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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. ......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."

"[ABSTRAKGlioma adalah tumor otak primer yang sampai saat ini sering timbul resistensiterapi. Sel punca glioma diduga berperan penting dalam resistensi dan rekurensisel tumor. Sel punca glioma memiliki penanda permukaan CD133 dan mampuberpluripotensi dengan mengekspresikan Oct4. Kondisi hipoksia tumor jugaberperan dalam self renewal sel punca glioma. Tujuan dari penelitian ini adalahuntuk mengetahui hubungan keberadaan sel punca glioma dengan keganasan,pluripotensi dan kondisi hipoksia. Cross sectional digunakan sebagai desainpenelitian dengan jumlah sampel sebanyak 35 jaringan, terdiri atas 15 gliomaderajat keganasan tinggi dan 20 glioma derajat keganasan rendah. Pengukuranekspresi relatif mRNA CD133, Oct4 dan HIF-1α menggunakan metode qRTPCR.Protein HIF-1α dilihat ekspresinya melalui teknik imunohistokimia.Ekspresi relatif mRNA CD133 dan Oct4 lebih tinggi bermakna (p < 0.05, Mann-Whitney) pada glioma derajat keganasan tinggi dibanding glioma derajatkeganasan rendah. Protein HIF-1α lebih tinggi bermakna (p < 0,01, Mann-Whitney) pada glioma derajat keganasan tinggi dibanding glioma derajatkeganasan rendah. Terdapat hubungan ekspresi sel punca glioma CD133 denganpluripotensi serta kondisi hipoksia (r = 0,518, r = 0,339; Spearman?s rho) sertapluripotensi dengan kondisi hipoksia pada derajat keganasan tinggi (r = 0,749;Spearman?s rho). Ekspresi relatif mRNA CD133, Oct4 dan HIF-1α meningkatseiring dengan peningkatan derajat keganasan. Terdapat hubungan yang bermaknaantara keberadaan penanda sel punca glioma CD133 dengan pluripotensi dankondisi hipoksia pada glioma derajat keganasan tinggi.

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ABSTRACTGlioma is primary brain tumor with frequent therapeutic resistance. Gliomacancer stem cells were considered to play a role in resistance and recurrence oftumor cells. Glioma cancer stem cells expressed CD133 on their surface andcapable of pluripotency as expressed by Oct4 positive. Tumor hypoxic conditionalso play a role in glioma cancer stem cells self renewal. Aim of this study is toinvestigate correlation between glioma cancer stem cells, degree of malignancy,pluripotency and hypoxia. Design of this study is cross sectional with 35 gliomasamples comprises of 20 low grade malignant glioma and 15 high grade malignantglioma. Expression of mRNA CD133, Oct4 and HIF-1α were measured usingqRT-PCR. HIF-1α protein expression was detected by immunohistochemistryfrom glioma sample. mRNA CD133 and Oct4 expression significantly higher (p <0.05, Mann-Whitney) in high grade malignant glioma compared to low grademalignant glioma. HIF-1α tissue expression significantly higher (p < 0,01, Mann-Whitney) in high grade malignant glioma compared to low grade malignantglioma. There was correlation between expression of CD133 glioma cancer stemcells marker with pluripotency and hypoxia (r = 0,518, r = 0,543; Spearman?s rho)and pluripotency with hypoxia in high grade malignant glioma (r = 0,749;Spearman?s rho). mRNA CD133, Oct4 and HIF-1α expression increased withhigh grade malignant glioma. There was significant correlation between CD133glioma cancer stem cell marker with pluripotency and hypoxia in high grademalignant glioma, Glioma is primary brain tumor with frequent therapeutic resistance. Gliomacancer stem cells were considered to play a role in resistance and recurrence oftumor cells. Glioma cancer stem cells expressed CD133 on their surface andcapable of pluripotency as expressed by Oct4 positive. Tumor hypoxic conditionalso play a role in glioma cancer stem cells self renewal. Aim of this study is toinvestigate correlation between glioma cancer stem cells, degree of malignancy,pluripotency and hypoxia. Design of this study is cross sectional with 35 gliomasamples comprises of 20 low grade malignant glioma and 15 high grade malignantglioma. Expression of mRNA CD133, Oct4 and HIF-1α were measured usingqRT-PCR. HIF-1α protein expression was detected by immunohistochemistryfrom glioma sample. mRNA CD133 and Oct4 expression significantly higher (p <0.05, Mann-Whitney) in high grade malignant glioma compared to low grademalignant glioma. HIF-1α tissue expression significantly higher (p < 0,01, Mann-Whitney) in high grade malignant glioma compared to low grade malignantglioma. There was correlation between expression of CD133 glioma cancer stemcells marker with pluripotency and hypoxia (r = 0,518, r = 0,543; Spearman’s rho)and pluripotency with hypoxia in high grade malignant glioma (r = 0,749;Spearman’s rho). mRNA CD133, Oct4 and HIF-1α expression increased withhigh grade malignant glioma. There was significant correlation between CD133glioma cancer stem cell marker with pluripotency and hypoxia in high grademalignant glioma]"

"This book examines innovative methods in glioma immunology and immunotherapy. It reviews the basic and clinical background and proceeds from basic science at the bench to the bedside to give a realistic evaluation of the immunology and immunotherapy of glioma. "