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"ABSTRACTBackground: increased serum alpha fetoprotein (AFP) levels are often found in patients with advanced hepatocellular carcinoma (HCC). Cluster Differentiation 44 (CD44) and CD90 are stem cell biomarkers that have been assumed as the early HCC markers and associated with onset and progressivity of HCC. The study related to HCC stem cell has not been available in Indonesia. The present study aimed to evaluate the expression of cancer stem cell markers (CD44, CD90) and AFP levels in patients with advanced liver disease. Methods: an observational study was conducted in 41 patients with chronic hepatitis B and/or C infection, liver cirrhosis, and HCC at dr. Saiful Anwar General Hospital. CD44 and CD90 expressions were measured with flow cytometry, and AFP serum levels with ELISA. Data on patient characteristics were evaluated using bivariate and multivariate statistical analysis (One-way ANOVA, Mann-Whitney, Chi-Square, Kruskal-Wallis). Data of CD44, CD90 and AFP were analyzed using Kruskal Wallis test with a significance value of p<0.05, and diagnostic power was analyzed using receiver operating characteristic (ROC). Results: the subjects of our study were 16 patients with chronic hepatitis, 15 patients with liver cirrhosis, and 10 patients with HCC. There was a significant difference regarding CD44+CD90+ and AFP among those three groups (p=0.001; p=0.000) specifically in chronic hepatitis compared to liver cirrhosis (p=0.002; p=0.000) and HCC (p=0.002; p=0.000) respectively. ROC analysis showed the best diagnostic power for the combination of CD44+CD90+ and AFP (AUC=0.981; p=0.000). Conclusion: there are higher expressions of CD44+CD90+ and serum AFP levels in patients with HCC compared to the other two groups (those with chronic hepatitis and liver cirrhosis). The combination of both parameters has the best diagnostic power of HCC."

"Tujuan: untuk menganalisis penanda biologi CXCR4, IL11-RA, TFF1 dan MLF1P, klinikopatologi dan profil ekspresi genetik mRNA sebagai penanda peningkatan kejadian metastasis tulang pada pasien kanker payudara stadium lanjut.Metode: studi ini merupakan penelitian potong lintang. Analisis dilakukan pada total 92 pasien kanker payudara, terdiri atas 46 pasien metastasis tulang dan 46 pasien dengan metastasis nontulang. Analisis imunohistokimia dan microarray, dilakukan pada 81 sampel formalin fixed paraffin embedded (FFPE) dari 81 pasien yang didapat. Data dikumpulkan melalui rekam medis, pemeriksaan imunohistokimia (IHK), dan microarray dengan nanoString nCounterTM.Hasil: artikel ini merupakan bagian satu dari dua tahap pelaporan hasil penelitian. Pada tahap satu diperoleh hasil analisis IHK, IL11-RA dengan cut-off ≥103,5 menunjukkan peningkatan kejadian metastasis tulang, dengan OR 3,803 (95 % interval kepercayaan [IK], 1,375-10,581), p=0,010, dan MLF1P dengan cut-off ≥83,0 menunjukkan peningkatan kejadian metastasis tulang, dengan OR 2,784 (95% IK, 1,009-7,681), p=0,048. Status ER+ menunjukkan peningkatan kejadian metastasis tulang, dengan OR 7,640 (95 % IK, 2,599-22,459), p<0,000. AUC gabungan IL-11RA, MLF1P dan ER+, mempunyai ketepatan hampir 80% (meningkat dibandingkan AUC masing-masing secara terpisah), untuk membedakan dan menjelaskan kejadian metastasis tulang, pada kanker payudara stadium lanjut.Kesimpulan: IL11-RA, MLF1P dan ER+, merupakan determinan peningkatan kejadian metastasis tulang pasien kanker payudara stadium lanjut.

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Aim: to analyze expression of biomarkers CXCR4, IL11-RA, TFF1 and MLF1P, and clinico pathology in advanced breast cancer patients with bone metastatic.Methods: this is a cross-sectional study. Analysis was done against a total of 92 breast cancer patients, including 46 bone metastatic patients and 46 non-bone metastatic patients. Immunohistochemistry and microarray analysis was performed in 81 formalin fixed paraffin embedded (FFPE) samples from 81 patients were used. Data were collected through medical records, immunohistochemistry (IHC), and microarray with nanoString nCounterTM. Results: this article is part one of a two stage reporting research results. In part one we got the results of the IHC analysis, IL11-RA with cut-off ≥103.5 showed OR 3.803 (95 % confidence interval [CI], 1.375-10.581), p=0.010, MLF1P with cut-off ≥83.0 OR 2.784 (95% CI, 1.009-7.681), p=0.048, and ER+ OR 7.640 (95 % CI, 2.599-22.459), p<0.000, were associated with bone metastastic incidences in advanced breast cancer, and were statistically significantly different. A combination of IL-11RA, MLF1P and ER+, showed an accuracy of approaching 80% to discriminate between bone metastatic and non bone metastatic in advanced breast cancer patients.Conclusion: IL11-RA, MLF1P, and ER+ were the determinants that were associated with increasing bone metastasis incidence."

"Latar Belakang : Karsinoma Sel Hati (KSH) merupakan kanker dengan prognosis yang buruk dan Indonesia termasuk negara dengan prevalensi hepatitis B yang tinggi. Performa alfa fetoprotein (AFP) sebagai penanda tumor pada surveilans KSH terutama dipengaruhi oleh etiologi penyakit hati yang mendasari. Titik potong AFP untuk surveilans KSH di Indonesia tidak berdasarkan etiologi penyakit hati yang mendasari.Tujuan : Mengetahui titik potong terbaik pemeriksaan biomarker AFP untuk surveilans KSH dengan etiologi hepatitis B kronik.Metode : Penelitian mengambil data rekam medis Divisi Hepatobilier RSUPN Dr. Cipto Mangunkusumo periode tahun 2017-2023. Sebanyak 506 subjek hepatitis B kronik semua spekturm (hepatitis B tanpa sirosis, sirosis hati, dan KSH stadium awal BCLC 0 dan A) diambil secara total sampling dalam kurun waktu 26 Juli 2023 hingga 31 Agustus 2023. Penentuan nilai titik potong AFP dilakukan dengan metode receiver operating characteristics (ROC).Hasil : Untuk surveilans KSH dengan etiologi hepatitis B, analisis kurva ROC memberikan area under the curve (AUC) didapatkan 0.792 (IK 95%, 0.719-0.866), dan titik potong dengan index Youden tertinggi adalah 8.7 ng/ml, dengan nilai sensitivitas 58%, spesifisitas 94%, nilai duga positif (NDP) 56.14%, nilai duga negatif (NDN) 94.43%. Analisis kurva ROC dilanjutkan berdasarkan status sirosis pasien. Untuk menentukan titik potong yang membedakan KSH dengan sirosis hati dari sirosis hati saja, menghasilkan AUC 0.803 (IK 95%, 0.722-0.884) dengan titik potong yang didapatkan adalah 8.6 ng/ml, dengan sensitivitas, spesifisitas, NDP, NDN, dan RK + adalah 60.5%, 92.4%, 45,10%, 95,24%, dan 7,09 masing-masing. Untuk menentukan titik potong yang membedakan KSH tanpa sirosis hati dari hepatitis B kronik tanpa sirosis hati, menghasilkan AUC 0.777 (IK 95%, 0.631-0.923) dengan titik potong yang didapatkan adalah 6.6 ng/ml yang memberikan hasil sensitivitas, spesifisitas, NDP, NDN, dan RK positif adalah 63.16%, 98.35%, 85.71%, 94.44%, dan 38.21 masing-masing.Kesimpulan : Titik potong surveilans KSH dengan etiologi spesifik hepatitis B lebih rendah dibandingkan dengan nilai titik potong AFP surveilans KSH sebelumnya yang tidak spesifik etiologi. Nilai titik potong 8.7 ng/ml menghasilkan sensitivitas dan spesifisitas terbaik untuk titik potong surveilans KSH dengan etiologi hepatitis B. Pada pasien KSH non sirosis, titik potong surveilans AFP lebih rendah yakni 6.6 ng/ml. Hal ini perlu menjadi perhatian klinisi dalam surveilans kelompok pasien hepatitis B kronik tanpa sirosis.

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Background: Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis. Indonesia is a country with a high prevalence of chronic hepatitis B infection. The performance of alpha fetoprotein (AFP) as a tumor marker in HCC surveillance is primarily influenced by the etiology of the underlying liver disease. The AFP cutoff value for HCC surveillance in Indonesia is not based on the etiology of the underlying liver disease.

Objective: To determine the best cut-off value of AFP biomarker examination for HCC surveillance in chronic hepatitis B patients.

Methods: The study took medical record data from the Hepatobiliary Division of RSUPN Dr. Cipto Mangunkusumo for the 2017-2023 period. A total of 506 chronic hepatitis B subjects of all spectrums (hepatitis B without cirrhosis, liver cirrhosis, and early stage HCC, BCLC 0 and A) were taken by total sampling in the period 26 July 2023 to 31 August 2023. Determination of the AFP cut-off value was carried out using the receiver operating characteristics (ROC) method.

Results: For HCC surveillance caused by hepatitis B virus, ROC curve analysis gave an area under the curve (AUC) of 0.792 (95% CI, 0.719-0.866), and the cut-off value with the highest Youden index was 8.7 ng/ml, with a sensitivity value of 58%, specificity 94%, positive predictive value (PPV) 56.14%, negative predictive value (NPV) 94.43%. ROC curve analysis was then performed based on the patient's cirrhosis status. ROC curve analysis to determine the cut-off point that distinguishes HCC with liver cirrhosis from liver cirrhosis alone, resulted in an AUC of 0.803 (95% IK, 0.722-0.884) with a cut-off point 8.6 ng/ml, with sensitivity, specificity, PPV, NPV, and LR+ of 60.5%, 92.4%, 45.10%, 95.24%, and 7.09 respectively. ROC curve analysis to determine the cut-off point that distinguishes HCC without liver cirrhosis from chronic hepatitis B without liver cirrhosis resulted in an AUC of 0.777 (95% CI, 0.631-0.923) with a cut-off point 6.6 ng/ml which gave sensitivity, specificity, PPV, NPV, and LR positive results of 63.16%, 98.35%, 85.71%, 94.44%, and 38.21 respectively.

Conclusion: The cut-off value of AFP in HCC surveillance on hepatitis B specific etiology is lower than the cut-off value of AFP in previous HCC surveillance which was not etiology specific. The cut-off value of 8.7 ng/ml produces the best sensitivity and specificity for the cut-off value for HCC surveillance with hepatitis B etiology. In non- cirrhotic HCC patients, the AFP surveillance cut-off point is lower than cirrhotic HCC patients (6.6 ng/ml). This needs to be of concern to clinicians in surveillance of groups of chronic hepatitis B patients without cirrhosis."

"Mouth breathing has been reported to affect gingival health in children. However, studies on the effect of mouthbreathing in adult patients are scarce. Objective: To examine the relationship between mouth breathing and gingivalcondition and to evaluate the distribution of gingival inflammation in young adult mouth breathing patients.Methods: Study groups comprised of participants with mouth breathing (test group) and nose breathing (controlgroup) patients with gingivitis. Both the groups underwent periodontal examination. PI, GI and BOP % sites wererecorded and analyzed statistically for the differences in mean values. Results: Mouth breathing patients showedhigher full mouth GI and BOP scores. Upper anterior segment in mouth breathing patients showed highest GI andBOP followed by lower anterior segment, lower posterior and upper posterior region. Conclusion: Within the limitsof present study, our findings suggest that relative to control group participants, test group i.e. patients with mouthbreathing had higher gingival inflammation and bleeding sites in upper anterior region."

"Latar belakang: Karsinoma sel hati (KSH) merupakan jenis keganasan primer hatitersering dengan gambaran histologik menunjukkan diferensiasi sel hepatoselular. Selaininsiden yang tinggi, beban yang berat dari keganasan ini adalah prognosis yang sangatburuk dengan angka rekurensi yang tinggi. Terdapat banyak faktor resiko secaraklinikopatologik yang telah diketahui mempengaruhi prognosis KSH, seperti kadar alfafetoprotein, derajat diferensiasi, dan invasi mikrovaskular. Secara molekular, mutasi p53dan β-catenin merupakan dua mutasi tersering dalam KSH. β-catenin merupakan proteinmultifungsi yang dikode oleh gen CTNNB1 yang dapat ditemukan pada 3 kompartemensel, yaitu di membran sel, sitoplasma dan inti. Jalur Wnt/β-catenin meregulasi prosesseluler yang terkait inisiasi, pertumbuhan, survival, migrasi, diferensiasi, dan apoptosis.Meski sudah banyak diketahui beberapa jalur patofisiologi molekularhepatokarsinogenesis, hubungan dengan aplikasi klinik membutuhkan pemahaman lebihmengenai hubungan sifat molekuler dan sifat fenotip tumor, terutama dalam penentuanfaktor prognosis dan pengembangan terapi target. Penelitian ini bertujuan untuk menilaiekspresi β-catenin pada KSH dan hubungannya dengan berbagai faktor prognosis yaituAFP, derajat diferensiasi dan invasi mikrovaskular.Bahan dan cara: Penelitian ini menggunakan desain potong lintang. Sampel terdiri atas35 kasus KSH yang sudah ditegakkan diagnosisnya berdasarkan pemeriksaanhistopatologik dan/atau imunohistokimia di RSCM dari Januari 2013 sampai September2019. Dilakukan pulasan β-catenin dan analisis statistik dengan uji komparatif terhadapberbagai karakteristik klinikopatologik dan faktor resiko berupa AFP, derajat diferensiasidan invasi mikrovaskular.Hasil: Terdapat perbedaan bermakna ekspresi β-catenin terhadap AFP (p=0,037) danderajat diferensiasi (p=0,043) pada KSH. Ekspresi β-catenin pada inti dengan/tanpasitoplasma lebih sering ditemukan pada kasus KSH dengan kadar AFP rendah dan derajatdiferensiasi baik-sedang. Tidak ditemukan perbedaan bermakna ekspresi β-cateninterhadap invasi mikrovaskular pada KSH (p=1,000).Kesimpulan: Terdapat perbedaan bermakna ekspresi β-catenin terhadap AFP dan derajatdiferensiasi pada KSH.

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Background: Hepatocellular carcinoma (HCC) is the most common primary livercancer, displaying histologically hepatocellular differentiation. In addition to its highincidence, the disease burden of HCC is due to its poor prognosis with high recurrencerate. Some of the previously known clinicopathologic prognostic factors of HCC includealpha-fetoprotein (AFP) level, tumor grade and microvascular invasion. At molecularlevel, p53 and β-catenin are the two most common driver mutations in HCC that aremutually exclusive. β-catenin is a multifunction protein that is encoded by CTNNB1 gen.It is found in 3 compartments of cells, which are membrane cell, cytoplasm and nucleus.Wnt/ β-catenin pathway regulates cellular process which is related to initiation, growth,survival, migration, differentiation and apoptosis. Although molecular pathogenesispathways of hepatocarcinogenesis are known, clinical application warrants moreunderstanding in terms of molecular characteristic and tumor phenotype, especially indetermining prognosis and target therapy development. This current study aims to analyzethe expression of β-catenin and its association with prognostic factors, such as AFP,tumor grade and microvascular invasion.Material and method: A cross-sectional study was conducted comprising 35 samples ofsurgically resected HCCs between January 2013 to September 2019 in CiptoMangunkusumo General Hospital. The cases were diagnosed based on histopathologicaland immunohistochemical findings and was then performed β-catenin staining. β-cateninexpression was analyzed with statistical tests to determine expression difference betweenAFP level, tumor grade and microvascular invasion.Result: There were statistically significant difference of β-catenin expression in AFPlevel and tumor grade (p=0.037 and 0.043, respectively). Nuclear with/withoutcytoplasmic expression of β-catenin was more frequently found in HCC with low AFPlevel and well-to-moderately differentiated tumors. No significant difference wasobserved in β-catenin expression between HCC with and without microvascular invasion(p=1.000).Conclusion: β-catenin expression was significantly different in AFP level and tumorgrade."

"ABSTRACTAtherosclerosis, a chronic inflammatory disease in arterial blood vessels, is one of the major causes of death in worldwide. Meanwhile, periodontal disease is a chronic inflammatory disease caused by infection with periodontal pathogens such as P. gingivalis (Porphyromonas gingivalis). Several studies have reported association between periodontal infection and atherosclerosis, but direct investigation about the effects of periodontal treatment on atherosclerosis has not been reported. We have planned Japanese local clinics to determine the relationship between periodontal disease and atherosclerosis under collaborative with medical and dental care. A prospective, multicentre, observational study was conducted including 38 medical patients with lifestyle-related diseases in the stable period under consultation at participating medical clinics and 92 periodontal patients not undergoing medical treatment but who were consulting at participating dental clinics. Systemic and periodontal examinations were performed before and after periodontal treatment. At baseline, LDL-C (low-density lipoprotein cholesterol) levels and percentage (%) of mobile teeth were positively related to plasma IgG (immunoglobulin) antibody titer against P. gingivalis with multivariate analysis. Corresponding to improvements in periodontal clinical parameters after treatment, right and left max IMT (maximum intima-media thickness) levels were decreased significantly after treatment (SPT-S: start of supportive periodontal therapy, SPT-1y: at 1 year under SPT, and SPT-3y: at 3 years under SPT). The present study has clarified our previous univariate analysis results, wherein P. gingivalis infection was positively associated with progression of atherosclerosis. Thus, routine screening using plasma IgG antibody titer against P. gingivalis and periodontal treatment under collaborative with medical and dental care may prevent cardiovascular accidents caused by atherosclerosis."

"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.

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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."

"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.

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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."

"Latar belakang: Karsinoma sel hati (KSH) merupakan salah satu kanker dan penyebab kematian akibat kanker tersering. Magnetic resonance imaging (MRI) abdomen multifase adalah modalitas pilihan untuk diagnosis KSH, karena dapat menggambarkan perubahan patofisiologi selama hepatokarsinogenesis melalui sekuens dynamic contrast enhanced (DCE), T1-weighted imaging (T1WI) dengan chemical shift imaging, T2- weighted imaging (T2WI), diffusion-weighted imaging (DWI), peta apparent diffusion coefficient (ADC), serta fase hepatobilier. Alpha fetoprotein (AFP) sebagai penanda serologis KSH terkait surveilans, diagnostik, dan prognostik, juga berperan dalam hepatokarsinogenesis dengan menunjukkan perbedaan agresivitas tumor. Penelitian ini bertujuan menganalisis hubungan antara temuan morfologi dan karakteristik KSH pada MRI dengan kadar serum AFP.Metode: Studi retrospektif ini dilakukan pada pasien KSH yang menjalani MRI abdomen multifase kontras spesifik hepatobilier dan kadar serum AFP di RSUPN dr. Cipto Mangunkusumo, serta belum menjalani prosedur pengobatan apapun. Dilakukan analisis menggunakan uji Chi Square atau uji Mutlak Fisher antara temuan morfologis dan karakteristik KSH pada MRI, serta menggunakan uji Mann-Whitney antara nilai rerata apparent diffusion coefficient (ADC) dengan kadar serum AFP.Hasil: Diperoleh 82 subyek dengan usia rerata subyek 58 tahun, diameter tumor >5cm (58,5%) dan tumor multipel (59,8%) paling banyak ditemukan, serta memiliki perbedaan proporsi yang bermakna dengan kadar serum AFP (nilai p = 0,030 dan p = 0,000). Vaskularisasi tumor, kapsul tumor, lemak intratumoral, tumor hiperintens T2, restriksi difusi, dan tumor hipointens fase hepatobilier lebih banyak ditemukan pada kadar serum AFP ≥ 100ng/mL, namun tidak ditemukan perbedaan proporsi bermakna. Terdapat perbedaan bermakna nilai rerata ADC antara 39 subyek dengan kadar serum AFP < 100ng/mL dan 43 subyek dengan AFP ³ 100ng/mL. Median nilai rerata ADC 1,19 (0,71 – 2,20) pada subyek dengan kadar serum AFP < 100ng/mL, median 0,97 (0,72 – 1,77) pada subyek dengan AFP ≥ 100ng/mL, dan nilai p = 0,003.Simpulan: Proporsi tumor berdiameter > 5cm dan tumor multipel pada subyek dengan AFP ≥ 100ng/mL secara bermakna lebih tinggi dibandingkan pada subyek dengan AFP < 100ng/mL. Nilai rerata ADC pada subyek dengan AFP ≥ 100ng/mL secara bermakna lebih rendah dibandingkan AFP < 100ng/mL. Sehingga nilai rerata ADC dapat membantu memprediksi kadar serum AFP pada pasien KSH.

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Background: Hepatocellular carcinoma (HCC) is one of the most common cancers and cancer-related death. Multiphase contrast-enhanced abdominal magnetic resonance imaging (MRI) is the modality of choice for the diagnosis of KSH, as it can depict pathophysiologic changes during hepatocarcinogenesis through sequences: dynamic contrast enhanced (DCE), T1-weighted imaging (T1WI) with chemical shift imaging, T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and hepatobiliary phase. Alpha fetoprotein (AFP) as a serological marker of HCC related to surveillance, diagnostics, and prognostics, also plays a role in hepatocarcinogenesis by showing differences in tumor aggressiveness. This study aims to analyze the relationship between morphological findings and characteristics of HCC on MRI with serum AFP levels.

Methods: This retrospective study was conducted on HCC patients who underwent hepatobiliary-specific contrast-enhanced multiphase abdominal MRI and serum AFP levels at Dr. Cipto Mangunkusumo Hospital, had not undergone any treatment procedures. Chi Square or Fisher's exact test between morphological findings and characteristics of HCC on MRI, and Mann-Whitney test between mean apparent diffusion coefficient (ADC) values and serum AFP levels were analyzed.

Results: There were 82 subjects with a mean age of 58 years, tumor size >5cm (58.5%) and multiple tumors (59.8%) were more common, had a significant difference in proportion with AFP serum levels (p value = 0.030 and p = 0.000). Tumor vascularization, tumor capsule, intratumoral fat, T2 hyperintense tumor, diffusion restriction, and hepatobiliary phase hypointense tumor were more common in serum AFP level ≥ 100ng/mL, but there was no significant difference in proportion. There was a significant difference in mean ADC between 39 subjects with serum AFP level < 100ng/mL and 43 subjects with AFP 100ng/mL. The median ADC score was 1.19 (0.71 – 2.20) in subjects with serum AFP level < 100ng/mL, median 0.97 (0.72 – 1.77) in subjects with AFP ≥ 100ng/mL, and p value is 0.003.

Conclusion: The proportion of tumors > 5cm in diameter and multiple tumors in subjects with AFP ≥ 100ng/mL was significantly higher than that in subjects with AFP < 100ng/mL. The mean value of ADC in subjects with AFP ≥ 100ng/mL was significantly lower than AFP < 100ng/mL. So that the mean value of ADC can help predict serum AFP levels in patients with HCC."

"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."