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Wiendo Syah Putra Yahya
Profil efikasi dan toksisitas terapi target baru golongan Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKi) pada pasien kanker paru karsinoma bukan sel kecil non skuamosa dengan mutasi EGFR positif dibandingkan dengan kemoradioterapi pada EGFR Wild type = Profile of efficacy and toxicity the new targeted therapy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKi) in non small cell lung cancer non squamous with mutated EGFR compared with chemoradiotherapy in wild type
"Latar belakang : Terapi target baru golongan EGFR-TKi telah direkomendasikan sebagai terapi lini pertama untuk pasien KPKBSK non skuamosa dengan mutasi EGFR positif. Belum tersedia data di Indonesia tentang efikasi dan toksisitas terapi target baru EGFR-TKi pada pasien KPKBSK dengan mutasi EGFR positif dibandingkan dengan kemoradioterapi pada EGFR wild type di RSUP Persahabatan Jakarta.
Metode : Disain penelitian ini kohort retrospektif melalui resume medis pasien KPKBSK non skuamosa di RSUP Persahabatan periode Januari 2010 sampai Juli 2014. Teknik pengambilan sampel adalah consequtive sampling. Jumlah sampel 61 pasien yang terdiri dari 31 pasien KPKBSK non skuamosa dengan mutasi EGFR positif yang diberikan terapi target baru EGFR-TKi dan 30 pasien dengan EGFR wild type yang diberikan kemoradioterapi.
Hasil : Karakteristik pasien KPKBSK non skuamosa dengan mutasi EGFR yang positif adalah laki-laki sebanding dengan perempuan, bukan perokok, mutasi delesi di ekson 19 sebanding dengan mutasi L858R di ekson 21, angka tahan hidup 1 tahun 48,37%, rata-rata time to progression 284 hari sedangkan pasien EGFR wild type adalah laki-laki lebih dominan, perokok, angka tahan hidup 1 tahun 33,3% dan rata-rata time to progression 210 hari dan overall survival 293 hari. Uji T independen menunjukan terdapat hubungan yang bermakna antara terapi target baru EGFR-TKi dengan lama time to progression (p=0,028). Toksisitas yang sering ditemukan pada terapi target baru EGFR-TKi adalah mual- muntah (6,8%) diare (16,2%), alopesia (3,2%) dan kelainan kulit kemerahan (12,9%) sedangkan pada kelompok kemoradioterapi toksisitas yang ditemukan adalah anemia (13,3%), leukopenia (6,7%) dan trombositopenia (3,3%).
Kesimpulan : Pasien KPKBSK non skuamosa dengan mutasi EGFR yang positif dan diberikan terapi target baru EGFR-TKi memiliki time to progression yang lebih lama dan toksisitas yang dapat ditoleransi.
Background: The new targeted therapy of EGFR-TKi has been recommended as first-line therapy for patients with NSCLCC non-squamous with mutated EGFR. There are no data about the efficacy and toxicity of the new targeted therapy of EGFR-TKi in NSCLC non-squamous with mutated EGFR compared with chemotradiotherapy in wild type at Persahabatan Hospital, Jakarta.
Methods: The design of study are retrospective cohort through medical records of NSCLC non-squamous patients in the Department of Pulmonology and Respiratory Persahabatan Hospital in January 2010 to July 2014. The sampling technique is consequtive sampling. The number of samples are 61 patients consisted of 31 patients with NSCLC non-squamous with mutated EGFR treated the new targeted therapy of EGFR-TKi and 30 patients with EGFR wild type treated chemoradiotherapy.
Results: The characteristics of NSCLC non-squamous patients with positive mutated EGFR are male compared to women, non-smokers, a deletion mutation in exon 19 L858R mutation comparable with in exon 21, 1-year survival 41,9%, mean time to progression is 284 days and patients of wild-type mutation are more dominant in males, smokers, 1-year survival 33,3% and mean time to progression is 210 days and overall survival is 293 days . The independent t test showed a significant relationship between the new targeted therapy with EGFR-TKi and TTP (p = 0.028). The most common adverse events in the EGFR-TKi group are nausea and vomitus 96,8%), diarrhea (16,2%), alopecia (3,2%) and rash (12,9%) and in the chemotherapy group, anemia (13,3%), leucopenia (6,7%) and thrombocytopenia (3,3%).
Conclusions: The EFGR-TKi for patients with advanced non small cell lung cancer who are selected on the basis of EGFR mutations improve time to progression with acceptable toxicity."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014
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UI - Tugas Akhir  Universitas Indonesia Library
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Kasum Supriadi
Angka tahan hidup pasien kanker paru kelompok bukan sel kecil non skuamosa yang mendapat terapi target Epidermal Growth Factor Receptor-Tyrosin Kinase Inhibitor dan yang mendapat kemoterapi lini pertama di Rumah Sakit Persahabatan = The survival rate of non squamous by non small cell lung carcinoma patiens who are given by target therapy Epidermal Growth Facttor Receptor-Tyrosin Kinase Inhibitors and those given by first line kemotheraphy treatment at Persahabatan Hospital
"[ABSTRAK
Pendahuluan. Kanker paru jenis karsinoma bukan sel kecil (KPKBSK) terdiri dari nonskuamosa dan skuamosa. Kanker paru jenis karsinoma bukan sel kecil nonskuamosa adalah adenokarsinoma dan karsinoma sel besar. Saat ini terapi kanker paru sangat berkembang dari agen kemoterapi sampai terapi target terutama EGFR-TKI. Penelitian ini bertujuan untuk menilai angka tahan hidup pasien KPKSBK nonskuamosa yang mendapat kemoterapi lini pertama dibandingkan terapi EGFR-TKI di RSUP Persahabatan.
Metode. Penelitian ini adalah penelitian retrospektif antara tahun 2010 sampai 2013 dari rekam medis pasien KPKBSK non skumosa yang mendapatkan kemoterapi lini pertama dan EGFR-TKI. Pasien dikemoterapi dengan platinum baseddan EGFR-TKI diterapi gefitinib 1x250 mg/hari atau erlotinib 1x150 mg/hari. Angka tahan hidup dinilai dari mulai tegak diagnosis sampai pasien meninggal atau saat penelitian dihentikan.
Hasil. Dari 96 sampel KPKBSK non skuamosa terdiri dari 48 pasien yang mendapat kemoterapi lini pertama dan 48 pasien yang diterapi EGFR-TKI. Berdasarkan karakteristik pasien, usia terbanyak adalah 40-60 tahun (kemoterapi 32 (66,7%) dan EGFR-TKI 31 (64,6%) dengan jenis kelamin laki-laki yang mendominasi (kemoterapi 25(52,1%), EGFR-TKI 27 (56,2%). Pasien merokok yang mendapat kemoterapi lini pertama 41,7% dan EGFR-TKI 56,3% dengan IB terbanyak untuk kemoterapi (IB ringan 27,1%) dan untuk EGFR-TKI (IB sedang 22,9%). Jenis histologi adenokarsinoma 95,8% dengan dominasi stage IV 89,6% (kemoterapi 91,7% dan EGFR-TKI 87,5%) disertai tampilan status 2 59,4%. Angka tahan hidup pasien (ATH) 6 bulan 74%, ATH 1 tahun 22,90% dan ATH 2 tahun 6,20%. Masa tengah tahan hidup (MTTH) pasien yang mendapat EGFR-TKI lebih lama sedikit dibandingkan yang mendapat kemoterapi lini pertama (263 hari versus 260 hari.
Kesimpulan. Masa tahan hidup 1 tahun pasien KPKBSK non skuamosa yang diterapi EGFR-TKI sedikit lebih lama dibandingkan kemoterapi lini pertama (263 hari vs 260 hari). Sedangkan ATH 1 tahun pasien kemoterapi lini pertama lebih besar dibandingkan EGFR-TKI (25% vs 20,8%). Faktor yang paling mempengaruhi angka tahan hidup adalah stage dengan nilai p<0,05.
ABSTRACT
Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.
Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.
Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).
Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.;Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.
Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.
Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).
Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.;Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.
Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.
Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).
Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.;Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.
Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.
Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).
Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05., Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients of non-squamous type who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Persahabatan hospital.
Methods. This study is a retrospective study between 2010 to 2013 from the medical records of NSCLC patients of non-squmous type who receive first-line chemotherapy and thise who recieve EGFR-TKI.Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued.
Result. From 96 subject of NSCLC patients with non-squamous type consisted of 48 patients who receive first-line chemotherapy, and 48 patients are treate with EGFR-TKI. Based on the characteristics of the patients, most are 40-60 years old (chemotherapy 32 (66.7%) and EGFR-TKI 31 (64.6%) with the male gender that dominates (chemotherapy 25 (52.1%), EGFR-TKI 27 (56.2%). Smoking patients who received first-line chemotherapy are 41.7% and 56.3% of EGFR-TKIs with chemotherapy highest IB (mild IB 27.1%) and for EGFR-TKI (moderate IB are 22.9%). 95.8% of adenocarcinoma histology type with a predominance of stage IV 89.6% (91.7% for chemotherapy and EGFR-TKI 87.5%) with performance status 2 59.4% . Survival rate of patients are 74% for 6 months survival, 1 year survival rate is 22.90% and 2 years survival rate of 6.20%. Median period of survival rate in patients who receiving EGFR-TKI longer than they received first-line chemotherapy (263 days versus 260 days).
Conclusion. Median survival rate of non-squamous NSCLC that treated by EGFR-TKI is longer than first-line chemotherapy (263 days vs 260 days). Although 1 year survival rate first-line chemotherapy in patients is greater than EGFR-TKI (25% vs 20.8%). The factors that most influence the survival rate is stages with p value<0.05.]"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014
T58765
UI - Tesis Membership  Universitas Indonesia Library
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Marscha Iradyta Ais
Proporsi gambaran penyakit paru interstisial pada pasien kanker paru karsinoma bukan sel kecil dengan terapi epidermal growth factor receptor tyrosine kinase inhibitor di RSUP Persahabatan = The proportion of interstial lung disease features in patients with non small cell lung cancer treated with epidermal growth factor receptors tyrosine kinase inhibitor at Persahabatan Hospital
"Latar Belakang: Jumlah kasus KPKBSK diperkirakan 85% dari seluruh kasus kanker paru dan 40% diantaranya adalah jenis adenokarsinoma. Sebanyak 10%-30% pasien adenokarsinoma mengalami mutasi EGFR dan mendapatkan terapi EGFR-TKI. Mayoritas pasien KPKBSK memiliki respons dan toleransi baik terhadap terapi EGFR- TKI tetapi sebagian kecil pasien mengalami penyakit paru interstisial akibat EGFR- TKI. Penelitian ini bertujuan untuk mengetahui proporsi gambaran penyakit paru interstisial pada pasien KPKBSK dengan terapi EGFR-TKI di RSUP Persahabatan.
Metode: Penelitian ini merupakan penelitian observasional analitik dengan pendeketan kohort retrospektif yang dilakukan bulan Januari 2021 hingga Juni 2022. Subjek penelitian adalah pasien KPKBSK yang mendapatkan terapi EGFR-TKI. Subjek penelitian dipilih sesuai kriteria inklusi dan eksklusi. Pengambilan data melalu data sekunder berupa rekam medis dan hasil CT scan toraks pasien yang kontrol di poliklinik onkologi RSUP Persahabatan.
Hasil: Pada penelitian ini diperoleh 73 subjek penelitian, pasien KPKBSK dengan mutasi EGFR yang mendapatkan terapi EGFR-TKI di RSUP Persahabatan. Sebanyak 12 dari 73 subjek penelitian mengalami gambaran ILD yang dievaluasi berdasarkan CT scan toraks RECIST I dan II dengan karakteristik jenis kelamin laki-laki (22,2%), kelompok usia 40-59 tahun (19,4%), perokok (24,1%), indeks brinkman berat (42,9%) dan mendapatkan terapi afatinib (26,1%). Proporsi gambaran ILD pada pasien KBPKBSK dengan terapi EGFR-TKI adalah opasitas retikular (58,3%), parenchymal band (33,3%), ground-glass opacities (25%), traction bronchiectasis (25%) dan crazy paving pattern (8,3%). Hasil analisis bivariat dan multivariat menunjukkan tidak terdapat perbedaan antara faktor-faktor seperti jenis kelamin, usia, jenis EGFR-TKI, riwayat merokok, indeks brinkman, riwayat penyakit paru dan tampilan status terhadap gambaran ILD.
Kesimpulan: Gambaran ILD pada pasien KPKBSK dengan terapi EGFR-TKI meliputi opasitas retikular, parenchymal band, ground-glass opacities, traction bronchiectasis dan crazy paving pattern. Tidak terdapat perbedaan bermakna secara statistik antara faktor-faktor yang memengaruhi terhadap gambaran ILD.
Background: The number of cases of NSCLC is estimated around 85% of all lung cancer cases and 40% among them are adenocarcinoma. Approximately 10%-30% of adenocarcinoma patients have EGFR mutations and receive EGFR-TKI therapy. The majority of NSCLC patients have a good response and tolerance to EGFR-TKI therapy, but a small group of patients experience EGFR-TKI induced interstitial lung disease. This study aims to determine the proportion of features of interstitial lung disease ini NSCLC patients treated with EGFR-TKI at Persahabatan Hospital.
Methods: This study was an analytic observational with a retrospective cohort approach that was conducted from January 2021 until June 2022. The subject were NSCLC patients who received EGFR-TKI treatment. The inclusion and exclusion criteria were used to determine which subjects will be included in the study. Data collection through secondary data from medical record and chest CT scan results of patients controlled at oncology polyclinic at Persahabatan Hospital.
Result : In this study, there were 73 subjects of NSCLC with EGFR mutations and received EGFR-TKI therapy at Persahabatan Hospital. There were 12 out of 73 subjects had ILD features which were evaluated based on RECIST I and II chest CT scan with predominant of male (22.2%), age group 40-59 years old (19.4%), smokers (24.1%), severe Brinkman index (42.9%) and received afatinib (26.1%). The proportion of ILD features in NSCLC patients with EGFR-TKI therapy are reticular opacities (58.3%), parenchymal bands (33.3%), ground-glass opacities (25%), traction bronchiectasis (25%) and crazy paving pattern (8.3%). The results of bivariate and multivariate analyzes showed that there was no differences between factors such as sex, age, type of GEFR-TKI, smoking history, Brinkman index, history of lung disease and performance status with features of ILD.
Conclusion: Features of ILD in NSCLC patients with EGFR-TKI therapy include reticular opacities, parenchymal bands, ground-glass opacities, traction bronchiectasis and crazy paving pattern. There is no statistically significa"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Tugas Akhir  Universitas Indonesia Library
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Nathanael Andry Mianto
Model machine learning dan molecular docking untuk prediksi senyawa fitokimia dengan aktivitas epidermal growth factor receptor tyrosine kinase inhibitor terhadap mutasi reseptor T790M, C797S dan insersi ekson 20 = Machine learning and molecular docking model to predict phytochemical with EGFR TKI activity against EGFR mutation T790M, C797S and exon 20 insertion
"Latar belakang: Terapi target dengan EGFR TKI merupakan terapi utama untuk kanker paru, khususnya KPKBSK. Selain permasalahan efektivitas harga, permasalahan lain terkait penggunaan EGFR TKI adalah resistansi primer dan sekunder seperti T790M, C797S dan insersi ekson 20. Penelitian in silico QSAR berbasis machine learning dan molecular docking dapat mempercepat penemuan senyawa EGFR TKI baru berbasis senyawa fitokimia.
Metode: Penelitian ini adalah penelitian in silico untuk mengembangkan model QSAR berbasis machine learning yang dilanjutkan dengan molecular docking untuk penapisan senyawa fitokimia yang memiliki efek EGFR TKI terhadap mutasi T790M, C797S dan insersi ekson 20. Model machine learning dibuat untuk memprediksi nilai IC50 berdasarkan struktur kimia senyawa. Data pembelajaran berasal dari pangkalan data ChEMBL, data senyawa fitokimia dari KEGG, dan data makromolekul dari RCSB PDB. Simulasi molecular dynamics dilakukan untuk memvalidasi lebih lanjut hasil molecular docking.
Hasil: Didapatkan 8627 senyawa EGFR TKI dari ChEMBL, yang dibagi menjadi set pembelajaran dan set uji dengan rasio 9:1. Model machine learning dengan algoritma LGBM berhasil dikembangkan dengan nilai R2 sebesar 73%. Lima senyawa fitokimia dengan nilai IC50 prediksi terbaik adalah orobol, norswertianin, isokaempferide, isoathyriol, dan norathyriol. Kelima senyawa memiliki profil farmakokinetik dan toksikologi yang cukupbaik. Hasil molecular docking menunjukkan norswertianin memiliki kemampuan ikatan terbaik terhadap EGFR mutasi T790M dan T790M/C797S/L858R, sedangkan orobol terhadap mutasi T790M/C797S dan insersi ekson 20. Kedua senyawa dapat membentuk ikatan yang stabil pada simulasi molecular dynamics.
Kesimpulan: Model QSAR berbasis machine learning dengan algoritma LGBM dapat digunakan untuk memprediksi nilai IC50 EGFR TKI senyawa berdasarkan struktur kimianya. Senyawa fitokimia dapat digunakan sebagai dasar pengembangan EGFR TKI baru. Senyawa norswertianin dan orobol memiliki potensi terbesar sebagai EGFR TKI yang efektif untuk mutasi T790M, C797S dan insersi ekson 20.
Background: Targeted therapy with EGFR TKI has been the mainstay of lung cancer treatment, especially NSCLC. Besides the poor cost-effectiveness, primary and secondary resistances, such as T790M, C797S, and exon 20 insertion mutation, have been problematic in EGFR TKI clinical utilization. In silico research, such as machine learning-based QSAR dan molecular docking, has the potential to hasten the discovery of novel EGFR TKI based on phytochemicals.
Method: This study is an in silico research to develop a machine learning-based QSAR model, followed by molecular docking experiments for virtual screening of phytochemicals that have bioactivity as EGFR TKI against T790M, C797S, and exon 20 insertion mutation. A machine learning model will be developed to predict IC50 based on chemical structure. The learning set is sourced from the ChEMBL database, phytochemical data from KEGG, and macromolecule data from RCSB PDB. Molecular dynamic simulation is carried out to validate the molecular docking result further.
Results: A total of 8627 compounds was procured from ChEMBL database, which was split into training and test sets with a ratio of 9:1. LGBM based machine learning model with considerable accuracy can be developed, with R2 of 73%. The five compounds with the best predicted IC50 value was orobol norswertianin, isokaempferide, isoathyriol, and norathyriol. All compounds possess a good pharmacokinetics and toxicology profile. The molecular docking result showed that norswertianin has the best binding affinity against EGFR with T790M and T790M/C797S/L8568R. Orobol has the best binding affinity against EGFR with T790M/C797S and exon 20 insertion. Both compounds can form a stable binding in molecular dynamics simulation.
Conclusions: Machine learning-based QSAR model utilizing the LGBM algorithm can predict IC50 value as EGFR TKI based on the compound’s chemical structure. Phytochemicals can be used as the basis for novel EGFR TKI. Norswertianin and orobol have the best EGFR TKI potential against T790M, C797S, and exon 20 insertion mutations."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Tugas Akhir  Universitas Indonesia Library
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Jamaluddin M
Efikasi dan toksisiti erlotinib/gefitinib sebagai terapi lini kedua pada pasien kanker paru jenis karsinoma bukan sel kecil = Efficacy and toxicity erlotinib/gefitinib as second line therapi in non small cell lung cancer patients
"ABSTRAK
Tesis ini menilai efikasi dan toksisiti Erlotinib/Gefitinib sebagai terapi lini kedua
pada pasien KPKBSK yang mengalami progresifitas. Ini adalah sebuah penelitian
kohor retrospektif antara tahun 2009 sampai 2013 dari rekam medis pasien
KPKBSK yang mengalami progresifitas. Respons (subjektif, semisubjektif dan
objektif) dievaluasi setiap bulan. Toksisiti dinilai setiap minggu sejak pemberian
Erlotinib/Gefitinib berdasarkan kriteria WHO. Hasil evaluasi respons objektif,
tidak ada pasien yang memberikan respons komplit. Best overall response rate
dari 31 pasien, 48,8% menetap, 22,6% perburukan,12,9% respons sebagian dan
6,5% tidak dinilai/inevaluable. Pada penilaian respons semisubjektif didapatkan
19.4% peningkatan berat badan, 51,6% penurunan berat badan dan 29,0%
menetap. Waktu tengah tahan hidup mencapai 18 bulan, rerata masa tahan hidup
1 tahunan 80,6% dan masa tahan hidup keseluruhan 6,50%. Data menunjukkan
tidak ada timbul toksisiti hematologi berat (grade ¾) dan data penilaian toksisiti
non hematologi sangat jarang timbul toksisiti berat (grade ¾). Efikasi monoterapi
EGFR-TKI (Erlotinib/Gefitinib) cukup tinggi dengan toksisiti yang ditimbulkan
tidak berat. Dengan demikian Erlotinib/Gefitinib sebagai terapi lini kedua cukup
baik.ABSTRACT This thesis assesses the efficacy and toxicity of Erlotinib/Gefitinib as a second
line therapy in NSCLC patients. This is a retrospective cohort study between 2009
and 2013 from the medical records of patients who experienced progression
NSCLC. Therapeutic response was evaluated every month. Toxicity assessed
every month since giving Erlotinib/Gefitinib according to WHO?s criteria. Results
of objective response evaluation none of the patients complete response. Best
overall response rate of 31 patients with the most stable response are 48.8%. Most
semisubjective response obtained are 51.6% weight loss. The middle survival time
reached 18 month, the mean 1 year survival time are 80.6% and a 6.50% overall
survival. The data showed no hematologic toxicity arise severe (grade ¾) and
non-hematological toxicity very rarely arise severe toxicity. The efficacy of EGFR
TKI monotherapy (Erlotinib/Gefitinib) is high enough with toxicity cause not
severe. Thus Erlotinib/Gefitinib as second-line therapy is quite good. ;This thesis assesses the efficacy and toxicity of Erlotinib/Gefitinib as a second
line therapy in NSCLC patients. This is a retrospective cohort study between 2009
and 2013 from the medical records of patients who experienced progression
NSCLC. Therapeutic response was evaluated every month. Toxicity assessed
every month since giving Erlotinib/Gefitinib according to WHO?s criteria. Results
of objective response evaluation none of the patients complete response. Best
overall response rate of 31 patients with the most stable response are 48.8%. Most
semisubjective response obtained are 51.6% weight loss. The middle survival time
reached 18 month, the mean 1 year survival time are 80.6% and a 6.50% overall
survival. The data showed no hematologic toxicity arise severe (grade ¾) and
non-hematological toxicity very rarely arise severe toxicity. The efficacy of EGFR
TKI monotherapy (Erlotinib/Gefitinib) is high enough with toxicity cause not
severe. Thus Erlotinib/Gefitinib as second-line therapy is quite good. "
Fakultas Kedokteran Universitas Indonesia, 2015
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Sarifuddin
Analisis korelasi transforming growth factor 1 (TGF B-1) serum pada pasien kanker paru jenis karsinoma bukan sel kecil (KPKBSK) stage lanjut = The correlation analysis of transforming growth factor 1 (TGF B-1) serum in advanced non small cell lung cancer (NSCLC) patients
"Latar Belakang: Tingginya angka kejadian kanker paru menyebabkan diperlukan pemanfaatan suatu penanda biologis spesifik kanker paru untuk menilai progresifitas penyakit. Transforming growth factor-β adalah protein yang disekresi untuk meregulasi proliferasi, diferensiasi dan kematian dari berbagai jenis sel. Semua jenis sel kekebalan termasuk sel B, sel T, sel dendritik dan makrofag mensekresi TGF-β. Jenis TGF-β yang terbanyak adalah TGF-β1. Diperlukan pengukuran kadar TGF-β1 serum darah tepi sebagai faktor prognostik pada kanker paru khususnya KPKBSK stage lanjut
Metode: Penelitian ini merupakan studi perbandingan dengan disain potong lintang pada pasien kanker paru yang telah tegak diagnosis dan bersedia diambil serum darah tepi untuk pemeriksaan kadar TGF-β1 serum menggunakan Human TGF-β1 Quantikine ELISA kit dari R D. Kadar TGF-β1 serum diukur pada 68 subjek yang terdiri dari 30 subjek kelompok kanker paru dan 38 subjek kelompok bukan kanker paru.
Hasil: Kadar TGF-β1 serum pada kelompok kanker paru meningkat signifikan lebih tinggi dibandingkan kelompok bukan kanker paru (median; min-max) (3601.85; 2006.87-14995.25 pg/mL vs 2510.11; 646.31-5584.07 pg/mL) (P = 0.000). Tidak ditemukan hubungan antara kadar TGF-β1 serum dengan jenis kelamin, umur, riwayat merokok, gejala klinis, gambaran bronkoskopi, jenis sitologi/histopatologi, KPKBSK stage lanjut, dan status tampilan umum. Median Survival Time (95% CI) TGF-β1 < 3601.85 pg/mL adalah 9.7 (2.4-16.9) bulan sedangkan TGF-β1 ≥ 3601.85 pg/mL adalah 16.7 (7.7-25.7) bulan. Over all survival TGF-β1 13.3 (5.8-20.8) bulan
Kesimpulan: Kadar TGF-β1 serum meningkat pada kelompok kanker paru dibandingkan kelompok bukan kanker paru. Kadar TGF-β1 serum belum dapat digunakan sebagai marker prognostik kanker paru.
Beckground: The high incidence rate of lung cancer leads to the utilization of a specific biological marker of lung cancer to assess disease progression. Transforming growth factor-β is a secreted protein to regulate the proliferation, differentiation and death of different cell types. Types of immune cells are B cells, T cells, dendritic cells and macrophages secreting TGF-β. The most common type of TGF-β is TGF-β1. Therefore, measurement of serum level of TGF-β1 as a prognostic factors in lung cancer, especially advanced stage NSCLC, to assess progressivity of lung cancer is needed. Method: This study is a comparative study with cross-sectional design in lung cancer patients who had been diagnosed and were willing to be taken for examination of peripheral blood serum levels of TGF-β1 using the Quantikine Human TGF-β1 ELISA kit from R&D system. TGF-β1 serum levels were measured in 68 subjects consisted of 30 subjects with lung cancer group and 38 subjects controlled group.
Result: Serum level of TGF-β1 in lung cancer group increased significantly higher than control group (median; min-max) (3601.85; 2006.87-14995.25 pg/mL vs. 2510.11; 646.31-5584.07 pg/mL) (P = 0.000). There was no association between serum level of TGF-β1 with gender, age, smoking history, clinical symptoms, bronchoscopy, cytology/histopathology, advanced stage of NSCLC, and performance status. Median Survival Time (95% CI) TGF-β1 <3601.85 pg/mL was 9.7 (2.4-16.9) months while TGF-β1 ≥ 3601.85 pg/mL was 16.7 (7.7-25.7) months. Over all survival TGF-β1 13.3 (5.8-20.8) months.
Conclusion: Serum level of TGF-β1 is higher in the lung cancer group compared to controlled group. Serum TGF-β1 levels can not be used as a prognostic markers of lung cancer."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
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Moulid Hidayat
Peran Quiescent Lung Cancer Stem Cell (CSC) dalam Prosesresistans terhadap Agen Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) pada Adenokarsinoma Paru dengan Mutasi EGFR Positif = Role of Quiescent Lung Cancer Stem Cells in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR- TKI) Resistance in EGFR-Mutant Lung Adenocarcinoma
"Latar Belakang: Beberapa bukti menunjukkan bahwa quiescent cancer stem cell (CSC) terlibat dalam resistans terhadap gefitinib pada adenokarsinoma paru sebagai mekanisme nonmutasi. Kami sebelumnya telah mempublikasikan bahwa gefitinib- resistant persister (GRP) mengekspresikan stemness factor dengan level yang tinggi dan memiliki ciri khas fenotip CSC. Studi terbaru menunjukkan bahwa FBXW7, merupakan jenis protein F-box, memainkan peran penting dalam pemeliharaan quiescent CSC dengan memediasi degradasi protein c-MYC melalui proses ubiquination. Tujuan dari penelitian ini adalah untuk mengetahui peran FBXW7 dalam resistans terhadap gefitinib pada adenokarsinoma paru dengan mutasi EGFR.
Metode: Cell line dari sel adenokarsinoma paru, PC9, yang mengandung mutasi sensitif EGFR dipajankan pada gefitinib dengan konsentrasi tinggi untuk mengembangkan GRP. Kami mencoba melakukan abrogasi ekspresi gen FBXW7, dan mengevaluasi sensitivitasnya terhadap gefitinib dan populasi CD133-positive stem cell di GRP. Kami juga memasukkan plasmid FUCCI melalui proses infeksi lentiviral ke dalam sel dan kemudian menyelidiki siklus sel dan sel pada fase G0 dalam GRP. Selanjutnya, kami telah mengembangkan model gefitinib-resistant tumor (GRT) dengan menyuntikkan sel PC9 ke dalam mencit NOG diikuti dengan pemberian gefitinib setelah pertumbuhan tumor, dan mengevaluasi ekspresi mRNA dan ekspresi protein dari penanda terkait quiescence, FBXW7 in vivo.
Hasil: GRP menunjukkan ekspresi yang tinggi dari penanda cancer stem cell, CD133 dan penanda terkait quiescence, FBXW7 dan ekspresi c-MYC yang rendah pada tingkat protein secara in vitro. Analisis siklus sel menunjukkan bahwa mayoritas GRP berada pada fase G0/G1. TIndakan abrogasi gen FBXW7 menurunkan populasi sel CD133-positive di GRPs. Abrogasi FBXW7 juga meningkatkan kerentanan sel terhadap gefitinib, membalikkan populasi sel fase G0/G1 menjadi sel S/G2/M, dan menurunkan jumlah sel GRP. Secara in vivo, pada GRT setelah pengobatan gefitinib menunjukkan ekspresi FBXW7 yang tinggi dan ekspresi c-MYC yang rendah. Kami juga menemukan bahwa ekspresi FBXW7 dalam sel CD133-positive meningkat dan ekspresi c-MYC menurun pada mencit dan pada 9 dari 14 spesimen tumor dari pasien adenokarsinoma paru dengan mutasi EGFR resistan terhadap gefitinib.
Kesimpulan: Temuan ini menunjukkan bahwa FBXW7 dapat memainkan peran penting dalam pemeliharaan quiescence pada gefitinib-resistant lung CSC pada adenokarsinoma paru dengan mutasi positif EGFR
Background: Accumulating evidence indicates that quiescent cancer stem cells (CSCs) are involved in the resistance to gefitinib in non-small cell lung cancer (NSCLC) as non-mutational mechanism. We have previously reported that gefitinib-resistant persisters (GRPs) highly expressed stemness factors and had characteristic features of the CSCs phenotype. Recent studies demonstrate that FBXW7, a type of F-box protein, plays an important role in the maintenance of quiescent CSC by mediating the degradation of c-MYC protein by ubiquination. The aim of this study is to figure out the role of FBXW7 in the resistance to gefitinib in lung adenocarcinoma with EGFR mutation.
Methods: lung adenocarcnoma cell lines, PC9, harboring sensitive-EGFR mutation were exposed to high concentration of gefitinib in order to develop GRPs. We tried to knockdown FBXW7 gene expression, and evaluated their sensitivity to gefitinib and CD133-positive stem cell population in GRPs. We also introduced FUCCI plasmid via lentiviral infection in the cells and then investigated the cell cycle and G0-phase cells in GRPs. Furthermore, we established gefitinib-resistant tumor (GRT) model by injecting PC9 cells into NOG-mice followed by gefitinib administration after tumor growth, and evaluated mRNA and protein expression of quiescence-related markers including FBXW7 in vivo.
Results: In vitro, GRPs showed high expression of stem cell marker CD133 and quiescence-related markers including FBXW7 and low expression of c-MYC at protein level. Cell cycle analysis revealed that majority of GRPs existed in G0/G1 phase. Silencing of FBXW7 gene reduced CD133-positive cell population in GRPs. Knockdown of FBXW7 also increased susceptibility of cells to gefitinib, reversed population of G0/G1 cells to G2/S/M cells, and decreased cell number of GRPs. In vivo, GRTs after gefitinib treatment revealed high expression of FBXW7 and low expression of c-MYC. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in mice and in 9 out of
14 tumor specimens from EGFR-mutant lung adenocarcinoma patients with acquired resistance to gefitinib.
Conclusion: These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation- positive lung adenocarcinoma."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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Kinanti Khansa Chavarina Dwi Kartono
Analisis simulasi dinamika molekuler hasil penapisan virtual biota fungi laut terhadap inhibitor EGFR dan VEGFR-2 pada kanker paru karsinoma bukan sel kecil = Molecular dynamic simulation analysis of marine fungi compounds against EGFR and VEGFR-2 inhibitory activity in non small cell lung cancer
"Menurut International Agency for Research on Cancer IARC, penderita kanker paru telah mencapai 1,8 juta jiwa dan 85 berkontribusi pada kanker paru jenis karsinoma bukan sel kecil. Dalam beberapa tahun belakangan, penelitian terhadap terapi tertarget sedang dikembangkan karena terbukti memiliki hasil terapi yang lebih efektif dan kemungkinan efek samping yang lebih sedikit. Perkembangan penelitian terhadap biota fungi laut belum banyak dieksplorasi dalam pengobatan kanker paru bukan sel kecil. Pada penelitian ini dilakukan simulasi dinamika molekuler pada senyawa biota fungi laut hasil penapisan virtual terhadap makromolekul EGFR FU0015, FU0051, dan FU0202 dan VEGFR-2 FU0033 untuk melihat aktivitas inhibisi sebagai agen antiproliferatif dan antiangiogenesis menggunakan AutoDock dan AMBER dalam suhu 300K dan 310K yang dibandingkan dengan kontrol positif EGFR Gefitinib, Erlotinib, and Imatinib dan VEGFR-2 Nikotinamid dan Vatalanib. Hasil simulasi dinamika molekuler terhadap inhibitor EGFR pada suhu 310K menunjukkan energi bebas MMGBSA dan okupansi ikatan hidrogen tertinggi dimiliki oleh FU0051 -43,72 kkal/mol; 98,80 diikuti oleh FU0202 -31.64 kkal/mol; 49,35, dan FU0015 -15,55 kkal/mol; 3,35. Fungi FU0033 sebagai bahan uji inhibitor VEGFR-2 pada suhu 310K memiliki nilai energi bebas MMGBSA yang lebih besar dibandingkan kontrol positifnya dan okupansi ikatan hidrogen yang rendah 0,15. Data penelitian menunjukkan senyawa FU0051 dan FU0202 memiliki potensi untuk menjadi calon agen antiproliferasi sehingga layak diuji in vitro.
According to International Agency for Research on Cancer IARC, the number of lung cancer patients has reached 1,8 million lives and 85 of the number contribute to non small cell lung cancer. In the past years, research on targeted therapy has been developed due to its efficacy and a small number of side effects. Research on marine fungi compounds has not been explored to non small cell lung cancer therapy. This research uses molecular dynamic simulation method to marine fungi compounds that have been docked to EGFR FU0015, FU0051, FU0202 and VEGFR 2 FU0033 as antiproliferative and antiangiogenetic agent by inhibition activity using AutoDock and AMBER at 300K and 310K temperature using EGFR Gefitinib, Erlotinib, and Imatinib and VEGFR 2 Nicotinamide and Vatalanib as reference standards. Molecular dynamics results for EGFR inhibitors at 310K shows the best MMGBSA free energy and hydrogen occupancy in FU0051 43,72 kcal mol 98,80 followed by FU0202 31.64 kcal mol 49,35 , and FU0015 15,55 kcal mol 3,35. FU0033 fungi as a material for VEGFR 2 inhibitor shows higher MMGBSA free energy in compare to its reference standards and low hydrogen occupancy 0,15 at 310K. This research shows that FU0051 and FU0202 have potential to be an antiproliferative agent candidate, hence in vitro test should be obtained."
Depok: Fakultas Farmasi Universitas Indonesia, 2017
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Muhammad Resa
Desain inhibitor Epidermal Growth Factor Receptor (EGFR) dari senyawa flavonoid berbasis fragment-based drug design sebagai obat potensial untuk terapi kanker paru-paru non-sel-kecil = Epidermal growth factor receptor (egfr) inhibitor design from flavonoid compounds based on fragment-based drug design as a potential drug for non-small-cell lung cancer therapy
"Kanker paru-paru merupakan jenis kanker yang paling banyak diderita dan paling mematikan di dunia. Tipe kanker paru-paru paling banyak diderita merupakan kanker paru-paru non-sel-kecil (NSCLC). Senyawa flavonoid digunakan sebagai inhibitor protein reseptor faktor pertumbuhan epidermal (EGFR) dalam penelitian ini karena memiliki kemampuan bioaktivitas dan bioavailabilitas yang berpotensi sebagai obat antikanker. Penelitian ini menggunakan pendekatan in silico untuk menemukan senyawa flavonoid yang dapat menghambat protein reseptor EGFR secara efektif untuk dijadikan kandidat obat melalui desain obat berbasis fragmen. Beberapa metode komputasi yang digunakan adalah metode Protein-Ligand Interaction Fingerprint (PLIF), penentuan titik farmakofor, simulasi penambatan molekul, serta uji farmakologi dan toksisitas. Setelah dilakukan screening secara virtual melalui penambatan dengan protein EGFR (PDB. 1M17) menggunakan data flavonoid berasal dari basis data pubchem yang berjumlah 25.189 didapat dua fragmen terbaik yang memiliki tiga ikatan hidrogen untuk dilakukan fragment growing dan dari penambatan molekul senyawa hasil fragment growing yang berjumlah 25.600 diperoleh sepuluh senyawa terbaik, dengan parameter ΔGbinding lebih kecil dibanding standar erlotinib yaitu -8,8536 dan nilai RMSD lebih kecil dari 2,0 Å. Ligan tersebut diuji farmakologi dan prediksi toksisitas diperoleh dua senyawa sebagai kandidat inhibitor EGFR yaitu compound 980 dan compound 760 yang memiliki inhibisi CYP yang lebih sedikit dibanding standar dan tidak bersifat toksik untuk organ hati. Berdasarkan hasil tersebut maka compound 980 dan compound 760 dapat menjadi inhibitor EGFR yang potensial.
Lung cancer is the most suffered and deadly type of cancer in the world. The most common type of lung cancer is non-small cell lung cancer (NSCLC). Flavonoid compounds are used as epidermal growth factor receptor (EGFR) protein inhibitors in this study because they have the potential for bioactivity and bioavailability as anticancer drugs. This study uses an in silico approach to find flavonoid compounds that can effectively inhibit EGFR receptor proteins to be drug candidates through fragment-based drug design. Some computational methods used are the Protein-Ligand Interaction Fingerprint (PLIF) method, pharmacophore point determination, molecular tethering simulation, and pharmacology and toxicity tests. After a virtual screening with EGFR protein (PDB. 1M17) used flavonoid data from the pubchem database with totat number 25,189 is obtained the two best fragments that have three hydrogen bonds to do fragment growing and from molecular docking simulation of compound molecules from fragment growing totaling 25,600 is obtained the ten best compounds, with the parameter ΔGbinding smaller than the erlotinib standard which is -8.8536 and an RMSD value smaller than 2.0 Å. The ligand was tested pharmacologically and the the toxicity was predicted is obtained two compounds as EGFR inhibitor candidates namely compound 980 and compound 760, which had less CYP inhibition than standard and were not toxic to liver. Based on these results, compound 980 and compound 760 can be potential EGFR inhibitors.
"
Depok: Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Indonesia, 2020
T54605
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Putu Ayu Diah P S
Efikasi dan toksisiti kemoterapi karboplatin-vinorelbin pada pasien kanker paru jenis karsinoma bukan sel kecil (KPKBSK) stage lanjut di RSUP Persahabatan = Efficacy and toxicity of carboplatin vinorelbine chemotherapy in advanced non small cell lung cancer (NSCLC) patients at Persahabatan Hospital
"ABSTRAK
Latar Belakang : Paduan kemoterapi berbasis platinum dengan generasi ketiga khususnya karboplatin-vinorelbin sudah sering digunakan sebagai kemoterapi paliatif pada pasien KPKBSK stage lanjut di Indonesia khususnya Rumah Sakit Umum Pusat RSUP Persahabatan namun sampai saat ini belum terdapat data mengenai efikasi dan toksisiti paduan kemoterapi ini di RSUP Persahabatan.Metode : Desain penelitian ini adalah survey observasional retrospektif pada pasien KPKBSK stage lanjut IIIB dan IV yang menjalani kemoterapi lini I di RSUP Persahabatan dengan paduan kemoterapi karboplatin-vinorelbin sejak 1 Januari 2015 sampai 30 Maret 2017.Hasil : Total subjek dalam penelitian ini adalah 38 pasien yang mendapatkan paduan kemoterapi Karboplatin AUC-5 pada hari ke-1 dan vinorelbin 30 mg/m2 pada hari ke1 dan ke-8. Paduan kemoterapi karboplatin-vinorelbin mempunyai efikasi yang baik dengan Objective overall response rate ORR 12,5 dan clinical benefit rate CBR 87,5 . Overall survival OS pada penelitian ini adalah 34,2 dengan masa tengah tahan hidup 387 hari 12,9 bulan dan progression free survival 323 hari 10,7 bulan. Toksisiti hematologi dan nonhematologi yang paling sering terjadi adalah anemia derajat 1 38,4 dan keluhan mual, muntah derajat 2 57,9 . Pada penelitian ini terdapat 2 kasus perdarahan saluran cerna derajat 2 namun pasien masih dapat melanjutkan kemoterapi. Kami juga mendapatkan komplikasi tindakan kemoterapi berupa phlebitis ringan pada 24 pasien 65,7 dan phlebitis sedang pada 1pasien 2,6 .Kesimpulan: Paduan karboplatin-vinorelbin sebagai kemoterapi lini I memiliki efikasi yang baik serta efek toksisiti yang masih dapat ditoleransi sehingga aman diberikan pada pasien KPKBSK stage lanjut. Kata kunci: efikasi, toksisiti, hematologi, nonhematologi, objective overall response rate, clinical benefit rate, overall survival, MTTH, TTP, PFS
ABSTRAK
Background Combination of platinum base and third generation drugs Carboplatin and vinorelbine chemotherapy are frequently used as paliative chemotherapy for Non small cell lung cancer NSCLC patients in Indonesia especially in Persahabatan Hospital. But there are still no data about the activity and tolerability of this regiment in Persahabatan Hospital. This study is conducted to evaluate the efficacy and toxicity of this regiment as first line chemotherapy for advanced NSCLC patients in Persahabatan Hospital.Method This study is an observational survey retrospective study for advanced NSCLC patientswho receive carboplatin vinorelbine regiment as fisrt line chemotherapy since 1st January 2015 to 30th March 2017.Result We observea total of 38 patients who receive carboplatin 5 AUC on day 1 and vinorelbine 30mg m2 on day 1 and 8. This regiment has a good efficacy with overall response rate ORR 12,5 and clinical benefit rate CBR 87,5 . The overall survival OS is 34,2 with median of survival time 387 days 12,9 moths and PFS 323 days 10,7 moths . We found grade 1 anemia 38,4 and grade 2 nausea vomiting 57,9 as hematological and non hematological toxicity that frequently occur in this study. We found 2 cases of grade 2 gastrointestinal bleeding but the patients are still able to continue the chemotherapy after doing some correction for the haemoglobin Hb . We also found mild phlebitis in 24 patients 65,7 and 1 moderate phlebitis in 1 patient 2,6 as procedural complication of this chemotherapyConclusion Combination ofcarboplatin and vinorelbine as first line chemotherapy has a good efficacy and tolerability for advanced NSCLC patients. Key word efficacy, toxicity, haematological, non hematological, overall objective response rate ORR , clinical benefit rate CBR , overall survival OS , median time of survival, time to progression TTP and progression free survival PFS ."
2017
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