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Clinical, Molecular, and Histopathological Aspect of Primary Biliary Cholangitis Flora Dameria; Marini Stephanie; Ria Kodariah; Diah Rini Handjari; Ening Krisnuhoni; Nur Rahadiani
The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy Vol 20, No 3 (2019): VOLUME 20, NUMBER 3, December 2019
Publisher : The Indonesian Society for Digestive Endoscopy

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune liver disease which tends to be chronic and progressive in nature that is marked by the presence of cholangitis and small size biliary duct destruction which may cause cirrhosis or even liver failure. PBC incidence increases because PBC can now be diagnosed earlier and is due to the increasing survival rate of PBC patients. Diagnosis of PBC can be confirmed in asymptomatic state if in the indirect immunofluorescence (IIF) examination revealed AMA positive, and there is an abnormal liver function. Etiopathogenesis of PBC is multifactorial which involves genetic and environmental factors. Genetic factors which contribute to the incidence of PBC are HLA and non-HLA genes, while in the environmental factors, the triggering factors of PBC are bacterial infection and xenobiotic. Interaction of these factors causes the development of E2 subunit pyruvate dehydrogenase complex (PDC-E2) and antimitochondrial antibody (AMA) as the causing autoantigen of biliary duct desctruction in PBC, mediated by the immune system. PBC stage is divided into minimal, mild, moderate and severe. Ursodeoxycholic acid (UDCA) is the first line therapy for PBC, while obeticholic acid (OCA) and fibrate is used as the second line. Liver transplantation is the definitive therapy for PBC where disease progresses into the advanced stage, although the patients have received medical treatment.

RELA mRNA Expression in Epithelial Ovarian Cancer: Correlation with rs11820062 Gene Variant: Ekspresi mRNA RELA pada Kanker Ovarium Epitelial : Korelasinya dengan Varian Gen rs11820062 Benedikta D. Saraswati; Dwi A. Suryandari; Ria Kodariah; Dewi Sukmawati; Luluk Yunaini; Primariadewi Rustamadji; Puji Sari
Indonesian Journal of Obstetrics and Gynecology Volume 11 No. 2 April 2023
Publisher : Indonesian Socety of Obstetrics and Gynecology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32771/inajog.v11i2.1872

and its correlation to i mRNA expression in low-grade and high-grade EOC’s patients from Dr. Cipto Mangunkusumo General hospital, Indonesia. Methods: This study is cross-sectional with a total of 65 healthy subjects and 80 ovarian biopsies (15 ovarian cysts as expression calibrators, 36 low-grade EOC, and 29 high-grade EOC) were used in this study. The distribution of genotypes and alleles was analyzed using ARMS PCR. The mRNA expressions of RELA were determined by real-time polymerase chain reaction (qPCR) analysis.Results: There was no significant difference between genotype and allele distributions for RELA rs11820062 in normal and case group. RELA relative mRNA expression was significantly higher in low-grade and high-grade EOC compared to in ovarian cysts (p<0.01). RELA rs11820062 CC genotype correlated to higher RELA mRNA relative expression and the TT genotype of RELA rs11820062 correlated with lower RELA mRNA relative expression in low-grade and high-grade EOC.Conclusion: C allele in rs11820062 caused an increased expression of RELA mRNA, which individuals with CC genotype correlated with higher RELA expression in low-grade and high-grade EOC. In contrast, individuals with the T allele of RELA rs11820062 had a protective effect against EOC risk because the RELA TT genotype tended to have a lower RELA mRNA expression in EOC.Keywords: epithelial ovarian cancer, NF-kB, RELA, rs11820062.AbstrakTujuan: Mengetahui distribusi RELA rs11820062 dan korelasinya dengan ekspresi mRNA RELA pada pasien EOC low-grade dan high-grade di Rumah Sakit Dr. Cipto Mangunkusumo, Indonesia.Metode: Penelitian ini merupakan peneliatan potong lintang terhadap 65 sampel darah perempuan normal dan total 80 biopsi kanker ovarium dengan rincian: 15 kista ovarium sebagai kalibrator ekspresi, 36 EOC low-grade, dan 29 EOC high-grade. Distribusi genotipe dan alel dianalisis menggunakan ARMS PCR dan ekspresi mRNA RELA dikuantifikasi menggunakan teknik qPCR. Hasil: Tidak terdapat perbedaan distribusi genotipe dan alel antara kelompok normal dengan kasus EOC. Ekspresi relatif mRNA RELA meningkat secara signifikan pada kelompok EOC low-grade dan high-grade. Individu dengan genotipe RELA rs11820062 homozigot CC memiliki ekspresi mRNA yang lebih tinggi dibandingkan genotipe lain. Sebaliknya individu dengan genotipe TT memiliki korelasi dengan ekspresi mRNA RELA yang lebih rendah pada tipe low-grade dan high-grade EOC. Kesimpulan: Alel C pada RELA rs11820062 menyebabkan peningkatan ekspresi mRNA RELA pada pasien EO yang dilihat dari individu dengan genotipe CC cenderung memiliki ekspresi mRNA RELA yang lebih tinggi pada tipe EOC low-grade dan high-grade. Sebaliknya, individu dengan alel T RELA rs11820062 diduga memiliki efek protektif terhadap risiko EOC karena adanya korelasi antara genotipe TT dengan ekspresi mRNA RELA yang lebih rendah pada EOC.Kata kunci: kanker ovarium epitelial, NF-kB, RELA, rs11820062.

HGF/C-Met Expression in Epithelial Ovarian Carcinogenesis and Its Potential as Molecular Targeted Therapy Angeline Maranata; Tantri Hellyanti; Ria Kodariah
Indonesian Journal of Cancer Vol 17, No 3 (2023): September
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v17i3.1047

Background: The Mesenchymal-Epithelial Transition factor (C-Met) is a tyrosine kinase receptor (TKR) that binds to a ligand called Hepatocyte Growth Factor (HGF). Recent studies conducted on patients with epithelial ovarian cancer (EOC) reported that high expression of C-Met was associated with poorer clinicopathological grading and outcomes. Therefore, this study aimed to further explore the downstream pathway specifically activated when the HGF/C-Met complex was formed, the interplay between C-Met and other molecules, as well as the impact on EOC when these interactions were inhibited through designated molecular targeted therapy.Methods: The search strategy using the PubMed search engine (https://pubmed.ncbi.nlm.nih.gov/) was conducted on September 21, 2022, with the keywords: “HGF/C-Met and ovarian cancer”. The search resulted in 261 articles, and they were filtered by “published in the last five years,” which yielded 67 articles. These articles then underwent further screening, resulting in 40 articles for analysis. A systematic literature review was conducted to improve the quality of this study. Approximately 150 articles were thoroughly examined and organized using a reference manager, then 15 with the greatest impact and clinical relevance to this study were selected. Results: The HGF/C-Met complex was found to stimulate signaling pathways linked to the growth of epithelial cells and also caused the phosphorylation of tyrosine residues on other tyrosine receptors. The activation of C-Met affected the downstream pathways involving molecules associated with cell proliferation and survival, such as epidermal growth factor receptor (EGFR), p53, and KRAS. C-Met can be combined with other tyrosine kinase inhibitors in chemotherapy to enhance the initiation of cell death (apoptosis) in cancer cells.Conclusions: The HGF/C-Met mediated a signaling cascade that played an essential role in the tumorigenesis of ovarian carcinoma and had the potential to be a targeted molecular therapy in EOC

Peranan Gen HOXA10 terhadap Infertilitas Terkait Endometriosis Salinah; Ria Kodariah; Puspita Eka Wuyung
Jurnal Kedokteran dan Kesehatan : Publikasi Ilmiah Fakultas Kedokteran Universitas Sriwijaya Vol. 7 No. 1 (2020): Jurnal Kedokteran dan Kesehatan : Publikasi Ilmiah Fakultas Kedokteran Universi
Publisher : Fakultas Kedokteran Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32539/jkk.v7i1.129

Endometriosis merupakan penyakit yang bersifat progresif, kronik, rekuren dan hingga saat ini etiologi pastinya belum diketahui. Gejala yang ditimbulkan endometriosis bervariasi mulai dari asimptomatik, nyeri pelvis hingga infertilitas. Beberapa studi terakhir di bidang biologi molekular menunjukkan adanya kemungkinan endometriosis sebagai penyakit epigenetik dan salah satu gen yang diketahui mengalami perubahan epigenetik adalah gen HOXA10. Gen HOXA10 berperan mengatur reseptivitas endometrium selama proses implantasi. Keberhasilan proses implantasi merupakan salah satu faktor yang berperan pada fertilitas wanita dan Gen HOXA10 memiliki peranan penting dalam proses implantasi tersebut.Metilasi gen HOXA10 mengalami peningkatan yang signifikan pada endometrium eutopik wanita yang mengalami endometriosis. Pada endometrium wanita yang mengalami endometriosis terdapat penurunan ekspresi HOXA10 yang signifikan dan hal tersebut mengindikasikan adanya gangguan pada reseptivitas uterus yang dapat berperan dalam menurunnya tingkat kesuburan.

T HELPER 17 (Th17) AND REGULATORY T (Treg) CELLS PROFILE IN TYPE-2 DIABETES MELLITUS (T2DM) DWIKARJANTI, INDRANITA; KRISNAMURTI, DESAK GEDE BUDI; KODARIAH, RIA
BIOMA : Jurnal Ilmiah Biologi Vol. 14 No. 1 (2025): April 2025
Publisher : LPPM Universitas PGRI Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.26877/bioma.v14i1.1208

One of metabolic disorder disease is Type 2 Diabetes mellitus (DM), leading to increased glucose, cholesterol, and lipid levels in the blood. Type 2 DM results in insulin resistance within the body. Glycolysis, oxidative phosphorylation, and fatty acid are the three main metabolic pathways which provide energy for T cells. T cells will ploriferate, differentiate and become active into T Helper-17 and T regulator (Treg) cells because of these pathways. The profile of TH-17 cells and Treg cells in type 2 diabetes will be opposite in terms of the number of their populations caused by metabolic disorders in the body. Type 2 diabetes make an immunology response with increasingly number of TH-17 cells, while lack of Treg cells. Many studies have shown that diabetes mellitus as a metabolic disease effect populations of T Helper-17 and regulatory T cells. Glycolysis is the main energy metabolism becomes important factor that stimulate the proliferation and differentiation of Th-17 cells. The energy produced from this metabolism is in the form of ATP, which is the result of glucose synthesis using the Glucose transporter (GLUT). Glucose transporters (GLUT-1) are most dominantly expressed by Th-17 cells and Treg cells. Metabolic disorder causes an imbalance in the population of TH-17 cells with Treg cells. This review will explain the profiles of TH-17 and regulatory T cells in Diabetes mellitus and their relationship with body metabolism disease.

T HELPER 17 (Th17) AND REGULATORY T (Treg) CELLS PROFILE IN TYPE-2 DIABETES MELLITUS (T2DM) Indranita Dwikarjanti; Desak Gede Budi Krisnamurti; Ria Kodariah
BIOMA : Jurnal Ilmiah Biologi Vol. 14 No. 1 (2025): April 2025
Publisher : Prodi Pendidikan Biologi, FPMIPATI, Universitas PGRI Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.26877/bioma.v14i1.1208

One of metabolic disorder disease is Type 2 Diabetes mellitus (DM), leading to increased glucose, cholesterol, and lipid levels in the blood. Type 2 DM results in insulin resistance within the body. Glycolysis, oxidative phosphorylation, and fatty acid are the three main metabolic pathways which provide energy for T cells. T cells will ploriferate, differentiate and become active into T Helper-17 and T regulator (Treg) cells because of these pathways. The profile of TH-17 cells and Treg cells in type 2 diabetes will be opposite in terms of the number of their populations caused by metabolic disorders in the body. Type 2 diabetes make an immunology response with increasingly number of TH-17 cells, while lack of Treg cells. Many studies have shown that diabetes mellitus as a metabolic disease effect populations of T Helper-17 and regulatory T cells. Glycolysis is the main energy metabolism becomes important factor that stimulate the proliferation and differentiation of Th-17 cells. The energy produced from this metabolism is in the form of ATP, which is the result of glucose synthesis using the Glucose transporter (GLUT). Glucose transporters (GLUT-1) are most dominantly expressed by Th-17 cells and Treg cells. Metabolic disorder causes an imbalance in the population of TH-17 cells with Treg cells. This review will explain the profiles of TH-17 and regulatory T cells in Diabetes mellitus and their relationship with body metabolism disease.

VEGF mRNA Expression in Epithelial Ovarian Cancer: Correlation with rs699947 Gene Variant Prameswari, Yuda Nabella; Suryandari, Dwi Anita; Sukmawati, Dewi; Yunaini, Luluk; Kodariah, Ria
Journal of Biomedicine and Translational Research Vol 11, No 2 (2025): August 2025
Publisher : Faculty of Medicine, Universitas Diponegoro

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14710/jbtr.v11i2.26156

Background: Angiogenesis is the formation of new blood vessels, is crucial for cancer growth and metastasis, including in epithelial ovarian cancer (EOC). Vascular Endothelial Growth Factor (VEGF) regulates angiogenesis, and its elevated mRNA expression is linked to poor prognosis in cancer. Genetic variations, such as the rs699947 polymorphism in the VEGF gene, can affect VEGF expression and contribute to cancer progression.Objective: The primary aim of this study is to examine the distribution of the VEGF rs699947 polymorphism and its correlation with VEGF mRNA expression levels in patients with low-grade and high-grade EOC at Dr. Cipto Mangunkusumo Hospital, Indonesia.Methods: This research is a cross-sectional analysis involving 65 normal female whole blood samples and a total of 80 ovarian cancer biopsy samples, including 15 ovarian cysts as expression calibrators, along with 36 low-grade and 29 high-grade EOC samples. The distribution of genotypes and alleles of the VEGF rs699947 polymorphism was assessed through ARMS PCR analysis, while VEGF mRNA expression was quantified using real-time qPCR.Results: Significant differences were observed in both genotype (p<0,01) and allele (p=0,000) distributions between the normal and cases group. The relative mRNA expression of VEGF was significantly elevated in both low-grade and high-grade EOC. Individuals with the homozygous VEGF rs699947 AA genotype exhibited the highest mRNA expression compared to other genotypes. In contrast, individuals carrying the CC genotype showed the lowest correlation with VEGF mRNA expression in both low-grade and high-grade EOC.Conclusion: This study shows that the A allele of VEGF rs699947 is correlated with increased VEGF mRNA expression in EOC patients, particularly in those with the AA genotype. Conversely, the C allele may offer a protective effect against EOC, as the CC genotype is linked to lower VEGF mRNA expression. Genetic screening for VEGF rs699947 could facilitate early detection and inform targeted therapeutic strategies.

Analysis of H3k27me3 Expression in Malignant Peripheral Nerve Sheath Tumor (MPNST) and Other Spindle Cell Sarcoma Mimicking MPNST Yordana, William; Evelina, Evelina; Kodariah, Ria
Majalah Patologi Indonesia Vol. 32 No. 3, September 2023
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v32i3.585

Malignant Peripheral Nerve Sheath Tumor (MPNST) is a type of spindle cell sarcoma with approximately 5% of all sarcomas. Its diagnosis is challenging due to the absence of specific immunohistochemical markers. Recently, H3K27me3 was discovered as a potential specific immunohistochemical marker to differentiate MPNST from other sarcomas and distinguish between low and high-grade MPNST. Therefore, this research aims to investigate the use of the H3K27me3 as a potential specific marker for Malignant Peripheral Nerve Sheath Tumor (MPNST). A cross-sectional analysis was conducted on 50 cases of sarcomas, including 13 MPNST, 14 synovial sarcomas, 13 dermatofibrosarcoma protuberans (DFSP), and 10 leiomyosarcomas originating from the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital (FMUI-CMH) from January 2013 to December 2021. H3K27me3 images were obtained and categorized as complete loss when more than 95% of the tumor cells showed loss of nuclear staining. The results found in MPNST showed a loss of H3K27me3 expression, which is statistically significant compared to other sarcomas mimicking MPNST (p=0.021), indicating its potential as a diagnostic marker. There is a difference in the expression of H3K27me3 between the high and low-grade MPNST but it is not statistically significant (p=0.105). This showed that H3K27me3 loss of expression can be used to diagnose MPNST, especially high-grade MPNST, and differentiate it from other sarcomas mimicking MPNST.

Peran CD44 pada Progresivitas Non Alcoholic Steatohepatitis (NASH) Sarwanti; Marini Stephanie; Ria Kodariah
Majalah Patologi Indonesia Vol. 29 No. 2, Mei 2020
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v29i2.415

Non alcoholic Steatohepatitis (NASH) is part of a group of conditions called Non-Alcoholic Fatty Liver Diseases(NAFLD) where it is a chronic disease, which defined after elimination other causes of fatty liver, such as excessivealcohol consumption and other causes of chronic liver diseases. NASH is fatty liver disease which characterized byballooning of hepatocyte and lobular inflammation with or without fibrosis. Histopathology diagnose on NASH can bedefined by performing liver biopsy. The purpose of liver biopsy is to define level and degree of the disease. Cluster ofDifferentiation (CD) 44 is a transmembrane glycoprotein receptor which located on the surface of macrophage cells,lymphocytes and endothelial cells. In studies which conducted on mice and humans, showed that CD44 playsimportant role in the progression of NASH. CD44 regulates inflammation of adipose tissue and liver. CD44 ispresumed as a marker which increase macrophage infiltration and other inflammatory cells on liver. This processleads to ultimate increment on insulin resistance and fatty liver. Deficiency was discovered on mice which injectedwith methionine and choline deficiency diet (MCDD). CD44 is associated with preventive method to prevent livercomplication by reducing macrophage or monocyte and as well as neutrophil accumulation in liver which wasevaluated through reducing numbers of inflammatory focus, expression of inflammatory cytokines: tumor necrosisfactor Î± (TNFÎ±), interleukin (IL) -1B and nitric oxide synthesis (iNOS), and pro-inflammatory types of macrophage. Inobese patients, number of CD44 is predicted to be increasing.

Ekspresi Programmed Death Ligand-1 (PD-L1) pada Seminoma Testis sebagai Potensi Faktor Prognostik Boedijono, Freciyana; Tanurahardja, Budiana; Kodariah, Ria
Majalah Patologi Indonesia Vol. 29 No. 3, September 2020
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v29i3.448

BackgroundThe prognosis of testicular seminoma cases which failed to be cured with conventional therapy is poor. Several recurrent eventsafter chemotherapy were also found. PD-L1 is expressed in various types of malignancy and tumor infiltrating lymphocytes (TILs)and its role is known as a prognostic factor. This study was conducted to determine the role of PD-L1 expression seminoma indetermining overall survival (OS) and progression free survival (PFS).MethodsThis is a retrospective cohort study with survival analysis. Clinical data were obtained from medical record in RSUPN CiptoMangunkusumo since January 2011-December 2016 and observed for 2 years. Histopathological data were obtained fromAnatomical Pathology Department and PD-L1 immunohistochemical staining were performed.ResultsA significant correlation between PD-L1 expression in tumor cells with 2-year OS (p=0.023) and PFS (p=0.002) in testicularseminoma was found. No significant correlation between PD-L1 expression in TILs with 2-year OS (p=0.235) and PFS (p=0.111).We also found significant correlations between PD-L1 expression of tumor cells and TILs with PFS (p=0.019). A significantcorrelation between stage with 2-year OS (p=0.010) and PFS (p=0.000) and lymph node metastases with 2-year OS (p=0.010) andPFS (p=0.000).ConclusionPD-L1 expression of testicular seminoma cells were significantly correlated with OS and PFS. There were no statistically significantassociations between PD-L1 expression in TILs with OS and PFS.

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