• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2219-2225
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• 2015

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

• Journal of Korean Neurosurgical Society
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• v.38 no.2
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• pp.126-131
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• 2005

Objective : The choice of tumor antigen for dendritic cell[DC]-loading has still been an unresolved problem in the DC-based vaccine strategies against malignant gliomas that has not been found well-characterized tumor specific antigens. In this study, we compare tumor-specific T cell response induced by glioma apoptotic body[GAB]-pulsed DCs to response induced by glioma cell lysate-pulsed ones quantitatively. Methods : DCs generated in the presence of granulocyte macrophage-colony stimulating factor and interleukin[IL]-4 from peripheral blood mononuclear cells[PBMCs] of HLA-A2 positive healthy donors were cultured. Each GABs and glioma cell lysate generated from HLA-A2 positive T98G glioblastoma cells were co-incubated with DCs. $CD8^+$ T lymphocytes isolated from PBMCs of same donors were cultured in media containing IL-2 and either stimulated by GAB- or lysate-pulsed DCs three times at a weekly interval. The interferon[IFN]-${\gamma}$ concentrations of each cell culture supernate were measured by enzyme immunoassay technique. Cytolytic activity of the generated cytotoxic $CD8^+$ T cells either stimulated with GAB- or lysate-pulsed DCs was determined by a standard 4-h $^{51}Cr$-release assay. Results : IFN-${\gamma}$ production and cytolytic activity of effector T cells stimulated by GAB-pulsed DCs were significantly higher than those of T cells stimulated by lysate-pulsed ones. Conclusion : These results indicate the choice of antigen is a critical determinant in the induction of antitumor immunity against malignant glioma. Antigen preparations from GABs represent a promising alternative to glioma cell lysate in DC-based glioma vaccine strategies.

• Journal of Sasang Constitutional Medicine
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• v.16 no.1
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• pp.120-129
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• 2004

Yangkyuk-Sanhwa-Tang(YST) has been widely used as a formula for the Soyangin cerebral infarction (CI) patients according to Sasang constitutional philosophy. Brain cells produce cytokines and chemokines during the inflammatory process after stroke both in animal models and in patients. Previously, regulation of serum cytokine levels by YSThas been observed in individuals at the acute stage of CI disease, but there have not been other scientific investigations on YST. The author investigated the effect of YST on theproduction of various cytokines using peripheral blood mononuclear cells (PBMCs)from the Soyangin (CI) patients, and Soyangin normal group. The cytokine production was analyzed using enzyme-linked immunosorbent assay (ELISA). The amount of interleukin (IL)-1, IL-1, IL-6, IL-8, and tumor necrosis factor (TNF)- in culture supernatant significantly increased in the LPS-treated cells compared with unstimulated-cells (P < 0.05). However, in LPS-stimulated PBMCs, cytokines level in CI patients group was higher than that of normal group. YST (1 mg/ml) significantly inhibited IL-1, IL-1, and IL-8 production in PBMCs stimulated with LPS (about 85% for IL-1, 87% for IL-1, and 53% for IL-8, P < 0.05), but did not significantly inhibit IL-6 and TNF- production in the CI patients group. We also show that YST significantly increased LPS-induced IL-1, IL-6, and TNF- production in the normal group. Thesedata suggest that YST has a regulatoryeffect on the cytokine production, which might explain its beneficial effect in the treatment of CI.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.601-606
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• 2015

Background: Prostate cancer is predominately a disease of older men, with a median age of diagnosis of 68 years and 71% of cancer deaths occurring in those over 75 years of age. While prostate cancer screening is not recommended for men >70 years, fit elderly men with controlled comorbidities may have a relatively long life expectancy. We compare the use of age related PSA with the detection of primary malignant circulating prostate cells mCPCs to detect clinically significant PC in this population. Materials and Methods: All men undergoing PC screening with a PSA >4.0ng/ml underwent TRUS 12 core prostate biopsy (PB). Age, PSA, PB results defined as cancer/no-cancer, Gleason, number of positive cores and percentage infiltration were registered. Men had an 8ml blood sample taken for mCPC detection; mononuclear cells were obtained using differential gel centrifugation and mCPCs were identified using immunocytochemistry with anti-PSA and anti-P504S. A mCPC was defined as a cell expressing PSA and P504S; a positive test as at least one mCPC detected/sample. Diagnostic yields for subgroups were calculated and the number of avoided PBs registered. Esptein criteria were used to define small grade tumours. Results: A total of 610 men underwent PB, 398 of whom were aged <70yrs. Men over 70 yrs had: a higher median PSA, 6.24ng/ml versus 5.59ng/ml (p=0.04); and a higher frequency of cancer detected 90/212 (43%) versus 134/398 (34%) (p=0.032). Some 34/134 cancers in men <70yrs versus 22/90 (24%) of men >70yrs complied with criteria for active surveillance. CPC detection: 154/398 (39%) men <70yrs were CPC (+), specificity for cancer 86%, sensitivity 88%, 14/16 with a false (-) result had a small low grade PC. In men >70 years, 88/212 (42%) were CPC (+); specificity 92%, sensitivity 87%, 10/12 with a false (-) had small low grade tumours. False (+) results were more common in younger men 36/154 versus 10/88 (p<0.02). With a PSA cutoff of 6.5ng/ml, in men <70yrs, 108 PB would be avoided, missing 56 cancers of which 48 were clinically significant. Using CPC detection, 124 biopsies would be avoided, missing only 2 clinically significant cancers. In men >70 yrs using a PSA >6.5ng/ml would have resulted in 108 PB with 34 PC detected, of which 14(41%) were small low grade tumours. Conclusions: The use of CPC detection in the fit elderly significantly decreases the number of PBs without missing clinically significant cancers, indicating superiority to the use of age-related PSA.

• Journal of the Korean Chemical Society
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• v.43 no.6
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• pp.628-635
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• 1999

Direct preparative method of 2,6-diformyl-p-cresol and 2-hydroxy-3-hydroxy-5-methylbenzaldehyde from 2,6-bis(hydroxymethyl)-4-methylphenol using activated $Mn(IV)O_2$ was described. Hexadentate compartmental Iigands, $H_4L[A]\;and\; H_4L[B]$ were prepared by condensation reactions of 2-hydroxy-3-hydroxy methyl-5-methylbenzaldehyde with ethylenediamine and 1,3-diaminopropane respectively. By the reaction of macrocycle($H_4[20]DOTA$) with Ln(III) nitrate {Ln(III)=Pr, Sm, Cd, Dy }, discrete mononuclear Ln(III) complexes of the type $[Ln(H_2[20]DOTA)(ClO_4)(H_2O)]\;{\cdot}\;3H_2O$ were synthesized in the solid state. $[Ln([20]DOTA)(NO_3)(H_2O)](NO_3)_2\;{\cdot}\;xH_2O$ was placed in methanol for 2 days, and $[Ln([20]DOTA)(NO_3)(CH_3OH)]^{2+}$ was formed. The equilibrium constants(K) for the substitution of coordinated $CH_3OH$ in the Ln-[20]DOTA complexes by various auxiliary ligand, $L_a$(=salicylic acid, p-chlorobenzoic acid, benzoic acid, acetic acid, 4-bromophenol) were determined spectroscopically at 25$^{\circ}C$ and 0.1M $NaClO_4$. The K values calculated were in the order of salicylic acid > p-chlorobenzoic acid > benzoic acid > acetic acid > 4-bromophenol, while pKa of auxiliary ligands was in the opposite trend.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.23 no.4
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• pp.393-401
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• 2013

Objectives: Endotoxins in dust generated in occupational settings is known to contribute to the occurrence of respiratory illness among workers. The relationship between the level of endotoxins in total dust or respirable particulates collected from swine farms and immunological markers related with respiratory allergy was evaluated among swine husbandry workers. Materials and Methods: Peripheral blood samples were collected from ten workers at ten swine farms at Gyeonggi province, Korea. Peripheral mononuclear cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 48 hours. The levels of various cytokines produced at culture supernatants were determined using a commercially available ELISA kit. The concentration of particulate matter($PM_{10}$) in the indoor air of the swine farms was evaluated using a PVC membrane filter and mini volume air sampler, and endotoxin levels in the dust were measured by Limulus Amebocyte Lysate Kinetic QCL method. Results: Levels of endotoxins in the total dust were categorized into high(geometric mean: $109.35EU/m^3$) and low concentrations (geometric mean: $0.95EU/m^3$) for five swine farms. Interleukin-4 levels were higher in the high endotoxin group than in the low endotoxin group, while interferon-${\gamma}$ levels were lower in the high endotoxin group than in the low endotoxin group. The ratio (interferon-${\gamma}$ to interleukin-4), indicating immunologic skewedness against allergic reactivities, was lower in the high endotoxin group($1.15{\pm}0.60$) than the low endotoxin group($3.09{\pm}2.38$). In addition, the level of interleukin-13, another cytokine contributing to the occurrence of allergic responses, was significantly higher in the at the high endotoxin group($1.12{\pm}0.37ng/m{\ell}$) than in the low endotoxin group($0.37{\pm}0.04ng/m{\ell}$). Hematologic assessment showed significantly lower cellularity in the number of total leukocytes, neutrophils, and eosinophils in the high endotoxin group than in the low endotoxin group. Conclusions: Even though a sufficient number of swine workers and farms were not investigated, this study generlly suggests that the immunological function of swine farm workers exposed to high levels of endotoxin could be modulated toward allergic reactivities.

• The korean journal of orthodontics
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• v.23 no.4 s.43
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• pp.503-527
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• 1993

This paper describes a new method to create an animal model for TMJ internal derangement in the New Zealand white rabbits and the light and electron microscopical changes of posterior attachment of them. Twenty six rabbits(2.5-3.0kg), four normal and twenty two experimental, were used. The right disc of experimental animal was displaced anteriorly without sectioning the posterior attachment and tied to the zygomatic arch with nylon not to be reduced to the original position. The left TMJ was sham-operated to be compared with its right experimental one. Normal animals were sacrificed one day and eight weeks after experiment. Experimental animals were sacrificed one day, ten days, three weeks, five weeks and eight weeks after surgery respectively. They were fixed intravenously with $2\%$ glutaldehyde under general anesthesia and the samples of them were processed for light and electron microscopic examination. The purpose of this experiment is to make a suitable animal model of disc displacement without reduction for studying and understanding the cellular and morphologic events in posterior attachment of TMJ including early changes which were difficult to be observed in human TMJs. The results of this investigation suggest the following conclusions : 1. Authors induced anterior disc displacement surgically in rabbits with new method to examine histologic changes of posterior attachment. Tissue reactions of this model seem to be similar to those observed in human disc displacement. We think this animal model for anterior disc displacement may be used to explore and evaluate objectively the effects of many treatment modalities in disc displacements. 2. The animal disease model showed inflammation at early stage(one and ten days). At this stage there were mild-to-severe mononuclear inflammatory cell infiltration, numerous newly formed vessels, vessel dilatation and engormement and many fibroblasts. 3. At middle stage(three weeks), fibrosis occurred, where fibroblasts decreased in number, but their cytoplasm was profuse indicating high activity. Collagen fibers increased in number and the tissue looked more dense. 4. At late stage(five weeks and eight weeks) showed degenerative changes including perforation of posterior attachment, disintegration of collagen fiber bundles, degeneration of fibroblasts, metastatic ossification, and dystrophic calcification.

• Journal of Periodontal and Implant Science
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• v.44 no.5
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• pp.235-241
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• 2014

Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are known to play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the major antigen-presenting cells (APCs) for initiating these T-cell immune responses, of which $CD103^+$ DCs are derived from precursor human peripheral blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the capacity of these PBMC-derived $CD103^+$ DCs to promote the differentiation of antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from $CD14^+$ monocytes from the PBMCs of 10 healthy subjects. Once the $CD103^+$ DCs were purified, the cell population was enriched by adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heat shock protein 60 (HSP60) were synthesized to pulse $CD103^+$ DCs as a tool for presenting the peptide antigens to stimulate $CD3^+$ T cells that were isolated from human PBMC. Exogenous interleukin 2 was added as a coculture supplement. The antigen-specific T-cell lines established were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity to stimulate peptide-specific Tregs, whereas $CD103^+$ DCs showed a potent antigen presenting capability to promote the peptide-specific Tregs, especially for peptide 14. RA enhanced the conversion of $CD103^+$ DCs, which paralleled the antigen-specific Treg-stimulating effect, though the differences failed to reach statistical significance. Conclusions: We demonstrated that $CD103^+$ DCs can promote antigen-specific Tregs from naive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA was an effective reagent that induces mature DCs with the typical phenotypic expression of CD103 that demonstrated the functional capability to promote antigen-specific Tregs.

• Journal of the korean academy of Pediatric Dentistry
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• v.44 no.3
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• pp.289-297
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• 2017

Local and general factors have been attributed to root resorption occurred by injuries such as trauma and dental caries that affect periodontal ligament or dental pulp tissue. Pathologic root resorption is different from physiologic root resorption in terms of resorption pattern such as micromorphology of resorption fossae and types of observed cells. Microscopic morphologies and histologic features of physiologic and pathologic root resorption surface of maxillary primary central incisors resulting from trauma and periapical inflammation were observed by scanning electron microscope and light microscope. The morphology of physiologic resorption lacunae was small and oval or circular shape with regularities. The morphology of pathologic resorption lacunae was large and polygonal shape with irregularities compared with the physiologic resorption lacunae. Multinucleated giant cells and mononuclear cells were closely attached to the physiologic and pathologic resorption lacunae, whereas several kinds of mesenchymal cells with numerous inflammatory cells were found in the areas adjacent to the pathologic resorption surface. Compensating cementum formation took place along some of the areas of physiologic and pathologic resorption area resulting from trauma, but could not be observed on pathologic resorption area resulting from periapical inflammation.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.278-283
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• 2004

The incidence of a pulmonary leiomyosarcoma as a primary lung tumor is quite rare. We report a case of primary leiomyosarcoma with a cardiac invasion in a 76 year old man. He was admitted due to left anterior chest wall pain for one month. Chest computed tomography showed a $9{\times}8{\times}10cm$ sized, large round mass in the left upper and lower lobes, and an amorphous low density lesion within the left atrium. Chest magnetic resonance imaging showed a large round mass in the left upper and lower lobes with growth into the left atrium. A diagnosis of leiomyosarcoma with prominent osteoclast-like giant cells was made based on the microscopic and immunohistochemical findings of a permanent specimen by explothoracotomy. The pathologic features of the tumor showed round mononuclear hyperchromatic cells and multinucleated giant cells that resembled osteoclasts. The immunohistochemical staining showed that the giant cells are positive for CD68 but negative for the muscle markers while the round cells were positive for the muscle marker. The patient refused further treatment and died after two months.