PURPOSE: Chemokines are structurally related, small polypeptide signaling molecules that bind to and activate a family of transmembrane G proteincoupled receptors, the chemokine receptors. Recently, interaction between the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor 1 (SDF-1 or CXCL12), has been found to play an important role in tumorigenicity, proliferation, metastasis and angiogenesis in many cancers such as lung cancer, breast cancer, melanoma, glioblastoma, pancreatic cancer and cholangiocarcinoma. Hence, the goal of this study is to identify the correlation of clinicopathological factors and the up-regulation of SDF-1 expression in oral squamous cell carcinoma. MATERIAL AND METHODS: We studied the immunohistochemical staining of SDF-1, quantitative RT-PCR (qRT-PCR) of SDF-1 gene in 20 specimens of 20 patients with oral squamous cell carcinoma. RESULTS: 1. In the immunohistochemical study of poor differentiated and invasive oral squamous cell carcinoma, the high level staining of SDF-1 was observed. And the correlation between immunohistochemical SDF-1 expression and tumor nodes metastases (TNM) classification of specimens was significant.(chi-square test, P < 0.05) 2. In the SDF-1 gene qRT-PCR analysis, SDF-1 expression was more in tumor tissue than in carcinoma in situ tissue. Paired-samples analysis determined the difference of SDF-1 mRNA expression level between the cancer tissue and the carcinoma in situ tissue.(Student's t-test, P < 0.05) CONCLUSION: These findings suggest that up-regulation of the SDF-1 may play a role in progression and invasion of oral squamous cell carcinoma.
Breast Neoplasms ; Carcinoma in Situ ; Carcinoma, Squamous Cell ; Chemokine CXCL12 ; Chemokines ; Cholangiocarcinoma ; Glioblastoma ; Humans ; Lung Neoplasms ; Melanoma ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Receptors, Chemokine ; RNA, Messenger ; Up-Regulation

We analyzed 91 cases with seizures after stroke(except subarachnoid hemorrhage) to see, recurrence rate, onset time, lesion sites and electroencephalographic findings. Overall incidence of seizure was 5.73%[7.57% of all cerebral infarction(CI; 938 cases) and 3.0% of an intracerebral hemorrhage(ICH; 649 cases)] in all admitted stroke patient(l450) from Jan. 1980 to Jun. 1989 and all stroke patients visited out-patient department(137 ; from Sep. 1989 to Oct. 1989) in the department of neurology, Seoul National University Hosptal. And then, we excluded 22 cases because of insufficient clinical information.1) We followed up 69 patients and in those cases, seizures occurred rnore frequently in CI(51) than in ICH(18). 2) Seizures of ear!y onset(<2week) occurred in 25(49.0%) of 51 cases with cerebral infarction and in 12(66.7%) of 18 cases with IVH. 3) Seizures occurred more frequently in cortical lesions(71.0%)[CI: 71.4% and ICH ; 28.6%] than in subcortical lesions(24.6%)[CI ; 76.5% and ICH ; 23.5%]. 4) Recurrence rate (69.5%) of the patients without antiepileptic medication was signigicantly higher than (16.7%) of patients with medication[Spearman's Rho=0.52, p<0.001]. 5) Of those patients without medication, the recurrence rate was highest in the patients showing epileptiform discharge(100%) in EEG. Followed by focal slowing(66.7%), diffuse slowing(62.5%) and normal EEG features(33.3%)[Spearman's Rho=0.41, P=0.01]. 6) The recurrence of seizures was more frequent in the patients with CI(54.9%) than in ICH(22.2%).
Cerebral Infarction ; Electroencephalography ; Humans ; Incidence ; Neurology ; Outpatients ; Recurrence ; Seizures* ; Seoul ; Stroke

CD137, which is expressed on activated T cells, plays a critical role in inflammatory responses. However, the exact role that CD137 plays in monocytes is not fully known. Here we studied the expression and function of CD137 in human monocytic THP-1 cells, which we found constitutively expresses CD137 at the mRNA and protein level. Cross-linking of CD137 increased the secretion of IL-8 and TNF-alpha, promoted the expression of CD54 and CD11b, and increased adhesion to extracellular matrix (ECM) proteins. In particular CD137-induced adhesion of THP-1 cells was inhibited by an inhibitor of mitogen-activated protein kinase kinase (MEK), but not by a p38 kinase inhibitor. Taken together, these results show that the adhesion and cytokine production of THP-1 cells induced by CD137 occur via activation of MEK, which results in the activation of ERK-1/2 signaling pathways. Therefore, this study suggests that CD137 induces an activating and migrating signal during inflammatory processes.
Antigens, CD/biosynthesis/*immunology ; Antigens, CD11/biosynthesis ; *Cell Adhesion ; Cell Adhesion Molecules/biosynthesis ; Cell Line ; Cytokines/*biosynthesis ; Enzyme Activation ; Extracellular Matrix Proteins/metabolism ; Flow Cytometry ; Humans ; Immunity, Natural ; Intercellular Adhesion Molecule-1/biosynthesis ; Interleukin-8/biosynthesis ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Monocytes/metabolism/*physiology ; Phosphorylation ; Protein Binding ; Receptors, Nerve Growth Factor/biosynthesis/*immunology ; Receptors, Tumor Necrosis Factor/biosynthesis/*immunology ; Research Support, Non-U.S. Gov't ; Signal Transduction ; Tumor Necrosis Factor-alpha/biosynthesis ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors

Seizure activity increases glucose utilization within the brain in response to neuronal injury. In this study, we investigated the expression of two brain glucose transporter (GLUT) proteins, GLUT1 and GLUT3, in the mouse hippocampus after kainic acid (KA) treatment. Forty-eight hours after KA (30 mg/kg) injection, mice were sacrificed and a histological evaluation of KA-treated hippocampus revealed cell death using cresyl violet staining and immunohistochemistry for caspase-3. In KA-treated hippocampus, reactive astrocytic changes were confirmed by increased immunoreactivity of glial fibrillary acidic protein (GFAP). Enhanced GLUT1-positive endothelial cells were present in the hippocampus after KA treatment. However, GLUT3-positive neurons were not localized to the KAtreated hippocampus. In particular, although GLUT-3 was not expressed in the hippocampus, pronounced GLUT3- positive cells were observed in the hypothalamic paraventricular nucleus (PVN), which controls energy metabolism. Thus, these results indicate that changes in endothelial GLUT1 and neuronal GLUT3 levels in response to neural injury may play important roles in neuroprotection against brain excitotoxicity.
Animals ; Benzoxazines ; Brain ; Caspase 3 ; Cell Death ; Endothelial Cells ; Energy Metabolism ; Glial Fibrillary Acidic Protein ; Glucose ; Glucose Transport Proteins, Facilitative ; Hippocampus ; Immunohistochemistry ; Kainic Acid ; Mice ; Neurons ; Paraventricular Hypothalamic Nucleus ; Proteins ; Seizures ; Viola

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.