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"Radiasi merupakan terapi pilihan untuk kanker serviks stadium III B, namun permasalahan timbul karena adanya sifat radioresisten. Sel punca kanker SPK merupakan salah satu faktor yang diduga berkontribusi terhadap hal tersebut. SOX2 dan OCT4 merupakan faktor transkripsi yang mengekspresikan sifat-sifat SPK, yaitu mengontrol sifat pluripoten, self-renewal, berperan pada karsinogenesis, metastasis, resistensi terhadap terapi dan rekurensi tumor. Faktor apoptosis, DNA repair dan telomerase merupakan mekanisme yang berkaitan dengan radioresisten. Penelitian ini bertujuan untuk mempelajari hubungan antara SOX2 dan OCT4 sebagai penanda SPK terhadap respons terapi radiasi, serta kaitannya dengan faktor apoptosis caspase-3 , DNA repair Chk1 dan telomerase hTERT .Penelitian ini merupakan case control, terhadap 48 kasus karsinoma sel skuamosa serviks stadium III B yang telah menjalani terapi radiasi/kemoradiasi di RS Cipto Mangunkusumo/FKUI. Kasus dibagi dalam 2 kelompok, yaitu hasil terapi komplet 27 kasus dan hasil terapi inkomplet 21 kasus . Kasus dengan respons awal terapi radiasi baik dilakukan pemeriksaan bulan Pap smear dan HPV pada bulan ke-6 atau sampai ke-12 setelah terapi. Ekspresi SOX2, OCT4, caspase-3, Chk1 dan hTERT diperiksa secara imunohistokimia dari blok parafin biopsi awal.Ekspresi kuat SOX2 dan OCT4 dengan H-score masing-masing lebih dari 96,6 dan 61,9 mempunyai hubungan bermakna dengan respons awal terapi radiasi maupun respons akhir terapi radiasi SOX2 p = 0,017, p = 0,004 dan OCT4 p < 0,001, p < 0,001 . Ditemukan hubungan bermakna antara ekspresi Chk1 dan hTERT dengan respons awal terapi radiasi Chk1 p = 0,006, hTERT p = 0,029 . Tidak ditemukan hubungan yang bermakna antara ekspresi caspase-3, Chk1, hTERT dengan ekspresi SOX2 dan OCT4. Uji multivariat menunjukkan bahwa SOX2 dan OCT4 yang paling memengaruhi respons terapi OR = 5,12, p = 0,040 dan OR = 17,03, p < 0,001, secara berurutan . Uji probabilitas menunjukkan kemungkinan respons akhir terapi radiasi inkomplet sebesar 87,91 bila ekspresi kedua penanda SPK kuat.Ekspresi kuat SOX2 dan OCT4 dapat memprediksi hasil terapi radiasi inkomplet pada karsinoma serviks stadium III B.

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Radiotherapy is the main choice of treatment for stage III B cervical cancer, but radioresistance becomes a difficult matter. Cancer stem cell is one of the factors suspected involving in radioresistant cancers. SOX2 and OCT4 are transcription factors which have pluripotent cell characteristics, and self renewal ability. They also involved in carcinogenesis, metastasis, tumor recurrent, and resistance toward therapy. Apoptotic, DNA repair, and telomerase factors are mechanisms that also contribute to radioresistance. This study aims to know the role of SOX2 and OCT4 as CSC markers, apoptotic factor caspase 3 , DNA repair Chk1 and telomerase hTERT toward radiotherapy.The design of this study was case control with 48 cases of stage III B cervical squamous cell carcinoma patients who had finished receiving radiation chemo radiation therapy at Cipto Mangunkusumo Hospital FMUI, Jakarta. They were classified in 2 groups based on the final response of treatment, which were complete and incomplete one. Pap smear and DNA HPV were performed in month 6 or until month 12 after therapy for good initial therapy. Immunohistochemistry was done to analyze SOX2, OCT4, caspase 3, Chk1 and hTERT expression from the paraffin block of initial biopsy.Strong expression of SOX2 and OCT4 with each H score was higher than 96.6, and 61.9 had significant association with both initial and final therapy response SOX2 p 0.017, p 0.004 and OCT4 p 0.001, p 0.001, repectively . There was significant association between expression of Chk1 and hTERT, and initial therapy response p 0.006 for Chk1, and p 0.029 for hTERT . No significant differences were found between caspase 3, Chk1, hTERT, and SOX2 and OCT4. Multivariate analysis showed SOX2 and OCT4 were the most influenced antibodies for radiotherapy response OR 5.12, p 0.040, and OR 17.03, p 0.001, respectively . The likelihood of incomplete final therapy response was 87.91 if the expression both of CSC markers were strong.Expression of SOX2, and OCT4 could predict the incomplete radiotherapy of stage III B cervical cancer cases. "

"Pendahuluan: Kanker payudara triple-negatif merupakan subset keganasan yang menantang terkait dengan prognosis buruk akibat rendahnya ekspresi HER2 dan reseptor hormon, yang mengakibatkan kurangnya modalitas terapi yang ditargetkan secara spesifik. Selain itu, bagian dari keganasan ini mempunyai tingkat kekambuhan dini dan metastasis yang tinggi. Manganese superoxide dismutase (MnSOD), suatu enzim yang sangat penting untuk keseimbangan redoks, terlibat dalam tumorigenesis karena peran gandanya. Awalnya, MnSOD bertindak sebagai penekan tumor selama tumorigenesis awal, namun perannya bergeser seiring perkembangan penyakit. Kanker payudara triple-negatif diperkaya dengan subpopulasi sel dengan potensi tumorigenik tinggi dan stres oksidatif yang dikenal sebagai sel punca kanker. Sel-sel ini mengekspresikan faktor transkripsi Oct4 dan Sox2, yang mengatur pembaruan diri dan kepuncaan. Studi ini menyelidiki efek penekanan ekspresi MnSOD melalui KO gen CRISPR/Cas9 pada sel punca kanker BCSC triple-negatif dengan mengukur ekspresi mRNA OCT4 dan SOX2. Metode: Penelitian ini menggunakan kelompok kontrol BCSC tripel-negatif BT-549 tipe wild-type dan dua kelompok BT-549 KO MnSOD yang diberi perlakuan. Untuk setiap kelompok, tiga sampel ulangan digunakan. Ekspresi mRNA OCT4 dan SOX2 di setiap kelompok kontrol dan kelompok perlakuan dideteksi oleh RT-qPCR. Hasil masing-masing dihitung dengan Metode Livak untuk mengekstraksi rasio ekspresi. Uji T dua sampel dilakukan untuk menghitung signifikansinya. Hasil: Temuan ini menunjukkan tren penurunan ekspresi SOX2 dan ekspresi mRNA OCT4 yang tidak konsisten. Kesimpulan: Penekanan MnSOD dapat menjadi target potensial untuk mengubah sifat pluripotensi BCSC triple-negatif dengan memberikan efek tidak langsung pada ekspresi mRNA OCT4 dan SOX2.

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Introduction: Triple-negative breast cancer represents a challenging subset of malignancy associated with poor prognosis due to low expression of HER2 and hormone receptors, resulting in the lack of specific targeted therapeutic modalities. Additionally, this subset of malignancy acquires a high rate of early recurrence and metastasis. Manganese superoxide dismutase (MnSOD), an enzyme paramount for redox balance, is implicated in tumorigenesis by its dual role. Initially, MnSOD acts as a tumor suppressor during early tumorigenesis, but its role shifts as the disease advances. Triple-negative breast cancer is enriched with a subpopulation of cells with high tumorigenic potential and oxidative stress known as cancer stem cells (CSC). These cells expressed Oct4 and Sox2 transcription factors, which regulate self-renewal and stemness. This study investigates the effect of suppressing MnSOD expression through CRISPR/Cas9 gene knockout on the stemness of triple-negative BCSCs by measuring OCT4 and SOX2 mRNA expression. Methods: This study utilized a control group of wild-type BT-549 triple-negative BCSCs and two treated groups of MnSOD-knockout BT549 BCSCs. For each group, three replicate samples were used. The mRNA expression of OCT4 and SOX2 in each control and treated group was detected by RT-qPCR. Their respective results were calculated by the Livak Method to extract the expression ratio. A two-sample T-test was performed to calculate the significance. Results: The findings demonstrate a decreasing trend of SOX2 expression and an inconsistent OCT4 mRNA expression. Conclusion: MnSOD suppression may present as a potential target for altering the pluripotency properties of triple-negative BCSCs by exerting an indirect effect on OCT4 and SOX2 mRNA expression."

"Latar Belakang: Kanker payudara triple negatif dikenal sebagai jenis kanker yang memiliki prognosis yang lebih buruk daripada jenis kanker payudara lainnya karena kurangnya terapi target dan tingkat kekambuhan dini dan metastasis yang lebih tinggi. Manganese superoxide dismutase (MnSOD), pertahanan utama melawan superoksida, telah ditemukan untuk memiliki peran ganda dalam kanker. Meskipun MnSOD mungkin memiliki peran penekan tumor pada tahap awal tumorigenesis, MnSOD akan kemudian mempunyai peran penting untuk kelangsungan hidup sel kanker saat tumor berkembang. Sel punca kanker, ditemukan dalam tingkat yang tinggi dalam kanker payudara triple negatif, adalah subpopulasi sel tumor yang memiliki kapasitas tumorigenisitas dan stress oksidatif yang tinggi. Sel punca kanker mengekspresikan faktor transkripsi seperti Oct4 dan Sox2 yang mengatur gen yang diperlukan untuk pembaruan diri dan pluripotensi sel punca kanker ini. Penelitian ini bertujuan untuk mengetahui pengaruh penekanan ekspresi MnSOD melalui gen knockout terhadap pluripotensi sel punca kanker payudara triple negatif dengan mengukur ekspresi protein Oct4 dan Sox2. Metode: Penelitian ini menggunakan satu kelompok kontrol BT-549 sel punca kanker payudara triple negatif dan dua kelompok BT549 sel punca kanker payudara triple negatif yang telah diberi perlakuan knockout gen MnSOD. Untuk setiap kelompok sampel, tiga pasase digunakan (P2, P3, P4). Protein Oct4 dan Sox2 yang diekspresikan oleh setiap pasase dari setiap kelompok dideteksi menggunakan Western blot dan area pita masing-masing protein kemudian dianalisis menggunakan program ImageJ.Hasil: Ditemukan adanya tren penurunan ekspresi protein Oct4 dan tren peningkatan ekspresi protein Sox2. Kesimpulan: Penekanan ekspresi MnSOD mungkin bisa menjadi target untuk mengubah tingkat pluripotensi sel punca kanker payudara triple negatif melalui interaksi tidak langsung dengan Oct4 dan Sox2.

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Introduction: Triple negative breast cancer is considered to have a poorer prognosis than other subtypes of breast cancer due to the lack of targeted therapies and its higher rate of early recurrence and distant metastasis. Manganese superoxide dismutase (MnSOD), the primary defense against superoxides, have been found to have a dual role in cancer. Although MnSOD may have a tumor-suppressing role in the early stages of tumorigenesis, it later becomes essential for the survival of the cancer cells as the tumor progresses. Cancer stem cells (CSCs), enriched in triple negative breast cancer, are a population of tumor cells that possess high capacity of tumorigenicity and oxidative stress. They express transcription factors such as Oct4 and Sox2 which regulate genes necessary for the self-renewal and pluripotency of these CSCs. This study aims to determine the impact of suppressing MnSOD expression through gene knockout on the pluripotency of triple negative breast cancer stem cells by measuring Oct4 and Sox2 protein expression.

Methods: A control group of wild type BT-549 BCSCs and two groups of treated BT549 BCSCs were used in this study, with the treated groups having their MnSOD gene knocked out. For each group of samples, three passages were used (P2, P3, P4). The Oct4 and Sox2 proteins expressed by each passage number from each group were detected using Western blot and their respective area densities were then analyzed using the ImageJ program.

Results: There was a decreasing trend in Oct4 protein expression and an increasing trend in Sox2 protein expression.

Conclusion: Suppression of MnSOD expression may be a target to alter the pluripotency of triple negative BCSCs through its indirect interaction with Oct4 and Sox2. "

"Kanker ovarium memiliki mortalitas mencapai 70%, dan 85% dari pasien yang datang pada kondisi stadium lanjut. Sebanyak > 80% pasien stadium lanjut merespons pada kemoterapi lini pertama yang menggunakan obat berbasis platinum, namun median kesintasan bebas penyakitnya (disease-free survival) hanya mencapai 18 bulan, sebagian besar merupakan pasien kambuh, dan tidak merespons pada kemoterapi lini berikutnya. Pada moda moda kemoresistensi, yang paling dapat diintervensi adalah adanya sel punca kanker (CSC) pada jaringan kanker ovarium pasien. Kemoresistensi pada CSC memiliki beberapa mekanisme berbeda, salah satunya adalah tingginya aktivitas protein ATM dan ATR yang dapat bersifat kompetitif terhadap obat berbasis platinum dalam berikatan dengan DNA. Selama ini, telah banyak penelitian eksperimental yang menarget CSC kanker ovarium, namun penelitian terbaru menggunakan RNA microarray menemukan bahwa gen ADAM19 diekspresikan secara eksklusif pada CSC kanker ovarium sehingga dapat digunakan sebagai marker spesifik. Oleh karena itu, penelitian ini ditujukan untuk mengeksplorasi kemoresistensi pada CSC kanker ovarium dari jaringan segar pasien dan korelasinya dengan ekspresi gen ATM dan ATR, serta mengonfirmasi ekspresi gen ADAM19 sebagai marker spesifik subpopulasi CSC kanker ovarium yang dipilah menggunakan metode MACS dengan penanda CD133. Dari 67 pasien subjek penelitian yang diambil dan dikultur jaringan metastasisnya, dua di antaranya dapat dikultur tanpa batas, menghasilkan kultur dengan dominan sel epitel, dan tidak mengalami senescence. Setelah itu, sel-sel kultur dipilah menggunakan MACS dengan penanda CD133 untuk mendapatkan CSC, kemudian diuji menggunakan metode pembuatan sferoid, RT-qPCR, dan uji kemoresistensi. Dari pembentukan sferoid yang dilakukan pada tiga jenis sel yang digunakan, yakni lini sel SKOV3, serta kultur primer OV1 dan OVM1, ditemukan secara konsisten bahwa jumlah sferoid yang didapatkan pada kultur CSC CD133+ lebih banyak dibandingkan main population (MP) dan CD133-. Dari RT-qPCR juga ditemukan secara konsisten bahwa seluruh ekspresi gen ATM, ATR, NANOG, ADAM19, Ki-67, dan kaspase-3 pada CSC CD133+ lebih tinggi dibandingkan MP dan CD133. Pada uji kemoresistensi terhadap kemoterapi karboplatin, didapatkan bahwa sel CD133+ juga lebih kemoresisten dibandingkan dengan MP dan CD133-. Berdasarkan uji korelasi Spearman Rho, ekspresi gen ATM dan ATR berkorelasi positif sedang menuju sangat kuat dengan sifat kemoresistensi terhadap karboplatin. Pada akhir penelitian, disimpulkan bahwa CSC dengan CD133+ memiliki kemampuan proliferasi yang lebih tinggi dengan ekspresi gen Ki-67 yang meningkat, memiliki stemness yang lebih kuat terlihat pada ekspresi gen Nanog-nya yang lebih tinggi, dan memiliki kemampuan kemoresistensi yang lebih besar ditunjukkan oleh ekspresi gen ATM dan ATR-nya yang tinggi serta berkorelasi positif dengan hasil uji kemoresistensi.

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Ovarian cancer has a mortality rate of up to 70% where 85% of patients present at an advanced stage. More than 80% of advanced stage patients respond to first-line chemotherapy using platinum-based drugs, but the median disease-free survival is only 18 months. Most patients relapse, and do not respond to subsequent lines of chemotherapy. In the chemoresistance modes, the easiest way to intervene is through the presence of cancer stem cells (CSC) in the patient's ovarian cancer tissue. Chemoresistance in CSC has several different mechanisms, one of which is the high activity of ATM and ATR proteins that can be competitive against platinum-based drugs in binding to DNA. So far, there have been many experimental studies targeting ovarian cancer CSCs, but a recent study using RNA microarray found that ADAM19 gene expression is expressed exclusively in ovarian cancer CSCs so that it can be used as a specific marker. Therefore, this study aimed to explore chemoresistance in ovarian cancer CSC from fresh patient’s tissue and its correlation with ATM and ATR gene expression, as well as to confirm ADAM19 gene expression as a specific marker for ovarian cancer CSC subpopulations sorted using the MACS method with the CD133 marker. Out of 67 patients who were the subjects of the study, the samples were taken and cultured for their metastatic tissues, 2 of them could be cultured indefinitely, could produce cultures with a predominance of epithelial cells, and did not experience senescence. After that, the culture cells were sorted using MACS with the CD133 marker to obtain CSC, then tested using the spheroid preparation method, RT-qPCR, and chemoresistance test. From the spheroid culture performed on the 3 types of cells used, namely the SKOV3 cell line, as well as OV1 and OVM1 primary cultures, it was found consistently that the number of spheroids obtained in CD133+ CSC cultures was higher than the main population (MP) and CD133-. From RT-qPCR it was also found consistently that all genes expression ATM, ATR, NANOG, ADAM19, Ki-67, and Caspase-3 in CD133+ CSCs were higher than MP and CD133. In the chemoresistance test to carboplatin chemotherapy, it was found that CD133+ cells were also more chemoresistant than MP and CD133-. Based on the Spearman Rho correlation test, ATM and ATR gene expression had a moderately strong positive correlation with chemoresistance to carboplatin. At the end of the study, it was concluded that CSCs with CD133+ had a higher ability to proliferate with increased expression of the Ki-67 gene, had stronger stemness as seen in the higher expression of the NANOG gene, and had greater chemoresistance ability as indicated by the expression of the ATM gene. and high ATR and positively correlated with chemoresistance test results."

"Kanker payudara adalah kanker dengan insidensi dan tingkat mortalitas tertinggi untuk wanita di Indonesia berdasarkan Cancer Country Profile oleh WHO pada 2014. Salah satu hipotesis terbaru dalam dunia onkologi adalah keberadaan sel punca kanker yang mendorong tumorigenesis, metastasis, therapy resistance dan remission pada kasus kanker ganas. Sel punca kanker dianggap hidup dalam kondisi hipoksia in vivo, sejalan dengan keadaan sel punca pada umumnya. Kondisi inilah yang mendorong sel punca kanker untuk memiliki karakteristik stemness yang menganugerahkan mereka kapasitas self-renewal dan pluripotency hingga akhirnya memperoleh ciri malignansi. Sebagai salah satu cara untuk mendalami sifat unik ini, kultur sel punca kanker payudara yang telah difraksinasi menggunakan marker CD44 /CD24-, diekspos terhadap hipoksia dengan interval berbeda. Perubahan ekspresi dari Oct4 sebagai core regulator dan ALDH1 sebagai modulator dari stemness akan diukur dan dibandingkan dalam kondisi hipoksia dan normoksia.

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Breast cancer has the highest incidence and mortality rate in Indonesian women based on WHO Cancer Country Profiles 2014. One of the emerging hypothesis in the oncology world is on cancer stem cells, which are responsible for the tumorigenesis, metastasis, therapy resistance and remission in many cancer types and cases. Similar to stem cells, cancer stem cells live around hypoxic surrounding in vivo and this condition granted the cancer stem cells pluripotency and self renewal capability, thus the characteristic of stemness and malignancy. Breast cancer has been shown to also contain cancer stem cells and so to study the unique trait under hypoxic condition, the cells, which have been fractionated by markers CD44 and CD24 , are subjected to hypoxia. The expression of Oct4 and ALDH1 as the core regulator and modulator of stemness respectively are assessed and further compared between hypoxic and normoxic groups."

"Angka kematian kanker serviks masih tinggi karena banyak pasien datang berobat pada tahap lanjut. Respons terapi radiasi pada pasien kanker serviks stadium lanjut bervariasi walau dengan faktor klinikopatologi yang sama seperti stadium, massa tumor, jenis histopatologi, derajat diferensiasi, invasi limfovaskular, reaksi limfosit dan nekrosis. Oleh karena itu dipikirkan faktor prognosis lain seperti faktor apoptosis-survivin, telomerase dan sitokrom c. Penelitian ini bertujuan untuk mengetahui peran survivin, telomerase, dan sitokrom c sebagai prediktor respons terapi radiasi pada kanker serviks stadium lanjut khususnya stadium IIIB.Studi ini bersifat prospektif menggunakan metode nested case control. Pengambilan data dilakukan di Poliklinik Onkologi Departemen Obstetri dan Ginekologi RSCM serta Departemen Patologi Anatomi FKUI pada bulan Januari 2016 hingga Mei 2017. Pada subjek penelitian dilakukan wawancara, pemeriksaan histopatologi dan pemeriksaan biokimia secara ELISA untuk mengetahui kadar survivin, telomerase, sitokrom c, dan MRI pra-radiasi serta pasca-radiasi. Dari 90 subjek penelitian didapatkan rerata usia pasien 50 tahun, rerata massa tumor 6,7 cm dan sebagian besar berkeratin 84,4 , berdiferensiasi baik 81,1 , reaksi limfosit negatif 75,6 dan nekrosis 74,4 . Rerata faktor apoptosis-survivin, telomerase dan sitokrom c adalah 591,2 pg/mL, 5.223,2 pg/mL dan 191,3 ng/mL. Dari analisis bivariat didapatkan variabel yang berhubungan dengan respons terapi secara independen adalah massa tumor p = 0,1 , diferensiasi p = 0,17 , kadar survivin p = 0,01 , kadar telomerase p = 0,08 dan kadar sitokrom c p = 0,47. Hasil analisis multivariat didapatkan hubungan kadar survivin dan kadar telomerase dengan respons terapi radiasi p = 0,01 dan p = 0,07 . Tidak terdapat hubungan kadar sitokrom c dengan respons terapi radiasi p = 0,64 . Dengan model cox regresi survival didapatkan hazard ratio subjek dengan kadar survivin tinggi dan kadar telomerase tinggi terhadap respons terapi radiasi negatif adalah 4,20 dan 1,97.Simpulan: kadar survivin dan telomerase tinggi berhubungan dengan respons terapi radiasi negatif.

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Cervical cancer mortality rate is still high mostly due to patients seeking for help in advanced stage of the disease. Even with the same clinicopathologic features such as stage of the diseases, size of the tumor, histopathological types, level of differentiation, lymphocyte reaction and tumor necrosis, the radiotherapy outcomes still vary from patient to patient. Therefore, we thought another predictive factors like apoptosis inducing factors i.e. survivin, telomerase and cytochrome c as a new predictor of therapeutic resp onses on patients with stage IIIB squamous cell carcinoma of cervix.

This is a prospective study with nested case control method. Data collection was conducted in Oncology Polyclinic, Department of Obstetrics and Gynecology RSCM and Department of Pathological Anatomy of FKUI from January 2016 to May 2017. Subjects were interviewed, conducted histopathological and biochemical examination with ELISA to determine levels of survivin, telomerase, cytochrome c, and patients undergo pre and post radiation MR imaging.

There were 90 patients in this study with the mean of ages was 50 years, mean of tumor size was 6.7 cm and most subjects were keratinizing 84.4 , well differentiated 81.1 , negative lymphocyte reaction 75.6 and tumor necrosis 74.4 . The mean levels of apoptosis inducing factors survivin, telomerase and cytochrome c were 591.2 pg mL, 5,223.2 pg mL, and 191.3 ng mL.

Bivariate analysis showed the independent association between tumor size, level of differentiation, levels of survivin and telomerase p 0.1, p 0.17, p 0.01, p 0.08 . Multivariate analysis showed the correlation between levels of survivin and telomerase with radiation therapeutic response p 0.01 and p 0.07 and there was no association with level of cytochrome c p 0.64 With the survival cox regression models, the hazard ratio of subjects with high levels of survivin and telomerase on the negative radiation therapy responses were 4.20 and 1.97.Conclusion there were association between high levels of survivin and telomerase on the negative radiation therapy response. "

"Latar Belakang: Rekayasa jaringan tulang memerlukan tiga komponen utama, yaitu sel punca, scaffold, dan faktor pertumbuhan. IGF-1 merupakan salah satu faktor pertumbuhan yang berperan dalam proliferasi dan diferensiasi sel osteoblast. IGF-1 akan berikatan dengan reseptornya, yaitu IGF-1R untuk mengaktivasi jalur hilir. Dalam sirkulasi tubuh manusia, IGF berikatan dengan IGFBP-3 yang dapat memperpanjang waktu paruh serta menghambat IGF-1 berikatan dengan IGF-1R. Pada penelitian sebelumnya, tercatat bahwa tidak ada perbedaan kemampuan proliferasi dan diferensiasi antara DPSC subjek normal dan subjek CLP, namun ada perbedaan signifikan dalam jumlah ekspresi IGF-1. OCT-4, SOX-2 dan NANOG merupakan faktor transkripsi utama pluripotensi yang telah diteliti dapat mengatur pluripotensi, pembaruan diri, proliferasi, serta diferensiasi DPSC. Penelitian terbaru mencatat peningkatan ekspresi ketiga gen tersebut pasca dilakukan penghambatan jalur GSK-3 dan m-TOR yang merupakan jalur hilir dari aksi IGF-1 pada sel DPSC. Namun, belum diketahui secara pasti ekspresi ketiga gen tersebut pada DPSC subjek normal dan CLP setelah dilakukannya penghambatan IGF-1 menggunakan anti IGF-1R dan IGFBP-3. Tujuan: Menganalisis pengaruh anti IGF-1 dan IGFBP-3 terhadap ekspresi gen OCT4, SOX2, dan NANOG pada DPSC subjek normal dan CLP. Metode: Sampel RNA DPSC subjek normal (n=4) dan DPSC subjek CLP (n=3), sebelum dan setelah diberikan perlakuan anti IGF-1R atau IGFBP-3, diperoleh dari bahan biologis tersimpan di Laboratorium Oral Biologi Fakultas Kedokteran Gigi Universitas Indonesia. Selanjutnya, ekspresi gen OCT4, SOX2, NANOG, dan housekeeping gene GAPDH diuji dengan two step Real-Time PCR (RT-PCR). Hasil: Tidak terdapat perbedaan ekspresi gen OCT4, SOX2, dan NANOG, baik antara DPSC subjek normal dan CLP sebelum dan setelah diberikan perlakuan anti IGF-1R dan IGFBP-3 (p³0,05). Kesimpulan: Perlakuan anti IGF-1R dan IGFBP-3 tidak memengaruhi tingkat ekspresi gen OCT4, SOX2, dan NANOG sel punca pulpa gigi permanen subjek normal dan subjek celah bibir dan palatum

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Background: Bone tissue engineering requires three main components, namely stem cells, scaffold, and growth factors. IGF-1 is a growth factor that plays role in osteoblast proliferation and differentiation. IGF-1 will bind to its receptor, namely IGF-1R, to activate the downstream pathway. In the human body circulation, IGF binds to IGFBP-3 which can inhibit IGF-1 from binding to IGF-1R. Previous studies noted that there were no differences in the ability to proliferate and differentiate between DPSC from normal subjects and CLP subjects, yet there were significant differences in the level of IGF-1 expression. OCT-4, SOX-2 and NANOG are core pluripotency factors which regulate pluripotency, self-renewal, proliferation and differentiation of DPSC. Recent study has noted an increase in the expression of these three genes after inhibition of GSK-3 and m-TOR pathways, which are the downstream pathways of IGF-1 on DPSC cells. However, the expression of these three genes in DPSC from normal and CLP subjects after inhibition of IGF-1 using anti IGF-1R and IGFBP-3 is still unknown. Objective: To analyze the effect of anti IGF-1 and IGFBP-3 on OCT4, SOX2, and NANOG gene expression in DPSC of normal and CLP subjects. Methods: RNA samples of DPSC from normal and CLP subjects, before and after being treated with anti-IGF-1R or IGFBP-3, were obtained from Laboratory of Oral Biology, Faculty of Dentistry, Universitas Indonesia. Furthermore, the expression of OCT4, SOX2, NANOG, and housekeeping gene GAPDH were tested using two step Real-Time PCR (RT-PCR). Results: There was no difference between the expression of the OCT4, SOX2, and NANOG in DPSC from normal and CLP subjects before and after anti IGF-1R and IGFBP-3 treatment (p≥0.05). Conclusion: Anti-IGF-1R and IGFBP-3 did not affect the expression level of OCT4, SOX2, and NANOG in dental pulp stem cells of normal subjects and cleft lip and palate subjects.

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"[Latar Belakang: Kanker payudara masih merupakan kanker yang paling umumpada wanita. Identifikasi sel punca kanker payudara sangat penting dalammemberantas penyakit ini dari akarnya. Beberapa riset telah mengisolasi sel puncakanker payudara berdasarkan protein membran sel CD24/CD44 dan menemukansel punca kanker payudara pada sel CD24-/CD44+ yang menunjukkan sifatpluripotensi. Namun, beberapa riset lainnya menemukan CD24-/CD44+ tidakditemukan pada seluruh tipe kanker payudara, dan tidak selalu berhubungandengan perkembangan tumor. Maka dari itu, tingkat pluripotensi dari sel tersebutmasih diperdebatkan. Dalam riset ini, sifat pluripotensi sel punca kanker payudaradinilai berdasarkan ekspresi gen SOX2 yang merupakan gen untuk sifatkepuncaan dimana gen ini dapat mendorong pembelahan sel dan invasi.Metode: Sampel diambil dari situs primer kanker payudara dan difraksinasimelalui pemisahan sel magnetik. RT-qPCR dan elektroforesis digunakan untukmempelajari tingkat ekspresi gen SOX2 antara fraksi-fraksi sel punca kankerpayudara.Hasil: Kami berhasil memisahkan sel pluripoten dari spesimen klinis kankerpayudara. Fraksi CD24-/CD44- menunjukkan ekspresi gen SOX2 yang lebihtinggi secara signifikan dibanding CD24-/CD44+. Setelah melewati proses ultralowattachment, CD24-/CD44+ menunjukkan peningkatan ekspresi gen SOX2walaupun lebih rendah dari CD24-/CD44-.Kesimpulan: Pluripotensi yang tinggi, berdasarkan tingkat ekspresi gen SOX2,ditemukan pada fraksi CD24-/CD44-. Tingkat pluripotensi fraksi CD24-/CD44+lebih rendah dibandingkan fraksi CD24-/CD44-.;Background: Breast cancer remains as the most prevalent cancer in women.Identification of breast cancer stem cell (CSC) is crucial in eradicating the diseasefrom its root. Multiple research has isolated breast CSC based on CD24/CD44surface marker and discovered that CD24+/CD44- fraction indicates stemness andpluripotent characteristics. However, it was also found that CD24+/CD44- breastCSC is not present in all breast cancer types, and not always associated withtumor progression. Therefore, its pluripotency level remains debatable. In thisresearch, pluripotency of breast CSCs was assessed. Pluripotency was determinedbased on SOX2 gene expression, a gene responsible for stem-like properties,which can drive cellular proliferation and invasion.Method: The samples were taken from primary site of breast cancer andfractionated through magnetic cell sorting. RT-qPCR with subsequentelectrophoresis was used to study the expression level of SOX2 gene amongbreast CSC fractions.Results: We managed to separate the pluripotent cells from the bulk clinicalspecimen. CSC subset CD24-/CD44- showed a significantly higher SOX2expression in comparison to CD24-/CD44+. Following ultra-low attachment,CD24-/CD44+ showed an increase in SOX2 expression level although still lowerthan CD24-/CD44-.Conclusions: A high pluripotency based on SOX2 gene expression level wasfound in fraction CD24-/CD44-. The pluripotency level of fraction CD24-/CD44+was lower in comparison to fraction CD24-/CD44-., Background: Breast cancer remains as the most prevalent cancer in women.Identification of breast cancer stem cell (CSC) is crucial in eradicating the diseasefrom its root. Multiple research has isolated breast CSC based on CD24/CD44surface marker and discovered that CD24+/CD44- fraction indicates stemness andpluripotent characteristics. However, it was also found that CD24+/CD44- breastCSC is not present in all breast cancer types, and not always associated withtumor progression. Therefore, its pluripotency level remains debatable. In thisresearch, pluripotency of breast CSCs was assessed. Pluripotency was determinedbased on SOX2 gene expression, a gene responsible for stem-like properties,which can drive cellular proliferation and invasion.Method: The samples were taken from primary site of breast cancer andfractionated through magnetic cell sorting. RT-qPCR with subsequentelectrophoresis was used to study the expression level of SOX2 gene amongbreast CSC fractions.Results: We managed to separate the pluripotent cells from the bulk clinicalspecimen. CSC subset CD24-/CD44- showed a significantly higher SOX2expression in comparison to CD24-/CD44+. Following ultra-low attachment,CD24-/CD44+ showed an increase in SOX2 expression level although still lowerthan CD24-/CD44-.Conclusions: A high pluripotency based on SOX2 gene expression level wasfound in fraction CD24-/CD44-. The pluripotency level of fraction CD24-/CD44+was lower in comparison to fraction CD24-/CD44-.]"

"Latar Belakang : Kanker serviks stadium awal dapat ditatalaksana dengan baik, namun pada stadium lanjut lokal memiliki prognosis yang buruk. Terapi standar yang tersedia masih kurang optimal dan memiliki efek samping yang mengganggu. Pada keadaan tertentu tumor dapat mengalami metastases atau progresif, salah satunya karena adanya ikatan PD-L1 dengan sel limfosit T sehingga kanker serviks terhindar dari respon imun. Pemberian anti PD-L1 menjadi bagian yang penting dalam pengobatan imunoterapi kanker. Di Indonesia belum tersedia data empirik profil karakteristik yang berkaitan dengan ekspresi PD-L1 serta respon tumor terhadap radiasi pada kanker serviks. Metode: Penelitian ini memeriksa ekspresi PD-L1 intratumoral pada jaringan biopsi karsinoma sel skuamosa serviks pre dan paska radiasi eksterna dengan menggunakan metode ELISA dan IHK, pemeriksaan IHK menggunakan antibodi clone 28-8 dari Abcam. Pemeriksaan CT scan evaluasi sebelum radiasi dan 2 bulan setelah radiasi dipakai sebagai alat untuk menilai respon terapi radiasi. Hasil : Dari 31 pasien yang ikut serta, terdapat 29 pasien yang telah dilakukan pemeriksaan ekspresi PD-L1 sebelum dan sesudah radiasi, selanjutnya hanya 22 pasien yang telah menjalani CT scan evaluasi. Ekspresi PD-L1 ELISA paska radiasi eksterna berbeda bermakna pada tumor berukuran ≥5cm (p=0,015) dan ekspresi PD-L1 IHK berbeda bermakna pada sel tumor berkeratin (p=0,023), pada pasien dengan grade IHK yang difus (+3) resiko relatif untuk respon komplit 0,5 kali dibandingkan dengan grade IHK yang  tidak difus. Uji korelasi perbedaan selisih ekspresi (delta) dan rasio PD-L1 ELISA menunjukkan tidak ada korelasi (R2= 0,217) dan (R2= 0,194) terhadap respons, begitu juga hasil pada hasil pemeriksaan ekspresi PD-L1 IHK tidak ada perbedaan bermakna pada kategori kenaikan, tetap dan penurunan, tetapi ketika kategori dirubah menjadi penurunan dan tidak ada penurunan didapatkan nilai p yang lebih baik (p=0,161 vs p=.0,613).Kesimpulan : Tidak terdapat perbedaan bermakna antara ekspresi PD-L1 pre dan paska radiasi terhadap respon, akan tetapi terdapat tren penurunan kadar PD-L1 IHK berkaitan dengan respon terapi.

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Correlation of Intratumoral PD-L1 Expression Before and After External Radiation to The Radiation Response in Locally Advanced Cervical Cancer.

Background: Early-stage cervical cancer can be managed properly, but at a locally advanced stage it has a poor prognosis. The standard therapy available is still suboptimal and has disturbing side effects. In certain circumstances, tumors can undergo metastases or progressives, one of which is due to the binding of PD-L1 with T lymphocyte cells so that cervical cancer is protected from the immune response. In Indonesia, there is no available empirical data on the characteristic profiles related to PD-L1 expression and tumor response to radiation in cervical cancer.

Method: This study examined intratumoral PD-L1 expression in biopsy tissue of squamous cell carcinoma of cervical cells pre and post external radiation using ELISA and IHC methods, IHC examination using antibody clone 28-8 from Abcam. CT scan evaluation before radiation and 2 months after radiation are used as a tool to assess the response of radiation therapy.

Results: Of the 31 patients who participated, there were 29 patients who had examined the expression of PD-L1 before and after radiation, then only 22 patients who had undergone a CT scan evaluation. Expression of PD-L1 ELISA after external radiation was significantly different in tumors of ≥5cm (p=0.015) and expression of PD-L1 IHC was significantly different in keratinous tumor cells (p = 0.023), in patients with diffuse IHC grade (+3) relative risk to complete response of 0.5 times compared to the grade of IHC which is not diffuse. Correlation test difference in expression difference (delta) and PD-L1 ELISA ratio showed no correlation (R2=0.217) and (R2=0,194) to the response, as well as results on the examination results of PD-L1 IHC expression there was no significant difference in the increased category, constant and decrease, but when the category is changed to decrease and there is no decrease, a better p-value is obtained (p=0.161 vs p=0.613).

Conclusion: There was no significant difference between the expression of PD-L1 pre and post-radiation to the response, but there was a trend of decreasing PD-L1 IHC levels concerning therapeutic response."

"Latar Belakang: Kanker serviks stadium awal dapat ditatalaksana dengan baik, namun pada stadium lanjut lokal memiliki prognosis yang buruk. Terapi standar yang tersedia masih kurang optimal dan memiliki efek samping yang mengganggu. Pada keadaan tertentu tumor dapat mengalami metastases atau progresif, salah satunya karena adanya ikatan PD-L1 dengan sel limfosit T sehingga kanker serviks terhindar dari respon imun. Pemberian anti PD-L1 menjadi bagian yang penting dalam pengobatan imunoterapi kanker. Di Indonesia belum tersedia data empirik profil karakteristik yang berkaitan dengan ekspresi PD-L1 serta respon tumor terhadap radiasi pada kanker serviks.Metode: Penelitian ini memeriksa ekspresi PD-L1 intratumoral pada jaringan biopsi karsinoma sel skuamosa serviks pre dan paska radiasi eksterna dengan menggunakan metode ELISA dan IHK, pemeriksaan IHK menggunakan antibodi clone 28-8 dari Abcam. Pemeriksaan CT scan evaluasi sebelum radiasi dan 2 bulan setelah radiasi dipakai sebagai alat untuk menilai respon terapi radiasi.Hasil: Dari 31 pasien yang ikut serta, terdapat 29 pasien yang telah dilakukan pemeriksaan ekspresi PD-L1 sebelum dan sesudah radiasi, selanjutnya hanya 22 pasien yang telah menjalani CT scan evaluasi. Ekspresi PD-L1 ELISA paska radiasi eksterna berbeda bermakna pada tumor berukuran ≥5cm (p=0,015) dan ekspresi PD-L1 IHK berbeda bermakna pada sel tumor berkeratin (p=0,023), pada pasien dengan grade IHK yang difus (+3) resiko relatif untuk respon komplit 0,5 kali dibandingkan dengan grade IHK yang  tidak difus.Uji korelasi perbedaan selisih ekspresi (delta) dan rasio PD-L1 ELISA menunjukkan tidak ada korelasi (R2 = 0,217) dan (R2 = 0,194) terhadap respons, begitu juga hasil pada hasil pemeriksaan ekspresi PD-L1 IHK tidak ada perbedaan bermakna pada kategori kenaikan, tetap dan penurunan, tetapi ketika kategori dirubah menjadi penurunan dan tidak ada penurunan didapatkan nilai p yang lebih baik (p=0,161 vs p=.0,613)Kesimpulan: Tidak terdapat perbedaan bermakna antara ekspresi PD-L1 pre dan paska radiasi terhadap respon, akan tetapi terdapat tren penurunan kadar PD-L1 IHK berkaitan dengan respon terapi.

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Background: Early-stage cervical cancer can be managed properly, but at a locally advanced stage it has a poor prognosis. The standard therapy available is still suboptimal and has disturbing side effects. In certain circumstances, tumors can undergo metastases or progressives, one of which is due to the binding of PD-L1 with T lymphocyte cells so that cervical cancer is protected from the immune response. In Indonesia, there is no available empirical data on the characteristic profiles related to PD-L1 expression and tumor response to radiation in cervical cancer.

Method: This study examined intratumoral PD-L1 expression in biopsy tissue of squamous cell carcinoma of cervical cells pre and post external radiation using ELISA and IHC methods, IHC examination using antibody clone 28-8 from Abcam. CT scan evaluation before radiation and 2 months after radiation are used as a tool to assess the response of radiation therapy.

Results: Of the 31 patients who participated, there were 29 patients who had examined the expression of PD-L1 before and after radiation, then only 22 patients who had undergone a CT scan evaluation. Expression of PD-L1 ELISA after external radiation was significantly different in tumors of ≥5cm (p=0.015) and expression of PD-L1 IHC was significantly different in keratinous tumor cells (p = 0.023), in patients with diffuse IHC grade (+3) relative risk to complete response of 0.5 times compared to the grade of IHC which is not diffuse. Correlation test difference in expression difference (delta) and PD-L1 ELISA ratio showed no correlation (R2 =0.217) and (R2=0,194) to the response, as well as results on the examination results of PD-L1 IHC expression there was no significant difference in the increased category, constant and decrease, but when the category is changed to decrease and there is no decrease, a better p-value is obtained (p=0.161 vs p=0.613)

Conclusion: There was no significant difference between the expression of PD-L1 pre and post-radiation to the response, but there was a trend of decreasing PD-L1 IHC levels concerning therapeutic response."