Chronic neuroinflammation is an integral pathological feature of major neurodegenerative diseases. The recruitment of microglia to affected brain regions and the activation of these cells are the major events leading to disease-associated neuroinflammation. In a previous study, we showed that neuron-released alpha-synuclein can activate microglia through activating the Toll-like receptor 2 (TLR2) pathway, resulting in proinflammatory responses. However, it is not clear whether other signaling pathways are involved in the migration and activation of microglia in response to neuron-released alpha-synuclein. In the current study, we demonstrated that TLR2 activation is not sufficient for all of the changes manifested by microglia in response to neuron-released alpha-synuclein. Specifically, the migration of and morphological changes in microglia, triggered by neuron-released alpha-synuclein, did not require the activation of TLR2, whereas increased proliferation and production of cytokines were strictly under the control of TLR2. Construction of a hypothetical signaling network using computational tools and experimental validation with various peptide inhibitors showed that beta1-integrin was necessary for both the morphological changes and the migration. However, neither proliferation nor cytokine production by microglia was dependent on the activation of beta1-integrin. These results suggest that beta1-integrin signaling is specifically responsible for the recruitment of microglia to the disease-affected brain regions, where neurons most likely release relatively high levels of alpha-synuclein.
Animals ; Antigens, CD29/genetics/*metabolism ; Cell Line, Tumor ; *Cell Movement ; Cells, Cultured ; Culture Media, Conditioned/*pharmacology ; Gene Regulatory Networks ; Humans ; Mice ; Mice, Inbred C57BL ; Microglia/drug effects/metabolism/*physiology ; Neurons/*metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism ; alpha-Synuclein/*pharmacology

We studied a Monte Carlo simulation of the proton beam delivery system at the National Cancer Center (NCC) using the Geant4 Monte Carlo toolkit and tested its feasibility as a dose verification framework. The Monte Carlo technique for dose calculation methodology has been recognized as the most accurate way for understanding the dose distribution in given materials. In order to take advantage of this methodology for application to externalbeam radiotherapy, a precise modeling of the nozzle elements along with the beam delivery path and correct initial beam characteristics are mandatory. Among three different treatment modes, double/single.scattering, uniform scanning and pencil beam scanning, we have modeled and simulated the double.scattering mode for the nozzle elements, including all components and varying the time and space with the Geant4.8.2 Monte Carlo code. We have obtained simulation data that showed an excellent correlation to the measured dose distributions at a specific treatment depth. We successfully set up the Monte Carlo simulation platform for the NCC proton therapy facility. It can be adapted to the precise dosimetry for therapeutic proton beam use at the NCC. Additional Monte Carlo work for the full proton beam energy range can be performed.
Proton Therapy ; Protons* ; Radiotherapy

A 74-year-old male patient was conducted total thyroidectomy with functional neck dissection and final pathologic report confirm occult thyroid carcinoma. Although the frequency of occult thyroid cancer (OTC) has decreased owing to developments in cervical ultrasonography and improved accuracy of histological tests, rare cases are still reported. Due to the decreased frequency of OTC, a benign cervical neck lymph node mass is sometimes diagnosed, which can result in delays to more accurate diagnoses and appropriate treatment. Therefore, we report our case.
Aged ; Diagnosis ; Humans ; Lymph Nodes ; Male ; Neck Dissection ; Neck ; Neoplasm Metastasis ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Ultrasonography

PURPOSE: Neoadjuvant chemotherapy (NC) is yet to be established as the definitive treatment regimen for locally advanced breast cancer (LABC). The aim of this study was to determine the efficacy and toxicity of NC with epirubicin and paclitaxel. METHODS: Between March 2007 and January 2009, 50 patients with LABC were enrolled in an open-label, phase II, multicenter study carried out at five distinct institutions. All patients were scheduled to receive four cycles of 60 mg/m2 epirubicin and 175 mg/m2 paclitaxel every 3 weeks, preoperatively, unless they developed profound side effects or disease progression. After curative surgery, two additional cycles of chemotherapy were administered to patients who had shown a positive response to NC. RESULTS: In all, 196 cycles of chemotherapy were administered preoperatively; 47 of the 50 patients (94%) underwent all four cycles of designated treatment. Complete disappearance of invasive foci of the primary tumor, and negative axillary lymph nodes were confirmed in eight patients (16.0%), post operation. The cumulative 5-year disease-free survival rate was 70.0% for patients with complete remission (CR) and partial remission (PR), and 33.3% for patients with stable disease (SD) and progressive disease (PD) (p=0.018). The cumulative 5-year overall survival was 90.0% for patients who achieved CR and PR and 55.6% for patients who had SD and PD (p=0.001). Neutropenia (42.0%) was the most common grade 3/4 toxicity. However, none of the toxicities resulted in cessation of the treatment. CONCLUSION: The encouraging pathologic response observed in the patients treated with epirubicin plus paclitaxel NC in this study suggests that epirubicin could be a substitute for doxorubicin, which is the most cardiotoxic agent.
Breast Neoplasms* ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; Drug Therapy* ; Epirubicin* ; Humans ; Lymph Nodes ; Neoadjuvant Therapy ; Neutropenia ; Paclitaxel

BACKGROUND: Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new anti??neoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. METHODS: Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine 1000mg/m2 and intravenous vinorelbine 25mg/m2 on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. RESULTS: A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria.?The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. CONCLUSION: The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.
Carcinoma, Non-Small-Cell Lung ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Korea ; Lung Neoplasms ; Lung* ; Neutropenia ; Paclitaxel ; Survival Rate