• 생명과학회지
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• 제27권2호
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• pp.149-154
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• 2017

미만성 거대 B 세포 림프종(DLBCL)은 비호지킨 림프종에서 가장 흔한 형태이다. DLBCL에서 약물치료에 대한 연구가 많은 진전을 보였지만, 아직 많은 환자의 경우 DLBCL로 인한 사망률이 상당하다. 따라서 DLBCL에 대한 이해와 새로운 표적 치료제의 개발이 필요하다. PDE (인산이에스테르 가수분해효소)4B는 최근 시행된 유전자 발현 프로파일링에서 약제내성을 가지는 DLBCL에서 과발현 되는 유전자로 밝혀졌다. PDE4B의 주된 역할은 이차전달자인 고리형 AMP (cylclic AMP, cAMP)를 5'AMP로의 가수분해를 촉진시켜 cAMP를 비활성화 시키는 것이다. cAMP는 B 세포에서 세포증식 저해와 세포사멸을 유도하고 PDE4B는 B 세포에서 이러한 cAMP의 기능을 소멸시키는 것으로 알려져 있다. 그러나 PDE4B의 과발현이 어떤 기작에 의한 것인지는 연구가 미비하다. 본 논문에서는 비정상적으로 발현된 마이크로 RNA (microRNA, miRNA)가 PDE4B의 과발현에 관련되어 있을 것이라는 가정하에 실험을 진행하였다. PDE4B 3'-UTR에는 세 개의 miR-23b 예상 결합부위가 존재하고, 이는 luciferase reporter assay를 통해서 확인하였다. 흥미롭게도, miR-23b 결합 부위들은 인간에서부터 도마뱀에 이르기까지 진화적으로 보존되어 있었고, 이는 세포 생리학적 측면에서 PDE4B-miR-23b 사이의 상호작용이 중요한 역할을 수행함을 암시하고 있다. miR-23b의 과발현은 PDE4B의 mRNA 발현을 감소시키고 세포내의 cAMP의 농도를 증가시켰다. 뿐만 아니라, miR-23b의 발현은 아데닐산고리화효소(adenylyl cyclase)의 활성약제인 forskolin이 처리된 경우에만 DLBCL 세포들의 증식과 생존을 억제하였다. 이는 miR-23b는 PDE4B 발현을 감소시킴으로써 세포증식과 생존을 조절함을 보여주는 것이다. 이를 통해 생각해 볼 때, miR-23b는 PDE4B를 억제함으로써 DLBCL에서 나타나는 항암제 내성을 극복할 수 있고, 따라서 miR-23b는 잠재적 종양 억제자로서 효과적인 치료적 타겟으로 예상된다.

• 대한세포병리학회지
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• 제16권1호
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• pp.47-51
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• 2005

Plasmablastic lymphoma (PBL) is a recently described aggressive B-cell neoplasm, which usually manifests as a localized disease of the oral mucosa in individuals infected with human immunodeficiency virus (HIV). Recently we encountered a case of plasmablastic lymphoma manifesting in the left maxillary sinus and cervical lymph node of a previously healthy HIV-negative man, 48 years of age. we conducted a fine-needle aspiration smear of the cervical lymph node, and this was found to be highly cellular with numerous large cells exhibiting eccentrically positioned nuclei, prominent nucleoli, and moderate quantities of basophilic cytoplasm. A biopsy of the mass in the maxillary sinus evidenced diffuse growth of similar plasmablastic cells. These tumor cells were negative for the leukocyte common antigens, CD20, CD3, CD30, and EMA. However, the cells tested positive for CD79a and CD138/syndecan-1. The tumor cells also exhibited L-light-chain restriction. The Ki-67 proliferation index was measured at almost 100%. The patient was diagnosed with plasmablastic lymphoma. After three cycles of combination chemotherapy and radiotherapy, the patient went into complete remission, and currently remains in this state.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7769-7773
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• 2014

Background: Some tumor types are related to HIV, including non-Hodgkin lymphoma (NHL). The morbidity and mortality of NHL has remained high, even after highly active antiretroviral therapy (HAART) was introduced. We collected cases of AIDS with NHL, and evaluated the imaging features and strategies for diagnosis. Materials and Methods: There were 27 patients with AIDS and tumors confirmed by pathology. There were 9 patients with Burkitt lymphoma, 16 with diffuse large B cell lymphomas (DLBCLs), and 2 with primary central nervous system (PCNS) lymphomas. All of the patients underwent a series of imaging studies. Three radiologists analyzed the images, and any disagreement was discussed until consensus was reached. Results: The radiologic manifestations of AIDS with NHL were mainly masses and lymphadenopathy, 3 patients having one mass and 12 two or more masses. 7 patients had lymphadenopathy in one site and 3patients had lymphadenopathy in two or more sites. Coarse mucosal folds, thickening of the gastrointestinal wall, and lumen narrowing were typical manifestations of NHL within the gastrointestinal tract. There were 4 patients with masses and 5 with lymphadenopathy inthe 9 with Burkitt lymphoma, and 11 patients with masses 5 with lymphadenopathy in the 16 with DLBCLs. Conclusion: NHL is a malignancy that usually occurs in patients with AIDS. Imaging is an important method by which to evaluate lesions, masses, and lymphadenopathy. Fine needle aspiration biopsy and stereotaxis biopsy are useful methods by which to diagnose NHL.

• Radiation Oncology Journal
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• 제34권4호
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• pp.273-279
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• 2016

Purpose: Although each Waldeyer's ring sub-site is considered an independent prognostic factor, few studies have assessed the prognosis and treatment of tonsillar lymphoma. Treatment outcomes were analyzed in patients with primary tonsillar lymphoma who were treated with chemotherapy and radiotherapy (RT). Materials and Methods: Nineteen patients with diffuse large B-cell lymphoma were evaluated, with a median follow-up of 53 months. Age, sex, and histology, amongst other factors, were reviewed. Progression-free survival (PFS) and overall survival (OS) rates were analyzed. Results: Most patients had Ann Arbor stage I-II (94.7%), IPI score of 0 (89.5%), and complete remission after chemotherapy (89.5%). The 5-year PFS and OS rates were 74.6% and 80%, respectively. In univariate analysis, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen resulted in a better PFS than the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (88.9% vs. 50.0%; p = 0.053). RT dose was related to the survival outcome (p = 0.010 for PFS, p = 0.044 for OS). Patients were classified into the CHOP + RT (>40 Gy) group and R-CHOP + RT (${\leq}40Gy$) group. The 5-year PFS rates were 50% in the CHOP + RT group, and 100 % in the R-CHOP + RT group (p = 0.018). The 5-year OS rates were 66.7% and 100%, respectively (p = 0.087). Conclusion: Primary tonsillar lymphoma patients typically have favorable outcomes. Chemotherapy (R-CHOP) combined with relatively lower dose consolidative RT may be safe and effective for primary tonsillar lymphoma.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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• pp.357-360
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• 2005

In this paper we consider the well-known semiparametric proportional hazards (PH) models for survival analysis. These models are usually used with few covariates and many observations (subjects). But, for a typical setting of gene expression data from DNA microarray, we need to consider the case where the number of covariates p exceeds the number of samples n. For a given vector of response values which are times to event (death or censored times) and p gene expressions (covariates), we address the issue of how to reduce the dimension by selecting the significant genes. This approach enable us to estimate the survival curve when n < < p. In our approach, rather than fixing the number of selected genes, we will assign a prior distribution to this number. The approach creates additional flexibility by allowing the imposition of constraints, such as bounding the dimension via a prior, which in effect works as a penalty. To implement our methodology, we use a Markov Chain Monte Carlo (MCMC) method. We demonstrate the use of the methodology to diffuse large B-cell lymphoma (DLBCL) complementary DNA(cDNA) data.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10421-10425
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• 2015

Background: While the incidence of non-Hodgkins lymphoma (NHL) has been rising worldwide, the reasons remain undefined. Recent research has focused on effect of red andf processed meat intake as a risk factor, but with inconclusive results. We therefore conducted a meta-analysis of data published to date, to ascertain the overall association between intake and NHL. Materials and Methods: A published literature search was performed through Pubmed, Cochrane Library, Medline, and Science Citation Index Expanded databases for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity was assessed using Chi-square and I2 statistics. Dissemination bias was evaluated by funnel plot analysis.We performed a formal meta-analysis using summary measures from these studies. Results: In total, 11 published studies were included in the final analysis. The combined analysis revealed that there was significant association between the red meat and NHL risk (OR=1.10, 95%CI: 1.02 to 1.19, p=0.01). Additionally, there was showed significance association between processed red meat and NHL risk (OR=1.17, 95%CI: 1.06 to 1.29, p=0.001). In subgroup analysis, a statistical significant association was noted between diffuse large B-cell lymphoma (DLBCL) (OR=1.20, 95%CI: 1.04 to 2.37, P=0.01) and red meat intake. Conclusions: In this meta-Analysis, there was evidence for association between consumption of red meat, or processed meat and risk of NHL, particularly with the DLBCL subtype in the red meat case.

• Radiation Oncology Journal
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• 제11권1호
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• pp.159-166
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• 1993

A retrospective analysis was done for 69 patients with Stage I and II non-Hodgkin's lymphoma who were treated from May 1981 to December 1990, in the Department of Radiadtion Oncology, Korea University Hospital. We used Ann Arbor Staging system and Working Formulation for histological classification. Forty-three patients (43/69, $62.3{\%}$) were Stage I and 26 patients (26/69, $37.7{\%}$) were Stage II, and B symptom was found in $10.1{\%}$ (7/69). Nodal lymphoma was $21.7{\%}$ (15/69); 14 patients with supradiaphragmatic disease and 1 patient with infradiaphragmatic disease. Extranodal lymphoma was $78.3{\%}$ (54/69): $64.8{\%}$ (35/54) for head and neck, $25.9{\%}$ (14/54) for gastrointestinal tract. Histologically, low grade consists of $8.7{\%}$ (6/69), intermediate grade $84.2{\%}$ (56/69), high grade $10.1{\%}$ (7/69), and diffuse large cell type was the most frequent form with 36 patients (36/69, $52.2{\%}$). Eighteen patients ($26.1{\%}$) were treated with radiation therapy alone,20 patients ($29.0{\%}$) with radiation therapy combined with chemotherapy, 15 patients ($21.7{\%}$) with radiation therapy combined with surgery and chemotherapy, Median survival duration was 28 months, and the range of survival time was from 1 month to 134 months. Overall five-year survival rate for Stage I and II disease was $54.2{\%}$, with $64.5{\%}$ for Stage I and $37.1{\%}$ for Stage II. For nodal lymphoma,5-year survival rate was $45.9{\%}$, and $56.5{\%}$ for extranodal lymphoma; $60.6{\%}$ for head and neck, $52.9{\%}$ for GI tract primary disease. Local control rate for all patients was $88.4{\%}$ (61/69), with $80{\%}$ (12/15) for nodal lymphoma and $90.7{\%}$ (49/54) for extranodal lymphoma. The total failure rate was $34.8{\%}$ (24/69). Five of 24 ($20.8{\%}$) patients who were failed developed local failure only, $12.5{\%}$ (3/24) local failure with distant failure, and distant failure only were found in $66.7{\%}$ (16/24). Between nodal lymphoma and extranodal lymphoma, there was no significant survival difference, but extranodal lymphoma showed higher incidence.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7207-7211
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• 2014

Background: The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkin's lymphoma (pENL) patients, focusing on treatment and survival outcome. Materials and Methods: Between October 2003 and March 2012, 802 patients with non-Hodgkin's lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. Results: pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5-1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. Conclusions: Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5945-5950
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• 2015

A 6-year retrospective cohort study was conducted among Thai hematologic malignancy (HM) patients receiving intensive chemotherapy. Of the 145 eligible patients receiving 893 chemotherapy sessions, 46.9% were female, median age was 52 years, and the most common HM diagnosis was diffuse large B-cell lymphoma (46.2%). Febrile neutropenia (FN) occurred in 14.9% of chemotherapy sessions with an incidence of 24.8 per 1,000 chemotherapy cycles per year. Independent factors associated with FN were receiving the first chemotherapy cycle [adjusted hazard ratio (aHR) 4.1], having hemoglobin ${\leq}100g/L$ (aHR 3.7) and platelet ${\leq}140,000/{\mu}L$ (aHR 2.7) on chemotherapy day and receiving acute myeloid leukemia regimens (aHR 20.8). Granulocyte colony stimulating factor was significantly associated with reduced rate of FN when given in those receiving CHOP regimen. With the median follow-up time of 16 months, the overall survival time was significantly longer in patients without FN than those with FN (61.7 vs. 20.8 months; p<0.001).

• 한국통계학회:학술대회논문집
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• 한국통계학회 2005년도 춘계 학술발표회 논문집
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• pp.17-23
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• 2005

In this paper we consider the well-known semiparametric proportional hazards models for survival analysis. These models are usually used with few covariates and many observations (subjects). But, for a typical setting of gene expression data from DNA microarray, we need to consider the case where the number of covariates p exceeds the number of samples n. For a given vector of response values which are times to event (death or censored times) and p gene expressions(covariates), we address the issue of how to reduce the dimension by selecting the significant genes. This approach enables us to estimate the survival curve when n ${\ll}$p. In our approach, rather than fixing the number of selected genes, we will assign a prior distribution to this number. The approach creates additional flexibility by allowing the imposition of constraints, such as bounding the dimension via a prior, which in effect works as a penalty To implement our methodology, we use a Markov Chain Monte Carlo (MCMC) method. We demonstrate the use of the methodology to diffuse large B-cell lymphoma (DLBCL) complementary DNA (cDNA) data and Breast Carcinomas data.