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"DNA topoisomerases represent an essential family of DNA processing enzymes and a large number of topoisomerase inhibitors are used clinically for the treatment of various human cancers. Novels drugs are in clinical development both against type I and type II topoisomerases. The book will include basic biochemical and structural reviews for the cancer-relevant topoisomerases. It will describe how topoisomerase dysfunctions can damage the genome and increase the risk of cancers, and the involvement of topoisomerases in programmed cell death. The book will also present the various topoisomerase inhibitors in clinical use and development and their molecular and cellular mechanisms of action."

"The development and progression of cancer and the experimental reversal of tumorigenicity are companied by complex changes in the pattern of gene expression.DNA micro-array technology is used to profile complex disease and discover novel disease-related genes. This technique has been successfully used to investigate gene expression in processes as complex as inflammatory disease, tumor suppression and to identify heat shock in human T cell.DNA micro-arrays or DNA-chip technology allows expression monitoring of hundreds and thousands of genes simultaneously and provide a format for identifying genes as well as changes in their activity. The DNA micro-array helps us study genome-wide expression patterns in complex biological systems. These tools have shown great promise in finding the meaning of complex diseases such as cancer.There is some interest in the potential application of DNA micro-array analysis for gene expression profiling in human cancers. Micro-arrays of DNA provide a powerful tool for studying the development and progression of cancer phenomena. It might be useful for tumor classification, for the elucidation of regulatory networks that are disturbed in tumor cells and for the identification of genes that might be of use for diagnostic purposes or as therapeutic targets."

"Penyakit kanker disebabkan oleh peristiwa karsinogenesis dan ditandai dengan adanya kerusakan oksidatif DNA. Senyawa tert-butilhidroquinon TBHQ diduga sebagai pemicu terjadinya peristiwa karsinogenesis. Tujuan penelitian ini adalah untuk mengetahui dan mengidentifikasi adanya pembentukan DNA adduct 8-hidroksi-2 rsquo;-deoksiguanosin 8-OHdG akibat adanya paparan senyawa TBHQ pada 2 rsquo;-deoksiguanosin dan calf thymus DNA secara in vitro dengan variasi pH, waktu, dan suhu. Penelitian ini dilakukan menggunakan 2 39;-deoksiguanosin-5 39;-monophosphat dan TBHQ melalui reaksi fenton dengan variasi pH yaitu 7,4 dan 8,4, variasi waktu inkubasi yaitu 1 jam dan 3 jam, dan variasi suhu yaitu 37oC dan 60oC. Kemudian sampel dari 2 rsquo;-deoksiguanosin dianalisis menggunakan HPLC, sedangkan sampel dari calf thymus DNA dianalisis menggunakan UV-Vis. Dilakukan juga uji kestabilan 8-OHdG dengan variasi pH menggunakan HPLC. Hasil yang diperoleh menunjukkan bahwa konsentrasi pembentukan 8-OHdG lebih banyak terjadi berturut-turut pada pH 8,4 daripada pH 7,4, dengan waktu inkubasi 3 jam daripada dengan waktu inkubasi 1 jam, dan pada suhu 60oC daripada suhu 37oC, serta menunjukkan adanya reaksi fenton. Rasio kemurnian calf thymus DNA pada ?260/?280 yang digunakan dalam penelitian ini adalah 1,83. Terjadi pergeseran puncak panjang gelombang maksimum dari hasil inkubasi calf thymus DNA dan senyawa TBHQ serta Fe2 yang menandakan terjadinya perubahan struktur DNA. Hasil uji kestabilan 8-OHdG pada kondisi asam dan basa menunjukkan 8-OHdG mengalami kerusakan.

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Cancer is caused by a carcinogenesis and is characterized by DNA oxidative damage. The tert butylhydroquinone TBHQ compound is thought to be the trigger for the carcinogenesis. The aim of this study was to investigate and identify the formation of 8 hydroxy 2 39 deoxyguanosine 8 OHdG adduct DNA due to exposure of TBHQ compounds to 2 39 deoxyguanosine and calf thymus DNA in vitro by pH, time, and temperature variations.

This study was carried out using 2 39 deoxyguanosine 5 39 monophosphate and TBHQ by fenton reaction with pH variation of 7.4 and 8.4, variation of incubation time ie 1 hour and 3 hours, and temperature variation ie 37oC and 60oC. Then a sample of 2 39 deoxyguanosine was analyzed using HPLC, while samples from the calf thymus DNA were analyzed using UV Vis. It also performed a stability test of 8 OHdG with pH variation using HPLC.

The results show that the concentration of 8 OHdG formation occurs more successively at pH 8.4 than pH 7.4, with an incubation time of 3 hours than with an incubation time of 1 hour, and at a temperature of 60 C rather than 37 C, fenton reaction. The purity ratio of calf thymus DNA in 260 280 used in this study was 1,83. There is a maximum wavelength peak shift from the incubation of the calf thymus DNA and the TBHQ and Fe2 compounds indicating the change in DNA structure. Stability test results of 8 OHdG on acid and base conditions showed 8 OHdG damage."

"Deteksi DNA adduct dapat dijadikan sebagai pendekatan untuk mendeteksi dini risiko kanker. Salah satu produk kerusakan oksidatif DNA adalah 8-hidroksi-2’-deoksiguanosin (8-OHdG). Penelitian ini dilakukan untuk mendeteksi 8-OHdG secara in vitro dan in vivo. Studi in vitro dilakukan dengan inkubasi 2’-deoksiguanosin dengan H2O2 dan akrilamida pada variasi pH 7,4 dan 8,4 selama 24 jam dalam suhu 37 oC. Kemudian hasil inkubasi dianalisis menggunakan HPLC. Sedangkan secara in vivo dilakukan deteksi 8-OHdG dalam urin pasien kanker paru stadium III-IV, urin perokok, dan urin non perokok dengan menggunakan LCMS/MS. Pada validasi instrumen HPLC diperoleh nilai regresi linier 0,9985, nilai LOD dan LOQ sebesar 6,108 ppb dan 20,361 ppb. Sedangkan untuk LCMS/MS diperoleh nilai regresi linier sebesar 1, nilai LOD dan LOQ sebesar 1,819 ppb and 6,066 ppb. Hasil penelitian menunjukkan bahwa paparan H2O2 dan akrilamida dapat membentuk 8-OHdG. Konsentrasi 8-OHdG yang terbentuk dari inkubasi 2-deoksiguanosin dan H2O2 serta 2-deoksiguanosin, H2O2, dan akrilamida maksimum pada pH 8,4 yakni sebesar 2,151 ppm dan 2,617 ppm. 8-Hidroksi-2’-Deoksiguanosin terdeteksi dalam urin pasien kanker paru, perokok, dan non perokok masing-masing sebesar 4,668 – 19,919 ppb, 6,873 – 12,111 ppb, -0,502 – 6,578 ppb. Nilai rata-rata konsentrasi 8-OHdG dalam sampel urin pasien kanker paru, perokok dan non perokok masing-masing sebesar 9,710 ppb, 10,226 ppb, dan 3,080 ppb.

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DNA adduct detection could be an approach to early detection of risk cancer. One of oxidative DNA damage products is 8-hydroxy-2’-deoxyguanosine (8-OHdG). This study was conducted to detect DNA adduct 8-OHdG in vitro and in vivo. In vitro study was started to incubate 2’-deoxyguanosine added by H2O2 and acrylamide in various pH for 24 hours at 37 oC. Then the result was analyzed with HPLC. In vivo study was conducted detection 8-OHdG in urine of lung cancer patients with stage III-IV disease, smokers and non smokers using LCMS/MS. Instrument validation (HPLC) was yielded linear regression value 0,9985, LOD and LOQ as much as 6,108 ppb and 20,361 ppb as well as validation instrument of LCMS/MS was yielded linier regression value 1, LOD and LOQ as much as 1,819 ppb and 6,066 ppb.The results of study found exposure of H2O2 to 2-deoxyguanosine induced 8-OHdG formation and the addition of acrylamide increased 8-OHdG formation. The highest 8-OHdG level obtained by incubation of 2’-deoxyguanosine and H2O2 then 2’deoxyguanosine, H2O2 and acrylamide at pH 8,4 as much as 2,151 ppm and 2,617 ppm. 8-Hydroxy-2’-Deoxyguanosine was detected in urine of lung cancer patients, smokers and non smokers respectively 4,668 – 19,919 ppb, 6,873 – 12,111 ppb, -0,502 – 6,578 ppb. The mean value of 8-hydroxy-2’-deoxyguanosine in urine of lung cancer patients, smokers and non smokers as much as 9,710 ppb, 10,226 ppb, and 3,080 ppb."

"ABSTRAKKanker payudara merupakan jenis kanker dengan prevalensi yang tinggi di dunia yang umumnya terjadi pada wanita. Kanker payudara memiliki angka tertinggi yang mencapai hingga 40 per 100.000 kasus setiap tahunnya, dan sebnayak 12,9 diantaranya dapat menyebabkan kematian. Perubahan epigenetik berperan penting dalam proses pembentukan dan penyebaran sel kanker. Metilasi DNA merupakan salah satu jenis dari perubahan epigenetik yang sering terjadi yang dapat memicu terjadinya pertumbuhan sel kanker. Metilasi DNA dikatalisis oleh enzim DNA Metiltransferase 1 DNTM1 yang dapat memindahkan gugus metil dari S-adenosil metionin SAM ke sitosin pada dinukleotida CpG. Pada penelitian ini, dilakukan penapisan virtual senyawa bahan alam sebagai inhibitor enzim DNMT1. Penapisan dilakukan terhadap 26.731 senyawa bahan alam yang diperoleh dari NCBI Pubchem databsase. Simulasi penambatan molekul dilakukan dengan menggunakan Molecular Operating Environment MOE 2014.09 untuk mendapatkan 10 ligan terbaik berdasarkan interaksi kompleks ligan-enzim dan energi bebas Gibbs. Karakteristik farmakologi meliputi sifat fsikokimia, toksisitas, karsinogenisitas-mutagenisitas serta bioaktivitas menggunakan online software maupun offline software. Uji farmakologi dilakukan untuk mengetahui karakteristik fisikokimia, toksisitas, karsinogenisitas-mutagenisitas dan bioaktivitas menggunakan software DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR dan SWISSADME. Hasil dari penelitian ini ialah terdapat 3 ligan terbaik yang berasal dari kelompok senyawa bahan alam fenolik yang terpilih berdasarkan karakteristik farmakologi yang dapat dijadikan sebagai kandidat obat untuk terapi kanker payudara.

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ABSTRACTBreast cancer is the most prevalent cancer in woman worldwide. It has the highest number of new cases which amounted to 40 per 100,000 cases per year, 12,9 of which leads to death. Epigenetic alteration plays a vital role in the process of cancer cell formation and propagation. DNA methylation is one of the most common types of epigenetic alteration which generally leads to breast cancer DNA Methylation, a transfer the methyl group from S adenosyl methionin SAM to cytosine in the CpG dinucleotide, is catalyzed by DNMT1 enzyme. In the present study, we performed a virtual screening of natural product compounds as an inhibitors of DNMT1 enzyme. Virtual screening was conducted on 26,731 natural products obtained from the NCBI PubChem database. Three steps of rigid and one step of flexible molecular docking simulations were performed using MOE 2014.09. Through the simulations, 10 ligands based on the Gibbs free binding energies Gbinding and the ligand enzyme complex interactions were identified. Pharmacological test was conducted to observe the psychochemical, toxicity, carcinogenicity mutagenicity, and bioactivity properties by employing DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR and SWISSADME software. The results revealed that three best ligands from phenolic group were selected due to their exceptional pharmacological characteristics as the drug candidate for breast cancer therapy. "

"Dengan tersedianya data genom berupa sekuen DNA pada domain publik, banyak peneliti dari berbagai lintas bidang yang memfokuskan penelitian mereka dalam studi genom untuk analisa ekstrasi informasi dan analisa data. Penelitian pada sekuen DNA dilakukan dengan menggunakan metode pengolahan signal digital disebut dengan Genomic Signal Processing (GSP). GSP dapat digunakan untuk mendiagnosis penyakit genetik yang muncul karena mutasi pada sekuen DNA, seperti kanker. Saat ini, kanker menduduki peringkat kedua sebagai penyebab kematian di dunia. Pada tingkat yang paling mendasar, kanker adalah penyakit DNA, dimana perubahan sekuen DNA dan molekul yang berinteraksi dengan DNA pada akhirnya menyebabkan profilerasi sel yng tidak terkendali. Pada skripsi ini, akan dilakukan simulasi untuk membandingkan tranformasi fourier dengan transformasi wavelet dalam mendeteksi kanker. Perancangan diawali dengan mengkonversi sekuen DNA menjadi sekuen numerik menggunakan binary sequence method. Selanjutnya,transformasi fourier / wavelet digunakan untuk menganalisa karakteristik spektral dan IIR Low Pass Filter Butterworth digunakan untuk meningkatkan akurasi dengan menekan noise. Berdasarkan simulasi, diperoleh bahwa transformasi wavelet dapat digunakan untuk mendeteksi kanker melalui analisa sekuen DNA dimana wavelet ortogonal memberikan hasil lebih baik daripada biortogonal. Dibandingkan transformasi fourier, transformasi wavelet memiliki performa yang lebih baik dalam mendeteksi sel kanker.

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With the enormous amount of genomic data of DNA sequence available in the public domain, many researcher from various cross fields have concentrated their research in genomic study for information extraction and data analysis technique that is used to analyze DNA sequences using Digital Signal Processing (DSP) is Genomic Signal Processing (GSP). GSP can be used to diagnose genetic diseases that appear due to mutations in DNA sequences, such as cancer. Cancer is the second leading disease that cause of death in the world. Cancer is the disease of DNA because a permanent change in the DNA can develop cancer cells.

This thesis will design a simulation to compare between fourier transformation and wavelet transformation for cancer detection. The design begins by converting the DNA sequence into numerical sequences using binary sequence method. Furthermore, the fourier/wavelet transform is used to analyze the spectral characteristics of DNA sequence and IIR Butterworth Low Pass Filter is used to improve the accuracy in predicting and identifying cancer cells.

The result of simulation shows that wavelet transform can be used to detect a cancer through DNA sequence analysis. Wavelet transform shows the better performance than fourier transformation. In wavelet transform, orthogonal wavelet give better result that biorthogonal wavelet."

"Latarbelakang: Cell-free DNA (cfDNA) sebagai liquid biopsy dapat digunakan sebagai alat diagnostik noninvasif pada kanker paru. Cell-free DNA membawa informasi genetik sel kanker dan berkorelasi dengan karakteristik tumor. Penelitian ini mengevaluasi perancf DNA dalam menentukan prognosis pada pasien Kanker Paru Bukan Karsinoma Sel Kecil (KPKBSK).Metode: Cell-free DNA diisolasidari 23 serum pasien adenokarsinoma paru di Hiroshima University Hospital pada tahun 2006-2018. Mutasi gen EGFR ekson 19 E745-A750del dan ekson 21 L858R pada tumor diperiksa pada saat diagnosis. Deteksimutasi gen EGFR ekson 19 E745-A750del dan ekson 21 L858R pada cfDNA dilakukan dengan menggunakan droplet digital PCR.Hasil: Dari total 23 pasien, 10 pasien dengan delesi E745-A750del dan 13 pasien dengan mutasi L858R terdeteksi pada tumor. Delesi E745-A750del dan mutasi L858R pada cfDNA terdeteksi pada 6 dan 8 pasien, secara berurutan. Variant allele frekuency yang terdeteksis ebesar 0,01%-18,6%. Median angka tahan hidup untuk pasien yang terdeteksi cfDNA adalah 42 bulan dan pasien yang tidak terdeteksi cfDNA adalah 76 bulan. (p=0,29).Kesimpulan: Terdeteksi nya cfDNA merupakan petanda noninvasif prognosis yang lebihburuk pada pasien KPKBSK.

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Background: Cell-free DNA (cfDNA) as liquid biopsy can be used as a nonivasive diagnostic tool in lung cancer. Cell-free DNA carries genetic information from cancer cells and correlated with the tumor characteristics. The present study evaluated the role of cfDNA to predict the prognosis in the nonsmall cell lung cancer (NSCLC

Methods: Cell-free DNA were isolated from 23 serum from lung adenocarcinoma patients in Hiroshima University Hospital in 2006-2018. EGFR exon 19 E740-A750 del and exon 21 L858R in the tumor were analyzed at the time of diagnosis. EGFR exon 19 E740-A750 del and exon 21 L858R in cfDNA were detected using droplet digital PCR.

Results: Of 23 patients. 10 patients with E745-A750del and 13 patients with L858R. E745-A750 del and L858R mutations on cfDNA were detected in 6 and 8, respectively. Variant allele frequency detected ranged from 0.01% to 18.6%. Median overall survival in patient with detected cfDNA was 42 months and in patient with no cfDNA detected was 76 months (p=0.29).

Conclusions: Cell-free DNA detected in the serum is a noninvasif biomarker for worse prognosis in NSCLC."

"Integrasi data gene expression dan DNA copy number berbasis kernel digunakan untuk menganalisis pola gen pada penyakit kanker payudara cell line. Clustering pada data integrasi dilakukan tanpa adanya informasi jumlah k cluster, teknik ini disebut fully unsupervised clustering. Pada penelitian ini, intelligent kernel K-Means dikembangkan dengan menggabungkan teknik intelligent K-Means dan kernel K-Means. Berdasarkan hasil eksperimen, nilai pada kernel RBF mempengaruhi jumlah cluster yang ditemukan. Hasil clustering dievaluasi menggunakan nilai R, global silhouette, indeks Davies-Bouldien, akurasi LS-SVM dan visualisasi. Hasil esperimen terbaik yaitu 3 cluster yang memperoleh akurasi LS-SVM sebesar 97.3% dengan standar deviasi 0.2%.

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In this thesis, kernel based data integration of gene expression and DNA copy number would be utilized to analyze pattern of genes in breast cancer cell line. The cluster analysis on the integrated data will be conducted with has no prior information with regards the number of k clusters which is called fully unsupervised clustering technique. In this work, intelligent kernel K-Means is proposed by combining intelligent K-Means and kernel K-Means. From the experiments, the value of of Radial Basis Function (RBF) has important role for finding the optimal of number of cluster. The clusters those to be found will be evaluated based on global silhouette, Davies-Bouldien Index, LS-SVM accuracy and visualization. The experiment result show that three clusters are successfully to be found. Those clusters produce average accuracy of LS-SVM around 97.3 % with standard deviation 0.2 %."

"ABSTRAKKanker kolorektal merupakan kanker ketiga tersering di Amerika Serikat dengan angka mortalitas menempati peringkat kedua tahun 2012. Mortalitas kanker ini dapat ditekan melalui deteksi dini saat perkembangan kanker pada tahap polip, salah satunya dengan diagnosis biologi molekuler keberadaan DNA pada tinja maupun serum. Penelitian ini dilakukan untuk menganalisis konsentrasi cell free DNA (cfDNA) sebagai penanda tumor pada karsinogenesis kolorektal dengan menggunakan sampel serum darah mencit balb/C yang sebelumnya dinduksi oleh azoxymethane (AOM) dan promosi oleh dextan sulfate sodium (DSS). Penelitian ini merupakan penelitian eksperimental quasi menggunakan hewan uji mencit Balb/C. Sampel terdiri atas 6 mencit Balb/C yang setiap sampelnya mendapatkan 4 perlakuan secara serial dalam rentang waktu tertentu. Perlakuan pertama adalah pengambilan sampel serum sebelum induksi-promosi, pengambilan kedua pada minggu ke-1 (1 minggu setelah induksi azoxymethane), pengambilan ketiga minggu ke-2 (1 minggu setelah induksi-promosi oleh azoxymethane-dextran sulfate sodium) dan pengambilan ketiga minggu ke-6 (5 minggu setelah induksi-promosi oleh azoxymethane-dextran sulfate sodium). Kuantifikasi cfDNA terhadap serum dilakukan dengan metode fluoresensi SYBR Green II menggunakan Rotor Gene 6000 dan pemeriksaan histopatologis untuk melihat karsinogenesis dilakukan pada minggu ke-0, ke-1, ke-2 dan ke-6. Konsentrasi cfDNA menunjukkan perbedaan yang signifikan antara kelompok sampel sebelum induksi dan promosi (1238,49±674,84 pg/μL ) dibandingkan kelompok sampel yang serumnya diambil minggu ke-6 dengan gambaran histopatologis pra-kanker (2244,04±726,57 pg/μL ). Terdapat kenaikan cfDNA pada minggu ke-1 hanya dengan induksi AOM maupun minggu ke-2 setelah dinduksi dan dipromosi (1358,57±803,81 pg/μL ) dan 1317,23±735,92 pg/μL ), namun perbedaan ini tidak bermakna secara statistik.

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ABSTRACTColorectal cancer was third of the most cancer in United States and second for the most mortal at 2012. Mortality should be decreased by early screening of the polyp stadium by molecular biology diagnoze of faecess’s DNA and serum’s DNA.The focus of this study is cell free DNA's potency as tumor marker of colorectal carcinogenesys within blood serum sample that was taken from balb/C mice induced by azoxymethane (AOM) and promoted by dextran sulfate sodium (DSS). This study is quasi experimental research. Samples were taken from 6 Balb/C mices, which are serial treated by the time. First, pre induction-promotion blood serum (week 0), second were one week post azoxymethane induction week 1st), third were one week post azoxymethane and dextran sulfate sodium induction-promotion (week 2nd), and fourth were fifth week post azoxymethane and dextran sulfate sodium induction-promotion (week 6th). Cell free DNA Quantification was performed by fluoresence of SYBR Green II method and confirmed by histopathology examination at null, 1st, 2nd and 6th week. Cell free DNA concentration show there was significant differencies of cfDNA before induction and promotion (1238,49±674,84 pg/μL ) compared to cfDNA 6th week after induction and promotion (2244,04±726,57 pg/μL ) statistically, but no significant differencies to the group of 1st week after AOM induction only and the group of 2nd week after induction and promotion, even both of those groups show increament of cfDNA concentration (1358,57±803,81 pg/μL and 1317,23±735,92 pg/μL )."