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Subandi
"ABSTRAK
Koriokarsinoma merupakan keganasan yang sangat invasive berasal dari villi plasentra dan trofoblas. Mola invasif dan koriokarsinoma sangat reponsif terhadap kemoterapi dengan angka kesembuhan lebih dari 90 , yang memungkinkan tercapainya kesembuhan tanpa mengganggu fungsi reproduksi. Methotrexate MTX merupakan terapi yang sering digunakan pada beberapa keganasan dan merupakan protokol kemoterapi pada koriokarsinoma, namun MTX memiliki banyak efek samping. Berbagai penelitian pada setengah abad terakhir menunjukan fungsi penting nanokurkumin. Penelitian in vitro dan in vivo menujukkan perannya seperti anti inflamasi, pengeluaran sitokin, anti oksidan dan imunomodulator. Namun, sapai saat ini belum ada penelitian mengenai efek antikanker nanokurkumin pada koriokarsinoma. Penelitian eksperimental sederhana ini menggunakan uji Shapiro-Wilk, uji t sampel bebas, dan uji Anova One Way. Pada penelitianini, kami meneliti dan mebandingkan efek pemberian MTX atau kombinasi dengan nanokurkumin pada berbagai jalur sinyal. Pada penelitian ini, 4 kelompok sel BeWo diberikan kombinasi MTX dan nanokurkumin, 1 kelompok sel BeWo diberikan MTX sebagai control positif, dan 1 kelompok sel BeWo sebagai control negatif. Penelitian ini menunjukkan terdapat penurunan ekspresi telomerase, ekspresi NF- B, dan indeks proliferasi BrdU yang signifikan dengan pemberian kombinasi MTX dan nanokurkumin dibandingkan dengan MTX saja ABSTRACT
Choriocarcinoma is a highly invasive malignant tumor arising from the placental villous and extravillous trophoblast. IM and CCA, which make up the majority of these tumors, are highly responsive to chemotherapy with an overall cure rate exceeding 90 , making it usually possible to achieve cure while preserving reproductive function. Methotrexate is a frequently used for the treatment of several malignancies and is part of the chemotherapy protocols used for choriocarcinoma; however, side-effect are common. Extensive research over the last half century has revealed important functions of nanocurcumin. Invitro and in vivoresearch has shown various activities, such as anti-inflammatory, cytokines release, antioxidant, and immunomodulatory. However, to date no study has been carried out to elucidate its anticancer activity of nanocurcumin in choriocarcinoma. In this study, we investigated and compared the effects of methotrexate alone or in combination with nanocurcumin on various signalling pathway. In this simple experiment stury, we used Saphiro-Wilk test, independent sample t test, and Anova One Way test to analize data. To study the potential cooperative effect of both against, 4 BeWo cell lines were treated with the combination of methotrexate and nanocurcumin, 1 BeWO cell line was treated with methotrexate alone as a positive control, and 1 BeWo cell line as a negative control. This study demonstrated significant reduction of telomerase activity, NF- B expression, and proliferation index BrdU of BeWo cell line treated with a combination of nanocurcumin and methotrexate compared with methotrexate alone. It shows that the effect of nanocurcumin and methotrexate are syngergistic suggest potential for the clinical use of methotrexate in combination with curcumin which will allow effective anticancer effect in choriocarcinoma. "
2018
SP-PDF
UI - Tugas Akhir  Universitas Indonesia Library
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Popi Sopiah
"ABSTRAK
Latar belakang. Proses inflamasi kronik dan persisten mempengaruhi tingginya rekurensi dan survival endometriosis pasca pembedahan. Hal ini menjadi permasalahan endometriosis, sehingga perlu pengembangan terapi target salah satunya yaitu asam galat. Asam galat terbukti efektif sebagai antikanker, anti tumor, anti inflamasi dan antibakterial pada beberapa cell line, namun efektifitasnya pada sel endometriosis harus dibuktikan. Tujuan. membuktikan efek asam galat dan senyawa turunannya terhadap regulasi inflamasi pada kultur primer endometriosis ditinjau dari ekspresi mRNA NF-kB, serta sekresi TNF-? dan IL-6. Metode. Sel endometriosis berasal dari jaringan endometriosis pasien yang menjalani laparaskopi, diisolasi secara enzimatis dan dikultur primer. Sel kultur diberi perlakuan asam galat, heptil dan oktil galat dengan dosis 25,6 g/mL, 51,2 g/mL dan 102,4 g/mL selama 48 jam, kemudian diinduksi dengan LPS 500 ng/mL selama 24 jam. Regulasi inflamasi dinilai dari ekspresi mRNA NF-kB dengan qRT-PCR, kadar sekresi TNF-? dan IL-6 dengan ELISA, serta inhibisi viabilitas sel dengan MTS Assay. Hasil. Setelah data dirasiokan dengan kontrol, ketiga zat signifikan menghambat viabilitas sel endometriosis p value 0,000 dengan inhibisi tertinggi pada dosis 102,4 g/mL. Terjadi penurunan ekspresi relatif NF-kB yang dirasiokan dengan kontrol dan IL-6 meskipun secara statistik tidak bermakna. Konsentrasi TNF? tidak berbeda secara bermakna p value 0,340 . Kesimpulan. Asam galat dan senyawa turunannya berpengaruh terhadap inhibisi viabilitas sel, penurunan ekspresi relatif NF-kB dan IL-6, namun tidak bermakna terhadap penekanan sitokin TNF-?. Perlu dilakukan studi lanjut untuk menilai efektifitas asam galat sebagai kandidat obat antiinflamasi pada endometriosis ditinjau aspek lain.

ABSTRACT
Background. Endometriosis is a benign gynecological disorder characterized by the growth of the lining of the endometrium like tissue outside the uterus. The cause of the growth of endometriosis is not known well, chronic and persistent inflammatory process is suspected to be one of the pathogenesis that contributes to the high recurrence and survival endometriosis. One of the potential therapeutic agents is a gallic acid which proved effective in earlier studies as an anti cancer, anti tumor, anti inflammatory and antibacterial in several cell line. The Effectiveness of gallic acid to the endometriosis cell is a preliminary study and have not found evidence of publication yet. Object. Proving the effect of gallic acid and its derivatives on the inflammatory regulation of endometriosis primary culture study on mRNA expression of NF kB, TNF , and IL 6 secretion. Method. Endometriosis cells from Indonesian endometriosis patients tissues who had undergone laparoscopy surgery were isolated by the enzymatic reaction and primary cultured. Cultured cells treated by gallic acid and alkyl ester synthetic derivatives of the gallic acids heptyl gallate and octyl gallate each with the dosage of 25,6 g mL, 51,2 g mL, and 102.4 g mL for 48 hours and then induced by LPS 500 ng mL for 24 hours. Parameter research was assessed by qRT PCR for mRNA expression of NF kB, ELISA for the quantification of TNF and interleukin 6, and MTS assay was used to observe endometriosis cell viability. Results. After the data was rationalized with the control, three substances showed significant inhibition of endometriosis cell viability. The highest inhibition for all treatment was at doses 102,4 g mL. Overall there was an inhibition of relative expression of mRNA NF kB were rationalized to controls and suppression of IL 6 in octyl gallate groups. The concentration of TNF among the groups did not differ significantly p value 0.340 . Conclusion. Gallic acid and its derivatives have significantly inhibition effect toward cell viability, mRNA expression of NF kB, and IL 6 but have not significantly effect toward cytokine TNF . Further studies need to be conducted to assess the effectiveness of gallic acid as an anti inflammatory drug candidate toward to any pathway."
2017
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Hendrik Kurniawan
"Latar Belakang : Kanker payudara merupakan salah satu penyebab kematian tertinggi akibat kanker pada wanita di Indonesia. Hal ini diantaranya disebabkan karena adanya resistensi terhadap terapi berlandaskan ROS seperti pada radioterapi maupun kemoterapi. Sel punca kanker payudara (cancer stem cells, CSCs) memiliki peran pada mekanisme resistensi ini. Penelitian terhadulu menunjukkan kemampuan CSCs untuk bertahan terhadap kondisi stress oksidatif pada pemberian rotenon. Karena itu, dalam penelitian ini dilakukan analisis terhadap faktor transkripsi NF-kB pada sel kanker payudara baik CSC maupun non CSC, terkait peran NF-kB dalam mempertahankan viabilitas sel kanker pada kondisi stress oksidatif.
Metode: Penelitian dilakukan pada sel punca kanker payudara manusia (CD24-/CD44+) maupun non sel punca (CD24-/CD44-) yang diberi H2O2 dengan konsentrasi 1.1µM, 11µM, dan 110µM dengan kontrol sel yang tidak diberi H2O2. Penilaian dilakukan terhadap parameter ekspresi mRNA NF-kB, dan viabilitas sel. Uji statistik dilakukan menggunakan IBM-SPSS dengan nilai α < 0.05.
Hasil: Pemberian H2O2 pada konsentrasi 11µM menunjukkan peningkatan yang signifikan pada ekspresi mRNA NFkB CSCs dibanding non CSCs (p<0.05). Sedangkan untuk hasil uji viabilitas pada seluruh konsentrasi H2O2 nampak bahwa CSCs mampu mempertahankan viabilitasnya dibandingkan dengan non CSCs yang mengalami penurunan viabilitas (p<0.05)..
Kesimpulan: Kondisi stres oksidatif akibat pemberiaan H2O2 dapat meningkatkan ekspresi mRNA NF-kB pada CSCs sehingga viabilitasnya tetap dapat dipertahankan.

Introduction: Breast cancer is one of the highest causes of death from cancer in women in Indonesia. This is partly due to the resistance to ROS-based therapies such as radiotherapy and chemotherapy. Breast cancer stem cells (cancer stem cells, CSCs) have a role in this resistance mechanism. Previous studies demonstrated the ability of CSC to survive oxidative stress conditions due to rotenone administration. Therefore, in this study an analysis was carried out on the transcription factor NF-kB in breast cancer cells, both CSCs and Non CSCs, related to the role of NF-kB in maintaining the survival of cancer cells under conditions of oxidative stress.
Methods: The study was conducted on human breast cancer stem cells (CD24-/CD44+) and non stem cells (CD24-/CD44-) which were given H2O2 at concentrations of 1.1µM, 11µM, and 110µM with control cells not given H2O2. Assessment was carried out on the parameters of NF-kB mRNA expression, and cell viability. Statistical tests were performed using IBM-SPSS with a value of α < 0.05.
Results: Administration of H2O2 at a concentration of 11µM showed a significant increase in the expression of NFk-B CSCs mRNA compared to non CSCs (p<0.05). As for the viability test results at all concentrations of H2O2 it appears that CSCs was able to maintain its viability compared to non CSCs which experienced a decrease in viability (p<0.05).
Conclusion: Conditions of oxidative stress due to administration of H2O2 can increase the expression of NF-kB mRNA in CSCs so that its viability can be maintained.
In this study, conditions of oxidative stress due to administration of H2O2 led to an increase in the expression of NF-kB mRNA in CSCs so that cell viability could be maintained.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014
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UI - Tesis Membership  Universitas Indonesia Library
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Rio Handi Sanjaya
"Stroke merupakan penyakit yang menyebabkan kematian nomor dua dan kontributor penyebab disabilitas tertinggi di dunia dengan jenis stroke iskemik menjadi penyebab umum stroke. Saat ini, terapi standar stroke yang disetujui oleh Food and Drug Administration (FDA) hanya recombinant tissue plasminogen activator (rtPA). Penelitian mengenai efektivitas terapi rtPA menunjukkan rtPA memiliki tingkat keberhasilan untuk sembuh sepenuhnya hanya sebesar 35%. Oleh karena itu, terapi restoratif dikembangkan untuk penanganan stroke salah satunya terapi berbasis sel menggunakan sekretom dari mesenchymal stem cells (MSC). Dalam patofisiologis stroke, berbagai cascade reaksi molekuler internal sel memiliki peran yang kompleks. Contoh faktor yang terlibat dalam cascade molekuler tersebut adalah Protein kinase B (AKT) sebagai faktor penunjang survivability sel, dan Nuclear factor-kappa B (NF-kB) sebagai faktor pengaktif jalur inflamasi. Dalam penelitian ini, profil ekspresi gen tersebut diteliti dari sel punca MSC yang berasal dari Macaca fascicularis dengan diberikan perlakuan prakondisi hipoksia oksigen 3% selama 48 jam. Tingkat ekspresi mRNA gen tersebut diinvestigasi dengan metode RT-qPCR. Hasil uji ekspresi gen menunjukan peningkatan mRNA gen protein AKT1 dan penurunan mRNA gen protein NF-kB pada MSC prakondisi hipoksia. Hal tersebut menunjukkan potensi sekretom prakondisi sebagai terapi restoratif yang ditunjukkan dari perubahan profil ekspresi gen yang mengarah pada survivability cell.

Stroke is the second leading cause of death and the highest contributor to disability worldwide, with ischemic stroke being the most common type. Currently, the only FDA-approved standard therapy for stroke is recombinant tissue plasminogen activator (rtPA). Research on the effectiveness of rtPA therapy indicates that it has a full recovery success rate of only 35%. Consequently, restorative therapies, including cell-based therapies using secretomes from mesenchymal stem cells (MSCs), are being developed for stroke treatment. In the pathophysiology of stroke, various internal cellular molecular cascades play a complex role. Examples of factors involved in these molecular cascades include Protein kinase B (AKT), which supports cell survivability, and Nuclear factor-kappa B (NF-kB), which activates inflammatory pathways. In this study, the gene expression profiles of these factors were investigated in MSCs derived from Macaca fascicularis, subjected to hypoxic preconditioning with 3% oxygen for 48 hours. The mRNA expression levels of these genes were analyzed using the RT-qPCR method. The results showed an increase in AKT1 protein mRNA expression and a decrease in NF-kB protein mRNA expression in hypoxia-preconditioned MSCs. These findings indicate the potential of hypoxia-preconditioned secretomes as restorative therapy, as evidenced by changes in gene expression profiles that promote cell survivability."
Depok: Fakultas Farmasi Universitas Indonesia, 2024
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UI - Skripsi Membership  Universitas Indonesia Library
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Rafida Amalia Salma
"Pendahuluan: Penyakit Crohns merupakan subtipe penyakit radang usus kronis (IBD) yang umumnya terdapat di usus halus. Prevalensi penyakit ini adalah 100 kasus per 100.000 orang. Pengobatan lini pertama untuk IBD adalah kortikosteroid dan asam 5-aminosalisilat (5-ASA). Namun, ada efek samping yang mungkin ditimbulkan, pengobatan alternatif dari bahan alami dapat dipertimbangkan sebagai pengobatan. Konsumsi asam elagat yang terdapat pada kulit buah delima dapat menjadi alternatif pengobatan anti inflamasi.
Tujuan: Penelitian ini dilakukan untuk mengetahui efektivitas ekstrak etanol kulit buah delima sebagai anti inflamasi yang difokuskan pada ekspresi NF-κB pada usus halus mencit yang diinduksi DSS.
Metode: Penelitian ini menggunakan desain eksperimental in vivo dengan menggunakan simpanan bahan biologis jaringan usus halus mencit yang telah diberi perlakuan: tanpa intervensi (N); kontrol negatif (K-) menyebabkan DSS 2%; kontrol positif 1 (KA +) menginduksi DSS 2% dan aspirin; kontrol positif 2 (KE +) menginduksi DSS 2% dan asam elagat; kelompok dosis 1 (D1) diinduksi DSS2% dan ekstrak kulit buah delima dalam dosis kecil (240 mg / kgBB), dan kelompok dosis 2 (KD2) diinduksi oleh DSS2% dan ekstrak kulit buah delima dalam dosis tinggi (480mg / kgBW).
Hasil: Hasil uji One Way ANOVA menunjukkan hasil yang signifikan. Hasil uji Post Hoc Games Howell menunjukkan bahwa terdapat perbedaan yang signifikan antara KN dan K- (p = 0,018), KA + (p = 0,024), KE + (p = 0,034); Kelompok uji D1 dan K- (p = 0,004), KA + (p = 0,001), KE + (p = 0,005); Kelompok uji D2 dan K- (p = 0,020), dan KA + (p = 0,030).
Kesimpulan: Pemberian etanol kulit buah delima dapat menurunkan ekspresi NF-κB pada sel epitel usus halus mencit yang diinduksi oleh DSS 2%.

Introduction: Crohns disease is a chronic inflammatory bowel disease (IBD) subtype that commonly located in the small intestine. The prevalence of this disease is 100 cases per 100.000 individuals. The first-line treatment for IBD is corticosteroids and 5-aminosalicylic acid (5-ASA). However, there are side effects that may be caused, alternative medicines from natural ingredients can be considered as the treatment. The consumption of elagic acid, which is found in pomegranate peels, can be an alternative anti-inflammatory treatment.
Objective: This study was conducted to determine the effectiveness of pomegranate peel ethanol extract as an anti-inflammatory focused on the NF-κB expression on mice small intestine induced by DSS.
Method: This study used an in vivo experimental design using stored biological material of mice small intestine tissue which had been treated: without intervention (N); negative control (K-) induced DSS 2%; positive control 1 (KA +) induced DSS 2% and aspirin; positive control 2 (KE +) induced DSS 2% and elagic acid; dose 1 group (D1) induced DSS2% and pomegranate peel extract in a small dose (240 mg/kgBW), and the dose 2 group (KD2) induced by DSS2% and pomegranate peel extract in a high dose (480mg / kgBW).
Results: The One Way ANOVA test results showed significant results. The results of the Post Hoc Games Howell test showed that there were significant differences between KN and K- (p = 0.018), KA + (p = 0.024), KE + (p = 0.034); D1 test group and K- (p = 0.004), KA + (p = 0.001), KE + (p = 0.005); D2 test group and K- (p = 0.020), and KA + (p = 0.030).
Conclusion: The administration of pomegranate peel ethanol can reduce the expression of NF-κB in mice small intestinal epithelial cells induced by DSS 2%."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Siti Yaoman Ely
"[ABSTRAK
Latar belakang : Rekonstruksi tulang pada regio kraniofasial membutuhkan bahan tandur sebagai matriks dalam proses regenerasi tulang, untuk mereplikasi struktur tulang yang hilang. Membran perikardium bovine adalah biomaterial yang kaya akan kolagen yang merupakan unsur utama matriks ekstraselular tulang. Bagaimana perilaku osteoblas terhadap bahan membran perikardium bovine produksi BATAN, Jakarta, Indonesia masih belum di teliti.
Tujuan : Mengevaluasi perilaku osteoblas manusia MG63 dalam proses regenerasi tulang setelah ditambahkan dengan membran perikardium bovine (Batan, Jakarta, Indonesia).
Metoda : Sel osteoblas manusia MG63 dibiakan sampai jumlah mencukupi, kemudian dibagi menjadi 2 kelompok, kelompok pertama ditambahkan dengan membran perikardium bovine dan kelompok kedua tanpa perlakuan sebagai kontrol. Dilakukan pengukuran proliferasi sel osteoblas dalam 24 jam dengan MTT assay. Ekspresi osteokalsin dan deposisi ion kalsium dievaluasi pada hari ke 7, 14, 21, dan 28 setelah perlakuan.
Hasil : Membran perikardium bovine meningkatkan rerata proliferasi sel osteoblas, menurunkan level ekspresi osteokalsin pada tahap akhir kalsifikasi sel yang mengindikasikan perlambatan proses down regulation kalsifikasi sel osteoblas, serta meningkatkan deposisi ion kalsium pada biakan sel osteoblas manusia MG63.
Kesimpulan : Membran perikardium bovine produksi BATAN, Jakarta, Indonesia meningkatkan proses diferensiasi dan mineralisasi sel osteoblas.

ABSTRACT
Background : Bone reconstruction of the craniofacial region requires graft material for the bone regeneration process, to replicate structure of the bone. As a graft biomaterial, Bovine pericardium membrane is rich in collagen fibers, which is the main element of bone extracellular matrix. The human cell line behavior in regeneration process after transplantation of bovine pericardium membrane produced by BATAN, Jakarta, Indonesia has not been reported.
Objective : The objective of this study was to evaluate the behavior of human osteoblast cell line MG63 in bone regeneration process, after transplantation of bovine pericardium membrane (BATAN, Jakarta, Indonesia).
Method : Human osteoblast cell line culture was divided into 2 groups, first group transplanted with bovine pericardium membrane and second group without bovine pericardium membrane as a control. After 24 hours, the proliferation of osteoblast cell are analyzed using MTT assay test, 7, 14, 21, 28 days after transplantation, expression of osteocalcin and deposition of Ca++ was evaluated.
Results: Bovine pericardium membrane improved the mean proliferation of osteoblast, lowering the expression level of osteocalcin, that indicate a slowdown in down-regulation process of osteoblast cells calcification, and increase deposition of Ca++ in human osteoblast cell line MG63.
Conclusions : Bovine pericardium membrane produced by BATAN, Jakarta, Indonesia has to increase differentiation and mineralization of osteoblast cell.;Background : Bone reconstruction of the craniofacial region requires graft material for the bone regeneration process, to replicate structure of the bone. As a graft biomaterial, Bovine pericardium membrane is rich in collagen fibers, which is the main element of bone extracellular matrix. The human cell line behavior in regeneration process after transplantation of bovine pericardium membrane produced by BATAN, Jakarta, Indonesia has not been reported.
Objective : The objective of this study was to evaluate the behavior of human osteoblast cell line MG63 in bone regeneration process, after transplantation of bovine pericardium membrane (BATAN, Jakarta, Indonesia).
Method :Human osteoblast cell line culture was divided into 2 groups, first group transplanted with bovine pericardium membrane and second group without bovine pericardium membrane as a control. After 24 hours, the proliferation of osteoblast cell are analyzed using MTT assay test, 7, 14, 21, 28 days after transplantation, expression of osteocalcin and deposition of Ca++ was evaluated.
Results: Bovine pericardium membrane improved the mean proliferation of osteoblast, lowering the expression level of osteocalcin, that indicate a slowdown in down-regulation process of osteoblast cells calcification, and increase deposition of Ca++ in human osteoblast cell line MG63.
Conclusions : Bovine pericardium membrane produced by BATAN, Jakarta, Indonesia has to increase differentiation and mineralization of osteoblast cell., Background : Bone reconstruction of the craniofacial region requires graft material for the bone regeneration process, to replicate structure of the bone. As a graft biomaterial, Bovine pericardium membrane is rich in collagen fibers, which is the main element of bone extracellular matrix. The human cell line behavior in regeneration process after transplantation of bovine pericardium membrane produced by BATAN, Jakarta, Indonesia has not been reported.
Objective : The objective of this study was to evaluate the behavior of human osteoblast cell line MG63 in bone regeneration process, after transplantation of bovine pericardium membrane (BATAN, Jakarta, Indonesia).
Method :Human osteoblast cell line culture was divided into 2 groups, first group transplanted with bovine pericardium membrane and second group without bovine pericardium membrane as a control. After 24 hours, the proliferation of osteoblast cell are analyzed using MTT assay test, 7, 14, 21, 28 days after transplantation, expression of osteocalcin and deposition of Ca++ was evaluated.
Results: Bovine pericardium membrane improved the mean proliferation of osteoblast, lowering the expression level of osteocalcin, that indicate a slowdown in down-regulation process of osteoblast cells calcification, and increase deposition of Ca++ in human osteoblast cell line MG63.
Conclusions : Bovine pericardium membrane produced by BATAN, Jakarta, Indonesia has to increase differentiation and mineralization of osteoblast cell.]"
Fakultas Kedokteran Gigi Universitas Indonesia, 2015
SP-PDF
UI - Tugas Akhir  Universitas Indonesia Library
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Roselina Panghiyangani
"Pendahuluan: Sindroma ovarium polikistik (SOPK) merupakan masalah reproduksi yang sering terjadi pada perempuan usia reproduksi, namun hingga saat ini etiopatogenesis SOPK masih belum jelas. Penelitian ini bertujuan menganalisis peran sel granulosa folikel ovarium dalam etiologi SOPK, keterkaitan genotip FSHR Asn680Ser dengan patogenesis SOPK dan peran gen CYP19A1(aromatase) dalam patogenesis SOPK.
Metode: Penelitian ini menggunakan desain penelitian analitik observasional berbentuk studi seran lintang (cross sectional study) dan dilakukan di Departemen Biologi FKUI, Klinik Yasmin-RSCM Kencana dan Laboratorium terpadu FKUI pada tahun 2011-2014. Sebanyak 142 subyek penelitian (66 pasien SOPK dan 76 pasien bukan SOPK) terlibat dalam penelitian ini. Sampel penelitian berupa darah tepi dan cairan folikel ovarium yang diaspirasi ketika proses ovum pick up sebagai sumber sel granulosa. Dilakukan isolasi DNA untuk analisis RFLP polimorfisme FSHR Asn680Ser, dilakukan kultur sel granulosa untuk mengetahui kemampuan proliferasi sel granulosa dan analisis ekspresi mRNA aromatase sel granulosa dengan metode RT-qPCR.
Hasil: Indeks proliferasi sel dan ekspresi mRNA aromatase sel granulosa pada kelompok SOPK lebih rendah secara bermakna dibandingkan bukan SOPK (p<0,05). Tidak ditemukan perbedaan bermakna distribusi genotip FSHR Asn680Ser antara kelompok SOPK dan bukan SOPK (p>0,05), tidak ditemukan perbedaan bermakna antara kadar hormon FSH basal berdasarkan variasi genotip FSHR Asn680Ser pada kelompok SOPK dan bukan SOPK (p>0,05). Tidak ditemukan perbedaan yang bermakna indeks proliferasi sel granulosa berdasarkan variasi genotip FSHR Asn680Ser baik pada kelompok SOPK maupun bukan SOPK (p>0,05). Tidak terdapat korelasi antara indeks proliferasi sel granulosa dengan ekspresi mRNA aromatase (p>0,05).
Kesimpulan: Indeks proliferasi sel dan tingkat ekspresi mRNA aromatase sel granulosa kelompok SOPK menurun dibandingkan kelompok bukan SOPK. Genotip FSHR Asn680Ser tidak menentukan kerentanan individu untuk menderita SOPK. Kadar hormon FSH basal dan indeks proliferasi sel granulosa tidak berbeda antara kelompok SOPK dan bukan SOPK berdasarkan variasi genotip FSHR Asn680Ser. Tidak ada korelasi antara indeks proliferasi sel dengan ekspresi mRNA aromatase sel granulosa pada penelitian ini.

Introduction: Polycystic ovary syndrome (PCOS) is a common reproductive problem in women at reproductive age, but until now aetiopathogenesis of PCOS has not been fully understood. The objective of this study was to analyse interrelationship between proliferation of ovarian follicular granulosa cells, CYP19A1 expression and polymorphism at codon 680 of FSHR towards the etiology of PCOS.
Methods: Observational analytic in the form of cross-sectional study was used in this research. The study was carried out between 2011-2014 at the Department of Biology, Integrated laboratory of Faculty of Medicine University of Indonesia and Yasmin clinic at the Cipto Mangunkusumo Hospital. A total of 142 subjects (66 patients with PCOS and 76 patients without PCOS) were involved in this study. Granulosa cells for culture were obtained from ovarian follicular fluid and total RNA was isolated from the cells. DNA samples were extracted from peripheral blood. Granulosa cell proliferation index was determined by counting under a phase-contrast microscope. CYP19A1 expression was measured by qRT-PCR, whereas polymorphism at Asn680Ser FSHR was performed by RFLP.
Result: Cell proliferation index and CYP19A1 mRNA expression levels in the granulosa cells of the PCOS group was significantly lower than non-PCOS (p < 0.05). There was no significant difference found in Asn680Ser FSHR genotype distribution between PCOS and non-PCOS group (p > 0.05). Based on Asn680Ser FSHR genotype variation, no significant difference was found between basal FSH hormone levels in the PCOS and non- PCOS group (p > 0.05) and FSHR genotype variation did not correlate with granulosa cell proliferation index between PCOS and non-PCOS group (p > 0.05). Moreover, there was no correlation between the granulosa cell proliferation index with aromatase mRNA expression levels (p > 0.05).
Conclusion: Cell proliferation index and CYPA1 expression of granulosa cells in PCOS group were lower compared to the non PCOS group although no correlation was found between the two parameters. Asn680Ser FSHR genotype did not correlate with individual susceptibility to PCOS. FSHR genotype variation did not correlate with basal FSH levels and granulosa cell proliferation index between PCOS and non-PCOS.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015
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UI - Disertasi Membership  Universitas Indonesia Library
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Isabelle Deli
"[ABSTRAK
Latar belakang: Neoplasma sel plasma (NSP) adalah proliferasi sel plasma neoplastik yang tumbuh soliter menjadi plasmasitoma tulang soliter (PTS) dan plasmasitoma ekstrameduler (PEM) serta multipel (MM)). Saat ini perjalanan penyakit dari plasmasitoma menjadi MM sulit diprediksi. Bartl mengklasifikasikan derajat keganasan berdasarkan histomorfologik menjadi rendah, sedang dan tinggi. Penelitian ini bertujuan menggunakan klasifikasi Bartl untuk menilai perjalanan PTS dan PEM menjadi MM dihubungkan dengan ekspresi TP53 dan Ki-67.
Bahan dan cara: Pada 32 kasus NSP yang berasal dari PTS 14 kasus, PEM 5 kasus, maupun MM sebanyak 13 kasus, diklasifikasikan menjadi 3 kelompok derajat keganasan menurut Bartl yaitu derajat keganasan ringan, sedang dan tinggi. Selanjutnya dilakukan pulasan IHK TP53 dan Ki-67 pada seluruh kasus dan dihitung persentase positifitas.
Hasil: Berdasarkan derajat keganasan, derajat rendah ditemukan pada 10 (31,2%) MM, derajat sedang pada 5 (15,6%) PTS dan derajat tinggi pada 2 (6,2%) PTS dan PEM. Peningkatan ekspresi TP53 ditemukan pada derajat Bartl yaitu median derajat rendah 4%, derajat sedang 16%, dan derajat tinggi 10%. Terdapat perbedaan ekspresi TP53 yang bermakna antara derajat keganasan rendah dan sedang (p=0,004). Rerata indeks proliferasi Ki-67 pada derajat keganasan rendah 57%, derajat sedang 44,6%, dan derajat tinggi 32,6%. Tidak ditemukan perbedaan antara indeks proliferasi Ki-67 dengan derajat keganasan menurut Bartl (p=0,339). Tidak terdapat hubungan antara ekspresi TP53, Ki-67 dengan usia. Kesimpulan: Peningkatan ekspresi TP53 pada NSP sejalan dengan peningkatan derajat keganasan Bartl, terutama pada derajat rendah dan sedang. Klasifikasi Bartl ditambah dengan pulasan TP53 saja tidak cukup untuk memprediksi perkembangan PTS dan PEM menuju MM.

ABSTRACT
Background: Plasma cell neoplasm (PCN) is a neoplastic plasma cells proliferation including solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Until now the development of disease to MM is unpredictable. Bartl classifies the degrees of malignancy histomorphologically as low, intermediate and high. This research aims using Bartl's classification and expression of TP53 and Ki-67 to assess the development of SBP and EMP to MM.
Materials and methods: In 32 cases of PCN derived from 14 cases of SBP, 5 cases of EMP, and 13 MM case, then classified into 3 groups based on Bartl's degrees of malignancy as low, intermediate, and high. Furthermore all cases stained by IHC TP53 and Ki-67 and evaluated the percentage of positivity. Results: Bartl's low degree was found in 10 (31,2%) MM case, intermediate in 5 (15,6%) SBP and high in 2 (6,2%) SBP and EMP. TP53 expression, obtainable at 4% of low, 16% of intermediate, and 10% of high degree. There is significant difference between TP53 expression in low and intermediate degree (p = 0,004). Mean proliferation index of Ki-67 is 57% in low, 44,6% in intermediate and 32,6% in high degree. There is no significant difference of Ki-67 proliferation indexes among the group (p = 0,339). There is no correlation between expressions TP53, Ki-67 and age.
Conclusion: Increasing expression TP53 is in line with Bartl's degrees of malignancy, especially on low and inter.;Background: Plasma cell neoplasm (PCN) is a neoplastic plasma cells proliferation including solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Until now the development of disease to MM is unpredictable. Bartl classifies the degrees of malignancy histomorphologically as low, intermediate and high. This research aims using Bartl?s classification and expression of TP53 and Ki-67 to assess the development of SBP and EMP to MM.
Materials and methods: In 32 cases of PCN derived from 14 cases of SBP, 5 cases of EMP, and 13 MM case, then classified into 3 groups based on Bartl?s degrees of malignancy as low, intermediate, and high. Furthermore all cases stained by IHC TP53 and Ki-67 and evaluated the percentage of positivity. Results: Bartl?s low degree was found in 10 (31,2%) MM case, intermediate in 5 (15,6%) SBP and high in 2 (6,2%) SBP and EMP. TP53 expression, obtainable at 4% of low, 16% of intermediate, and 10% of high degree. There is significant difference between TP53 expression in low and intermediate degree (p = 0,004). Mean proliferation index of Ki-67 is 57% in low, 44,6% in intermediate and 32,6% in high degree. There is no significant difference of Ki-67 proliferation indexes among the group (p = 0,339). There is no correlation between expressions TP53, Ki-67 and age.
Conclusion: Increasing expression TP53 is in line with Bartl?s degrees of malignancy, especially on low and inter, Background: Plasma cell neoplasm (PCN) is a neoplastic plasma cells proliferation including solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Until now the development of disease to MM is unpredictable. Bartl classifies the degrees of malignancy histomorphologically as low, intermediate and high. This research aims using Bartl’s classification and expression of TP53 and Ki-67 to assess the development of SBP and EMP to MM.
Materials and methods: In 32 cases of PCN derived from 14 cases of SBP, 5 cases of EMP, and 13 MM case, then classified into 3 groups based on Bartl’s degrees of malignancy as low, intermediate, and high. Furthermore all cases stained by IHC TP53 and Ki-67 and evaluated the percentage of positivity. Results: Bartl’s low degree was found in 10 (31,2%) MM case, intermediate in 5 (15,6%) SBP and high in 2 (6,2%) SBP and EMP. TP53 expression, obtainable at 4% of low, 16% of intermediate, and 10% of high degree. There is significant difference between TP53 expression in low and intermediate degree (p = 0,004). Mean proliferation index of Ki-67 is 57% in low, 44,6% in intermediate and 32,6% in high degree. There is no significant difference of Ki-67 proliferation indexes among the group (p = 0,339). There is no correlation between expressions TP53, Ki-67 and age.
Conclusion: Increasing expression TP53 is in line with Bartl’s degrees of malignancy, especially on low and inter]"
Fakultas Kedokteran Universitas Indonesia, 2015
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UI - Tugas Akhir  Universitas Indonesia Library
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Susi Rahmiyati
"Hem merupakan komponen penyusun hemoprotein, salah satunya yaitu sitoglobin. Sitoglobin diketahui memegang peranan dalam perkembangan kanker. Saat ini, belum diketahui peran hambatan hem terhadap ekspresi CYGB pada sel lini sel kanker hati, HepG2 Penelitian ini bertujuan untuk melihat kemampuan penghambatan hem dalam mencegah proliferasi sel HepG2. Penghambatan hem dilakukan dengan menggunakan suksinil aseton.  Analisis aktivitas enzim ALAD diukur secara kolorimetrik. Analisis viabilitas dan proliferasi (doubling time) dilakukan dengan menggunakan MTT assay. Analisis ekspresi mRNA CYGB dilakukan dengan qRT-PCR. Ekspresi protein CYGB dianalisis dengan ELISA. Hasil yang diperoleh adalah hambatan sintesis hem pada sel HepG2 dengan menggunakan suksinil aseton berhasil dilakukan. Penurunan sintesis hem berdampak pada menurunnya ekspresi CYGB baik tingkat mRNA maupun protein. Viabilitas dan proliferasi sel HepG2 menurun seiring dengan meningkatnya konsentrasi suksinil aseton. Sebagai kesimpulan, pemberian suksinil aseton mampu menghambat sintesis hem karena menekan ekspresi CYGB yang berdampak pada penurunan viabilitas dan proliferasi sel HepG2.

Hem is a component of hemoprotein, one of which is cytogloblin. Cytoglobin is known to play a role in cancer development. Currently, the role of heme inhibitors on CYGB expression in the liver cancer cell line, HepG2, is unknown. This study aims to see the ability of heme inhibition in preventing HepG2 cell proliferation. Hem inhibition was carried out using succinyl acetone. Analysis of ALAD enzyme activity was measured colorimetrically. Viability and proliferation (doubling time) analyzes were performed using the MTT assay. Analysis of CYGB mRNA expression was performed by qRT-PCR. CYGB protein expression was analyzed by ELISA. The results obtained were thatinhibition of hem synthesis in HepG2 cells using succinyl acetone was successfully carried out. Decreased heme synthesis resulted in decreased CYGB expression both at the mRNA and protein levels. HepG2 cell viability and proliferation decreased with increasing succinyl acetone concentration. In conclusion, succinyl acetone was able to inhibit hem synthesis cause it suppressed CYGB expression which had an impact on reducing the viability and proliferation of HepG2 cells."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Tesis Membership  Universitas Indonesia Library
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Lisnawati
"Radiasi merupakan terapi pilihan untuk kanker serviks stadium III B, namun permasalahan timbul karena adanya sifat radioresisten. Sel punca kanker SPK merupakan salah satu faktor yang diduga berkontribusi terhadap hal tersebut. SOX2 dan OCT4 merupakan faktor transkripsi yang mengekspresikan sifat-sifat SPK, yaitu mengontrol sifat pluripoten, self-renewal, berperan pada karsinogenesis, metastasis, resistensi terhadap terapi dan rekurensi tumor. Faktor apoptosis, DNA repair dan telomerase merupakan mekanisme yang berkaitan dengan radioresisten. Penelitian ini bertujuan untuk mempelajari hubungan antara SOX2 dan OCT4 sebagai penanda SPK terhadap respons terapi radiasi, serta kaitannya dengan faktor apoptosis caspase-3 , DNA repair Chk1 dan telomerase hTERT .Penelitian ini merupakan case control, terhadap 48 kasus karsinoma sel skuamosa serviks stadium III B yang telah menjalani terapi radiasi/kemoradiasi di RS Cipto Mangunkusumo/FKUI. Kasus dibagi dalam 2 kelompok, yaitu hasil terapi komplet 27 kasus dan hasil terapi inkomplet 21 kasus . Kasus dengan respons awal terapi radiasi baik dilakukan pemeriksaan bulan Pap smear dan HPV pada bulan ke-6 atau sampai ke-12 setelah terapi. Ekspresi SOX2, OCT4, caspase-3, Chk1 dan hTERT diperiksa secara imunohistokimia dari blok parafin biopsi awal.Ekspresi kuat SOX2 dan OCT4 dengan H-score masing-masing lebih dari 96,6 dan 61,9 mempunyai hubungan bermakna dengan respons awal terapi radiasi maupun respons akhir terapi radiasi SOX2 p = 0,017, p = 0,004 dan OCT4 p < 0,001, p < 0,001 . Ditemukan hubungan bermakna antara ekspresi Chk1 dan hTERT dengan respons awal terapi radiasi Chk1 p = 0,006, hTERT p = 0,029 . Tidak ditemukan hubungan yang bermakna antara ekspresi caspase-3, Chk1, hTERT dengan ekspresi SOX2 dan OCT4. Uji multivariat menunjukkan bahwa SOX2 dan OCT4 yang paling memengaruhi respons terapi OR = 5,12, p = 0,040 dan OR = 17,03, p < 0,001, secara berurutan . Uji probabilitas menunjukkan kemungkinan respons akhir terapi radiasi inkomplet sebesar 87,91 bila ekspresi kedua penanda SPK kuat.Ekspresi kuat SOX2 dan OCT4 dapat memprediksi hasil terapi radiasi inkomplet pada karsinoma serviks stadium III B.

Radiotherapy is the main choice of treatment for stage III B cervical cancer, but radioresistance becomes a difficult matter. Cancer stem cell is one of the factors suspected involving in radioresistant cancers. SOX2 and OCT4 are transcription factors which have pluripotent cell characteristics, and self renewal ability. They also involved in carcinogenesis, metastasis, tumor recurrent, and resistance toward therapy. Apoptotic, DNA repair, and telomerase factors are mechanisms that also contribute to radioresistance. This study aims to know the role of SOX2 and OCT4 as CSC markers, apoptotic factor caspase 3 , DNA repair Chk1 and telomerase hTERT toward radiotherapy.The design of this study was case control with 48 cases of stage III B cervical squamous cell carcinoma patients who had finished receiving radiation chemo radiation therapy at Cipto Mangunkusumo Hospital FMUI, Jakarta. They were classified in 2 groups based on the final response of treatment, which were complete and incomplete one. Pap smear and DNA HPV were performed in month 6 or until month 12 after therapy for good initial therapy. Immunohistochemistry was done to analyze SOX2, OCT4, caspase 3, Chk1 and hTERT expression from the paraffin block of initial biopsy.Strong expression of SOX2 and OCT4 with each H score was higher than 96.6, and 61.9 had significant association with both initial and final therapy response SOX2 p 0.017, p 0.004 and OCT4 p 0.001, p 0.001, repectively . There was significant association between expression of Chk1 and hTERT, and initial therapy response p 0.006 for Chk1, and p 0.029 for hTERT . No significant differences were found between caspase 3, Chk1, hTERT, and SOX2 and OCT4. Multivariate analysis showed SOX2 and OCT4 were the most influenced antibodies for radiotherapy response OR 5.12, p 0.040, and OR 17.03, p 0.001, respectively . The likelihood of incomplete final therapy response was 87.91 if the expression both of CSC markers were strong.Expression of SOX2, and OCT4 could predict the incomplete radiotherapy of stage III B cervical cancer cases.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2017
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UI - Disertasi Membership  Universitas Indonesia Library
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