PURPOSE: This study was performed to investigate whether the E2F1 protein expression can be used as a prognostic factor in clinical breast cancer. METHODS: The expressions of E2F1 and retinoblastoma protein (pRB) were analyzed in 165 lymph node positive breast cancers. All patients underwent adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) after curative surgery. RESULTS: E2F1 was expressed in 43.6% and pRB was expressed in 46.1%. E2F1 expression was significantly increased in pRB-expressing tumors and was associated with S-phase fraction. By univariate survival analyses, E2F1 expression and ER were the significant prognostic factors for the disease recurrence and patient survival. E2F1 was the only significant prognostic factor for the patient outcome after FAC chemotherapy by multivariate analysis. CONCLUSION: Conclusion The results of the current study indicate that abnormal expression of E2F1 and pRB is prevalent and are intimately associated with each other in clinical breast cancer. A significant association between E2F1 expression and patient survival after FAC chemotherapy mondates a further validation study.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Cyclophosphamide ; Doxorubicin ; Drug Therapy ; Fluorouracil ; Humans ; Lymph Nodes ; Multivariate Analysis ; Prognosis ; Recurrence ; Retinoblastoma Protein

BACKGROUND: Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. OBJECTIVE: Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. METHODS: Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. RESULTS: Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. CONCLUSION: Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment.
Desonide ; Diffusion ; Epidermis ; Glucocorticoids ; Inflammation ; Permeability ; Retention (Psychology) ; Skin ; Steroids

BACKGROUND/AIMS: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. METHODS: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. RESULTS: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. CONCLUSIONS: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.
Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Apoptosis/drug effects ; Autophagy/drug effects ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Survival/*drug effects ; Deoxycytidine/analogs & derivatives/pharmacology ; Drug Resistance, Neoplasm/*drug effects ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Microtubule-Associated Proteins/metabolism ; Pancreatic Neoplasms/*drug therapy ; Quercetin/pharmacology

Intestinal tuberculosis is a common disease of extrapulmonary tuberculosis. A diagnosis of intestinal tuberculosis is difficult as the symptoms and laboratory findings are not specific for the disease. Intestinal tuberculosis may cause various complications, such as intestinal obstruction, intestinal perforation, intraabdominal abscess, intestinal hemorrhage and fistula formation. A duodenal fistula caused by tuberculosis is an especially rare condition. We experienced a case of intestinal tuberculosis with a duodenal fistula as a complication. The patient was a 25-year-old man that presented with weight loss and diarrhea. Esophagogastroduodenoscopy showed a deep ulcerative lesion on the third portion of the duodenum with a fistula opening. A histological finding revealed granulomatous inflammation with multinucleated giant cells. In addition, the result of a Tb PCR assay was positive. After two months of treatment with the appropriate medication, the symptoms improved and the fistula has closed completely. We report the case with a review of the literature.
Abscess ; Adult ; Diagnosis ; Diarrhea ; Duodenum ; Endoscopy, Digestive System ; Fistula* ; Giant Cells ; Hemorrhage ; Humans ; Inflammation ; Intestinal Obstruction ; Intestinal Perforation ; Polymerase Chain Reaction ; Tuberculosis* ; Ulcer ; Weight Loss

Background/Aims: Irreversible electroporation (IRE) is a relatively new ablation method. However, the application of IRE ablation in the treatment of biliary disease has not been attempted. A minimally invasive approach using endoscopic retrograde cholangiopancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we aimed to investigate the feasibility of endoscopic IRE for the biliary tract using an animal model. Methods: A new catheter-type electrode was developed for endoscopic IRE ablation of the biliary tract. We performed ERCP and endoscopic IRE ablations in the normal common bile duct of Yorkshire pigs. The experimental setting of IRE was 500 V/cm (50 pulses, 100-µs length). The animals were sacrificed after 24 hr, and the ablated bile duct was examined. Results: Well-demarcated focal color changes were observed on the mucosa of the common bile duct. The depth of change after IRE was confined to the mucosal and submucosal layers. Apoptotic changes in the bile duct were observed only around the IRE ablation area. Immunohistochemistry assay showed cell death in the bile duct along the electrode. Conclusions Endoscopic IRE ablation using ERCP was successfully performed in the common bile duct. It can be a potential option for the treatment of biliary tumors.

Background/Aims: Gastric electrical stimulation (GES) is a feasible modality for the treatment of gastroparesis; however, the presently available device requires invasive surgical implantation for long-term stimulation and repeated surgical procedure after a period of time. This study is aimed at developing a wireless miniature GES device and testing its endoscopic insertion in animal models. Methods: Endoscopic gastric implantation of the GES device was performed on 5 healthy weaner pigs under general anesthesia. We created an endoscopic submucosal pocket and inserted the gastro-electrical stimulator. In vivo gastric slow waves were recorded and measured during electrical stimulation. A multi-channel recorder, called an electrogastrogram, was used to record the gastric myoelectrical activity in the study. Results: The gastric slow waves on the electrogastrogram were more consistent with GES on the gastric tissues compared to no stimulation. The frequency-to-amplitude ratio was also significantly altered after the electrical stimulation. Conclusions GES is feasible with our minimally invasive wireless device. This technique has the potential to increase utilization of GES as a treatment alternative.

Background/Aims: Irreversible electroporation (IRE) is a relatively new ablation method. However, the application of IRE ablation in the treatment of biliary disease has not been attempted. A minimally invasive approach using endoscopic retrograde cholangiopancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we aimed to investigate the feasibility of endoscopic IRE for the biliary tract using an animal model. Methods: A new catheter-type electrode was developed for endoscopic IRE ablation of the biliary tract. We performed ERCP and endoscopic IRE ablations in the normal common bile duct of Yorkshire pigs. The experimental setting of IRE was 500 V/cm (50 pulses, 100-µs length). The animals were sacrificed after 24 hr, and the ablated bile duct was examined. Results: Well-demarcated focal color changes were observed on the mucosa of the common bile duct. The depth of change after IRE was confined to the mucosal and submucosal layers. Apoptotic changes in the bile duct were observed only around the IRE ablation area. Immunohistochemistry assay showed cell death in the bile duct along the electrode. Conclusions Endoscopic IRE ablation using ERCP was successfully performed in the common bile duct. It can be a potential option for the treatment of biliary tumors.

Porphyria cutanea tarda (PCT) is a metabolic disorder that results in a decrease in uroporphyrinogen decarboxylase activity. It is characterized by photosensitivity, bullae formation, and skin pigmentation. There are four types of PCT: acquired, familial, toxic, and hepatoerythropoietic. Uroporphyrin levels are elevated in the urine of PCT patients. PCT can be differentiated from other porphyrias by its clinical characteristics and the porphyrin levels in the serum, erythrocytes, urine, and feces. This metabolic disorder can lead to liver dysfunction as well as histological changes such as fatty infiltration or hepatic fibrosis. PCT rarely manifests as liver cirrhosis. We report herein a case of PCT-induced liver cirrhosis that progressed to hepatic failure.
Blister ; Erythrocytes ; Feces ; Fibrosis ; Humans ; Liver ; Liver Cirrhosis ; Liver Diseases ; Liver Failure ; Porphyria Cutanea Tarda ; Porphyrias ; Skin Pigmentation ; Uroporphyrinogen Decarboxylase

BACKGROUND/AIMS: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB). METHODS: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system. RESULTS: In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05). CONCLUSIONS: Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.
Cytoplasm ; Fibrosis ; Hepatitis B Core Antigens* ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens* ; Hepatitis B* ; Hepatitis B, Chronic* ; Hepatitis* ; Hepatitis, Chronic* ; Hepatocytes* ; Humans ; Viral Load ; Viremia

BACKGROUND/AIMS: Capsule endoscopy (CE) has become a valuable modality for the detection of small bowel lesions. The usefulness of CE for obscure gastrointestinal (GI) bleeding has been established with an overall diagnostic yield of 60%. It is unknown whether CE is of equal value in all the patients or of greater benefit in selected groups in Korea. We evaluated the factors that affect the diagnostic yields of CE in patients with obscure GI bleeding. METHODS: CE was performed in 126 consecutive patients [74 men and 52 women mean age : 52.5 years (25-75 yrs), 23 with active bleeding] with obscure GI bleeding between September 2002 and July 2004. Patients were divided into two groups: those with documented bleeding lesions and those with non specific CE findings. We analyzed the clinical characteristics and other parameters that influenced the diagnostic yields of CE. RESULTS: A definite or probable cause for obscure GI bleeding was found in 69% (80/116) of the patients. NSAID induced ulcer (16.4%) and angiodysplasia (12.1%) were the most common diagnoses. In patients with active bleeding, the diagnostic yield was significantly greater than that of the patients with occult bleeding (80% vs. 68.3%, p<0.05). However, there was no significant difference in parameters between patients with abnormal CE and those with normal CE in respect to gender, age, previous bleeding history, need for transfusion, cecum imaging, and bowel preparation. CONCLUSIONS: The diagnostic yield of CE in patients with obscure GI bleeding is 69%. It is significantly higher in patients with active bleeding.
Adult ; Aged ; *Capsule Endoscopy ; Female ; Gastrointestinal Hemorrhage/*diagnosis/etiology ; Humans ; Intestinal Diseases/*diagnosis ; Male ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity