scholarly journals Korelasi ekspresi IL-6 dengan STAT3 pada metastasis penderita KNF WHO tipe 3 LMP-1 positif

2019 ◽  
Vol 49 (20) ◽  
Author(s):  
S. Soehartono ◽  
Monika Teresa Prasetyo ◽  
Hendradi Surjotomo ◽  
Hendy Setyo Yudhanto

Latar belakang: Karsinogenesis karsinoma nasofaring sangat kompleks, dan disebabkan oleh interaksi antara infeksi kronis Epstein-Barr Virus (EBV), faktor lingkungan, dan perubahan genetik serta epigenetik. Latent Membrane Protein (LMP)-1 merupakan antigen utama EBV. LMP-1 diyakini menstimulasi ekspresi sitokin yang memengaruhi perilaku sel epitel, salah satunya adalah Interleukin (IL)- 6. IL-6 akan mengaktivasi jalur Signal Transducer and Activator of Transcription (STAT)3. Peningkatan ekspresi IL-6 dan STAT3 memiliki kaitan erat dalam lingkungan mikro tumor KNF, namun peran IL-6 dan STAT3 dalam modulasi migrasi dan invasi sel KNF masih belum jelas diketahui. Tujuan: Mengetahui korelasi antara ekspresi IL-6 dan ekspresi STAT3 di jaringan nasofaring dengan metastasis penderita KNF WHO tipe III LMP-1 positif. Metode: Penelitian observasional analitik dengan pendekatan cross-sectional yang melibatkan 15 penderita KNF WHO tipe III LMP-1 positif. Pemeriksaan ekspresi LMP-1, IL-6, dan STAT3 menggunakan metode pewarnaan imunohistokimia, dan hasilnya dihitung dengan menggunakan software ImmunoRatio. Penentuan stadium klinis metastasis berdasarkan pemeriksaan klinis dan penunjang radiologis, kemudian dievaluasi nilai TNM menggunakan AJCC 2017. Hasil: Analisis statistik ekspresi IL-6 dan STAT3 menunjukkan korelasi yang signifikan (p=0,020) dengan koefisien korelasi r=0,592. Tidak terdapat perbedaan ekspresi IL-6 yang bermakna di antara penderita stadium III, IVa, dan IVb (p=0,116). Terdapat perbedaan ekspresi STAT3 yang signifikan di antara penderita dengan stadium III, IVa, dan IVb (p=0,038). Kesimpulan: Semakin tinggi ekspresi IL-6 maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif semakin meningkat. Semakin tinggi stadium klinis, maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif akan meningkat. Kata kunci: karsinoma nasofaring, Virus Epstein-Barr, LMP-1, IL-6, STAT3 ABSTRACT Background:Carcinogenesis of NPC is complex interactions among chronic EBV infection, environmental factors, genetic and epigenetic. LMP-1 is EBV’s antigen most expressed in NPC cases. LMP-1 is believed to stimulate expression of cytokines that affect the behavior of epithelial cells, i.e. Interleukin-6 (IL-6) which will activate the STAT3 pathway. Increased expression of IL-6 and STAT3 has a close relationship in tumor microenvironment of NPC patients, but the role of IL-6 and STAT3 themselves in modulation of migration and invasion of NPC cells are not yet fully understood. Purpose: To find out the correlation between IL-6 expression and STAT3 expression in the nasopharyngeal tissue of NPC patients with LMP-1 positive metastatic WHO type III. Method: Observational analytic study with cross-sectional approach involving 15 patients WHO type III LMP-1 positive NPC patients. Examination of LMP-1, IL-6, and STAT3 using immunohistochemical, and the results were calculated using ImmunoRatio. Clinical staging of metastases based on clinical examination and radiological imaging then synchronized with AJCC 2017. Result: Expressions of IL-6 and STAT3 showed significant correlation (p=0.020) with coefficient r=0.592. There were no differences in IL-6 expression among patients with stage III, IVa, and IVb (p=0.116). There were significant differences in STAT3 expression among patients with stage III, IVa, and IVb (p=0.038). Conclusion: There was a significant positive correlation between IL-6 and STAT3 in tissue from WHO type III LMP-1 positive NPC patients. The higher the clinical stage, the expression of STAT3 in the nasopharyngeal tissue of positive WHO type III LMP-1 NPC patients will increase. 

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Timothy Martin ◽  
Morgan Mweene

Background: The World Health Organization (WHO) and the Zambian Ministry of Health set out new guidelines on combination antiretroviral therapy (cART) in 2013 expanding the eligibility criteria for patients with HIV.Objectives: The primary objective were to determine when cART was initiated in HIV-positive outpatients according to clinical and immunological criteria, and to identify what proportion of patients who were eligible for cART according to 2013 WHO and 2013 Zambian cART guidelines were currently on cART.Methodology: This was a clinical audit of HIV-positive outpatients attending the cART clinic at Ndola Central Hospital in Ndola, Zambia, with retrospective cross-sectional chart review and survey design. Data were collected from clinical records and interviews with patients.Results: A total of 99% of patients eligible for cART according to 2013 guidelines were on treatment. Clinical staging of patients at initiated on cART (n = 206) was as follows: 28% clinical stage I, 21% clinical stage II, 36% clinical stage III and 15% clinical stage IV. The median CD4 count when patients were started on cART was 147 cells/mm3 .Conclusion: The results show that a majority of patients were initiated on cART late in their disease course according to immunological (CD4 < 200 cell/mm3 ) and clinical criteria (stage III or IV). However, the vast majority of patients eligible for cART were currently on treatment. The late initiation of cART appears to be a result of late diagnosis of HIV.


2019 ◽  
Vol 12 (04) ◽  
pp. 2055-2061
Author(s):  
I Ketut Suanda ◽  
I Gde Ardika Nuaba ◽  
Ni Made Alit Ardianti

Nasopharyngeal carcinoma is caused by interaction of Epstein-Barr virus chronic infection, environtment, and genetic factors. Epstein-Barr virus (EBV) infect nasopharyngeal ephitelial cell in latent period. This infection will cause mutation and further causing malignancy. This is a cross-sectional study in undifferentiated type NPC patients after hystopatological examination and were examined in RSUP Sanglah Denpasar from January 2017 to December 2018. This study is using 62 subjects who meets inclusion criteria. Univariate analysis was done to show subject characteristics which include age, gender, occupation, clinical stage, gene allele and rs3813865 polymorphism CYP2E1 gene. Mean age of subject is 48.05 years with standard deviation of 10.86 years. The youngest is 17 years old and the oldest is 73 years old. The most are men as many as 47 subjects (75.8%), and the most occupation are government employee as many as 17 subjects (27.4%). The most clinical stage of undifferentiated type NPC are stage II as many as 7 subjects (11.3%). Based on TNM, the most are T4 as many as 32 subjects (51.6%), N3 as many as 21 subjects (33.9%), and M0 as many as 60 subjects (96.8%).


2020 ◽  
Vol 2 (02) ◽  
pp. 59-61
Author(s):  
Ismi Cahyadi ◽  
Yussy Afriani Dewi ◽  
Nur Akbar Aroeman

Abstract Introduction: Nasopharyngeal carcinoma is the most found head and neck cancer, which originated from a nasopharyngeal epithelial cell, and predilection site commonly at rosen muller fossa. S100 protein inflammatory mediators are involved in the regulation of cellular processes including inflammation and malignancy. S100 protein plays a central role in the proliferation, regulation of cell apoptosis and metastasis causing continuing growth of cancer cells through activation of STAT3 by IL-6, NF-κB, ROS. Objective: This study aimed to determine the correlation between S100 protein expression levels to the clinical stage of NPC WHO type III. Method: This research is a cross-sectional analytic study. This study was held in the Anatomical Pathology Department of Hasan Sadikin Hospital from August until October 2015. The study was conducted using 29 pieces of secondary data, medical records and paraffin blocks anatomical pathology of NPC patients were examined S100 protein immunohistochemistry. Result: This study was performed from 29 subjects (18 males and 9 females). There was a strong positive correlation between histoscore S100 protein expression with clinical staging p<0.05. There is a significant correlation between S100 protein expression with the clinical stage of NPC WHO type III using double regression analysis (F=15.676, p=0.000). Conclusion: There were significant correlation S100 protein expression levels to clinical stage nasopharyngeal carcinoma WHO type III.


2009 ◽  
Vol 50 (4) ◽  
pp. 427-429 ◽  
Author(s):  
Corinne Amiel ◽  
Jérôme LeGoff ◽  
François Xavier Lescure ◽  
Marianne Coste-Burel ◽  
Claire Deback ◽  
...  

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 237 ◽  
Author(s):  
Asuka Nanbo ◽  
Harutaka Katano ◽  
Michiyo Kataoka ◽  
Shiho Hoshina ◽  
Tsuyoshi Sekizuka ◽  
...  

Infection of Epstein–Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing. We found that the biogenesis of exosomes is upregulated in type III latently infected cells compared with EBV-negative and type I latently infected cells. We also observed that viral and several specific host microRNAs were predominantly incorporated in the exosomes released from the cells in type III latency. We confirmed that multiple viral microRNAs were transferred to the epithelial cells cocultured with EBV-infected B cells. Our findings indicate that EBV infection, in particular in type III latency, modulates the biogenesis of exosomes and the profile of exosomal microRNAs, potentially contributing to phenotypic changes in cells receiving these exosomes.


Author(s):  
Humberto Jácome-Santos ◽  
Naira da Silva e Silva ◽  
Renata Gonçalves Resende ◽  
Helder Henrique Costa Pinheiro ◽  
Luiz Fernando Almeida Machado ◽  
...  

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 442-447 ◽  
Author(s):  
Paul G. Murray ◽  
Lucinda J. Billingham ◽  
Hassan T. Hassan ◽  
Joanne R. Flavell ◽  
Paul N. Nelson ◽  
...  

Abstract We have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin’s disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P = .05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P = .02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P = .18 andP = .40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.


2019 ◽  
Vol 10 (11) ◽  
Author(s):  
ShiJuan Mai ◽  
RuoWen Xiao ◽  
Lu Shi ◽  
XiaoMin Zhou ◽  
Te Yang ◽  
...  

Abstract miR-18a has been reported to be upregulated in nasopharyngeal carcinoma (NPC) tissues by microarray assays. However, the roles and the underlying mechanisms of miR-18a in NPC remain poorly understood. Here we demonstrated by real-time RT-PCR that miR-18a expression is upregulated in NPC tissues, and positively correlated with tumor size and TNM stage. Moreover, miR-18a expression could be upregulated by NF-κB activation or Epstein-Barr virus encoded latent membrane protein 1 expression. The ectopic expression of miR-18a promoted NPC cell proliferation, migration and invasion, while the repression of miR-18a had opposite effects. Candidate genes under regulation by miR-18a were screened out through a whole-genome microarray assay, further identified by a reporter assay and verified in clinical samples. SMG1, a member of the phosphoinositide 3-kinase-related kinases family and an mTOR antagonist, was identified as functional target of miR-18a. Our results confirmed that miR-18a exerts its oncogenic role through suppression of SMG1 and activation of mTOR pathway in NPC cells. Importantly, in vivo xenograft tumor growth in nude mice was effectively inhibited by intratumor injection of miR-18a antagomir. Our data support an oncogenic role of miR-18a through a novel miR-18a/SMG1/mTOR axis and suggest that the antitumor effects of antagomir-18a may make it suitable for NPC therapy.


2020 ◽  
Vol 12 (1) ◽  
pp. e2020035
Author(s):  
Yusuke Ito ◽  
Kensuke Takaoka ◽  
Kazuhiro Toyama ◽  
Yoshitaka Wakabayashi ◽  
Aya Shinozaki-Ushiku ◽  
...  

This is the first case of concurrent Mycobacterium genavense lymphadenitis and Epstein-Barr virus (EBV)-positive lymphoproliferative disorder (LPD) in the same lymph node with no immunocompromised history. M. genavense infection is a rare opportunistic infection mainly for human immunodeficiency virus (HIV)-infected patients. Although no immunodeficiency was detected in our patient, our case indicates that the immunodeficiency in the background of EBV latency type III and the immunosuppression by malignant lymphoma itself might induce the M. genavense lymphadenitis. This case highly alerts clinicians the immunosuppressive state of EBV-positive LPD with latency type III even if any serological immunodeficient factors are not detected.


Sign in / Sign up

Export Citation Format

Share Document