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Exploring TLR2 Gene Polymorphisms in Cervical Cancer Development

Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Human papillomavirus is a pathogen that directly infects cervical keratinocytes and may cause persistent infection that leads to cervical cancer. Toll like receptors (TLRs) play an essential role in initiating antiviral immune responses. Therefore, polymorphisms in TLR gene may contribute to cancer susceptibility. This study aimed to explore the TLR2 gene distribution and susceptibility to cervical cancer. In this case-control study, cervical cancer patients and their controls were recruited from the Department of Obstetrics and Gynecology, Dr. Hasan Sadikin General Hospital. Genomic DNA was extracted from blood of patients with histopathologically confirmed cervical cancer (n=100) and from unrelated, healthy female controls (n=100) during 2011. Three single nucleotide polymorphisms (SNPs) of the TLR2 gene were genotyped on the BeadXpress Reader system (Illumina)®. Chi square test was used to calculate the role of TLR2 and susceptibility to cervical cancer. Only subjects with complete clinical and genetic data were analyzed. Analysis of TLR2 rs3804099, rs4696480 and rs5743708 of cervical cancer patients and controls showed no significant association with the cervical cancer risk (p 0.424, p 0.275, p 0.209, respectively). Further classification in the FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) criteria for lower stage (FIGO I/II) and higher stage (FIGO III/IV) showed a lack of association between TLR2 and cancer development, suggesting the possibility that TLR2 polymorphism does not play a role in the susceptibility to cervical cancer in this study. Other toll like receptors may be involved in the cancer susceptibility. The significance of TLR polymorphism should be further studied. [MKB. 2013;45(4):257–62]Key words: Cervical cancer, toll like receptor, TLR2 Polimorfisme Gen TLR2 dan Perkembangan Kanker ServiksKanker serviks disebabkan oleh human papillomavirus (HPV), patogen yang dapat langsung menginfeksi keratinosit serviks secara persisten dan dapat berkembang menjadi kanker. Toll like receptors (TLR) berperan dalam merangsang respons imun, sehingga polimorfisme gen TLR dapat berkontribusi dalam kerentanan terhadap kanker. Tujuan penelitian ini adalah untuk mengetahui distribusi gen TLR2 dan peranannya terhadap kerentanan kanker serviks. Pada studi kasus kontrol, DNA genomik diekstraksi dari darah penderita kanker serviks yang terdiagnosis secara histopatologi (n=100) dan kontrol dengan Pap smear normal (n=100) tahun 2011 di Departemen Obstetri dan Ginekologi RSUP Dr. Hasan Sadikin Bandung. Pemeriksaan tiga single nucleotide polymorphisms (SNP)gen TLR2 dilakukan menggunakan BeadXpress Reader system (Illumina). Hanya subyek dengan data klinik dan genetik lengkap yang dianalisis dengan menggunakan uji chi square. Analisis dari TLR2 rs3804099, rs4696480 dan rs5743708 antara pasien dan kontrol tidak menunjukkan perbedaan yang bermakna (p 0.424, p 0.275 dan p 0.209). Di antara pasien dengan klasifikasi FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) tingkat rendah (FIGO I/II) dan tingkat tinggi (FIGO III/IV) juga tidak tampak perbedaan yang bermakna. Dari penelitian ini terbukti polimorfisme TLR2 tidak berperan dalam proses kerentanan maupun perkembangan terjadinya kanker serviks. Kemungkinan TLR yang lain seperti TLR 1, 3, 9 lebih berperan dalam perkembangan terjadinya kanker serviks. [MKB. 2013;45(4):257–62]Kata kunci: Kanker serviks, toll like receptor, TLR2 DOI: http://dx.doi.org/10.15395/mkb.v45n4.173

Penurunan Nyeri Persalinan Primigravida Kala I Fase Aktif Pascapenghirupan Aromaterapi Lavender

Majalah Kedokteran Bandung Vol 44, No 1 (2012)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Nyeri persalinan merupakan bagian pada proses normal yang tidak jarang menyebabkan stres fisiologis dan psikologis terhadap ibu yang berdampak pada ibu maupun janin. Sebagian besar persalinan (90%) disertai nyeri, bahkan sampai nyeri berat. Penanganan nonfarmakologi merupakan salah satu alternatif untuk mengurangi nyeri persalinan. Penelitian ini bertujuan untuk menganalisis efek analgesik penghirupan aromaterapi lavender pada nyeri persalinan primigravida kala I fase aktif. Rancangan yang digunakan adalah studi praeksperimental, satu kelompok diobservasi sebelum dan sesudah perlakuan terhadap 30 ibu bersalin di Rumah Bersalin (RB) Kasih Ibu Jatirogo kabupaten Tuban provinsi Jawa Timur sebagai sampel yang dipilih secara konsekutif. Pengukuran variabel menggunakan skala nyeri numerik. Dilakukan analisis univariabel kuantitatif untuk mengetahui nyeri sebelum dan sesudah perlakuan. Analisis kuantitatif bivariabel Wilcoxon signed ranks test digunakan untuk mengetahui pengurangan nyeri dengan tingkat kemaknaan p<0,05. Penelitian ini dilakukan periode 14 September–31 Oktober 2009. Hasil analisis univariabel menyatakan bahwa skor nyeri rata-rata sebelum perlakuan 7,3 (SD 1,1) dansesudah perlakuan 5,9 (SD 1,4). Hasil uji Wilcoxon signed ranks test menunjukkan pengurangan nyeri yang bermakna pascapenghirupan aromaterapi lavender (Z=-4,338; p=0,000). Simpulan, terdapat pengurangan nyeri persalinan pascapenghirupan aromaterapi lavender. [MKB. 2012;44(1):19–25].Kata kunci: Nyeri persalinan, penghirupan aromaterapi lavender Labor Pain Reduction in Primigravida Active Phase after Inhalation of Lavender AromatherapyLabor pain is part of a normal process, which often causes physiological and psychological stress to mother. These stress have impact to both mother and fetus. Largely (90%) labor comes with pain and in some cases severe pain. Non-pharmacological approach is one of alternatives to reduce labor pain. This research aims to analyse the analgesic effect of lavender aromatherapy inhalation on labor pain in primigravida in the active phase. The study was pra-experimental by observing one group before and after treatment. The group involved 30 parturients in RB Kasih Ibu Jatirogo district of Tuban, East Java. The sampling method was based on consecutive admission. The variables were measured by using numerical rating scales (NRS). Univariable quantitative analysis was applied to describe the pain before and after treatment. Wilcoxon signed ranks test bivariable quantitative analysis was used to investigate pain relief with significance level of p<0.05. The univariable analysis result revealed that mean pain score before treatment was 7.3 (SD 1.1) and after treatment 5.9 (SD 1.4). Wilcoxon signed ranks test result showed significant pain relief after lavender aromatherapy inhalation (Z=-4.338, p=0.000). The research shows that there is a reduction of labor pain after lavender aromatherapy inhalation. [MKB. 2012;44(1):19–25].Key words: Inhalation lavender aromatherapy, labor pain DOI:  http://dx.doi.org/10.15395/mkb.v44n1.210

Perancangan Kembali Identitas Korporat untuk Museum Sejarah Jakarta

Jurnal Inosains (Desain Industri) Vol 7, No 1 (2012)
Publisher : Universitas Esa Unggul

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Abstract

Identitas korporat Museum Sejarah Jakarta merupakan salah satu media bagi pihak manajemen Museum Sejarah Jakarta untuk mengatur media korporasi yang teratur dan terorganisir agar dapat menjadi dan berkembang menjadi suatu lembaga yang lebih independen dalam hal mempromosikan nilai jual dari muse- um tersebut, juga berfungsi sebagai media komunikasi efektif bagi para pengun- jungnya. Untuk mewujudkan sebuah media identitas korporat yang kuat, harus di- dasarkan pada pembuktian dan penguatan teori sehingga dapat dipertanggung- jawabkan secara utuh keabsahan dan kekuatan dari media korporat yang ber- sangkutan. Untuk meningkatkan promosinya, sebagai media perwujudan program dan wahana baru, Museum SejarahJakartaakan dicanangkan beroperasi da- lam dua kurun waktu operasional. Selain itu diharapkan juga dapat menjadikan Museum Sejarah Jakarta menjadi pusat intelektual kebudayaan Batavia, atraksi, dan rekreasi sesuai dengan apa yang telah menjadi visi dan misi dari Museum Sejarah Jakarta, juga tidak lupa untuk mengingatkan masyarakat akan sebuah eksistensi dari Museum Sejarah Jakarta sebagai media refleksi untuk melihat ke masa lampau. Kata kunci: night and day museum, pusat kebudayaan, rekreasi dan atraksi

Perancangan Panduan Lengkap Pariwisata Toraja

Jurnal Inosains (Desain Industri) Vol 7, No 1 (2012)
Publisher : Universitas Esa Unggul

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Abstract

Keanekaragaman seni budaya dan tradisi di Indonesia merupakan kekuatan dan modal besar masyarakat Indonesia, tuntutan untuk turut serta dalam melestarikan identitas  bangsa dengan melindungi warisan budaya sangat besar, mengingat nilai-nilai budaya  barat begitu mengekang masyarakat Indonesia, inilah saatnya masyarakat  memberikan  pengetahuan budaya Indonesia ke masyarakat dunia. Bangsa  yang  sangat  kaya  akan  keindahan  panorama  alam  dan keunikan  budaya. tidak dapat dinilai harganya, belum termasuk sumber daya alam yang berlimpah merupakan warisan bangsa Indonesia dan dunia, demikian banyaknya peninggalan berharga dari nenek moyang Bangsa Indonesia yang tidak dimiliki bangsa lain, salah satu Kekayaan adat istiadat Tana Toraja dipadu dengan pemandangan nan indah, hamparan tanah yang subur, keunikan arsitektur serta fenomena ritual mitologis yang sangat jarang dijumpai di tempat lain. dengan tetap menjaga dan menjunjung tinggi tradisi adat istiadat ataupun kepercayaan Aluk Todolo dirangkum dalam Buku panduan yang berguna sebagai jembatan informasi, dengan adanya sebuah buku panduan yang membahas khusus mengenai pariwisata Tana Toraja diharapkan persoalan kurangnya perhatian pemerintah dalam dunia pariwisata di Indonesia akan mendapatkan tanggapan yang lebih baik dan konkret, tidak hanya sebatas wacana, dan mampu memfasilitasi keinginan masyarakat agar terciptanya perkembangan ekonomi yang dapat diandalkan dari prospek cerah dari pariwisata Indonesia.  Kata kunci: perancangan, informasi, budaya

Cloning, Expression and Bioinformatic Analysis of Human Papillomavirus Type 52 L1 Capsid Gene from Indonesian Patient

Microbiology Indonesia Vol 8, No 3 (2014): September 2014
Publisher : Indonesian Society for microbiology

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Abstract

Human papillomavirus (HPV) type 52 is the most prevalent type for causing cervical cancer in Indonesian population. Cervical cancer becomes the most common cancer suffered by Indonesian women. Prevention of HPV infection can be achieved using HPV virus-like particle (VLP) vaccine derived from L1 major capsid protein.  This study aimed to clone and analyze HPV-52 L1 gene. DNA obtained from biopsy of a cervical cancer patient was amplified using specific primers designed from Asian originated HPV-52 L1 gene available in the GenBank. The isolated HPV-52 L1 gene sequence was submitted to GenBank with accession number [KF225497]. Expression of HPV-52 L1 gene was performed using pRSET/EmGFPEscherichia coli expression vector. We analyzed and compared the HPV-52 L1 gene expressions from recombinant E.coli BL21 (DE3) that had been induced for 3 hours with 1 mM IPTG and without induction. The protein was expressed in insoluble form. We performed the following bioinformatic analyses: construction of phlyogenetic tree, T-cell epitopes prediction and 3D proteins structure modelling. We utilized the following softwares: MEGA5 for phylogenetic tree, IEDBann for MHC prediction, CLC DNA Workbench 6.5 for hydrophobicity analysis and PDB-Viewer Deep for 3D protein structure analysis. The phylogenetic tree which was developed based on [KF225497] sequence showed that it shared a branch with Asian countries (Philippines and Thailand). The deduced amino acid sequences of the predicted epitopes that were consistent in all of the programs were 259GTLGDPVPGDLYIQGS274 and 345KKESTYKNE353. This information may be useful to design diagnostic strategies and vaccine suitable for Indonesian population.

Analisis Filogenetik Gen L1 Human Papillomavirus 16 pada Penderita Kanker Serviks di Bandung

Majalah Kedokteran Bandung Vol 47, No 3 (2015)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Infeksi human papillomavirus (HPV) tipe high risk (hr) yang kronik dapat menyebabkan kanker serviks. Berbagai genotipe hrHPV telah teridentifikasi dan HPV-16 merupakan genotipe yang tersering menginfeksi serviks. Fragmen L1 HPV dapat digunakan untuk mengidentifikasikan asal usul HPV. Tujuan penelitian ini adalah mengeksplorasi asal usul HPV-16 dengan membuat pohon filogenetik. Metode penelitian yang digunakan adalah metode deskriptif analisis. Penelitian dilakukan di Laboratorium Genetika Molekuler Unit Penelitian Kesehatan, Fakultas Kedokteran Universitas Padjadjaran Bandung pada Februari hingga Agustus 2013. Isolat biopsi dari pasien kanker serviks disumbangkan oleh Departemen Kebidanan Fakultas Kedokteran Universitas Padjadjaran, Bandung. Isolasi DNA dibuat dari biopsi jaringan kanker serviks dan fragmen L1 diamplifikasi dengan desain primer sendiri. Infeksi dengan HPV-16 dikonfirmasi dengan Linear Array test (Roche). Sekuens urutan basa kemudian dimasukkan dalam program filogenetik (MEGA5). Hasil konstruksi menunjukkan isolat pasien kanker serviks dari Bandung berada dalam satu subgrup dengan HPV asal Asia dan Asia Timur. Simpulan, cluster HPV Indonesia berada pada galur Asia dan Asia Timur. [MKB. 2015;47(3):174–78]Kata kunci: Filogenetik, fragmen L1,  human papillomavirus 16 (HPV-16)Phylogenetic Analysis of Human Papillomavirus 16 L1 Gene from Cervical Cancer Patient in BandungAbstractChronic infection with high-risk (hr) human papillomavirus (HPV) can lead to cervical cancer. Various hrHPV genotypes have been identified and HPV genotype 16 is the most common genotypes that infect cervical cancer. HPV L1 fragment can identify the origin of HPV. The purpose of this study was to explore the origins of HPV-16 by making a phylogenetic tree. This study used analytical descriptive method and was  was conducted at the Laboratory of Molecular Genetics, Health Research Unit, Faculty of Medicine, Universitas Padjadjaran Bandung in the period of February to August 2013. Biopsy from cervical cancer patient was donated by the Department of Obstetrics, Faculty of Medicine, Universitas Padjadjaran, Bandung. Isolation of DNA was prepared from tissue biopsies of cervical cancer and L1 fragment was amplified with the specific primer. Infection with HPV-16 was confirmed by Linear Array test (Roche) design. The sequence then was constructed using the phylogenetic program (MEGA5). Results showed that the isolate from patient with cervical cancer from Bandung was in one subgroup with HPV from Asia and East Asia. In conclusion, cluster HPV of Bandung is in the same strain as the strain in Asia and East Asia. [MKB. 2015;47(3):174–78]Key words: Human papillomavirus 16 (HPV-16), L1 fragment, phylogenetic DOI: 10.15395/mkb.v47n3.598

Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

Universa Medicina Vol 33, No 1 (2014)
Publisher : Faculty of Medicine, Trisakti University

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Abstract

BACKGROUND Persistent infection of high risk genotypes of human papilloma virus (hrHPV) has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. METHODS During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche). The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. RESULTS Of 96 cervical cancer tissue samples, 76 (79.2%) were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. CONCLUSION The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

Epidermal growth factor polymorphism most prevalent in stage II cervical carcinoma

Universa Medicina Vol 33, No 3 (2014)
Publisher : Faculty of Medicine, Trisakti University

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Abstract

Background    Cervical cancer ranks second among female cancers worldwide and is widely associated with human papilloma virus (HPV) infection. However, HPV infection progression is influenced by various host factors. Epidermal growth factor (EGF) is a host factor important for proper epithelial proliferation and development, and may play a role in cervical cancer progression. A functional A61G polymorphism in the EGF gene has been hypothesized to alter EGF concentration in vivo with increasing guanine content associated with greater EGF level. However, a map of A61G polymorphism distribution is not available for any population, including Indonesia. This study aims to determine the distribution of EGF A61G polymorphism among cervical cancer patients at Dr. Hasan Sadikin General Hospital.MethodsA retrospective cross-sectional study was conducted between July-November 2010. Included were 61 cervical cancer patients of various stages at Dr. Hasan Sadikin hospital, who had previously undergone blood sample collection, DNA isolation and finally genotyping for EGF gene using Illumina BeadXpress®. Chi-square test was used to analyse the data. ResultsThe EGF A61G polymorphism was exhibited by 88.5% of patients (as genotypes A/G and G/G). The majority of patients with this polymorphism were of moderate severity (FIGO stage II and III, 42.6% and 38.1% respectively). Patients with the polymorphism but with the lightest severity (FIGO stage I) accounted for 22.2% of the population. ConclusionEGF A61G polymorphism affected the majority of cervical cancer patients and that once stratified, the patients showed intermediate severity in terms of their cancerous growth.

IFNG Polymorphism (+874 T>A) is not a risk factor for cervical cancer

Universa Medicina Vol 32, No 1 (2013)
Publisher : Faculty of Medicine, Trisakti University

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Abstract

INTRODUCTION Cervical cancer cases are rising and many women are infected with human papillomavirus (HPV). Interferon gamma (IFN-ã) is one of the key regulatory cytokines that influence the HPV clearance. The production and the function of IFN-ã may impaired by the defect of the IFNG gene leading to the cervical malignant progression. This study aimed to examine the association between IFNG+874 T>A polymorphism and cervical cancer in women METHODS In a case-control study design, consecutive untreated women with cervical cancer who showed for the first time in Hasan Sadikin Hospital Bandung were enrolled (n=98) and for controls women who came for PAP smear (n = 81). Controls were not matched in ages and ethnicities. DNA extracted from blood was amplified by amplification refractory mutation system - polymerase chain reaction method (ARMS – PCR) to detect IFNG+874 T>A polymorphism. RESULTS The distribution of IFNG genotypes TT, TA and AA for women with cervical cancer who met the inclusion criteria (n= 64) and with negative intraepithelial lesion or malignancy (n=42) were 14.1%, 50.0%, 35.9% and 7.1%, 52.4%, 40.5%, respectively. No significant differences could be observed between both groups (p=0.64). Stratifying the cervical cancer women into a group of squamous cell carcinoma (n = 54) revealed no statistical different. CONCLUSION IFNG +874 T>A polymorphismseems not to contribute in susceptibility to cervical cancer. Identification of other variants in IFNG gene signaling and its role in the development of cervical cancer diseases need to be further examined.

Paclitaxel-carboplatin chemotherapy induced hematologic toxicities among epithelial ovarian cancer patients

Universa Medicina Vol 35, No 3 (2016)
Publisher : Faculty of Medicine, Trisakti University

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Abstract

BackgroundEpithelial ovarian cancer (EOC) is one of the most common cancers diagnosed in Indonesian women. A combination of paclitaxel and carboplatin is used to treat EOC as standard chemotherapy which is known to have hematologic toxicities. This study aimed to investigate the effect of combined paclitaxel-carboplatin chemotherapy on hematologic status in EOC patients managed at Dr. Hasan Sadikin General Hospital, Bandung, West Java.MethodsAll patients with confirmed pathological diagnosis of EOC at Dr. Hasan Sadikin General Hospital in the period of 2013 to 2014 were registered. Only patients with complete hematologic data before and after chemotherapy were collected and compared using the paired non-parametric Wilcoxon and McNemar tests. ResultsIn total there were 147 patients with EOC (median age 46 ± 12 years), with the most dominant pathological diagnosis of mucinous (32.7%) and serous (29.3%) types. Only 33 patients had hematologic data before the initiation of chemotherapy. There was a significant decrease after chemotherapy including hemoglobin level (12.0 vs 10.9 g/dL, p=0.013), erythrocyte count (4.53 vs 3.74 million/mL, p<0.001), leukocyte count (7,700 vs 4,000/mm3 p<0.001) and platelet count (343,000 vs 215,000/mm3, p<0.001). Interestingly, anemia cases after chemotherapy were predominant (87.9%) compared with erythopenia, leukopenia, thrombocytopenia i.e. 39.4%, 57.6%, and 27.3% respectively. ConclusionsThis study confirmed the hematologic toxicities after paclitaxel-carboplatin chemotherapy in EOC patients treated in Hasan Sadikin General Hospital, West Java. The hemoglobin concentration may serve as prognostic factor. Further studies directed to other factors such as genetic factor for polymorphisms may be encouraged to explore the decrease of the hematologic indices.

Co-Authors - Tarsikah, - Aditiyono, Aditiyono Afandi Charles, Afandi Akhmad Yogi Pramatirta, Akhmad Yogi Alfiana, Ratih Devi Anandayu Pradita Andi Kurniadi, Andi Ani Melani Maskoen Ardhanu Kusumanto Armini, Luh Nik Bethy S Hernowo, Bethy S Birgitta M Dewayani, Birgitta M Birgitta M. Dewayani, Birgitta M. Cynthia Kurniawan Dany Hilmanto Deni Sunjaya, Deni DEWI AYU KENCANA UNGU Dodi Suardi Edhyana Sahiratmadja Endang Susilowati Endang Sutedja Firman F Wirakusumah Firman Fuad Wirakusumah Firman Wirakusumah, Firman Fitri Rahmi Fadhilah, Fitri Rahmi Gatot N.A. Winarno Goenawan, Adrian Hadyana Sukandar Harsono, Ali Budi Herri S. Sastramihardja Heru Prayitno HIDAYAT, YUDI M Hitatami, Esti Husin, Farid Ika Agus Rini, Ika Agus Islami - Judistiani, Tina Juntika Nurihsan, Juntika Jusuf Sulaeman Effendi Kevin Dominique Tjandraprawira, Kevin Dominique Kurniawati Kurniawati Latief, Mutia Lestari, Bony Lestari, Vera Amalia Lucky Saputra, Lucky Madjid, Tita Madjid8, Tita Husnitawati Maringan D.L Tobing, Maringan D.L Maringan Tobing Muhammad Fauzi Muhammad Noor Arrazeen N.A.W, GATOT Nanan Sekarwana Nur Hasanah Nurhasanah Nurhasanah Pradini, Gita Widya Pradini, Gita Widya Purwana, Hasan Rahmat, Akbar Ramdan Panigoro Ratu Safitri Salima, Siti Samsudin Surialaga Sedjati, Adjat Shahib, Muhammad Nurhalim Sofie Rifayani Krisnadi SONY SUHANDONO Sri Endah Rahayuningsih Supriadi Gandamihardja TATI KRISTIANTI Tono Djuwantono Udin Sabarudin Winarno, Gatot Nyarumenteng Adhipurnawan Yanuarita, Sisilia P Yoni Syukriani, Yoni Yudi Mulyana Hidayat Zakaria, Hasballah