.66) in 14 (37.8%) of 37 cervical carcinomas comparing to control groups (mean: 0.32+/-0.09) and abnormally low TSP-1 mRNA expression levels (<0.72) in 13 (35.1%) of 37 cervical carcinomas comparing to control groups (mean: 0.51+/-0.07). MVC was higher in tumors showing decreased expression of TSP-1 (but not statistically) (p<0.18) and overexpression of VEGF (p<0.05). When VEGF overexpression was accompanied with reduced TSP-1 expression, the microvessel density showed significantly increased pattern (p<0.05). CONCLUSION: Our study demonstrates that reduced expression of TSP-1 mRNAs and overexpression of VEGF mRNAs may be an important contributing factor in cervical carcinomas. Moreover, the inversed correlation of VEGF and TSP-1 mRNA expression can be an evidence of angiogenic role in cervical carcinomas.
Cell Proliferation ; Humans ; Microvessels* ; Neoplasm Metastasis ; RNA, Messenger* ; Thrombospondin 1 ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A* ; von Willebrand Factor

PURPOSE: We used optical coherence tomography (OCT) for longitudinal evaluation of structural changes in the peripapillary retinal nerve fiber layer (RNFL), the macular ganglion cell-inner plexiform layer (GC-IPL), and the macula in patients with traumatic optic neuropathy. METHODS: From May 2012 to April 2015, the medical records of 20 patients with monocular traumatic optic neuropathy who were followed up for over 6 months were retrospectively analyzed. Best-corrected visual acuity was checked and Cirrus high-definition optical coherence tomography (HD-OCT) was used to measure the thicknesses of the peripapillary RNFL, macular GC-IPL, and macula of both eyes at the first visit (within 4 weeks after trauma), at 10 and 24 weeks after trauma, and at the final visits. The differences over time in the parameters of the traumatic and fellow eyes were analyzed. RESULTS: The final best-corrected visual acuities of the traumatic and fellow eyes differed significantly from those at the first visit (p = 0.007). The average thicknesses of the peripapillary RNFL, the macular GC-IPL, and the macula differed significantly between the traumatic and fellow eyes commencing 10 weeks after trauma (p < 0.001, p = 0.002, p = 0.003, respectively). CONCLUSIONS: Significant changes in visual acuity preceded structural changes in the retina. Objective assessment of retinal structural changes using OCT yields helpful information on the clinical course of patients with traumatic optic neuropathy.
Ganglion Cysts ; Humans ; Medical Records ; Nerve Fibers ; Optic Nerve Injuries ; Retina ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity

PURPOSE: To report the clinical manifestations and computed tomography (CT) findings of patients with a trapdoor type medial orbital wall blowout fracture.METHODS: From March 2009 to October 2016, the clinical records and computed tomography findings of patients who underwent surgical treatment for a trapdoor type medial orbital wall blowout fracture were retrospectively analyzed.RESULTS: A total of eight patients (six males and two females) were enrolled with a combined mean age of 14.4 years. Clinical manifestations were eyeball movement limitation (abduction and adduction) and ocular motility pain (eight patients, 100%), diplopia (seven patients, 87.5%), and nausea and vomiting (four patients, 50%). On CT, the distance from the orbital apex to the fracture site was an average of 22.0 mm and occurred in the middle position of the entire wall. Two patients had missed rectus completely dislocated into the ethmoid sinus through the fracture gap and six patients had definite involvement in the fracture gap and edema of the medial rectus muscle. The medial rectus muscle cross-sectional area was 47.7 mm² which was edematous compared to the contralateral eye (40.1 mm²). Orbital wall reconstruction was performed an average of 4.1 days after the injury. In all patients with oculocardiac reflex-like nausea and vomiting immediately improved after surgery. Six out of eight patients who had eyeball movement limitations (abduction and adduction) preoperatively showed adduction limitation after surgery. The eyeball movement limitation and diplopia disappeared 11.7 days and 46.7 days after surgery, respectively.CONCLUSIONS: Patients with trapdoor type medial wall blowout fracture showed characteristic computed tomographic findings and clinical manifestations such as eyeball movement limitation, ocular motility pain, diplopia, and oculocardiac reflex. An understanding of clinical findings and quick surgical treatment are therefore required. The type of eyeball movement limitation was abduction and adduction limitation preoperatively and adduction limitation postoperatively.
Diplopia ; Edema ; Ethmoid Sinus ; Humans ; Male ; Nausea ; Orbit ; Reflex, Oculocardiac ; Retrospective Studies ; Vomiting

PURPOSE: RKIP (Raf kinase inhibitor protein) is a novel candidate tumor suppressor, known to inhibit the MAPK signaling by interfering with the MEK phosphorylation by Raf-1. The aim of this study was to investigate the expression of RKIP and analyze the pattern of inactivation and mutation of the RKIP gene in human gastric cancer. METHODS: To explore if RKIP inactivation is implicated in gastric tumorigenesis, an expression analysis on the transcription and protein expression levels and a mutational analysis of RKIP were performed in 15 human gastric cancer cell lines and 92 primary carcinoma tissues. RESULTS: Abnormal reduction of the level of RKIP expression was frequently detected in the cancer cell lines and primary tumor tissues, at both the transcript and protein levels. Moreover, the expression level of RKIP in the tumor cells was inversely correlated with the level of Erk phosphorylation, indicating that RKIP plays a key role in the regulation of the Raf-MEK-Erk signaling pathway in human gastric cells. While the expression of the RKIP transcript was not re-activated in low expressor cells by treatment with the demethylating agent 5'Aza-dC, the genomic RKIP was detected at low levels in many cancer cell lines, suggesting that an abnormal reduction of level of RKIP expression in tumors might be caused by allelic deletion of the gene rather than transcriptional silencing due to aberrant DNA hypermethylation. A loss of heterozygosity study, using an intragenic polymorphic marker, revealed that approximately 21% of the gastric cancers harbored allelic loss of the RKIP gene. CONCLUSION: Collectively, this study has demonstrated that RKIP is a tumor suppressor, whose expression is frequently downregulated by allelic deletion in human gastric cancers. This study also suggests that an altered expression of RKIP might contribute to the development of gastric cancer via abnormal elevation of the Raf-Erk signaling pathway.
Carcinogenesis ; Cell Line ; DNA ; Humans* ; Loss of Heterozygosity ; Phosphorylation ; Phosphotransferases* ; Stomach Neoplasms*

OBJECTIVE: X-linked inhibitor of apoptosis (XIAP) is the most potent member of IAP family that exerts antiapoptotic effects by interfering with activities of caspases. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. We explore the candidacy of XAF1, Smac/DIABLO and HtrA2 as a tumor suppressor in cervical carcinogenesis and determine the mechanisms of altered XAF1 expression. METHODS: We investigated the expression and mutation status of the genes in 64 cervical cancer tissues, 5 cervical cancer cell lines and 10 normal cervical tissues. RESULTS: XAF1 transcript was not expressed or extremely low levels in 40% (2/5) of cancer cell line and in 31% (20/64) of primary carcinomas whereas Smac/DIABLO and HtrA2 are normally expressed in all cells. As somatic mutations of the gene was not detected, expression of XAF1 transcript was reactivated in all nonexpressor cell lines after 5-aza-2-deoxycytidine treatment. Bisulfite DNA analysis for CpG sites in the promoter region revealed a strong association between CpG sites hypermethylation and gene silencing. CONCLUSION: XAF1 undergoes epigenetic silencing in a considerable proportion of cervical carcinomas by aberrant promoter hypermethylation rather than genetic alterations, and closely associated with reduced gene expression. Although additional studies are required to determine the biological significance of XAF1 inactivation, it will be valuable to examine the expression status of XAF1 could be a clinically useful marker for cancer treatment.
Apoptosis ; Carcinogenesis ; Caspases ; Cell Line ; DNA ; Epigenomics* ; Gene Expression ; Gene Silencing ; Humans* ; Mitochondrial Proteins ; Promoter Regions, Genetic ; Uterine Cervical Neoplasms

OBJECTIVE: Measure the over-expression of p73 and analyze as the prognostic as well as angiogenic factor of cervical cancer by comparing the degree of expression of VEGF and TSP-1 by RT-PCR. METHODS: 7 normal and 37 cervical cancer specimens were put through RT-PCR and the expression of p73, VEGF and TSP-1 were measured. After immunohistochemical staining, the number of microvessels was counted. With the level of expression, investigated the relationship with the clinicopathological characteristics and the number of microvessels. RESULTS: 57% of cancer tissues showed abnormally high levels of p73 mRNA. In quantitative genomic DNA PCR, the p73 was over-expressed in the transcription level. Through allotyping with Sty I polymorphism, the over-expression of p73 was due to the transcription activity of the silent allele. In RT-PCR-SSCP analysis of over-expressed specimens, sequence alterations was not seen. In 73%, VEGF was over-expressed while TSP-1 was under-expressed in 35%. There was no association between the number of microvessels with the over-expression of p73 and VEGF, but inversely associated with the under-expression of TSP-1. There was no correlation between the over-expression of p73 and the clinicopathological characteristics. The over-expression of p73 coincided 80% with the over-expression of VEGF, and 40% with the under-expression of TSP-1. CONCLUSION: These data support the expression of p73 was increased in cervical cancer tissues and was associated with the over-expression of the VEGF but not associated with the under-expression of TSP-1. The biological and clinical significance of the over-expression of p73 should be studied further in the future.
Alleles ; Angiogenesis Inducing Agents ; DNA ; Microvessels ; Polymerase Chain Reaction ; RNA, Messenger ; Thrombospondin 1* ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A*

BACKGROUND/AIMS: Saccharomyces boulardii has been reported to be beneficial in the treatment of inflammatory bowel disease. The aim of this work was to evaluate the effect of S. boulardii in a mice model of 2,4,6-trinitrobencene sulfonic acid (TNBS) induced colitis and analyze the expression of genes in S. boulardii treated mice by microarray. METHODS: BALB/c mice received TNBS or TNBS and S. boulardii treatment for 4 days. Microarray was performed on total mRNA form colon, and histologic evaluation was also performed. RESULTS: In mice treated with S. boulardii, the histological appearance and mortality rate were significantly restored compared with rats receiving only TNBS. Among 330 genes which were altered by both S. boulardii and TNBS (>2 folds), 193 genes were down-regulated by S. boulardii in microarray. Most of genes which were down-regulated by S. bouardii were functionally classified as inflammatory and immune response related genes. CONCLUSIONS: S. boulardii may reduce colonic inflammation along with regulation of inflammatory and immune responsive genes in TNBS-induced colitis.
Animals ; Colitis/chemically induced/genetics/*therapy ; Colon/metabolism/pathology ; Gene Expression Profiling ; Mice ; Mice, Inbred BALB C ; Oligonucleotide Array Sequence Analysis ; *Probiotics ; *Saccharomyces ; Trinitrobenzenesulfonic Acid

PURPOSE: Recently, a key role of tumor necrosis factor (TNF) in the development of inflammatory bowel disease (IBD), especially Crohn's disease (CD), has emerged. In Japan, 3 single base pair polymorphisms in the 5'-flanking region of the TNF-alpha gene at position 1031, 863, and 857, which are related to high transcriptional promoter activity, have been identified in the Japanese CD patients. And the polymorphisms of the TNF-alpha gene at position 308, 238 have been reported in western CD patients. So, in order to find the same polymorphisms in Korean population and CD patients, the author evaluate the patients diagnosed with CD, ulcerative colitis (UC) and healthy controls (HCs). METHODS: Blood samples were obtained from 70 patients with CD, 72 patients with UC and 52 healthy controls. Polymorphisms in the TNF-alpha gene at their respective positions were analyzed by single strand conformational polymorphism (SSCP), and allele frequencies in CD and UC patients were compared with those in healthy controls. RESULTS: Allele frequencies of 1031C, 863A, and 857T in health controls were 18.3%, 8.7%, and 19.2%, respectively. Polymorphic allele frequencies of 1031C, 863A, 857T were 22.9%, 27.1%, and 24.3% in CD patients respectively. The frequencies at all 3 positions were higher in CD patients than in HCs. However, the frequency at 863A was statistically significant (P=0.000). The allele frequencies of 308A and 238A alleles were 0.7% and 3.6% in CD, 0.7% and 2.1% in UC, and 1.9% and 4.8% in HCs, respectively. The allele frequency of 1031C was significantly higher in B3 than in B2 (P=0.033). CONCLUSION: Polymorphisms of 5'-flanking region of the TNF-alpha at positions 1031 (T/C), 863 (C/A) and 857 (C/T) may be associated with susceptibility of CD.
Alleles ; Asian Continental Ancestry Group ; Base Pairing ; Colitis, Ulcerative ; Crohn Disease* ; Gene Frequency ; Humans* ; Inflammatory Bowel Diseases ; Japan ; Korea ; Tumor Necrosis Factor-alpha*

OBJECTIVE: Angiogenesis, the formation of blood vessels by sprouting from pre-existing ones, is essential for the growth of solid tumors beyond 2-3mm in diameter and for tumor metastasis. Vascular endothelial growth factor (VEGF), is known as vascular permeability factor(VPF) and mediates vascularization and tumor-induced angiogenesis. This study examined the potential of growth, invasion, and metastasis of uterine cervical carcinomas associated with neovascularization. METHODS: From January 1996 to December 1999, at the Department of Obstetrics and Gynecology, Kyung-Hee University Hospital, 37 uterine cervical carcinomas and 7 normal cervical tissues were obtained and the samples were immediately frozen and stored at -70 degrees C. Immunohistochemical staining for VEGF was carried out to study VEGF localization, and the levels of VEGF subtype mRNAs were determined by quantitative RT-PCR in specimens. The relation between VEGF subtypes expression of cervical cancers was analysed. RESULTS: The positive staining for VEGF is seen dominantly in the cytoplasm of the cancer cells, and faintly in interstitial cells. The intensity of staining was stronger in squamous carcinomas than in adenocrcinomas, but there was no significant difference (p>0.05). Quantitative RT-PCR analysis demonstrated significantly increased VEGF121/VEGF165 mRNA expression levels (>0.56 / >0.72) in 21 (56.8%) and 15 (40.5%) of 37 cervical carcinomas comparing to control groups (mean: 0.28 / 0.36). There was no obvious relationship between VEGF121/VEGF165 mRNA expression levels and the clinical parameters examined including age, pathology, differentiation, tumor size, lymphovascular space invasion, LN involvement and invasion depth except clinical stage (p<0.05). CONCLUSIONS: The overexpression of VEGF mRNA may be an important contributing factor in cervical carcinomas. There is no significant differenece of VEGF mRNAs levels according to clinical parameters, so it seems that the expression of VEGF is involved in the promotion of angiogenesis on cervical cancer and plays an important role in early invasion.
Blood Vessels ; Capillary Permeability ; Carcinoma, Squamous Cell ; Cytoplasm ; Gynecology ; Neoplasm Metastasis ; Obstetrics ; Pathology ; RNA, Messenger* ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A*