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*

To characterize the TGF-beta1 response of monocytic leukemia cells, we analyzed the effects of TGF-beta1 on cell proliferation, differentiation, and apoptosis of human monoblastic U937 cells. Treatment of cells with TGF-beta1 in the absence of growth factors significantly enhanced cell viability. Flow cytometric analysis of DNA content and CD14 expression revealed that TGF-beta1 does not affect cell proliferation and differentiation. Consistent with these results was the finding that no transcriptional induction of Cdk inhibitors such as p21Waf1, p15Ink4b, and p27Kip1 was detected following TGF-beta1 treatment. Interestingly, however, pretreatment of TGF-beta1 significantly inhibited Fas-, DNA damage-, and growth factor deprivation-induced apoptosis. This antiapoptotic effect was totally abrogated by anti-TGF-beta1 antibody. Quantitative RT-PCR analysis demonstrated a dose- and time-dependent transcriptional up-regulation of Bcl-X(L), suggesting its implication in the TGF-1-mediated antiapoptotic pathway. We also observed elevated expression of c-Fos and PTEN/MMAC1. But, no detectable change was recognized in expression of c-Jun, Fas, Fadd, Fap-1, Bcl-2, and Bax. Taken together, our study shows that TGF-beta1 enhancement of cellular viability is associated with its antiapoptotic effect, which may result from the transcriptional up-regulation of Bcl-X(L).
Antigens, CD14/metabolism ; Antigens, CD95/metabolism ; Apoptosis/drug effects* ; Cell Cycle/drug effects ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cell Survival/drug effects ; DNA/analysis ; DNA Damage ; Gene Expression Regulation, Neoplastic/genetics* ; Genes, Suppressor, Tumor/genetics ; Human ; Leukemia, Myeloid/genetics ; Neoplasm Proteins/metabolism ; Phosphoric Monoester Hydrolases/genetics ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; RNA, Messenger/metabolism ; Receptors, Antigen, T-Cell/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Transforming Growth Factor beta/pharmacology* ; U937 Cells ; Up-Regulation (Physiology)

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*

OBJECTIVE: TGF-beta signaling is dependent on the heterodimerization of the type II TGF-beta receptor (TbetaR-II) with the type I TGF-beta receptor (TbetaR-I). which mediate intracellular signals through Smad proteins. Whereas physiologic concentrations of SnoN and Ski allow a feedback regulation of TGF-beta signaling, deregulation of SnoN or Ski expression leads to total inhibition of TGF-beta signaling and of the tumor suppressors Smad2 and Smad4, which can explain the role of SnoN and Ski as oncogenes. In order to identify possible molecular mechanisms responsible for TGF-beta resistance, the author investigated the mutation and expression of TGF-beta1, its receptors, Ski/SnoN in cervical carcinomas. METHODS: From December 1995 to December 1999, 45 carcinomas and 7 normal cervical tissue specimens were obtained by surgical resection in the Kyung Hee University Medical Center. Tissue specimens were snap-forzen in liquid N2 and stored at -70 degrees C until used. Total RNA was extracted from specimens and evaluated the expression levels using densitometric analysis of quantitative RT-PCR products (TGF-beta1, Tbeta1R-I, Tbeta1R-II, Ski/SnoN), and the mutations were investigated by quantitative genomic-PCR followed by nonisotopic RT-PCR-SSCP analysis (Tbeta1R-II, Tbeta1R-I, Ski/SnoN). The abnorally expressed levels of RT-PCR products (TGF-beta1, Tbeta1R-II) were analysed for the clinicopathologic characteristics. RESULTS: Quantitative RT-PCR analysis demonstrated variable expression of TGF-beta1 mRNA (0.05-0.89) in tumors and significantly increased TGF-beta1 expression level (>0.48) in 15 of 45 samples (33.3%). There is no significant reduction of Tbeta1R-I expression (<0.38) in tumors, but 9 of all tumors (20.0%) show significantly reduced levels of Tbeta1R-II expression (<0.58). Using quantitative DNA-PCR analysis, all of 9 specimens with abnormally low Tbeta1R-II expression show abnormally low levels (<0.47) of the Tbeta1R-II gene at genomic level which suggests allelic deletion of the gene in these specimens. Gene mutations of TGF-beta1 receptors were analysed using specific primers by RT-PCR-SSCP analysis, and the results revealed no mutational alterations of TGF-beta1 receptors and no mutation in poly (A) region of Tbeta1R-II. Quantitative RT-PCR analysis demonstrated variable expression of Ski/SnoN (0.65-1.46/0.75-1.62) in tumors and significantly increased Ski expression level (>1.36) in 2 of 45 samples (4.4%), and there is no amplification of Ski/SnoN gene by quantitative genomic-PCR analysis. CONCLUSIONS: The overexpression of TGF-beta1 mRNA and the reduced or absent expression of Tbeta1R-II may be an important contributing factors, and the abnormally low genomic levels and no mutational alterations of Tbeta1R-II is caused by monoallelic deletion suggesting that Tbeta1R-II might play as a tumor suppressor of haloinsufficiency in cervical carcinomas. We could not show that high levels of Ski/SnoN expression could produce a disruption of TGF-beta signaling in cervical carcinomas.
Academic Medical Centers ; Oncogenes ; Receptors, Transforming Growth Factor beta ; RNA ; RNA, Messenger* ; Smad Proteins ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1

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

The Peutz-Jeghers syndrome has three cardinal features: gastrointestinal polypasis, mucocutaneous piginentation and autosomal dominant heredity. This syndrome is ciinically important because of the complication caused by the gastrointestinal ployp, leading to abdominal pain, gastrointestinal bleeding and intussusception. We experienced a case of Peutz-Jeghers syndrome who complained of dizziness, vague abdominal pain, melanin pigmentations of the lips, oral mucosa and digits and reported with the review of the literature.
Abdominal Pain ; Anemia* ; Dizziness ; Hemorrhage ; Heredity ; Intussusception* ; Lip ; Melanins ; Mouth Mucosa ; Peutz-Jeghers Syndrome ; Pigmentation