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Abstrak :
Latar belakang: Kanker nasofaring merupakan keganasan yang unik dimana angka kejadiannya termasuk jarang disebagian besar negara, namun endemis di wilayah tiongkok selatan, dan asia tenggara termasuk Indonesia. Histopatologi kanker nasofaring di daerah endemik biasanya merupakan karsinoma jenis tidak berkeratin tidak berdiferensiasi dan selalu terkait dengan infeksi EBV. Berbagai jenis protein virus diekspresikan pada infeksi laten EBV termasuk EBNA1 dan LMP1 mungkin berkontribusi dalam perkembangan kanker. Oleh karenanya, kami ingin menginvestigasi peran onkoprotein virus tersebut terhadap agresivitas dan respon terapi kanker nasofaring. Metode: Spesimen biopsi jaringan dan darah yang diambil dari pasien kanker nasofaring diukur kadar EBNA1 dan LMP1 dengan menggunakan pemeriksaan ELISA kit masing-masing dari DRG® dan MyBioSource® kemudian dikorelasikan dengan voume tumor dan KGB terlibat yang dinilai berdasarkan delineasi berbasis pencitraan 3D. Pasien kemudian menjalani terapi standar, dan dilakukan penilaian 3 bulan paska terapi. Respon terapi akan dinilai hubungannya dengan kadar EBNA1 dan LMP1. Hasil: 23 subjek dimasukan kedalam studi, 69,5% berada pada stadium IVA keatas, dengan mayoritas laki-laki sebanyak 61%. Median volume tumor primer dan volume KGB masing masing 41,4cc (13,2-128,8) dan 40,1cc (1,2-633,5). Uji korelasi Spearman mendapatkan hubungan bermakna (p=0,032) antara kadar LMP1 jaringan dan volume tumor sebelum terapi (r=0,448). Tren korelasi yang moderat terlihat pada kadar EBNA1 di jaringan dengan di darah, kadar EBNA1 di jaringan dengan volume tumor primer, kadar EBNA1 di darah dengan volume KGB, serta Kadar LMP1 baik di jaringan maupun di darah dengan volume KGB, meskipun secara keseluruhan tidak bermakna secara statistik. Sementara itu, pengaruh kadar LMP1 dan EBNA1 terhadap respon terapi belum dapat disimpulkan. Kesimpulan: Semakin tinggi kadar LMP1 di jaringan tumor akan diikuti oleh semakin besarnya volume tumor primer nasofaring. Korelasi moderat tidak signifikan pada variabel lain mungkin diakibatkan oleh jumlah sampel yang kurang. Penambahan besar sampel diperlukan untuk konfirmasi signifikansi dari korelasi tersebut. ......Background: Nasopharyngeal cancer is an unique malignancy where the incidence is rare in most countries but endemic in Southern China and Southeast Asia, including Indonesia. The histopathology of nasopharyngeal cancer in endemic areas is usually an undifferentiated nonkeratinizing type carcinoma and is always associated with EBV infection. Various viral proteins are expressed in latent EBV infection, including EBNA1 and LMP1. These viral oncoproteins may contribute to cancer development, but they are not always be defined. Therefore, we want to investigate the role of these viral oncoproteins when it comes to the aggressivity and treatment response of nasopharyngeal cancer. Methods: Tissue biopsy and blood specimens taken from nasopharyngeal cancer patients were measured for EBNA1 and LMP1 using the ELISA kit examination from DRG® and MyBioSource® respectively, then correlated with primary tumor and nodal volume, which was calculated by delineation based on 3D imaging. Patients then underwent standard therapy, and was assessed 3 months post-therapy. Response to therapy will be assessed in relation to levels of EBNA1 and LMP1. Results: 23 subjects were included in the study, 69.5% was at stage IVA and above with the majority being males (61%). The median primary tumor and lymph node volume were 41.4cc (13.2-128.8) and 40.1cc(1,2-633.5), respectively. Spearman correlation test found a significant relationship (p=0.032) between tissue LMP1 levels and tumor volume before therapy (r=0.448). A moderate correlation trend was seen in EBNA1 levels in tissue with blood, EBNA1 levels in tissue with primary tumor volume, EBNA1 levels in blood with lymph node volume, and LMP1 levels both in tissue and in blood with lymph node volume, although overall it was not statistically significant. Meanwhile, the effect of LMP1 and EBNA1 levels on the response to therapy cannot be concluded. Conclusion: The higher the level of LMP1 in the tumor tissue, the larger the volume of primary nasopharyngeal tumor will be. Moderately insignificant correlation on the other variables may be caused by a small number of samples. The addition of the sample size is needed to confirm the significance of the correlation.

Abstrak :
Latar belakang: kanker nasofaring (KNF) adalah keganasan yang umum dijumpai pada nasofaring. Cukup banyak bukti menunjukkan adanya keterkaitan KNF dengan sistem kekebalan tubuh. Tidak semua subset sel T merupakan sel T efektor. Sel T regulator (TReg) yang merupakan salah satu subset dari sel T, memiliki peran penting dalam mengatur imunitas anti tumor. Sampai saat ini belum dapat disimpulkan bahwa keberadaan sel TReg pada lokasi tumor pasti akan memicu pertumbuhan tumor. Akan tetapi, adanya sel T CD4+ dan CD8+ tentunya berpengaruh terhadap kontrol perkembangan tumor. Studi ini bertujuan untuk menilai karakterisitik CD4, CD8 dan FOXP3 pada pasien KNF dan hubungannya terhadap agresivitas tumor. Metode: penelitian ini merupakan studi kohort prospektif. Sel TReg dinilai menggunakan marker FOXP3. Jumlah protein CD4, CD8 dan FOXP3 pada jaringan biopsi tumor dideteksi dan diukur dengan ELISA. Volume tumor primer dan volume total metastasis kelenjar getah bening regional didapatkan dari proses delineasi dengan pencitraan 3D. Spearmen-rho test digunakan untuk menilai korelasi antara CD4, CD8 dan FOXP3 dengan volume tumor primer dan volume total metastasis kelenjar getah bening regional. Hasil: Sebanyak 23 subjek penelitian (14 pria dan 9 wanita) terkumpul berdasarkan kriteria inklusi dan eksklusi. Stadium KNF terbanyak pada studi ini adalah stadium IV (AJCC edisi ke-8). Analisis dengan uji Spearman menunjukkan korelasi kuat antara konsentrasi protein FOXP3 dan volume tumor primer (p=0.02, r=0.60), dan juga antara konsentrasi protein CD8 dan volume tumor primer (p=0.00, r=0.81). Menariknya, juga ditemukan korelasi antara konsentrasi CD8 dan FOXP3 (p=0.00, r=0.85). Tidak ditemukan korelasi antara konsentrasi protein CD4, CD8 dan FOXP3 dengan volume total metastasis kelenjar getah bening regional. Tidak ditemukan juga korelasi antara konsentrasi FOXP3 dan stadium KNF. Sayangnya, belum dapat disimpulkan hubungan antara konsentrasi FOXP3 dan respons terapi pada penelitian ini. Kesimpulan: Keberadaan sel TReg berpengaruh terhadap agresivitias lokal tumor yang ditandai dengan peningkatan volume massa tumor primer. Korelasi antar konsentrasi CD4, CD8 dan FOXP3 memberikan gambaran interaksi dan mekanisme respons imunitas tubuh dalam menjaga keseimbangan antara sel T efektor dan sel T regulator. ......Background: nasopharyngeal cancer (NPC) is a common malignancy found in the nasopharynx area. There is quite a lot of evidence showing a link between NPC and the immune system. Regulatory T cells (TReg), a subset of T cells, have an essential role in regulating anti-tumor immunity. It has not been confirmed that TReg cells at the tumor site will trigger tumor growth. However, the presence of CD4+ and CD8+ T cells certainly affects the control of tumor growth. This study aims to assess the characteristics of CD4, CD8, and FOXP3 in NPC patients and their relationship with tumor aggressiveness. Methods: a prospective cohort study was conducted on 23 subjects (14 men and 9 women) based on the inclusion and exclusion criteria. TReg cells were assessed using the FOXP3 marker. The number of CD4, CD8, and FOXP3 proteins in tumor biopsy tissue was detected and measured by ELISA kit (MBS2702975, MBS165145, MBS162054). The volume of the primary tumor and the total volume of regional lymph node metastases were obtained from the delineation process based on 3D imaging. Spearmen-rho test was used to assess the correlation of CD4, CD8, and FOXP3 with primary tumor volume and total volume of regional lymph node metastases. Results: A total of 23 study subjects (14 men and 9 women) were collected based on the inclusion and exclusion criteria. The most common NPC stage in this study was stage IV (AJCC 8th edition). Analysis by the Spearman-rho test showed a strong correlation between; concentration of FOXP3 protein and primary tumor volume (p=0.02, r=0.60) and the concentration of CD8 protein and primary tumor volume (p=0.00, r=0.81). Interestingly, a correlation was also found between the concentration of CD8 protein and FOXP3 (p=0.00, r=0.85). There was no correlation between CD4, CD8, and FOXP3 proteins and the total volume of regional lymph node metastases. There was also no correlation between FOXP3 concentration and NPC stage. Unfortunately, it is impossible to conclude the relationship between FOXP3 concentration and treatment response in this study. Conclusions: the presence of TReg cells affects the local aggressiveness of the tumor, which is characterized by an increase in the volume of the primary tumor. The correlation between CD4, CD8, and FOXP3 concentrations provides an overview of the interactions and mechanisms of the body's immune response to maintain a balance between effector T cells and regulatory T cells.