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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: Metilasi dari gen promoter O6-methylguanine-DNA methyltransferase (MGMT) adalah salah satu faktor yang berperan pada karsinogenesis dan berkembang menjadi marker dalam menilai progresivisitas dan respons terapi astrositoma. Tujuan: Untuk mendapatkan gambaran frekuensi status metilasi gen promoter MGMT pada pasien astrositoma menggunakan methylation specific polymerase chain reaction (MS-PCR) dan methylation specific high resolution melting (MS-HRM). Metode: Dilakukan pengumpulan data klinis, imajing dan blok parafin jaringan astrositoma di RSCM dalam kurun waktu 2008-2012. Status metilasi gen promoter MGMT dianalisis menggunakan MS-PCR dan MS-HRM serta dihubungkan dengan berbagai faktor prognostik klinis. Penelitian ini adalah penelitian potong-lintang. Hasil: Didapatkan 13 sampel yang terdiri dari 7 astrositoma derajat rendah dan 6 astrositoma derajat tinggi. Metilasi gen promoter MGMT didapatkan pada 1/13 sampel astrositoma dengan MS-PCR dan 4/13 sampel dengan MS-HRM yang seluruhnya adalah astrositoma derajat rendah. Terdapat perbedaan yang bermakna antara status metilasi gen promoter MGMT dengan derajat keganasan astrositoma yaitu astrositoma derajat rendah 4/7 sampel, tanpa ditemukan pada astrositoma derajat tinggi (p=0.049) sedangkan faktor lain seperti usia, jenis kelamin, karnofsky performance scale (KPS), lokasi astrositoma dan derajat WHO tidak terdapat perbedaan yang bermakna (p= 1,000; p= 0,657; p= 0,354; p= 0,538). Simpulan: Penelitian saat ini menunjukkan frekuensi status metilasi gen promoter MGMT pada astrositoma sedikit berbeda dengan berbagai penelitian lain sebelumnya yaitu hipermetilasi hanya terjadi pada astrositoma derajat rendah. Penelitian ini merupakan penelitian pertama di Indonesia yang melaporkan gambaran status metilasi gen promoter MGMT pada pasien astrositoma.

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Background: Astrocytoma is the most common primary central nervous system tumor with difficult management as it requires a combination of surgery, chemotherapy and radiotherapy. This multimodal approach increases patients survival rate significantly, however chemotherapy resistance is now commonly seen. One of the potential causes of chemotherapy resistance is the epigenetic factors from O6 methylguanine-DNAmethyltransferase (MGMT) gene. MGMT gene has role in DNA repair and also have a protective effect against exyogen and endogeneous alkylating agent. The methylation of MGMT gene promoter leads to the decrease of MGMT protein, attenuating its function. Therefore, the methylation status of MGMT gene promoter can act as an indicator for astrocytomas progresivity and treatment aggressiveness.

Objective: To determine the frequency of MGMT gene promoter methylation among patients with astrocytomas using methylation specific polymerase chain reaction (MS-PCR) and methylation sensitive high resolution melting (MS-HRM).

Methods: Clinical data, imaging and parafin blocks from astrocytoma patients were collected in RSCM from 2008-2012. The methylation status of MGMT gene promoter was confirmed using MS-PCR and MS-HRM. This is cross-sectional study.

Results: The total of 13 samples collected including 7 low-grade and 6 high-grade astrocytomas. The MGMT gene promoter was methylated in 1/13 cases using MS-PCR and 4/13 cases using MS-HRM. All methylated cases were low-grade astrocytoma. There was significant association between methylation status of MGMT gene promoter with degree of malignancy which is 4/7 samples hypermethylated in low-grade with no hypermethylation in high-grade astrocytomas (p=0.049). While other factors like age, sex, KPS and astrocytomas location have no significant association (p= 1,000; p= 0,657; p= 0,354; p= 0,538).

Conclusions: The present study showed difference of methylation of MGMT gene promoter in astrocytomas with others studies which is hypermethylated MGMT only found in low grade astrocytomas. Our study was the first to report the frequency of MGMT promoter methylation among Indonesian astrocytoma patients."

"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. "