• Title/Summary/Keyword: Age-associated B cell

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Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

  • Bodoor, Khaldon;Matalka, Ismail;Hayajneh, Rami;Haddad, Yazan;Gharaibeh, Waleed
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3037-3046
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    • 2012
  • The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors with uneven survival outcomes - germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB). In the present study, we investigated the expression of GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46 Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition, survival curves were calculated with reference to marker expression, age, sex and nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being associated with better overall survival (p = 0.02), whereas positive CD138 was linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1 had no impact on the overall survival. Among the clinical characteristics studied, diagnosis at an early age, nodal involvement and maleness were associated with a higher overall survival for DLBCL patients. Our results underline the importance of BCL-6 as a marker of better prognosis and CD138 as a marker of poor prognosis for DLBCL patients.

ESCRT, autophagy, and frontotemporal dementia

  • Lee, Jin-A;Gao, Fen-Biao
    • BMB Reports
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    • v.41 no.12
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    • pp.827-832
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    • 2008
  • Many age-dependent neurodegenerative diseases are associated with the accumulation of abnormally folded proteins within neurons. One of the major proteolytic pathways in the cell is the autophagy pathway, which targets cytoplasmic contents and organelles to the lysosomes for bulk degradation under various physiological and stressful conditions. Although the importance of autophagy in cellular physiology is well appreciated, its precise roles in neurodegeneration remain largely unclear. Recent studies indicate that components of the endosomal sorting complex required for transport (ESCRT) are important in the autophagy pathway. Reduced activity of some ESCRT subunits leads to the accumulation of autophagosomes and failure to clear intracellular protein aggregates. Interestingly, rare mutations in CHMP2B, an ESCRT-III subunit, are associated with frontotemporal dementia linked to chromosome 3 (FTD3). Mutant CHMP2B proteins seem to disrupt the fusion of autophagosomes and lysosomes in cell culture models. These findings suggest a potential mechanism for the pathogenesis of FTD3 and possibly other neurodegenerative diseases as well.

Evaluation of BCL6 and MUM1 Expression in Patients with Diffuse Large B cell Lymphoma and their Correlations with Staging and Prognosis in Iran

  • Rahimi, Hossein;Jafarian, Amirhossein;Samadi, Alireza;Meamar, Bahram;Rahmani, Shaghayegh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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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.

Clinicopathology Significance of p53 and p63 Expression in Indonesian Cervical Squamous Cell Carcinomas

  • Romus, Ilhami;Triningsih, F.X. Ediati;Mangunsudirdjo, Sagiri;Harijadi, Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7737-7741
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    • 2013
  • Background: Human papilloma virus infection is associated with genesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Roles of the p53 homolog p63 have also been postulated, E6 expression leading to TAp63b degradation allowing anchorage independent growth. Molecular studies correlated with clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and need to be clarified. Aim: To investigate expression of p53 and p63 in cervical squamous cell carcinomas in correlation with age, FIGO staging, morphology, and cancer cell proliferation. Materials and Methods: Expression of p53 and p63 immunohistochemical staining in a total of 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, was evaluated for correlation with clinicopathological parameters. The Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean p53 and p63 expression. The Spearman correlation test was applied to correlate p53 and p63 expression with that of Ki-67. A p-value of <0.05 was considered statistically significant. Results: There were significant associations between p53 expression with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki-67 expression. There were no links between p63 expression and age, morphology, FIGO staging or Ki-67. Conclusions: This study indicated that p53 has a prognostic value in cervical squamous cell carcinomas given the relation with FIGO staging.

Underutilization of Curative Treatment among Patients with Non Small Cell Lung Cancer: Experience from a Tertiary Care Centre in India

  • Malik, Prabhat Singh;Malik, Anita;Deo, Suryanarayana Venkata;Mohan, Anant;Mohanti, Bidhu Kalyan;Raina, Vinod
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2875-2878
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    • 2014
  • Background: Lung cancer is one of the commonest and most lethal cancers throughout the world. The majority of the patients present at advance stage and are not suitable for curative intent treatment. Even among patients with localized disease, there has been underutilization of curative treatment modalities. The aim of this study was to analyze the radical treatment utilization rates in patients with non small cell lung cancer (NSCLC) treated at our centre. Materials and Methods: We analyzed case records of 104 patients with a pathologically confirmed diagnosis of NSCLC having stage 1-3B disease who were treated at our centre over last 3 years, to assess the utilization of curative treatment modalities i.e. surgery or radical radiotherapy. Results: The median age of this cohort was 58 years. Out of 104 patients only 33 (31.7%) received curative intent treatment, 14 undergoing curative resection and 19 receiving radical doses of radiotherapy. The baseline characteristics of both the groups (with or without radical treatment) were not different. Major factors associated with underutilization with curative treatment were progressive disease or loss of follow up after chemotherapy and inappropriate use of TKI and/or palliative radiotherapy in patients with stage 1-3B disease. Patients who did not receive radical treatment had inferior PFS and OS than those who received radical treatment. Conclusions: In our practice we observed gross underutilization of curative intent treatment modalities in patients with NSCLCs which is associated with inferior survival.

Leu432Val Polymorphism of CYP1B1 is Not Associated with Squamous Cell Carcinoma of Esophagus - a Case-Control Study from Kashmir, India

  • Shah, Idrees Ayoub;Mehta, Promila;Lone, Mohd Maqbool;Dar, Nazir Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5337-5341
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    • 2015
  • Background: Individual susceptibility to cancer has been attributed to polymorphisms in xenobiotic metabolizing genes. To evaluate the association of the Leu432Val polymorphism of cytochrome P4501B1 (CYP1B1) with esophageal squamous cell carcinoma (ESCC), we conducted a case control study in Kashmir, India, an area with a relatively high incidence of ESCC. Materials and Methods: We recruited 404 histopathologically confirmed ESCC cases, and an equal number of controls, individually matched for sex, age and district of residence to respective cases. Information was obtained on various dietary, lifestyle and environmental factors in face to face interviews, using a structured questionnaire, from each subject. Genotypes were analysed by polymerase chain reaction, restriction fragment length polymorphism and sequencing of randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Among the three possible variants, we did not find any Leu432Leu genotype of CYP1B1 in the study population and the genotypic distribution of Val432Val and Leu432Val carriers was nearly equal in both cases (89.6% and 10.4%) and controls (88.9% and 11.1%) respectively. We did not find any risk associated with this polymorphism in the current study (OR = 0.64; 95% CI: 0.55 - 1.64). Conclusions: The study indicates that (Leu432Val) polymorphism of CYP1B1, is not associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate the findings.

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

  • Sujin Lee;Jeong In Yang;Joo Hee Lee;Hyun Woo Lee;Tae Jin Kim
    • IMMUNE NETWORK
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    • v.22 no.6
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    • pp.50.1-50.19
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    • 2022
  • Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138int B cells consisted of IgMlowIgDhigh follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138int FO B cells was confirmed by attenuated Ca2+ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138int FO B cells was distinct from that of the CD138- FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca2+ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

Multicentre Hospital-based Case-control Study of Diffuse Large B-cell Lymphoma in Shanghai, China

  • Fan, Rong;Zhang, Lu-Yao;Wang, Hong;Yang, Bo;Han, Tao;Zhao, Xiao-Li;Wang, Wei;Wang, Xiao-Qin;Lin, Guo-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3329-3334
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    • 2012
  • Background: Several potential risk factors have been identified for diffuse large B-cell lymphoma (DLBCL); however, epidemiological studies investigating the association between these risk factors and DLBCL have yielded inconsistent results. Objectives: To investigate potential medical, lifestyle, and environmental risk factors of DLBCL in Shanghai, China through a hospital-based case-control study. Method: One-hundred-and-forty-seven newly diagnosed DLBCL patients and 294 sex- and age-matched controls were recruited from 11 hospitals in Shanghai between 2003 and 2007. A standardized structured questionnaire was used to obtain patient data on demographics, medical history, family history, lifestyle, and environmental exposures. Conditional logistic regression models were used to estimate odds ratios (ORs), with 95% confidence intervals (CIs), for risk associated with each data category. Results: History of tuberculosis (TB) infection and "living on a farm" were positively associated with DLBCL (TB: OR=3.05, 95% CI: 1.19-7.80; farm: OR=1.82, 95% CI: 1.21-2.73). In contrast, taking traditional Chinese medicine was negatively associated with DLBCL (OR=0.36, 95% CI: 0.14-0.89). No significant correlation with DLBCL risk was found for any of the other potential risk factors (p>0.05), including but not limited to hair dyes, alcohol drinking, smoking, and home/workplace renovation within one year. Conclusions: Consistent with results from previous studies in other DLBCL case populations, traditional Chinese medicine appeared to have a direct or indirect protective effect against DLBCL. However, this study also identified a possible predisposition for DLBCL in TB sufferers and farmers.

Aging of Immune System (면역 반응체계의 노화)

  • Chung, Kyung Tae
    • Journal of Life Science
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    • v.29 no.7
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    • pp.817-823
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    • 2019
  • Immune system provides defense integrity of body against external invaders. In order to accomplish the important defending role immune system is composed of many different components which are regenerated continuously during lifespan. The key components are professional killing cells such as macrophage, neutrophil, natural killer cell, and cytotoxic T cell and professional blocking molecule, antibody, which is produced by plasma cell, the terminal differentiated B cell. Immune response is orchestrated harmoniously by all these components mediated through antigen presenting cells such as dendritic cells. Immune responses can be divided into two ways: innate immune response and adaptive immune response depending on induction mechanism. Aging is a broad spectrum of physiological changes. Likewise other physiological changes, the immune components and responses are wane as aging is progressing. Immune responses become decline and dysregulating, which is called immunosenescense. Immune components of both innate and adaptive immune response are affected as aging progresses leading to increased vulnerability to infectious diseases. Numbers of immune cells and amounts of soluble immune factors were decreased in aged animal models and human and also functional and structural alterations in immune system were reduced and declined. Cellular intrinsic changes were discovered as well. Recent researches focusing on aging have been enormously growing. Many advanced tools were developed to bisect aging process in multi-directions including immune system area. This review will provide a broad overview of aging-associated changes of key components of immunity.

PRIMARY EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA OF MUCOSA-ASSOCIATED LYMPHOID TISSUE IN THE ORAL CAVITY : A CASE REPORT (구강 내에 발생한 원발성 점막관련 림프양 림프종의 치험례)

  • Son, Jang-Ho;Park, Su-Won;Choi, Byoung-Hwan;Cho, Yeong-Cheol;Sung, Iel-Young;Byun, Ki-Jeong
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.31 no.1
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    • pp.77-80
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    • 2009
  • Mucosa-associated lymphoid tissue(MALT) lymphoma is thought to originate from marginal zone B-cells. In the WHO classification, Extranodal marginal zone lymphoma of MALT is classified B-cell Non-Hodgkin lymphoma. Common sites of MALT lymphoma include stomach, lung and the ocular-adnexa. Although less common in other sites, it is the most common low-grade lymphoma of the breast, thyroid, bowel skin and soft tissue. No strong age or gender predominance exists in MALT lymphoma. Dissemination to other sites can occur. In the oral cavity, MALT lymphoma is rare. Herein, we present a case of intra-oral MALT lymphoma. 66 year-old woman without any background of immunodeficiency or autoimmune disease admitted department of oral & maxillofacial surgery in Ulsan university hospital for evaluation of long-standing mild upper lip swelling. The lesion was completely resected and biopsied. Histological and immunohistochemical stains(CD3, CD5, CD20, CD21, CK) findings were used to confirm the lesion. Bone marrow biopsy was done and no bone marrow involvement was found. She did not receive chemotherapy and radiotherapy after surgery. No recurrence has been noted in the 22 months to date.