Mesenchymal stem cells (MSCs) are attractive candidates for clinical repair or regeneration of damaged tissues. Oct4 and Sox2, which are essential transcription factors for pluripotency and self-renewal, are naturally expressed in MSCs at low levels in early passages, and their levels gradually decrease as the passage number increases. Therefore, to improve MSC proliferation and stemness, we introduced human Oct4 and Sox2 for conferring higher expansion and differentiation capabilities. The Oct4-IRES-Sox2 vector was transfected into human adipose tissue MSCs (ATMSCs) by liposomal transfection and used directly. Oct4 and Sox2 were successfully transfected into ATMSCs, and we confirmed maintenance of MSC surface markers without alterations in both red fluorescent protein (RFP) (control) and Oct4/Sox2-ATMSCs. Enhanced proliferative activity of Oct4/Sox2-ATMSCs was shown by WST-1 assay, and this result was further confirmed by cell counting using trypan blue exclusion for a long period. In addition, FACs cell cycle analysis showed that there was a reduction in the fraction of Oct4/Sox2-ATMSCs in G1 with a concomitant increase in the fraction of cells in S, compared with RFP-ATMSCs. Increased levels of cyclin D1 were also seen in Oct4/Sox2-ATMSCs, indicating acceleration in the transition of cells from G1 to S phase. Furthermore, Oct4/Sox2-overexpressing ATMSCs showed higher differentiation abilities for adipocytes or osteoblasts than controls. The markers of adipogenic or osteogenic differentiation were also upregulated by Oct4/Sox2 overexpression. The improvement in cell proliferation and differentiation using Oct4/Sox2 expression in ATMSCs may be a useful method for expanding the population and increasing the stemness of ATMSCs.
Adipose Tissue/cytology ; *Cell Differentiation ; *Cell Proliferation ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells/cytology/*metabolism/physiology ; Octamer Transcription Factor-3/genetics/*metabolism ; SOXB1 Transcription Factors/genetics/*metabolism

A 12-years-old female admitted to the hospital with the complaint of pain on the right upper chest area which persisted about 1 month prior to admission. Cafe-au-lait spots of various size laying on a whole body and freckling on the axilla were found on physical examination. A huge mass was found on the plain chest X-ray and on chest MRI. The mass encroached thoracic spine, posterior rib, back muscles, and then into the neural canal and compressed thoracic spinal cord. On the 5th day of hospitalization, the patient complained tingling on the both legs and 2 days later, monoparesis on the right leg. Open thoracotomy and decompressive laminectomy was done to remove mass. Pathologic reports confirmed rhabdomyosarcoma, embryonal type.
Axilla ; Back Muscles ; Cafe-au-Lait Spots ; Female ; Hospitalization ; Humans ; Laminectomy ; Leg ; Magnetic Resonance Imaging ; Mediastinum* ; Neural Tube ; Paresis ; Physical Examination ; Rhabdomyosarcoma* ; Rhabdomyosarcoma, Embryonal ; Ribs ; Spinal Cord Compression* ; Spinal Cord* ; Spine ; Thoracotomy ; Thorax

PURPOSE: The purpose of this study was to determine the potential role of three-dimensional conformal radiotherapy (3D-CRT) in the treatment of primary unresectable hepatocellular carcinoma. The preliminary results on the efficacy and the toxicity of 3D-CRT are reported. MATERIALS AND METHODS: Seventeen patients were enrolled in this study, which was conducted prospectively from January 1995 to June 1997. The exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child-Pugh classification C, tumors occupying more than two thirds of the entire liver, and a performance status of more than 3 on the ECOG scale. Two patients were treated with radiotherapy only while the remaining 15 were treated with combined transcatheter arterial chemoembolization. Radiotherapy was given to the field including the tumor plus a 1.5 cm margin using a 3D-CRT technique. The radiation dose ranged from 36~60 Gy (median; 59.4 Gy). Tumor response was based on a radiological examination such as the CT scan, MR imaging, and hepatic artery angiography at 4~8 weeks following the completion of treatment. The acute and subacute toxicities were monitored. RESULTS: An objective response was observed in 11 out of 17 patients, giving a response rate of 64.7%. The actuarial survival rate at 2 years was 21.2% from the start of radiotherapy (median survival; 19 months). Six patients developed a distant metastasis consisting of a lung metastasis in 5 patients and bone metastasis in one. The complications related to 3D-CRT were gastro-duodenitis (>or= grade 2) in 2 patients. There were no treatment related deaths and radiation induced hepatitis. CONCLUSION: The preliminary results show that 3D-CRT is a reliable and effective treatment modality for primary unresectable hepatocellular carcinoma compared to other conventional modalities. Further studies to evaluate the definitive role of the 3D-CRT technique in the treatment of primary unresectable hepatocellular carcinoma are needed.
Angiography ; Carcinoma, Hepatocellular* ; Classification ; Hepatic Artery ; Hepatitis ; Humans ; Liver ; Liver Cirrhosis ; Lung ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Prospective Studies ; Radiotherapy ; Radiotherapy, Conformal* ; Survival Rate ; Tomography, X-Ray Computed

Small-breed dogs (n = 168; weight < 15 kg) diagnosed with myxomatous mitral valve degeneration based on a routine clinical examination, radiology, electrocardiography, and echocardiography at the Seoul National University Veterinary Medical Teaching Hospital were included in this study. Survival periods were determined, and there were significant differences in survival rates among the three International Small Animal Cardiac Health Council classes. The mean follow-up period was 14.3 ± 12.1 months. Univariate analysis revealed that dyspnea, pulmonary edema, and vertebral heart score were significantly associated with survival time (p < 0.05). Additionally, age, left atrial-to-aortic root ratio, ejection fraction, and left ventricular end diastolic volume were associated with an increased risk of death (p < 0.1), while body weight, body condition score, systolic blood pressure, arrhythmia, syncope, fractional shortening, and end systolic volume were not associated with an increased risk of death. These results suggest that among the assessed variables dyspnea, pulmonary edema, and vertebral heart score could be useful prognostic factors for providing patient information to owners.
Animals ; Arrhythmias, Cardiac ; Blood Pressure ; Body Weight ; Dogs* ; Dyspnea ; Echocardiography ; Electrocardiography ; Follow-Up Studies ; Heart ; Heart Failure ; Hospitals, Teaching ; Humans ; Mitral Valve* ; Prognosis ; Pulmonary Edema ; Retrospective Studies* ; Seoul ; Stroke Volume ; Survival Rate ; Syncope

Seventeen dogs were treated with L-ornithin-L-aspartate (LOLA; experimental group). Three dogs were treated with lactulose recognized therapy (control group). Following LOLA administration, 15 dogs experienced a significant decrease in ammonia level (p < 0.05) and showed clinical signs of improvement. However, there were no clinical signs of improvement in two dogs, even though the ammonia level decreased. Conversely, the clinical signs of the control group also improved and the ammonia level decreased, although these changes were not significant (p > 0.05). These results suggest that LOLA is an effective drug to treat hyperammonemia in veterinary medicine.
Ammonia ; Animals ; Dogs* ; Dipeptides* ; Hepatic Encephalopathy* ; Hyperammonemia ; Lactulose ; Veterinary Medicine

Severe acute pancreatitis (SAP) is associated with systemic complications and high mortality rate in dogs. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential in several inflammation models. In the present study, the effects of canine adipose tissue-derived (cAT)-MSCs in a rat model of SAP induced by retrograde injection of 3% sodium taurocholate solution into the pancreatic duct were investigated. cAT-MSCs labeled with dioctadecyl-3,3,3′-tetramethylindo-carbocyanine perchlorate (1 × 10⁷ cells/kg) were systemically administered to rats and pancreatic tissue was collected three days later for histopathological, quantitative real-time polymerase chain reaction, and immunocytochemical analyses. Greater numbers of infused cAT-MSCs were detected in the pancreas of SAP relative to sham-operated rats. cAT-MSC infusion reduced pancreatic edema, inflammatory cell infiltration, and acinar cell necrosis, and decreased pancreatic expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, -6, -12, -17, and -23 and interferon-γ, while stimulating expression of the anti-inflammatory cytokines IL-4 and IL-10 in SAP rats. Moreover, cAT-MSCs decreased the number of clusters of differentiation 3-positive T cells and increased that of forkhead box P3-positive T cells in the injured pancreas. These results indicate that cAT-MSCs can be effective as a cell-based therapeutic strategy for treatment of SAP in dogs.
Acinar Cells ; Animals ; Anti-Inflammatory Agents ; Cytokines ; Dogs ; Edema ; Inflammation ; Interleukin-10 ; Interleukin-4 ; Interleukins ; Mesenchymal Stromal Cells* ; Models, Animal ; Mortality ; Necrosis ; Pancreas ; Pancreatic Ducts ; Pancreatitis* ; Rats* ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes* ; T-Lymphocytes, Regulatory ; Taurocholic Acid

Biliary hamartoma and congenital hepatic fibrosis belong to fibrocystic disorders originating from ductal plate malformation. A 66-year-old man who had incidentally been diagnosed with biliary hamartoma two years ago presented to us with recurrent acute cholangitis. In the first episode, he had presented with septic shock and was treated with endoscopic retrograde cholangiopancreatography (ERCP) and cholecystectomy under the diagnosis of acute cholecystitis and cholangitis. However, during a two-month follow-up period, the patient experienced four episodes of acute cholangitis. Because he showed normal ERCP, and biliary hamartoma is usually asymptomatic, a liver biopsy was performed. Pathology revealed combined features of biliary hamartoma and congenital hepatic fibrosis, characterized as periportal fibrosis and intrahepatic ductular dysplasia. During follow-up for the last six months, he had experienced two episodes of acute cholangitis and was treated with antibiotics. A follow-up abdominal CT scan revealed aggravated hepatosplenomegaly compared to that of two years ago. We report a case of combined congenital hepatic fibrosis and biliary hamartoma and a literature review.
Aged ; Anti-Bacterial Agents ; Biopsy ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis* ; Cholecystectomy ; Cholecystitis, Acute ; Diagnosis ; Fibrosis* ; Follow-Up Studies ; Hamartoma* ; Humans ; Liver ; Pathology ; Shock, Septic ; Tomography, X-Ray Computed