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Abstrak :
Latar belakang: Alfa fetoprotein (AFP) merupakan antigen onkofetal yang berperan penting dalam perkembangan ontogenik dan onkogenik. Kadar AFP dalam darah pasien hepatocellular carcinoma (HCC) diketahui meningkat dibandingkan orang sehat. Publikasi terakhir menunjukkan bahwa AFP menyebabkan disfungsi sel dendritik derivat monosit sebagai antigen presenting cell (APC) yang dapat mengakibatkan respon antitumor menjadi tidak efisien. Penelitian pendahuluan ini bertujuan untuk mengetahui apakah efek AFP terhadap disfungsi sel dendritik derivat monosit sebagai APC adalah melalui jalur sinyal NF-κB dengan menggunakan lipopolisakarida (LPS) sebagai penginduksi aktifasi NF-κB. Metode: Sel monosit dikultur dalam medium yang mengandung GM-CSF (800 ng/mL) dan IL-4 (1000 ng/mL) dengan atau tanpa penambahan AFP dan diinkubasi selama enam hari agar berdiferensiasi menjadi sel dendritik imatur. Sel dendritik matur kemudian diperoleh dengan menambahkan LPS ke kultur dan diinkubasi selama 30 menit. Deteksi translokasi NF-κB dilakukan menggunakan uji imunofluoresens (IFA). Hasil: Pada kelompok kontrol, induksi LPS menyebabkan terjadinya translokasi NF-κB sedangkan kelompok AFP menunjukkan hasil yang berlawanan yaitu translokasi NF-κB tidak terjadi. Kesimpulan: Penelitian ini menunjukkan bahwa AFP mencegah aktifasi dan translokasi NF-κB sehingga menyebabkan gangguan fungsi sel dendritik derivat monosit sebagai APC. Hasil yang diperoleh diharapkan memberikan pemahaman baru mengenai peran AFP dalam mekanisme supresi respon antitumor.

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Background: Alpha fetoprotein (AFP) is a tumor-associated Ag that has a function in both ontogenic and oncogenic growth and its serum level is elevated in patients with hepatocellular carcinoma (HCC). A recent study showed that the immunoregulatory effect of AFP was through impairment of dendritic cell function as antigen presenting cell (APC), a mechanism that is known to hamper efficient antitumor response. However, the underlying intracellular mechanism of action of AFP required elucidation. As an initial step to determine the signaling pathway of AFP, we analyzed whether LPS induced NF-κB translocation occured in AFP-treated monocyte-derived dendritic cell (MDDC), which was induced by lipopolysaccharide (LPS). Methods: Monocytes were cultured in GM-CSF (800 ng/mL) and IL-4 (1000 ng/mL) containing medium and incubated for six days to generate immature MDDCs with or without the presence of AFP. Mature MDDC was generated by stimulation of the immature MDDC with LPS for another 30 minutes. The analysis of NF-κB translocation was measured by fluorescent microscopy. Results: Following activation of MDDC by LPS, the control group showed a marked nuclear staining of NF-κB. However, the AFP-treated group showed negative nuclear staining similar as observed in unactivated MDDC. Conclusion: This study demonstrated that AFP prevented the activation and nuclear translocation of NF-κB and subsequently might cause the impairment of MDDC function as APC. This finding provides a new insight on the role of AFP in the suppression mechanism of anti tumor immune response.

Abstrak :
Publikasi terakhir menunjukkan bahwa AFP menyebabkan disfungsi sel dendritik asal monosit MDDC sebagai antigen presenting cell APC . Disfungsi ini memiliki ciri seperti berkurangnya ekspresi beberapa molekul permukaan sel dan sitokin yang berperan penting dalam fungsi sebuah sel dendritik mature mDC . AFP juga, dalam peranannya sebagai faktor sel tumor, meningkatkan toleransi terhadap sel tumor dengan cara menginduksi fungsi regulatori dari sistem imun. Tujuan studi ini adalah untuk mendapatkan gambaran yang lebih jelas lagi tentang efek AFP terhadap DC dalam aktivasi respon imun antitumor dan induksi toleransi imun terhadap tumor. Metode: Sel monosit dikultur dalam medium yang mengandung GM-CSF dan IL-4 dan diinkubasi selama 6 hari agar berdiferensiasi menjadi DC immature imDC . AFP ditambahkan pada kelompok perlakuan di awal kultur. Di hari ke-6, dilakukan pengamatan kontak induksi antara LPS dan imDC dengan LPS binding assay menggunakan flow cytometry. DC mature mDC kemudian diperoleh dengan cara penambahan lipopolysaccharide LPS ke kultur dan inkubasi selama 48 jam. Di hari ke-8 dilakukan pengamatan molekul permukaan DC berdasarkan analisa ekspresi HLA-DR, CD11c, CD40, CD83, CD80, dan CD86 menggunakan flow cytometry. Di hari yang sama, juga dilakukan kuantifikasi sitokin TGF-? pada medium kultur dengan metode ELISA. Sel dendritik selanjutnya dikulturkan bersama dengan PBMC autolog dalam kultur MLR selama 5 hari. Di hari ke-13, proliferasi sel T naive CD4 yang diinduksi oleh DC diamati berdasarkan dilusi Carboxyfluorescein succinimidyl ester CFSE menggunakan flow cytometry. Hasil: Penambahan AFP pada awal kultur MDDC menurunkan jumlah kontak induksi antara LPS dan imDC, menurunkan ekspresi molekul fungsional HLA-DR, CD40, CD80, CD86, dan CD83 pada permukaan mDC, meningkatkan kuantitas sekresi sitokin TGF-? oleh DC, dan menurunkan jumlah proliferasi total sel T CD4 naive yang diinduksi oleh DC. Kesimpulan: AFP mempengaruhi karakteristik dan fungsi kerja DC melalui berbagai cara pada tahap yang berbeda-beda, yang secara garis besarnya menurunkan respon imun tipe efektor dan meningkatkan respon imun tipe regulator. Hal ini diyakini mengakibatkan toleransi terhadap antigen, yang bersifat mendukung survivabilitas sel tumor pada kasus HCC dengan kadar AFP tinggi. ...... Recent publications showed that AFP causes the dysfunction of monocyte derived dendritic cell MDDC as in its role as antigen presenting cell APC . This dysfunction is characterized by the lack of expression of several stimulator molecules and cytokines that play important roles in the function of mature dendritic cells mDC . AFP also, in its role as a tumor factor, promotes tolerance towards tumor cells by inducing regulatory functions of the immune system. The purpose of this study is to obtain a clearer picture regarding effects of AFP in the stimulation of antitumor immune response and the induction of immune tolerance towards tumor. Methods Monocytes was cultured in medium contains GM CSF 800 ng ml and IL 4 1000 ng ml and incubated for six days to generate immature DC imDC . AFP was added into the treatment group at the beginning of the culture. On the 6th day, induction contact between LPS and imDC was observed with LPS binding assay by flow cytometry. Mature DC mDC was generated by addition of lipopolysaccharide LPS into the culture and incubation for another 48 hours. On the 8th day, DC surface markers was observed based on the expression of HLA DR, CD11c, CD40, CD83, CD80, and CD86 by flow cytometry. On the same day, cytokine TGF in the medium was also quantified by ELISA method. Dendritic cells are then combined with autologous PBMC in MLR culture for 5 days. On the 13th day, the proliferation of DC induced naive CD4 T cells was observed based on CFSE dilution by flow cytometry. Results Addition of AFP in early MDDC culture decreases the induction contact between LPS and imDC, decreases the expressions of functional molecules HLADR, CD40, CD80, CD86, and CD83 on mDC surface, increases the quantity of cytokine TGF secretion by DC, and decreases the total proliferation of DC induced naive CD4 T cells. Conclusion AFP alters characteristics and functions of DC through various ways and within different phases, which decreases the effector immune responses and increases the regulatory immune response in overall. This allegedly leads to tolerance towards antigens and is supportive towards the survivability of tumor cells in cases of HCC patients showing high level of AFP.

Abstrak :
Latar Belakang: Tumor sel germinal mediastinum merupakan kelompok neoplasma gonad yang sensitif terhadap kemoterapi, namun agresif dan memiliki prognosis buruk. Penegakkan diagnosis dini yang tepat adalah hal yang penting dan salah satunya adalah dengan penilaian penanda tumor alpha fetoprotein (AFP) dan beta human chorionic gonadotropin (ßHCG). Metode: penelitian ini dilakukan dengan desain uji diagnostik dengan pendekatan potong lintang terhadap pasien tumor sel germinal nonseminoma mediastinum di RSUP Persahabatan sejak Januari 2015 hingga Desember 2022 dengan mengukur kadar Alfa Fetoprotein dan Human Chorionic Gonadotropin serum dan dilakukan pemeriksaan histopatologi. Analisis data dilakukan untuk menguji sensitivitas, spesifisitas, nilai duga positif, nilai duga negatif, akurasi diagnostik, dan analisis kurva receiver operating characteristic (ROC). Hasil: Dari total 362 subjek yang memenuhi kriteria inklusi, dari kedua penanda tumor AFP dan ßHCG didapatkansensitivitas 90,77% (IK 95% 80,98% - 96,54%), spesifisitas 97,98% (IK 95% 95,65% - 99,26%), nilai duga positif 90,77% (IK 95% 81,61% - 95,61%), nilai duga negatif 97,98% (IK 95% 95,77% - 99,05%), rasio kekerapan positif 45,4 (IK 95% 20,27 – 99,58), rasio kekerapan negatif 0,09 (IK 95% 0,04 – 0,2), serta nilai akurasi diagnostik sebesar 96,69% (IK 95% 94,28% - 98,28%). Kesimpulan: Pemeriksaan kadar Alfa fetoprotein dan ßhuman chorionic gonadotropin memiliki akurasi 96,69%, sensitivitas 90,77% spesifisitas 97,98%, nilai duga positif 90,77%, nilai duga negatif = 97,98% dalam penegakkan diagnosis tumor sel germinal nonseminoma mediastinum ......Background: Mediastinal germ cell tumors are a group of gonadal neoplasms that are sensitive to chemotherapy, but very aggressive and have poor prognosis. Early and correct diagnosis is important, one of them is by measuring tumor markers in serum: alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (βHCG). Method: This study was conducted with a diagnostic test with a cross sectional approach design on patients with mediastinal germ cell tumors at RSUP Persahabatan from January 2015 to December 2022, and also assessment of tumor markers alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (βHCG) serum and histopathology examination. Data analysis was carried out to find the sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and receiver operating characteristic (ROC) Results: Of a total of 362 eligible subjects, the sensitivity was 90.77% (95% CI 80.98% - 96.54%), the specificity was 97.98% (95% CI 95.65% - 99.26%), the positive predictive value was 90.77% (95% CI 81.61% - 95.61%), the negative predictive value was 97.98% (95% CI 95.77% - 99.05%), the positive likelihood ratio was 45.4 (95% CI 20.27 - 99.58), the negative likelihood ratio was 0.09 (95% CI 0.04 - 0.2), and the diagnostic accuracy was 96.69% (95% CI 94.28% - 98.28%). Conclusion: the sensitivity was 90.77%, the specificity was 97.98%, the positive predictive value was 90.77%, the negative predictive value was 97.98%, and the diagnostic accuracy was 96.69%.

Abstrak :
Karsinoma hepatoseluler (KHS) adalah salah satu kanker dengan laju mortalitas tertinggi di dunia. Kadar serum alfa-fetoprotein (AFP) dapat digunakan sebagai biomarker untuk menegakkan diagnosis dini. Tetapi, perbandingan antara kadar serum AFP dan KHS dengan etiologi infeksi virus dan etiologi non infeksi virus belum diketahui. Mengetahui perbandingan antara kadar serum AFP dan KHS dengan etiologi infeksi virus dan etiologi non infeksi virus. Penelitian potong lintang dilakukan di RSUPN Cipto Mangunkusumo, Jakarta pada Januari-Oktober 2018 dengan melihat data rekam medis dari 287 pasien yang terdiagnosis KHS dalam periode 2013-2017. Nilai median (minimum-maksimum) dari kadar AFP pada pasien KHS dengan etiologi infeksi VHB atau VHC adalah 419 (0.8-400.000). Nilai median (minimum-maksimum) kadar AFP pada pasien KHS dengan etiologi non infeksi VHB-VHC adalah 7.18 (0.6-90.944). Terdapat perbedaan bermakna antara kadar AFP dengan KHS dengan etiologi infeksi VHB atau VHC dan etiologi non infeksi VHB-VHC. ......Hepatocellular carcinoma (HCC) is one of the highest rates of mortality in the world. Serum alpha-fetoprotein (AFP) levels can be used as a biomarker for early diagnosis. However, the comparison between serum AFP and HCC with viral infections etiology and non-viral etiology is unknown. This research aims to determine the comparison between serum AFP and HCC with viral infections etiology and non-viral aetiology. A cross-sectional study conducted in Cipto Mangunkusumo Hospital, Jakarta in January to October 2018 by reviewing 287 medical records of patients diagnosed with HCC from 2013-2017 period of time. The median (minimum-maximum) value of AFP levels in HCC patients with the etiology of HBV or HCV infection is 419 (0.8-400,000). The median value (minimum-maximum) of AFP levels in HCC patients with the etiology of non HBV-HCV infection was 7.18 (0.6-90,944). There were significant differences between AFP levels and KHS with the etiology of HBV or HCV infections and the etiology of non HBV-HCV infections.