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"ABSTRAKLatar Belakang Giant cell tumor (GCT) merupakan tumor jinak yang bersifat lokal agresif destruksif. Tumor ini memiliki rekurensi yang tinggi sebanyak 25-50% setelah tindakan pembedahan. Berbagai macam pemberian zat kimia lokal sebagai terapi ajuvan, telah digunakan pada tatalaksana pembedahan. Namun perbandingan efektifitas untuk masing-masing zat kimia ini belum diketahui. Studi mengenai sitotoksisitas dan mekanisme kematian sel dengan membandingkan pemberian etanol dan H2O2 pada sel GCT tulang secara in vitro masih sedikit dan belum ada di Indonesia.Metode Penelitian ini merupakan studi in vitro eksperimental dengan mengambil empat sampel jaringan tumor dari pasien yang didiagnosis GCT tulang dan dilakukan isolasi-kultur sel. Cell line yang didapatkan dikarakterisasi melalui analisis morfologi serta pemeriksaan ekspresi penanda gen Nanog dan Oct 4 dengan Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Sel yang telah 80% konfluens dilakukan terapi dengan H2O2 1%, 3%, 5% dan etanol 75%, 85%, 95% selama10 menit serta dosis in vitro H2O2 (0,003%, 0,005%, 0,01%, 0,03%, 0,1%, 0,3%) selama 5 menit serta inkubasi selama 24 jam. Morfologi sel dievaluasi dibawah mikroskop cahaya dengan membandingkan kontrol dan setelah pemberian zat kimia, viabilitas sel dihitung menggunakan automatic cell counter serta toksisitas sel dinilai dengan uji Annexin V dan Propidium Iodida (PI) pada flow cytometry.Hasil Kultur jaringan sel GCT dengan metode eksplan dan kolagenase mempunyai angka keberhasilan yang sama dalam mendapatkan cell line GCT. Namun metode eksplan membutuhkan waktu yang lebih cepat dan memiliki jumlah sel yang lebih banyak. Sel yang tumbuh dari jaringan GCT terkarakterisasi dengan analisis morfologi serta ekspresi gen Oct 4 dan Nanog. Viabilitas sel GCT menurun secara signifikan setelah paparan terhadap dosis klinis H2O2 1% (p = 0,046), H2O2 3% (p = 0,043), dan H2O2 5% (p = 0,043) selama 10 menit dibandingkan dengan kontrol. Tidak ada perbedaan yang bermakna untuk viabilitas sel antara konsentrasi H2O2 1%, 3% dan 5%. Sementara pada konsentrasi in vitro (0,003%, 0,005%, 0,01%, 0,03%, 0,1%, 0,3%), konsentrasi H2O2 0,3% (p < 0,001) selama 5 menit memiliki efektivitas paling baik dalam sterilisasi GCT secara in vitro. Terdapat fenomena fiksasi sel setelah pemberian etanol pada semua konsentrasi. Dari uji RT-PCR didapatkan penurunan ekspresi gen Oct 4 dan Nanog seiring dengan peningkatan konsentrasi H2O2 pada dosis in vitro. Flow cytometry dengan marker Annexin V dan propidium iodide (PI) didominasi oleh marker PI yang menunjukkan kematian sel akibat nekrosis dengan persentase terbesar pada konsentrasi 0,3%.Kesimpulan Eksplan merupakan metode terbaik dalam isolasi dan kultur sel GCT. Semua sel hasil isolasi dan kultur terkarekterisasi sebagai GCT. Pemberian ajuvan kimia lokal dengan dosis klinis H2O2 konsentrasi 1%, 3%, dan 5% selama 10 menit secara in vitro mempunyai efektivitas yang sama dalam membunuh sel GCT. Sedangkan konsentrasi H2O2 0,3% selama 5 menit merupakan terapi optimal dalam sterilisasi GCT secara in vitro dengan mekanisme kematian nekrosis sel.

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ABSTRACTBackground Giant cell tumor (GCT) is a benign, aggressive local tumor with high tendency to recur after surgery. Various chemicals have been used as an adjuvant treatment for GCT. However, the comparative effect of these chemicals remains unclear. To date, there are no studies about the cytotoxicity and mechanism of injury to etanol and H2O2 in GCT in Indonesia especially in vitro experiment. The present study aims to find the best method to isolation and culture of GCT from primary human patients, the optimal treatment of etanol and H2O2 for reducing GCT recurrence.Methods This is an experimental in vitro study that took four tumor tissue samples from patients diagnosed with bone GCT and conducted cell-culture isolation. Cell line characterized by morphology, gene markers Nanog and Oct 4 expression with Polymerase Chain Reaction (RT-PCR) Reverse Transcriptase was obtained. Cells that had 80% confluence were treated with H2O2 1%, 3%, 5% and etanol 75%, 85%, 95% for 10 minutes and in vitro doses of H2O2 (0.003%, 0.005%, 0.01%, 0.03 %, 0.1%, 0.3%) for 5 minutes and were incubated for 24 hours. Cell morphology was evaluated under a light microscope by comparing the morphology of controls and after exposure a chemical agents, cell viability was calculated using automatic cell counter and cell toxicity was assessed by Annexin V and Propidium Iodida (PI) on flow cytometry.Results Collagenase and explant methods had the same success rate in obtaining GCT cell line characterized by morphology, the gene expression Oct 4 and Nanog. But explants need a less time and had more cell than collagenase method. Viability of GCT cells decreased significantly after exposure to the clinical dose of H2O2 1% (p = 0,046), H2O2 3% (p = 0,043), and H2O2 5% (p = 0,043) for 10 minutes compared to controls. There was no significant difference for cell viability between 1%, 3% and 5% H2O2 concentrations. While in in vitro doses (0,003%, 0,005%, 0,01%, 0,03%, 0,1%, 0,3%), 0.3% H2O2 concentration for 5 minutes has the best effectivity in sterilizing GCT in vitro. There was a phenomenon of cell fixation after exposure of GCT cells to etanol in various concentrations, in which all cells die and its viability could not be analyzed. From the RT-PCR test it was found that there was a decrease in the expression of Oct 4 and Nanog genes along with an increase in the concentration of H2O2 in vitro. Flow cytometry using Annexin V in conjunction with propidium iodide (PI) was dominated with PI marker detection which showed cell death due to necrosis, with the highest concentration amounted to 0.3%Conclusion Explant was the best method for isolation and GCT cell culture. All of the cell from isolation and culture result had a characterization of GCT. Giving local a chemical adjuvants with clinical doses of H2O2 concentrations of 1%, 3%, and 5% for 10 minutes in vitro had the same effectiveness in killing GCT cells. While the concentration of 0.3% H2O2 for 5 minutes is the optimal therapy in GCT sterilization in vitro with necrosis cell death mechanism."

"Sesoot (G. picrorrhiza Miq.) merupakan sumber daya hayati yang memiliki potensi sitotoksik terhadap sel kanker payudara. Potensi ini memberikan peluang untuk penatalaksanaan kanker payudara melalui permodelan doksorubisin dan kombinasinya dengan sampel herbal. Penelitian ini untuk membuktikan potensi antikanker payudara terhadap sel MCF-7 dan T47D dari daging buah dan kulit buah sesoot (G. picrorrhiza Miq.) yang selanjutnya disebut buah. Telah dilakukan karakterisasi sampel secara kimia dan biomolekuler sehingga menghasilkan sampel terkarakterisasi, GpKar. Sitotoksisitasnya ditentukan dengan metode MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) Assay, lalu dilakukan uji kombinasi dengan doksorubisin untuk mendapatkan Combination Index (CI). Pengamatan induksi apoptosis dilakukan dengan metode Double Staining dan ekspresi protein Caspase 3 dengan metode Enzyme-linked Immunosorbent Assay (ELISA). GpKar memiliki LC50 terhadap larva Artemia salina Leach sebesar 21,110 μg/mL (paling kecil di antara 15 sampel lainnya). Pada uji terhadap sel Vero dengan konsentrasi 250 μg/mL hanya mematikan 11,844 %, tetapi mematikan sel T47D 50,825 % dan MCF-7 31,743 %. Kombinasinya dengan doksorubisin menghasilkan efek sinergis dalam mematikan sel MCF-7 pada konsentrasi 0,200 μg/mL doksorubisin dan konsentrasi GpKar maksimal 125,238 μg/mL (1/4 IC50) juga terhadap sel T47D pada konsentrasi 0,200 μg/mL doksorubisin dan konsentrasi GpKar maksimal 61,799 μg/mL (1/4 IC50). GpKar mempengaruhi induksi apoptosis pada konsetrasi 500,951 μg/mL (1 IC50) dengan menghasilkan persentasi kematian sel MCF-7 paling tinggi yaitu 99 % dan terhadap Sel T47D sebesar 91 %, pada konsentrasi 61,799 μg/mL (1/4 IC50) sedangkan terhadap sel Vero dapat menghasilkan persentase kematian paling rendah yaitu 2,100 % pada konsentrasi 132,943 μg/mL (1/4 IC50). Kombinasinya dengan doksorubisin menghasilkan persentase kematian yang lebih rendah akibat induksi apoptosis. GpKar dan kombinasinya dengan doksorubisin mampu meningkatan konsentrasi protein Caspase 3.

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Sesoot (G. picrorrhiza Miq.) is a medicinal plant which has cytotoxic activity against breast cancer cells. This potency provides the opportunity for treatment of breast cancer through doxorubicin modelling and its combination with herb. This study was done to prove the anti-breast cancer potency of the fruit and the hull of sesoot (G. picrorrhiza Miq.) hereinafter referred to as the fruit against MCf-7 cell and T47D cell. Chemical and Biomolecular Characterizations were done to obtain the characterized sample of GpKar. The cytotoxicity effect was determined using the method of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) Assay, and the combination test with doxorubicin resulting the Combination Index (CI). The apoptotic induction was observed using Double Staining Method and the Caspase 3 protein expression was observed using the method of Enzyme-Linked Immunosorbent Assay (ELISA). The LC50 of GpKar against the larvae of the Artemia salina Leach was 21.110 μg/mL (the least among 15 samples). The Gpkar concentration of 250 μg/mL was the least toxic in term of mortality against Vero cell (11.844 %), but toxic in term of mortality against T47D cell (50.825 %) and MCF-7 cell (31.743 %). The combination with doxorubicin resulted in the synergystic effect against MCF-7 cell (0.200 μg/mL doksorubicin with the maximum GpKar concentration of 125.238 μg/mL (1/4 IC50)) and also against T47D cell (0.200 μg/mL doxorubicin with the maximum GpKar concentration of 61.799 μg/mL (1/4 IC50)). GpKar induced the apoptosis at the concentration of 500.951 μg/mL (1 IC50) resulting the mortality percentage of the MCF-7 cell up to 99 % and up to 91 % against T47D cell at the concentration of 61.799 μg/mL (1/4 IC50) of GpKar, whereas the concentration of 132.943 μg/mL (1/4 IC50) of GpKar resulted in the lowest mortality percentage against Vero cell which was 2.100 %. The combination of GpKar with doxorubicin resulted in the lower mortality percentage as the consequence of apoptotic induction. GpKar and its combination with doxorubicin increased the concentration of the Caspase 3 protein."

"ABSTRAKPendahuluan: Kanker laring bertanggung jawab terhadap 0,6 kematian yang disebabkan kanker di dunia. Kedelai hitam adalah salah satu bahan alami yang berpotensi dikembangkan sebagai antikanker. Penelitian dilakukan untuk mengetahui sitotoksisitas ekstrak etanol kedelai hitam dalam menghambat pertumbuhan sel kanker laring epidermal Hep-2 sehingga dapat digunakan sebagai terapi tambahan. Metode: Analisis fitokimia, yaitu uji Kromatografi Lapis Tipis KLT dan uji fitokimia ekstrak etanol kedelai hitam, dilakukan untuk mengetahui senyawa yang terkandung dalam ekstrak tersebut. Ekstrak kedelai hitam diujikan terhadap sel kanker Hep-2 secara in vitro dengan tujuh variasi konsentrasi, yaitu 6,25 ?g/mL, 12,5 ?g/mL, 25 ?g/mL, 50 ?g/mL, 100 ?g/mL, 200 ?g/mL, 400 ?g/mL, dan 800 ?g/mL. Kontrol positif yang digunakan adalah cisplatin dengan konsentrasi sama. Setiap kelompok dibuat pengulangan tiga kali triplo . Setelah diinkubasi selama 24 jam, setiap kelompok diuji dengan metode MTT assay dan hasil absorbansi dibaca menggunakan ELISA reader. Hasil: Terdapat enam komponen dalam ekstrak etanol kedelai hitam berdasarkan uji KLT. Ekstrak etanol kedelai hitam mengandung alkaloid, flavonoid, tanin, triterpenoid, saponin, dan glikosida berdasarkan uji fitokimia. MTT assay menunjukkan nilai Inhibitory Concentration 50 IC50 ekstrak etanol kedelai hitam sebesar 118,061 ?g/mL dan terdapat perbedaan bermakna

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ABSTRACTIntroduction Laryngeal cancer responsible for 0,6 of death caused by cancer in the world. Wild bean is one of natural ingredients that potential to be developed as an anticancer. The study was conducted to determine the cytotoxicity of wild bean ethanol extract in inhibiting the growth of epidermal laryngeal cancer cell Hep 2 so it can be used as additional therapy. Method Phytochemical analysis, which are Thin Layer Chromatography and phytochemical screening test of wild bean ethanol extract, was conducted to determine the compounds contained in the extract. Furthermore, wild bean ethanol extract were tested against Hep 2 cancer cells in vitro in seven variation concentrations, which are 6.25 g mL, 12.5 g mL, 25 g mL, 50 g mL, 100 g mL, 200 g mL, 400 g mL, and 800 g mL. The positive control used is cisplatin with the same concentration. Each group is repeated three times triplo . After incubation for 24 hours, each group was assayed by MTT assay method and absorbance result was read using ELISA reader. Result There are six components in wild bean ethanol extract based on TLC test. Wild bean ethanol extract contains alkaloids, flavonoids, tannins, triterpenoids, saponins, and glycosides based on phytochemical tests. MTT assay showed the value of Inhibitory Concentration 50 IC50 of ethanol extract of wild bean was 118,061 g mL and there was significant difference p "

"ABSTRAKJumlah kasus kanker paru terus mengalami peningkatan secara global. Disamping kasusnya yang terus bertambah, terapi kanker paru hingga saat ini masih banyak menimbulkan efek samping yang tidak jarang menggangu kualitas hidup pasien. Maka dari itu, skripsi ini mengevaluasi aktivitas antioksidan dan antikanker dari rumput laut Eucheuma cottonii dan Eucheuma spinosum yang berasal dari pantai Labuan Aji, Nusa Tenggara Barat terhadap sel paru A-549.  Pada penelitian ini digunakan empat jenis ekstrak, yakni heksana, kloroform, etil asetat, dan etanol. Uji aktivitas antioksidan dilakukan dengan metode DPPH sedangkan untuk aktivitas antikanker dievaluasi dengan metode MTT cell proliferation assay. Masing-masing ekstrak akan dinilai laju inhibisinya dan nilai IC50. Berdasarkan hasil percobaan, ekstrak etanol Eucheuma cottonii dengan nilai IC50 35,51 ppm memiliki aktivitas antioksidan yang paling poten dibandingkan dengan ekstrak lain yang diuji. Ekstrak etanol E. cottonii juga memiliki aktivitas antikanker terbaik, dengan nilai IC50 54,83 mg/mL. Untuk Eucheuma spinosum, ekstrak etil asetat memiliki aktivitas antioksidan dan antikanker yang paling baik, dengan nilai IC50 10,16 mg/mL. Dengan demikian, dapat disimpulkan bahwa baik Eucheuma cottonii maupun Eucheuma spinosum berpotensi sebagai antioksidan alami dan memiliki efek antikanker terhadap sel paru A-549. 

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ASTRACTNumber of people suffering from lung cancer continue to increase globally. Yet, the treatment methods for lung cancer still have many effects that often interfere patients quality of life. Therefore, objective from this paper is to evaluate the antioxidant and anticancer activity from macroalgae Eucheuma cottonii and Eucheuma spinosum, which was taken from Labuan Aji beach, Nusa Tenggara Barat, against A-549 lung cell. This research used four types of extracts, including hexane, chloroform, ethyl acetate, and ethanol. Antioxidant activity was evaluated using DPPH method. As for anticancer activity was evaluated by MTT cell proliferation assay. Each extracts have its own inhibitory rate and IC50 value. Based on this experiment, ethanol extract of Eucheuma cottonii with IC50 value 35,51 ppm had the most potent antioxidant activity than other extracts that were tested. Ethanol extract also showed the best anticancer activity with IC50 value 54,83mg/mL. As for Eucheuma spinosum, ethyl acetate extract has the best antioxidant and anticancer activity, with IC50 value 10,16 mg/mL. Thus, it can be concluded that both Eucheuma cottonii and Eucheuma spinosum are potent natural antioxidant and have anticancer effect against A-549 lung cacner cell. "

"Latar Belakang: Kanker payudara merupakan jenis penyakit kanker paling umum di dunia dan di Indonesia. Temu kunci (Kaempferia pandurata Roxb.) adalah tanaman herbal dari Asia Tenggara, yang telah diteliti dapat menghambat pertumbuhan sel kanker payudara golongan Estrogen Reseptor (ER) + (positif mengekspresikan reseptor estrogen). Namun, efek temu kunci terhadap sel kanker payudara ER- masih belum banyak diteliti. Nanopartikel merupakan bentuk sediaan yang telah diteliti mampu mengoptimalkan kerja suatu senyawa ke sel target.Tujuan: Menguji efek sitotoksisitas ekstrak dan nanopartikel temu kunci pada sel kanker payudara ER- (MDA-MB-231).Metode: Serbuk rimpang temu kunci dikeringkan dan diekstraksi menggunakan pelarut n-heksana. Proses sintesis nanopartikel ekstrak temu kunci menggunakan CaCl2, dimer chitosan, dan alginat melalui proses pengadukan, penyesuaian pH, dan sentrifugasi. Sediaan nanopartikel hasil sintesis dianalisis menggunakan metode spektrofotometri UV/VIS dan transmission electron microscopy (TEM). Efek sitotoksisitas ekstrak n-heksana temu kunci dan nanopartikelnya diuji dengan metode MTT. Hasil uji MTT akan menghasilkan data persentase inhibisi dan nilai IC50.Hasil: Ekstrak n-heksana temu kunci dapat disintesis menjadi bentuk nanopartikelnya dengan persen yield (hasil) sebesar 99,43%. Aktivitas antikanker ekstrak dan nanopartikel n-heksana temu kunci tergolong moderat dengan nilai IC50 sebesar 87,23 μg/ml dan 24,23 μg/ml. Nanopartikel n-heksana temu kunci memiliki aktivitas antikanker yang lebih baik daripada ekstraknya.Diskusi: Ekstrak dan nanopartikel n-heksana temu kunci memiliki efek sitotoksisitas terhadap sel kanker MDA-MB-231. Nanopartikel dapat meningkatkan efek sitotoksisitas ekstrak n-heksana temu kunci karena sifatnya yang hidrofobik dan ukuran nanometer.

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Introduction: Breast cancer is the most common cancer worldwide and in Indonesia. Kaempferia pandurata Roxb. is a herbal plant from South-East Asia which is known for its ability to inhibit the growth of Estrogen Receptor (ER) + breast cancer cell line from the former study. However, its effect on ER- breast cancer cell lines had not been studied. Therefore, we want to examine the cytotoxicity effect of K. pandurata Roxb. on ER-breast cancer cell line (MDA-MB-231). Nanoparticle is a form of preparation that optimizes the activity of any compound to the targeted cell. Therefore, it is expected that it can increase the effectivity of anticancer in Kaempferia pandurata Roxb.

Method: The rhizome of K. pandurata Roxb. trituration was dried and extracted with n-hexane solvent. Nanoparticle of K. pandurata Roxb. was synthesized with CaCl2, chitosan, and alginate by stirring with a magnetic stirrer, adjusting pH, and centrifugation. Then, nanoparticle was analized by UV/VIS spectrofotometry and transmission electron microscopy (TEM). The cytotoxicity of K. pandurata Roxb. extract and nanoparticle

were examined with MTT assay. The result of this test is data of inhibition percentage and IC50 value.

Results: n-Hexane extract of K. pandurata Roxb. is synthesized into nanoparticle form with 99,43% yield percentage (entrapment value). Anticancer activity of n-hexane extract and nanoparticle of K. pandurata Roxb. is moderate with IC50 value of the extract is 87,23 μg/ml and the nanoparticle is 24,23 μg/ml. The nanoparticle’s activity is better than the extract.

Discussion: n-Hexane extract and nanoparticle of K. pandurata Roxb. has cytotoxicity effects towards MDA-MB-231 cell line. Nanoparticle can increase the cytotoxicity effect of K. pandurata Roxb. extract because its hydrophobic feature and nanometer size."

"Latar Belakang: Perawatan endodontik regeneratif (ER) adalah perawatan yang dirancang untuk menggantikan struktur gigi yang rusak secara fisiologis. Penggunaan medikamen pada prosedur perawatan ER menggunakan Calcium hydroxide yang telah ditentukan sebagai bahan medikamen utama yang ditetapkan American Association of Endodontik (AAE). Bahan medikamen lainnya seperti Triple antibiotic paste (TAP) juga banyak digunakan pada perawatan ER dalam konsentrasi 1 mg/ml. Tujuan: Mengetahui sitotoksisitas medikamen Ca(OH)2, TAP, dan kombinasi keduanya terhadap sel punca pulpa.Cs) yang telah 80% confluent (telah melalui uji stem cell marker CD 90 98%, CD 105 88,7%, CD 73 94%, LinNeg 0,5%) dan mencapai P3-P4 dilakukan starvation 24 jam,  diberikan perlakuan berupa Ca(OH)2, TAP 0,1 dan 1 mg/ml dan kombinasi Ca(OH)2dan TAP 0,1 dan 1 mg/ml dengan DMEM sebagai kontrol. Pengamatan viabilitas dan sitotoksisitas hDPSCs dengan uji kuantitatif MTT assay dan uji kualitatif pewarnaan DAPI. Hasil: Tidak terdapat perbedaan sitotoksisitas kombinasi medikamen Ca(OH)2 + TAP 0,1 mg/ml dan Ca(OH)2 + TAP 1 mg/ml dibandingkan dengan Ca(OH)2, TAP 0,1 mg/ml dan TAP 1 mg/ml terhadap sel punca pulpa. Kesimpulan: Bahan medikamen Ca(OH)2, TAP, dan kombinasi keduanya tidak toksik terhadap sel punca pulpa.

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Background: Regenerative endodontic treatment (ER) is a treatment designed to replace damaged tooth structure physiologically. In regenerative endodontic treatment (ER) procedures, the medicament used is calcium hydroxide, which has been determined as the primary medicament recommended by the American Association of Endodontics (AAE). Another medicament used in ER treatment is Triple antibiotic paste (TAP), typically at a concentration of 1 mg/ml.

Objective: To determine the cytotoxicity of Ca(OH)2, TAP, and their combination on dental pulp stem cells (hDPSCs).

Methods: Primary human dental pulp stem cells (hDPSCs), which have reached 80% confluence (tested for stem cell markers CD90 98%, CD105 88.7%, CD73 94%, LinNeg 0.5%), and have reached passages 3rd to 4th, were subjected to 24-hour starvation. They were then treated with Ca(OH)2, TAP at concentrations of 0.1 and 1 mg/ml, and a combination of Ca(OH)2 and TAP at the same concentrations, with DMEM as the control. The viability and cytotoxicity of hDPSCs were observed using the quantitative MTT assay and qualitative DAPI staining.

Results: There was no significant difference in the cytotoxicity between the combination of Ca(OH)2+ TAP 0.1 mg/ml and Ca(OH2 + TAP 1 mg/ml compared to Ca(OH)2  0.1 mg/ml and TAP 1 mg/ml in dental pulp stem cells.

Conclusion: The medicaments Ca(OH)2, TAP, and their combination are not toxic to dental pulp stem cells."

"Pendahuluan: World Health Organization (WHO) mendefinisikan Giant Cell-Tumour (GCT) merupakan tumor tulang yang bersifat jinak, mempunyai sifat dan kecenderungan untuk agresif lokal. Tujuan tata laksana GCT adalah menghilangkan jaringan tumor, mempertahankan fungsi tulang yang terkena, serta mencegah rekurensi. Sampai saat ini belum ada konsensus seragam untuk tata laksana GCT primer. Denosumab merupakan antibodi monoklonal yang berikatan dengan RANKL. Dengan adanya ikatan antara denosumab dengan RANKL, ikatan antara RANKL dengan RANK tidak terjadi, sehingga diharapkan tidak terjadi pertumbuhan tumor. Akan tetapi masih ada beberapa masalah yang masih menjadi pertanyaan antara lain: apakah pemakaian denosumab menurunkan angka rekurensi dibandingkan tata laksana konvensional sebelumnya, bagaimana efikasi denosumab pada tata laksana GCT, serta berapa dosis dan lama terapi denosumab diberikan. Dengan belum adanya pedoman baku penggunaan denosumab, dan belum adanya telaah sistematis serta penelitiannya di Indonesia, maka meta-analisis ini dilakukan untuk menjawab pertanyaan-pertanyaan tersebut dalam membantu menyusun pedoman penggunaannya sehingga menghasilkan kebijakan baru dalam tata laksana GCT di Indonesia.Metode: Telah dilakukan pencarian dalam lima database menggunakan kata kunci ("DENOSUMAB" AND ("GIANT CELL TUMOR" OR "GCT") AND "OUTCOME"). Penilaian risiko bias studi dengan desain randomized controlled trial dilakukan dengan Cochrane Collaboration’s tool for assessing risk of bias, sedangkan penilaian risiko bias studi dengan desain nonrandomized controlled trial dan kohort dilakukan dengan Newcastle-Ottawa Quality Assessment Form for cohort study.Hasil Setelah diseleksi, didapatkan 21 studi yang dilakukan penilaian risiko bias. Meta-analisis menemukan bahwa terdapat 85,5% (IK95%: 74,9-96,0%) pasien mendapatkan perbaikan klinis; perbaikan radiologis pada 82.4% (95% IK: 73,3-91,4%) pasien; perubahan histopatologis pada 96,5% (95% IK: 93,6-99,3%) pasien; serta rekurensi sebesar 27,2% (95% IK: 18,7-35,7%) dan rekurensi pada denosumab dibanding kontrol yakni RR: 2,6 (95% CI: 1,66-4,09); total kejadian efek samping berat pada rahang sebesar 2,7% (95% IK: 1,4-4,0%).Kesimpulan: Administrasi Denosumab pada pasien GCT sebagai terapi sistemik memiliki efikasi yang baik dalam perbaikan klinis; perbaikan radiologis; penurunan aktivitas sel GCT; potensi efek samping yang rendah; akan tetapi angka kejadian rekurensi lebih tinggi dibanding kontrol. Meski demikian, studi komparatif eksperimen acak terkontrol dirasa perlu lebih banyak untuk meningkatkan kualitas hasil studi.

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Introduction: The World Health Organization (WHO) defines GCT as a benign bone tumor, with the nature and tendency for local aggressiveness. The goal of GCT management is to remove tumor tissue, maintain the function of the affected bone, and prevent recurrence. To date there has been no uniform consensus for primary GCT management. Denosumab is a monoclonal antibody that binds to RANKL. With the bond between denosumab and RANKL, the bond between RANKL and RANK does not occur, so that no tumor growth is expected. However, there are still a number of questions that remain questionable, among others: whether the use of denosumab reduces recurrence rates compared to previous conventional management, how the efficacy of denosumab in the management of GCT, and how much dose and duration of denosumab therapy is given. With no standard guidelines for using denosumab, and no systematic study and research in Indonesia. This meta-analitic study was conducted to answer these questions in helping to develop guidelines for their use so as to produce new policies in the management of GCT in Indonesia.

Methods: Five databases have been searched using keywords ("DENOSUMAB" AND ("GIANT CELL TUMOR" OR "GCT") AND "OUTCOME"). After being selected, 21 studies were carried out with a bias risk assessment with the Newcastle-Ottawa Quality Assessment Form for cohort studies for studies with cohort designs and nonrandomized controlled trials while for one study a randomized controlled trial was conducted with the Cochrane Collaboration's tool for assessing risk of bias with results 4 poor quality studies.

Results: The meta-analysis found that there were 85.5% (CI 95%: 74.9-96.0%) patients received clinical improvement, there was a reduction in VAS scale pain in 98.9% (CI 95%: 96.5-101.4% ) patient; radiological improvement in 85.5% 82.4% (95% CI: 73.3-91.4%) patients; histopathological changes in 96.5% (95% CI: 93.6-99.3%) patients; and recurrence of 27.2% (95% CI: 18.7-35.7%) and recurrence in denosumab compared to controls namely RR: 2.6 (95% CI: 1.66-4.09); the total incidence of severe side effects on the jaw was 2.7% (95% CI: 1.4-4.0%).

Conclusions: Denosumab administration in GCT patients as a systemic therapy has good efficacy in clinical improvement; radiological repair; decreased GCT cell activity; low potential for side effects; however the recurrence rate is higher than the control. However, comparative studies of randomized controlled trials are deemed necessary to improve the quality of study results."

"[ABSTRAKPendahuluan: GCT tulang merupakan lesi jinak tetapi secara lokal dapat bersifat agresif pada daerah epifisis. Angka rekurensi yang tinggi, dilaporkan mencapai 75%. Tumor dapat bermetastasis ke paru (2-9%) dan tercatat 0-37% angka mortalitas akibat metastasis. Beberapa penelitian menghasilkan variasi berbeda penanganan tumor ini terhadap luaran onkologi dan fungsional serta angka kematian paska pembedahan. Penelitian ini bertujuan melaporkan pengalaman dalam penatalaksanaan pembedahan tumor ini dan untuk melihat adanya hubungan antara tatalaksana pembedahan dengan dampak klinis.Metode: Penelitian ini merupakan kohort retrospektif, sebanyak 99 pasien GCT tulang menjalani tindakan kuretase ataupun wide resection di Rumah Sakit Cipto Mangunkusumo pada 1995 - 2014. Luaran onkologi berdasarkan angka rekurensi lokal, metastasis tumor serta mortalitas dan luaran fungsional berdasarkan sistem penilaian Musculoskeletal Tumor Society (MSTS).Hasil: Lokasi tumor terutama di distal femur (25,2%). Rekurensi lokal terjadi pada 4 pasien, terutama di distal femur (50%). Rekurensi lokal terjadi seimbang pada wide resection dan kuretase dan secara statistik tidak bermakna (p 0.578, uji eksak Fischer). Tidak dijumpai kejadian rekurensi lokal pada seluruh pasien yang mengalami metastasis. Metastasis terjadi pada kelompok wide resection. Kematian terjadi pada 4 pasien yang mengalami metastasis. Sebagian besar pasien (51,1%) menunjukkan luaran fungsional kategori sangat baik (skor MSTS di atas 75%). Analisis kesintasan bebas rekurensi lokal secara statistik tidak bermakna (p 0.564). Analisis multivariat (regresi Cox) hanya faktor metastasis yang berpengaruh pada mortalitas (p. 0.001)Kesimpulan: Terdapat hubungan yang bermakna antara stadium tumor dengan metastasis dan jenis tindakan operasi. Tidak terdapat perbedaan bermakna antara kejadian rekurensi lokal dan metastasis serta luaran fungsional dengan jenis tindakan operasi.

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ABSTRACTIntroduction: Giant cell tumor of bone is benign lesion with ability to be locally aggressive in epiphysis. Its recurrence rate was reported as high as 75%. Tumor can metastasize to lungs (2-9%) and up to 37% mortality rate due to metastasis. Several studies have reported different rates of local recurrence, lung metastasis, mortality rate, and functional outcome. This study aims to report our experience and analyze the correlation between surgery and clinical findings.Methods: In this retrospective cohort, 99 patients GCT of bone undergone curettage or wide resection in Cipto Mangunkusumo Hospital during 1995-2014. Oncological outcome were analyzed according to local recurrence rate, metastasis, and mortality rate, while functional outcome were measured according to Musculoskeletal Tumor Society Score (MSTS).Results: Tumor location were predominantly in distal femur (25.2%). Local recurrence were observed in 4 patient and mainly in distal femur (50%). Local recurrence were evenly balanced between surgical curettage and wide resection (50% each) and thus not statistically significant (Exact Fischer, p=0.578). Metastasis were observed in patients who undergone wide resection, however, no significant correlation were found between metastasis incidence and types of surgical intervention (Exact Fischer, p=0.318). Four have died related to metastasis. No local recurrence were observed in patients suffering from metastasis. In more than half of patients (51.5%), the functional status were very good (MSTS >75. Recurrence-free survival analysis not significant statistically (p 0.564).Multivariate analysis (Cox regression) showed that only metastasis was found to be significantly correlated to mortality (p. 0.001).Conclusion: Tumor stage was correlated to metastasis, and type of surgical intervention. No significant correlation were found between local recurrence, metastasis, and functional outcome to types of surgical intervention., Introduction: Giant cell tumor of bone is benign lesion with ability to be locally aggressive in epiphysis. Its recurrence rate was reported as high as 75%. Tumor can metastasize to lungs (2-9%) and up to 37% mortality rate due to metastasis. Several studies have reported different rates of local recurrence, lung metastasis, mortality rate, and functional outcome. This study aims to report our experience and analyze the correlation between surgery and clinical findings.Methods: In this retrospective cohort, 99 patients GCT of bone undergone curettage or wide resection in Cipto Mangunkusumo Hospital during 1995-2014. Oncological outcome were analyzed according to local recurrence rate, metastasis, and mortality rate, while functional outcome were measured according to Musculoskeletal Tumor Society Score (MSTS).Results: Tumor location were predominantly in distal femur (25.2%). Local recurrence were observed in 4 patient and mainly in distal femur (50%). Local recurrence were evenly balanced between surgical curettage and wide resection (50% each) and thus not statistically significant (Exact Fischer, p=0.578). Metastasis were observed in patients who undergone wide resection, however, no significant correlation were found between metastasis incidence and types of surgical intervention (Exact Fischer, p=0.318). Four have died related to metastasis. No local recurrence were observed in patients suffering from metastasis. In more than half of patients (51.5%), the functional status were very good (MSTS >75. Recurrence-free survival analysis not significant statistically (p 0.564).Multivariate analysis (Cox regression) showed that only metastasis was found to be significantly correlated to mortality (p. 0.001).Conclusion: Tumor stage was correlated to metastasis, and type of surgical intervention. No significant correlation were found between local recurrence, metastasis, and functional outcome to types of surgical intervention.]"

"Latar belakang: Giant Cell Tumor of Bone (GCT tulang) adalah tumor tulang primer yang bersifat jinak-agresif dan dapat bermetastasis. Rentang usia pasien GCT tulang adalah antara 13 sampai 69 tahun. Tumor ini sering ditemukan di bagian distal femur, distal radius, dan proximal tibia. Berdasarkan tipe tulang, GCT tulang sering ditemukan pada ujung tulang panjang. Namun, GCT tulang juga dapat ditemukan pada tipe tulang lainya. Pada beberapa keganasan tulang, seperti osteosarcoma, terdapat korelasi antara usia dengan lokasi tumor. Namun, untuk GCT tulang korelasi ini masih belum diketahui. Penelitian ini bertujuan untuk melihat adanya korelasi usia dengan lokasi pada GCT tulangMetode: Peneliti mengambil data rekam medis pasien GCT tulang di RSUPN dr.Cipto Mangunkusumo dari tahun 2016 sampai 2020. Kemudian, data usia dengan lokasi (topografi dan tipe tulang) dianalisis menggunakan tabel baris kolom.Hasil: Pada kelompok usia 10-39 tahun ditemukan 52 kasus pada tulang apendikular dan 1 kasus pada tulang axial. Pada kelompok usia 40-69 tahun ditemukan 29 kasus pada tuang apendikular dan 4 kasus pada tulang axial. Korelasi antara usia dan lokasi topografis tidak bermakna (p>0.05). Pada kelompok usia 10-39 tahun ditemukan 49 kasus pada tipe tulang panjang dan 4 kasus pada tipe tulang lainnya. Pada kelompok usia 40-69 tahun, ditemukan 27 kasus pada tulang panjang dan 6 kasus pada tipe tulang lainnya. Korelasi antara usia dengan lokasi tipe tulang tidak bermakna (p>0.05).Kesimpulan: Tidak ada hubungan bermakna antara usia dengan lokasi tumor (topografi dan tipe tulang) pada kasus GCT tulang

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Introduction: Giant cell tumor of bone (GCTB) is a primary bone tumor with benign- aggressive behavior and capacity to metastasize. The age range for GCTB is 13 to 69 years old. GCTB is commonly in distal femur, distal radius, and proximal tibia. Based on bone type, GCTB is frequently found on meta epiphyseal site of long bone. Although, some GCTB can be found on other bone type such as flat bone, short bone, and irregular bone. In some bone neoplasms, like osteosarcoma, there is a correlation between age and tumor site. Unfortunately for GCTB, this correlation is still unknown. This study aims to determine the correlation between age and tumor site of GCTB

Method: Medical record of patients with the diagnosis of GCTB in RSUPN dr.Cipto Mangukusumo from 2016 to 2020 is included in this study. Age at diagnosis and tumor site (topographically and bone type) of patient are analyzed using cross tabulation. Result: For age group 10-39 years old, there are 52 cases of GCTB in appendicular skeleton and one case in axial skeleton. For age group 40-69 years old there are 29 cases of GCTB in appendicular skeleton and 4 cases in axial skeleton. The correlation between age and tumor topographic site is statistically not significant (p > 0.05). For the bone type, there are 49 cases of GCTB in long bone and 4 cases in other bone type for age group 10- 39 years old. For age group 40-69 years old, there are 27 cases of GCTB in long bone and 6 cases in other bone type. The correlation between age and bone type is statistically not significant (p> 0.05)

Conclusion: There are no significant correlation between age and tumor site (topographically and bone type) in GCTB"

"Latar belakang: Giant cell tumor of bone (GCT tulang) adalah tumor tulang lokal agresif dengan gambaran histopatologik terdiri atas kumpulan sel besar multinuklear dan proliferasi sel mononuklear di stroma. Berdasarkan data Departemen Patologi Anatomik RSUPN Dr. Cipto Mangunkusumo, terdapat 86 kasus GCT tulang pada tahun 2016-2020. Adanya invasi limfovaskular adalah petunjuk prognosis buruk beberapa tumor. Riset ini bertujuan untuk mengetahui hubungan kejadian invasi limfovaskular dengan lokasi tumor, ukuran tumor, dan kejadian rekurensi lokal pada pasien GCT tulang di RSUPN Dr. Cipto Mangunkusumo.Metode: Data dari 86 kasus GCT tulang di RSUPN Dr. Cipto Mangkunkusumo pada tahun 2016-2020 diambil melalui formulir pemeriksaan patologi anatomi. Variabel bebas berupa lokasi tumor, ukuran tumor, dan kejadian rekurensi lokal diuji statistik menggunakan uji kai-kuadrat dengan variabel terikat berupa invasi limfovaskular. Hasil: Invasi limfovaskular ditemukan pada 18 (20,9%) pasien GCT tulang. Uji statistik kai-kuadrat menunjukkan hubungan tidak bermakna lokasi tumor pada ekstremitas atas (p=0,227) dan ekstremitas bawah (p=0,521) dengan invasi limfovaskular. Hubungan ukuran tumor <8 cm dengan invasi limfovaskular ditemukan tidak bermakna (p=0,956). Hubungan kejadian rekurensi lokal dengan invasi limfovaskular juga tidak bermakna (p=0,692 dengan uji Fisher).Kesimpulan: Tidak terdapat hubungan invasi limfovaskular dengan lokasi tumor, ukuran tumor, dan kejadian rekurensi lokal pada pasien GCT tulang di RSUPN Dr. Cipto Mangunkusumo.

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Introduction:Giant cell tumor of bone is a local aggressive bone tumor with histopathologic features of multinuclear large cell aggregates and mononuclear cell proliferation in the stroma. According to data from Department of Anatomical Pathology RSUPN Dr. Cipto Mangunkusumo, there are 86 giant cell tumor of bone cases in 2016- 2020. Lymphovascular invasion is believed to have a bad prognostic sign for some tumors. Hence, this research aims to describe the association between tumor location, tumor size, and tumor local recurrence with lymphovascular invasion in giant cell tumor of bone patients at RSUPN Dr. Cipto Mangunkusumo.

Method: 86 giant cell tumor of bone cases at RSUPN Dr. Cipto Mangkunkusumo in 2016-2020 were collected from anatomical pathology examination form. Independent variables being tumor location, tumor size, and tumor local recurrence are statistically tested with the dependent variable, being lymphovascular invasion. A Chi-square test was used to describe the association.

Result: Lymphovascular invasion was found in 18 (20,9%) giant cell tumor of bone patients. Chi-square test showed no association between tumor location at upper extremity (p=0,227) and lower extremity (p=0,521) with lymphovascular invasion. Association of tumor size <8 cm with lymphovascular invasion was also not found (p=0,956). Similarly, association of tumor local recurrence with lymphovascular invasion was not found (p=0,692, using Fisher’s test).

Conclusion: No association was found between tumor location, tumor size, and tumor local recurrence with lymphovascular invasion of giant cell tumor of bone patients at RSUPN Dr. Cipto Mangunkusumo in 2016-2020."