• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1015-1018
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• 2016

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6439-6443
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• 2013

Objective: To investigate whether the expression level of valosin-containing protein (VCP) is correlated with the prognosis of primary orbital mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: VCP expression in 58 samples from primary orbital MALT lymphoma patients was determined by immunohistochemisty using monoclonal antibodies. Correlations between VCP expression level and prognosis were clarified by statistical analysis. Results: It was found that the percentage of VCP positive cells in samples of primary orbital MALT lymphoma ranged from 32% to 95%. The samples were divided into two groups (level 1 and level 2) according to the median value (45%) of the percentage of VCP positive cells. It was found that the expression level of VCP was significantly correlated with recurrence (P=0.003) and tumor size (P=0.008). At the same time, the 5-year disease-free and overall survival rate of patients of level 1 was significantly better than that of level 2 (P=0.001; P=0.032). There was no observed correlation between the expression level of VCP and other clinical features. Conclusion: VCP could be a useful marker for predicting the prognosis of primary orbital MALT lymphoma.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.401-411
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• 2015

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-${\beta}_1$, ${\alpha}$-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-${\beta}_1$, AR, ${\alpha}$-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ${\alpha}$-SMA and collagen I induced by TGF-${\beta}_1$, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-${\beta}_1$-induced proliferation of fibroblasts, up-regulation of ${\alpha}$-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.83-90
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• 2012

Objectives : Modified Bo-Yang-Hwan-O-Tang (mBHT) is a polyherbal medicine of twelve herbs traditionally used in the treatment of cerebral and cardiac stroke and vascular dementia. The purpose of this study was to evaluate the neuroprotective effect, pyramidal neuronal cell, inflammation and apoptosis of mBHT against global ischemia in rats. Methods : Global ischemia was produced by two-vessel occlusion(2-VO) in SD male rats. mBHT at dose of 500 mg/kg was orally administrated for 2 weeks or 6 weeks after global ischemia. The histopathological changes of ischemic brain were observed by staining of hematoxylin and eosin (H&E) and Nissl and immunohistochemisty with anti-GFAP (glial fibrillary acidic protein) antibody as a astrocyte marker. The expression of inducible nitric oxide synthase (iNOS) and apoptotic proteins such as Bax, Bcl-2 and caspase-3 was determined by western blot. Results : mBHT treatment significantly inhibited the pyramidal neuronal loss in CA1 of hippocampus of global ischemic rats by 2-VO. mBHT also suppressed the activation of astrocytes in the CA1 at 6 weeks after ischemia. In addition, mBHT significantly increased the expression of anti-apoptotic protein, Bcl-2 on iscemic brain, and significantly attenuated the expression of apoptotic proteins, Bax and caspase-3. Conclusions : These results indicate that mBHT inhibits neuronal cell damage induced in global ischemia by 2-VO, suggesting that mBHT may be a potential candidate for the treatment of vascular dementia.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.12 no.1
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• pp.46-54
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• 2001

Background and Objectives : Nitric oxide(NO) is a short-lived molecule with messenger and cytotoxic functions in nervous, cardiovascular, and immune systems. Among the three distinct NOS isoforms, the neuronal isoform is expressed in small, discrete neuronal populations of CNS and PNS. Axonal injury in adult animals results in a dramatic NOS up-regulation in many types of central and peripheral neurons which normally lack the enzyme or express it only at very low levels. In previous study, we confirmed the efficacy of PEMS on the early functional recovery in rats with surgically transected and reanastomosed recurrent laryngeal nerve. Therefore, after we obtained functionally recovered rats using PEMS in this study, we studied to evaluate the expression of nNOS through the analysis of the difference between functional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 84 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The rats in group A(n=42) received PEMS by placing them in custom cages equipped with Helm-holz coils(3 hr/day, 5 days/wk, for 12 wk). The rats in group B(n=42) were handled the same way as the group A, except that they did not receive PEMS. Laryngovideoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining using monoclonal anti-neuronal nitric oxide synthase(nNOS) antibody was performed to detect nNOS in recurrent laryngeal nerve and nodose ganglion. Results : 20 rats(63%) in group A and 5 rats(17%) in the group B showed recovery of vocal fo1d motion. The number of NOS-positive cells was increased in functionally-recovered rats. NOS-staining intensity was reduced 12 weeks after nerve injury. The difference between PEMS group and non-stimulated group was not found. Conclusion : This study shows that nNOS may exert a beneficial effect on nerve regeneration and functional repair.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.4
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• pp.1-15
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• 2010

Objectives : This study was performed to evaluate the effects of Hwangryunhaedok-tang(Huanglianjiedu-tang HHT) water extract on locomotor dysfunction induced by spinal cord injury(SCI) in rats. Methods : SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. HHT was orally given once a day for 14 days after SCI. Neurological behavior was examined with the Basso-Beattie-Bresnahan locomotor rating scale. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue staining. Using immunohistochemisty, cellular damage to neurons and nerve fibers were examined against Bax and MAP-2. As inflammatory response markers, iNOS and COX-2 expressions were also examined. Results : 1. HHT ameliorated the locomotor dysfunction of the SCI-induced rats. 2. HHT attenuated the reduction of motor neurons in the ventral horn of the SCI-induced rat spinal cord. 3. HHT significantly reduced the number of Bax positive cells in the peri-lesion of the SCI-induced rat spinal cord. 4. HHT attenuated the reduction of MAP-2 positive cells in the peri-lesion of the SCI-induced rat spinal cord. 5. HHT significantly reduced the number of iNOS and COX-2 positive cells in the peri-lesion of the SCI-induced rat spinal cord. Conclusions : These results suggest that HHT improves the locomotor dysfunction of SCI by protecting motor neurons from cell death through anti-inflammatory effect.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.12 no.2
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• pp.126-132
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• 2001

Background and Objectives : Signal traduction through phospholipase C(PLC) participate in the regulation of cell growth and differentiation. Growth factors bind to their receptors and thereby induce tyrosine phophorylation of the phospholipase C-${\gamma}$1(PLC-${\gamma}$1). PLC-${\gamma}$1 is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. Tyrosine kinase phosphorylation of PLC-${\gamma}$1 stimulates PLC activation and cell proliferation. However the signal transduction pathway and the significance of PLC in injured recurrent laryngeal nerve regeneration is unknown. Therefore after we obtained fuctionally recovered rats using PEMF in this study, we attempt to provide some evidence that PLC plays a role in nerve regeneration itself and regeneration related to PEMF through the analysis of the difference between fucntional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 32 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The experimental group(n=16) received PEMS by placing them in custom cages equipped with Helm-holz coils(3hr/day, 5days/wk, for 12wk). The control group(n=16) were handled the same way as the experimental group, except that they did not receive PEMS. Laryngo-videoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining and Western blotting analysis using monoclonal antibody was performed to detect PLC-${\gamma}$1 in recurrent laryngeal nerve and nodose ganglion. Results : 10 rats(71%) in experimental group and 4 rats(38%) in the control group showed recovery of vocal fold motion. Functionally-recoverd rats show PLC-${\gamma}$1 positive cells in neuron and ganglion cells after 12 weeks from nerve injury. Conclusion : This study shows that PLC1-${\gamma}$ involved in singnal trasduction pathway in functinal recovery of injured recurrent laryngeal nerve and PEMF enhance the functional recovery by effect on this molecule.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.28 no.4
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• pp.383-391
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• 1995

In order to find out the distribution of neuropeptide Y (NPY) recently known as the gonadotropin (GtH) stimulation neurohormone in the brain tissues of marine teleost, detection and localization of NPY like substance in brain of two rockfish species, Sebastes oblongus and S. schlekeli were done by immunohistochemisty. Distribution of GtH cells in hypophysis were also observed by aldehyde fuchsin (AF)-fast green-orange G stain to compare with gonadal phases of the rockfish species. NPY immunoreactive cells were detected in olfactory bulb, telencephalon and mesencephalon of the brain, and NPY immunoreactive fibers were distributed not only in olfactory bulb, telencephalon and mesencephalon but also in optic nerve, hypothalamus and optic tectum. Regardless of ovarian maturation in two rockfish species, NPY immunoreactive fibers were observed in the neurohypophysis adjacent to the AF negative cells in the rostral pars distalis of hypophysis in both species. Moreover, the fibers were distributed in the rostral and proximal pars distalis near to the GtH cells of the hypophysis in both species possessing the growing or mature oocytes. Slight AF stainable GtH cells were detected in hypophysis of two species before parturition (S. oblongus) and in mature stage (S. schlegeli), but AF stainability of the cells in the proximal pars distalis after parturition was more increased than that of the cells Tn mature stage or before parturition. The size and nucleus diameter of GtH cells in S. oblongus and S. schlegeli before parturition were significantly bigger than those of GtH cells in individuals after parturiton (S. oblongus) or with resting ovary (S. schlegeli) (P<0.01).

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.101-119
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• 2014

Objectives: This study was performed to investigate the effects of Hominis Placenta pharmacopuncture (HPP) therapy on the experimentally-induced endometriosis in the rats. Materials and Methods: Endometriosis was induced in rats by autotransplanting uterine tissue to the peritoneum and divided them into three groups: (1) sham-operated group (n=8), (2) surgically induced endometriosis and untreated control group (n=8), (3) surgically induced endometriosis and HPP treated group. Sham-operated group and control group were inject with normal saline once a every other day for 30days, while treated group was injected with HPP extract once a every other day for same duration. Injected point of HPP and normal saline were subcutaneous tissue at Gwanwon (CV4) acupoint. Then we measured the body weight, the volume of endometriotic implants, the weigh of uterus and ovaries, and investigated the concentration of cytokines (MCP-1, TNF-${\alpha}$) in peritoneal fluids. Histopathology, immunohistochemisty for COX-2 and VEGF, and histochemistry for mast cell in transplanted uterine tissue were performed. Results: The volume ($mm^2$) of endometriotic implants in HPP treated group ($55.4{\pm}41.6$) was significantly decreased (p<0.01) compared with control group ($140{\pm}66.1$). And the concentration (pg/ml) of MCP-1 in peritoneal fluids in HPP treated group ($1117.6{\pm}60.5$) was significantly decreased (p<0.01) compared with control group ($1446.2{\pm}280.3$). The concentration (pg/ml) of TNF-${\alpha}$ in peritoneal fluids in HPP treated group ($80.6{\pm}31.4$) was decreased (p<0.01) compared with control group ($145.3{\pm}86.9$). Histopathologically, proliferation of endometriotic epithelia, infiltration of inflammatory cell and angiogenesis in transplanted uterine tissue of HPP treated group were weakly observed than those of control group. The COX-2 expression in endometrial, epithelial and stromal cells in transplanted uterine tissue of HPP treated group was decreased compared with control group. The VEGF expression of endometriotic epithelia, neovascular endothelia and stromal cell in transplanted uterine tissue of HPP treated group were weakly observed than those of control goup. Conclusions: HPP is effect on Endometriosis of rats by Experimentally-induced.

• 한국환경농학회:학술대회논문집
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• 2009.07a
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• pp.273-282
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• 2009

The transmissible spongiform encephalopathies (TSEs) disease group are fatal neurodegenerative disorders affecting a wide range of hosts. The group includes kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats and Bovine spongiform encephalopathy (BSE) in cattle. The exact nature of the infectious agent involved in the transmission of these diseases remains controversial. However, a central event in their pathogenesis is the accumulation in infected tissues of an abnormal form of a host-encoded protein, the prion protein (PrP). Whereas the normal cellular protein is fully sensitive to protease ($PrP^{sen}$), the disease-associated prion protein ($PrP^d$) is only partly degraded ($PrP^{res}$), its amino-terminal end being removed. BSE was first reported in the mid-80s in the UK. Ten years later, a new form of human prion disease, variant CJD (vCJD) developed in the wake of the BSE epidemic, and there is now strong scientific evidence that vCJD was initiated by the exposure of humans to BSE-infected tissues, thus indicating a zoonotic disease. However, the ban on the feeding of animal-derived proteins to ruminants, and the apparent lack of vertical transmission of BSE, have led to a decline in the incidence of the disease within cattle herd and therefore, an assumed decreased risk for human contacting vCJD. The origin of the original case(s) of BSE still remains an enigma even though three hypotheses have been raised. Hypotheses are i) sheep- or goat-derived scrapie-infected tissues included in meat and bone meal fed to cattle, ii) a previously undetected sporadic or genetic bovine TSE contaminating cattle feed or iii) originating from a human TSE through animal feed contaminated with human remains. A host cellular membrane protein ($PrP^C$), which is abundant in central nervous system tissue, appear to be conformationally altered in the diseased host into a prion protein ($PrP^{Sc}$). This $PrP^{Sc}$ is detergent insoluble and partially protease-resistant ($PrP^{res}$). The term $PrP^{res}$ is normally used to describe the protein detected after protease treatment, in techniques such as Western immunoblotting, and enzyme-linked immunosorbant assay using fresh/frozen tissue. Immunohistochemistry may performed with formalin-fixed tissues. Also, clinical signs of the BSE are one of the major diagnostic indicators. Recently, atypical forms (known as H- and L-type) of BSE have appeared in several European countries, Japan, Canada and the United States. An unusual case was also reported in a miniature zebu. The atypical BSE fall into two groups based on the relative molecular mass (Mm) of the unglycosylated $PrP^{res}$ band relative to that of classical BSE, one of the higher Mm (H-type) and the other lower (L-type). Both types have been detected worldwide as rare cases in older animals, at a low prevalence consistent with the possibility of sporadic forms of prion diseases in cattle. This raises the unwelcome possibility that vCJD could increase in the human population. Now, active surveillance program against BSE is going on in Korea. In regional veterinary service lab, ELISA is applied to screen the BSE in slaughter and confirmatory tests by Western immunoblotting and immunohistochemisty are carried out if there are positive or suspect in the screening test. Also, the ruminant feed ban is rigorously enforced. Removal of specified risk materials such as brain and spinal cord from cattle is mandatory process at slaughter to prevent the infected material from entering the human food chain.