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Erico Wanafri
Efek nanokurkumin terhadap fungsi ginjal dan inflamasi pada tikus model kanker ovarium yang mendapat cisplatin = The effects of nanocurcumin on kidney function and inflammatory markers in rat model of ovarian cancer treated with cisplatin
"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."
Depok: Fakultas Kedokteran Universitas Indonesia, 2021
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Muhammad Farrasy Ammar
Pengaruh Nanokurkumin terhadap kadar antioksidan endogen jaringan hati pada model kanker ovarium yang mendapat cisplatin pada tikus = Effects of Nanocurcumin on hepatic endogenous antioxidants in cisplatin-treated rat ovarian cancer model
"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."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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Muhammad Yusuf
Efek antiproliferasi dan apoptosis kombinasi cisplatin dan nanokurkumin pada kultur sel hayati kanker ovarium skov3 = Effects of antiproliferation and apoptosis combination of cisplatin and nanocurcumin in culture of ovarian cancer cells skov3 / 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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Pinky Nur Alfaini
Peran kurkumin sebagai ko-kemoterapi cisplatin pada model kanker ovarium tikus yang diinduksi 7,12-dimethylbenz[a]anthracene (DMBA) melalui mekanisme endothelin-1 (et-1) = The role of curcumin as co-chemotherapy of cisplatin in ovarian cancer rats model-induced by 7,12-dimethylbenze[a]anthracene (DMBA) through endothelin-1 (et-1) mechanism.
"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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Ersal Rasyid Saharso
Uji Sitotoksisitas dan Fitokimia Ekstrak Biji Kemang (Mangifera kemanga) terhadap Sel Kanker Kolorektal HT-29 = Cytotoxicity and Phytochemistry test of Kemang (Mangifera kemanga) Seed Extract in HT-29 Colorectal Cancer Cells
"Latar Belakang: Ekstrak mangga memiliki efek anti kanker kolorektal, namun kemang (Mangifera kemanga) sebagai kerabat dari mangga belum banyak diteliti dan diduga memiliki efek yang serupa.
Tujuan: Mengetahui kandungan golongan senyawa yang terdapat dalam ekstrak etanol, etil asetat, dan n-heksan biji kemang serta menguji efek sitotoksisitasnya terhadap sel kanker kolorektal HT-29
Metode: Biji kemang diekstraksi menggunakan pelarut etanol, etil asetat dan n-heksan. Dilaksanakan uji fitokimia dan kromatografi lapis tipis untuk mengetahui kandungan fitokimia yang terdapat di dalam ketiga ekstrak tersebut. Uji MTT dilaksanakan pada ketiga ekstrak yang diuji terhadap sel HT-29 untuk mengetahui efek anti kanker sampel dengan mengukur nilai IC50
Hasil: Ekstrak etanol biji kemang memiliki senyawa fitokimia flavonoid, triterpenoid, tanin, dan alkaloid, namun ekstrak etil asetat hanya memiliki senyawa triterpenoid dan tanin sementara ekstrak n-heksan hanya memiliki senyawa tanin. Uji kromatografi lapis tipis dengan eluen non-polar menunjukkan dua titik dengan Rf 0,42 dan 0,82 pada ekstrak etanol; lima titik dengan Rf 0,25, 0,39, 0,75, 0,86, dan 0,95 pada ekstrak etil asetat; dan dua titik dengan Rf 0,71 dan 0,89 pada ekstrak n-heksan. Uji MTT mendapatkan nilai IC50 terhadap sel HT-29 dari ekstrak etanol, etil asetat, dan n-heksan secara berturut-turut adalah 28,645, 0,1858, dan 11,1363 ppm.
Diskusi: Kandungan fitokimia dalam ekstrak biji kemang memiliki efek anti kanker terhadap sel kanker kolorektal. Aktivitas anti kanker dari ekstrak etil asetat lebih baik dibandingkan dengan ekstrak etanol dan n-heksan biji kemang.
Background: Mango extract has been shown to have anticancer effects against colorectal cancer, however kemang (Mangifera kemanga), a relative of mango, which has not been widely studied is thought to have a similar effect.
Objective: To identify the compounds contained in the ethanol, ethyl acetate, and n-hexane extract of kemang seed and examine its cytotoxic effect to HT-29 colorectal cancer cells.
Methods: Kemang seed was extracted using ethanol, ethyl acetate, and n-hexane solvents. Phytochemical test and thin-layer chromatography were carried out to determine the phytochemical contents contained in the extracts. An MTT test using the three extracts was done to determine the anticancer effect of the sample by measuring IC50 value.
Results:. The ethanol extract of kemang seed contained flavonoid, triterpenoid, tannin, and alkaloid phytochemical compounds, however the ethyl acetate extract only contains triterpenoid and tannin compounds while the n-hexane extract only contains tannin compounds. Thin-layer chromatography test with non-polar eluent showed two spots with Rf of 0,42 and 0,82 in ethanol extract; five spots with Rf of 0,25, 0,39, 0,75, 0,86, and 0,95 in ethyl acetate extract; and two spots with Rf of 0,71 and 0,89 in n-hexane extract. The IC50 value of the ethanol, ethyl acetate, and n-hexane extracts on HT-29 cells respectively are 28,645, 0,1858, and 11,1363 ppm.
Discussion: The phytochemical contents in kemang seed has anticancer effect on colorectal cancer cells. Anticancer activity of ethyl acetate extract is better than that of ethanol or n-hexane kemang seed extract"
Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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Ekida Rehan Firmansyah
Modulasi Jalur Inflamasi oleh Ko-kemoterapi Kurkumin dan Nanokurkumin terhadap Hepatotoksisitas Cisplatin pada Model Kanker Ovarium Tikus = Modulation of Inflammatory Pathway by Co-chemotherapy Curcumin and Nanocurcumin toward Cisplatin-induced Hepatotoxicity in Ovarian Cancer Rat Model
"Salah satu obat antikanker yang sekarang paling efektif digunakan sebagai kemoterapi kanker ovarium adalah cisplatin. Namun, cisplatin memiliki banyak efek samping pada berbagai organ, salah satunya hepar. Hepatotoksisitas akibat cisplatin menyebabkan terbatasnya dosis kemoterapi cisplatin. Salah satu faktor kunci patofisiologi kerusakan akut hepar adalah inflamasi. Kurkumin merupakan senyawa alami yang memiliki sifat antiinflamasi tetapi bioavailabilitasnya rendah. Untuk itu, diformulasikan nanokurkumin untuk meningkatkan bioavailabilitasnya. Meskipun begitu, efek kurkumin dan nanokurkumin dalam memodulasi jalur inflamasi hepatotoksisitas akibat cisplatin pada kanker ovarium belum diamati. Penelitian ini bertujuan untuk membandingkan pengaruh kurkumin dan nanokurkumin sebagai ko-kemoterapi terhadap hepatotoksisitas cisplatin dalam jalur inflamasi. Penelitian in vivo dilakukan pada tikus Wistar betina yang diinduksi DMBA untuk mendapatkan model kanker ovarium. Kemudian, tikus-tikus diberi perlakuan terapi dengan cisplatin secara intraperitoneal (4 mg/kgBB/minggu) dan kombinasinya dengan kurkumin (100 mg/kgBB/hari) dan nanokurkumin (100 mg/kgBB/hari) per oral. Tikus-tikus tersebut dibagi menjadi kelompok: tikus normal, model kanker ovarium saja, terapi cisplatin, terapi cisplatin + kurkumin, dan terapi cisplatin + nanokurkumin. Setelah 1 bulan, tikus di-sacrifice dan organ hepar disimpan beku. Ekspresi mRNA relatif NF-κB dan IL-1β serta kadar protein IL-6 diukur dengan metode qt RT-PCR dan ELISA secara berurutan. Data hasil pengukuran IL-6 dan data hasil transformasi logaritma NF-κB dan IL-1β dianalisis menggunakan uji one-way ANOVA, menggunakan perangkat lunak SPSS20. Tidak terdapat perbedaan signifikan secara statistik antar kelompok perlakuan dalam mRNA NF-κB (p=0,503), mRNA IL-1β (p=0,237), dan protein IL-6 (p=0,157). Tidak ada perbedaan yang signifikan antara kurkumin dan nanokurkumin dalam memodulasi jalur inflamasi hepatotoksisitas cisplatin pada model kanker ovarium tikus.
Up to now, one of the most effective anticancer drug as ovarian cancer chemotherapy is cisplatin. Nevertheless, cisplatin has many side effects on several organs, one of which is liver. Cisplatin-induced hepatotoxicity causes limited cisplatin chemotherapy dose. One of the pathophysiological key factor of acute liver injury is inflamation. Curcumin is natural compound which has antiinflamation properties but the bioavailability is low. To overcome it, nanocurcumin is made to increase its bioavailability. Nonetheless, curcumin and nanocurcumin effect on modulating inflammatory pathway toward cisplatin-induced hepatotoxicity in ovarian cancer rat model has not been observed. This study aims to compare the effect of curcumin and nanocurcumin as co-chemotherapy toward cisplatin-induced hepatotoxicity in inflammatory pathway. An in vivo study was done on female Wistar rats induced by DMBA to achieve ovarian cancer model. Then, rats was treated with cisplatin intraperitoneally (4 mg/kgBW/week) and the combination with per oral curcumin (100 mg/kgBW/day) and nanocurcumin (100 mg/kgBW/day). Those rats were divided into groups, which are normal rat, only ovarian cancer model, cisplatin therapy, cisplatin + curcumin therapy, and cisplatin + nanocurcumin therapy. After 1 month, rats are sacrificed and liver organs are stored frozen. mRNA relative expression of NF-κB and IL-1β as well as protein level of IL-6 was measured using qt RT-PCR and ELISA method, respectively. The result data from the measurement of IL-6 and the data from logarithmic transformation of NF-κB and IL-1β was analysed using one-way ANOVA test using SPSS20 software. There is no significant differences between groups in mRNA NF-κB (p=0.503), mRNA IL-1β (p=0.237), and protein IL-6 (p=0.157). There is no significant differences between curcumin and nanocurcumin in modulating inflammatory pathway of cisplatin-induced hepatotoxicity in ovarian cancer rat model."
Jakarta: Fakultas Kedokteran Universitas Indonesia , 2020
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Dimas Kirana Mahaputra
Efek Nanokurkumin pada Histologi Fibrosis Hati yang Diinduksi 7,12-dimethylbenz(a)anthracene dan Cisplatin sebagai Model Kanker Ovarium pada Tikus = The Effects of Nanocurcumin on Histology of Liver Fibrosis Induced with 7,12-dimethylbenz(a)anthracene and Cisplatin as a Rat Ovarian Cancer Model
"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
Pengaruh nanokurkumin terhadap hepatotoksisitas cisplatin pada kanker ovarium tikus ditinjau dari TNF-α dan TGF-β1 = Effects of nanocurcumin on cisplatin-induced hepatotoxicity in rat ovarian cancer in terms of TNF-α and TGF-β1
"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."
Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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Pelupessy, Nugraha Utama
Marker cancer stem cells (CD133, CD44 dan ALDH1A1) sebagai faktor prognostik pada kanker ovarium tipe epitelial = Cancer stem cell CD133, CD44 and ALDH1A1 markers as prognostic factors on epithelial ovarian cancer
"ABSTRAK
Nama :Nugraha Utama PelupessyProgram Studi :S3 Ilmu KedokteranJudul :Marker Cancer Stem Cells CD133, CD44, dan ALDH1A1 Sebagai Faktor Prognostik pada Kanker Ovarium Tipe Epitelial Kanker ovarium merupakan penyakit yang bersifat heterogen dan kebanyakan pasien datang dengan stadium lanjut. Kanker ovarium epitelial tipe II mempunyai sifat pertumbuhan tumor yang cepat dan secara genetik labil dibandingkan tipe I. Keberadaan cancer stem cells CSC dianggap sebagai salah satu faktor prognostik terjadinya kemoresisten dan kesintasan hidup yang rendah.Penelitian ini bertujuan untuk membuktikan CSC sebagai faktor prognostik dengan menggunakan marker CD133, CD44, dan ALDH1A1 pada kanker ovarium tipe epitelial.Marker CD133, CD44, dan ALDH1A1 diperiksa dengan imunohistokimia dan flowcytometry. Hasil ekspresi marker CSC pasien kanker ovarium tipe I dan tipe II dimasukkan kedalam suatu tabel yang dihubungkan dengan respons kemoterapi dan kesintasan hidup. Analisis data dilakukan dengan program computer STATA 14. Analisis kesintasan dilakukan dengan analisis Kaplan-Meier dan uji asumsi cox proportional hazard. Analisis multivariat dipakai untuk model prognosis selama 10 bulan. Sistem skoring dibuat dengan menggunakan receiver operating characteristic ROC curve analyses.Data demografi kelompok terbanyak adalah usia ge; 45 tahun; 40 sampel 72,7 , stadium I, 23 sampel 41,8 , diferensiasi buruk 30 sampel 54,5 , dan tipe II 16 sampel 29,1 . Perbedaan yang bermakna antara tipe histopatologi dengan marker CSC hanya terlihat pada marker CD44. Skor Prediksi Kemoresisten SPKr 10 bulan yang dihubungkan dengan 4 variabel yaitu usia ge; 45 tahun, tipe II, stadium III minus;IV, dan CD44 tinggi dengan ROC 72,47 dan probabilitas post test 82,5 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 negatif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841. Skor Prediksi Kematian SPKm 10 bulan yang dihubungkan dengan 3 variabel yaitu stadium III minus;IV, tipe II, dan CD44 tinggi dengan AUC 80,44 dan probabilitas post test 78,7 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 positif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841.Simpulan: Marker CD44 terbukti berperan pada kanker ovarium tipe II. Skor Prediksi Kemoresisten dan Skor Prediksi Kematian dapat ditentukan selain dengan faktor klinikopatologi, juga dengan memakai marker CSC. Kata kunci: ALDH1A1, CD44, CD133, CSC, kanker ovarium epitelial, kesintasan hidup, respons kemoterapi.
ABSTRACT
Name : Nugraha Utama PelupessyStudy Program : Doctoral Program Medical SciencesTitle :Cancer Stem Cell CD133, CD44 andALDH1A1 Markers As Prognostic Factors on Epithelial Ovarian Cancer. Ovarian cancer is a heterogeneous disease and most of the patients came with an advanced stage. Epithelial ovarian cancer type II has the characteristic of rapid tumor growth and genetically more labile than that of type I. The presence of cancer stem cells CSC is considered as one of the prognostic factors of low mortality and survival.The aims of this study was to prove CSC as prognostic factors using CD133, CD44, and ALDH1A1 markers on epithelial ovarian cancer.Clinicopathology and demographic data were collected from medical records. CD133, CD44, and ALDH1A1 markers were examined with flowcytometry and immunohistochemistry. CSC marker expression of the patients with ovarian cancer type I and II was connected with chemotherapy and survival response. Data analysis was done by using STATA 14 software. Survival analysis was done by using Kaplan-Meier analysis and Cox proportional hazard test. Multivariate analysis is used for prognosis model for ten months. Receiver Operating Characteristic ROC curve analyses was used as the system scoring. The highest group demographic data were age ge; 45 years; 40 samples 72.7 , stage I, 23 samples 41.8 , poor differentiation 30 samples 54.5 , and type II 16 samples 29.1 . A significant difference between the histopathologic type and the CSC marker was seen only in CD44 marker. Chemoresistance Prediction Score in 10 months was associated with 4 variables ie age ge; 45 years, type II, stage III minus;IV, and CD44 high with ROC 72.47 and posttest probability 82.5 . The highest chemoresitency scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, negative CD133, high CD44, and high ALDH1A1, was 0.841. Mortality Prediction Score in 10 months was associated with 3 variables is stage III minus;IV, type II, and CD44 high with AUC 80.44 and posttest probability 78.7 . The highest mortality scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, positive CD133, high CD44, and high ALDH1A1, was 0.841. Conclusion: The CD44 marker has a role in type II ovarian epithelial cancer. Chemoresistance Prediction Score and Mortality Prediction Score can be determined from clinicopathological factors and using CSC marker. Keywords: ALDH1A1, CD44, CD133, chemotherapy response, CSC, Epithelial Ovarian Cancer, survival"
Depok: Fakultas Kedokteran Universitas Indonesia, 2018
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Leo Alfath Araysi
Efek Kurkumin Sebagai Ko-Kemoterapi Cisplatin terhadap Ekspresi Reseptor Endothelin A (ETAR) dan Gambaran Histopatologi pada Ginjal Tikus Model Kanker Ovarium = Effects of Curcumin as Cisplatin Co-Chemotherapy upon The Expression of Endothelin Receptor A (ETAR) and Histopathological Appearance in Rat’s Kidney with Ovarian Cancer
"Latar belakang: Kanker ovarium diduga dapat menyebabkan penurunan fungsi dan kerusakan ginjal. Cisplatin salah satu terapi kanker ovarium bersifat nefrotoksik. Kerusakan ginjal ini terjadi melalui berbagai mekanisme, salah satunya adalah peningkatan ekspresi ETAR. Kurkumin diduga mampu menurunkan ekspresi ETAR pada jaringan ginjal yang rusak. Penelitian ini bertujuan untuk mengetahui efek ko-kemoterapi kurkumin pada cisplatin terhadap ekspresi ETAR serta gambaran histopatologi jaringan ginjal pada tikus model kanker ovarium. Metode: 24 tikus wistar betina dibagi menjadi empat kelompok: Kelompok normal sham (N), kanker ovarium tanpa perlakuan (Ca), kanker ovarium yang mendapat 4 mg/KgBB cisplatin (Cis), dan kanker ovarium yang mendapat 4 mg/KgBB cisplatin +100 mg/KgBB kurkumin (Cis+Cur). Setelah 3 minggu tikus dikorbankan, ginjal tikus diambil untuk pengamatan histopatolgi serta ekspresi mRNA ETAR. Hasil: Pada pengamatan histopatologi Masson Trichrome ditemukan fokus fibrosis pada kelompok tikus Ca dan Cis. Melalui qRT-PCR diketahui bahwa ekspresi mRNA pada kelompok Ca dan Cis relatif sama, namun meningkat masing-masing sebesar 133% (2,33 kali lipat) dan 123% (2,23 kali lipat) dibandingkan dengan kelompok normal. Sedangkan pada kelompok Cis+Cur terdapat penurunan ekspresi mRNA sebesar 31,5% (0.315 lebih rendah) dan 34,4% (0.344 lebih rendah) berurutan dibanding kelompok Cis dan Cur. Tidak ditemukan perbedaan bermakna secara statistik antar kelompok uji. Kesimpulan: Kanker ovarium dapat memicu kerusakan ginjal pada tiku dibuktikan dengan peningkatan ekspresi mRNA ETAR dan fokus fibrosis. Pemberian cisplatin pada dosis terapeutik tidak meningkatkan ekspresi mRNA ETAR pada jaringan tikus model kanker ovarium, meski demikian pemberian kurkumin sebagai ko-kemoterapi menurunkan ekspresi mRNA ETAR dan fokus fibrosis meskipun tidak bermakna secara statistik.
Background: Ovarian cancer is believed can lead to renal functional deterioration Furthermore, cisplatin as chemotherapeutic agent has nephrotoxic effects. Increased expression of the Endothelin A receptor (ETAR) is thought to be one of the mechanisms. Curcumin is believed to have protective effects in injured kidney. This study is to evaluate the co-chemotherapy effects of curcumin for cisplatin upon ETAR expression and histopathological appearances in rats’ kidney. Method: Total of 24 wistar rats, devided into four treatment groups: normal group (N), ovarian cancer without treatment group (Ca), ovarian cancer which received cisplatin 4 mg/kgBW group (Cis), and ovarian cancer which received cisplatin 4 mg/kgBW + 100 mg/kgBW curcumin group (Cis+Cur). Kidney tissue specimen was obtained for histopathological examination and ETAR messenger ribonucleic acid (mRNA) expression. Results: Fibrosis foci were found at kidney tissue of Ca and Cis group. The mRNA expression level among Ca and Cis group were relatively equivalent; however increased by 133% (2,33 fold) and by 123% (2,23 fold), respectively compared to N group. Meanwhile, the Cis + Cur group decreased by 31.5% (0.315 lower) and 34.4 % (0.344 lower) compared to Cis and Ca group respectively. There are no statistical significant among the experiment groups. Conclusion: Ovarian cancer is associated with kidney injury, demonstrated by increased of ETAR mRNA and fibrosis foci formation. Therapeutic dose cisplatin do not increased ETAR mRNA in the kidney of ovarian cancer rat. Curcumin administration as co-chemotherapeutic agent result in the decrease of ETAR mRNA level and the decrease of fibrosis foci formation."
Depok: Fakultas Kedokteran Universitas Indonesia, 2021
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