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"Infertilitas merupakan penyakit yang kompleks dan dapatdisebabkan oleh faktor laki-laki dan perempuan. Etiologi darikedua faktor infertilitas tersebut perlu ditelusuri lebih lanjut.Terdapat beberapa pendekatan untuk memahami infertilitas,salah satunya adalah epigenetik. Modifikasi epigenetik terdiridari metilasi DNA, modifikasi histon, dan pembentukankromatin. Sel germinal laki-laki dan perempuan mengalamimodifikasi epigenetik secara dinamis dan membentuk sel spermadan oosit yang matang. Pada laki-laki, perubahan metilasi DNApada spermatogenesis dapat menyebabkan kelainan berupaoligo/astenozoospermia. Selain itu, metilasi dan asetilasi histonserta modifikasi histon lainnya dapat menyebabkan spermatidak mampu untuk membuahi oosit. Serupa dengan laki-laki,pada perempuan pun dapat terjadi perubahan metilasi DNAdan modifikasi histon yang dapat mempengaruhi oogenesis,menciptakan anueploidi pada oosit yang terbuahi, danmengakibatkan kematian janin di uterus. Perubahan pada polamodifikasi epigenetik dapat mengakibatkan infertilitas, baikpada laki-laki maupun perempuan."

"ABSTRACTDiabetes mellitus (DM) is one of the most abundant diseases in the 21st century and believed as result of interaction between genes and environment exposure. There is a hypotesis of epigenetic mechanisms, using molecular basis to explain about the mechanism of DM. Because of the enviromental exposure including nutrition status and hyperglycemia state, the risk of DM has started since pre-conception, last until adulthood and will be inhireted trans-generational . Mainly, there are 3 epigenetic mechanisms that have role in DM. Epigenetic mechanisms are also have role in the metabolic memory that the DM complications may still developed although the blood glucose level is already normal. The restriction of calory intake may help delaying the development and onset of degerative diseases including DM by stabilizing genome through epigenetic mechanisms."

"Pendahuluan: Tata laksana yang tersedia untuk kanker kolorektal masih kurang efektif dan memiliki berbagai efek samping. Protein lunasin dapat mempengaruhi kanker melalui berbagai mekanisme, salah satunya epigenetik, melalui asetilasi histon. Dengan kemampuan kemopreventif dan kemoterapeutiknya, lunasin berpotensi sebagai adjuvant untuk terapi konvensional kanker.Metode: Tiga puluh mencit Swiss Webster dibagi menjadi enam kelompok, yaitu normal, kontrol positif dan negatif, dan tiga kelompok perlakuan. Selain kelompok normal, dilakukan induksi karsinogenesis dengan injeksi AOM + DSS. Mencit perlakuan diberikan ekstrak kedelai dengan dosis 250 mg/kgBB, 300 mg/kgBB, dan 350 mg/kgBB selama 4 minggu. Ekspresi histon deasetilase (HDAC) dinilai dengan IHC optical density score.Hasil: Rata-rata ekspresi HDAC pada kelompok normal = 202,4%; kontrol negatif = 239,3%; kontrol positif = 175,25%; dosis 250 mg/kgBB = 202,03%, dosis 300 mg/kgBB = 219,53%, dosis 350 mg/kgBB = 166,68%. Ekspresi HDAC pada dosis ekstrak kedelai 250 mg/kgBB (p=0,221) dan 300 mg/kgBB (p=0,347) tidak berbeda signifikan dengan kontrol negatif. Terdapat perbedaan signifikan ekspresi HDAC pada dosis sebesar 350 mg/kgBB (p=0,014).Kesimpulan: Lunasin dalam ekstrak kedelai dengan dosis 350 mg/kgBB dapat menurunkan ekspresi HDAC pada model karsinogenesis kanker kolorektal.

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Background: The available treatments for colorectal cancer still have limited efficacy and various side effects. There are various mechanisms for lunasin protein to affect cancer, one of them is epigenetics, by histone acetylation. Lunasin has the potential to be conventional cancer therapy adjuvant with its chemopreventive and chemotherapeutic abilities.

Method: Thirty Swiss Webster mice is divided into six groups: normal, positive control, negative control, and three experimental groups. Except normal group, mice undergo carcinogenesis induction with AOM + DSS injection. Experimental mice receive soy extract with 250 mg/kgBW, 300 mg/kgBW and 350 mg/kgBW dosage for 4 weeks. Histone deacetylase (HDAC) expression is measured with IHC optical density score.

Result: Average HDAC expression on normal groups = 202,4%; negative control = 239,3%; positive control = 175,25%; 250 mg/kgBW dose = 166,68%; 300 mg/kgBW dose = 219,53%, 350 mg/kgBW dose = 166,68%. There is no significant difference between HDAC expression in 250 mg/kgBW (p=0,221) and 300 mg/kgBW (p=0,347) dose of soy extract with negative control. There is significant difference of HDAC expression with 350 mg/kgBW dose of soy extract (p=0,014).

Conclusion: Lunasin in soy extract with 350 mg/kgBW dose can decrease HDAC expression in colorectal cancer carcinogenesis model."

"Respons tumor terhadap radiasi dipengaruhi oleh berbagai faktor yang dapat digolongkan ke dalam faktor intrinsik yang bersifat genetik dan faktor-faktor lingkungan mikro (microenvirontment) yang disebut faktor epigenetik. Faktor intrinsik dapat ditunjukkan dengan 'predictive assay' yang dapat memperlihatkan sensitivitas individual tumor. Faktor epigenetik terdiri dari berbagai faktor termasuk hipoksia, vaskularisasi dan fraksi pertumbuhan. Dan berbagai penelitian dapat ditunjukkan hubungan antara beberapa faktor itu dengan respons tumor, maupun antara ketiga faktor tersebut. Dapat diasumsikan bahwa faktor hipoksia, vaskularisasi dan fraksi pertumbuhan merupakan indikatorindikator Iingkungan tumor yang dapat merupakan prediktor terhadap respons radiasi pada jaringan tumor tersebut. Pada penelitian ini, fraksi pertumbuhan tumor akan diteliti kaitannya dengan respons tumor dan pemanfaatannya dalam pengobatan gabungan untuk meningkatkan respons pada tumor yang mempunyai prognosis buruk. Berdasarkan asumsi bahwa tumor dengan fraksi pertumbuhan rendah relatif hipoksik, maka dilakukan pengobatan gabungan radiasi dengan MMC, suatu sitostatika yang bekerja efektif dalam keadaan hipoksik pada kelompok-kelompok tumor yang sudah digolongkan ke dalam fraksi pertumbuhan yang rendah dan yang tinggi. Pemilahan pasien berdasarkan besarnya fraksi pertumbuhan dilakukan dengan pemeriksaan imunohistokimia pada jaringan biopsi segar penderita kanker leher rahim menggunakan antibodi monoklonal Ki-67. Penderita KLR yang diteliti adalah penderita stadium lanjut lokal (stadium II b sampai III b menurut FIGO) yang datang ke Sub Bagian Onkologi Bagian Obstetri dan Ginekologi FKUI/RSCM dan kemudian dikirim ke Sub Bagian Radioterapi Bagian Radiologi FKUI/RSCM

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Response of tumors toward radiation is affected by various factors that can be classified as intrinsic factors, which are genetic, and epigenetic factors, which are micro environment. The intrinsic factors can be demonstrated through a "predictive assay" which can show the sensitivity of individual tumor.Epigenetic factors consist of many factors including hypoxia, vascularization, and growth fraction. From results of many studies, can' be shown that there is a relation between these last factors with response of tumor. There is also relation among these three factors. We can assume that hypoxia, vascularization and growth fraction are indicators of tumor's environment which can also be predictors of response to radiation in tumor tissue.In this study, the rate of tumor growth will be studied in it's relation to tumor's response and the uses in combined treatment to increase the response of tumors with bad prognosis.Based on an assumption that tumors with low growth fraction are relatively hypoxic, combination of radiation with MMC is used, a cytostatic agent that effectively work on hypoxic condition in groups of tumors which have been classified as having low growth fraction. Patients grouping were performed based on the growth fraction as seen in immunohisto chemistry examination on fresh biopsy tissue of patients with cancer of cervix, using Ki-67 monoclonal antibody. Those patients of cancer of the cervix included in this study were patients in locally advanced stages (stage IIb - IIIb by FIGO classification), who came to Oncology Sub Department of the Department of Obstetric and Gynecology Faculty of Medicine University of Indonesia/Dr. Cipto Mangunkusumo Hospital, and referred to Radiotherapy Sub Department of the Department of Radiology at the same institute.After going through inclusion and exclusion criteria, 146 patients were found to be suitable for evaluation with the prescribed protocol. The patients were sorted into 4 groups according the growth fraction and type of treatment to be performed. Group I and Group II were patients with Ki-67 index less than 40% with a difference that Group I underwent radiation therapy only, while Group II was treated with combination of radiation therapy and MMC. Group III and IV were patients with Ki-67 index 40% or higher, with a difference that Group III underwent radiation therapy only, while Group IV was treated with combination of radiation therapy and MMC. The 40 % Ki-67 criterion was determined based on results of preliminary study which set the level around 40%.The radiation therapy consisted of external radiation to the pelvis area in 28 sessions with a dose of 180 cGy per sessions or 5040 cGy total dose given in around 5.5 weeks. After a 1 - 2 week rest, radiation therapy were continued in the form of intra cavitary radiation using High Dose Rate (HDR) system in 2 sessions, I week apart, each in a dose of 850 cGy, giving a total dose of 1700 cGy. A small number of patients (42 patients) were given with Low Dose Rate (LDR) intra cavitary system in similar session and interval with those patients with HDR system. The dose was 1300 cGy per session or total dose of 2600 cGy being equal to the total dose of 1700 cGy in HDR system. Mitomycin-C was given in the combined treatment groups, with a dose of 15 mglm2, as a bolus injection intravenously, at the first day of external radiation and the first intracavitary insertion.Routine blood examinations were performed to each patient before treatment and once a week until the radiation therapy were completed. Liver function tests were performed before treatment, at the end of external radiation and after all radiation therapy completion."

"Kanker merupakan penyebab kematian utama di seluruh dunia. Salah satu faktor terjadinya kanker adalah modifikasi epigenetik yang abnormal (hipermetilasi). Hipermetilasi yang terjadi pada gen diyakini bahwa yang berperan besar dalam proses karsinogenesis adalah enzim DNA metiltransferase (DNMT). Penelitian-penelitian yang dilakukan saat ini untuk menemukan senyawa inhibitor DNMT dari bahan alam. Salah satu metode yang mendukung untuk analisis ini adalah metode in silico. Dalam penelitian ini, diteliti beberapa senyawa pilihan dari basis data herbal Indonesia hasil penapisan virtual terhadap aktivitasnya sebagai inhibitor DNMT. Hasil penambatan molekuler senyawa Cassiamin C, Procyanidin B2, Ent-epicatechin-4alpha-8-ent-epicatechin, Epicatechin-4beta-8-epicatechin-3-O-gallate, Neorhusflavanone, 3-O-galloylepigallocatechin-4beta-6-epicatechin-3-O-gallate, Withanolide, 3-O-galloylepigallocatechin-4beta-6-epigallocatechin-3-O-gallate, Cyanidin-3-6''-caffeylsophoroside-5-glucoside, Epifriedelinol, Gallo-catechin-4alpha-8-epicatechin, Scutellarein-7-glucosyl-1-4-rhamnoside, Epigallo-catechin-3-gallate (EGCG) (kontrol positif), dan sinefungin (kokristal) didapatkan nilai ΔG secara berturut-turut, -9.34, -10.95, -7.95, -11.01, -8.78, -8.87, -11.49, -7.98, -5.92, -8.92, -9.17, -8.76, -9.70, dan -9.11 kkal/mol. Senyawa cassiamin C, procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, withanolide, dan gallocatechin-4alpha-8-epicatechin memiliki ΔG lebih rendah dari senyawa sinefungin (kokristal) dan EGCG (kontrol positif). Sehingga, tahap selanjutnya akan dilakukan simulasi dinamika molekuler terhadap tujuh ligan tersebut. Hasil simulasi dinamika molekuler menunjukkan aktivitas terbaik secara keseluruhan yaitu pada senyawa procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, dan gallocatechin-4alpha-8-epicatechin. Residu asam amino yang penting bagi aktivitas inhibitor DNMT1 adalah Phe1145, Glu1168, Met1169, Cys1191, Glu1266, Ala1579, dan Val1580.

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Cancer is the leading cause of death worldwide. Factors of cancer is an abnormal epigenetic modifications (hypermethylation). Hypermethylation that occur in genes believed that played a major role in process of carcinogenesis is DNA methyltransferase (DNMT) enzyme. Recent studies is conducted to find DNMT inhibitor compounds from natural materials. Method that support for this analysis is in silico studies. In this study, several selected compounds from herbal database Indonesia results of virtual screening will be studying for the activity as an inhibitor DNMT. Results molecular docking of Cassiamin C, Procyanidin B2, Epicatechin-4alphaent-8-ent-epicatechin, Epicatechin-4beta-8-epicatechin-3-O-gallate, Neorhusflavanone, 3-O-galloylepigallocatechin-4beta-6-epicatechin-3-O-gallate, Withanolide, 3-O-galloylepigallocatechin-4beta-6-epigallocatechin-3-O-gallate, Cyanidin-3-6''-caffeylsophoroside-5-glucoside, Epifriedelinol, Gallocatechin-4alpha-8-epicatechin, Scutellarein-7-glucosyl-1-4-rhamnoside, Epigallocatechin-3-gallate (EGCG) (positive control), and Sinefungin (co-crystal) compounds, ΔG values obtained -9.34, -10.95, -7.95, -11.01, -8.78, -8.87, -11.49, -7.98, -5.92, -8.92, -9.17, -8.76, -9.70, and -9.11 kcal/mol, respectively. Cassiamin C, Procyanidin B2, Epicatechin-4beta-8-epicatechin-3-O-gallate, Withanolide, and Gallocatechin-4alpha-8-epicatechin compounds had lower ΔG than Sinefungin (co-crystal) and EGCG (positive control) compounds. Therefore, molecular dynamic simulation of seven selected compounds will be performed. The results of molecular dynamic simulation shows the best overall activity is Procyanidin B2, Epicatechin-4beta-8-epicatechin-3-O-gallate, and Gallocatechin-4alpha-8-epi-catechin compounds. Amino acid residues which are important for the activity of DNMT1 inhibitor is Phe1145, Glu1168, Met1169, Cys1191, Glu1266, Ala1579, and Val1580."

"ABSTRAKKanker payudara merupakan jenis kanker dengan prevalensi yang tinggi di dunia yang umumnya terjadi pada wanita. Kanker payudara memiliki angka tertinggi yang mencapai hingga 40 per 100.000 kasus setiap tahunnya, dan sebnayak 12,9 diantaranya dapat menyebabkan kematian. Perubahan epigenetik berperan penting dalam proses pembentukan dan penyebaran sel kanker. Metilasi DNA merupakan salah satu jenis dari perubahan epigenetik yang sering terjadi yang dapat memicu terjadinya pertumbuhan sel kanker. Metilasi DNA dikatalisis oleh enzim DNA Metiltransferase 1 DNTM1 yang dapat memindahkan gugus metil dari S-adenosil metionin SAM ke sitosin pada dinukleotida CpG. Pada penelitian ini, dilakukan penapisan virtual senyawa bahan alam sebagai inhibitor enzim DNMT1. Penapisan dilakukan terhadap 26.731 senyawa bahan alam yang diperoleh dari NCBI Pubchem databsase. Simulasi penambatan molekul dilakukan dengan menggunakan Molecular Operating Environment MOE 2014.09 untuk mendapatkan 10 ligan terbaik berdasarkan interaksi kompleks ligan-enzim dan energi bebas Gibbs. Karakteristik farmakologi meliputi sifat fsikokimia, toksisitas, karsinogenisitas-mutagenisitas serta bioaktivitas menggunakan online software maupun offline software. Uji farmakologi dilakukan untuk mengetahui karakteristik fisikokimia, toksisitas, karsinogenisitas-mutagenisitas dan bioaktivitas menggunakan software DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR dan SWISSADME. Hasil dari penelitian ini ialah terdapat 3 ligan terbaik yang berasal dari kelompok senyawa bahan alam fenolik yang terpilih berdasarkan karakteristik farmakologi yang dapat dijadikan sebagai kandidat obat untuk terapi kanker payudara.

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ABSTRACTBreast cancer is the most prevalent cancer in woman worldwide. It has the highest number of new cases which amounted to 40 per 100,000 cases per year, 12,9 of which leads to death. Epigenetic alteration plays a vital role in the process of cancer cell formation and propagation. DNA methylation is one of the most common types of epigenetic alteration which generally leads to breast cancer DNA Methylation, a transfer the methyl group from S adenosyl methionin SAM to cytosine in the CpG dinucleotide, is catalyzed by DNMT1 enzyme. In the present study, we performed a virtual screening of natural product compounds as an inhibitors of DNMT1 enzyme. Virtual screening was conducted on 26,731 natural products obtained from the NCBI PubChem database. Three steps of rigid and one step of flexible molecular docking simulations were performed using MOE 2014.09. Through the simulations, 10 ligands based on the Gibbs free binding energies Gbinding and the ligand enzyme complex interactions were identified. Pharmacological test was conducted to observe the psychochemical, toxicity, carcinogenicity mutagenicity, and bioactivity properties by employing DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR and SWISSADME software. The results revealed that three best ligands from phenolic group were selected due to their exceptional pharmacological characteristics as the drug candidate for breast cancer therapy. "