• Archives of Plastic Surgery
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• v.32 no.3
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• pp.369-375
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• 2005

Apoptosis is a physiologic or programmed cell death process which is controlled by genes. It is essential for the function and the appropriate development of multicellular organism. It is also thought to be one of the main mechanisms of cell death in ischemic tissues. The effect of prostaglandin $E_1$($PGE_1$) is proven to be useful in the recovery of ischemic changes by inducing vasodilation of peripheral vessels and platelet disaggregation. $PGE_1$ is also known to suppress apoptosis in human liver sinusoidal endothelial cell from ischemia-reperfusion injury. The purpose of this study is to evaluate the effects of $PGE_1$ on the apoptosis in the ischemia reperfusion injury of rat intestine. Thirty Sprague-Dawley rats were used. In control group(N=15), superior mesenteric artery was occluded for 60 minutes and after removing the vessel clamp, it was reperfused for 60 minutes and harvested. In experimental group(N=15), a jejunal flap was also made as in the control group except for the intraarterial administration of the $PGE_1$ right after clamping the artery and removing the clamp. H&E, TUNEL and immunohistochemical stains for p53, bax, and bcl-2 were performed. There were ischemic changes in gross and microscopic findings in both groups. The apoptotic index was significantly lower in the experimental group($1.29{\pm}0.82$(p=0.003)) than in the control group ($2.33{\pm}0.95$). The rat intestinal ischemia apoptosis by ischemia-reperfusion was partly related to the modulating of bcl-2, bax, and p53 expression. Our results indicate that $PGE_1$ suppresses the apoptosis in the ischemic jejunal flap and this effect is probably the result of a increase in expression of bcl-2.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1565-1570
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• 2016

Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. Aim: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. Materials and Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. Results: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer-Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.60-71
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• 2020

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([¹⁸F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [¹⁸F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [¹⁸F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [¹⁸F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

• Journal of Oral Medicine and Pain
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• v.24 no.2
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• pp.145-161
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• 1999

The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

• Journal of Veterinary Clinics
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• v.30 no.4
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• pp.292-295
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• 2013

A 9-year-old, male, Doberman pinscher dog with 5-month history of intermittent hematuria, vomiting and glucosuria was referred to local animal hospital. Abdominal ultrasonography showed an irregular and hyperechoic mass in the renal medulla of the enlarged left kidney. Grossly atrophied renal cortex and medulla and marked hydronephrosis were observed on the cut surface of kidney. A single, numerous papillary projected, pedunculated mass 4~5.5 cm in diameter was occupied in renal pelvis, and extended from pelvis to the inlet of ureter. Histopathologically, the mass had numerous papillary structures with arboriform pattern. These papillae were consisted of fibro-vascular stalks that were lined by multiple layers of neoplastic urothelium (transitional epithelium) with marked cellular atypia. Immnohistochemical (IHC) staining demonstrated that the neoplastic cells showed strong positive reactions for cytokeratin (CK) 7, CK 19, CK clone MNF116 and CK high molecular weight, but negative signals for CK 8 low molecular weight. Based on the gross findings, histopathology and CKs profile using IHC staining, this mass was diagnosed as renal pelvis transitional cell carcinoma in a dog.

• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.117-129
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• 2000

This study was carried out to examine proliferative activity and expression of c-myc oncoprotein and p2lras in normal and preneoplastic rat livers induced by an in vivo mid-term chemical carcinogenesis assay. Sixty, six-week-old male specific pathogen free Sprague-Dawley male rats were randomly divided into five groups. Group I was received a single intraperitoneal(IP) dose(200mg/kg) of diethylnitrosamine(DEN). Group 2(10 rats) was operated partial hepatectomy(PH) and Group 3 was received IP(200mg/kg) DEN, fed two weeks later with 500ppm of phenobarbital(PB). Group 4 was received IP(200mg/kg) DEN, fed two weeks later 500ppm(PB) and PH at week 3 after the onset of experiment. While group 5(20 rats) was not treated and used as a control group. All the rats were sacrificed at age 14 weeks except 10 rats from group 5 were sacrificed at the onset of experiment. Livers of all rats were examined for 5-bromo-2'-deoxyuridine(BrdU) incoporation, proliferating cell nuclear antigen(PCNA), silver-binding nucleolar organizer regions(AgNORs) counts per nucleus and expression of c-myc oncoprotein and p21ras. Both the number and area of the preneoplastic lesions were significantly(p<0.01) compared to other groups. A significant(p<0.01) increase in immunoreactive cells were detected in preneoplastic hepatocytes in Groups 3 and 4 by PCNA and BrdU immunohistochemical stain. The number of the positive cells were significantly(p<0.05) lower in normal 14-week-old rats than those of 6-week-old rats. The results showed that proliferative activity of the hepatocytes was increased by treatment with DEN, PH and PB. Meanwhile, AgNORs counts per nucleus were significantly(p<0.05) increased in the preneoplastic hepatocytes of rats in both groups 3 and 4. The expression of c-myc oncoprotein and p21ras were more readily localized within the hepatic preneoplastic lesions such as hyperplastic nodules. Especially, group 4 showed significantly (p<0.05) overexpressed levels compared to groups 1 and 3. These findings suggest that PCNA, BrdU and AgNORs are significantly increased and c-myc oncoprotein and p21ras are significantly overexpressed in hepatic preneoplastic lesions induced by mid-term carcinogenesis. So these parameters can be an effective markers for hepatic prencoplastic lesions.

• Korean Journal of Veterinary Research
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• v.32 no.4
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• pp.497-510
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• 1992

This study was attempted to comparative investigate the types and regional distribution of the endocrine cells in several vertebrates immunohistochemically using seven antisera. From carp pancreas could be observed 4 types which are insulin-, glucagon-, som- and BPP-immunoreactive cells. Insulin-immunoreactive cells were mainly distributed at the periphery and a few cells occupied the central region of the islets. Glucagon-immunoreactive cells were distributed at the periphery of the islets, and som - and BPP-immunoreactive cells were located at the central region. From frog pancreas could be observed 4 types which are insulin-, glucagon-, som- and BPP-immunoreactive cells. Insulin-immunoreactive cells were distributed throughout the islets. Som-immunoreactive cells were distributed at the periphery of the islets, and glucagon- and BPP-immunoreactive cells were found as single cell or as small groups located between the pancreatic acini. From snake pancreas could be observed 3 types which are insulin-, glucagon- and som -immunoreactive cells. Insulin-immunoreactive cells were distributed throughout the small islets, and they also were scattered at the periphery of the large islets. Glucagon-immunoreactive cells were distributed at the periphery of the islets, whereas som-immunoreactive cells were occupied the central region. From Ogolgae pancreas could be observed 4 types which are insulin-, glucagon-, som-and BPP-immunoreactive cells. Insulin-immunoreactive cells were distributed throughout the small islets, but at the periphery of the large one. Glucagon- immunoreactive cells were distributed at the periphery of the small islets and in the large islets showed scattering entired. Som-immunoreactive cells were distributed at the periphery of the small islets and in the large islets were located at the central region. A small numbers of BPP-immunoreactive cells were located at the periphery of the small islets and the exocrine regions. From the pancreas of the Korean native goat could be observed 6 types which are insulin-, glucagon-, som-, BPP-, 5-HT- and porcine-CG-immunoreactive cells. Insulin-immunoreactive cells were distributed throughout the islets. Som-immunoreactive cells were located at the periphery of the islets, but a tew were scattered at the central region of islets and in the epithelium of the secretory duct. Glucagon-, BPP-, 5-HT- and porcine CG-immunoreactive cells were distributed at the periphery of the islets. These findings indicated that the regional distribution patterns and cell types of pancreatic endocrine cells in vertebrates varies considerably among phylogenetically different vertebrates.

• Korean Journal of Veterinary Research
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• v.46 no.3
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• pp.177-184
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• 2006

Experimental autoimmune encephalomyelitis (EAE) is a disease model of multiple sclerosis (MS) that is characterized by remittance and relapse of the disease and autoimmune and demyelinating lesions in the central nervous system (CNS). Autoimmune inflammation is maintained by secretion of a large number of protein. Previous studies have suggested that transcripts encoding osteopontin (OPN) are frequently detected in the mRNA population of MS plaques. To elucidate the functional role of OPN in initiation and development of EAE, we examined the expression and localization of OPN in the spinal cord during acute EAE. We demonstrated that OPN significantly increased at the early stage of EAE and slightly declined thereafter by western blot analysis. An immunohistochemical study revealed that OPN was constitutively expressed in some glial cells (microglia, astrocytes) of white matter and neurons in the CNS of control rats. OPN expression was shown to be increased in the same cells at the early and peak stage of EAE. To identity cells expressing OPN by double-immunofluorescence labeling, we labeled rat spinal cord sections for OPN with a monoclonal OPN antibody and with mAbs for astrocyte (GFAP), microglia/macrophage (OX42)-specific markers. The major cell types of OPN-expressing cells were activated astrocytes and microglia in the adjacent inflammatory lesions. Interestingly, OPN was mainly expressed in the end feet of astrocytes around vascular cell adhesion molecule-1 (VCAM-1) expressing endothelial cells of CNS blood vessel. These findings suggest that increased levels of OPN in activated glial cell may play an important role in the recruitment of inflammatory cells into the CNS parenchyma during EAE.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.39
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• pp.8.1-8.8
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• 2017

Background: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor $(TGF)-{\beta}1$, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. Methods: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. Results: The concentrations of IGF-1, VEGF, and $TGF-{\beta}1$ in MSC-CM were $1515.6{\pm}211.8pg/mL$, $465.8{\pm}108.8pg/mL$, and $339.8{\pm}14.4pg/mL$, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. Conclusions: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.43 no.4
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• pp.281-287
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• 2017

Stress in skin plays a significant role in both the direct/indirect regulation of cellular processes occurring in hair, which in turn affect the hair cycle. However, experimental data regarding the effects of stress-related corticotropin releasing factor (CRF) released by stress on the apoptotic process involved in hair is limited. Therefore, we investigated the acceleration of early-stage apoptosis induced by atopy-related stress using a 2,4-dinitrochlorobenzene NC/Nga mice model. Expression of CRF, its related proteins, annexin V, and mitochondrial dysfunction were measured by immunohistochemical analyses. Atopic stress strongly stimulated stress hormones response, such as CRF and adrenocorticotropic hormone, in outer epithelial sheath of the hair. Moreover, its stress induced mitochondrial damage and early-stage apoptosis of cells in hair root. These findings suggest that hair damage due to apoptosis in atopy model is accelerated in a high CRF environment. Importantly, the effect of stress-related CRF on apoptosis processes involved in atopy dermatitis-related hair loss, suggests that the CRF-regulating development or maintenance materials may provide effective therapeutic strategies for hair health.