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"Tujuan dan latar belakang : High grade glioma mecakup hanya 2% dari seluruh kanker, namun memiliki morbiditas dan mortalitas yang tinggi walaupun dengan menggunakan pendekatan terapi multimodal menggunakan kombinasi modalitas operasi, radiasi, kemoterapi dan targetd therapy. Penelitian ini bertujuan untuk mengetahui korelasi kadar MGMT, sebuah protein repair, yang diperiksa menggunakan teknik ELISA dengan respon tumor terhadap radiasi pada High Grade Glioma sehingga diharapkan dapat menambah pemahaman mengenai sifat biomolekuler dari High grade Glioma. Metode : Studi ini merupakan sebuah studi restrospektif yang melibatkan 14 pasien yang telah didiagnosa sebagai High Grade Glioma berdasarkan histopatologi dan telah mendapatkan radiasi postoperasi dengan dan/atau tanpa chemosensitizer temozolomide di Departemen Radioterapi RSUPN Cipto Mangunkusumo dari tahun 2004-2015. MGMT diperiksa dengan teknik ELISA dari jaringan tumor yang sudah diparafinisasi. Respon tumor dihitung berdasarkan perubahan volume tumor pada imaging CT/MRI pre dan pasca radiasi. Hasil: Rerata kada MGMT adalah 184 (160-206) pg/mL. Rerata penyusutan tumor adalah 10,64% (-75.64-80.20%). Tidak didapatkan korelasi antara kadar MGMT dengan respon tumor, dengan r= 0.065 (p=0.825). Pada kelompok yang hanya mendapat radiasi didapatkan r= 0.199 (p=0.607) dan pada kelompok yang mendapat kemoradiasi dengan TMZ didapatkan korelasi negatif dengan r= -0,447 (p=0.45). Kesimpulan : Tidak ada korelasi antara kadar MGMT dengan respon radiasi. Baik pada kelompok yang mendapatkan radiasi saja ataupun pada kelompok yang mendapatkan kemoradiasi dengan TMZ.

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Purpose and background : High Grade Glioma comprises just 2% of all cancer, but it disproportionally has the 6th lowest survival of all cancer found. Despite combined multimodality approach that has been used by clinician which can be the combination of two or more modalities of such : surgery, radiation, chemotherapy and targeted therapy, the mortality and morbidity of HGG remains high. This study aims to know the correlation between MGMT protein expression, a repair protein well known in glioma, with the radiation response, in order to gain more knowledge of the bio molecular behavior of HGG.

Material and Methods : This study is a retrospective study that involves 14 patients which were diagnosed as HGG based on histopathological findings and received postoperative radiation with or without concurrent Temozolomide (TMZ) at the Radiotherapy Department of Cipto Mangunkusumo Hospital from 2004-2015. Tumor MGMT concentration was quantified by Enzyme-Linked Immunosorbent Assay from Formalin-Fixed Paraffin-Embedded (FFPE) tissue. Tumor response was evaluated by comparing pre and post radiation tumor volume by CT and MRI.

Result: MGMT concentration was 184 (160-206) pg/mL. Mean tumor volume shrinkage was 10,64% (-75.64-80.20%). There were no correlation between MGMT concentration and tumor response (r= 0.065, p=0.825). The sample was split according to use of TMZ. In the group that had radiation only, the correlation between MGMT concentration and tumor response was not significant (r= 0.199, p=0.607). In the chemoradiation group there was a moderate negative correlation, but was not significant (r= -0,447, p=0.45).

Conclusion: MGMT protein expression was not correlated with the tumor radiation response. There was a negative moderate correlation between MGMT concentrasion and tumor response in patients who underwent chemoradiation with TMZ, but this correlation was not statistically significant."

"Latar Belakang: Enzim O6-methylguanine-DNA methyltransferase MGMT merupakan suatu DNA-repair enzyme yang dapat menghambat proses kematian sel tumor akibat proses alkilasi oleh zat alkilasi termasuk zat kemoterapi. Enzim ini berhubungan dengan mekanisme pertahanan tumor terhadap zat kemoterapi. Eskpresi dari enzim MGMT ini ditemukan tinggi pada pada berbagai tumor termasuk glioma. Metilasi promoter MGMT mengakibatkan gen dalam sel tumor berhenti menghasilkan MGMT. Adanya metilasi dari promoter MGMT dihubungkan dengan respon yang lebih baik terhadap zat alkilasi termasuk kemoterapi. Status metilasi dari promoter MGMT pada pasien glioma dapat digunakan untuk memperkirakan efektifitas kemoterapi dengan zat alkilasi. Tujuan: Penelitian ini bertujuan untuk mengetahui profil enzim O6-methylguanine-DNA methyltransferase MGMT pada pasien glioma derajat tinggi dan glioma derajat rendah dan karakteristik pasien glioma di Departemen Bedah Saraf RS Cipto Mangunkusumo Jakarta. Metode: Peneliti mengumpulkan data profil MGMT yang diperiksa menggunakan methylation-specific polymerase chain reaction pada pasien glioma derajat tinggi dan glioma derajat rendah yang menjalani pembedahan di Departemen Bedah Saraf Rumah Sakit Cipto Mangunkusumo Jakarta dalam periode 1 tahun. Data berupa usia, jenis kelamin, Karnofsky Performance Scale KPS, and derajat serta jenis histopatologi tumor dikumpulkan. Hasil: Dalam periode 1 tahun terdapat 17 pasien dengan hasil histopatologi glioma derajat tinggi dan derajat rendah yang masuk kriteria inklusi. Promoter MGMT termetilasi ditemukan pada 11 pasien 64,7 dan tidak termetilasi pada 6 pasien 35,3. Promoter MGMT termetilasi methylated MGMT lebih banyak didapatkan pada pasien berusia ge; 40 tahun dibandingkan pasien yang berusia < 40 tahun 85,7 vs 50 dan pada pasien laki-laki dibandingkan perempuan 77,7 vs 50. Sedangkan berdasarkan KPS, promoter MGMT termetilasi ditemukan lebih banyak pada pasien dengan KPS > 70 dibandingkan dengan KPS le; 70 70 vs 57,1. Berdasarkan derajat keganasan, promoter MGMT termetilasi ditemukan lebih banyak ditemukan pada glioma derajat rendah WHO grade II dibandingkan pada glioma derajat tinggi WHO grade III dan IV 85,7 vs 50. Pada glioma derajat tinggi, promoter MGMT termetilasi ditemukan lebih banyak pada astrositoma/oligoastrositoma anaplastik WHO grade III dibandingkan glioblastoma WHO grade IV 66,6 vs 42,8. Pada glioma derajat rendah, promoter MGMT termetilasi ditemukan lebih banyak pada oligoastrositoma dibandingkan astrositoma difus 100 vs 75. Kesimpulan: Promoter MGMT termetilasi lebih sedikit ditemukan pada derajat tumor yang lebih tinggi WHO grade IV, KPS yang rendah, usia lebih muda saat diagnosis dan pasien wanita, meskipun perbedaannya belum dibuktikan signifikan secara statistik. Promoter MGMT termetilasi ditemukan lebih banyak pada tumor dengan komponen oligodendroglioma. Dibutuhkan penelitian lebih lanjut dengan jumlah sampel yang lebih besar untuk menentukan apakah metilasi promoter MGMT memiliki hubungan yang signifikan dengan faktor-faktor tersebut.

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Background: O6 methylguanine DNA methyltransferase MGMT is a DNA repair enzyme that correlates with resistance mechanism of tumors to chemotherapy. MGMT inhibits the killing process of tumor cells by alkylating agents including chemotherapy MGMT expression has been noted higher in several tumors including glioma.. Methylation of MGMT promoter inhibits the cells to produce MGMT. Methylation status of the MGMT promoter in gliomas is useful to predict the effectiveness of chemotherapy with alkylating agents.

Objective: The purpose of this study was to evaluate profile of MGMT enzyme and characteristic of low grade and high grade glioma patients in Neurosurgery Department of Cipto Mangunkusumo Hospital Jakarta.

Methods: We evaluated data of MGMT promoter methylation status from methylation specific polymerase chain reaction result in low grade and high glioma patients who underwent surgical resection in Department of Neurosurgery, Cipto Mangunkusomo Hospital Jakarta. Demographic characteristic and clinical data of glioma patiens including age, sex, Karnofsky Performance Scale KPS, and grading of tumor were collected.

Results: In one year period, there are 17 patients with pathological finding of low grade and high grade gliomas met criteria of inclusion. Methylated MGMT promoter was found in 11 patients 64.7 and unmethylated in 6 patients 35.3. MGMT promoter methylation was observed more often in patients diagnosed in age more than 40 years old than in patient less than 40 years old 85,7 vs 50, and men than women 77,7 vs 50. In patients with KPS more than 70 and KPS 70 or less, methylation of MGMT promoter was observed in 70 and 57,1, respectively. Base on tumors grading, MGMT promoter methylation was observed more often in low grade gliomas WHO grade II than high grade gliomas WHO grade II and IV 85,7 vs 50. In high grade glioma, methylation was observed more often in grade III tumors anaplastic astrocytomas oligoastrocytomas than grade IV tumors glioblastomas 66,6 vs 42,8. In low grade gliomas, methylation was observed more in oligoastrocytomas than difus astrocytomas 100 vs 75.

Conclusions. MGMT promoter methylation was observed less in higher grade of tumors grade IV, lower KPS, younger age at time of diagnosis and female patients, although the differences were not statistically significant. MGMT promoter methylation was observed more often in gliomas with oligodendroglioma component. Further and larger scale of research is needed to determine whether MGMT promoter methylation significantly correlates with these factors. "

"[ABSTRAKPendahuluan: Osteopontin merupakan salah satu penanda molekuler hipoksiaendogen tumor. Hipoksia adalah salah satu faktor yang menentukan agresifitaspenyakit. Kadar osteopontin tinggi pada berbagai keganasan termasuk gliomamaligna. Peningkatan kadar osteopontin akan menyebabkan respon terapi berkurang.Penelitian ini bertujuan untuk mengetahui korelasi antara kadar osteopontin praradiasidengan respon radiasi pada glioma maligna.Metode: Penelitian ini merupakan studi retrospektif kohort terhadap 15 pasienmaligna glioma yang menjalani terapi radiasi dari juli 2004 sampai mei 2015 diRSUPN. DR. Cipto Mangunkusumo. Osteopontin diperiksa menggunakan metodeELISA dari sampel parafin blok. Volume tumor dihitung dari CT scan atau MRIberdasarkan pengukuran volume tiga dimensi. Respon tumor dinilai denganmembandingkan volume tumor sebelum dan sesudah radiasi dengan menggunakanCT dan MRI.Hasil: Didapatkan rerata kadar osteopontin sebesar 0,49 ± 0,45 ng/ml, reratapersentase perubahan volume tumor 8,59 ± 54,22 %. Volume tumor yang membesar60%. Tumor yang progresif sebesar 26,7%. Secara keseluruhan terdapat korelasinegatif lemah yang tidak bermakna ( r -0,39 dan p 0,146 ) antara kadar osteopontindengan respon radiasi. Terdapat korelasi positif kuat yang tidak bermakna ( r +0,68dan p 0,219 ) antara kadar osteopontin dengan respon radiasi pada kelompok yangmenggunakan kemosensitizer temozolamide.Kesimpulan: Terdapat korelasi negatif lemah yang tidak bermakna antara kadarosteopontin dengan respon radiasi. Terdapat korelasi positif kuat yang tidakbermakna antara kadar osteopontin dengan respon radiasi pada kelompok yangmenggunakan kemosensitizer temozolamide.

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ABSTRACTIntroduction : Osteopontin is an endogenous molecular marker of tumor hypoxia,which is one of factors that determine the aggressiveness of the disease. Increasedlevel of osteopontin will decrease therapeutic response which will eventuallyinfluence the success of therapy.The purpose of this study is to determine thecorrelation between osteopontin level and radiation response in malignant glioma.Method : This is a retrospective cohort study of 15 malignant glioma patients whounderwent radiation from July 2004 to May 2015 at Cipto Mangunkusumo Hospital.Osteopontin level was measured with ELISA from paraffin embedded tissue. Tumorvolume was calculated by measuring three dimensional volume of tumor imagingfrom CT or MRI. Tumor response was evaluated by comparing pre-irradiation withpost-irradiation tumor volume seen in CT and MRI.Result : The mean osteopontin level was 0.49 ± 0.45 ng/ml and the mean percentageof change in tumor volume was 8.59 ± 54.22 %. Enlargement of tumor volume was60 %. Progressive disease was found in 26.7 % of patients. Overall, there was aninsignificant weak negative correlation (r -0.39 and p 0.146) between level ofosteopontin and radiation response. There was an insignificant strong positivecorrelation (r +0.68 and p 0.219) between level of osteopontin and radiation responsein the group that received radiation therapy concurrent with temozolamide.Conclusion : Overall, there was an insignificant weak negative correlation betweenlevel of osteopontin and radiation response. In the group that received radiationtherapy concurrent with temozolamide, there was an insignificant strong positivecorrelation between level of osteopontin and radiation response, Introduction : Osteopontin is an endogenous molecular marker of tumor hypoxia,which is one of factors that determine the aggressiveness of the disease. Increasedlevel of osteopontin will decrease therapeutic response which will eventuallyinfluence the success of therapy.The purpose of this study is to determine thecorrelation between osteopontin level and radiation response in malignant glioma.Method : This is a retrospective cohort study of 15 malignant glioma patients whounderwent radiation from July 2004 to May 2015 at Cipto Mangunkusumo Hospital.Osteopontin level was measured with ELISA from paraffin embedded tissue. Tumorvolume was calculated by measuring three dimensional volume of tumor imagingfrom CT or MRI. Tumor response was evaluated by comparing pre-irradiation withpost-irradiation tumor volume seen in CT and MRI.Result : The mean osteopontin level was 0.49 ± 0.45 ng/ml and the mean percentageof change in tumor volume was 8.59 ± 54.22 %. Enlargement of tumor volume was60 %. Progressive disease was found in 26.7 % of patients. Overall, there was aninsignificant weak negative correlation (r -0.39 and p 0.146) between level ofosteopontin and radiation response. There was an insignificant strong positivecorrelation (r +0.68 and p 0.219) between level of osteopontin and radiation responsein the group that received radiation therapy concurrent with temozolamide.Conclusion : Overall, there was an insignificant weak negative correlation betweenlevel of osteopontin and radiation response. In the group that received radiationtherapy concurrent with temozolamide, there was an insignificant strong positivecorrelation between level of osteopontin and radiation response]"

"Latar Belakang: Gen MGMT berperan dalam mekanisme perbaikan DNA melalui transfer alkil mencegah terjadinya mutasi gen ? gen terkait orofacial cleft. Metilasi pada promoter gen MGMT mempengaruhi regulasi ekspresi gen tersebut.Tujuan: Mengetahui gambaran kejadian metilasi gen MGMT penderita orofacial cleft.Metode: Dua puluh empat sampel orofacial cleft dan 24 sampel normal dilakukan deteksi status metilasi melalui methylation specific-PCR (MSP).Hasil: Diperoleh 33.3% orofacial cleft berstatus fully methylated dan 66.7% partially methylated. Sedangkan pada kontrol, 100% berstatus partially methylated.Kesimpulan: Terjadi metilasi gen MGMT pada penderita orofacial cleft dan distribusinya berbeda dengan individu normal (p=0.004).

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Background: MGMT gene plays a role in DNA repair mechanisms via the transfer of alkyl to prevent mutation of gene related orofacial cleft. Methylation at MGMT gene promoter has effect in the regulation of gene expression.

Objective: To determine MGMT gene methylation status in orofacial cleft.

Methods: Methylation status were detected in 24 orofacial cleft and 24 healthy individuals samples by methylation-specific PCR (MSP).

Results: 33.3% orofacial cleft were fully methylated and 66.7% were partially methylated. Meanwhile, in control group, 100% were partially methylated.

Conclusion: MGMT gene methylation occurred in orofacial cleft and the distributions are different from healthy individuals (p=0.004)."

"HIF-2α adalah mediator yang penting dalam reaksi hipoksia di situasi keganasan dan tingginya tingkat ekspresi HIF-2α berkorelasi dengan konsep metastasis, resistensi terapi dan penurunan kualitas prognosis dalam berbagai bentuk pertumbuhan kanker. Karena kemampuan sel glioma otak yang sangat infiltratif, glioma tidak dapat sepenuhnya dihilangkan dengan pembedahan dimana tingkat kekambuhan juga tinggi. Tujuan penelitian ini untuk mengidentifikasi ekspresi relatif dari gen HIF-2α dihubungkan dengan keganasan glioma. Spesimen yang digunakan dalam penelitian ini terdiri dari 22 sampel yang diperoleh dari Departemen Bedah Saraf Fakultas Kedokteran Universitas Indonesia- Rumah Sakit Cipto Mangunkusumo. Ekspresi relatif HIF-2α dianalisis dengan menggunakan quantitative RT-PCR. Hasil penelitian menunjukkan peningkatan ekspresi relatif HIF-2α pada glioma derajat tinggi dibandingkan dengan glioma derajat rendah, namun tidak bermakna secara statistik. Dengan demikian kemungkinan HIF-2α dapat digunakan sebagai penanda prognostik untuk pasien yang didiagnosis glioma, meskipun eksperimen tambahan perlu dilakukan untuk memperkuat fakta ini."

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Glioma adalah tumor yang bermula dari tulang belakang atau otak yang berasal dari sel glial, dan merupakan salah satu keganasan yang sering ditemukan di Indonesia. TGF-I²1 mempunyai peran yang penting dalam mengontrol homeostasis jaringan dan peranjakan keganasan kanker, oleh sebab itu TGF-I²1 mempunyai potensi untuk menjadi biomarker untuk membedakan antar glioma keganasan tinggi dan rendah. Tujuan dari penelitian ini adalah untuk menganalisis ekspresi relatif TGF-I²1 glioma tingkat tinggi dan rendah, untuk melihat potensi menjadi biomarker. Dalam eksperimen terdapat 28 sampel yang digunakan dalam studi ini,16 jaringan dengan keganasan rendah, 10 dengan keganasan tinggi dan 2 jaringan otak normal yang didapat dari Rumah Sakit Cipto Mangunkusumo, Indonesia. Jaringan telah digolongkan berdasarkan klasifikasi yang diberikan oleh World Health Organization, derajat 1 dan 2 sebagai keganasan rendah dan derajat 3 dan 4 sebagai derajat tinggi. Ekspresi relatif dari TGF-I²1 dianalisa menggunakan Real-Time RT PCR dengan 18sRNA sebagai houskeeping gene. Dari hasil terlihat bahwa adanya penurunan ekspresi relatif TGF-I²1 di glioma keganasan tinggi saat dibandingkan dengan ekspresi di glioma keganasan rendah. Tetapi setelah dianalisis secara statistik, hasil penemuan ini tidak signifikan. Kegunaan dari TGF-I²1 sebagai biomarker belum terbukti, maka dari itu studi lebih lanjut harus dilakukan untuk menjelaskan fungsi dari TGF-I²1 sebagai biomarker untuk glioma.

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Glioma is a term used to describe tumors which originate from the spinal cord or brain, specifically the glial cells. This type of tumor is one of the most commonly found brain malignancies in Indonesia. TGFI²1 has a key role in the maintenance of tissue homeostasis and progression of cancer, due to this fact TGF-I²1 has the potential as a tissue biomarker to differentiate low grade and high grade gliomas. The goal of this study is to analyze the relative expression of TGF-²1 in both high grade and low grade glioma to explore its potential as a biomarker. In the experiment there was a total of 28 samples, 16 low grade glioma, 10 high grade glioma and 2 normal brain tissue obtained from Cipto Mangunkusumo Hospital, Indonesia. The sample was categorized to low grade and high grade glioma based on the guideline given by the World Health Organization. Grades 1 and 2 are considered to be low grade gliomas and grades 3 and 4 are considered to be high grade gliomas. The relative expression of TGF-I²1was measured through Real-Time RT-PCR with 18sRNA as a housekeeping gene. It was seen that there was a decrease in the expression of TGF-I²1 in high grade glioma as to low grade glioma. However, when the result was analyzed it is proven to be statistically insignificant.The role of TGF-I²1 as a definitive biomarker for glioma grading is yet to be proven, therefore further research must be conducted to elaborate the role of the gene as a glioma biomarker.

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"Hipermetilasi DNA adalah sebuah proses epigenetik abnormal yang dikatalis oleh DNA Metiltransferase dan merupakan salah satu faktor penyebab munculnya penyakit tidak menular seperti kanker, diabetes, dan penyakit gangguan metabolisme lainnya. Hipermetilasi DNA dapat dihambat dengan inhibitor DNA Metiltransferase1 (DNMTi). Penelitian ini dilakukan dengan tujuan menemukan kandidat inhibitor DNA Metiltrasnferase yang berasal dari bahan alam. Pencarian senyawa yang berpotensi sebagai inhibitor dilakukan dengan penapisan virtual terhadap basis data senyawa aktif tanaman herbal Indonesia (HerbalDB) menggunakan peranti lunak Autodock Vina. Dua puluh lima senyawa yang diketahui memiliki efek inhibisi terhadap DNMT1 digunakan sebagai kontrol positif dan sebagai referensi untuk membuat pengecoh menggunakan Directory of Useful Decoys: Enchanced. Penapisan yang dilakukan mendapatkan lima senyawa aktif yang berpotensi sebagai inhibitor DNA metiltransferase 1 yaitu Procyanidin B2, Ent-epicatechin-4alpha-8-ent-epicatechin, Epicatechin-4beta-8-epicatechin-3-o-gallate, Neorhusflavanone, dan Cyanidin-3-6''-caffeylsophoroside-5-glucoside.

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DNA Hypermethylation is an abnormal epigenetic process catalyzed by DNA Methyltranferase 1 (DNMT1), it is also one of the factor causing non-communicable disease such as cancer, diabetes, and other metabolic disease. DNA hypermethylation can be surpressed by DNA Methyltransferase inhibitor (DNMTi). This study was conducted to obtain inhibitor candidate from natural products. The search for potential inhibitors was done by conducting a virtual screening against Indonesian Herbal Compound Database (Herbal DB) utilizing Autodock Vina as docking software. Twenty-five compunds known for their inhibitory activity against DNMT1 were used as actives and as reference for generating decoys, facilitated by Directory of Useful Decoys: Enhanced. The virtual screening yields five potential DNMT1 inhibitor, Procyanidin B2, Ent-epicatechin-4alpha-8-ent-epicatechin, Epicatechin-4beta-8-epicatechin-3-o-gallate, Neorhusflavanone, and Cyanidin-3-6''-caffeylsophoroside-5-glucoside."

"Latar belakang:Untuk menganalisis hubungan antara stres oksidatif pada sel glioma manusia dengan derajat keganasan, sehingga dapat mengeksplorasi peranan stress oksidatif sebagai petanda tumor dalam menentukan progresi tumor.Metode: Sampel terdiri dari 21 jaringan tumor dan 5 jaringan otak normal dari penderita glioma. Stres oksidatif dianalisis melalui pengukuran Malondyaldehida (MDA) yang menggambarkan kerusakan lipid dan kadar karbonil untuk kerusakan protein, serta 8-hydroxy-2?-deoxyguanosine/ 8-OHdG untuk kerusakan DNA. Selain itu, dilakukan analisis terhadap ekspresi Manganese Superoxide Dismutase (MnSOD) sebagai enzim antioksidan utama yang berperan dalam stres oksidatif. Ekspresi MnSOD dianalisis melalui pengukuran mRNA MnSOD menggunakan Real Time PCR dan aktivitas spesifik enzim MnSOD menggunakan inhibisi xantin oksidase (kit RanSOD). Derajat keganasan ditentukan berdasarkan pemeriksaan histopatologis. Analisis statistik dengan menggunakan t-test dan uji korelasi Pearson.Hasil: Kadar MDA, karbonil dan 8-OHdG sebagai parameter stres oksidatif pada glioma lebih tinggi bermakna dibandingkan dengan otak normal. Kadar MDA dan karbonil ini meningkat sesuai dengan derajat keganasan. Ekspresi relatif mRNA MnSOD dan aktivitas spesisifik enzim MnSOD pada glioma lebih tinggi bermakna dibandingkan dengan otak normal. Ekspresi relatif mRNA MnSOD tersebut meningkat bermakna sesuai dengan derajat keganasan. Namun, aktivitas spesifik enzim MnSOD pada glioma derajat tinggi lebih rendah bermakna dibandingkan glioma derajat rendah, dengan demikian terdapat ketidak sesuaian antara sintesis mRNA MnSOD dengan aktivitas spesifiknya. Terdapat korelasi positif antara mRNA MnSOD dengan kadar MDA.Kesimpulan: Kerusakan oksidatif yang terjadi pada sel glioma berhubungan bermakna dengan derajat keganasan. Tingginya mRNA dan aktivitas spesifik MnSOD pada sel glioma berhubungan dengan tingginya kerusakan oksidatif.

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AbstractThe goal of this study was to analyze the correlation of oxidative stress in human glioma cells with tumor grade in order to explore the role of oxidative stress as a marker in determining the tumor progression.Methods: Samples were 21 brain tumors and 5 normal brain tissues from glioma patients. Oxidative stress was analyzed by measuring malondialdehyde (MDA), carbonyl and 8-hydroxy-2?-deoxyguanosine (8-OhdG). Additionaly, we analyzed MnSOD expression by measuring the MnSOD mRNA using real time RT-PCR and MnSOD enzyme activity using RanSOD kit. Tumor grade was determined by histopathologic examination. Data was statistically analyzed using t-test and Pearson correlation.Results: Levels of MDA, carbonyl and 8-OHdG reflecting oxidative stress in glioma cells were significantly higher than in normal brain tissue. The MDA and carbonyl levels were significantly correlated with tumor grade. Relative expression of MnSOD mRNA and specific enzyme activity in glioma cells were significantly higher than in normal brain cells. The relative expression of MnSOD mRNA increased significantly in accordance with the tumor grade. Surprisingly, MnSOD specific activity was significantly lower in high grade than in low grade glioma indicating a discrepancy between mRNA synthesis and its enzyme specific activity. Furthermore, there was a positive correlation between MnSOD mRNA and MDA levels.Conclusion: The high level of oxidative damage in human glioma cells was significantly correlated with tumor grade. The high level of MnSOD expression in human glioma cells was correlated with the high level of oxidative damage."

"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."

"[ABSTRAKPendahuluan : Glioma adalah jenis tumor yang paling umum dari neoplasma intraserebralprimer. Tumor ganas primer sistem saraf pusat (SSP) mencapai sekitar 2% dari semua kankerdan high grade glioma adalah jenis yang paling banyak ditemukan. High grade gliomamenyebabkan tingkat morbiditas dan mortalitas yang tinggi. Saat ini belum ada data yangmenggambarkan profil pasien glioma yang menjalani radioterapi di Indonesia.Metode penelitian : Penelitian ini merupakan penelitian retrospektif deskriptif analitikterhadap 121 pasien glioma yang mendapat radiasi di departemen Radioterapi RSUPN Dr.Cipto mangunkusumo dari Januari 2009 sampai Januari 2014. Data diperoleh dari catatanmedisdan hasil penelusuran melalui telepon terhadap pasien atau keluarganya. Respon tumordianalisa terhadap 22 pasien yang mempunyai CT scan atau MRI pre dan post radiasi denganmenggunakan kriteria RECIST.Hasil : Sebagian besar pasien adalah laki-laki (53,7%), dengan usia rata-rata 45 tahun.Histopatologi yang paling banyak ditemukan adalah astrositoma. Prosedur bedah yang palingbanyak ditemukan pada penelitian ini adalah craniotomi removal tumor (70%). Teknik 3DCRT paling banyak digunakan yaitu pada 77,7% pasien. Nimotuzumab sebagai antibodimonoklonal digunakan pada 9% pasien. Respon parsial ditemukan 59,1%. Analisis kesintasanhidup tiga tahun dari seratus sebelas pasien yang memenuhi kriteria didapatkan angkakesintasan yaitu 46,15%. Analisis kaplan meyer menunjukkan overall treatment timemerupakan faktor prognostik untuk kesintasan hidup (p = 0,016).Kesimpulan : Teknik operasi terbanyak pada pasien glioma yang menjalani radiasi didepartemen radioterapi RSUPN DR. Cipto Mangunkusumo adalah kraniotomi removal tumor(70,9%). Teknik 3D CRT adalah teknik radiasi yang paling banyak digunakan. Responparsial ditemukan 59,1%. Kesintasan hidup tiga tahun pasien glioma yaitu 46,2% dan overalltreatment time merupakan faktor prognostik yang bermakna untuk kesintasan hidup

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ABSTRACTIntroduction : Glioma is the most common type of primary intracerebral neoplasms. Highgrade glioma being the most frekuent type found (70,9%) causes a high morbidity andmortality rate. There is currently no data describing the profile management of patientsundergoing radiotherapy glioma in Indonesia.Methods : This study Retrospective analytic descriptive study of 121 glioma patients fromjanuari 2009 until december 2014. The data was obtained from medical records and indivualcontact via telephone. Tumor response was evaluated in 22 patients with pre and postirradiation imaging (CT or MRI) using 3D volumetric data and assessed via RECISTcriteria.Results : Most of our patients were male (53,7%), with median age 45 years old.Astrocytoma was the most histopathological type found. 70.9% of Patients who receivedradiotherapy in Cipto Mangunkusumo hospital were post craniotomi tumor removal. 3DConformal technique was used in 81.0% of patients. Seventy nine point three had a two graydose perfraction. Provision of chemotherapy in patients undergoing radiation still only at7.4% of patients. Nimotuzumab as a monoclonal antibody used on 9% patient. The medianoverall treatment time was 45 days and delay treatment time 38 days. Fifty nine point onepercent of partial respon was found. Local recurrences were found throughout the follow-upof 6.6%. Analysis kaplan meyer showed that overall treatment time was a prognostic factorfor overal survival rate (p=0,016).Conclusions : : Almost seventy one percent of glioma patients who received radiotherapyhad craniotomy removal tumor. 3D Conformal techniques is the most widely used. Fifty ninepoint one percent of partial respon founded. Three years overall survival was 46,2% andoverall treatment time was found as a factor that significantly affects overall survivalprognosis.;Introduction : Glioma is the most common type of primary intracerebral neoplasms. Highgrade glioma being the most frekuent type found (70,9%) causes a high morbidity andmortality rate. There is currently no data describing the profile management of patientsundergoing radiotherapy glioma in Indonesia.Methods : This study Retrospective analytic descriptive study of 121 glioma patients fromjanuari 2009 until december 2014. The data was obtained from medical records and indivualcontact via telephone. Tumor response was evaluated in 22 patients with pre and postirradiation imaging (CT or MRI) using 3D volumetric data and assessed via RECISTcriteria.Results : Most of our patients were male (53,7%), with median age 45 years old.Astrocytoma was the most histopathological type found. 70.9% of Patients who receivedradiotherapy in Cipto Mangunkusumo hospital were post craniotomi tumor removal. 3DConformal technique was used in 81.0% of patients. Seventy nine point three had a two graydose perfraction. Provision of chemotherapy in patients undergoing radiation still only at7.4% of patients. Nimotuzumab as a monoclonal antibody used on 9% patient. The medianoverall treatment time was 45 days and delay treatment time 38 days. Fifty nine point onepercent of partial respon was found. Local recurrences were found throughout the follow-upof 6.6%. Analysis kaplan meyer showed that overall treatment time was a prognostic factorfor overal survival rate (p=0,016).Conclusions : : Almost seventy one percent of glioma patients who received radiotherapyhad craniotomy removal tumor. 3D Conformal techniques is the most widely used. Fifty ninepoint one percent of partial respon founded. Three years overall survival was 46,2% andoverall treatment time was found as a factor that significantly affects overall survivalprognosis.;Introduction : Glioma is the most common type of primary intracerebral neoplasms. Highgrade glioma being the most frekuent type found (70,9%) causes a high morbidity andmortality rate. There is currently no data describing the profile management of patientsundergoing radiotherapy glioma in Indonesia.Methods : This study Retrospective analytic descriptive study of 121 glioma patients fromjanuari 2009 until december 2014. The data was obtained from medical records and indivualcontact via telephone. Tumor response was evaluated in 22 patients with pre and postirradiation imaging (CT or MRI) using 3D volumetric data and assessed via RECISTcriteria.Results : Most of our patients were male (53,7%), with median age 45 years old.Astrocytoma was the most histopathological type found. 70.9% of Patients who receivedradiotherapy in Cipto Mangunkusumo hospital were post craniotomi tumor removal. 3DConformal technique was used in 81.0% of patients. Seventy nine point three had a two graydose perfraction. Provision of chemotherapy in patients undergoing radiation still only at7.4% of patients. Nimotuzumab as a monoclonal antibody used on 9% patient. The medianoverall treatment time was 45 days and delay treatment time 38 days. Fifty nine point onepercent of partial respon was found. Local recurrences were found throughout the follow-upof 6.6%. Analysis kaplan meyer showed that overall treatment time was a prognostic factorfor overal survival rate (p=0,016).Conclusions : : Almost seventy one percent of glioma patients who received radiotherapyhad craniotomy removal tumor. 3D Conformal techniques is the most widely used. Fifty ninepoint one percent of partial respon founded. Three years overall survival was 46,2% andoverall treatment time was found as a factor that significantly affects overall survivalprognosis., Introduction : Glioma is the most common type of primary intracerebral neoplasms. Highgrade glioma being the most frekuent type found (70,9%) causes a high morbidity andmortality rate. There is currently no data describing the profile management of patientsundergoing radiotherapy glioma in Indonesia.Methods : This study Retrospective analytic descriptive study of 121 glioma patients fromjanuari 2009 until december 2014. The data was obtained from medical records and indivualcontact via telephone. Tumor response was evaluated in 22 patients with pre and postirradiation imaging (CT or MRI) using 3D volumetric data and assessed via RECISTcriteria.Results : Most of our patients were male (53,7%), with median age 45 years old.Astrocytoma was the most histopathological type found. 70.9% of Patients who receivedradiotherapy in Cipto Mangunkusumo hospital were post craniotomi tumor removal. 3DConformal technique was used in 81.0% of patients. Seventy nine point three had a two graydose perfraction. Provision of chemotherapy in patients undergoing radiation still only at7.4% of patients. Nimotuzumab as a monoclonal antibody used on 9% patient. The medianoverall treatment time was 45 days and delay treatment time 38 days. Fifty nine point onepercent of partial respon was found. Local recurrences were found throughout the follow-upof 6.6%. Analysis kaplan meyer showed that overall treatment time was a prognostic factorfor overal survival rate (p=0,016).Conclusions : : Almost seventy one percent of glioma patients who received radiotherapyhad craniotomy removal tumor. 3D Conformal techniques is the most widely used. Fifty ninepoint one percent of partial respon founded. Three years overall survival was 46,2% andoverall treatment time was found as a factor that significantly affects overall survivalprognosis.]"