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"Pendahuluan: Proses karsinogenesis adenokarsinoma prostat terjadi akibat disregulasi kadar zinc dalam sel. Molekul zinc intrasel berperan dalam metabolisme aerob mitokondria dan induksi apoptosis. Penyerapan zinc diatur oleh protein ZIP1, berperan meningkatkan kandungan zinc sitoplasmik intrasel dengan membawa zinc dari cairan ekstrasel. Kadar zinc yang tinggi dan ekspresi protein ZIP1 banyak ditemukan pada epitel prostat normal, sedangkan pada kanker prostat ditemukan sedikit atau tidak ada ekspresi protein ZIP1. Penurunan ekspresi ZIP1 diduga dapat menghambat apoptosis, serta memacu perkembangan adenokarsinoma prostat. Penelitian ini bertujuan menganalisis korelasi ekspresi protein ZIP1 dan Caspase- 3 pada jaringan adenokarsinoma prostat berdasarkan Gleason score yang berbeda. Metode: Desain studi analitik retrospektif dengan desain potong lintang. Sampel penelitian ini adalah 31 sediaan blok parafin adenokarsinoma prostat yang memenuhi kriteria inklusi. Sediaan dipulas menggunakan teknik imunohistokimia untuk mengetahui ekspresi protein ZIP1 dan caspase-3. Ekspresi protein pada pulasan slide dihitung menggunakan program imageJ. Gleason score sebagai data sekunder yang didapatkan dari laporan kasus. Korelasi ekspresi kedua protein berdasarkan Gleason score dianalisis dengan uji korelasi Pearson menggunakan SPSS 11.5. Hasil: Rerata positivitas ekspresi ZIP1 pada adenokarsinoma prostate adalah 35% dan rerata positivitas caspase-3 adalah 33%. Terdapat korelasi positif bermakna antara ekspresi ZIP1 dan caspase-3 (r = 0.379 , p = 0,018). Terdapat korelasi positif antara ekspresi ZIP1 dan caspase-3 pada kelompok intermediate grade (r = 0.73, p = 0.01) dan korelasi lemah tidak bermakna pada kelompok high grade (r = 0.04, p = 0.48). Kesimpulan: Terdapat korelasi positif antara ekspresi ZIP1 dan ekspresi caspase- 3 pada adenokarsinoma prostat.

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Introduction: Carcinogenesis of adenocarcinoma of the prostate occurs due to dysregulation of zinc level within the cells. Intracellular zinc molecules contributes to mitochondrial aerobic metabolism. Its influx is regulated by a transporter protein ZIP1, whose non-presence is predicted to inhibit apoptosis, thus leads to the development of prostate adenocarcinoma. This study was aimed to analyze the correlation of ZIP1 and Caspase-3 expression in prostate adenocarcinoma with respect to its grading as represented by Gleason Score.

Methods: This was a cross-sectional, retrospective analytical study on 31 formalyn-fixed, paraffin-embedded tissue that meet inclusion criteria. The specimen was stained using immunohistochemical technique for ZIP1 and Caspase-3. Protein expression of each case were counted using ImageJ analysis. Gleason score were acquired as secondary data from the cases’ reports. The correlation of their expression with respect of Gleason score were analyzed with Pearson’s correlation using SPSS 11.5.

Results: Mean expression level of ZIP1 and Caspase-3 in prostate adenocarcinoma were 35% and 33%, respectively. There was a significantly positive correlation between ZIP1 and Caspase-3 expression (r=0.379; p=0.018). However, their correlation was stronger in intermediate-grade group (r=0.73; p=0.01) and the correlation was much weaker in high-grade group (r=0.04; p=0.48).

Conclusion: There was a positive correlation between ZIP1 and caspase-3 expression in adenocarcinoma prostate."

"Latar belakang: Kanker kolon merupakan salah satu kanker yang paling sering didiagnosis di dunia, termasuk Indonesia. Pengobatan yang tersedia memiliki tingkat keberhasilan tidak memuaskan dengan berbagai komplikasi sekunder. Lunasin telah dikembangkan karena aktivitasnya yang mencolok dalam menghambat perkembangan kanker. Caspase-3 merupakan mediator utama apoptosis yang digunakan sebagai penanda kemanjuran terapi kanker. Penelitian ini bertujuan untuk membuktikan pengaruh lunasin terhadap ekspresi Caspase-3 pada kolon mencit yang diiinduksi DSS dan AOM. Metode: Mencit Swiss-Webster jantan berjumlah tiga puluh ekor dengan rerata berat badan 20 gram dibagi dalam enam kelompok yang terdiri dari kontrol normal, kontrol negatif, kontrol positif, lunasin dosis 250 mg/kgBB, 300 mg/kgBB, dan 350 mg/kgBB. Seluruh kelompok kecuali kontrol normal diinduksi DSS dan AOM. Kontrol positif menerima aspirin. Kolon mencit dibuat preparat menggunakan pewarnaan imunohistokimia dan HE sebagai counterstain. Preparat dibaca di mikroskop dan h-score menggunakan immunohistochemistry profiler. Hasil: Seluruh kelompok kontrol normal (mean=250,13), kontrol negatif (mean=133,22), kontrol positif (mean=214,83), lunasin dosis 250 mg/kgBB (mean=163,35), 300 mg/kgBB (mean=189,94), dan 350 mg/kgBB (mean=216,43) terdapat perbedaan signifikan kecuali antara kelompok kontrol positif dengan dosis 350 mg/kgBB. Selain itu, terdapat ekspresi Caspase-3 lebih tinggi yang signifikan seiring peningkatan dosis lunasin. Kesimpulan: Lunasin dosis 250 mg/kgBB, 300 mg/kgBB, dan 350 mg/kgBB terbukti berpengaruh meningkatkan ekspresi Caspase-3 kolon mencit yang diinduksi DSS dan AOM.

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Background: Colon cancer is one of the most frequently diagnosed cancers in the world, including Indonesia. Currently available treatment has an unsatisfactory success rate with a variety of secondary complications. Lunasin has been developed for its striking activity in inhibiting the development of cancer. Caspase-3 is the main mediator of apoptosis which is used as a marker of cancer therapeutic efficacy. This study aimed to prove the effect of lunasin on Caspase-3 expression in the colon of mice induced by DSS and AOM. Methods: Thirty male Swiss-Webster mice with an average body weight of 20 grams were divided into six groups consisting of normal control, negative control, positive control, doses of lunasin 250 mg/kgBW, 300 mg/kgBW, and 350 mg/kgBW. All groups except normal controls were induced by DSS and AOM. Positive controls received aspirin. Mice colons were prepared using immunohistochemical staining and HE as a counterstain. The preparations were read under a microscope and h-score using an immunohistochemistry profiler.

Results: In all groups of normal control (mean=250.13), negative control (mean=133.22), positive control (mean=214.83), doses of lunasin 250 mg/kgBW (mean=163.35), 300 mg/kgBW (mean=189.94), and 350 mg/kgBW (mean=216.43) there were significant differences except between the positive control group with 350 mg/kgBW group. In addition, there was a significantly higher Caspase-3 expression as the dose of lunasin increased.

Conclusion: Lunasin 250 mg/kgBW, 300 mg/kgBW, and 350 mg/kgBW proved to have an effect on increasing the expression of Caspase-3 in the colon of mice induced by DSS and AOM."

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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.

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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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