[Show abstract][Hide abstract] ABSTRACT: Background and objectives:
Failure of vascular smooth muscle apoptosis and inflammatory response in pulmonary arterial hypertension (PAH) is a current research focus. The goals of this study were to determine changes in select gene expressions in monocrotaline (MCT)-induced PAH rat models after human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) transfusion.
Materials and methods:
The rats were separated into 3 groups i.e., control group (C group), M group (MCT 60 mg/kg), and U group (hUCB-MSCs transfusion) a week after MCT injection.
TUNEL assay showed that the U group had significantly lowered positive apoptotic cells in the lung tissues, as compared with the M group. mRNA of caspase-3, B cell leukemia/lymphoma (Bcl)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in the lung tissues were greatly reduced at week 4 in the U group. Immunohistochemical staining of the lung tissues also demonstrated a similar pattern, with the exception of IL-6. The protein expression of caspase-3, Bcl-2 VEGF, IL-6, TNF-α and brain natriuretic peptide in the heart tissues were significantly lower in the U group, as compared with the M group at week 2. Furthermore, the protein expression of VEGF, IL-6 and BNP in the heart tissues were significantly lower in the U group at week 4. Collagen content in the heart tissues was significantly lower in the U group, as compared with M group at weeks 2 and 4, respectively.
hUCB-MSCs could prevent inflammation, apoptosis and remodeling in MCT-induced PAH rat models.
Preview · Article · Jan 2016 · Korean Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: The calcium-sensing receptor (CaSR) is known to have differential expression in various carcinomas and normal tissues. It has been shown to be involved in carcinogenesis or tumor suppression. However, its role in gastric cancer remains unknown. This study was performed to determine the CaSR expression level in gastric cancer and non-tumor gastric tissues and to examine the related clinicopathological factors.
Thirty-one pairs of gastric cancer tissues and matched non-tumor gastric tissues were obtained from surgical tissues after gastrectomy. Using real-time polymerase chain reaction, we measured CaSR mRNA expression. We evaluated the association between CaSR mRNA expression and clinicopathological variables based on the downregulation or upregulation of CaSR mRNA expression in gastric cancer tissues compared to those of matched non-tumor gastric tissues. By immunohistochemistry, we confirmed CaSR expression levels in gastric cancer tissues.
Downregulation of CaSR mRNA was observed in 77.4% of gastric cancer tissues compared to their matched normal tissues. Downregulated CaSR was associated with a tendency for deeper invasion into the proper muscle (p = 0.028) and more advanced stage (II-IV; p = 0.012).
We conclude that downregulation of CaSR may contribute to the prevention or suppression of tumor outgrowth.
No preview · Article · Jul 2015 · Scandinavian Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Pulmonary arterial hypertension (PAH) causes right ventricular failure due to a gradual increase in pulmonary vascular resistance. The purposes of this study were to confirm the engraftment of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) placed in the correct place in the lung and research on changes of hemodynamics, pulmonary pathology, immunomodulation and several gene expressions in monocrotaline (MCT)-induced PAH rat models after hUCB-MSCs transfusion. The rats were grouped as follows: the control (C) group; the M group (MCT 60 mg/kg); the U group (hUCB-MSCs transfusion). They received transfusions via the external jugular vein a week after MCT injection. The mean right ventricular pressure (RVP) was significantly reduced in the U group after the 2 week. The indicators of RV hypertrophy were significantly reduced in the U group at week 4. Reduced medial wall thickness in the pulmonary arteriole was noted in the U group at week 4. Reduced number of intra-acinar muscular pulmonary arteries was observed in the U group after 2 week. Protein expressions such as endothelin (ET)-1, endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 significantly decreased at week 4. The decreased levels of ERA, eNOS and MMP-2 immunoreactivity were noted by immnohistochemical staining. After hUCB-MSCs were administered, there were the improvement of RVH and mean RVP. Reductions in several protein expressions and immunomodulation were also detected. It is suggested that hUCB-MSCs may be a promising therapeutic option for PAH.
Full-text · Article · May 2015 · Journal of Korean medical science
[Show abstract][Hide abstract] ABSTRACT: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that may progress to end stage liver cirrhosis. Benefits of ursodeoxycholic acid (UDCA) treatment has been investigated through large clinical studies. However, most of the studies were done in western countries and recent increase in prevalence of this relatively uncommon chronic liver disease draws attention in Korea. As early UDCA treatment effectively prevent the grave consequences of PBC progression, early diagnosis and lifelong management with UDCA is important. This study was designed to investigate the clinical features of PBC and response rates of UDCA treatments in Ewha Womans University Medical Center.
[Show abstract][Hide abstract] ABSTRACT: Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established. We sought to examine the expression pattern of adiponectin and adiponectin receptors (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications of adiponectin in colorectal carcinogenesis.
Serum adiponectin concentrations, and the mRNA and protein expression of adiponectin and AdipoRs were examined using serum and tissues from patients with CRC, advanced adenoma, and a normal colon. mRNA expression of AdipoRs and epithelial-mesenchymal transition regulators including E-cadherin, cyclooxygenase-2 (COX-2) and T-cadherin were examined in HCT116 cells treated with adiponectin.
Serum adiponectin concentrations in patients with advanced adenoma and CRC were lower than those in controls. Adiponectin mRNA was not detected in colonic tissue, whereas AdipoRs mRNA was lower in advanced adenoma and CRC than that in normal colon tissues. Immunohistochemical staining demonstrated that adiponectin was expressed in spindle-shaped cells of the subepithelial layer in normal colon tissues, whereas ill-defined overexpression of adiponectin was seen in the stroma of advanced adenoma and CRC tissues. AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues. Adiponectin downregulated COX-2 mRNA expression in vitro, but upregulated T-cadherin in HCT116 cells.
Systemic adiponectin and local AdipoRs expression in the colon may be associated with anti-tumorigenesis during the early stages of CRC. These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: Background:
One hundred forty nine stromal nodules (SNs) from transurethral resection of benign prostatic hyperplasia specimens in 39 patients (57-85 years with mean of 70.9) were investigated to characterize the SNs and to outline the etiopathogenesis of solitary fibrous tumors (SFTs) and gastrointestinal stromal tumors (GISTs) of prostate by immunohistochemistry performed on tissue microarray sections.
Antibodies used included smooth muscle actin, desmin, vimentin, and S-100 protein for subtyping, vascular endothelial growth factor, insulin-like growth factor-1, fibroblast growth factor, and TGF-ß as growth factors; CD133, c-KIT, CD34, and CD44 as stem cell markers; and estrogen (ER), progesterone (PR), and androgen receptor (AR) as hormone receptors.
SNs were classified into four subtypes: (1) immature mesenchymal (n = 7, 4.7%); (2) fibroblastic (n = 74, 49.7%); (3) fibromuscular (n = 53, 35.6%); and (4) smooth muscular (n = 15, 10.1%) types. There were linear trends of the expression of all growth factors (VEGF, IGF-1, FGF, TGF-ß), but only CD44 stem cell marker and AR hormone receptor as maturation progressed from immature mesenchymal to smooth muscular type (Ptrend < 0.05). S-100, c-KIT, and ER were not expressed in any types of SNs. CD34 was positive in 55% of the SNs (82/149).
The data suggest that AR and growth factors are important factors for maturation of SNs, but not influenced by the administration of 5-alpha reductase inhibitor (5ARI). Although the cells comprising the SNs seem to be not associated with the origin of prostatic GISTs, there is a possibility of a tentative link of SFTs arising from SNs of the prostate.
[Show abstract][Hide abstract] ABSTRACT: Obstructive jaundice caused by tuberculous lymphadenitis is a rare manifestation of tuberculosis (TB), with 15 cases having been reported in Korea. We experienced a case of obstructive jaundice caused by pericholedochal tuberculous lymphadenitis in a 30-year-old man. The patient's initial serum total bilirubin level was 21.1 mg/dL. Abdominal computed tomography revealed narrowing of the bile duct by a conglomerated soft-tissue mass involving the main portal vein. Abrupt obstruction of the common bile duct was observed on cholangiography. Pathologic analysis of a ultrasonography-guided biopsy sample revealed chronic granulomatous inflammation, and an endoscopic examination revealed esophageal varices and active duodenal ulceration, the pathology of which was chronic noncaseating granulomatous inflammation. Hepaticojejunostomy was performed and pathologic analysis of the conglomerated soft-tissue mass revealed chronic granulomatous inflammation with caseation of the lymph nodes. Tuberculous lymphadenitis should be considered in patients presenting with obstructive jaundice in an endemic area.
Full-text · Article · Jun 2014 · Clinical and molecular hepatology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Our study examines thyroid transcription factor 1 (TTF-1) expression in 40 primary adenoid cystic carcinomas (ACCs) arising in various sites and compares TTF-1 expression between primary and metastatic ACCs in 12 cases with distant metastases.
Forty patients with ACCs, including 12 pairs of primary and metastatic ACCs, were evaluated for the immunohistochemical expression of TTF-1 (clone SPT24). In addition, 10 metastatic ACCs to the lung were tested on napsin A and a different TTF-1 antibody (clone 8G7G3) for further evaluation.
No primary ACCs showed TTF-1 immunoreactivity (clone SPT24). TTF-1 was positive in five (41.7%) of 12 metastatic ACCs; all five cases were found only in the lung and comprised five (50.0%) of 10 cases. In all positive cases, staining was focal and detected only in the cribriform histologic subtype. Staining patterns using both antibodies (both SPT24 and 8G7G3) were very similar, and TTF-1-positive tumor cells were also positive for napsin A. Extrapulmonary ACCs were all negative for TTF-1 regardless of origination and metastasis.
TTF-1- and napsin A-positive ACCs in the lung should not be considered primary ACCs because TTF-1 and napsin A can be expressed in metastatic ACCs of the lung.
Preview · Article · May 2014 · American Journal of Clinical Pathology
[Show abstract][Hide abstract] ABSTRACT: Wegener's granulomatosis (WG) is a systemic vasculitis affecting small and medium-sized vessels with granulomatous formation. Though it is known for respiratory tract and kidney involvement, neurologic manifestation has been also reported. Herein we report a patient who suffered pansinusitis with multiple lower cranial nerve palsies but reached remission by immunosuppressant after the diagnosis of WG. A 54-yr-old female visited with headache, hearing difficulty, and progressive bulbar symptoms. She experienced endoscopic sinus surgeries due to refractory sinusitis. Neurologic examination revealed multiple lower cranial nerve palsies. Vasculitic markers showed no abnormality. Nasal biopsy revealed granulomatous inflammation and vasculitis involving small vessels. Given cyclophosphamide and prednisolone, her symptoms were prominently improved. WG should be considered in the patient with multiple cranial nerve palsies, especially those with paranasal sinus disease. Because WG can be lethal if delayed in treatment, prompt immunosuppressant is warranted after the diagnostic tissue biopsy.
Full-text · Article · Nov 2013 · Journal of Korean medical science
[Show abstract][Hide abstract] ABSTRACT: To examine the expression of FOXP3, IL-10, TGF-β1, IL-17A and T helper 17 (Th17) cells/FOXP3+regulatory T cells (Tregs) balance in the gastric mucosa of children with Helicobacter pylori infection, in relation to the gastric histopathology.
Antral mucosal biopsies were obtained from 20 children with H. pylori(+) gastritis and 20 age-, and sex-matched normal control. Histopathology was assessed by the updated Sydney classification. Gene expression of FOXP3, IL-10, and TGF-β1 were analyzed by quantitative real-time polymerase chain reaction. Immunohistochemical stains for FOXP3+Tregs and Th17 cells were performed.
The gene expression levels of FOXP3, TGF-β1 and IL-10 mRNA and the number of FOXP3+Tregs in the H. pylori(+) gastritis group were significantly higher than in the control group (P < 0.01). FOXP3 mRNA levels were correlated positively with TGF-β1 and IL-10 mRNA levels in the H. pylori(+) gastritis group (P < 0.05). Furthermore, FOXP3 mRNA levels were correlated positively with the bacterial density, infiltration of polymorphonuclear cells (PMN), and mononuclear cells (MNC) in the H. pylori(+) gastritis group (P < 0.05). The number of Th17 cells was significantly higher in the H. pylori(+) gastritis group than in the control group (P < 0.05). In addition, the number of Th17 cells was correlated negatively with the bacterial density and positively with the inflammatory scores of PMN and MNC in the H. pylori(+) gastritis group (P < 0.05). A negative correlation between the Th17 cells/FOXP3+Tregs ratio and the bacterial density was demonstrated in the H. pylori(+) gastritis group (P < 0.05).
This study suggested that Th17/Tregs balance toward a Tregs-biased response favors the persistence of bacteria causing a chronic active gastritis.
No preview · Article · Oct 2013 · Journal of pediatric gastroenterology and nutrition
[Show abstract][Hide abstract] ABSTRACT: Apoptotic cell instillation after bleomycin induces persistent HGF production and protects from pulmonary fibrosis, but the underlying mechanism remains unclear. We investigated immediate and prolonged effects of in vivo instillation of apoptotic cells into bleomycin-stimulated mouse lungs (2 days old) on COX-2 expression in lung tissue and alveolar macrophages and PGE2 production in BALF. Furthermore, functional interaction between these molecules and HGF, following apoptotic cell instillation in a bleomycin-induced lung fibrosis model, was assessed. Apoptotic cell instillation results in enhanced immediate and prolonged expression of COX-2 and PGE2 when compared with those from bleomycin-only-treated mice. Coadministration of the COX-2-selective inhibitor NS398 or the selective PGE2R EP2 inhibitor AH6809 inhibited the increase in HGF production. Inhibition of HGF signaling using PHA-665752 inhibited increases in COX-2 and PGE2. Long-term inhibition of COX-2, PGE2, or HGF reversed the reduction of TGF-β, apoptotic and MPO activities, protein levels, and hydroxyproline contents. Up-regulation of COX-2/PGE2 and HGF through a positive-feedback loop may be an important mechanism whereby apoptotic cell instillation exerts the net results of anti-inflammatory, antiapoptotic, and antifibrotic action.
Preview · Article · Aug 2013 · Journal of leukocyte biology
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor (TNF)-α is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-α antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model.
Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-α, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)2, and tissue inhibitor of matrix metalloproteinase (TIMP).
The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intra-acinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-α, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28).
Infliximab administration induced early changes in pathological findings and expression levels of TNF-α, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.
Preview · Article · Mar 2013 · Korean Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Fibrous dysplasia (FD) is a benign skeletal disorder in which abnormally overgrowing bony lesion replaces normal bone. FD can affect one bone (monostotic form) or multiple bones (polyostotic form). The craniofacial bones are involved in about 10% of subjects with monostotic FD. However, its occurrence in the sinonasal tract is very rare. We report a case of monostotic FD developed only in the inferior turbinate in a 29-year-old woman. To the best of our knowledge, it is the second report of monostotic FD involving the inferior turbinate in the medical literature. We, therefore, report this rare case with a review of literature.
No preview · Article · Feb 2013 · International journal of clinical and experimental pathology
[Show abstract][Hide abstract] ABSTRACT: Sunitinib an inhibitor of the vascular endothelial growth factor receptor, is highly effective against renal cell carcinoma and is now widely used in patients with metastatic disease. Gastroesophageal reflux disease (GERD) is rarely reported as a side effect of sunitinib. We report two cases of GERD with upper gastrointestinal bleeding related to sunitinib administration. Both cases responded well to conservative management. Microscopic findings in both cases showed cellular atypia such as hyperchromasia, increases in nuclear size, and multinucleation. The cellular atypia of the squamous mucosa appears to be associated with reparative processes.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ET(A)) were significantly decreased in the shRNA group in week 4. The protein levels of ET(A) were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-α and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension.
Preview · Article · Dec 2012 · Journal of Korean medical science
[Show abstract][Hide abstract] ABSTRACT: The renin angiotensin system seems to play an important role in the development of cardiac and vascular hypertrophy in hypertension. The changes in pathology, and gene expressions of the angiotensin II receptor type 1A (ATIA) and angiotensin converting enzyme (ACE) were investigated in order to explore the effects of losartan in spontaneously hypertensive rat (SHR) models.
Twelve week-old male Wistar rats were grouped as follows: control (C) group, hypertension (H) group, and losartan (L) group in which SHR was treated with losartan (10 mg/kg/day). Western blot and reverse transcription-polymerase chain reaction analysis regarding seven genes such as endothelin-1, ACE, ATIA, neutrophil cytosolic factor, brain natriuretic peptide, troponin I, endothelial nitric oxide synthase were performed.
Systolic blood pressure was significantly decreased in the L group compared with the H group in weeks 3 and 5. ACE and ATIA proteins in the L group were lower than H group in week 5.
Losartan reduced blood pressure, cardiac hypertrophy and protein expressions of ACE and ATIA. Changes of protein expressions were more sensitive than changes in pathology. Further study is needed for the differing doses of losartan in SHR models.
Preview · Article · Nov 2012 · Korean Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: Background
Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis.
The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining.
For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05).
MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression.
Preview · Article · Oct 2012 · World Journal of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Ischemic colitis is a rare complication of interferon administration. Only 9 cases in 6 reports have been described to-date. This report describes a case of ischemic colitis during pegylated interferon and ribavirin treatment for chronic hepatitis C, and includes a review of the relevant literature. A 48-year-old woman was treated with pegylated interferon α-2a and ribavirin for chronic hepatitis C, genotype Ib. After 19 wk of treatment, the patient complained of severe afebrile abdominal pain with hematochezia. Vital signs were stable and serum white blood cell count was within the normal range. Abdominal computed tomography showed diffuse colonic wall thickening from the splenic flexure to the proximal sigmoid colon, which is the most vulnerable area for the development of ischemic colitis. Colonoscopy revealed an acute mucosal hyperemic change, with edema and ulcerations extending from the proximal descending colon to the sigmoid colon. Colonic mucosal biopsy revealed acute exudative colitis. Polymerase chain reaction and culture for Mycobacterium tuberculosis were negative and the cultures for cytomegalovirus, Salmonella and Shigella species were negative. After discontinuation of interferon and ribavirin therapy, abdominal pain and hematochezia subsided and, following colonoscopy showed improvement of the mucosal ulcerations. Ischemic colitis cases during interferon therapy in patients with chronic hepatitis C reported so far have all involved the descending colon. Ischemic colitis is a rarely encountered complication of interferon administration in patients with chronic hepatitis C and should be considered when a patient complains of abdominal pain and hematochezia.
Full-text · Article · Aug 2012 · World Journal of Gastroenterology