CD46 is a membrane-bound complement regulatory protein (mCRP) possessing a regulatory role with the complement system. CD46 protects the host cells from damage by complement. Expression of CD46 is also highly maintained in many cancers, including bladder cancers, and thus functions as a receptor for many cancer therapeutic viruses.In this study we report a unique role of CD46 as a progression factor of cancer cells in bladder cancers. Resulting data from a DNA microarray using CD46-altered HT1376 bladder cancers demonstrated a pool of target genes, including complement C3  chain (C3), matrix Gla protein (MGP), AFAP-AS1, follicular dendritic cell secreted protein (FDCSP), MAM domain containing 2 (MAMDC2), gamma-aminobutyric acid A receptor pi (GABRP), transforming growth factor, beta-induced (TGFBI), a family of cytochrome P450 (CYP24A1), sialic acid binding Ig-like lectin 6 (SIGLEC6), metallothionein 1E (MT1E), and several members of cytokeratins. Subsequent studies using quantitative RT-PCR and Western blot analyses confirmed CD46-mediated regulation of C3, MGP, and keratin 13 (KRT13). MGP and KRT13 are known to be involved in cell migration and cancer cell metastasis. A cell migration assay demonstrated that CD46 enhanced migratory potential of bladder cancer cells. Taken all together, this report demonstrated that CD46 is generally overexpressed in bladder cancers and plays a unique role in the promotion of cancer cell migration. Further detailed studies are needed to be performed to clarify the action mechanism of CD46 and its application to cancer therapeutics.

Purpose: Parkinson disease (PD) is a progressive neurodegenerative disorder in which dopaminergic (DAergic) systems are destroyed (particularly in the nigrostriatal system), causing both motor and nonmotor symptoms. Hippocampal neuroplasticity is altered in PD animal models, resulting in nonmotor dysfunctions. However, little is known about the precise mechanism underlying the hippocampal dysfunctions in PD. Methods: Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in adult Sprague Dawley rats. Both motor and nonmotor symptoms alongside the expression of tyrosine hydroxylase (TH) in the substantia nigra and striatum were confirmed in 6-OHDA-lesioned rats. The neuronal architecture in the hippocampus was analyzed by Golgi staining. Results: During the 7–8 weeks after infusion, the 6-OHDA-lesioned rats exhibited motor and nonmotor dysfunctions (especially anxiety/depression-like behaviors). Rats with unilateral 6-OHDA infusion displayed reduced TH+ immunoreactivity in the ipsilateral nigrostriatal pathway of the brain. Golgi staining revealed that striatal 6-OHDA infusion significantly decreased the dendritic complexity (i.e., number of crossing dendrites, total dendritic length, and branch points) in the ipsilateral hippocampal conus ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions. Additionally, the dendritic spine density and morphology were significantly altered in the CA1 apical/basal and DG subregions following striatal 6-OHDA infusion. However, alteration of microglial and astrocytic distributions did not occur in the hippocampus following striatal 6-OHDA infusion. Conclusions The present study provides anatomical evidence that the structural plasticity in the hippocampus is altered in the late phase following striatal 6-OHDA infusion in rats, possibly as a result of the prolonged suppression of the DAergic system, and independent of neuroinflammation.

OBJECTIVE: Pituitary adenomas (PAs) are often detected as incidental findings. However, the natural history remains unclear. The objective of this study was to evaluate the natural history and growth pattern of untreated PAs.METHODS: Between 2003 and 2014, 59 PAs were managed with clinico-radiological follow up for longer than 12 months without any kind of therapeutic intervention. Tumor volumes were calculated at initial and last follow-up visit, and tumor growth during the observation period was determined. Data were analyzed according to clinical and imaging characteristics.RESULTS: The mean initial and last tumor volume and diameter were 1.83±2.97 mL and 13.77±6.45 mm, 2.85±4.47 mL and 15.75±8.08 mm, respectively. The mean annual tumor growth rate was 0.33±0.68 mL/year during a mean observation period of 46.8±32.1 months. Sixteen (27%) PAs showed tumor growth. The initial tumor size (HR, 1.140; 95% confidence interval, 1.003–1.295; p=0.045) was the independent predictive factor that determined the tumor growth. Six patients (11%) of 56 conservatively managed non-symptomatic PAs underwent resection for aggravating visual symptoms with mean interval of 34.5 months from diagnosis. By Cox regression analysis, PAs of last longest diameter over 21.75 mm were a significant prognostic factor for eventual treatment.CONCLUSION: The initial tumor size of PAs was independently associated with the tumor growth. Six patients (11%) of conservatively managed PAs were likely to be treated eventually. PAs of last follow-up longest diameter over 21.75 mm were a significant prognostic factor for treatment. Further studies with a large series are required to determine treatment strategy.
Diagnosis ; Follow-Up Studies ; Humans ; Incidental Findings ; Natural History ; Pituitary Neoplasms ; Prognosis ; Tumor Burden

PURPOSE: This study was aimed to evaluate whether the size of the changed area included in the registration area affects the validity of superimposition in three-dimensional (3D) images. MATERIALS AND METHODS: Ten mannequin heads which were sectioned to simulate maxillary and mandibular setback surgery were used. A total of 30 images, including 10 initial images, 10 images after moving both middle and lower faces, and 10 images after moving only lower face, were obtained. The 9 landmarks which consisted of the bilateral and midline landmarks of the upper, middle, and lower faces respectively were used. Each 3D image obtained after simulation was superimposed 3 times according to the different 3 registration areas. The one-way ANOVA and post-hoc analysis were performed.RESULT: In the case of moving middle and lower faces, there was no significant difference in all markers when superimposition was performed based on no changed area and forehead area. However, in the case of superimposition by the whole face, all measurements showed a significant difference (P<0.05) except for Pn (P>0.05). In the case of moving only lower face, all measurements did not show a significant difference regardless of the registration area. CONCLUSION The validity of 3D superimposition in 3D images could be affected by the size of changed areas included in the registration area. In the postoperative evaluation of mandibular surgery, the registration area does not affect the accuracy of the 3D superposition. However, after the maxilla-mandibular surgery, the registration area should be set except for the changed soft tissue.

BACKGROUND: The purpose of this study was to evaluate the treatment outcome of our optic nerve sheath meningioma (ONSM) case series in terms of preventing tumor growth and preserving vision in ONSM patients. METHODS: Between July 2003 and March 2015, 1,398 patients with intracranial meningioma were diagnosed at Seoul National University Bundang Hospital. Among them, only 13 patients (0.93%) were diagnosed with ONSM and enrolled in the present study. Tumor volume changes of ONSM patients and their visual acuity were evaluated before and after treatments. RESULTS: The median follow-up time was 50 months (range, 12–133 months). Visual acuity was evaluated in 12 of 13 patients, and visual acuity was found to be preserved in 9 of 12 patients (75%). Tumor volume was reduced in all patients. The tumor control rate was 100% in the present study. The difference in tumor volume between pretreatment and last follow-up was statistically significant (p=0.015). CONCLUSION: Intensity-modulated radiotherapy (IMRT) and gamma knife radiosurgery (GKS) could maintain visual acuity and stabilize tumor volume in ONSM patients, suggesting that IMRT and GKS may be effective therapies for ONSM. However, which treatment is the more effective modality must be confirmed by prospective studies and longer-term follow-up.
Follow-Up Studies ; Humans ; Meningioma* ; Optic Nerve* ; Prospective Studies ; Radiosurgery ; Radiotherapy, Intensity-Modulated ; Seoul ; Treatment Outcome ; Tumor Burden ; Visual Acuity

OBJECTIVE: To investigate the efficacy of adjuvant treatment in patients with high-grade meningioma. METHODS: A retrospective analysis was performed for patients with high-grade meningioma, World Health Organization grade 2 or 3, in a single center between 2003 and 2014. The patients were reviewed according to age at diagnosis, sex, the location of meningioma, degree of tumor resection, histological features, and type of adjuvant treatment. These factors were analyzed by Firth logistic regression analyses. RESULTS: Fifty-three patients with high-grade meningioma were enrolled. Thirty-four patients received adjuvant treatment; conventional radiotherapy or radiosurgery. Clinical follow-up ranged from 13–113 months with a median follow-up of 35.5 months. Gross total removal (GTR), Simpson grade 1 or 2, was achieved in 29 patients and, among them, 13 patients received adjuvant treatment. In the other 24 patients with non-GTR, conventional adjuvant radiotherapy and radiosurgery were performed in 11 and 10 patients, respectively. The other 3 patients did not receive any adjuvant treatment. Radiation-related complications did not occur. Of the 53 patients, 19 patients had suffered from recurrence. The recurrence rate in the adjuvant treatment group was 23.5% (8 out of 34). On the other hand, the rate for the non-adjuvant treatment group was 57.9% (11 out of 19) (odds ratio [OR]=0.208, p=0.017). In the GTR group, the recurrence rate was 7.5% (1 out of 13) for patients with adjuvant treatment and 50% (8 out of 16) for patients without adjuvant treatment (OR=0.121, p=0.04). CONCLUSION: Adjuvant treatment appears to be safe and effective, and could lead to a lower recurrence rate in high-grade meningioma, regardless of the extent of removal. Our results might be used as a reference for making decisions when planning adjuvant treatments for patients with high-grade meningioma after surgery.
Diagnosis ; Follow-Up Studies ; Hand ; Humans ; Logistic Models ; Meningioma* ; Radiosurgery ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; World Health Organization

Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau protein in the brain, leading to the increase in inflammation and neuronal loss. Recently, evidences to support the association between type 2 diabetes mellitus (T2DM) and AD have markedly increased by clinical researches and experimental studies. Reduced insulin action and impaired glucose metabolism in the brain leads to diabetes induced AD. Androgen, a male sex hormone, was known to regulate inflammatory response, Aβ deposition in AD, insulin signaling, and synaptic plasticity in brain. Clinical studies demonstrated that androgen deficiency results in the increased risk of AD and its severe progression in male subjects. We reviewed the significant evidences to support that low testosterone levels are linked to diabetes-induced AD based on previous studies. Thus, we highlight the therapeutic potential of androgen in diabetes induced AD.
Alzheimer Disease* ; Amyloid ; Brain ; Diabetes Mellitus, Type 2 ; Glucose ; Humans ; Inflammation ; Insulin ; Insulin Resistance ; Male ; Metabolism ; Neuronal Plasticity ; Neurons ; tau Proteins ; Testosterone

BACKGROUND: The incidence of brain metastasis (BM) in gynecologic cancers has risen recently, due to prolonged survival times and an early diagnosis. We analyzed treatment outcomes of patients with BM from gynecologic cancers. METHODS: Among 951 patients with BM who were treated in neurosurgical department from July 2003 to February 2016, a total of 20 (2%) patients were from gynecologic cancers. The patients' clinical characteristics were collected by using medical records. There were 14 (66.7%) ovarian cancers, 4 (19.0%) uterine cancers, and 2 (9.5%) cervical cancers. As a primary treatment modality, 11 patients were treated with Gamma Knife surgery (GKS), 6 with surgical resection followed by whole brain radiation therapy (WBRT), and 3 with WBRT only. Overall and progression-free survival according to the primary origin and the primary treatment were analyzed. RESULTS: Median overall survival time was 28 months, and progression-free survival was 15 months. In patients with ovarian cancer, median overall survival did not reach during the follow-up periods and progression-free survival time was 15 months. Median overall survival time in patients who received GKS as the primary treatment was 17 months and that in patients who underwent surgical resection followed by WBRT was 37.3 months (p=0.16). The median value of progression-free survival time in patients who received GKS as the primary treatment was 12 months and that in patients who underwent surgical resection with WBRT was 42 months (p=0.042). Median follow up period of over all patients was 13 months. CONCLUSION: BM from gynecologic cancer is rare (2%), but our findings suggest that the prognosis might not always be poor. In our small series, surgical resection with WBRT was a treatment modality significantly associated with a longer progression-free survival. Additional studies with more cases and multi-institutional cooperation are needed to determine which treatment modality leads to better outcomes.
Brain* ; Disease-Free Survival ; Early Diagnosis ; Follow-Up Studies ; Gynecology ; Humans ; Incidence ; Medical Records ; Neoplasm Metastasis* ; Ovarian Neoplasms ; Prognosis ; Retrospective Studies* ; Uterine Neoplasms

This study was performed to validate the effectiveness and safety of concurrent chemoradiotherapy and adjuvant therapy with temozolomide for newly diagnosed glioblastoma multiforme as a standard treatment protocol. Between 2004 and 2011, patients newly diagnosed with glioblastoma who were treated with temozolomide during concurrent chemoradiotherapy and adjuvant chemotherapy were included from a single institution and analyzed retrospectively. The primary endpoint was overall survival, and the secondary endpoints were progression-free survival, response, and safety. A total of 71 patients were enrolled in this study. The response rate was 41% (29/71), and the tumor control rate was 80% (57/71). In the 67 patients who completed the concurrent chemoradiotherapy with temozolomide, the median overall survival was 19 months and the 1- and 2-yr overall survival rates were 78.3% and 41.7%, respectively. The median progression free survival was 9 months, and the 1- and 2-yr progression free survival rates were 33.8% and 14.3%, respectively. The mean duration of survival after progression of disease in salvage treatment group was 11.9 (1.3-53.2) months. Concurrent chemoradiotherapy with temozolomide resulted in grade 3 or 4 hematologic toxic effects in 2.8% of the patients. The current protocol of temozolomide during and after radiation therapy is both effective and safe and is still appropriate as the standard protocol for treatment of glioblastoma. An active salvage treatment might be required for a better prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Alkylating/administration & dosage ; Brain Neoplasms/diagnosis/*mortality/*therapy ; Chemoradiotherapy, Adjuvant/methods/mortality ; Comorbidity ; Dacarbazine/administration & dosage/*analogs & derivatives ; Female ; Glioblastoma/diagnosis/*mortality/*therapy ; Hematologic Diseases/*mortality ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prevalence ; Radiotherapy, Conformal/mortality ; Republic of Korea/epidemiology ; Risk Factors ; Survival Rate ; Treatment Outcome ; Young Adult

This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anorexia/etiology ; Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use ; Brain Neoplasms/*drug therapy/pathology/radiotherapy ; Dacarbazine/adverse effects/*analogs & derivatives/therapeutic use/toxicity ; Female ; Glioma/*drug therapy/pathology/radiotherapy ; Hematologic Diseases/etiology ; Humans ; Male ; Middle Aged ; Nausea/drug therapy/etiology ; Neoplasm Staging ; Republic of Korea ; Retrospective Studies ; Severity of Illness Index ; Sex Factors ; Vomiting/drug therapy/etiology ; Young Adult