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Sun-Joo Jang,
Dok Hyun Yoon,
Shin Kim,
Shinkyo Yoon,
Dal Yong Kim, Chan-Sik Park,
Jooryung Huh,
Sang-Wook Lee,
Dae Ho Lee,
Jin-Sook Ryu,
Cheolwon Suh
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ABSTRACT: Extranodal involvement is common in patients with Burkitt lymphoma (BL). We evaluated the pattern of extranodal involvement and its impact on clinical outcomes in a single center cohort of adult Korean patients with sporadic BL. We retrospectively identified 64 patients with BL in the registry of non-Hodgkin lymphoma of the Asan Medical Center between 1996 and 2009. We assessed their clinical features and distribution of extranodal sites and analyzed clinical outcomes, including complete response rate after chemotherapy, overall survival, and progression-free survival, relative to baseline characteristics and involved extranodal sites. Extranodal involvement was found in 57 patients (89 %), with 34 (53.1 %) having two or more extranodal sites. The stomach (26.6 %) was the most common site, followed by the small and large intestines (25 %), bone marrow (23.4 %), genitourinary tract (21.9 %), and bones (18.8 %). Two patients (3.1 %) showed central nervous system (CNS) involvement. Complete response rates to chemotherapy were not related to sites of extranodal involvement. Two-year overall survival rates were lower in patients with bone marrow (33.3 vs. 74.6 %, p = 0.010) and CNS (0.0 vs. 66.6 %, p = 0.048) involvement than in patients with involvement at other extranodal sites. The stomach, genitourinary tract, and bones were the most commonly involved extranodal sites in Korean BL patients, but site had no prognostic significance.
Annals of Hematology 08/2012; · 2.62 Impact Factor
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ABSTRACT: We analyzed the innate immunity markers, C-reactive protein (CRP), serum amyloid P component (SAP) and pentraxin-3 (PTX-3), and metalloproteinase-9 (MMP-9) in coronary atherectomy tissues obtained from patients with acute ST elevation myocardial infarction (STEMI) (n=27) or stable angina (n=15). The relative areas immunopositive for CRP and SAP were similar in the two groups. In contrast, the proportion of areas immunopositive for PTX-3 and MMP-9 was higher in the STEMI group, compared to the stable angina group. PTX-3 or MMP-9-stained areas largely overlapped with those positive for CD68. We concluded that PTX-3 plays a role in the pathogenesis of STEMI.
Biomarkers 03/2012; 17(3):209-15. · 2.21 Impact Factor
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ABSTRACT: ADAMTS (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) proteases are emerging as key participants in the pathogenesis of vascular diseases. We studied the expression of ADAMTS-2, -3, -4 and -14 in the culprit plaques from patients presenting with acute myocardial infarction (AMI) versus stable angina. Tissue samples were gathered from 52 patients with AMI (n = 35) or stable angina (n = 17) who underwent directional coronary atherectomy. The specimens were stained with hematoxylin-eosin and analyzed immunohistochemically using antibodies specific to ADAMTS-2, -3, -13 and -14, and markers for endothelial cells, macrophages, and smooth muscle cells. Baseline characteristics of the groups were mostly similar. The proportion of smooth muscle α-actin-immunopositive area was smaller in the AMI group than in the stable angina group, but the areas immunopositive for CD31 or CD68 were higher in the AMI group. The relative areas immunopositive for ADAMTS-2, -3, and -13 in AMI were significantly larger than those in stable angina. However, the proportion of areas immunopositive for ADAMTS-14 did not differ between the two groups. Areas that stained for ADAMTS-2, -3, -13, and -14 largely overlapped with those positive for CD31 or CD68. The areas immunopositive for ADAMTS proteases were significantly correlated with CD31- or CD68-immunostained areas. In conclusions, ADAMTS-2, -3, and -13 expression, but not that of ADAMTS-14, are increased in plaques causing AMI compared those associated with stable angina. These results support a role for these enzymes in the pathogenesis of AMI.
Journal of Thrombosis and Thrombolysis 12/2011; 33(4):362-70. · 1.48 Impact Factor
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ABSTRACT: JL1 is a novel molecule expressed in the surface of hematopoietic precursor cells, but not on any other mature human tissue. Accordingly, JL1 is expressed in acute lymphoblastic leukemia (ALL) cells and can be used both for specific diagnosis and as a target for treatment. However, expression of JL1 by lymphomas has not been thoroughly assessed. Burkitt lymphoma is a potentially curable aggressive lymphoma, but prognostic markers that stratify risk have not been established. We therefore assayed JL1 expression in Burkitt lymphoma patients to assess its value as a prognostic marker for this disease. Tissue microarray blocks of formalin-fixed paraffin-embedded tissue samples from patients with Burkitt lymphoma and other B-cell lymphomas, at the Asan Medical Center and Seoul National University Hospital from January 1998 to December 2008 were immunohistochemically assayed using a mouse monoclonal antibody against JL1. We found that 30.2% of Burkitt lymphoma samples, but no other lymphoma samples, were positive for JL1. JL-1 expression was significantly correlated with patient survival (P = 0.022), but not with other clinical manifestations of the disease, with 91.6% of JL1-positive patients achieving complete remission in response to chemotherapy and 6.25% experiencing disease recurrence. JL1 positivity was significantly correlated with prolonged overall survival by both Kaplan-Meier survival (P = 0.035) and Cox proportional hazard model (P = 0.043) analysis. JL1 expression in Burkitt lymphoma was positively correlated with overall survival and better response to chemotherapy, suggesting that JL1 may be a prognostic marker for risk stratification in these patients.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2011; 459(4):353-9. · 2.49 Impact Factor
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ABSTRACT: It remains uncertain why some plaque ruptures trigger acute coronary syndrome (ACS), whereas others do not. We investigated the anatomic features and tissue factor (TF) expression at the sites of plaque rupture in 42 patients presenting with ACS (n = 23) or stable angina (n = 19). Intravascular ultrasound examination was performed before directional coronary atherectomy. Specimens were stained with antibodies against TF, CD68 positive phagocytic cells, and smooth muscle cells; and intravascular ultrasound and immunohistochemistry results were compared. Baseline demographic and clinical characteristics, as well as vessel and lumen sizes at both reference and lesion sites, were comparable in the two groups. However, the remodeling index and plaque burden at lesion sites were significantly greater in the ACS than in the stable angina group. The TF-immunopositive areas were significantly greater in the ACS than in the stable angina group (0.07%; IQR [0.02-0.16%] vs. 0.02%; IQR [0.01-0.05%], P = 0.022), whereas the proportions of CD68-positive and smooth muscle cell areas were similar. There was a significant correlation between areas positive for TF and those positive for CD68 (r = 0.83, P < 0.001). In conclusion, ruptured plaques in patients with ACS show stronger TF expression, a greater plaque burden, and a higher remodeling index than do plaques in those with stable angina, suggesting that both lesion morphology and local thrombogenicity are related to clinical symptoms after plaque rupture.
Journal of Thrombosis and Thrombolysis 04/2011; 32(2):150-7. · 1.48 Impact Factor
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ABSTRACT: ADAMTS (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) proteases might contribute to plaque destabilisation by weakening the fibrous cap. However, little is known about the expression of ADAMTS proteases in coronary atherosclerotic plaques.
To examine the expression of ADAMTS proteases in coronary atherectomy samples obtained from patients with acute myocardial infarction (AMI) or stable angina.
Atherectomy specimens were obtained from 34 patients with AMI (n=23) or stable angina (n=11) who underwent directional coronary atherectomy. The specimens were stained with H&E and analysed immunohistochemically using antibodies specific to ADAMTS-1, -4 and -5; versican cleavage products; and markers for endothelial cells, macrophages and smooth muscle cells.
Baseline characteristics were similar between the two groups. The proportion of CD31 and CD68 immunopositive areas did not differ between the two groups, but the area immunopositive for smooth muscle α-actin was smaller in the AMI group. The relative area immunopositive for ADAMTS-1 in AMI (1.04% (IQR 0.59-2.09%)) was significantly greater than that in stable angina (0.24% (0.15-0.39%); p<0.001). In contrast, the proportion of areas immunopositive for ADAMTS-4 or -5 was similar in the two groups. Areas that stained for ADAMTS-1 largely overlapped with those positive for CD68 and versican cleavage products. The areas immunopositive for ADAMTS-1 were significantly correlated with CD68 immunostained areas (r=0.50, p=0.003).
ADAMTS-1, -4 and -5 were present in human coronary atherosclerotic plaques, and ADATS-1 was more strongly expressed in AMI plaques than in stable plaques. ADAMTS-1 may play a role in plaque instability.
Journal of clinical pathology 02/2011; 64(5):399-404. · 2.43 Impact Factor
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Soon Man Yoon,
Seung-Jae Myung,
Byong Duk Ye,
In-Wha Kim,
Nam Gon Lee,
Yeon Mi Ryu,
Kyeongsoon Park,
Kwangmeyung Kim,
Ick Chan Kwon,
Young Soo Park, Chan-Sik Park,
Dae Hyuk Moon,
Do Hoon Kim,
Mi Young Do,
Jeong-Sik Byeon,
Suk-Kyun Yang,
Jin-Ho Kim
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ABSTRACT: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages.
WE UTILIZED TWO MURINE COLON CANCER MODELS: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe.
Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa.
NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease.
Gut and liver 12/2010; 4(4):488-97. · 0.83 Impact Factor
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ABSTRACT: The germinal centre (GC) is a specialized microenvironment where high-affinity antibodies are produced through hypermutation and isotype switching. Follicular dendritic cells (FDCs) are the stromal cells of the GC. The timely expansion and establishment of an FDC network is essential for a protective GC reaction; however, only a few factors modulating FDC development have been recognized. In this study, we report that interleukin-15 (IL-15) enhances human primary FDC proliferation and regulates cytokine secretion. The FDCs express IL-15 receptor complexes for IL-15 signal transduction as well as for specific binding. Moreover, the secretion of chemokines CCL-2, CCL-5, CXCL-5 and CXCL-8 was reduced by blocking IL-15 signalling while the secretion of other cytokines, and the expression of CD14, CD44, CD54 (ICAM-1) and CD106 (VCAM-1) proteins remained unchanged. These results suggest that IL-15 plays a crucial role in the development of FDC networks during GC reaction, offering a new target for immune modulation.
Immunology 03/2010; 130(4):536-44. · 3.32 Impact Factor
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ABSTRACT: Specific differentiation of leukemia cutis (LC) from nonleukemic dermatoses is crucial to ensure proper treatment for the disease. Because of the exceptionally variable histologic features of LC and the frequent nonleukemic dermatoses in leukemia patients, identification of leukemic cells that infiltrate skin lesions is important. Here, we introduce JL1, a novel leukemia-associated surface antigen, which is not expressed in mature human tissue but in cortical thymocytes and small subpopulations of bone marrow hematopoietic precursors.
To assess the expression pattern of JL1 in LC and compare it with other commonly used markers. Also, to evaluate the expression of JL1 in other cutaneous lesions that need differential diagnoses.
Immunohistochemical staining with anti-JL1 and other commonly used markers for LC was performed on paraffin-embedded skin biopsies from 32 cases of LC with acute lymphoblastic leukemia/lymphoma and acute myelogenous leukemia. Immunohistochemical staining score was evaluated in each case according to the proportion of positive tumor cells found. JL1 staining was also done on 96 reactive or neoplastic cutaneous lesions.
JL1 was detected in 7 of 11 acute lymphoblastic leukemia/lymphoma LC (63.6%) and 7 of 21 acute myelogenous leukemia LC (33.3%), with invariably high-staining scores. None of the other cutaneous lesions or normal tissues expressed JL1. The expression pattern of JL1 was not altered in 2 patients with follow-up biopsies.
Our finding that JL1 is expressed exclusively and stably by leukemic cells suggests that it can be used as a useful adjunctive marker for initial diagnosis and follow-up biopsy of LC, particularly in cases of scarce infiltrates.
Archives of pathology & laboratory medicine 01/2010; 134(1):95-102. · 2.58 Impact Factor
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ABSTRACT: To investigate the anticancer activity of transarterial embolization with arsenic trioxide (As(2)O(3)) oil emulsion, as well as its hepatic and renal toxicity, in a rabbit VX2 liver model.
VX2 carcinomas were grown in rabbit livers, followed by transarterial embolization with high-dose As(2)O(3) (5 mg/kg with 0.2 mL Lipiodol, n = 7), low-dose As(2)O(3) (1 mg/kg with 0.2 mL Lipiodol, n = 7), or control (0.2 mL Lipiodol, n = 7). The growth ratios and residual viable proportions of the tumors were estimated by multi-detector row computed tomography and histopathologic examination, respectively. Hepatic and renal toxicity was evaluated by means of blood biochemical analysis.
The growth ratios of the tumors differed significantly among the three groups (P = .008). The high-dose As(2)O(3) group showed significantly lower tumor growth ratios than the control group (mean +/- SD, 14.8% +/- 78.6 vs 794.0% +/- 156.2; P = .008). The residual viable proportions of the tumors were significantly lower in the high-dose (9.5% +/- 8.8) and low-dose (13.0% +/- 9.1) As(2)O(3) groups than in the control group (44.5% +/- 5.2; P < .017). Blood chemical concentrations indicating hepatic and renal toxicity did not differ among the three groups before or after transarterial embolization (P > .05).
Transarterial embolization with As(2)O(3) iodized oil emulsion in rabbit VX2 liver tumors has anticancer effects without significant increase in hepatic and renal toxicity.
Journal of vascular and interventional radiology: JVIR 09/2009; 20(10):1365-70. · 1.81 Impact Factor
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ABSTRACT: To establish a new animal model of tracheal stenosis in dogs that involves combined bronchoscopic electrocautery and ethanol injection.
Ten mongrel dogs were included in the study. With flexible bronchoscopic and fluoroscopic guidance, a combination of electrocautery (30 W) and ethanol injection (total volume 2 mL) was circumferentially applied to the trachea at the third thoracic vertebra level. Dogs were euthanized 4 weeks later and the stenosis diameter and histologic findings were evaluated.
All procedures were successful. Eight of the 10 dogs survived to 4 weeks, whereas two died from respiratory failure before the planned endpoint. For the eight full-term dogs, the mean percentage diameter stenosis (+/-SD) was 70.8%+/-9.3%, with a range of 56%-81%. Microscopic analysis showed that the maximum tracheal wall thickness was 2.48 mm+/-0.77. The degree of inflammatory cell infiltration varied, but cartilage destruction and mucosal ulceration were evident in all cases.
A new tracheal stenosis model was developed in dogs with use of combined bronchoscopic electrocautery and ethanol injection. This animal model is a technically simple, reliable, and tracheotomy-free model for the creation of tracheal stenosis.
Journal of Vascular and Interventional Radiology 06/2008; 19(5):764-9. · 2.08 Impact Factor
