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

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

1997 ◽  
Vol 111 (12) ◽  
pp. 1147-1150 ◽  
Author(s):  
H. Huang ◽  
J. H. Zhou ◽  
S. M. Zhou ◽  
J. H. Hu ◽  
X. H. Pan ◽  
...  

AbstractEpstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). The BHRF1 EBV protein is expressed at high levels in productively infected cells and certain latently infected cells. In order to investigate the effect of expression of BHRF1 on the biological behaviour of NPC cells, we constructed the BHRF1 high expression vector and transfected it into the NPC cell line, CNE2. Then, the alteration of proliferation and apoptotic rates in the cells were tested before and after camptothecin treatment. After treatment by camptothecin, BHRF1-CNE2cells could constantly and slowly proliferate and its apoptotic rate was less than in control groups, and the number of cells in the G phase decreased and in the S phase increased. So, it suggests that BHRF1 expression can enhance the resistibility of CNE2cells to DNA damaging agents that cause apoptosis.


2013 ◽  
Vol 19 (8) ◽  
pp. 2175-2186 ◽  
Author(s):  
Marlinda Adham ◽  
Astrid E. Greijer ◽  
Sandra A.W.M. Verkuijlen ◽  
Hedy Juwana ◽  
Sabine Fleig ◽  
...  

2012 ◽  
Vol 42 (2) ◽  
Author(s):  
Sunardo Budi Santoso ◽  
Muhardjo M ◽  
Made Setiamika ◽  
Imam Prabowo ◽  
Dyah Ratna Budiani

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.


2020 ◽  
Vol 18 (4) ◽  
pp. 348-353
Author(s):  
Suli Lu ◽  
Jun Zhang ◽  
Yue Wang

Epstein Barr virus-positive lymphoma results from the loss of homeostatic balance between Epstein Barr virus and immune cells. In this study, we investigated the mechanism underlying reduction in Epstein Barr virus-positive lymphoma cell proliferation and apoptosis by silymarin, an anti-inflammatory/antioxidant molecule extracted from Silybum�marianum (milk thistle). We examined the effect of silymarin on Raji cell proliferation, apoptosis, the expression of latent membrane protein�1, the proteins related to apoptosis, and the activation of nuclear factor kappa-B. Results showed that silymarin inhibited the proliferation and promoted apoptosis of Raji cells in a concentration-dependent manner. Also, silymarin reduced phosphorylated inhibitor of nuclear factor kappa-B and p65 levels. Silymarin treatment elevated latent membrane protein 1 expression and knockdown of this protein led to increased proliferation inhibition and apoptosis by silymarin. In conclusion, nuclear factor kappa-B and latent membrane protein 1 knockdown could work in concert with silymarin in suppressing Epstein Barr virus-positive lymphoma cell proliferation and inducing apoptosis.


2021 ◽  
Vol 11 ◽  
Author(s):  
Lisheng Zhu ◽  
Tao Ouyang ◽  
Ying Xiong ◽  
Li Ba ◽  
Qiuting Li ◽  
...  

BackgroundIn this study, we evaluated the prognostic value of the plasma levels of Epstein-Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma (NPC) at different treatment stages.MethodsWe retrospectively analyzed the Data of 206 patients with NPC. Pre-neoadjuvant chemotherapy (pre-NACT), post-NACT, post-radiotherapy, and post-treatment plasma EBV DNA levels were used to establish prognostic nomograms. The concordance index (C-index) and calibration curves were used to compare the prognostic accuracy of the nomograms. The results were confirmed in a validation cohort consisting of patients who were tested for EBV DNA levels at all four stages of treatment. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Survival differences were calculated using the log-rank test.ResultsEBV DNA-positive patients had worse 3-year PFS and 5-year OS than EBV DNA-negative patients; this was true for pre-NACT (PFS: 82.7% vs. 57.3%, P < 0.001; OS: 90.9% vs. 68.7%, P = 0.08) and post-NACT (PFS: 85.0% vs. 50.6%, P < 0.001; OS: 91.7% vs. 65.7%; P = 0.001) EBV DNA levels but not for post-radiotherapy (PFS: 72.2% vs. 60.9%, P = 0.192; OS: 73.1% vs. 77.2%, P = 0.472) or post-treatment (PFS: 77.3% vs. 59.2%, P = 0.063; OS: 77.5% vs. 79.7%, P = 0.644) levels. Nomograms combining pre-NACT and post-NACT EBV DNA levels had a superior prognostic ability than those of post-radiotherapy and post-treatment EBV DNA levels.ConclusionPre-NACT EBV DNA levels combined with post-NACT EBV DNA levels can more reliably predict survival outcomes in patients with NPC.


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