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"ABSTRAKTesis ini membahas osteopontin pada karsinoma nasofaring stadium lanjut dan hubungannya dengan karakter klinis pasien tahap lanjut yang ada pada penelitian ini serta hubungannya dengan fragmen prothrombin 1+2 yang merupakan petanda hypercoagulable state. Penelitian ini adalah penelitian dengan desain potong lintang. Hasil penelitian menemukan tingginya kadar osteopontin pada pasien karsinoma nasofaring stadium lanjut dan tidak menemukan hubungan dengan kadar fragmen prothrombin 1+2. Disarankan untuk melakukan penelitian dengan skala lebih besar untuk mengevaluasi aktivasi trombosit dan sel-sel endotel.

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ABSTRACTThe focus of this study is osteopontin in advanced stage nasopharyngeal cancer. The purpose of this study is to determine the correlation of osteopontin with patient’s characteristics and fragmen prothrombin 1+2 as a marker of hypercoagulable state. Study design is cross sectional and the results showed the high level of osteopontin in advanced stage nasopharyngeal cancer and there is no correlation with fragmen prothrombin 1+2. It is recommended to conduct a research with larger scale to also evaluate platelet activation and endothelial cells respectively."

"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."

"[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: 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."

"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."

"Tooth eruption is a complex process that involves osteoclasts to form the eruption pathway. Lipopolysaccharide (LPS) is a bacterial component that plays multifunctional roles in inflammatory reactions, and one of these roles is powerful stimulation of bone resoption. Osteopontin (OPN) is a phosphorylated glycoprotein the expression of which is associated with migration, attachment and signaling of osteoclast. The objective of this study was to investigate the effect of LPS on rat alveolaris bone osteopontin during the period of tooth eruption. Fifty five Wistar male albino rats, five days of age were divided into three groups. The first group was not subjected to any treatment. The second group was inducted with LPS at five days of age. The third group was inducted with LPS at nine days of age. Expression of OPN was analyzed by immunohistochemical (IHC) approach. The results showed significant differences in OPN expression (p<0.05) within the treated subjects. It was concluded that LPS induction during tooth eruption increases the level of alveolar bone osteopontin."

"Manifestasi klinis demam berdarah Dengue (DBD) adalah kebocoran plasma dan trombositopenia. Salah satu teori penyebab kedua hal tersebut adalah kadar trombin yang meningkat akibat aktivasi koagulasi. Kadar trombin dapat diwakili oleh kadar F1.2. Tujuan penelitian ini adalah untuk mengetahui hubungan antara kadar F1.2 dengan kebocoran plasma dan trombositopenia pada infeksi Dengue. Desain penelitian ini adalah potong lintang, mengggunakan plasma EDTA dari pasien terinfeksi virus Dengue. Subyek penelitian adalah 10 subyek dengan kebocoran plasma dan 10 subyek tanpa kebocoran plasma pada infeksi Dengue, 6 sampel berpasangan untuk perbandingan fase kritis dan fase konvalesen, 26 sampel untuk uji korelasi antara kadar F1.2 dengan jumlah trombosit.Hasil penelitian menunjukkan kadar F1.2 pada pasien terinfeksi virus Dengue dengan kebocoran plasma (rerata ± 2SD) 147,4 ± 105,82 pg/mL lebih tinggi secara bermakna dibanding tanpa kebocoran plasma 51,3 ±39,92 pg/mL. Kadar F1.2 pada fase kritis dengan median 186,3 (108,6-223,2) pg/mL lebih tinggi secara bermakna dibanding fase konvalesen 46,5(27,4-51,9) pg/mL. Terdapat korelasi negatif yang bermakna dengan kekuatan sedang antara kadar F1.2 dengan jumlah trombosit, nilai r = - 0,609. Dari hasil penelitian disimpulkan bahwa terdapat peningkatan aktivasi koagulasi yang ditunjukkan dengan peningkatan kadar F1.2 pada fase kritis, berkaitan dengan kebocoran plasma dan trombositopenia pada pasien terinfeksi virus Dengue.

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Clinical manifestations of Dengue haemorrhagic fever are plasma leakage and thrombocypenia. Both manifestations are thought to be caused by an increased thrombin level due to activation of coagulation. The aim of this study was to look for any association between F1.2 level and plasma leakage and also between F1.2 level and thrombocytopenia in Dengue infected patients. The study design was cross sectional. This study used EDTA plasma from patients infected with Dengue virus. The thrombin level was represented by the prothrombin fragment 1.2 (F1.2) level. Twenty subjects were enrolled in this study, consisted of 10 subjects with plasma leakage and 10 without plasma leakage, 6 pair samples in critical phase and convalescent phase, 26 samples for correlation test between F1.2 level and platelet count. In this study, it was found that the F1.2 level in patients with plasma leakage (mean ± 2 SD) 147.4 ± 105.82 pg/mL was significantly higher compared to patients without plasma leakage 51.3 ±39.92 pg/mL, and the F1.2 level in critical phase had a median of 186.3 (108.6-223.2) pg/mL which was significantly higher compared to convalescent phase 46.5(27.4-51.9) pg/mL. Also there was a significant negative correlation with moderate degree of relationship between F1.2 level and the thrombocyte count, r = - 0.609.

The results of the study demonstrated that there was increased coagulation activation at critical phase in patients infected with Dengue virus, as shown by F1.2 as indicator, associated with plasma leakage and thrombocytopenia."

"Latar Belakang : Infeksi sering didapatkan pada pasien kenker nasofaring yang menjalani kemoterapi. Infeksi disebabkan oleh rusaknya barier fisik karena efek kemoterapi atau efek kemoterapi yang akan menurunkan imunitas tubuh,Infeksi pasca kemoterapi akan menunda kemoterapi berikutnya, akibatnya respon kemoterapi menjadi tidak optimal. Tujuan : Mendapatkan data status imunitas selular primer dan sekunder, pasca kemoterapi neoajuvan 3 siklus, data kekerapan infeksi dan perbandingan kekerapan infeksi pada pasien KNF stadium lanjut yang mendapatkan kemoterapi neoadjuvan 3 siklus pada pasien kanker nasofaring stadium lanjut, antara yang imunitas selular menurun dan yang tidak menurun. Metode : Penelitian one group before and after observasional, 1 kelompok tanpa kontrol selama 3 bulan di gedung A lantai 8 RSCM, juli ndash; september 2015.Penurunan rerata jumlah lekosit, netrofil, CD4 , CD8, kejadian infeksi dianalisis bivariat dengan uji T berpasangan atau uji Mann Whitney.Penelitian ini juga melihat kekerapan kejadian infejsi post kemoterapi neoadjuvan.Penelitian ini menggunakan tingkat kemaknaan 0,005, interval kepercayaan 95. Hasil : Tidak ada penurunan status imunitas selular primer, lekosit p=0,356 dan netrofil p=0,289.Terdapat penurunan status imunitas selular sekunder, CD 4 P=0,002, CD 8 P=0,001, dengan ratio CD 4 /CD 8 tidak berubah rerata CD 4 sudah rendah sejak sebelum kemoterapi.Mukositis oral dan pneumonia merupakan infeksi yang kerap didapatkan. CD4 yang rendah pada kelompok sebelum kemoterapi meningkatkan potensi infeksi selama dan sesudah kemoterapi neoadjuvan.Penurunan imunitas seluler sekunder nilai rerata jumlah CD4 berhubungan dengan peningkatan kejadian infeksi pasca siklus ke 2 p=0,016. Kesimpulan : Tidak terdapat penurunan imunitas selular primer dan didapatkan penurunan imunitas selular sekunder pada pasien karsinoma nasofaring stadium lanjut yang menjalani kemoterapi neoadjuvan 3 siklus.Pada pasien dengan penurunan imunitas selular sekunder terdapat peningkatan kejadian infeksi mukositis oral dan pneumonia CD 4 yang rendah merupakan prediktor kejadian infeksi. Penurunan imunitas selular sekunder hanya akan meningkatkan kejadian infeksi pasca siklus ke 2 kemoterapi neoadjuvan.

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Background: The infections especially in a the oropharynx often get on cancer patients nasopharyngeal .One of the causes of infection include breakdowns physical mucous barier because the tumor growth or because the effects of chemotherapy and radiation .Chemotherapy and radiation will result in side effects namely the inflammation and ulceration mouth and the oropharynx mucous called mukositis oral.selama endure chemotherapy, besides mukositis oral, infections of the also often found .Chemotherapy resulted in an emphasis on cell production immune response that result in the lekopenia with rob possibilities infection become larger.

The purpose: To asess of immunity cellular status on advanced stage nasaofaringeal patient to get 3 cycle neoadjuvan chemotherapy and assess the incident lung infection and tumor area after undergoing 3 cycle neoadjuvan chemotherapy.

The methode: Research one group before and after observational use 1 group without control. The research was done during the three months in the building a floor 8 Ciptomangunkusumo Hospital juli september 2015. The Data on the background respondents will be analyzed by a sort of descriptive set by using analysis univariat.hubungan between chemotherapy neoadjuvan and an immune response cellular will be analyzed bivariat by test wilcoxon sign rank test. In this research also be seen the proportion of the infection before pre and post chemotherapy neoadjuvan .This research using level evidence 0.05 to the interval trust 95.

Results: From 17 subject of research , 12 subjects 70,6 is laki laki , women made up subjects 29,4 .Median age patient is 46,7 , 10 patients 58,8 less than median age , 7 patients 42,2 more of age median.stadium 4a obtained on 4 patients 23,5 patients , while stadium 4 b obtained on 13 patients 76,5 .Seen from the infection after chemotherapy neoadjuvan 9 subjects 52,8 never would have experienced infection , 8 subjects 47,2 experienced infection. Looks the relationship between chemotherapy neoadjuvan 3 cycle in immunity cellular p 0,007 on cds 4 and p 0,005 on cds 8 , the immunity cellular decline in the infection look after chemotherapy neoadjuvan cycle to 2 p 0,016 on cds 4 while after cycle to 3 not seen the relationship between chemotherapy neoadjuvan 3 cycle in the infection .Count of leukosit and lymphocytes cannot be used to predict a decrease in an immune response cellular after undergoing 3 cycle neoadjuvan chemotherapy.

Conclusions: Immune response decreased on advanced stage nasopharynx carcinoma patient are undergoing 3 cycle neoadjuvan chemotherapy neoadjuvan 3 . The Decreased of cellular immune response has played of increased infection in the lung and tumor area post 2 cycle neoadjuvan chemotherapy. "

"Latar Belakang: Kanker nasofaring (KNF) endemik di Indonesia dan kebanyakan datang dengan stadium lokal lanjut. Angka rekurensi KNF stadium lokal lanjut hingga kini masih cukup tinggi. Berbagai variabel terkait klinis dan patologis yang ada saat ini belum sepenuhnya mampu menstratifikasi pasien yang akan mendapatkan manfaat jika diberikan kemoterapi ajuvan terutama pada pasien yang tercapai objective respons rateberupa remisi lengkap dan parsial.Perkembangan mekanisme petanda molekuler yang terlibat pada jalur onkogenesis KNF berkembang pesat hingga saat ini, di antaranya Vascular Endothelial Growth Factor(VEGF) dan osteopontin (OPN). Beberapa studi sebelumnya menunjukkan VEGF dan OPN berkorelasi dengan progresifitas dan luaran klinis tumor padat, termasuk KNF. Tujuan: Mengetahui progression-free survival (PFS)3 tahun pasien KNF stadium lokal lanjut pasca kemoradiasi berbasis platinum serta hubungannya dengan ekspresi VEGF dan OPN. Metode: Penelitian ini menggunakan disain kohort retrospektif dengan subyek merupakan pasien KNF stadium lokal lanjut yang berobat di RSCM pada periode 2015-2017. Penelusuran data klinis dilakukan bersamaan dengan pewarnaan imunohistokimia VEGF dan OPN masing-masing menggunakan antibodi monoklonal Santa Cruz® sc-7267 dan Akm2A1. Intensitas pewarnaan dihitung dengan histoscore menggunakan piranti imageJ. Penilaian PFS dilakukan dengan analisis kesintasan Kaplan Meier. Analisis hubungan VEGF dan OPN terhadap PFS 3 tahun menggunakan kurva Kaplan Meier dan uji dengan log rankdengan batas kemaknaan p<0,05. Hasil:Angka PFS 3 tahun pada subyek sebesar 39% dengan median 23 bulan. Ekspresi VEGF dideteksi pada 113 (72,9%) subyek, dan ekspresi OPN positif pada 99 (63,8%) subyek. Kurva Kaplan-Meier menunjukkan PFS 3 tahun untuk VEGF (+) dan (-) berturut-turut yaitu 40% (SE 5%) dan 36% (SE 8%), log rank p=0,584. PFS untuk OPN (+) dan (-) berturut-turut yaitu 41% (SE 6%) dan 35% (SE 7%), log rank p=0,747.Analisis subgrup pasien dengan stadium IVB dan ukuran tumor N3, ekspresi VEGF dan OPN yang positif berhubungan dengan PFS 3 tahun yang lebih baik dibandingkan ekspresi negatif. Untuk subgrup pasien yang mendapatkan kemoterapi neoajuvan, ekspresi VEGF yang positif memberikan PFS 3 tahun yang lebih baik dibandingkan ekpresi negatif.Simpulan: Penelitian ini menunjukkan PFS 3 tahun KNS stadium lokal lanjut yang maih cukup rendah, dan tidak terdapat hubungan antara ekspresi VEGF dan OPN dengan PFS 3 tahun.

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Background: Nasopharyngeal carcinoma (NPC) is endemic in Indonesia and most patients were admitted to hospital when they already in locally advanced stage.The recurrence rate of locally advanced NPC is still quite high. Various clinical and pathological variables that exist today are not fully capable of stratifying patients who will benefit if adjuvant chemotherapy is given, especially in patients whom are complete and partial remission.To date,the development of molecular marker mechanismsinvolved in the oncogenesis pathway of NPC has grown rapidly, including Vascular Endothelial Growth Factor (VEGF) and Osteopontin (OPN). Previous studies have shown VEGF and OPN to be correlated with the progression and clinical outcome of solid tumors, including nasopharyngeal cancer.

Objective: This study aimed to determine 3-years progression-free survival (PFS) of locally

advanced nasopharyngeal carcinoma after platinum-based concurrent chemoradiation and its

association with VEGF and OPN.

Methods: A retrospective cohort study was conducted in subjects of NPC patients at Cipto Mangunkusumo Hospital from 2015 until 2017. Clinical data was collected from hospital registries, and immunohistochemistry staining of VEGF and OPN was perfomed by using monoclonal antibodySanta Cruz® sc-7267 and Akm2A1, respectively.We calculated H-score according to Allred criteria with computer software imageJ. We determined PFS byKaplan Meier survival analysis. Association of VEGF and OPN with 3 years-PFS was analyzed using Kaplan Meier with log-rank test p<0.05.

Results: The 3-years PFS rate in subjects was 39% with a median of 23 months. VEGF expression was detected in 113 (72.9%) samples, and positive OPN expression in 99 (63.8%) samples. The Kaplan-Meier curve shown the 3-years PFS for VEGF (+) and (-) were 40% (SE 5%) and 36% (SE 8%), respectively with log rank p=0.584. While 3-years PFS for OPN (+) and (-) were 41% (SE 6%) and 35% (SE 7%), respectively with log rank p=0.747. Subgroup analysis of patients with stage IVB and tumor size N3 showed that positive VEGF and OPN expression were associated with better3-years PFS than negative expression. For the subgroup of patients receiving neoadjuvant chemotherapy, positive VEGF expression showed better 3-years PFS than negative expression.

Conclusions: This study showed that the 3-years PFS of locally advanced NPC was quite low, and there was no relationship between VEGF and OPN expression with 3-years PFS. "

"[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.]"