Hyunee Yim

Induction of Apoptosis with an Extract of Artemisia asiatica Attenuates the Severity of Cerulein-Induced Pancreatitis in Rats

The aim of this study was to test the hypothesis that apoptosis can protect against experimental pancreatitis and induction of apoptosis by an extract of Artemisia asiatica (DA-9601) is beneficial in cerulein-induced pancreatis in rats. Pancreatitis was induced in 6-week-old male SPF Sprague-Dawley rats by two intravenous (iv) administrations of 40

Enhanced glycogenesis is involved in cellular senescence via GSK3/GS modulation

mUg/kg cerulein. To investigate the effects of DA-9601 on the seventy of pancreatitis and extent of apoptosis, rats were treated with intragastric DA-9601, 30 mg/kg (D30), 100 mg/kg (D100), or 300 mg/kg (D300), intraperitoneal superoxide dismutase, 10,000

Sonographic Differentiation of Benign and Malignant Papillary Lesions of the Breast

mU/kg (SOD), and iv gabexate mesilate, 40 mg/kg (Foy), three times (30 min before cerulein injection, 30 and 90 min after cerulein injection). The control group was administered vehicle alone. Ten rats were included in each treatment group and control group. Rats were sacrificed 5 h after cerulein treatment. Serum amylase, histological activity index (HAI), pancreatic lipid peroxide levels, and apoptotic index [in situ hybridization by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL)] were determined. Gel electrophoresis was performed for the presence of DNA fragmentations. The results were as follows. Serum amylase was significantly increased in all cerulein-treated groups compared to normal controls p <0.001). The HA1 was significantly decreased in only the D300 group compared to the controls p <0.05). The apoptotic index of the cerulein-alone group was 3.8 ± 2.7, but the mean apoptotic indexes of the SOD and Foy groups were 16.4 ± 4.6 and 13.3 ± 1.8, respectively, a significant increase (p <0.01). The apoptotic index was more significantly increased in the DA-9601-treated groups, dose dependently (8.4 ± 3.4 in D30, 14.8 ± 4.3 in D100, 24.2 ± 4.7 in D300). A smearing pattern of DNA electrophoresis was noted in the DA-9601-treated groups. In conclusion, DA-9601, an extract of Artemisia, induced apoptosis of pancreatic acinar cells dose dependently and concomitantly attenuated the severity of pancreatitis.

Self-expandable covered metallic esophageal stent impregnated with beta-emitting radionuclide: an experimental study in canine esophagus.

Glycogen biogenesis and its response to physiological stimuli have often been implicated in age‐related diseases. However, their direct relationships to cell senescence and aging have not been clearly elucidated. Here, we report the central involvement of enhanced glycogenesis in cellular senescence. Glycogen accumulation, glycogen synthase (GS) activation, and glycogen synthase kinase 3 (GSK3) inactivation commonly occurred in diverse cellular senescence models, including the liver tissues of aging F344 rats. Subcytotoxic concentrations of GSK3 inhibitors (SB415286 and LiCl) were sufficient to induce cellular senescence with increased glycogenesis. Interestingly, the SB415286‐induced glycogenesis was irreversible, as were increased levels of reactive oxygen species and gain of senescence phenotypes. Blocking GSK3 activity using siRNA or dominant negative mutant (GSK3β‐K85A) also effectively induced senescence phenotypes, and GS knock‐down significantly attenuated the stress‐induced senescence phenotypes. Taken together, these results clearly demonstrate that augmented glycogenesis is not only common, but is also directly linked to cellular senescence and aging, suggesting GSK3 and GS as novel modulators of senescence, and providing new insight into the metabolic backgrounds of aging and aging‐related pathogenesis.

Prevention of intraperitoneal adhesions and abscesses by polysaccharides isolated from Phellinus spp in a rat peritonitis model.

The purpose of this study was to evaluate sonographic findings of breast papillary lesions and the effectiveness of the American College Radiology Breast Imaging Reporting and Data System sonographic assessment system for differentiation of benign and malignant papillary lesions.

Immunohistochemical characterization of cellular infiltrate in nasal polyp from aspirin-sensitive asthmatic patients.

PURPOSE A specially designed self-expandable covered metallic stent impregnated with the beta-emitting radioisotope 166Ho (166Ho, energy: 1.85 and 1.76 MeV, T12: 26.8 h) was developed at our institute for the purpose of intraluminal palliative brachytherapy, as well as for treating malignant esophageal stricture and swallowing difficulty. The aim of this study was to evaluate the tissue response to brachytherapy and the safety of the radioactive metallic stent with regard to the normal canine esophagus before clinical application. METHODS AND MATERIALS 166Ho was impregnated into the polyurethane membrane (50 micron thickness) covering the outer surface of a self-expandable metallic stent (diameter, 18 mm; length, 40 mm). Stents with radioactivity 4.0-7.8 mCi (Group A, n = 15), 1.0-1.8 mCi (Group B, n = 5), and 0.5-0.7 mCi (Group C, n = 5) were placed in the esophagi of 25 healthy beagle dogs, and the stents were tightly anchored surgically to prevent migration. The estimated radiation dose calculated by Monte Carlo simulation was 194-383 Gy in Group A, 48-90 Gy in Group B, and 23-32 Gy in Group C. The dogs were killed 8-12 weeks after insertion of the stents, and histologic examinations of the esophageal walls were performed. RESULTS In Group A, 3 of 15 dogs died of wound infection, so specimens were obtained from only 12 dogs; all 12 cases showed esophageal stricture with mucosal ulceration. Microscopically, severe fibrosis and degeneration of the muscular propria were found in 3 dogs, complete fibrosis of the entire esophageal wall was found in 7 dogs, and esophageal fibrosis with radiation damage within periesophageal soft tissue was found in 2 dogs. However, esophageal perforation did not develop, despite extremely high radiation doses. In Group B, glandular atrophy and submucosal fibrosis were found, but the muscular layer was intact. In Group C, no histologic change was found in 3 dogs, but submucosal inflammation and glandular atrophy with intact mucosa were found in 2 dogs. CONCLUSIONS A radioactive, self-expandable covered metallic stent can be used as an alternative therapeutic modality for the palliative treatment of malignant esophageal stricture.

Magnetic resonance imaging patterns of tumor regression after neoadjuvant chemotherapy in breast cancer patients: correlation with pathological response grading system based on tumor cellularity

Objective:To assess whether polysaccharides isolated from fungi, Phellinus spp, could reduce the adhesion and abscess formation in a rat peritonitis model. Summary Background Data:Although polysaccharides from Phellinus spp is a well-known material with antiinflammatory properties, little is known regarding its ability to prevent intraperitoneal adhesions. We have assessed the adhesion- and abscess-reducing effect of polysaccharides from Phellinus gilvus (PG) and Phellinus linteus (PL) in a rat peritonitis model. Methods:In 60 SD rats, experimental peritonitis was induced using the cecal ligation and puncture model (CLP). Animals were randomly assigned to 5 groups; ringer lactate solution (RL group), polysaccharides from PG and PL (PG and PL group), hyaluronic acid (HA group), and carboxymethylcellulose (CMC group). Intraperitoneal adhesions and abscesses were noted at 7 day after CLP. RT-PCR assay for urokinase-type plasminogen activator (uPA), its cellular receptor (uPAR), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tumor necrosis factor (TNF)- α was performed to assess the cecal tissue. Results:Adhesion formation was significantly reduced in PG, PL, CMC, and HA groups (P < 0.001) compared with that in RL group. The incidence of abscesses was also significantly reduced in PG and PL groups (P < 0.05) compared with that in the RL group. The level of uPA, uPAR, tPA, and TNF-α was highly expressed in PG and PL group, as compared with the RL group. Conclusions:We concluded that PG and PL had significant adhesion- and abscess-reducing effects and may act by modulating fibrinolytic capacity of uPA and/or tPA produced from macrophages in a rat peritonitis model.

Is there any correlation between model-based perfusion parameters and model-free parameters of time-signal intensity curve on dynamic contrast enhanced MRI in breast cancer patients?

BACKGROUND The immunopathologic mechanism of nasal polyp in aspirin-sensitive asthma remains to be further defined. OBJECTIVE To characterize the features of the inflammatory cellular infiltrate in the nasal polyp tissue from aspirin-sensitive asthmatic patients. METHODS We have taken nasal polyp tissue during nasal polyp resection from 13 aspirin-sensitive asthma, 6 allergic, and 12 non-allergic subjects. Immunohistochemistry was employed to stain and enumerate the individual inflammatory cell types using monoclonal antibodies against tryptase (AA1) to identify mast cells, against secreted forms of eosinophil cationic protein (EG2), to identify activated eosinophils, against neutrophil elastase (NE) for neutrophils and against T cell surface markers (CD3) to identify total T cells. RESULTS There were no significant differences in AA1 + cells among three groups (P>.05). EG2 + cells tended to be higher in ASA-sensitive asthmatic patients than in allergic and non-allergic subjects, but no statistical significance was observed. NE+ cells were found in most subjects of the three groups and their numbers were significantly higher in allergic subjects than in aspirin-sensitive asthma (P<.05). Some patients had CD3+ cells with no statistical significance among the three groups. Significant correlation was found in numbers between NE+ cell and AA1+ cell (r=.44, P=.01), and between NE+ cell and EG2+ cell (r=.40, P=.02). CONCLUSION These findings suggested that major effector cells such as mast cells and eosinophils might be placed in the center of the inflammatory response of nasal polyps, regardless of their association with aspirin sensitivity.

Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression.

Purpose The objectives of the study were to analyze the tumor shrinkage pattern on magnetic resonance imaging (MRI) after neoadjuvant chemotherapy and to evaluate whether there is any difference in shrinkage pattern between pathological responder and nonresponder groups. In addition, we wanted to compare tumor diameter obtained from MRI with histological diameter according to the tumor shrinkage pattern. Methods Between July 2008 and December 2010, 55 consecutive patients (56 lesions) with pathologically proven breast cancer who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. The shrinkage pattern was classified into 4 categories: I (concentric shrinkage without surrounding lesion), II (concentric shrinkage with surrounding lesions), III (shrinkage with residual multinodular lesions, and IV (diffuse contrast enhancement in whole quadrants). Histological regression was scored on a 5-point scale regarding tumor cellularity reduction (Miller-Payne grading system). Patients with Miller-Payne grade 1 or 2 were classified into the nonresponder group, and patients with grade 3, 4, or 5 were in the responder group. Results Of 56 lesions, pattern I was seen in 29 lesions, pattern II in 13 lesions, pattern III in 5 lesions, and pattern IV in 4 lesions. Three lesions were not visualized on MRI after neoadjuvant chemotherapy, and 2 lesions were increased in size. There was a statistically significant difference in the tumor shrinkage pattern between responder and nonresponder groups (P = 0.017). All 5 lesions with type III shrinkage pattern were found in the responder group, and all 4 lesions with pattern IV were in the nonresponder group. Magnetic resonance imaging diameter of lesions with types I, II, and IV patterns showed significant correlation with the histological diameter. Among them, the correlation factor was highest in pattern IV (&rgr; = 0.94, P < 0.001) followed by pattern I (&rgr; = 0.67, P < 0.01) and pattern II (&rgr; = 0.502, P = 0.08). However, in type III shrinkage pattern, tumor size measured on MRI was not significantly correlated with histological size (P = 0.87). Conclusions Types III and I shrinkage patterns were more frequently observed in the pathological responder group, and type IV was more frequently noted in the nonresponder group. Tumor diameter measured on MRI showed strong correlation with histological diameter in lesions with types I and IV shrinkage patterns, whereas lesions with type III did not show significant correlation. Type II pattern showed similar frequencies between the 2 groups and moderate correlation between sizes obtained from MRI and histology.

Prognostic role of MRI enhancement features in patients with breast cancer: value of adjacent vessel sign and increased ipsilateral whole-breast vascularity.

ObjectiveTo find out any correlation between dynamic contrast-enhanced (DCE) model-based parameters and model-free parameters, and evaluate correlations between perfusion parameters with histologic prognostic factors.MethodsModel-based parameters (Ktrans, Kep and Ve) of 102 invasive ductal carcinomas were obtained using DCE-MRI and post-processing software. Correlations between model-based and model-free parameters and between perfusion parameters and histologic prognostic factors were analysed.ResultsMean Kep was significantly higher in cancers showing initial rapid enhancement (P = 0.002) and a delayed washout pattern (P = 0.001). Ve was significantly lower in cancers showing a delayed washout pattern (P = 0.015). Kep significantly correlated with time to peak enhancement (TTP) (ρ = −0.33, P < 0.001) and washout slope (ρ = 0.39, P = 0.002). Ve was significantly correlated with TTP (ρ = 0.33, P = 0.002). Mean Kep was higher in tumours with high nuclear grade (P = 0.017). Mean Ve was lower in tumours with high histologic grade (P = 0.005) and in tumours with negative oestrogen receptor status (P = 0.047). TTP was shorter in tumours with negative oestrogen receptor status (P = 0.037).ConclusionsWe could acquire general information about the tumour vascular physiology, interstitial space volume and pathologic prognostic factors by analyzing time-signal intensity curve without a complicated acquisition process for the model-based parameters.Key points• Kep mainly affected the initial and delayed curve pattern in time–signal intensity curve.• There is significant correlation between model-based and model-free parameters.• We acquired information about tumour vascular physiology, interstitial space volume and prognostic factors.