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"[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]"

"[ABSTRAKPendahuluan : Kanker kolorektal termasuk salah satu morbiditas terbanyak di Indonesia dengan hasil terapi yang cenderung memprihatinkan untuk stadium lanjut lokal. Oleh karena itu diperlukan kemoradiasi neoajuvan yang merupakan terapi standar sesuai guideline untuk kanker rektum stadium lanjut lokal, meskipun demikian espons yang dihasilkan sangat bervariasi dan dipengaruhi oleh berbagai faktor, termasuk hipoksia jaringan. Osteopontin adalah penanda hipoksia endogen yang berkorelasi signifikan dengan tekanan oksigen tumor. Osteopontin juga merupakan penanda hipoksia kronis yang lebih akurat dibandingkan Carbonic Anhydrase IX (CAIX), Glucose Transporter 1 (GLUT1), dan Lactate Dehydrogenase A (LDH A) tetapi belum pernah dilakukan penelitian yang mengukur kadar OPN secara kuantitatif pada jaringan kanker rektum serta mengkorelasikannya dengan respons pengecilan tumor pada kemoradiasi neoajuvan.Metode dan Materi: Dilakukan skrining data pasien dari Rekam Medis Departemen Radioterapi. Empat belas pasien yang memenuhi kriteria inklusi dan eksklusi dianalisis retrospektif dari bulan Februari sampai dengan bulan Mei 2015. Pencitraan radiologi pasca kemoradiasi dibandingkan dengan sebelum kemoradiasi, sementara jaringan rectum didapatkan dari blok parafin yang didapatkan dari biopsi sebelum kemoradiasi. Evaluasi radiologi diukur menggunakan kriteria RECIST 1.1. Kadar OPN diperiksa menggunakan metode ELISA dan diukur menggunakan spektrofometer.Hasil : Rerata kadar OPN adalah 0.5678 ± 0.26 ng/mL. Terdapat korelasi berbanding terbalik yang kuat (r= -0.630, p= 0.016) antara kadar OPN dan pengecilan tumor. Nilai ambang batas OPN ≥0.538 ng/mL memprediksikan ketidakresponsifan terhadap kemoradiasi neoajuvan dengan tingkat sensitivitas 100% dan spesifisitas 81,8%. Meskipun demikian, tidak terdapat korelasi antara kadar OPN dengan Hemoglobin.Kesimpulan : Penelitian ini menunjukkan bahwa hipoksia terdapat pada pasien dengan kanker rektum stadium lanjut lokal dan merupakan karakter yang menandai turunnya respons pengecilan tumor terhadap kemoradiasi neoajuvan. Kadar OPN yang makin tinggi menunjukkan kondisi hipoksia yang lebih buruk dan respons yang lebih buruk untuk pengecilan tumor.

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ABSTRACTIntroduction: Colorectal carcinoma is one of the common cancer in Indonesia with concerned clinical outcome for locally advanced stage, therefore neoadjuvant chemoradiation (CRT) is needed. Neoadjuvant CRT is the mainstay treatment for locally advanced rectal carcinoma, however the response is varied due to many factors, including tissue hypoxia. Osteopontin (OPN) is an emerging endogen hypoxic marker with significant correlation with tumor pO2, also more accurate chronic hypoxic marker compared to Carbonic Anhydrase IX (CAIX), Glucose Transporter 1 (GLUT1), and Lactate Dehydrogenase A (LDH A) but there's no research that measured OPN quantity in rectal cancer tissue and correlate it with tumor shrinkage response in neoadjuvant CRT.Methods and Materials: Patients? data was screened from Radiotherapy Department Medical Record Archieves. Fourteen patients that meet the inclusion and exclusion criteria were analyzed retrospectively from February to May 2015. Radiology imaging post CRT compared to the imaging pre CRT, while the rectum tissue obtained from Formalin-Fixed Paraffin Embedded (FFPE) tissue from biopsy sampling before CRT. Radiology evaluation was measured using RECIST 1.1. OPN level was conducted using ELISA method and measured with spectrophotometry.Results: The mean OPN concentration is 0.5678 ± 0.26 ng/mL. There was a significant strong negative correlation (r = -0.630, p= 0.016) between the OPN level and tumor shrinkage. OPN cut off value ≥0.538 ng/ml predicts non-responsiveness of neoadjuvant CRT with 100% sensitivity and 81.8% specificity. However, there is no correlation between OPN concentration and Hemoglobin concentration.Conclusion: This study showed that hypoxia occurs in patients with locally advanced rectal carcinoma, and characterizes decreasing tumor shrinkage response in neoadjuvant CRT. Higher level of OPN suggests worse level of hypoxic condition and worse response of tumor shrinkage., Introduction: Colorectal carcinoma is one of the common cancer in Indonesia with concerned clinical outcome for locally advanced stage, therefore neoadjuvant chemoradiation (CRT) is needed. Neoadjuvant CRT is the mainstay treatment for locally advanced rectal carcinoma, however the response is varied due to many factors, including tissue hypoxia. Osteopontin (OPN) is an emerging endogen hypoxic marker with significant correlation with tumor pO2, also more accurate chronic hypoxic marker compared to Carbonic Anhydrase IX (CAIX), Glucose Transporter 1 (GLUT1), and Lactate Dehydrogenase A (LDH A) but there’s no research that measured OPN quantity in rectal cancer tissue and correlate it with tumor shrinkage response in neoadjuvant CRT. Methods and Materials: Patients’ data was screened from Radiotherapy Department Medical Record Archieves. Fourteen patients that meet the inclusion and exclusion criteria were analyzed retrospectively from February to May 2015. Radiology imaging post CRT compared to the imaging pre CRT, while the rectum tissue obtained from Formalin-Fixed Paraffin Embedded (FFPE) tissue from biopsy sampling before CRT. Radiology evaluation was measured using RECIST 1.1. OPN level was conducted using ELISA method and measured with spectrophotometry. Results: The mean OPN concentration is 0.5678 ± 0.26 ng/mL. There was a significant strong negative correlation (r = -0.630, p= 0.016) between the OPN level and tumor shrinkage. OPN cut off value ≥0.538 ng/ml predicts non-responsiveness of neoadjuvant CRT with 100% sensitivity and 81.8% specificity. However, there is no correlation between OPN concentration and Hemoglobin concentration. Conclusion: This study showed that hypoxia occurs in patients with locally advanced rectal carcinoma, and characterizes decreasing tumor shrinkage response in neoadjuvant CRT. Higher level of OPN suggests worse level of hypoxic condition and worse response of tumor shrinkage.]"

"Osteopontin merupakan salah satu sitokin yang banyak dihubungkan dengan proses resorpsi tulang, namun perannya di dalam proses penyembuhan periodontal masih didapatkan hasil yang berbeda-beda sedangkan Tumor Necrosis Factor-α (TNF-α)merupakan sitokin pro-inflamasi yang berperandalam inflamasi kronis dan proses resorpsi tulang. Penelitian ini bertujuan menganalisis perbedaan tingkat ekspresi Osteopontin dan TNF-αpada pasien periodontitis sebelum terapi dengan setelah terapi skeling dan penghalusan akar (diukur setelah 7 hari, 14 hari, dan 28 hari). Tingkat ekspresi Osteopontin dan TNF-αdalam cairan krevikuler gingiva (CKG)dari 28 subjek penderita periodontitis berusia ≥ 30 tahun dan dari 8 subjek sehat diukur dengan menggunakan qPCR. Dilakukan juga uji korelasi Spearmanantara tingkat ekspresi Osteopontin dan TNF-αdalam CKG dengan pemeriksaan klinis berupa modified gingival index (MGI).Uji Wilcoxontingkat ekspresi Osteopontin dan TNF-αdalam CKG pada pasien periodontitis sebelum dan setelah 28 hari terapi skeling dan penghalusan akar menunjukkan perbedaan bermakna (p < 0,05). Uji korelasi Spearmanmenunjukkan korelasi positif lemah antara tingkat ekspresi OPNdengan skor MGI(r=0,213;p<0,05) dan antara tingkatekspresi TNF-αdengan skor MGI(r=0,256;p<0,05). Penelitian ini menyimpulkan bahwa terdapat perbedaan tingkat ekspresi Osteopontin dan TNF-αpada subjekperiodontitis antara sebelum terapi dengan 28 hari setelahterapi skeling dan penghalusan akar gigi. Adakorelasi positif antara tingkat ekspresi OPNdengan MGIdan tingkat ekspresi TNF-αdengan MGI.

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Osteopontin is one of many cytokines that is often associated with bone resorption process, but the role in the periodontal healing is still not clear accordingto some studies presenting different results, while Tumor Necrosis Factor-α (TNF-α) is a well-known pro-inflammatory cytokine which stimulates bone resorption. The objective of this study was to analyze different Osteopontin and TNF-α expression level on patients with periodontitis before (baseline) and 7 days, 14 days, 28 days following scaling and root planing. Osteopontin and TNF-α level on gingival crevicular fluid (GCF) from 28 subjects with periodontitis aged ≥ 30years old and 8 healthy patients (control subjects)were measured by qPCR. Spearman correlation test between GCF Osteopontin and TNF-α level and modified gingival index (MGI) was also done. Wilcoxon test between Osteopontin and TNF-α level before scaling and root planing and 28 days after scaling and root planing showed a significant difference (p < 0.05). Spearman correlation test between TNF-α level on GCF and MGI showed a positive correlation (r=0.256; p<0.05). Conclusions of this study was a significant difference of OPN and TNF-αexpression level between baseline and 28 days after scaling and root planing in periodontitis subjects and a positive correlation between GCF OPN level and MGI and also between TNF-α expression level and MGI."

"Latar Belakang: Perawatan yang telah ada selama ini tidak memberikan hasil yang maksimal pada defek besar sehingga berkembang konsep rekayasa jaringan yang memiliki komponen scaffold, signaling molecule, dan sel. Scaffold yang digunakan adalah chitosan karena karakteristiknya yang biokompatibel dan biodgradable. RGD ditambahkan sebagai signaling molecule, yang berfungsi berperan untuk merangsang sel berdiferensiasi dan memproduksi matriks untuk perkembangan sel dalam membentuk jaringan. Tujuan: Mengetahui ekspresi protein OPN sebagai indikator regenerasi jaringan periodontal setelah pemberian bahan regeneratif. Metode dan Bahan: Model defek tulang horizontal pada tulang alveolar di sekitar gigi insisif lateral M.nemestrina yang dipaparkan bahan regeneratif chitosan atau RGD modified chitosan. 4 minggu setelah pemaparan bahan regeneratif jaringan dibiopsi dan diproses dengan metode IHK dengan antibodi OPN yang menandakan regenerasi jaringan periodontal, dianalisis melalui % area pewarnaan dan intensitas warna dengan metode grid pada aplikasi ImageJ. Hasil: Tidak ada perbedaan bermakna secara statistik antara kelompok chitosan dengan median % area pewarnaan positif 21,81 yang lebih tinggi dibanding RGD modified chitosan dengan median % area pewarnaan positif 10,88. Kesimpulan: Terapi regeneratif dengan pemberian chitosan atau RGD modified chitosan berpotensi meregenerasi jaringan periodontal. Penambahan RGD pada chitosan dievaluasi secara histologis tidak mempengaruhi ekspresi OPN.

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Background: Treatment that has existed so far doesn’t provide maximum results in large defects, so develops concept of tissue engineering that have scaffold, signaling molecule, and cell as components. The scaffold material used is chitosan because of its charactheristics which have high viscocity, the ability to bind to water, biocompatible, and biodgradable. RGD is added as a signaling molecule, which act to stimulate cells to differentiate and produce matrices for cell development in forming tissue.

Objective: To know expression of OPN as periodontal tissue regeneration indicator after exposure with regenerative materials.

Methods and Materials: The horizontal bone defect model in the M.nemestrina’s alveolar bone around lateral insisive was exposed by chitosan or RGD modified chitosan and biopsied after 4 weeks. Slides were processed through IHC method with OPN as antibody. The expression of OPN signifies periodontal tissue regeneration, analized through % area of staining and color intensity with grid method on ImageJ.

Result: There was no significant difference stastically between chitosan with % positive staining area median 21.81 which was higher than RGD modified chitosan with % positive staining area median 10.88.

Conclusion: Regenertive theraphy with chitosan or RGD modified chitosan potentially regenerate the periodontal tissue. Addition of RGD to chitosan evaluate histologically didn’t affect the expression of OPN."

"Latar Belakang: Terapi regeneratif jaringan periodontal pada kasus kerusakan tulang alveolar horizontal telah dilaporkan dapat meningkatkan perlekatan jaringan periodontal secara klinis. Tetapi, efek perawatan pada sintesis matriks ekstraseluler tulang belum diketahui. Osteopontin merupakan salah satu marker penanda tulang sehingga dapat digunakan dalam menganalisis keberhasilan regenerasi jaringan periodontal pascaterapi regeneratif. Tujuan: Menganalisis ekspresi osteopontin pascaterapi regeneratif PDL cell sheet + RGD-modified chitosan dan PDL cell sheet + chitosan scaffold terhadap regenerasi jaringan periodontal. Metode dan Bahan: Sampel penelitian adalah sediaan mikroskopik jaringan periodontal M.nemestrina yang telah ditanam bahan regeneratif PDL cell sheet + RGD-modified chitosan dan PDL cell sheet + chitosan scaffold selama empat minggu setelah perawatan. Sediaan diwarnai dengan metode imunohistokimia menggunakan antibodi osteopontin. Ekspresi osteopontin dianalisis area dan intensitas pewarnaannya dengan metode grid pada ImageJ, serta uji statistik menggunakan SPSS. Hasil: Median area pewarnaan positif pada PDL cell sheet + RGD-modified chitosan 74,81% (53,48%-81,06%) lebih besar dari PDL cell sheet + chitosan scaffold 63,99% (52,43%-80,31%), namun tidak berbeda bermakna secara statistik pada kedua bahan tersebut (p >0,05). Median intensitas area pewarnaan positif lemah 43,05% (14,16%-61,52%), sedang 14,49% (6,70%-22,81%), dan kuat 17,82% (3,66%-20,20%) pada kelompok PDL cell sheet + RGD-modified chitosan lebih besar dibanding PDL cell sheet + chitosan scaffold, namun tidak berbeda bermakna secara statistik. Kesimpulan: Ekspresi osteopontin lebih tinggi pada kelompok PDL cell sheet + RGD-modified chitosan dibanding kelompok PDL cell sheet + chitosan scaffold, meskipun kedua bahan tersebut tidak menunjukkan perbedaan bermakna secara statistik.

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Background: Periodontal regenerative therapy in bone horizontal defect cases has been reported to increase clinical periodontal tissue attachment. However, the outcome treatment on the synthesis of bone extracellular matrix is unknown. Osteopontin is one of the bone markers that can be used in analyzing the effectiveness regeneration after periodontal regenerative therapy.

Objectives: To analyse osteopontin expression after periodontal regenerative therapy with PDL cell sheet + RGD-modified chitosan and PDL cell sheet + chitosan scaffold.

Methods and Materials: Specimen was used from M.nemestrina periodontal tissue that had been planted for four weeks after regenerative therapy with PDL cell sheet + RGD-modified chitosan and PDL cell sheet + chitosan scaffold.

Results: Median value of positive staining area in PDL cell sheet + RGD-modified chitosan with 74.81% (53.48%-81.06%) is greater than in PDL cell sheet + chitosan scaffold with 63.99% (52.43%-80.31%), and the two groups statistically showed no significant differences. Median value of positive staining intensity in weak area 43.05% (14.16%-61.52%), moderate 14.49% (6.70%-22.81%), and strong 17.82% (3.66%-20.20%) in PDL cell sheet + RGD-modified chitosan is greater than PDL cell sheet + chitosan scaffold, but there were no significant differences between the two groups.

Conclusion: Regenerative therapy with PDL cell sheet + RGD-modified chitosan increased osteopontin expression higher than PDL cell sheet + chitosan scaffold, even though there were no significant differences between the two groups."