scholarly journals Pengaruh kemoterapi neoadjuvant terhadap LMP1 dan rasio CD4+/CD8+ pada karsinoma nasofaring tak-berdiferensiasi

2012 ◽  
Vol 42 (2) ◽  
Author(s):  
Sunardo Budi Santoso ◽  
Muhardjo M ◽  
Made Setiamika ◽  
Imam Prabowo ◽  
Dyah Ratna Budiani
Keyword(s):  
Immune System ◽  
Neoadjuvant Chemotherapy ◽  
Epstein Barr Virus ◽  
Regression Result ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Undifferentiated Type ◽  
Before And After ◽  
Epstein Barr ◽  
The Relationship

Background: Epstein-Barr virus (EBV) infection in undifferentiated type nasopharyngealcarcinoma (NPC) will express antigenic proteins such as LMP1 and triggering a cascade ofimmunocompetent cells (CD4+ and CD8+). The ratio of CD4+/CD8 illustrates the potential eliminationof intracellular pathogens and tumor cells. Neoadjuvant chemotherapy will suppress the growth of tumorcells and immune system cells   that leads to cellular immune decline. Objective: To know the influence ofneoadjuvant chemotherapy on the expression of LMP1, the immune system and the relationship betweenthe expression of LMP1 with the ratio of CD4+/CD8++. Method: The design was one group before andafter intervention, with 10 samples of undifferentiated NPC, biopsied before and after neoadjuvant chemotherapy, and got immunohistochemical examination. We used mouse antihuman LMP1, mouse monoclonal antihuman CD4+ and antihuman CD8 antibodies. Data were analyzed with the WilcoxonSigned Ranks test, and Spearman’s Linear Regression. Result: After neoadjuvant chemotherapy, we + found statistically significant decline in LMP1 expression (p = 0.007), CD4+ (p = 0.041) and CD8   (p= 0.005). The ratio of CD4+/CD8 increase was not statistically significant (p = 0.646). The relationshipbetween the expression of LMP1 with the ratio of CD4++/CD8was very weak (r = 0.17) and no statisticallysignificant (p = 0.646). Conclusion: Neoadjuvant chemotherapy in undifferentiated type NPC causes adecrease in the expression of LMP1 and immunological status (CD4 + +, CD8 ) and increase in the ratioof CD4+/CD8+. The relationship between the expression of LMP1 with the ratio of CD4+ was veryweak and not significant. Keywords: nasopharyngeal carcinoma, expression of LMP1, CD4+, CD8++/CD8, ratio of CD4,neoadjuvant chemotherapy.+++/CD8+  Abstrak :  Latar belakang: Infeksi Epstein-Barr virus (EBV) pada karsinoma nasofaring (KNF) jenis takberdiferensiasiakanmengekspresikan protein antigen antara lain LMP1 dan memicu hadirnyasel-selimunokompeten(CD4+ dan CD8+). Rasio CD4+/CD8 menggambarkan potensi eliminasi patogen intraseldan sel tumor. Kemoterapi neoadjuvant akan menghambat pertumbuhan sel tumor dan juga menghambatpembentukan sel-sel sistem imun tubuh sehingga berefek pada penurunan imunitas seluler. Tujuan:Mengetahui pengaruh kemoterapi neoadjuvant terhadap ekspresi LMP1, sistem imun dan hubunganantara ekspresi LMP1 dengan rasio CD4+/ CD8++. Metode: Desain penelitian one group before and afterintervention, menggunakan 10 sampel biopsi KNF tak-berdiferensiasi, sebelum dan sesudah kemoterapineoadjuvant dilakukan pemeriksaan imunohistokimia. Antibodi yang digunakan ialah antibodi mouseantihuman LMP1, monoclonal mouse antihuman CD4+ dan antihuman CD8. Data penelitian dianalisisdengan Wilcoxon Signed Ranks test, Regresi Linier dan Spearman’s dengan program statistik SPSS forWindows. Hasil: Setelah kemoterapi neoadjuvant terjadi penurunan signifikan secara statistik baikekspresi LMP1 (p=0,007); CD4+ (p=0,041), maupun CD8+ (p=0,005). Rasio CD4++/CD8 meningkat tidaksignifikan secara statistik (p=0,646).   Hubungan antara ekspresi LMP1 dengan rasio CD4 sangatlemah (r = 0,17) dan tidak signifikan secara statistik (p=0,646). Kesimpulan: Kemoterapi neoadjuvantpada KNF jenis tak-berdiferensiasi menyebabkan penurunan ekspresi LMP1 dan status imunologi(CD4+,CD8+) serta peningkatan rasio CD4+/CD8++++/CD8/CD8. Hubungan antara ekspresi LMP1 dengan rasio CD4/CD8 sangat lemah dan tidak signifikan. Kata kunci: karsinoma nasofaring, ekspresi LMP1, CD4++, CD8+, rasio CD4, kemoterapineoadjuvant.

The Clinical Significance of IGF-1R and Relationship with Epstein–Barr Virus Markers: LMP1 and EBERs in Tunisian Patients with Nasopharyngeal Carcinoma

2020 ◽  
Vol 129 (10) ◽  
pp. 1011-1019
Author(s):  
Nehla Mokni Baizig ◽  
Ben Ayoub Wided ◽  
Olfa El Amine ◽  
Said Gritli ◽  
Michele ElMay
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Immunohistochemical Method ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Epstein Barr ◽  
The Relationship

Objectives: Tunisia is in the endemic area of nasopharyngeal carcinoma. Epstein–Barr virus (EBV) based assays have been commonly used as standard markers for screening and monitoring the disease. So, it is very important to find novel factors for the early diagnostic and prognostic evaluation of this cancer. The aim of the study was to evaluate the expression of IGF-1R (Insulin Growth Factor Receptor 1), LMP 1 (Latent Membrane Protein 1) and EBERs (EBV encoded RNAs) in order to determine their correlation with clinicopathologic parameters and survival rates in patients with nasopharyngeal carcinoma (NPC). We also looked for the relationship between these biomarkers. Methods: IGF-1R and LMP1 expression was performed by means of immunohistochemical method and EBERs were detected using in situ hybridization of paraffin embedded tumor tissues of 94 patients with nasopharyngeal carcinoma and 45 non-cancerous nasopharyngeal mucosa samples. Results: Our findings demonstrated that IGF-1R was over expressed in 47.87% of NPC patients and only in 2.22% of controls. Positive LMP1 expression was detected in 56.38% of NPC patients and all NPC patients were positive for the EBV-encoded RNAs staining. A statistically significant positive correlation was observed between IGF-1R expression and the tumor size ( P < .001). Kaplan–Meier survival curves showed that NPC patients with a strong IGF-1R expression level have shorter median and 5-year Overall Survival than those with weak expression rates (100.15 vs 102.68 months, P = .08). In addition, median and 5-year Disease-Free Survival was significantly lower in the LMP1 positive NPC patients than in the LMP1 negative ones (53.38 vs 93.37 months, P = .03). Moreover, LMP1 expression correlated strongly with IGF-1R expression ( P = .018). The relationship between these two biomarkers could influence patient survival. Conclusion: IGF1-R and LMP1 could be valuable prognostic markers in Tunisian NPC patients.

scholarly journals Pengaruh kemoterapi neoadjuvant terhadap ekspresi NFκB dan c-myc pada karsinoma nasofaring jenis undifferentiated

2012 ◽  
Vol 42 (1) ◽  
Author(s):  
Farida Nurhayati ◽  
Muhardjo M ◽  
Made Setiamika ◽  
Dyah Ratna Budiani
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Epstein Barr Virus ◽  
Nuclear Factor ◽  
Barr Virus ◽  
Nuclear Factor Kappa ◽  
Nasopharyngeal Biopsy ◽  
Before And After ◽  
Nuclear Factor Kappa Beta ◽  
Epstein Barr

Background: Epstein Barr, virus ( EBV ) infection has been frequently related with Nasopharyngeal Carcinoma (NPC), this virus makes the tissue of nasopharyng express Nuclear Factor Kappa Beta  (NFκB). NFκB and c-myc are two transcriptional factor for proliferation. NFκB and c-myc are two sign system for malignancy. The administration of neoadjuvant chemotherapy may prevent the apoptosis and inhibit the proliferation. Purpose: To evaluate the effect of neoadjuvant chemotherapy upon the expression level of NFκB and c-myc in undifferentiated NPC. Method: Quasi Experimental research by one group before and after intervention design. Ten sampels were collected from nasopharyngeal biopsy tissue which had been diagnosed as undifferentiated NPC. Wilcoxon signed Ranks test and Spearman’s were used to analized data, utilizing SPSS 15.0 underwindows program. Result: After neoadjuvant chemotherapy,   there were significant increase (p=0.005) for expression of NFκB (1.11 ± 1.14 / 4.92 ± 2.79) and significant  increase for expression of c-myc (1.15 ± 0,78 / 3.04 ± 1.91). There were significant corelation between  expresion of NFκB and c-myc in undifferentiated NPC (p=0.001). Conclussion: There were significant increase in expression of NFκB and c-myc after neoadjuvant chemotherapy in undifferentiated NPC, and   significant corelation between expresion of NFκB and c-myc in undifferentiated NPC. Keywords: nasopharyngeal carcinoma, neoadjuvant chemotherapy, NFκB and c-myc   Abstrak :  Latar belakang: Patogenesis Karsinoma Nasofaring (KNF) banyak dikaitkan dengan infeksi virus Epstein Barr. Virus ini menyebabkan jaringan mengekspresikan Nuclear Factor Kappa Beta (NFκB). NFκB  dan c-myc merupakan faktor transkripsi, yang menyebabkan proliferasi jaringan. Adanya ekspresi NFκB dan c-myc merupakan dua faktor penting sebagai penanda terjadinya keganasan. Pemberian kemoterapi neoadjuvant diharapkan dapat menghambat proses proliferasi dan menyebabkan terjadinya apoptosis. Tujuan: Mengetahui pengaruh kemoterapi neoadjuvant terhadap ekspresi NFκB dan c-myc pada KNF jenis undifferentiated dan hubungan antara ekspresi NFκB dan c-myc. Metode dan bahan penelitian: Penelitian eksperimen kuasi dengan rancangan one group before and after intervention.  Sebanyak 10 sampel dari jaringan biopsi KNF jenis undifferentiated, masing-masing dilakukan pemeriksaan ekspresi NFκB dan     c-myc sebelum dan sesudah pengobatan. Analisa dengan Uji statistk Wilcoxon signed Ranks test dan Spearman’s menggunakan SPSS 15.0 program underwindow. Hasil penelitian: Setelah kemoterapi neoadjuvant terjadi peningkatan signifikan (p=0,005) ekspresiNFκB (1,11 ± 1,14 dibanding 4,92 ± 2,79) dan terjadi peningkatan signifikan (p=0.025) ekspresi c–myc (1,15 ± 0,78 dibanding 3,04 ± 1,91). Analisis hubungan antara ekspresi NFκB dengan c-myc pada KNF jenis undifferentiated memenuhi garis liniar dan signifikan (p=0,001). Kesimpulan: Terdapat peningkatan ekspresiNFκB dan c-myc sesudah kemoterapi neoadjuvant yang signifikanpada KNF jenis undifferentiated. Terdapat hubungan signifikan antara ekspresi NFκB dengan c-myc pada KNF jenis undifferentiated. Kata kunci: karsinoma nasofaring, kemoterapi neoadjuvant, NFκB dan c-myc

scholarly journals Tumor Suppressor p53 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1

2017 ◽  
Vol 91 (20) ◽  
Author(s):  
Qianli Wang ◽  
Amy Lingel ◽  
Vicki Geiser ◽  
Zachary Kwapnoski ◽  
Luwen Zhang
Keyword(s):  
Dna Damage ◽  
Tumor Suppressor ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Tumor Suppressor P53 ◽  
Viral Oncogene ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo. The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. IMPORTANCE The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and DNA damage-mediated cellular stresses. This seems to be the first report that p53 activates a viral oncogene; therefore, the discovery would be interesting to a broad readership from the fields of oncology to virology.

Repeat arrays in cellular DNA related to the Epstein-Barr virus IR3 repeat

1985 ◽  
Vol 5 (3) ◽  
pp. 457-465
Author(s):  
M Heller ◽  
E Flemington ◽  
E Kieff ◽  
P Deininger
Keyword(s):  
Epstein Barr Virus ◽  
Tandem Repeats ◽  
Protein Domain ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr ◽  
Cellular Dna ◽  
The Relationship ◽  
Simple Sequence ◽  
Tandem Arrays

We isolated clones and determined the sequence of portions of mouse and human cellular DNA which cross-hybridize strongly with the IR3 repetitive region of Epstein-Barr virus. The sequences were found to be tandem arrays of a simple sequence based on the triplet GGA, very similar to the IR3 repeat. The cellular repeats have distinct differences from the viral repeat region, however, and their sequences do not appear capable of being translated into a purely glycine-plus-alanine protein domain like the portion of the Epstein-Barr nuclear antigen coded by IR3. Although the relationship between IR3 and the cellular repeats is left unclear, the cellular repeats have many interesting features. The tandem arrays are about 1 to several kilobases long, much shorter than satellite tandem repeats and larger than other interspersed, tandem repeats. Each of the repeats is a distinct variation, perhaps diverged from a common sequence, (GGA)n. This family is present in the genomes of all species tested and appears to be a ubiquitous feature of all higher eucaryotic genomes.

Epstein-Barr virus: exploiting the immune system

2001 ◽  
Vol 1 (1) ◽  
pp. 75-82 ◽  
Author(s):  
David A. Thorley-Lawson
Keyword(s):  
Immune System ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Hypothesis: Engrafted Human Bone Marrow and Blood Cells in Culture

Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 754-758 ◽  
Author(s):  
Hans W. von Heyden ◽  
George E. Moore
Keyword(s):  
Bone Marrow ◽  
Epstein Barr Virus ◽  
Lymphoblastic Leukemia ◽  
Growth Potential ◽  
Barr Virus ◽  
Before And After ◽  
Immunosuppressed Patients ◽  
Epstein Barr ◽  
Lymphoid Cell Lines

Abstract Lymphoblasts appearing in immunosuppressed patients after bone marrow transfusion are compared to those that can be established in vitro as permanent lymphoid cell lines. It is suggested that Epstein-Barr virus (EBV) could be responsible for the recurrent "lymphoblastic leukemia" in these patients and that the transplanted cells may be a clone of nonmalignant cells that has become capable of growing without normal restraints. It is important that in future patients the transplanted cells be characterized as to morphology, chromosome constitution, relative clonability and transplantability, the presence of EBV, T or B cell-like traits, and their growth potential in immunosuppressed heterologous hosts. The antibody titer to EBV should be measured before and after leukocyte transfusion.

scholarly journals A Positive Autoregulatory Loop of LMP1 Expression and STAT Activation in Epithelial Cells Latently Infected with Epstein-Barr Virus

2003 ◽  
Vol 77 (7) ◽  
pp. 4139-4148 ◽  
Author(s):  
Honglin Chen ◽  
Lindsey Hutt-Fletcher ◽  
Liang Cao ◽  
S. Diane Hayward
Keyword(s):  
Epithelial Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Ebv Infection ◽  
Lmp1 Expression ◽  
Cell Line Hela ◽  
Epstein Barr ◽  
Phosphorylated Stat3

ABSTRACT STAT3 and STAT5 are constitutively activated and nuclear in nasopharyngeal carcinoma (NPC) cells. In normal signaling, STATs are only transiently activated. To investigate whether Epstein-Barr virus (EBV), and in particular the protein LMP1, contributes to sustained STAT phosphorylation and activation in epithelial cells, we examined STAT activity in two sets of paired cell lines, HeLa, an EBV-converted HeLa cell line, HeLa-Bx1, the NPC-derived cell line CNE2-LNSX, and an LMP1-expressing derivative, CNE2-LMP1. EBV infection was associated with a significant increase in the tyrosine-phosphorylated forms of STAT3 and STAT5 in HeLa-Bx1 cells. This effect correlated with LMP1 expression, since phosphorylated STAT3 and STAT5 levels were also increased in CNE2-LMP1 cells relative to the control CNE2-LNSX cells. No change was observed in STAT1 or STAT6 phosphorylation in these cell lines, nor was there a significant change in the levels of total STAT3, STAT5, STAT1, or STAT6 protein. Tyrosine phosphorylation allows the normally cytoplasmic STAT proteins to enter the nucleus and bind to their recognition sequences in responsive promoters. The ability of LMP1 to activate STAT3 was further established by immunofluorescence assays in which coexpression of LMP1 in transfected cells was sufficient to mediate nuclear relocalization of Flag-STAT3 and by an electrophoretic mobility shift assay which showed that LMP1 expression in CNE2-LNSX cells was associated with increased endogenous STAT3 DNA binding activity. In addition, the activity of a downstream target of STAT3, c-Myc, was upregulated in HeLa-Bx1 and CNE2-LMP1 cells. A linkage was established between interleukin-6 (IL-6)- and LMP1-mediated STAT3 activation. Treatment with IL-6 increased phosphorylated STAT3 levels in CNE2-LNSX cells, and conversely, treatment of CNE2-LMP1 cells with IL-6 neutralizing antibody ablated STAT3 activation and c-Myc upregulation. The previous observation that STAT3 activated the LMP1 terminal repeat promoter in reporter assays was extended to show upregulated expression of endogenous LMP1 mRNA and protein in HeLa-Bx1 cells transfected with a constitutively activated STAT3. A model is proposed in which EBV infection of an epithelial cell containing activated STATs would permit LMP1 expression. This in turn would establish a positive feedback loop of IL-6-induced STAT activation, LMP1 and Qp-EBNA1 expression, and viral genome persistence.

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