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"ABSTRAKLatar Belakang: Persistensi infeksi HPV onkogenik merupakan penyebab kanker serviks. Retinol sebagai mikronutrien antioksidan memiliki peran esensial dalam sistem imun mencegah persistensi. Retinol memodulasi sel T CD4+/CD8+ serta produksi sitokin. Tumor Necrosis Factor-Alpha (TNF-) adalah sitokin pro-inflamasi yang mampu mengendalikan HPV, namun pada infeksi persisten TNF- justru memicu karsinogenesis. Rasio sel T CD4+:CD8+ dan TNF- yang adekuat di awal infeksi HPV merupakan titik kunci klirens. Penelitian ini bertujuan untuk mengetahui tingkat kecukupan deposit retinol, ekspresi TNF-, dan rasio sel T CD4+:CD8+ pada kelompok serviks normal, infeksi subklinis HPV klirens, persisten, dan kanker serviks.Metode: Tingkat kecukupan deposit retinol diketahui berdasarkan pemeriksaan darah perifer dengan metode ELISA. Stimulasi spesifik epitop E6 HPV tipe 16 dilakukan pada sel sekret servikovaginal yang telah diinkubasi 24 jam, diamati ekspresi TNF- secara semikuantitatif dengan metode ELISpot. Pemeriksaan sel T CD4+ dan CD8+ dari sekret servikovaginal secara kuantitatif dengan metode flowsitometri.Hasil: Deposit retinol yang cukup pada kelompok serviks normal, infeksi subklinis HPV klirens, persisten, dan kanker serviks berturut-turut adalah 85%, 75% (OR 1,89), 33,3% (OR 11,33), dan 75% (OR 1,89). Ekspresi TNF- pada kelompok serviks normal adalah 10%, sedangkan kanker serviks 75% (OR 27,00; p<0,001). Tidak tampak ekspresi TNF- pada kelompok infeksi subklinis HPV klirens dan persisten. Rasio sel T CD4+:CD8+ yang tinggi pada kelompok serviks normal adalah 10% dan kanker serviks 25% (OR 0,33). Tidak terdapat rasio sel T CD4+:CD8+ yang tinggi pada kelompok infeksi subklinis HPV klirens (OR 1,22) dan persisten (OR 0,95). Tidak terdapat hubungan bermakna antara tingkat kecukupan deposit retinol dengan ekspresi TNF- (p=0,147), tingkat kecukupan deposit retinol dengan rasio sel T CD4+:CD8+ (p=0,726), dan rasio sel T CD4+:CD8+ dengan ekspresi TNF- (p=0,690).Kesimpulan: Penelitian ini mampu membuktikan bahwa tingkat kecukupan deposit retinol tertinggi dijumpai pada kelompok serviks normal dan ekspresi TNF- tertinggi pada kelompok kanker serviks (OR 27,00; p<0,001). Tingkat kecukupan deposit retinol terendah bukan pada kelompok kanker serviks, melainkan pada infeksi subklinis HPV persisten (OR 11,33). Tidak terdapat perbedaan bermakna pada tingkat kecukupan deposit retinol dan rasio sel T CD4+:CD8+. Terdapat perbedaan bermakna pada ekspresi TNF- antara kelompok kanker serviks dengan serviks normal (p<0,001), kanker serviks dengan infeksi HPV subklinis klirens (p=0,024), dan klirens dengan persisten (p=0,007). Tidak terdapat perbedaan bermakna ekspresi TNF- antara kelompok kanker serviks dengan infeksi HPV subklinis persisten (p=0,058). Tidak bermaknanya beberapa hasil terkait imunitas masih mungkin dikarenakan tingkat kecukupan deposit retinol kelompok kanker serviks pada penelitian ini sangat baik dimana bertentangan dengan kepustakaan.

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ABSTRACT

Background: Persistency of oncogenic-HPV infection is the cause of cervical cancer. Retinol is one of antioxidant micronutrients that plays essential roles in immune system to prevent the persistency by modulating CD4+ and CD8+T cells and cytokines production. Tumor Necrosis Factor-Alpha (TNF-) is an acute pro-inflammatory cytokine which has many crucial roles in controlling HPV. In contrast, when persistent infection occurs, TNF- induces carcinogenesis. Ratio of CD4+:CD8+ T cells and adequate TNF- production in acute HPV infection are keypoints for clearance. The aim of this research is to analyze sufficency level of retinol deposit, expression of TNF-, and ratio of CD4+:CD8+ T cells in normal cervix, clearance and persistent HPV subclinical infection, and cervical cancer group.

Methods : Sufficiency level of retinol deposit was analyzed from peripheral blood by ELISA method. The cervicovaginal secretions which had 24 hours incubated were stimulated specifically by E6 epitope HPV type-16, measuring TNF- expression semiquantitatively by ELISpot method and CD4+/CD8+ T cells quantitatively by flowcytometry method.

Results: Sufficient level of retinol deposit in normal cervix, clearance HPV subclinical infection, persistent, and cervical cancer group was 85%, 75% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89), respectively. The expression of TNF- in normal cervix group was 10%, while in cervical cancer was 75% (OR 27.00; p<0.001). There were no expression in clearance and persistent HPV subclinical infection groups. High ratio of CD4+:CD8+ T cells in normal cervix and cervical cancer group was 10% and 25% (OR 0.33). There were no high ratio of CD4+:CD8+ T cells in clearance (OR 1,22) and persistent (OR 0.95) HPV subclinical infection groups. There was no significant correlation between sufficiency level of retinol deposit and TNF- expression (p=0.147), sufficiency level of retinol deposit and ratio of CD4+:CD8+ T cells (p=0.726), ratio of CD4+:CD8+ T cells and TNF- expression (p=0.690).

Conclusions: This study was able to prove that normal cervix group has the highest retinol deposit sufficiency level and cervical cancer group has the highest TNF- expression (OR 27,00; p<0,001). The lowest of retinol deposit sufficiency level was not in cervical cancer, but in persistent HPV subclinical infection group (OR 11.33). There was no significant correlation in sufficiency level of retinol deposit and ratio of CD4+:CD8+ T cells. There was significant correlation in TNF- expression between cervical cancer and normal cervix (p<0.001), cervical cancer and clearance subclinical HPV infection (p=0.024), and between clearance and persistent group (p=0.007). There was no significant correlation in TNF- expression between cervical cancer and persistent subclinical HPV infection group (p=0.058). Not significant some results related immunity that might be due to retinol deposit sufficiency level in cervical cancer group in this study was very good, which conflicted with literatures."

"This book provides a state-of-the-art approach to the molecular basis of hematologic diseases and its translation into improved diagnostics and novel therapeutic strategies. Several representative hemato-oncologic malignancies are analyzed in detail: acute lymphoblastic leukemia, acute myeloid leukemia, B-cell Non-Hodgkin lymphomas, multiple myeloma, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. Experts in the field describe the molecular methods applied for modern diagnostics and therapies, such as hematopoietic stem cell transplantation, donor recipient matching, banking of biological material, analyses of post-transplant chimerism, and minimal residual disease monitoring. The volume concludes with an extensive section comprising thorough step-by-step protocols of molecular techniques in hematology, all of them validated in the authors? own laboratories."

"ABSTRAKLatar belakang: Human papillomavirus (HPV) merupakan etiologi kanker serviks dan kanker oral. Berbeda dengan kanker serviks, data infeksi HPV oral di Indonesia belum diketahui. Prevalensi infeksi HPV oral yang pernah diteliti pada populasi normal sebesar 1,3−9,2% dan meningkat pada pasien dengan infeksi HPV serviks (18,1%). Tujuan: Mengetahui prevalensi infeksi HPV oral pada pasien kanker serviks dan distribusi tipe HPV, serta mengevaluasi faktor yang berperan dalam terjadinya infeksi. Metode: Penelitian desain potong lintang pada 30 subjek penelitian kanker serviks. Dilakukan pengambilan sampel dari rongga mulut dan orofaring dengan menggunakan brushing untuk mendeteksi DNA HPV dengan nested-PCR elektroforesis dilanjutkan pemeriksaan genotyping HPV metode hibridisasi. Hasil: Prevalensi infeksi HPV oral pada pasien kanker serviks 56,7% dengan tipe HPV risiko tinggi ditemukan 43,3%. HPV tipe 51, 16, dan 18 merupakan tipe HPV risiko tinggi yang paling sering ditemukan di mukosa oral. Tidak didapatkan lesi oral pada seluruh subjek penelitian. Terdapat 1 subjek yang mempunyai tipe HPV yang sesuai antara oral dan serviks (11,1%). Simpulan: Hasil prevalensi infeksi HPV oral yang tinggi menunjukkan perlunya deteksi infeksi HPV oral dan mengetahui faktor risiko yang berhubungan dengan infeksi, serta perkembangannya dalam proses keganasan.

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ABSTRACTBackground: Human papillomavirus (HPV) is an etiologic agent for both oropharyngeal and cervical cancers. In contrast to cervical cancer, the data of oral HPV infection in Indonesia is not yet known. The prevalence of oral HPV infection in normal population is about 1,3−9,2% and increase in patients with cervical infection (18,1%). Objective: To evaluate the prevalence and type distributions of oral HPV infections in patients with cervical cancer, and evaluate the risk factor which contribute to its occurrence. Methods: Cross-sectional study on 30 subjects, previously diagnosed with cervical carcinoma. Oral mucosal cells were collected by brushing from their oropharyngeal area. HPV DNA detection was caried out using nested-PCR and the HPV Genotyping (HPV genoflow array test). Results: The prevalence of oral HPV infection of patients with cervical cancer is 56,7%, the high-risk HPV type prevalence is 43,3%. The HPV high risk 51, 16 and 18 were most found in oral mucosa. Clinically healthy oral mucosa without any lession was observed in all cases. Only one subject has same HPV type in oral and cervical mucosa (11,1%). Conclusion: Results show a high prevalence of oral HPV infection. It is important to detect HPV in oral and the risk factors associated with infection and progression to malignancy."

"Molecular pathology of lung cancer bridges the gap between the molecular specialist and the clinical practitioner, including the surgical pathologist who now has a key role in decisions regarding molecular targeted therapy for lung cancer. Molecular pathology of lung cancer provides the latest information and current insights into the molecular basis for lung cancer, including precursor and preinvasive lesions, molecular diagnosis, molecular targeted therapy, molecular prognosis, molecular radiology and related fields for lung cancer generally and for the specific cell types. As many fundamental concepts about lung cancer have undergone revision in only the past few years, this book will likely be the first to comprehensively cover the new molecular pathology of lung cancer. It provides a foundation in this field for pathologists, medical oncologists, radiation oncologists, thoracic surgeons, thoracic radiologists and their trainees, physician assistants, and nursing staff."