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Renindra Ananda Aman

Identifikasi faktor prediksi radiosensitivitas tumor sel GLIA : tinjauan khusus pada angiogenesis, proliferasi dan apoptosis sebagai perangai biologik tumor

Depok: Fakultas Kedokteran Universitas Indonesia, 2008

D1744

UI - Disertasi Open Universitas Indonesia Library

Paul Steven

Ekspresi imunohistokimia Ki-67 dan p53 sebagai faktor prediktor rekurensi giant cell tumor tulang = Expression of Ki-67 And p53 as an immunohistochemistry predict marker for recurrence in giant cell tumor of bone

"Pendahuluan : Giant Cell Tumor tulang (GCT) merupakan tumor tulang jinak yang dapat secara lokal bersifat agresif dengan tingkat rekurensi mencapai 20%. Antigen Ki-67 dan p53 adalah penanda imunohistokimia pada GCT yang menandakan proliferasi sel dan supresi tumor. Penelitian ini menganalisis hubungan antara penanda Ki-67 dan p53 dengan rekurensi pada kasus GCT.

Metode : Penelitian adalah suatu studi Cross-sectional kategorikal. Data yang dikumpulkan adalah data demografis pasien, keterangan terkait diagnosis dan tindakan serta hasil pemeriksaan Ki-67 dan p53. Data pasien Ekspresi Ki-67 dan p53 dievaluasi dengan teknik pewarnaan imunohistokimia menggunakan metode avidin-biotin complex perioxidase dengan menggunakan kit LSAB2.

Hasil : Terdapat 26 laki-laki dan 37 perempuan dengan usia rata-rata adalah 34,77 tahun berkisar antara 16 sampai 61 tahun. 13 kasus dengan rekurensi lokal. Tidak terdapat hubungan antara rekurensi dengan karakteristik tumor (jenis kelamin, usia, ukuran tumor, lokasi tumor, stadium tumor dan tindakan operasi). Tidak ada hubungan antara Ki-67 (p=0.524) dan rekurensi lokal serta terdapat hubungan yang signifikan antara p53 dengan rekurensi lokal (p=0.048).

Kesimpulan : Ekspresi Ki-67 tidak berhubungan dengan rekurensi, sedangkan ekspresi p53 berhubungan dengan rekurensi giant cell tumor tulang. Tidak terdapat hubungan antara rekurensi lokal dengan karakteristik tumor (jenis kelamin, usia, lokasi tumor, ukuran tumor, stadium tumor dan tindakan operasi).

Introduction : Giant cell tumor of bone (GCTB) is a benign neoplasm that may be locally aggressive with recurrence rate reaching 20%. Ki-67 and p53 are immunochemistry markers that marked cell proliferations and tumor suppression. This research analyze the association between Ki-67 and p53 with recurrence of GCT.

Method :This study is a Cross-sectional categorical study. Demography of the patients, diagnosis and treatment related to the GCT, and Ki-67 and p53 results were taken. The expression of Ki-67 and p53 were evaluated using a immunochemistry staining with avidin-biotin complex peroxidase by using KSAB2 kit.

Result : There are 26 men and 37 women with an average age is 34.77 years ranged from 16 to 61 years. 13 cases with local recurrence. There is no association between recurrence and tumor characteristics (sex, age, tumor size, tumor location, stage and operation). There is no association between Ki-67 with local recurrence (p=0,524) and a significant association between p53 and local recurrence (p=0,048).

Conclusion : Ki-67 was not associated with recurrence, mean while p53 was associated with recurrence of GCT. There is no association between recurrence and tumor characteristics (sex, age, tumor size, tumor location, stage, and operation)."

Depok: Fakultas Kedokteran Universitas Indonesia, 2017

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UI - Tugas Akhir Universitas Indonesia Library

Kusmardi

Analisis daya sitotoksik sel killer mencit C3h dan Gr yang diaktivasi interleukin-2 terhadap sel tumor kelenjar susu mencit Singenik dan Alogenik

"ABSTRAK

Ruang lingkup dan Cara penelitian :

Pemberian interleukin-2 (IL-2) pada sel killer tidak selalu menghasilkan peningkatan daya sitotoksiknya terhadap sel tumor. Keberhasilan aktivasi IL-2 in vitro sangat dipengaruhi oleh sifat intrinsik balk sel killer sebagai sel efektor imunologik maupun sel tumor sebagai sel sasaran. Untuk melihat pengaruh beberapa faktor seperti pengayaan limfosit T, asal sel efektor dan perbedaan sifat genetik yang terkait pada sal killer akibat pemberian IL-2, pada penelitian ini digunakan 2 strain mencit yaitu C3H dan GR sebagai sumber limfosit dan sel tumor kelenjar susu, baik dalam kombinasi sigenik maupun alogenik.

Efektor imun yang dipakai berasal dari limpa dan kelenjar getah bening (KGB) mencit normal dan bertumor baik terlebih dahulu mengalami pengayaan limfosit T dengan nylon-wool maupun tidak sebelum mengalami aktivasi dengan rIL-2. Aktivasi limfosit dengan IL-2 rekombinan (rIL-2) dilakukan dengan menambahkan 250 UI/ml, 1000 UI/ml, 1500 UI/ml rIL-2 pada kultur sel efektor dan diinkubasi dalam inkubator CO2 selama 72 jam.

Sedangkan sel sasaran yang dipakai dalam kombinasi singenik dan alogenik untuk menguji daya sitotoksik sel killer, berupa biakan in vitro sel tumor kelenjar susu. Pengukuran daya sitotoksik dilakukan dengan menghitung persentase sel hidup dari sekurang-kurangnya 200 sel menggunakan pewarna eksklusi trypan blue. Daya sitotoksik absolut merupakan perbandingan antara selisih persentase sel hidup dalam mikrowell kontrol dan mikrowell sampei dengan persentase sel hidup dalam mikrowell kontrol, sedangkan daya sitotoksik relatif merupakan perbandingan antara selisih persentase sel sasaran hidup pada efektor mencit normal dan bertumor dengan persentase sel sasaran hidup pada efektor mencit normal.

Hasil dan kesimpulan:

Daya sitotoksik sel killer teraktivasi rIL-2 berasal dari organ limpa berbeda bermakna dengan efektor berasal dari kelenjar getah bening. Dengan menggunakan sel sasaran singenik, daya sitotoksik efektor berasal dari kelenjar getah bening mencit C3H yang tidak mengalami pengayaan, lebih tinggi dibandingkan efektor berasal dari limpa. Pada mencit GR terjadi sebaliknya, dengan kondisi yang sama, efektor berasal dari KGB lebih rendah daya sitotoksiknya dibandingkan efektor berasal dari limpa. Sedangkan daya sitotoksik, efektor berasal dari KGB terhadap sel sasaran alogenik tetap lebih tinggi dibandingkan efektor berasal dari limpa pada mencit C3H, dan hampir sama pada mencit GR.

Pengayaan limfosit T, tidak menunjukkan pengaruh terhadap daya sitotoksik sel killer baik berasal dari limpa maupun KGB mencit C3H kecuali daya sitotoksik efektor berasal dari KGB terhadap sel sasaran alogenik. Sebaliknya pada efektor berasal dari mencit GR, pengayaan limfosit T berpengaruh baik terhadap sel sasaran singenik maupun alogenik.

Penelitian ini juga menunjukkan pengaruh rIL-2 terhadap daya sitotoksik sel killer yang tinggi, umumnya dicapai dengan dosis pemberian 1000 UI/ml dengan pengujian FJT 2511 dan 50/1. Pemberian rIL-2 dengan dosis 250 UI/ml dan 1500 UI/ml juga dapat meningkatkan daya sitotoksik sel killer baik efektor berasal dari limpa maupun KGB mencit C3H dan GR terhadap sel sasaran singenik dan alogenik.

ABSTRACT
Analysis Of Interleukin-2 Activated Killer Cells Cytotoxicity Of C3H And Gr Mice Against Syngenic and Allogenic Mice Mammary Tumor CellsScope and methods of study: Interleukin-2 (IL-2) treatment on killer cells has not always result in increased cytotoxicity against tumor cells. The result of IL-2 in vitro activation is influenced by an intrinsic factor, both the killer cells as immunological effector and the tumor cells as target cells. In order to analyze the effect of several factors namely T lymphocytes enrichment, the origin of effector cells and the major histocompatibility complex (MHC) restriction, in this study we use two strains of mice, C3H and GR as the source of effector cells and mammary tumor cells, both in syngenic and allogenic combination.
The immune effector used were both spleen cells and lymph node cells derived from normal and tumor-bearing mice, with or without T lymphocytes enrichment through nylon-wool column, prior activation by recombinant IL-2 (A-2). Lymphocytes were activated by 250, 1000 and 1500 IU/ml rIL-2 for 72 hours in CO2 incubator.
In vitro culture of mammary tumor cells were used as target cells for testing the killer cells cytotoxicity both in syngenic and allogenic combination. The cytotoxicity was assesed by counting the reduction of living cells enumerated from at least 200 cells using trypan blue exclusion method. The absolute cytotoxicity was determined by the ratio between the difference of the percentage of living target cells in control and sample with percentage of living target cells in control. While the relative cytotoxicity was determined by the ratio between the difference the percentage living target cells in normal and tumor-bearing mice effector cells with the percentage of living target cells in normal mice effector cells.
Result and conclusion: The cytotoxicity of IL-2 activated killer cells derived from spleen showed a significant difference from the killer cells derived from lymph node. The cytotoxicity against singenic target cells of C3H mice effector derived from lymph node without T lymphocytes enrichment was higher than the effector derived from the spleen. In contrast, the cytotoxicity of effector cells derived from GR mice lymph node showed a lower cytotoxicity than effector cells derived from the spleen. While the cytotoxicity against allogenic combinations, effector derived from the lymph node remained higher as compared to the effector derived from the spleen of C3H mice, almost similar with the GR mice.
T lymphocytes enrichment did not influence the cytotoxicity of killer cells both derived from spleen and lymph node against allogenic target cells. On the other hand, T lymphocytes enrichment of effector derived from GR mice caused elevation of the cytotoxicity both in syngenic or allogenic combination.
This study also showed the effect of IL-2 in increasing the cytotoxicity of killer cells, which was usually achieved by the 1000 IU/ml dosage in E/T 25/1 and 50/1 ratio. However the 250 and 1500 IU/ml dosage also showed the effect of IL-2 in increasing the cytotoxicity of killer cells derived from spleen or lymph node of C3H and GR mice against both syngenic and allogenic target cells."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 1998

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UI - Tesis Membership Universitas Indonesia Library

Isabelle Deli

Ekspresi TP53 dan aktifitas proliferasi Ki-67 pada berbagai derajat klasifikasi Bartl di neoplasma sel plasma = The expression of TP53 and the proliferation activity Ki-67 at various degrees of Bartl's classification in plasma cell neoplasm

"[ABSTRAK

Latar belakang: Neoplasma sel plasma (NSP) adalah proliferasi sel plasma neoplastik yang tumbuh soliter menjadi plasmasitoma tulang soliter (PTS) dan plasmasitoma ekstrameduler (PEM) serta multipel (MM)). Saat ini perjalanan penyakit dari plasmasitoma menjadi MM sulit diprediksi. Bartl mengklasifikasikan derajat keganasan berdasarkan histomorfologik menjadi rendah, sedang dan tinggi. Penelitian ini bertujuan menggunakan klasifikasi Bartl untuk menilai perjalanan PTS dan PEM menjadi MM dihubungkan dengan ekspresi TP53 dan Ki-67.

Bahan dan cara: Pada 32 kasus NSP yang berasal dari PTS 14 kasus, PEM 5 kasus, maupun MM sebanyak 13 kasus, diklasifikasikan menjadi 3 kelompok derajat keganasan menurut Bartl yaitu derajat keganasan ringan, sedang dan tinggi. Selanjutnya dilakukan pulasan IHK TP53 dan Ki-67 pada seluruh kasus dan dihitung persentase positifitas.

Hasil: Berdasarkan derajat keganasan, derajat rendah ditemukan pada 10 (31,2%) MM, derajat sedang pada 5 (15,6%) PTS dan derajat tinggi pada 2 (6,2%) PTS dan PEM. Peningkatan ekspresi TP53 ditemukan pada derajat Bartl yaitu median derajat rendah 4%, derajat sedang 16%, dan derajat tinggi 10%. Terdapat perbedaan ekspresi TP53 yang bermakna antara derajat keganasan rendah dan sedang (p=0,004). Rerata indeks proliferasi Ki-67 pada derajat keganasan rendah 57%, derajat sedang 44,6%, dan derajat tinggi 32,6%. Tidak ditemukan perbedaan antara indeks proliferasi Ki-67 dengan derajat keganasan menurut Bartl (p=0,339). Tidak terdapat hubungan antara ekspresi TP53, Ki-67 dengan usia. Kesimpulan: Peningkatan ekspresi TP53 pada NSP sejalan dengan peningkatan derajat keganasan Bartl, terutama pada derajat rendah dan sedang. Klasifikasi Bartl ditambah dengan pulasan TP53 saja tidak cukup untuk memprediksi perkembangan PTS dan PEM menuju MM.

ABSTRACT

Background: Plasma cell neoplasm (PCN) is a neoplastic plasma cells proliferation including solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Until now the development of disease to MM is unpredictable. Bartl classifies the degrees of malignancy histomorphologically as low, intermediate and high. This research aims using Bartl's classification and expression of TP53 and Ki-67 to assess the development of SBP and EMP to MM.

Materials and methods: In 32 cases of PCN derived from 14 cases of SBP, 5 cases of EMP, and 13 MM case, then classified into 3 groups based on Bartl's degrees of malignancy as low, intermediate, and high. Furthermore all cases stained by IHC TP53 and Ki-67 and evaluated the percentage of positivity. Results: Bartl's low degree was found in 10 (31,2%) MM case, intermediate in 5 (15,6%) SBP and high in 2 (6,2%) SBP and EMP. TP53 expression, obtainable at 4% of low, 16% of intermediate, and 10% of high degree. There is significant difference between TP53 expression in low and intermediate degree (p = 0,004). Mean proliferation index of Ki-67 is 57% in low, 44,6% in intermediate and 32,6% in high degree. There is no significant difference of Ki-67 proliferation indexes among the group (p = 0,339). There is no correlation between expressions TP53, Ki-67 and age.

Conclusion: Increasing expression TP53 is in line with Bartl's degrees of malignancy, especially on low and inter.;Background: Plasma cell neoplasm (PCN) is a neoplastic plasma cells proliferation including solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Until now the development of disease to MM is unpredictable. Bartl classifies the degrees of malignancy histomorphologically as low, intermediate and high. This research aims using Bartl?s classification and expression of TP53 and Ki-67 to assess the development of SBP and EMP to MM.

Materials and methods: In 32 cases of PCN derived from 14 cases of SBP, 5 cases of EMP, and 13 MM case, then classified into 3 groups based on Bartl?s degrees of malignancy as low, intermediate, and high. Furthermore all cases stained by IHC TP53 and Ki-67 and evaluated the percentage of positivity. Results: Bartl?s low degree was found in 10 (31,2%) MM case, intermediate in 5 (15,6%) SBP and high in 2 (6,2%) SBP and EMP. TP53 expression, obtainable at 4% of low, 16% of intermediate, and 10% of high degree. There is significant difference between TP53 expression in low and intermediate degree (p = 0,004). Mean proliferation index of Ki-67 is 57% in low, 44,6% in intermediate and 32,6% in high degree. There is no significant difference of Ki-67 proliferation indexes among the group (p = 0,339). There is no correlation between expressions TP53, Ki-67 and age.

Conclusion: Increasing expression TP53 is in line with Bartl?s degrees of malignancy, especially on low and inter, Background: Plasma cell neoplasm (PCN) is a neoplastic plasma cells proliferation including solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Until now the development of disease to MM is unpredictable. Bartl classifies the degrees of malignancy histomorphologically as low, intermediate and high. This research aims using Bartl’s classification and expression of TP53 and Ki-67 to assess the development of SBP and EMP to MM.

Materials and methods: In 32 cases of PCN derived from 14 cases of SBP, 5 cases of EMP, and 13 MM case, then classified into 3 groups based on Bartl’s degrees of malignancy as low, intermediate, and high. Furthermore all cases stained by IHC TP53 and Ki-67 and evaluated the percentage of positivity. Results: Bartl’s low degree was found in 10 (31,2%) MM case, intermediate in 5 (15,6%) SBP and high in 2 (6,2%) SBP and EMP. TP53 expression, obtainable at 4% of low, 16% of intermediate, and 10% of high degree. There is significant difference between TP53 expression in low and intermediate degree (p = 0,004). Mean proliferation index of Ki-67 is 57% in low, 44,6% in intermediate and 32,6% in high degree. There is no significant difference of Ki-67 proliferation indexes among the group (p = 0,339). There is no correlation between expressions TP53, Ki-67 and age.

Conclusion: Increasing expression TP53 is in line with Bartl’s degrees of malignancy, especially on low and inter]"

Fakultas Kedokteran Universitas Indonesia, 2015

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UI - Tugas Akhir Universitas Indonesia Library

Lisnawati

Peran sel punca kanker, faktor apoptosis, DNA repair, dan telomerase terhadap respons terapi radiasi pada kanker serviks stadium III B: kajian khusus pada ekspresi SOX2 dan OCT4 = Role of cancer stem cell apoptotic factor DNA repair and telomerase toward radiation therapy response in stage iiib cervical cancer special study on SOX2 and OCT4 expression

"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.

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. "

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2017

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UI - Disertasi Membership Universitas Indonesia Library

Tri Asmaningrum Larasati

Model Prediksi Kebutuhan Tranfusi Packed Red Cell Perioperatif pada Operasi Tumor Tulang: Studi Retrospektif di Unit Pelayanan Bedah Terpadu Rumah Sakit Cipto Mangunkusumo = The Prediction Model for Red Blood Cell Tranfusion in Bone Tumor Surgery: A Retrospective Study in The Surgical Centre of Cipto Mangunkusumo Hospital

"Dua puluh persen dari operasi tumor tulang membutuhkan tranfusi darah Packed Red Cell (PRC) intraoperatif, dengan volume tranfusi rata-rata 1200 ml.¹^,². Kelebihan permintaan darah menimbulkan kerugian biaya. Selama januari-juli 2017, RSCM mengalami kerugian Rp 5,381,100,000 akibat terbuangnya 7972 kantung darah. Penelitian ini bertujuan membuat model prediksi kebutuhan tranfusi PRC peribedah pada operasi tumor tulang berdasarkan faktor-faktor letak, ukuran, karakteristik keganasan tumor, nilai Hb prabedah dan nilai ASA prabedah. Penelitian ini memiliki desain kohort retrospektif dan dilakukan pada pasien dewasa yang menjalani pembedahan tumor pada tahun 2015-2017. Analisis dilakukan pada 82 data yang didapat dari rekam medis. Uji bivariat menunjukkan letak tumor, ukuran tumor, karakteristik keganasan tumor, nilai Hb prabedah dan nilai ASA prabedah memiliki hubungan bermakna terhadap kebutuhan tranfusi PRC perioperatif. Analisis multivariat regresi linier menunjukan hanya letak tumor dan nilai Hb prabedah yang merupakan prediktor bermakna. Model alternatif hasil regresi logistik dan analisis tambahan dibuat untuk menentukan probabilitas tranfusi PRC perioperatif.

Twenty percent of bone tumor surgery requires intraoperative blood tranfusion, mostly Packed Red Cell (PRC). Approximately 1200ml or 4-6 unit of PRC transfusion is given in a bone tumor surgery.^1,2Less accurate estimation of the need of transfusion caused excessively wasted blood requests and led to high expense loss. In January-July 2017 there were 7972 wasted bags of blood product, resulting in a loss of Rp. 5,381,100,000 in Cipto Mangunkusumo Hospital. This study aimed to develop a prediction model for the need of perioperative red blood cell transfusion in bone tumor surgery. This is a retrospective cohort study of adults patients underwent bone tumor surgery between 2015 to 2017. Data was retrieved from the medical records and 82 subjects were included. The bivariate analysis showed that tumor location, size, malignancy, preoperative hemoglobin level and ASA physical status were significantly correlated with perioperative needs of red blood cell transfusion. However, the linear regression showed that only tumor location and preoperative hemoglobin level were considered as significant predictors. Therefore we obtained an alternative model from logistic regression to determine the probability of the need for perioperative PRC transfusion and add additional factors in the analysis."

2018

T-Pdf

UI - Tesis Membership Universitas Indonesia Library

Annisa Syafitri

Perbandingan circulating tumor cell sebelum dan setelah kemoterapi pada pasien kanker payudara stadium lokal lanjut dan lanjut serta faktor yang memengaruhinya = Comparison of circulating tumor cells (CTC) before and after chemotherapy for locally advance or advance breast cancer patients and its influencing factors

"Latar belakang: CTC sebagai bagian dari liquid biopsy berperan dalam melakukan monitoring pasien kanker payudara yang menjalani terapi. Adanya CTC menjadi pertanda resistensi terapi dan memengaruhi prognosis pasien. Penelitian ini bertujuan melihat adakah perubahan nilai CTC pada pasien kanker payudara stadium lokal lanjut atau lanjut yang mendapatkan kemoterapi serta melihat perubahan nilai CTC tersebut apakah dipengaruhi oleh usia, status menopause, subtipe, metastasis, dan grade.

Metode: Didapatkan 30 sampel pasien kanker payudara stadium lokal lanjut atau lanjut yang akan mendapatkan kemoterapi berbasis Anthracycline dan Taxan. Pre kemoterapi pasien diambil darah perifer dan dilakukan pemeriksaan CTC menggunakan flowcytometry dengan antibodi EpCAM. Pasien lalu menjalani siklus kemoterapi hingga lengkap. Setelah itu pasien kembali diambil darah perifer dan diperiksa nilai CTC post kemoterapi.

Hasil: Dari ke 30 sampel, didapatkan mean usia 47,93+7.30. Sebanyak 56,7 (n=17) belum menopause, 43,3% status tumor T3 dan T4, status kelenjar getah bening terbanyak adalah N0 dan N1 (43,3%). Hanya 2 pasien yang ditemukan ada metastasis. 56,7% pasien dengan grade 3, dan subtipe terbanyak adalah luminal B ( 63,4%, n=19). Terdapat 22 pasien (73,3%) dengan ER positif, 14 pasien (46,7%) dengan PR positif. Terdapat 11 pasien (36,7%) dengan Her2 positif dan 21 pasien (70%) dengan Ki67 high proliferation. Hasil CTC pre kemoterapi didapatkan nilai median 1460,50 sedangkan CTC post kemoterapi didapatkan nilai median 415,50 dilakukan uji Wilcoxon dan perbedaan bermakna dengan nilai p=0,002. Analisis multivariat regresi linier dihubungkan antara penurunan nilai CTC terhadap usia, status menopause, subtipe, metastasis, dan grading didapatkan status menopause berhubungan bermakna terhadap perubahan nilai CTC (p<0,05).

Kesimpulan: CTC pada pasien kanker payudara stadium lokal lanjut dan lanjut setelah kemoterapi lebih rendah bermakna dibandingkan sebelum kemoterapi. Status menopause memiliki hubungan bermakna terhadap penurunan jumlah CTC setelah kemoterapi pada kanker payudara stadium lokal lanjut dan lanjut

.
Background: As part of liquid biopsy, CTCs play a role in monitoring breast cancer patients undergoing therapy. The existence of CTCs is a sign of therapy resistance and affects patient prognosis. This study aims to examine whether there are changes in CTC values in patients with locally advanced or advanced breast cancer, who receive chemotherapy and are influenced by age, menopause status, subtype, metastasis, and grade.
Method: Of the 30 samples of locally advanced or advanced breast cancer patients receiving Anthracycline and Taxan-based chemotherapy were obtained. Pre-chemotherapy, peripheral blood, was drawn and CTCs were examined using flow cytometry with EpCAM antibody. Patients then undergo a complete chemotherapy cycle. After that, the patients were again taken peripheral blood and examined for post-chemotherapy CTC values.
Result: The study was conducted at Cipto Mangunkusumo Hospital, started from December 2022 to December 2023. Of the 30 samples with the mean age was 47,93+7,30. A total of 56,7 (n=17) were not menopause, 43,3% of tumor status with the T3 and T4, and the most common lymph node status with the N0 and N1 (43,3%). Only two patients were found to have metastasis. Then, 56,7% of patients had grade 3, and the most common subtype was luminal B (63,4%, n=19). There were 22 patients (73,3%) with ER positive, 14 patients (46,7%) with PR positive, 11 patients (36,7%) with Her2 positive, and 21 patients (70%) with Ki67 high proliferation. Pre-chemotherapy CTC results obtained a median value of 1460.50, Meanwhile, post-chemotherapy CTC obtained a median value of 415,50. Wilcoxon test was performed and the difference was significant with a value of p = 0,002. Multivariate linear regression analysis was correlated between the decrease in CTC values with age, menopause status, subtype, metastasis, and grading. The menopausal status has a significant association with decrease CTC values (p<0,05).
Conclusion: CTC in locally advanced and advanced breast cancer patients after chemotherapy was significantly lower than before chemotherapy. menopause status has a significant association with decreased CTC values after chemotherapy in locally advanced and advanced breast cancer."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2024

SP-pdf

UI - Tugas Akhir Universitas Indonesia Library

Irah Namirah

Isolasi dan identifikasi fraksi emestrin B pada fungi laut Emericella nidulans beserta uji aktivitas sitotoksik terhadap sel lestari kanker = Isolation and identification of emestrin B fraction in marine fungi Emericella nidulans and cytotoxicity assay to cancer cell lines

"ABSTRAK

Fungi Emericella nidulans strain MFW39 yang diisolasi dari ascidia Aplidium

longithorax dari Taman Nasional Laut Wakatobi, Sulawesi Tenggara memiliki aktivitas

sitotoksik terhadap beberapa sel lestari kanker. Senyawa yang berhasil diisolasi dan

bersifat sitotoksik adalah senyawa emestrin yang memiliki gugus ETP

(epipolithiodioxopiperazine). Senyawa emestrin memiliki beberapa jenis derivat. Pada

penelitian ini bertujuan untuk mengisolasi, mengidentifikasi dan menguji bioaktivitas

antikanker terhadap salah satu derivat senyawa emestrin. Dari hasil penelitian

didapatkan jenis derivat senyawa emestrin adalah emestrin B. Proses elusidasi struktur

dilakukan dengan metode HPLC, UPLC-MS, 1H-NMR dan 13C-NMR. Hasil uji

aktivitas sitotoksik dengan metode MTT (Microculture Tetrazolium Technique)

menunjukan IC50 fraksi emestrin B berkisar pada 0,18 􀂱 4,21 µg/mL. Urutan aktivitas

sitotoksik fraksi emestrin B terhadap sel lestari T47D [kanker payudara] (0,18 µg/mL) >

WiDr [kanker usus] (1,21 µg/mL) > HeLa [kanker serviks] (1,91 µg/mL). Fraksi

emestrin B juga bersifat sitotoksik terhadap sel lestari normal [Vero] (4,21 µg/mL). Oleh

karena itu fraksi emestrin yang berhasil diisolasi adalah emestrin B dengan rumus

struktur C27H22N2O10S3 dan memiliki potensi aktivitas antikanker.

ABSTRACT

Emericella nidulans marine fungi strain MFW39 was isolated from ascidia Aplidium

longithorax collected from Wakatobi Marine National Park, South East Sulawesi has a

biological activities to cancer cell lines. Emestrin was a compound with an ETP

(epipolithiodioxopiperazine) group that found in Emericella nidulans marine fungi have

cytotoxicity properties. Emestrin and another compound that related have the ETP

group. The research include isolation, identification and cytotoxicity assay of compound

that related with emestrin. Elucidation structure of molecule with HPLC, UPLC-MS,

1H-NMR and 13C-NMR. The fraction emestrin B have bioactivity to cancer cell lines in

range 0,18 􀂱 4,21 µg/mL with MTT (Microculture Tetrazolium Technique) assay method.

Order of anticancer activity was breast cancer cell line [T47D] (0,18 µg/mL) > colon

cancer cell line [WiDr] (1,21 µg/mL) > cancer cervic cell line [HeLa] (1,91 µg/mL). The

fraction of emestrin B have a toxicity to normal cell line [Vero] (4,21 µg/mL). The result

shows compound fraction that succeed to isolated was emestrin B (C27H22N2O10S3) and

have a potency anticancer activity."

Depok: Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Indonesia, 2013

T35069

UI - Tesis Membership Universitas Indonesia Library

Weny Yusnita

Peningkatan akurasi diagnosis fibroadenoma dan tumor filodes jinak payudara pada sediaan core biopsy dengan menggunakan skoring gambaran histopatologik = Increasing diagnostic accuracy of fibroadenoma and benign phyllodes breast tumor in core biopsy using histopathologic scoring system

"ABSTRAK

Latar belakang: Fibroadenoma dan tumor filodes jinak merupakan tumor

fibroepitelial dengan gambaran histopatologik yang tumpang tindih. Saat ini

banyak pengambilan jaringan tumor payudara secara core biopsy, termasuk pada

tumor fibroepitelial. Jumlah jaringan yang sedikit dan gambaran histopatologik

yang tumpang tindih sering menyulitkan Dokter Spesialis Patologi Anatomik

dalam menentukan diagnosis fibroadenoma dan tumor filodes jinak. Penelitian ini

bertujuan untuk mengetahui gambaran histopatologik apa saja yang bermakna

untuk mendiagnosis fibroadenoma dan tumor filodes jinak dan untuk menguji

apakah diagnosis fibroadenoma dan tumor filodes jinak pada core biopsy dengan

menggunakan sistem skoring lebih baik dibandingan tanpa skoring.

Bahan dan cara: Penelitian ini merupakan suatu uji diagnostik. 57 kasus

fibroadenoma dan tumor filodes jinak yang memiliki slaid core biopsy dan

mastektomi/lumpektomi/eksisi dinilai ulang tanpa sistem skoring dan

menggunakan skoring. Gambaran histopatologik yang dinilai pada sistem skoring

adalah selularitas stroma, atipia inti, fragmentasi jaringan, infiltrasi lemak, mitosis

dan heterogenitas stroma. Kemudian dilakukan analisis statistik, uji diagnostik

dan uji kappa.

Hasil: Selularitas stroma, heterogenitas stroma dan fragmentasi jaringan lebih

sering ditemukan pada tumor filodes jinak dan berbeda bermakna (p=0,001;

p=0,000; p=0,021). Spesifisitas pada sistem skoring meningkat sebesar 17,9%.

Nilai duga positif dan nilai duga negatif pada sistem skoring meningkat sebesar

11,9% dan 5,1%. Area under curve (AUC) meningkat 8,9%. Uji Cohen?s kappa

antara diagnosis core biopsy tanpa dan dengan skoring bernilai rendah (0,545).

Kesimpulan: Adanya peningkatan spesifisitas, nilai duga positif dan AUC

menunjukkan bahwa penilaian core biopsy sistem skoring lebih baik

dibandingkan tanpa skoring dan dapat menjadi acuan untuk diagnosis fibroadenoma dan tumor filodes jinak.

ABSTRACT

Background: Fibroadenoma and benign phyllodes tumor are kinds of fibroepithelial tumor which have overlapping histopathological features. Recently, core biopsy is commonly performed to determine breast tumor, including fibroepithelial tumor. Small amount of tissue and overlapped histopathological features often complicate the Pathologist in diagnosing both. This study aims to describe the histopathological appearance which needed to diagnose fibroadenoma and benign phyllodes tumor and to verify if the diagnosis of fibroadenoma and benign phyllodes tumor in core biopsy using scoring system is more accurate than without scoring system.

Method: This study was a diagnostic test, in which 57 cases of fibroadenoma and benign phyllodes tumor which had undergone core biopsy and mastectomy/excision were re-assessed using and without using scoring system. Histopathologic features which assessed using scoring system were stromal cellularity, nuclear atypia, tissue fragmentation, fat infiltration, mitotic figure, stromal heterogeneity. Analytical statistic, diagnostic test, accuracy test and Kappa test were done.

Results: Stromal cellularity, stromal heterogeneity and tissue fragmentation mostly found in benign phyllodes tumor and significantly different (p=0,001; p=0,000; p=0,021).There were significant differences between stromal cellularity (p=0,001), stromal heterogeneity (p=0,000), and tissue fragmentation (p=0,021) in diagnosis of benign phyllodes tumor. Specificity in scoring system increased by

17,9 %. Positive predictive value, negative predictive value and accuracy increased in scoring system (11,9% and 5,1%). Area under curve (AUC) increased by 8,9%. Cohen's Kappa test between core biopsy diagnosis without using and using scoring system had low result(0,545).

Conclusion: The increasing of specificity, positive predictive value, accuracy and AUC proved that core biopsy with scoring system is more accurate than without scoring. This can be used as reference to diagnose fibroadenoma and benign phyllodes tumor.;Background: Fibroadenoma and benign phyllodes tumor are kinds of fibroepithelial tumor which have overlapping histopathological features. Recently, core biopsy is commonly performed to determine breast tumor, including fibroepithelial tumor. Small amount of tissue and overlapped histopathological features often complicate the Pathologist in diagnosing both. This study aims to describe the histopathological appearance which needed to diagnose fibroadenoma and benign phyllodes tumor and to verify if the diagnosis of fibroadenoma and benign phyllodes tumor in core biopsy using scoring system is more accurate than without scoring system.

Fakultas Kedokteran Universitas Indonesia, 2015

SP-PDF

UI - Tugas Akhir Universitas Indonesia Library

Thia Sabel Permata

Implementasi algoritma markov clustering pada jaringan interaksi protein protein penghambat tumor (TP53) = Implementation of markov clustering algorithm on protein protein interaction network of tumor suppressor protein (TP53)

"Pembentukan dan perkembangbiakan sel tumor terjadi jika protein khusus yang mengatur pembelahan sel mengalami perubahan fungsi, ekspresi gen atau hilang keduanya. Salah satu protein penekan tumor yang berperan dalam pengendalian siklus sel adalah protein TP53. Pada sebagian besar perubahan genetik dalam tumor, baik delesi atau mutasi pada lebih dari 50% kanker pada manusia, ditemukan mutan TP53 yang merupakan faktor beresiko tinggi terhadap kanker. Oleh karena itu, penting untuk melakukan studi tentang pengelompokan interaksi protein-protein TP53. Interaksi protein secara umum disajikan dalam jaringan graf (graph network) dengan protein sebagai simpul dan interaksinya sebagai busur. Algoritma Markov Clustering (MCL) adalah satu metode graph clustering yang dibuat berdasarkan simulasi dari flow stokastik pada suatu graf. Dalam skripsi ini, dibahas mengenai implementasi algoritma MCL pada data interaksi protein-protein TP53 dengan menggunakan bahasa pemrograman Python. Algoritma MCL terdiri dari tiga operasi utama yaitu ekspansi, penggelembungan, dan pemotongan. Selanjutnya, dilakukan analisis hasil clustering dari simulasi algoritma MCL dengan menggunakan parameter ekspansi, penggelembungan dan faktor pengali yang berbeda-beda. Berdasarkan analisis hasil clustering yang dilakukan, algoritma MCL terbukti menghasilkan robust cluster dengan protein TP53 sebagai pusat cluster untuk setiap hasil clustering.

The formation and proliferation of tumor cells occurs if a special protein that regulates cell division changing the function, gene expression or lost both. One of the tumor suppressor protein that plays a role in controlling the cell cycle is the TP53 protein. In most of the genetic changes in the tumor, either deletions or mutations in more than 50% of human cancers, it found that mutant of TP53 is a high risk factor for cancer. Therefore, it is important to conduct studies on protein-protein interactions clustering of TP53. Protein interactions are generally presented in the graph network with proteins as nodes and interactions as edges. Markov Clustering (MCL) algorithm is a graph clustering method which is based on a simulation of stochastic flow on a graph. This minithesis discussed about the implementation of the MCL process on protein-protein interaction of TP53 data using the Python programming language. MCL algorithm consists of three main operations: expansion, inflation, and prune. Furthermore, the clustering simulation is using the different parameter of expansion, inflation and the multiplier factor. Based on the analysis of the clustering results, MCL algorithm is proven to produce robust cluster with TP53 protein as a centroid for each clustering results."

Depok: Universitas Indonesia, 2016

S62721

UI - Skripsi Membership Universitas Indonesia Library

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