• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5273-5280
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• 2016

Objective: To evaluate stromal cells of the bone marrow microenvironment (BMM) in bone marrow trephine biopsy (BMTB) specimens, with a focus on fibronectin, tumor necrosis factor- alpha (TNF-${\alpha}$) and L-selectin in Non-Hodgkin's lymphoma (NHL) patients, before and after therapy. Materials and Methods: A total of 80 de novo NHL patients, 64 with B-cell lymphomas 80%, (follicular cell lymphoma (FCL) in 32, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 12, and diffuse large cell lymphoma in 20) and 16 with T-cell lymphomas (20%) all diagnosed as T-Lymphoblastic lymphomas, were evaluated before and after therapy. For comparison, 25 age and sex matched BM donors, were included as a control group. BMTB material and BM aspirates were taken for morphological assessment of stromal cells, the plasma of these samples being examined for $TNF{\alpha}$ and L-selectin by ELISA, and fibronectin by radial immunodiffusion (RID). Results: BM stromal cells comprising reticular macrophages and fibroblasts were elevated in 53.3% of NHL cases at diagnosis, while BM fibronectin levels were decreased and BM $TNF{\alpha}$ and L-selectin were higher than in controls (p<0.05). In NHL cases, elevated values of BM $TNF{\alpha}$ and BM L-selectin were associated with signs of aggressive disease, including >1 extra nodal sites, detectable B symptoms, high grade, BM and CNS invasion, and a high International prognostic index (IPI) (p<0.05). Conclusion: BMM components, $TNF{\alpha}$, L-selectin and fibronectin, in NHL can be useful in evaluating disease activity, extent and response to treatment and as prognostic markers according to the IPI.

• Molecules and Cells
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• 제28권6호
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• pp.553-558
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• 2009

In the periphery, a galectin-1 receptor, CD7, plays crucial roles in galectin-1-mediated apoptosis of activated T-cells as well as progression of T-lymphoma. Previously, we demonstrated that $NF-{\kappa}B$ downregulated CD7 gene expression through the p38 MAPK pathway in developing immature thymocytes. However, its regulatory pathway is not well understood in functional mature T-cells. Here, we show that CD7 expression was downregulated by Twist2 in Jurkat cells, a human acute T-cell lymphoma cell line, and in EL4 cells, a mature murine T-cell lymphoma cell line. Furthermore, ectopic expression of Twist2 in Jurkat cells reduced galectin-1-induced apoptosis. While full-length Twist2 decreased CD7 promoter activity, a C-terminal deletion form of Twist2 reversed its inhibition, suggesting an important role of the C-terminus in CD7 regulation. In addition, CD7 expression was enhanced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate, which indicates that Twist2 might be one of candidate factors involved in histone deacetylation. Based on these results, we conclude that upregulation of Twist2 increases the resistance to galectin-1-mediated-apoptosis, which may have significant implications for the progression of some T-cells into tumors such as Sezary cells.

• Journal of Yeungnam Medical Science
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• 제27권2호
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• pp.105-112
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• 2010

병리조직학적으로 고환림프종으로 확진된 예들의 초음파검사 및 자기공명영상을 후향적으로 분석하여 다른 고환종양과 구분할 수 있는 소견이 있는지를 알아보기 위하여 본 연구를 시행하였다. 수술적 절제에 의해 확진된 7예와 초음파-유도하 조직생검으로 확진된 1예 등 총 8예를 대상으로 하였다. 종괴의 크기와 위치, 고환 이외에 침범된 장기를 조사하였고, 초음파검사에서는 종괴의 모양과 경계, 종괴 내부의 에코, 균일도와 함께 색도플러검사에서의 혈관분포상태를 조사하였다. 자기공명영상이 시행된 4예를 대상으로 종괴의 모양과 경계, 균일도, T1-및 T2-강조영상에서의 신호강도 및 조영증강 여부와 시간에 따른 조영증강의 변화를 조사하였다. 고환에 국한되어 있었던 경우는 2예에 불과하였고, 4예는 정삭을, 4예는 대동맥주위림프절을 침범하고 있었다. 초음파검사에서 종양의 외연은 6예에서 평활하였고 종괴의 에코는 7예에서 정상 고환 보다 저에코로 보였다. 4예는 균일하였고, 3예는 전반적으로는 균일하였으나 약간 불균일한 부분을 포함하고 있었고, 1예는 불균일하였다. 8예 모두에서 주변의 정상 조직보다는 현저하게 혈관분포상태 (vascularity)가 증가되어 있었다. 자기공명영상 T1-강조영상에서는 정상 고환과 유사한 신호강도로, T2-강조영상에서는 현저한 저신호강도로 관찰되었고 대체로 균일하였다. 조영 후 검사에서는 4예 모두 정상 고환 조직보다는 저신호강도로, 약하게, 균일하게 조영증강되었는데, 역동적 조영증강 검사가 시행된 1예에서는 시간이 감에 따라 점차 조영증강이 증가되는 소견을 관찰할 수 있었다. 이상의 결과를 토대로 50세 이상의 나이가 많은 환자에서 고환 종괴가 관찰되고, 초음파 검사에서 균일한 저에코로, 자기공명영상 T2-강조영상에서 균일한 저신호강도로 관찰될 때에는 고환림프종의 가능성을 가장 먼저 고려하여야할 것으로 생각한다.

• BMB Reports
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• 제28권6호
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• pp.556-561
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• 1995

The purpose of this study was to establish an in vitro culture method of tumor-specific T cells, and determine the efficacy of the cultured tumor-specific cytotoxic T-lymphocytes (CTL) as an agent of anti-tumor immunotherapy against a murine lymphoma, TIMI.4. Tumor-specific T-lymphocytes derived from C57BL/6 mice (thy-1.2) immune to TIMI.4 were activated by in vitro stimulation with the irradiated TIMI.4 cells, and expanded by restimulation with TIMI.4 in the presence of the concanavalin A-stimulated rat spleen culture supernatant, and splenic antigen-presenting cells. In vitro restimulation enhanced markedly the proportion of $CD8^+$, a predominant surface marker of CTL and the cytotoxic activity in the cultured immune T cell population. The resulting TIMI.4-specific T cells were adoptively transferred into nude mice. The tumor cells residing in the host after 7 days of adoptive transfer to B6.PL (thy-1.1) mice were quantified by use of an antibody directed to the thy-1.2 allele. The TIMI.4 cells in the recipient nude mice were decreased in a dose-dependent manner. Anti-tumor activity of the TIMI.4-specific T cells was also demonstrated by a survival test, where the tumor-bearing nu/nu mice which received the activated T-cells survived about 30% longer than the control mice which received the tumor cells alone. These suggest that adoptive transfer of TIMI.4-specific T cells could be a candidate for effective therapy of the murine lymphoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5825-5828
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• 2014

Background: Lymphomas represent the fifth most frequent cancer in Lebanon. However, little is known concerning epidemiologic characteristics and distribution of lymphoid neoplasms according to the 2008 WHO classification. Materials and Methods: We conducted a retrospective study of lymphoma cases diagnosed from 2008 till 2012 at $H\hat{o}tel$-Dieu de France University Hospital. Results: A total of 502 new cases of lymphoma were diagnosed at our institution during a five year period: 119 cases (24%) were Hodgkin lymphomas (HL) and 383 cases (76%) were non-Hodgkin lymphomas (NHL). HLs were equally distributed in both sexes with a mean age at diagnosis of 30 years. Among NHL, 87% (332 cases) were B cell lymphomas, 9% (34 cases) were T cell lymphomas and 4%(17 cases) were classified as precursor lymphoid neoplasms. Among B cell lymphomas, 44% (147 cases) were diffuse large B cell lymphomas (DLBCL), 20% (65 cases) follicular lymphomas and 8% (27 cases) mantle cell lymphomas. DLBCL were equally distributed in both sexes with a mean age of 58 years. Follicular lymphomas were characterized by a male predominance (57%) and a mean age of 60 years. Mantle cell lymphomas showed a pronounced male predominance (85%) with a mean age of 60 years in men and 70 years in women. Some 72% of patients having T cell lymphomas were men, with a mean age of 57 years in men and 45 years in women, while 65% of patients having precursor lymphoid neoplasms were women with a mean age of 22 years in women and 30 years in men. Conclusions: The lymphoma subtype distribution in Lebanon is unique when compared to other countries from around the world. In fact, Hodgkin and follicular lymphomas are more frequent than in most Far Eastern, European and American countries, while T-cell lymphomas and DLBCL are less frequent.

• Radiation Oncology Journal
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• 제29권3호
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• pp.174-180
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• 2011

Purpose: To evaluate the radiotherapy treatment outcome of patients in stage IE and IIE nasal natural killer/T-cell lymphoma. Materials and Methods: From August 1999 to August 2009, 46 patients with stage IE and IIE nasal natural killer/T-cell lymphoma were treated by definitive radiotherapy and chemotherapy. 33 patients were treated with chemotherapy followed by radiotherapy (CT + RT) and they received 50.4 Gy in 28 fractions. 13 patients were treated with concurrent chemoradiotherapy (CCRT) and they received 40 Gy in 20 fractions. Results: The median follow-up period was 4.6-137.6 months (median, 50.2 months) for all patients. The 4-year overall survival was 68.6% and 4-year disease free survival (DFS) was 61.9%. The 4-year locoregional recurrence free survival was 65.0%, and 4-year distant metastasis free survival (DMFS) was 66.2%. For patients treated with CT + RT, 15 patients (45.5%) achieved complete response after chemotherapy, and 13 patients (39.4%) achieved partial response. 13 patients (81.8%) achieved complete response after radiotherapy, and 6 patients (18.2%) achieved partial response. For patients treated with CCRT, 11 patients (84.6%) achieved complete response, and one patient (7.7%) achieved partial response. In univariate analysis, presence of cervical lymph node metastasis was only significant prognostic factor for DFS and DMFS. Conclusion: This study did not show satisfactory overall survival rate and disease free survival rate of definitive radiotherapy and chemotherapy for stage IE and IIE nasal natural killer/T-cell lymphoma. For patients with cervical lymph node metastasis, further investigation of new chemotherapy regimens is necessary to reduce the distant metastasis.

• Genomics & Informatics
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• 제14권4호
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• pp.205-210
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• 2016

Interleukin-10 (IL10) plays an important role in initiating and maintaining an appropriate immune response to non-Hodgkin lymphoma (NHL). Previous studies have revealed that the transcription of IL10 mRNA and its protein expression may be infl uenced by several single-nucleotide polymorphisms in the promoter and intron regions, including rs1800896, rs1800871, and rs1800872. However, the impact of polymorphisms of the IL10 gene on NHL prognosis has not been fully elucidated. Here, we investigated the association between IL10 polymorphisms and NHL prognosis. This study involved 112 NHL patients treated at the National Cancer Center, Korea. The median age was 57 years, and 70 patients (62.5%) were men. Clinical characteristics, including age, performance status, stage, and extra-nodal involvement, as well as cell lineage and International Prognostic Index (IPI), were evaluated. A total of four polymorphisms in IL10 with heterozygous alleles were analyzed for hazard ratios of overall survival (OS) and progression-free survival (PFS) using Cox proportional hazards regression analysis. Diffuse large B-cell lymphoma was the most common histologic type (n = 83), followed by T-cell lymphoma (n = 18), mantle cell lymphoma (n = 6), and others (n = 5). Cell lineage, IPI, and extra-nodal involvement were predictors of prognosis. In the additive genetic model results for each IL10 polymorphism, the rs1800871 and rs1800872 polymorphisms represented a marginal association with OS (p = 0.09 and p = 0.06) and PFS (p = 0.05 and p = 0.08) in B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). These findings suggest that IL10 polymorphisms might be prognostic indicators for patients with B-cell NHL treated with R-CHOP.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1585-1588
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• 2014

Background: Data regarding childhood and adolescent non Hodgkin lymphomas in Iran are limited. The aim of this study was to assess the epidemiological and histomorphological features and survival of affected patients in our center. Materials and Methods: The clinicopathologic features and outcome of 44 children and adolescents with non Hodgkin lymphoma diagnosed during 2004-2012, were investigated retrospectively. The influence of potential prognostic parameters in overall survival was investigated by log-rank test and Cox regression analysis. Results: The mean age at presentation was $13.8{\pm}6.16$ years with a male predilection (M: F=3:1). Malignant lymphoma, not otherwise specified, diffuse large cell lymphoma and Burkitt lymphoma were the three most common histological types observed. The tumors were 36.4% intermediate grade, 27.3% high grade and 34.1% belonged to the malignant lymphoma not otherwise specified group. Immunohistochemistry findings were available in 39 cases. Out of these cases 33 (84.6%) had B cell lineage, 4 (10.25%) T cell lineage and 2 (5.12%) of the cases belonged to miscellaneous group. 3 year and 5 year survivals were 48% and 30% respectively and median survival was 36 months (95%CI=21.7-50.3 months). Overall survival in patients with high grade tumors was 19.5 months, in the intermediate group,79 months, and for malignant lymphomas not otherwise specified it was 33.6 months (p value=0.000). Conclusions: The survival rate for children and adolescents with non Hodgkin lymphomas at our center during 2004-2012 was at a low level.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.83-86
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• 2015

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkins lymphoma (NHL), accounting for approximately 25% of NHL cases. The aim of this study was to evaluate the association between the BCL6 and MUM1 gene expression and patient prognosis and stage. Materials and Methods: After ethical approval, in a cross-sectional study, tissue samples of 80 patients with diffuse large B-cell lymphoma were analyzed for BCL6 and MUM1 gene expression. Immunohistochemical staining was performed with division into categories of 0-5%, 5-25%, 26-50%, 51-75% and more than 75%. Other clinical and histological information such as lymph node involvement, T-stage, B symptoms and patient outcome were also recorded. Data were analyzed with SPSS version 16 and a P-value less than 0.05 was considered significant. Results: The patient mean age was $46.9{\pm}10.5$ years ($47.6{\pm}10.7$ and $46.1{\pm}9.6$ for males and females, respectively). A significant association was seen between lymphoma stage and BCL6 (p=0.045) but not MUM1 expression (p=0.09). However, the latter was associated with mortality (p=0.006) as was also the BCL6 level (p=0.006). Conclusions: : Overexpression of MUM1 and BCL6 is associated with poor prognosis in patients with diffuse large B-cell lymphoma.

• Journal of Yeungnam Medical Science
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• 제28권2호
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• pp.187-191
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• 2011

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cells caused by the human T-cell lymphotrophic virus type I (HTLV-D. HTLV-I is endemic in some areas in Japan, the Caribbean basin, and Africa but has low prevalence in South Korea. Patients with ATLL are susceptible to opportunistic infections such as cytomegalovirus (CMV) infection, but CMV infection in chronic ATLL is uncommon. Reported herein is a case involving a 44-year-old woman with chronic ATLL who presented the symptoms of fever and diarrhea. She was suspected to have acute-type ATLL but was later diagnosed with CMV colitis.