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Abstrak :
[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. ......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., 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.]

Abstrak :
Latar Belakang: Kanker primer tahap lanjut dapat bermetastasis ke sistem saraf pusat (SSP) yaitu otak dan spinal, maupun ke selain SSP. Perbedaan gejala klinis antara metastasis SSP dan tanpa keterlibatan SSP adalah defisit neurologis pada metastasis SSP. Kedua metastasis tersebut dapat berisiko menyebabkan indeks massa otot skeletal yang rendah akibat gejala klinis dan peningkatan metabolisme akibat kanker. Namun, belum diketahui perbedaan di antara keduanya. Tujuan penelitian ini untuk mengetahui perbedaan appendicular skeletal muscle index (ASMI) pada pasien metastasis dengan dan tanpa keterlibatan SSP. Metode: Penelitian ini adalah studi potong lintang pada subjek berusia 18-65 tahun. Karakteristik subjek berupa usia, jenis kelamin, indeks massa tubuh, status gizi berdasarkan ASPEN, lokasi tumor primer, lokasi metastasis, waktu terdiagnosis metastasis, defisit neurologis, asupan energi dan protein, Karnofsky Performance Scale, kemoterapi, terapi glukokortikoid, dan nilai ASMI. Analisis bivariat digunakan untuk menilai perbedaan nilai ASMI antara metastasis SSP dan tanpa keterlibatan SSP. Hasil: Terdapat 59 subjek dengan nilai ASMI rendah. Rerata nilai ASMI pada metastasis SSP lebih rendah (3,81±1,19 kg/m2) dibandingkan dengan metastasis tanpa keterlibatan SSP (3,97±0,93 kg/m2) dengan perbedaan tidak signifikan pada kedua kelompok (p = 0,568). Terdapat perbedaan bermakna antara ASMI rendah dengan jenis kelamin (p=0,000), asupan energi (p=0,012), disfagia (p=0,027), nyeri kepala (p=0,033), dan gangguan kognitif (p=0,032). Kesimpulan: Tidak ditemukan perbedaan bermakna antara subjek yang memiliki ASMI rendah pada metastasis SSP dan tanpa keterlibatan SSP. Perbedaan bermakna ditemukan antara ASMI dengan karakteristik subjek yaitu jenis kelamin, asupan energi, disfagia, nyeri kepala, dan gangguan kognitif. ......Background: Advanced primary cancer can metastasize to the central nervous system (CNS), namely the brain and spinal cord, or to other than the CNS. The difference in clinical symptoms between CNS metastases and those without CNS involvement is the neurological deficit in CNS metastases. Both metastases may be at risk for low skeletal muscle mass index due to clinical symptoms and increased metabolism due to cancer. However, the differences between them are unknown. The aim of this study was to determine the difference of appendicular skeletal muscle index in metastatic patients with and without CNS involvement. Methods: This study was a cross-sectional study on subjects aged 18-65 years. Subject characteristics included age, gender, body mass index, nutritional status based on ASPEN, primary tumor location, metastasis location, time of metastasis diagnosis, neurological deficits, energy and protein intake, Karnofsky Performance Scale, chemotherapy, glucocorticoid therapy, and ASMI value. Bivariate analysis was used to assess the difference in ASMI value between CNS metastasis and without CNS involvement Results: There were 59 subjects with low ASMI values. The mean ASMI value in CNS metastasis was lower (3,81±1,19 kg/m2) compared to metastasis without CNS involvement (3,97±0,93 kg/m2) without significant difference in both groups (p=0,568). There was a significant difference between low ASMI and gender (p=0,000), energy intake (p=0,012), dysphagia (p=0,027), headache (p=0,033), and cognitive impairment (p=0,032). Conclusion: No significant difference was found between subjects who had low ASMI in CNS metastasis and without CNS involvement. Significant differences were found between ASMI and subject characteristics such as gender, energy intake, dysphagia, headache, and cognitive impairment.

Abstrak :
Latar Belakang: Tumor sistem saraf pusat (SSP) merupakan salah satu penyebab utama morbiditas di seluruh dunia yang menyebabkan disabilitas dan penurunan kualitas hidup. Tumor SSP menyebabkan defisit neurologis dan berisiko terjadinya kaheksia. Kaheksia dihubungkan dengan penurunan respons pengobatan dan penurunan kesintasan. Peradangan sistemik merupakan ciri khas kaheksia. Rasio neutrofil limfosit (RNL) merupakan penanda inflamasi sistemik yang mudah dan rutin diperiksa dengan harga yang tidak mahal. Belum diketahui hubungan antara RNL dengan kejadian kaheksia pada tumor SSP. Metode: Studi potong lintang ini dilakukan pada subjek berusia 18–65 tahun di RSUPN Dr. Cipto Mangunkusumo, yang dirawat dengan diagnosis tumor SSP pada bulan November hingga Desember 2023. Nilai RNL diambil dari pemeriksaan darah perifer lengkap dan dilakukan penegakan diagnosis kaheksia berdasarkan kriteria Evans. Dilakukan analisis hubungan RNL dengan kejadian kaheksia. Hasil: Terdapat 50 subjek dengan diagnosis tumor SSP. Median RNL adalah 4,13 (1,26; 23,22). Nilai RNL secara signifikan lebih tinggi pada kelompok subjek yang mengalami kaheksia (median RNL 7,19 (1,26; 23,22)) dibandingkan tanpa kaheksia (median RNL 3,10 (1,40; 8,48)) (p<0,001). Simpulan: RNL berhubungan dengan kejadian kaheksia pada tumor SSP. Subjek yang mengalami kaheksia memiliki RNL yang lebih tinggi dibandingkan dengan yang tidak kaheksia. ......Background: Central nervous system (CNS) tumors are one of the leading causes of morbidity worldwide, causing disability and decreased quality of life. Central nervous system tumors cause neurological deficits and are at risk of developing cachexia. Cachexia is associated with decreased treatment response and reduced survival. Systemic inflammation is the hallmark of cachexia. Neutrophil lymphocyte ratio (NLR) is a systemic inflammation that included in routine laboratory examination and inexpensive. The association between NLR and the incidence of cachexia in CNS tumors remain unknown. Methods: This cross-sectional study was conducted on subjects aged 18–65 years old at RSUPN Dr. Cipto Mangunkusumo Hospital, who were admitted with CNS tumor diagnosis from November to December 2023. The NLR value was taken from the complete peripheral blood examination and the diagnosis of cachexia was based on Evans criteria. The relationship between NLR and the incidence of cachexia was analyzed. Results: There were 50 subjects with CNS tumor diagnosis. The median NLR was 4,13 (1,26; 23,22). The mean NLR was significantly higher in the group of subjects with cachexia (median NLR 7,19 (1,26; 23,22)) than without cachexia (median NLR 3,10 (1,40; 8,48)) (p<0,001). Conclusion: NLR is associated with the incidence of cachexia in CNS tumors. Subjects with cachexia had higher NLR compared to those withoit cachexia.

Abstrak :
Tumor sistem saraf pusat (SSP) dapat menurunkan massa otot dan massa bebas lemak akibat defisit neurologis yang terjadi serta efek sistemik karena keganasan. Penurunan massa bebas lemak dan massa otot dengan inflamasi saling memengaruhi serta dikaitkan dengan prognosis yang buruk. Penelitian ini bertujuan untuk mengetahui korelasi indeks massa bebas lemak (FFMI) dengan indeks inflamasi imun sistemik (SII) pada pasien tumor SSP. Studi ini merupakan studi potong lintang pada pasien dewasa dengan diagnosis tumor SSP di RSUPN Dr. Cipto Mangunkusumo. Pengukuran FFMI menggunakan bio impedance analysis (BIA). Nilai SII didapatkan dari hasil pemeriksaan laboratorium darah perifer lengkap. Terdapat 74 pasien tumor SSP dengan mayoritas perempuan (59,5%) dan lokasi tersering adalah tumor di otak (79,7%). Proporsi jenis tumor primer maupun sekunder adalah sama (50%). Median indeks massa tubuh (IMT) yaitu 22,85 kg/m2 (11,99–37,60 kg/m2) dengan kategori IMT terbanyak adalah berat badan normal (33,8%). Rerata FFMI yaitu 16,05±3,12 kg/m2 dengan 51,4% pasien memiliki FFMI yang rendah. Median SII sebesar 1140,9 (103,6–8745,6). Tidak didapatkan korelasi antara FFMI dengan SII pada pasien tumor SSP. Pada analisis tambahan didapatkan korelasi negatif bermakna antara FFMI dengan SII pada wanita (r=- 0,351; p=0,019), sebaliknya pada pria tidak ditemukan adanya korelasi (r=-0,096; p=0,613). ......Central nervous system (CNS) tumors can reduce muscle mass and fat-free mass due to neurological deficits and systemic effects of malignancy. Decreased fat-free mass and muscle mass with inflammation are mutually influential and associated with poor prognosis. This study aimed to determine the correlation between fat-free mass index (FFMI) and systemic immune inflammation index (SII) in patients with CNS tumors. This is a cross-sectional study of CNS tumors adult patients at Dr. Cipto Mangunkusumo National General Hospital. FFMI measurements were obtained using bioimpedance analysis (BIA). SII values obtained from complete peripheral blood laboratory examination results. There were 74 patients with CNS tumors, with the majority being female (59.5%), and the most common location was brain tumors (79.7%). The proportion of primary and secondary tumor types was equal (50%). The median body mass index (BMI) was 22.85 kg/m2 (11.99– 37.60 kg/m2), with the majority falling under the normal weight category (33.8%). The mean FFMI was 16.05±3.12 kg/m2, with 51.4% of patients having a low FFMI. The median SII was 1140.9 (103.6–8745.6). There was no correlation between FFMI and SII in patients with CNS tumors. In additional analysis, a significant negative correlation was found between FFMI and SII in women (r=-0.351; p=0.019), whereas in men, no correlation was found (r=-0.096; p=0.613).

Abstrak :
Latar Belakang : Inflamasi kronik berhubungan dengan tumor dan menyebabkan prognosis yang buruk pada pasien kanker. Salah satu penanda inflamasi yang meningkat pada tumor adalah C-Reactive Protein (CRP). Kadar CRP meningkat pada lebih dari 50% pasien keganasan. Peningkatan CRP berhubungan kuat dengan keparahan penyakit pada beberapa kanker. Salah satu zat gizi dalam inflamasi adalah asam lemak omega-3. Asam lemak omega-3 dapat meningkatkan pembentukan specialized pro-resolving mediators (SPM) yang berfungsi meningkatkan mediator antiinflamasi, melindungi blood brain barrier, menurunkan sitokin proinflamasi, menurunkan apoptosis neuron. Penelitian ini bertujuan untuk menilai hubungan asupan asam lemak omega-3 dengan CRP pada pasien tumor sistem saraf pusat. Metode : Studi potong lintang ini dilakukan pada subjek berusia 18-65 tahun di RSUPN Cipto Mangunkusumo pada bulan November hingga Desember 2023. Pengukuran CRP menggunakan metode immunoturbidimetric assay. Pengambilan asupan asam lemak omega-3 menggunakan Food Frequency Questionnaires semikuantitatif. Analisis bivariat digunakan untuk menilai hubungan antara variabel bebas dan terikat. Hasil : Dari total 63 subjek penelitian, sebanyak 35 subjek (55,6%) pada kelompok asupan asam lemak omega-3 < 2 g/hari dan 28 subjek (44,4%) pada kelompok asupan asam lemak omega-3 ≥ 2 g/hari. Nilai median CRP 8,3 (0,6 – 71,5) mg/L. Tidak terdapat hubungan yang bermakna (p = 0,714) antara asupan asam lemak omega-3 dengan CRP pada pasien tumor sistem saraf pusat. Kesimpulan : Tidak terdapat hubungan bermakna antara asupan asam lemak omega-3 dengan CRP pada pasien tumor sistem saraf pusat. ......Background: Chronic inflammation is associated with tumors and causes poor prognosis in tumor patients. One of the inflammatory markers that increase in tumors is C-Reactive Protein (CRP). CRP levels are elevated in more than 50% of patients with malignancies. Elevated CRP is associated with disease severity in some cancers. One of the nutrients in inflammation is omega-3 fatty acids. Omega-3 fatty acids can increase the formation of specialized pro-resolving mediators (SPM) which function to increase anti-inflammatory mediators, protect the blood brain barrier, reduce pro-inflammatory cytokines, reduce neuron apoptosis. This study aims to assess the relationship between omega-3 fatty acid intake and CRP in patients with central nervous system tumors. Methods: This cross-sectional study was conducted on subjects aged 18-65 years at Cipto Mangunkusumo Hospital from November to December 2023. CRP measurement using immunoturbidimetric assay method. Omega-3 fatty acid intake was collected using semiquantitative Food Frequency Questionnaire. Bivariate analysis was used to assess the relationship between independent and dependent variables. Results: From the total 63 research subjects, 35 subjects (55,6%) in the omega-3 fatty acid intake group < 2 g/day and 28 subjects (44,4%) in the omega-3 fatty acid intake group ≥ 2 g/day. The median CRP value was 8.3 (0.6 - 71.5) mg/L. There was no significant relationship (p = 0,714) between omega-3 fatty acid intake and CRP in patients with central nervous system tumors. Conclusion: There is no significant relationship between omega-3 fatty acid intake and CRP in patients with central nervous system tumors.

Abstrak :
The most recent developments in diagnostic and therapeutic aspects of gliomas (glioblastoma) in the brain are presented. The importance of personalized medicine and clinical validation for targeted therapy are discussed. The identification of various types of biomarkers (determined by molecular genetics) is included, along with their advantages and limitations as markers in tumor detection and diagnosis. The identification and validation of brain cancer (glioblastoma) genes are discussed. The role of cancer stem cells in the initiation and persistence of malignant gliomas is explained, response of glioblastoma cancer stem cells to various growth factors, such as epidermal growth factor receptor kinase inhibitor, is explained. The use of surgical resection, chemotherapy (e.g., temozolomide), immunotherapy, and radiation therapy for glioblastoma patients is included. Biological impediments for chemotherapy and radiotherapy for malignant glioblastoma are pointed out. Standard (established) as well as newer imaging modalities (proton magnetic resonance spectroscopy) are discussed. Also included are proton magnetic resonance spectroscopy in intracranial gliomas, and the use of proton magnetic spectroscopic imaging in determining the infiltration zone in gliomas. The role of molecular signaling in the CNS cancer development is explained, including cell death signaling in glioblastoma multiforme.