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Muhammad Farrasy Ammar
"Latar Belakang: Cisplatin, agen kemoterapi utama dalam terapi kanker ovarium,
memiliki sifat hepatotoksik karena menginduksi stres oksidatif. Kurkumin dapat
meningkatkan kadar atau aktivitas antioksidan endogen seperti enzim superoksida
dismutase dan glutation. Formulasi nanopartikel kurkumin dapat meningkatkan
bioavailabilitas kurkumin dan distribusinya pada organ target. Penelitian ini
bertujuan untuk mengetahui pengaruh nanokurkumin terhadap hepatotoksisitas
akibat cisplatin melalui regulasi antioksidan endogen SOD dan GSH. Metode: 25
ekor tikus galur Wistar betina dibagi ke dalam 1 kelompok sham dan 4 kelompok
model kanker ovarium yang diinduksi DMBA pada penelitian in-vivo ini. Empat
kelompok tersebut adalah kelompok tanpa terapi, cisplatin 4 mg/KgBB
intraperitoneal, cisplatin dengan kurkumin konvensional 100 mg/KgBB per oral,
atau cisplatin dengan nanopartikel kurkumin dalam kitosan 100 mg/KgBB per oral.
Setelah perlakuan selama 1 bulan, hepar tikus diambil dan disimpan beku.
Pengukuran aktivitas SOD, kadar GSH, dan kadar GSSG dilakukan dengan metode
spektrofotometri. Hasil: Uji statistik pada kadar GSH, GSSG, dan aktivitas SOD
menunjukkan peningkatan yang signifikan pada kelompok ko-kemoterapi
kurkumin konvensional dibanding monoterapi cisplatin (p<0.05). Tidak ada
perbedaan yang bermakna antarkelompok pada rasio GSH/GSSG (p>0.05) dan
tidak ditemukan perbedaan bermakna antara kedua kelompok ko-kemoterapi pada
semua variabel (p>0.05). Kesimpulan: Kurkumin konvensional dan nanokurkumin
setara dalam meregulasi antioksidan endogen SOD dan GSH pada tikus model
kanker ovarium yang mendapat cisplatin.

Introduction: As the primary chemotherapeutic agent of choice for ovarian cancer,
cisplatin has hepatotoxic properties via oxidative stress induction. Curcumin can
increase the levels and activities of endogenous antioxidants like superoxide
dismutase enzyme and glutathione. Formulation of curcumin nanoparticles
increases its bioavailability and target organ distribution. This research aims to
elucidate the effects of nanocurcumin on cisplatin-induced hepatotoxicity via
regulation of endogenous antioxidants, SOD and GSH. Method: 25 Wistar female
rats were grouped into 1 sham group and 4 DMBA-induced ovarian cancer model
groups in this in-vivo study. Four cancer model groups were further divided into
no-treatment, 100 mg/KgBW intraperitoneal cisplatin therapy, cisplatin with oral
100 mg/KgBW conventional curcumin, and cisplatin with oral 100 mg/KgBW
curcumin nanoparticle in chitosan group. The liver of the rats were taken and frozen
after one month of treatment. Spectrophotometry was used to measure the activities
of SOD, levels of GSH, and levels of GSSG. Results: Statistic tests on levels of
GSH, GSSG, and activity of SOD showed significant increase in the curcumin cochemotherapy
against cisplatin monotherapy (p<0.05). There was no significant
difference within the groups of GSH/GSSG ratio (p>0.05) and no significant
difference was found between the curcumin co-chemotherapy and nanocurcumin
co-chemotherapy groups in all the variables (p>0.05). Conclusion: Conventional
curcumin and nanocurcumin administration are similar in regulating endogenous
antioxidants SOD and GSH on rats with ovarian cancer model treated with cisplatin.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Erico Wanafri
"Kemoterapi dengan cisplatin merupakan modalitas utama pada terapi pada kanker ovarium, walaupun telah diketahui toksisitasnya pada berbagai organ termasuk ginjal. Kurkumin, senyawa fenolik yang diperoleh dari Curcuma longa, diketahui memiliki efek proteksi pada ginjal akibat cisplatin pada berbagai model toksisitas in vivo. Namun, efek kurkumin pada ginjal dibatasi oleh bioavailabilitasnya yang rendah. Kelompok penelitian kami telah berhasil mengembangkan formulasi kurkumin nanopartikel baru yang telah terbukti memperbaiki efikasi cisplatin pada model kanker ovarium. Namun, belum diketahui apakah formulasi kurkumin nanopartikel ini juga dapat memperbaiki fungsi dan kondisi inflamasi pada ginjal yang disebabkan oleh cisplatin.
Metode Sebanyak 24 ekor tikus Wistar betina dibagi menjadi: 6 ekor tikus normal (sham treatment) dan 18 ekor tikus yang diinduksi menjadi kanker ovarium dengan DMBA. Tikus kanker ovarium dibagi menjadi 3 kelompok masing-masing 6 ekor yang menerima cisplatin 4 mg/kgBB/minggu atau cisplatin 4 mg/kgBB/minggu +kurkumin 100 mg/kgBB/hari atau cisplatin 4 mg/kgBB/minggu + nanokurkumin 100 mg/kgBB/hari. Terapi diberikan selama 4 minggu, kemudian dilakukan terminasi dan diambil darah dan organ ginjal untuk analisis penanda fungsi ginjal dan inflamasi.
Hasil Nanokurkumin dapat menurunkan kadar ureum serum signifikan dibandingkan kelompok cisplatin, namun tidak mempengaruhi kadar kreatinin dan sedikit menurunkan kadar neutrophil gelatinase-associated lipocalin (NGAL). Nanokurkumin tidak berhasil menurunkan kadar penanda inflamasi: TNF-, IL-1β dan IL-6.
Kesimpulan
Nanokurkumin memiliki kecenderungan untuk memperbaiki beberapa penanda fungsi ginjal dalam darah pada model kanker ovarium yang diberikan cisplatin, namun tidak mempengaruhi kadar penanda inflamasi di ginjal.

The effects of nanocurcumin on kidney function and inflammatory
markers in rat model of ovarian cancer treated with cisplatin
Cisplatin remains the main modality of treatment for ovarian cancer, despite its known toxic effects to various organs, including the kidney. Curcumin, a phenolic compound derived from Curcuma longa, was known to have a renoprotective effect on cisplatin- induced in vivo models. However, the beneficial effect of curcumin on the kidney is limited by its low bioavailability. Our research group has successfully developed a novel curcumin nanoparticle formulation that has been shown to improve the efficacy of cisplatin in ovarian cancer models. However, it is not yet known whether this curcumin nanoparticle formulation can also improve kidney function and inflammatory conditions caused by cisplatin in ovarian cancer models.
Method
A total of 24 female Wistar rats were divided into: 6 normal rats (sham treatment) and 18 rats induced to develop ovarian cancer with DMBA. Ovarian cancer rats were divided into 3 groups of 6 each receiving cisplatin 4 mg/kgBW/week or cisplatin 4 mg/kgBW/week + curcumin 100 mg/kgBW/day or cisplatin 4 mg/kgBW/week + nanocurcumin 100 mg/day. kgBB/day. Therapy was given for 4 weeks, then terminated and blood and kidney were taken for analysis of markers of kidney function and inflammation.
Results
Nanocurcumin lowered serum urea levels significantly compared to the cisplatin group. However, nanocurcumin did not alter creatinine levels and slightly reduced serum neutrophil gelatinase-associated lipocalin (NGAL) concentrations. Nanocurcumin was did not affect the inflammatory markers studied: TNF-, IL-1β and IL-6.
Conclusion
Nanocurcumin has a tendency to improve several markers of kidney function in cisplatin- treated ovarian cancer models. However, the effect was not associated by the alteration of inflammatory cytokines in the kidney.
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Depok: Fakultas Kedokteran Universitas Indonesia, 2021
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Dimas Kirana Mahaputra
"Latar Belakang: Cisplatin sebagai agen kemoterapi merupakan salah satu modalitas terapi pada kanker padat seperti kanker ovarium. Sejumlah studi membuktikan adanya efek samping hepatotoksik cisplatin. Hal ini dapat mengakibatkan kemoterapi tidak efektif, karena dosis cisplatin dikurangi atau bahkan dihentikan pemberiannya. Dewasa ini, obat berbasis tanaman banyak diteliti, salah satunya kurkumin. Kurkumin mempunyai efek hepatoprotektif namun bioavailabilitasnya sangat rendah. Sejumlah penelitian membuat formula nanokurkumin untuk meningkatkan bioavaibilitasnya. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian nanokurkumin pada gambaran histologis jejas liver yang diinduksi oleh cisplatin pada tikus model kanker ovarium. Metode: Penelitian ini menggunakan bahan biologis tersimpan dari penelitian sebelumnya. Terdapat 5 kelompok perlakuan; kontrol, DMBA; DMBA+Cisplatin; DMBA+Cis+kurkumin; dan DMBA+Cis+nanokurkumin. Pewarnaan Masson Trichrome dipakai untuk mengamati akumulasi kolagen sebagai penanda fibrosis. Selanjutnya dilakukan kuantifikasi jaringan kolagen /Collagen Proportionate Area (CPA), serta skoring fibrosis hati (skor ISHAK). Hasil: Induksi DMBA dan terapi cisplatin dapat mengakibatkan fibrosis hati, ditandai dengan deposisi kolagen yang lebih tinggi dibanding kelompok kontrol. Pemberian nanokurkumin menunjukkan adanya perbaikan secara histologis berupa fibrosis periportal yang ringan dan skor fibrosis yang lebih rendah secara signifikan (p<0.05) dibanding kelompok lainnya. Pemberian nanokurkumin juga menunjukkan persentase akumulasi kolagen (CPA) yang rendah, namun tidak signifikan (p>0.05) secara statistik. Kesimpulan: Pemberian nanokurkumin pada model kanker ovarium yang diterapi dengan cisplatin pada tikus menunjukkan efek hepatoprotektor dengan memperbaiki skor fibrosis dan mengurangi akumulasi kolagen pada jaringan liver. Diperlukan penelitian lebih lanjut yang membandingkan beragam dosis dan formulasi untuk mengetahui efikasi nanokurkumin yang paling baik sebagai hepatoprotektor pada model kanker ovarium yang diterapi dengan cisplatin.

Background: Cisplatin as a chemotherapy is one of the main modalities of therapy in patients with solid tumours like ovarian cancer. Studies have proven the hepatotoxicity of cisplatin, which causes dose reduction and even termination. Nowadays, herbal based drug is intensively studied, one of them is curcumin. Curcumin is known to have a hepatoprotective effect, albeit with very low bioavailability. To solve this, many research have formulated nanocurcumin to increase its bioavailability. This research aims to find out the effect of nanocurcumin in liver fibrosis induced by cisplatin in ovarian cancer of rat’s model. Method: Our study uses stored biological materials from previous study. The groups are; Control; DMBA; DMBA+Cisplatin; DMBA+Cisplatin+Curcumin; DMBA+Cisplatin+Nanocurcumin. Liver fibrosis is observed with Masson Trichrome stain to view collagen accumulation as fibrosis marker. Afterwards, quantification of collagen fibers (CPA) and liver fibrosis grading (ISHAK) is done. Results: Induction of DMBA with cisplatin treatment causes liver fibrosis, indicated by higher collagen deposition compared to the normal group. Administration of nanocurcumin shows improvement in histological structure such as milder periportal fibrosis and significantly lower liver fibrosis grade (p<0.05) compared to other groups. Administration of nanocurcumin also results in lower collagen percentage (CPA), however it is statistically insignificant (p>0.05). Conclusion: Administration of nanocurcumin in rat ovarian cancer model treated with cisplatin shows hepatoprotective effect by reducing both fibrosis grade and collagen accumulation in the liver. Further study is required with varying dose and formulations to know the nanocurcumin’s best efficacy as hepatoprotector in ovarian cancer model treated with cisplatin.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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Antasena Andra Sidqi
"Latar belakang: Cisplatin merupakan pilihan utama terapi kanker ovarium saat ini, namun memiliki efek samping diantaranya adalah hepatotoksisitas. Salah satu patofisiologi hepatotoksisitas ini adalah melalui jalur inflamasi dan fibrosis. Kurkumin merupakan senyawa yang memiliki efek antiinflamasi dan antifibrosis, namun memiliki bioavailabilitas yang rendah. Pemberian nanopartikel kurkumin diteliti dapat meningkatkan bioavailabilitas kurkumin dalam tubuh.
Tujuan: Penelitian ini bertujuan untuk mengetahui pengaruh nanokurkumin pada hepatotoksisitas akibat cisplatin, ditinjau dari kadar TNF-α dan TGF-β1 pada jaringan hati.
Metode: Penelitian in vivo dilakukan pada tikus betina galur Wistar yang dibagi menjadi 5 kelompok perlakuan (1 kelompok normal/sham, dan 4 kelompok diinduksi DMBA untuk mendapatkan model kanker ovarium). Tikus model kanker ovarium diberikan perbedaan perlakuan lagi yaitu satu kelompok tidak diterapi, satu kelompok diterapi cisplatin 4 mg/kgBB secara intraperitoneal, satu kelompok diterapi cisplatin dan kurkumin konvensional 100 mg/kgBB oral, dan satu kelompok diterapi cisplatin dan nanopartikel kurkumin 100 mg/kgBB per oral. Setelah satu bulan pemberian terapi, tikus dikorbankan dan disimpan beku organ hatinya. Pengukuran kadar TNF-α dan TGF-β1 jaringan hati dilakukan dengan metode ELISA.
Hasil: Tidak terdapat perbedaan yang signifikan antar kelompok perlakuan pada kadar TNF-α (p=0.675), dan tidak terdapat perbedaan yang signifikan antara kelompok terapi kurkumin dan nanokurkumin pada kadar TGF-β1 (p=0.992). Simpulan: Pemberian nanokurkumin tidak memengaruhi kadar TNF-α dan TGF-β1 di jaringan hati tikus model kanker ovarium yang mendapat terapi cisplatin.

Introduction: Cisplatin is currently the main choice for ovarian cancer therapy, but it has side effects including hepatotoxicity. One of the pathophysiology of cisplatin-induced hepatotoxicity is through inflammation and fibrosis. Curcumin is a compound that has anti-inflammatory and antifibrosis effects, but has a low bioavailability. The administration of curcumin nanoparticles under study can increase the bioavailability of curcumin in the body. Goals: This study aims to determine the effect of nanocurcumin on cisplatin-induced hepatotoxicity, in terms of levels of TNF-α and TGF-β1 in liver tissue.
Methods: In vivo research was carried out on female Wistar rats divided into 5 treatment groups (1 normal/sham group, and 4 groups induced by DMBA to obtain ovarian cancer models). The ovarian cancer model mice were further classified where one group got no treatment, one group treated with cisplatin 4 mg/kgBW intraperitoneally, one group was treated with cisplatin and conventional curcumin 100 mg/kgBW orally, and one group was treated with cisplatin and curcumin nanoparticles 100 mg/kgBW orally. After one month of therapy, the mice were sacrificed and kept their liver frozen. The measurement of TNF-α and TGF-β1 levels in liver tissue was carried out by the ELISA method.
Results: There was no significant difference between treatment groups in TNF-α levels (p = 0.675), and there was no significant difference between the curcumin and nanocurcumin therapy groups in TGF-β1 levels (p = 0.992).
Concluson: Nanocurcumin therapy did not affect TNF-α and TGF-β1 level in liver tissue in ovarian cancer model mice receiving cisplatin therapy.
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Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Muhammad Yusuf
"ABSTRAK
Latar Belakang: Kanker ovarium merupakan salah satu kanker yang menyebabkan kematian paling tinggi pada wanita. Tujuh puluh persen saat didiagnosis ditemukan pada stadium lanjut, dengan angka kesintsan dalam 5 tahun hanya 46 . Modalitas terapi saat ini adalah sitoreduksi dengan kemotterapi adjuvant platinum based sebagai lini pertama. Efektivitas kemoterapi hanya 60 pada stadium lanjut, untuk selanjutnya berkembang menjadi rekuren. Oleh karena itu dibutuhkan jenis terapi tambahan berdasarkan jenis atau agen yang bekerja spesifik di sel kanker dan dapat bersinergi dengan pengobatan standar saat ini. Kurkumin sebagai salah satu agen yang banyak diuji memiliki efek anti-kanker. Kurkumin berpotensi sebagai anti kanker dan bekerja pada semua multistep karsinogenesis. Kurkumin dapat bekerja sebagai antiproliferasi dan meningkatkan apoptosis.Tujuan: untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel hayati SKOV3.Metode: Penelitian ini dilakukan uji eksperimental in vitro dengan menggunakan sel hayati SKOV3 untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel tersebut. Uji analisis data dengan T tidak berpasangan bila sebaran normal / uji Mann Whitney bila sebaran tidak normal serta menggunakan Graph Pad Prism.Hasil: Berdasarkan penelitian ini, didapatkan cc50 nanokurkumin 67 m dan cc50 cisplatin 54 m dengan menggunakan metode MTT Assay. Viabilitas sel pada penelitian ini menurun sesuai dengan dose dependent, dimana pada dosis kombinasi nanokurkumin 134 m dengan cisplatin 108 m ditemukan sel hidup yang paling rendah 24.3 p

ABSTRACT
Background Ovarian cancer is one of the most leading cancers in women. Seventy percent at the time of diagnosis are found at an advanced stage, with a 5 year survival rate of only 46 . The current treatment modality is cytoreduction with platinum based adjuvant chemotherapy as first line. The effectiveness of chemotherapy is only 60 at an advanced stage, to further develop into recurrent. Therefore, additional types of therapy are required based on types or agents that work specifically in cancer cells and can synergize with current standard treatments. Curcumin as one of the many tested agents has anti cancer effects. Curcumin has the potential effect as an anti cancer and works on all multisteps of carcinogenesis. Curcumin can work as an antiproliferation and increase apoptosis.Objective to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on cell SKOV3.Methods This experimental study was conducted in vitro by using biological cell line SKOV3 to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on the cell. The data was analysed with unpaired T when normal distribution Mann Whitney test when distribution is not normal and also using Graph Pad Prism.Result Based on this result, cc50 of nanokurkumin is 67 m and cc50 of cisplatin is 54 m by using MTT Assay method. The viability of the cells in this study decreased according to the dose dependent, whereas in the combined dose of 134 m nanocurcumin with 108 m cisplatin found the lowest life cell 24.3 p "
2018
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Ni Nyoman Berlian Aryadevi Meylandari Putri
"Latar Belakang: Selama beberapa dekade, cisplatin menjadi kemoterapi paling aktif yang tersedia untuk kanker ovarium. Terlepas dari keunggulan hasilnya, cisplatin juga memiliki beberapa efek samping, salah satunya adalah hepatotoksisitas. Dalam perkembangan kedokteran, curcumin ditemukan memiliki efek hepatoprotektif dalam beberapa penelitian, tetapi ternyata memiliki bioavailabilitas yang rendah. Dengan demikian, nanocurcumin dibuat dan ditemukan untuk meningkatkan bioavailabilitasnya. Meskipun demikian, efek curcumin dan nanocurcumin dalam hepatotoksisitas yang disebabkan oleh terapi cisplatin pada kanker ovarium belum diamati. Penelitian ini bertujuan untuk menguji pengaruh kedua obat tersebut terhadap hepatotoksisitas yang diinduksi oleh cisplatin. Metode: Percobaan in vivo dilakukan pada tikus Wistar betina, dengan berat 150-200 gram, yang diinduksi oleh DMBA untuk mencapai model kanker ovarium. Kemudian, terapi cisplatin (4mg / kgBB / minggu) diberikan secara intraperitoneal pada tikus. Kemudian beberapa tikus juga diberi terapi kombinasi dengan curcumin (100 mg / kgBB / hari) dan nanocurcumin (100 mg / kgBB / hari). Tikus-tikus ini dibagi menjadi beberapa kelompok: tikus sehat, tidak ada pengobatan, terapi cisplatin, terapi cisplatin + curcumin, dan terapi cisplatin + nanocurcumin. Setelah sebulan, sampel darah diambil dan disentrifugasi untuk mendapatkan plasma. Tingkat AST, ALT, dan ALP diukur menggunakan spektrofotometer untuk menggambarkan fungsi hati. Hasilnya dianalisis menggunakan one-way ANOVA untuk ALT dan ALP dan Kruskall-Wallis untuk AST, menggunakan perangkat lunak SPSS24. Hasil: Tidak ada perbedaan statistik yang signifikan antara kelompok dalam AST plasma (p = 0,125), AlT (p = 0,154), dan ALP (p = 0,072). Kesimpulan: Tidak ada perbedaan yang signifikan untuk kurkumin dan nanokurkumin dalam mengurangi efek hepatotoksisitas cisplatin

Introduction: For decades, cisplatin has remained the most active chemotherapy available for ovarian cancer. Despite the excellence of the outcome, cisplatin also has severe side effects, one of which is hepatotoxicity. In the development of medicine, curcumin was found to exert a hepatoprotective effect in several studies, but it was found to have low bioavailability. Thus, nanocurcumin was established and discovered to improve its bioavailability. Nonetheless, the effect of curcumin and nanocurcumin in hepatotoxicity caused by cisplatin therapy in ovarian cancer has not been observed. This study aims to examine the effect of both drugs on the cisplatin-induced hepatotoxicity. Method: An in vivo experiment was done on female Wistar rats, weighing from 150-200 grams, which was induced by DMBA to achieve ovarian cancer models. Then, cisplatin therapy (4mg/kgBW/week) was given intraperitoneally to the rats. Then some of the rats were also given combination therapy with curcumin (100 mg/kgBW/day) and nanocurcumin (100 mg/kgBW/day). They were divided into groups of: healthy rats, no treatment, cisplatin therapy, cisplatin+curcumin therapy, and cisplatin+nanocurcumin therapy. After a month, blood sample was taken and centrifuged to obtain plasma. The AST, ALT, and ALP level was measured using spectrophotometer to depict the liver function. The result was analysed using one-way ANOVA for ALT and ALP and Kruskall-Wallis for AST using SPSS24 software. Results: Theres no significant statistical difference between groups in plasma AST (p=0.125), AlT (p=0.154), and ALP (p=0.072). Conclusion: There was no significant differences for both curcumin and nanocurcumin in reducing hepatotoxic effect of cisplatin."
Depok: Fakultas Kedokteran Universitas Indonesia, 2019
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Natasha Talya
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Latar Belakang: Cisplatin telah menjadi terapi lini pertama untuk kanker ovarium, namun efek samping terbesar cisplatin adalah peningkatan resistensi sel kanker yang menyebabkan hepatotoksisitas pada sel normal. Kurkumin terbukti memiliki sifat hepatoprotektif, tetapi efek terapeutik kurkumin terbatas karena memiliki bioavailabilitas yang rendah. Penggunaan kitosan nanopartikel pada kurkumin telah terbukti meningkatkan bioavailabilitas kurkumin sehingga efektivitasnya lebih besar. Penelitian ini dilaksanakan untuk melihat pengaruh nanokurkumin terhadap hepatotoksisitas akibat pemberian cisplatin. Tujuan: Membandingkan pengaruh kurkumin dan nanopartikel kurkumin untuk digunakan sebagai ko-kemoterapi dengan cisplatin pada kanker ovarium tikus yang ditinjau melalui jalur apoptosis, khususnya marker Bax dan Kaspase-3. Metode: Penelitian ini merupakan penelitian eksperimental in vivo pada model kanker ovarium tikus betina galur Wistar yang diinduksi 7,12-dimethybenzen[a]anthracene (DMBA) dan dilaksanakan di Departemen Farmakologi dan Terapeutik Fakultas Kedokteran Universitas Indonesia sejak bulan Juni 2019 hingga Juni 2020. Cisplatin diberikan dalam dosis sebesar 4 mg/kgBB secara intraperitoneal. Kurkumin dan nanokurkumin diberikan dalam dosis oral sebesar 100 mg/kgBB. Organ tersimpan hepar yang diambil dari 25 ekor tikus terbagi menjadi 5 kelompok perlakuan, yaitu kelompok tikus normal, model kanker ovarium tikus, terapi cisplatin, terapi cisplatin + kurkumin, dan terapi cisplatin + nanokurkumin. Setelah dikelompokkan, dilakukan homogenisasi sampel yang terpilih. Lalu, RNA Bax dan Kaspase-3 diisolasi dari homogenat sampel organ hepar dan cDNA kedua gen disintesis. Kemudian, tingkat ekspresi mRNA Bax dan Kaspase-3 pada hepar diukur menggunakan qRT-PCR. Data ekspresi mRNA Bax dan Kaspase-3 dianalisis dan diuji korelasi antarkelompok menggunakan aplikasi SPSS. Hasil: Tidak ada perbedaan yang signifikan antara kelima kelompok pada tingkat ekspresi mRNA Bax (p=0,372) dan Kaspase-3 (p=0,111). Kesimpulan: Tidak ditemukan pengaruh kurkumin dan nanokurkumin terhadap ekspresi mRNA Bax dan Kaspase-3 organ hepar pada model kanker ovarium tikus setelah pemberian terapi cisplatin.


Background: Cisplatin has become the first-line therapy for ovarian cancer, but it has a side effect of increasing cancer cell resistance which causes hepatotoxicity in normal cells. Curcumin has been shown to have hepatoprotective properties, but its therapeutic effect is limited because of its low bioavailability. The use of chitosan nanoparticles in curcumin has been shown to increase the bioavailability of curcumin. This research was conducted to see the effect of nanocurcumin on hepatotoxicity due to cisplatin administration. Aim: Comparing the effect of curcumin and curcumin nanoparticles as co-chemotherapy with cisplatin in rat ovarian cancer that is evaluated through apoptotic pathways, specifically Bax and Kaspase-3 markers. Methods: This research is an in vivo experimental study on a female ovarian cancer model of Wistar rats induced 7,12-dimethybenzen[a]anthracene (DMBA) and was carried out in the Department of Pharmacology and Therapeutics of the Faculty of Medicine, University of Indonesia from June 2019 to June 2020. Cisplatin is given in doses of 4 mg/kgBW intraperitoneal. Curcumin and nanocurcumin are given in oral doses of 100 mg/kgBW. Stored liver organs which was taken from 25 rats was divided into 5 treatment groups which are normal, ovarian cancer model, cisplatin therapy, cisplatin + curcumin therapy, and cisplatin + nanocurcumin therapy group. After the samples are grouped, homogenization of the selected sample is carried out. Then, the Bax and Kaspase-3 RNA were isolated from the homogenate samples and the cDNA of the two genes was synthesized. Then, the levels of Bax and Kaspase-3 mRNA expressions in the liver were measured using qRT-PCR. Bax and Kaspase-3 mRNA expressions were analyzed and tested intergroup correlations using the SPSS application. Results: There were no significant differences between the five groups in the expression levels of Bax mRNA (p=0,372) and Kaspase-3 (p=0,111). Conclusion: This study shows no effect of curcumin and nanocurcumin on the expression of Bax and Caspase-3 liver organ mRNA in rat ovarian cancer models after cisplatin therapy.

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Depok: Fakultas Kedokteran Universitas Indonesia , 2020
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Pinky Nur Alfaini
"Pendahuluan: Hampir 85% kasus karsinoma ovarium terjadi overekspresi endothelin-1 (ET-1) yang memodulasi persinyalan tumorigenesis dan metastasis. Disisi lain, cisplatin sebagai kemoterapi kanker ovarium menimbulkan efek samping dan resistensi terapi. Berbagai penelitian menunjukkan kurkumin berpotensi sebagai antikanker yang meningkatkan efikasi cisplatin dan menekan overekspresi ET-1 pada lini sel nonkanker. Namun, belum banyak penelitian yang mengidentifikasi penekanan ekspresi ET-1 oleh kurkumin dalam regimen terapi bersama cisplatin di kanker ovarium. Oleh karena itu, penelitian ini bertujuan melihat efek ko-kemoterapi kurkumin bersama cisplatin pada kanker ovarium terkait ekspresi relatif mRNA ET-1.
Metode: Jaringan ovarium tersimpan dari 24 tikus betina galur Wistar dibagi kedalam 4 kelompok: tikus yang hanya dibedah dan diberi aquadest (sham), tikus yang diimplantasi DMBA tanpa intervensi terapi, tikus yang diimplantasi DMBA dan diberi terapi tunggal cisplatin intraperitoneal 4 mg/kgBB/minggu, tikus yang diimplantasi DMBA dengan diberi terapi cisplatin 4 mg/kgBB/minggu dan kurkumin oral 100 mg/kgBB/hari. Implantasi DMBA dilakukan selama 28 minggu dan intervensi pada hewan coba selama 4 minggu. Setelah itu, jaringan ovarium tersimpan dianalisis ekspresi relatif mRNA ET-1 dengan mesin qRT-PCR menggunakan metode Livak-Schmittgen (2(-Ct)).
Hasil: Didapatkan rerata ekspresi relatif mRNA ET-1 [p=0,021] pada kelompok sham (0,349±0,24), kelompok DMBA (3,117±1,532), kelompok DMBA+cisplatin (0,993±0,651), dan kelompok DMBA+kurkumin+cisplatin (0,117±0,081). Ketiga kelompok tidak memiliki perbedaan bermakna dibandingkan sham. Meski demikian, terdapat perbedaan bermakna pada kelompok kombinasi cisplatin serta ko-kemoterapi kurkumin dengan kelompok tanpa intervensi terapi [p=0,019].
Kesimpulan: Terjadi penurunan ekspresi relatif mRNA endothelin-1 di jaringan ovarium model tikus yang diinduksi DMBA setelah pemberian kombinasi cisplatin dan ko-kemoterapi kurkumin.

Introduction: Endothelin-1 overexpression happens in 85% ovarian carcinoma cases that modulate metastatic and tumorigenesis. Meanwhile, cisplatin as ovarian cancer chemotherapy cause side effects and therapy resistances. Prior studies show potential effect of curcumin as an anticancer could enhance cisplatin efficacy and attenuate ET-1 overexpression in non-cancer cell lines. However, not many studies have identified suppression effect of ET-1 expression by curcumin with cisplatin in ovarian cancer. Therefore, this study is conducted to identify the effect of curcumin with cisplatin in ovarian cancer treatment especially its relation to relative expression of ET-1 mRNA.
Methods: Frozen ovarian tissue samples from 24 female Wistar rats were divided into 4 groups: a group that only operated on and treated with distilled-water (sham), group with DMBA-implantation, group with DMBA-implantation and intraperitoneal cisplatin 4mg/kgBW/week, group with DMBA-implantation and cisplatin with same dose as before plus oral curcumin 100mg/kgBW/day. After 28 weeks of DMBA-implantation and 4 weeks of intervention, frozen ovarian tissue samples were taken to measure its relative expression of ET-1 mRNA level with qRT-PCR machine.
Results: The mean of relative expression of ET-1 mRNA level [p=0,021] in frozen tissue sample of sham group (0,349±0,24), DMBA-implantation group (3,117±1,532), DMBA+cisplatin-treated group (0,993±0,651), and DMBA+curcumin+cisplatin-treated group (0,117±0,081). This study shows those 3 groups did not have significant difference compared with sham. But among group with cisplatin+curcumin-treated compared to DMBA-implantation shows a significant difference (p=0,019).
Conclusion: The relative expression of ET-1 mRNA in ovarian tissue of DMBA-induced rats model decreases after given by a combination of cisplatin+curcumin co-chemotherapy.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Fransisca Noela R.M.H.
"[ABSTRAK
Penelitian ini bertujuan untuk mengetahui gambaran umum kanker ovarium di Rumah Sakit Ciptomangunkusumo (RSCM) 5 tahun terakhir beserta faktor-faktor yang berhubungan dengan kanker ovarium. Penelitan ini mengambil data pasien kanker ovarium selain tipe borderline yang terdapat di Cancer Registry divisi Ginekologi Onkologi dan masih memiliki rekam medis di RSCM pada periode Januari 2010 – Desember 2014, dilakukan follow up untuk mengetahui kesintasan hidup selama 4 tahun. Kami mendapatkan 98 subyek penelitian. Pada penelitian ini didapatkan insidensi kanker ovarium terbanyak pada usia 45-54 tahun (33,6%), insidensi kanker ovarium menurun dengan bertambahnya jumlah anak, sebagian besar kanker ovarium merupakan tipe epitelial (76,5%) dan sebagian besar pasien didiagnosa pada stadium lanjut (55.1%). Kesintasan hidup 4 pasien kanker ovarium tipe epitelial 77%; tipe germinal 83.3%; tipe stroma 100%. Kesintasan hidup 4 tahun dengan terapi pembedahan 84.1%; pembedahan disertai kemoterapi adjuvan 83.3%; kemoterapi neoadjuvan sebelum pembedahan 68.4%. Terdapat 63% respon komplit pada kelompok kemoterapi adjuvan; dan 41.2% pada kelompok kemoterapi neoadjuvan.

ABSTRACT
The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.;The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.;The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy., The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.]"
Fakultas Kedokteran Universitas Indonesia, 2015
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UI - Tesis Membership  Universitas Indonesia Library
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Hari Sandi Sumardi Wiranegara
"Kanker ovarium masih menempati urutan kedua terbanyak dalam keganasan ginekologi dan merupakan penyebab utama kematian akibat kanker pada perempuan. Banyak bukti menunjukkan bahwa kanker ovarium umunya dalam pengaruh stress oksidatif. Dalam penelitian ini bertujuan untuk mengetahui aktivitas stress oksidatif melalui pengukuran enzim Superoxide Dismutase (SOD) dan kadar Malondialdehyde (MDA) pada penderita keganasan ovarium dibandingkan dengan penderita tumor jinak ovarium. Penelitian dilakukan dengan uji potong-lintang yang dilaksanalan di Ruang Rawat Kebidanan Ginekologi RSCM Jakarta, RS Persahabatan Jakarta dan RS Fatmawati Jakarta pada Juli hingga Desember 2018. Seluruh penderita keganasan ovarium dan penderita tumor jinak ovarium yang memenuhi kriteria diikutsertakan dalam penelitian ini. Darah penderita tumor ovarium diambil sebelum dilakukan operasi, lalu sampel dilakukan pengukuran kadar SOD dan MDA. Terdapat 35 penderita keganasan ovarium dan 43 penderita tumor jinak ovarium yang diikutsertakan dalam penelitian ini. Rerata atau median kadar SOD dan MDA pada penderita keganasan ovarium adalah 1,23 (0,24-5,709) dan 0,803 ± 0,316 , sementara rerata atau median kadar SOD dan MDA pada penderita tumor jinak ovarium adalah 0,488 (0,101-1,86) dan 0,634 ± 0,266. Terdapat perbedaan kadar SOD dan MDA yang bermakna antara kedua kelompok. Terdapat perbedaan kadar SOD yang bermakna antara penderita keganasan ovarium stadium awal dengan penderita keganasan ovarium stadium lanjut. Sementara pada pemeriksaan MDA tidak terdapat perbedaan bermakna antara penderita stadium awal dengan stadium lanjut. Kesimpullan pada penelitian ini terdapat perbedaan kadar SOD dan MDA yang bermakna antara penderita keganasan ovarium dengan penderita tumor jinak ovarium.

Ovarian cancer is the leading cause of death due to gynecological malignancies among women. A lot of evidence shows that ovarian cancer is generally influenced by oxidative stress. In this study aims to determine the activity of SOD enzymes and MDA levels in patients with ovarian malignancies and patients with benign ovarian tumors. The study was conducted by cross-sectional tests carried out in the RSCM Jakarta Gynecology Obstetric Room and Persahabatan Hospital Jakarta and Fatmawati Hospital Jakarta in July to December 2018. All patients with ovarian malignancies and patients with benign ovarian tumors who met the criteria were included in this study. Blood from ovarian tumor patients taken before surgery, then the samples were measured for SOD and MDA levels. There were 35 ovarian malignancies and 43 patients with benign ovarian tumors included in the study. The mean or median level of SOD and MDA in patients with ovarian malignancy is 1.23 (0.24 - 5.709) and 0.803 ± 0.316, while the mean or median level of SOD and MDA in patients with benign ovarian tumors is 0.488 (0.101-1.86) and 0.634 ± 0.266. There were significant differences in SOD and MDA levels between the two groups. There were significant differences in SOD levels between patients with early-stage ovarian malignancies and those with advanced ovarian malignancies. While on MDA examination there were no significant differences between patients with early stages with advanced stages. Conclusion in this study were significant differences in SOD and MDA levels between ovarian malignancies and patients with benign ovarian tumors"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Tugas Akhir  Universitas Indonesia Library
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