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

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.

OBJECTIVE: 6-Gingerol, one component of ginger (Zingiber officinale) compound, has been known to possess anti-inflammatory, analgesic, anti-emetic, and anti-cancer effects. In this study, the apoptotic ability of 6-gingerol was investigated in human prostate cancer cells. METHODS: 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) assay, flow cytometry, and western blot analysis were done in LNCaP human prostate cancer cell lines treated with the various doses of 6-gingerol for the different durations of drug exposure. RESULTS: 6-Gingerol in doses ranging from 100 to 300 microM induced dose- and time-dependent inhibition of cell viability in prostate cancer cells by using MTT assay. Maximal inhibition of cell viability was observed at 300 microM of 6-gingerol for 48 hours treatment in LNCaP cells. 6-Gingerol at the dose of 100 microM did not produce any significant change in apoptotic cells in flow cytometry analysis. However, significant increase in sub-G0/G1 phase was observed in cells treated with 200 and 300 microM of 6-gingerol. Any significant cell cycle arrest was not induced by 6-gingerol. In western blotting analysis, expression of caspase-3 was not evident in cells treated with 6-gingerol for 24 hours. However, 48 hours treatment with 6-gingerol altered the expression of caspase-3 in LNCaP cells. Expression of cleaved poly showed the dose-dependent fashion in both 24 hours and 48 hours treatment of 6-gingerol. CONCLUSION: These observations suggest that 6-gingerol may induce apoptosis in LNCaP human prostate cancer cells.
Apoptosis ; Blotting, Western ; Caspase 3 ; Catechols ; Cell Cycle Checkpoints ; Cell Line ; Cell Survival ; Fatty Alcohols ; Flow Cytometry ; Ginger ; Humans ; Poly(ADP-ribose) Polymerases ; Prostate ; Prostatic Neoplasms

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

Anatomical variations of the biceps brachii have been described by various authors, but the occurrence of bilateral asymmetric supernumerary heads is rare and has not been reported. We found three accessory heads of the biceps brachii muscle on right arm and an anomalous third head of biceps brachii on left arm. The third, fourth, and fifth heads of right arm originated from the body of humerus at the insertion site of coracobrachialis and inserted into the distal part of biceps brachii short head in order. The third head of left arm originated from humerus at the insertion site of coracobrachialis and combined with the distal part of biceps brachii and continued to the proximal part of common biceps tendon. Understanding the existence of bilateral asymmetric supernumerary heads of biceps brachii may influence preoperative diagnosis and surgery on the upper limbs.
Arm ; Head ; Humerus ; Muscles ; Tendons ; Upper Extremity

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.

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

To identify genes that participate in the abortion process, normal pregnant uteri were compared to lipopolysaccharide (LPS)-induced abortion uteri. At day 6 of pregnancy, mice were treated with LPS at various time points to induce an abortion. Total RNAs were applied to a cDNA microarray to analyze genes with altered expression. At the early stage (2 hours) of LPS-induced abortion, upregulated genes were mainly composed of immune responsive genes, including Ccl4, Ccl2, Cxcl13, Gbp3, Gbp2, Mx2, H2-Eb1, Irf1 and Ifi203. Genes related to toll-like receptor signaling were also overexpressed. At late stages of abortion (12-24 hours), many genes were suppressed rather than activated, and these were mainly related to the extracellular matrix, cytoskeleton, and anti-apoptosis. Altered expression of several selected genes was confirmed by real time reverse transcription-polymerase chain reaction. The results demonstrated that many known genes were altered in the LPS-treated pregnant uterus, implying that the molecular mechanisms of the genes involved in LPS-induced abortion are complicated. Further analysis of this expression profile will help our understanding of the pathophysiological basis for abortion.
Animals ; Cytoskeleton ; Extracellular Matrix ; Gene Expression ; Gene Expression Profiling ; Mice ; Oligonucleotide Array Sequence Analysis ; Pregnancy ; RNA ; Toll-Like Receptors ; Uterus

OBJECTIVE: Malignant gliomas are the most common primary cerebral neoplasms in adults. Despite multimodality treatments, the prognosis for patients with malignant glioma remains poor. However, recently, the effectiveness of concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) has been reported. We report for the first time preliminary results of the treatment with CCRT of newly diagnosed malignant gliomas in Korean people. METHODS: Thirty-two patients over the age of 17 years with newly diagnosed and histologically confirmed high-grade gliomas (HGG), from June 2004 to August 2007 were the subjects of this study. There were 17 men and 15 women, with a median age of 53.5 years (range, 17-74). Pathologically, glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, and gliomatosis cerebri had been diagnosed in eighteen, eight, four, and two patients, respectively. These 32 patients were treated with CCRT with TMZ. RESULTS: The median follow-up period was 12.5 months (range 3-48). At the time of this analysis, 13 patients died and three patients had been lost to follow-up. There was no mortality caused by drug toxicity. The median progression-free survival (PFS) of these patients was 9.0 months, and the six-month PFS rate was 72.4%. The median overall survival (OS) was 26 months, and the one-year OS rate was 83.6%. The 18 patients with glioblastoma were analyzed separately from the other patients with HGG, and the median OS was 18 months, and the one-year OS rates were 81.8%. The median PFS was seven months, and the six-month PFS rate was 75.0%. CONCLUSION: Our results are consistent with many other reports, confirming that CCRT with TMZ achieves good clinical outcomes in the treatment of HGG. Therefore, we suggest that CCRT with TMZ as adjuvant chemotherapy be considered as a standard therapy for patients with HGG.
Adult ; Astrocytoma ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Dacarbazine ; Disease-Free Survival ; Drug Toxicity ; Female ; Follow-Up Studies ; Glioblastoma ; Glioma ; Humans ; Lost to Follow-Up ; Male ; Neoplasms, Neuroepithelial ; Oligodendroglioma ; Prognosis ; Prospective Studies