Background: Despite the availability of various therapeutic strategies, the prognosis for patients with metastatic breast cancer remains poor. Epithelial-mesenchymal transition (EMT) is a critical mechanism driving metastasis in breast cancer, enabling tumor cells to lose epithelial characteristics and acquire enhanced motility and invasiveness. Results: This study investigates the role of 11alpha-hydroxyprogesterone (11α-OHP), a steroid hormone with an incompletely understood biosynthesis and metabolic pathway, in regulating lung metastasis in breast cancer. Using the MMTV-PyMT FVB mouse model, which spontaneously develops breast tumors we administered 11α-OHP for five weeks starting at 10 weeks of age. At 15 weeks, histological analysis revealed a significant reduction in lung metastasis in 11α-OHP-treated mice compared to controls, with notably smaller metastatic tumor areas in the lungs. Additionally, treated mice exhibited increased expression of epithelial cell adhesion proteins and decreased levels of focal adhesion kinase (FAK) in lung tissues. In vitro experiments using MDA-MB-231 cells corroborated these findings, showing that 11α-OHP significantly inhibited cell motility and invasiveness in scratch wound, transwell migration, and invasion assays. Notably, 11α-OHP did not significantly alter primary tumor growth in the MMTV-PyMT model. Conclusions These findings suggest that 11α-OHP may suppress breast cancer metastasis by modulating EMT, highlighting its potential as a therapeutic target for preventing metastatic progression.

Purpose: We developed immune checkpoint molecules to target recombinant dendritic cells (DCs) and verified their anti-tumor efficacy and immune response against prostate cancer. Materials and Methods: DCs were generated from mononuclear cells in the tibia and femur bone marrow of mice. We knocked down the programmed death ligand 1 (PD-L1) on monocyte-derived DCs through siRNA PD-L1. Cell surface antigens were immune fluorescently stained through flow cytometry to analyze cultured cell phenotypes. Furthermore, we evaluated the efficacy of monocyte-derived DCs and recombinant DCs in a prostate cancer mouse model with subcutaneous TRAMP-C1 cells. Lastly, DC-induced mixed lymphocyte and lymphocyte-only proliferations were compared to determine cultured DCs’ function. Results: Compared to the control group, siRNA PD-L1 therapeutic DC-treated mice exhibited significantly inhibited tumor volume and increased tumor cell apoptosis. Remarkably, this treatment substantially augmented interferon-gamma and interleukin-2 production by stimulating T-cells in an allogeneic mixed lymphocyte reaction. Moreover, we demonstrated that PD-L1 gene silencing improved cell proliferation and cytokine production. Conclusions We developed monocyte-derived DCs transfected with PD-L1 siRNA from mouse bone marrow. Our study highlights that PD-L1 inhibition in DCs increases antigen-specific immune responses, corroborating previous immunotherapy methodology findings regarding castration-resistant prostate cancer.

Objectives: The aim of this study is to investigate the clinical utility of contrast-enhanced computed tomography (CECT) in patient with non-obstrcutive acute pyelonephritis (APN). Methods: From 2007 to 2013, 537 APN patients who underwent a CE-CT scan within 24 hours after hospital admission were enrolled. We divided these patients into greater (50% or greater involvment, n = 143) and lesser (less than 50% involvement, n = 394) groups based on renal parenchymal involvement in CE-CT examination. We compared clinical characteristics between two groups and analyzed the clinical value of CE-CT scan as a reliable marker for predicting clinical severity and disease course in patient with non-obstructive APN. Results: The mean estimated glomerular filtration rate was 70.6 ± 25.5 mL/min/1.73m2. Compared with patients in lesser group, the patients in greater group had lower serum albumin levels (3.5 ± 0.5 vs 3.8 ± 0.6, P < 0.01) and longer hosptal stay (10.1 ± 4.7 vs 8.8 ± 4.5, P < 0.05). In addition, acute kidney injury (AKI) (23.1% vs 11.4%, P < 0.005) and bacteremia (36.4% vs 26.8%, P = 0.02) were frequently developed in greater group, respectively. The overall incidence of AKI was 14.8% based on RIFLE criteria. In a multivariate logistic regression analysis for predciting AKI, age, presence of diabetes mellitus and the presence of renal parenchymal involvement of greater than 50% in CE-CT were significant predictors of AKI. Conclusions The CE-CT scan could be useful to predict the clinical severity and course in non-obstructive APN patients with preserved renal function.

Although formaldehyde (FA) is known to be a major allergen responsible for allergic contact dermatitis, there are conflicting reports regarding correlation between FA exposure and interleukin (IL-4) expression. To investigate whether allergic responses including IL-4 expression were induced by repeated dermal exposure to low dose FA, alterations in the luciferase signal and allergic phenotypes were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice containing luciferase cDNA under control of the IL-4 promoter after exposure to 4% FA for 2 weeks. High levels of luciferase were detected in the abdominal region of the whole body and submandibular lymph node (SLN) of FA treated mice. Additionally, the ear thickness and IgE concentration were significantly upregulated in the FA treated group when compared with the acetone olive oil (AOO) treated group. FA treated mice showed enhanced auricular lymph node (ALN) weight, epidermis and dermis thickness, and infiltration of inflammatory cells. Furthermore, the expression of IL-6 among T helper 2 cytokines was higher in the FA treated group than the AOO treated group, while vascular endothelial growth factor (VEGF) levels remained constant. Overall, the results presented herein provide additional evidence that various allergic responses may be successfully induced in IL-4/Luc/CNS-1 Tg mice after exposure to low dose FA for 2 weeks. The luciferase signal under the IL-4 promoter may reflect general indicators of the allergic response induced by exposure to low dose FA.
Acetone ; Animals ; Cytokines ; Dermatitis, Allergic Contact ; Dermis ; DNA, Complementary ; Ear ; Epidermis ; Formaldehyde* ; Immunoglobulin E ; Interleukin-4 ; Interleukin-6 ; Interleukins ; Luciferases ; Lymph Nodes ; Mice ; Mice, Transgenic* ; Olea ; Phenotype ; Vascular Endothelial Growth Factor A ; Olive Oil

BACKGROUND/AIMS: The aim of this study was to investigate changes in the clinical and demographical characteristics of gallstone disease in Korea, based on 30 years of surgically treated patients at a single institute. METHODS: In total, 7,949 gallstone patients who underwent surgery between 1981 and 2010 were analyzed. Patients were divided into six time periods: period I (1981 to 1985, n=831), period II (1986 to 1990, n=888), period III (1991 to 1995, n=1,040), period IV (1996 to 2000, n=1,261), period V (2001 to 2005, n=1,651) and period VI (2006 to 2010, n=2,278). RESULTS: The total number and mean age of the patients gradually increased, and the male/female ratio decreased. The proportion of gallbladder (GB)-stone cases increased, whereas the proportions of common bile duct (CBD)- and intrahepatic duct (IHD)-stone cases decreased. Differences in patient geographical origins also decreased. Based on the relationship between changes in the prevalence of gallstone disease and socioeconomic status, the prevalence of CBD stones showed a strong correlation with Engel's coefficient (p<0.001). CONCLUSIONS: Our study indicates that although the total number of cases and the mean age of gallstone patients have continuously increased, there are trends of increasing GB-stone cases and decreasing CBD- and IHD-stone cases.
Adult ; Age Distribution ; Body Mass Index ; Choledocholithiasis/*epidemiology/surgery ; Female ; Gallstones/*epidemiology/surgery ; Humans ; Male ; Middle Aged ; Prevalence ; Republic of Korea/epidemiology ; Rural Population/trends ; Sex Ratio ; Socioeconomic Factors ; Urban Population/trends

BACKGROUND AND PURPOSE: The coexistence of carotid atherosclerosis in ischemic stroke patients with small-vessel disease (SVD) or intracranial large-vessel disease (ICLVD) was investigated using carotid duplex ultrasonography, and whether its coexistence affected the clinical prognosis was determined. METHODS: Ischemic stroke patients with SVD or ICLVD were enrolled (n=103). Risk factors, demographic data, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained for all of the subjects. Early neurological progression was defined by an increase in NIHSS score during the first 7 days. Carotid ultrasonography was performed to measure the intima-media thickness (IMT) and carotid plaques. RESULTS: Among the 103 patients who were retrospectively enrolled in this study (56 with SVD and 47 with ICLVD), 66 (64.1%) had an atherosclerotic plaque and 23 (22.3%) had increased IMT. Increased IMT was observed more frequently in ICLVD than in SVD [15/47 (31.9%) vs. 8/56 (14.3%), p=0.032]. An atherosclerotic plaque was observed on subsequent carotid ultrasonographic examination in 28 (50%) of the 56 patients whose computed tomography angiography scans of the neck vessels were interpreted as normal. There was no association between presence of atherosclerotic change and early neurologic progression (p=0.94). CONCLUSIONS: A coexisting atherosclerotic plaque or increased IMT was observed in 71.8% of patients with SVD or ICLVD. Whether the coexistence of carotid atherosclerotic change with either of these conditions affects the clinical prognosis remains to be elucidated.
Angiography ; Atherosclerosis ; Carotid Artery Diseases ; Humans ; National Institutes of Health (U.S.) ; Neck ; Plaque, Atherosclerotic ; Prognosis ; Retrospective Studies ; Risk Factors ; Stroke

In patients with acute ischemic stroke, carotid duplex ultrasonography has been used to assess atherosclerotic lesions at the extracranial carotid artery. We reported a unique sonographic finding of carotid artery thrombus in a patient with acute cardioembolic stroke and atrial fibrillation. An 81-year-old woman with atrial fibrillation was presented with dysarthria and left side hemiparesis. She had undergone surgical thrombectomy and angioplasty for her right brachial artery occlusion four days before the stroke onset. Diffusion-weighted MRI revealed multiple territorial infarctions suggestive of acute cardio-embolic stroke. CT angiography showed an occlusion of the right common carotid artery. On B-mode ultrasonography, longitudinal intraluminal tortuous cylinderic oscillating thrombus was observed on the right distal common carotid artery to the proximal internal carotid artery. This case illustrates a unique ultrasonographic finding of acute cardiogenic thrombus in the extracranial carotid artery.
Angiography ; Angioplasty ; Atrial Fibrillation ; Brachial Artery ; Carotid Arteries ; Carotid Artery, Common ; Carotid Artery, Internal ; Cerebral Infarction ; Dysarthria ; Female ; Humans ; Infarction ; Paresis ; Stroke ; Thrombectomy ; Thrombosis

With an increasing proportion of the elderly, dementia due to severe cerebral white matter change is frequently observed. Because these patients cannot express their symptoms effectively, the recognition of stroke can be delayed. In addition, clinical characteristics of their stroke might be different. We reported on three patients with severe leukoaraiosis, who exhibited altered consciousness after acute lacunar infarction in the corona radiata. This clinico-radiological discrepancy may have resulted from different susceptibility to ischemia in patients with severe white matter change.
Aged ; Cerebral Infarction ; Consciousness ; Dementia ; Dementia, Vascular ; Humans ; Ischemia ; Leukoaraiosis ; Stroke ; Stroke, Lacunar

BACKGROUND/AIMS: Signal transducers and activators of transcription (STATs) are a family of transcription factors that are activated in response to cytokines and growth factors. STAT3 activation has been implicated in modulating the activity of downstream mediators, such as Bcl-xL and matrix metalloproteinase-2 (MMP-2). The aim of this study was to investigate the immunohistochemical expression of STAT3, B-cell lymphoma-extra large (Bcl-xL), and MMP-2 proteins according to histopathological parameters in colon adenocarcinomas, including lymph node metastasis, tumor differentiation, the TNM stage and the tumor size. METHODS: Immunohistochemical staining with monoclonal STAT3, Bcl-xL, and MMP-2 antibodies was performed on paraffin-embedded specimens from 20 colon adenomas and 39 adenocarcinomas. RESULTS: The expression of STAT3, Bcl-xL, and MMP-2 was increased in the adenocarcinomas as compared with the adenomas (p<0.001). STAT3 expression was stronger in tumors with a distant metastasis than in tumors without a distant metastasis (p=0.012). A larger tumor size was related to an increase in STAT3 expression (p=0.035). CONCLUSIONS: STAT3, Bcl-xL, and MMP-2 may play important roles in the tumorigenesis of colorectal carcinoma. STAT3 may be indicative of a poor prognosis due to its correlation with distant metastases and a larger tumor size.
Adenocarcinoma ; Adenoma ; Antibodies ; B-Lymphocytes ; Cell Transformation, Neoplastic ; Colon ; Colorectal Neoplasms ; Cytokines ; Humans ; Intercellular Signaling Peptides and Proteins ; Lymph Nodes ; Matrix Metalloproteinase 2 ; Neoplasm Metastasis ; Prognosis ; Proteins ; Transcription Factors ; Transducers

Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-kappaB, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal-regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption.
Acid Phosphatase/genetics/metabolism ; Animals ; Anticholesteremic Agents/*pharmacology ; Blotting, Western ; *Cell Differentiation ; Cells, Cultured ; Hydrogen Peroxide/pharmacology ; Isoenzymes/genetics/metabolism ; Macrophages/cytology/drug effects/metabolism ; Mice ; Mitogen-Activated Protein Kinases/genetics/metabolism ; NF-kappa B/genetics/metabolism ; Osteoclasts/*cytology/*drug effects/metabolism ; RANK Ligand/metabolism ; RNA, Messenger/genetics ; Reactive Oxygen Species/*metabolism ; Real-Time Polymerase Chain Reaction ; Simvastatin/*pharmacology