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Johan S. Masjhur, Johan S.
FK-UNPAD
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Perancangan Hewan Coba Model untuk Karsinoma Payudara HER-2 Positif Menggunakan Agen Imunosupresan

Majalah Kedokteran Bandung Vol 48, No 1 (2016)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Pengembangan obat terapi keganasan di Indonesia sering kali terkendala karena ketidakmampuan menyediakan hewan model untuk uji preklinis. Hewan model tersebut adalah hewan model dengan massa keganasan yang mempunyai karakteristik khusus, bukan sekedar dengan massa tumor. Pada umumnya untuk tujuan tersebut digunakan hewan model yang tidak mempunyai daya tahan tubuh dan dipelihara dalam lingkungan yang steril. Fasilitas sistem perkandangan yang steril ini yang belum ada di Indonesia. Tujuan penelitian ini mengembangkan metode penyediaan hewan model mencit pengganti nude mice dengan daya tahan tubuh yang rendah, tetapi mampu hidup dalam lingkungan fasilitas pemeliharaan yang tidak steril. Penelitian dilakukan di Laboratorium Hewan dan Laboratorium Sitogenetik Pusat Teknologi Radioisotop dan Radiofarmaka, Batan, Serpong sejak bulan Juli sampai November 2014. Galur sel SKBR-3 diinokulasi pada 2 kelompok mencit sehat (Mus musculus) strain Balb/c, yaitu kelompok perlakuan dan kontrol, masing-masing 8 ekor. Cyclosporine A, agen penurun daya tahan tubuh hanya diberikan pada kelompok perlakuan sebelum dan setelah inokulasi. Pada kedua kelompok, pertumbuhan tumor secara makroskopik tidak terlihat di tempat inokulasi, tetapi tampak perbedaan bermakna antara kelompok perlakuan dan kontrol pada kadar leukosit (p:0,01), limfosit (p:0,01), monosit (p:0,01), dan segmen neutrofil (p:0,01). Pada 2 mencit kelompok perlakuan didapatkan gambaran sel degenerasi bengkak keruh di hati. Metode ini terbukti dapat menurunkan daya tahan tubuh hewan coba mencit (Mus musculus) strain Balb/c, walaupun belum mampu menumbuhkan keganasan. [MKB. 2016;48(1):39–44]Kata kunci: Ca payudara HER2 positif, hewan coba model onkologiDesigning Animal Models for HER2 Positive Breast Cancer Using Immunosuppressive AgentAbstractThe development of therapeutic drug for malignancy in Indonesia is often constrained because of the inability to provide animal models for preclinical study. These animal models are an animal model with a malignancy mass which have special characteristics, not just the tumor mass. Animal models that are usually used for this purpose is immunodeficient animals. This animal must be kept in sterile animal care, but the facility is not readily available in Indonesia. The purpose of this study was to develop a method for providing an animal model of nude mice replacement that has fairly low immunity but are still able to live in non-sterile animal care facilities. The study was conducted at the Laboratory Animal and Cytogenetics, Center for Radioisotope and Radiopharmaceuticals Technology, Batan, Serpong in the period of July to November 2014. SKBR-3 cell lines were inoculated on two groups of immunocompetent mice (Mus musculus) strain Balb/c, namely the treatment group (n=8) and controls (n=8). Cyclosporine A as an immunosupressan agent was given only to the treatment group before and after SKBR 3 inoculation. No macroscopically visible tumor growth at the site of inoculation in both of groups. There was a significant difference between the treatment group and the control group in leukocyte levels (p: 0.01), lymphocytes (p: 0.01), monocytes (p: 0.01), and neutrophil segments (p: 0.01). Two treatment groups of mice obtained cloudy degeneration in the liver. This method has significantly reduced the immunity of mice (Mus musclus) strain Balb/c but still cannot grow malignancies in experimental animals. [MKB. 2016;48(1):39–44]Key words: HER2 positive breast cancer, oncology animal models DOI: 10.15395/mkb.v48n1.732

Deteksi Natrium/Iodide Symporter (NIS) pada Galur Sel Kanker Payudara SKBR3 dengan Imunositofluoresens

Majalah Kedokteran Bandung Vol 48, No 1 (2016)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Galur sel SKBR3 adalah model kanker payudara positif human epidermal growth factor receptor2 (HER2). Pemberian kemoterapi memperlihatkan respons lengkap hanya pada 50% pasien kanker payudara dengan tipe positif HER2. Kemampuan jaringan tumor menangkap dan mengakumulasi iodium radioaktif dihubungkan dengan ekspresi natrium/iodide symporter (NIS). Tujuan penelitian ini adalah menilai ekspresi dan distribusi NIS pada galur sel SKBR3 serta menilai efek induksi epidermal growth factor (EGF) pada ekspresi NIS menggunakan imunositofluoresens-ISF. Penelitian ini dilakukan di Laboratorium Kultur Sel, Fakultas Kedokteran Universitas Padjadjaran (FKUP) mulai bulan September 2013 sampai dengan April 2014. Sel SKBR3 ditumbuhkan pada plat kultur dan ditunggu hingga konfluen 70%. Sel dibagi atas dua kelompok, yaitu kelompok yang diberi induksi dan kontrol. Induksi EGF diberikan dengan dosis 50 ng/mL. Pemeriksaan ISF menggunakan antibodi primer rabbit polyclonal antibody anti NIS dan antibodi sekunder goat anti rabbit IgG polyclonal antibody. Data hasil pengamatan dinilai secara semikuantitatif. Natrium/iodide symporter tampak terekspresi dan terdistribusi di sitoplasma. Sel yang diinduksi dengan EGF memperlihatkan peningkatan ekspresi NIS di sitoplasma dan distribusinya di membran sel secara bermakna. Sel SKBR3 mengekspresikan NIS yang terdapat di sitoplasma. Induksi EGF meningkatkan ekspresi NIS dan distribusinya di membran sel. Temuan ini dapat mengarah potensi kemampuan sel kanker payudara menangkap dan mengakumulasikan iodium radioaktif. [MKB. 2016;48(1):15–8] Kata kunci: Ekspresi NIS , galur sel SKBR3, kanker payudara, imunositofluoresensDetection of Natrium/Iodide Symporter (NIS) in SKBR-3 Breast Cancer Cell Line Using ImmunocytofluoresenceAbstractSKBR-3 cell line is a breast cancer model for human epidermal growth factor receptor2 (HER2) positive. Only 50% of patients of this type have fully responded to chemotherapy. Natrium iodide symporter expression correlates with the uptake and ability of cells to accumulate radioiodine. The aim of this study was to examine natrium/iodide symporter (NIS) expression and its distribution with and without epidermal growth factor (EGF) treatment using immunocytofluoresence (ICF). This study was conducted at the Cell Culture Laboratory, Faculty of Medicine, Universitas Padjadjaran from September 2013 to April 2014. SKBR3 cells were cultured until 70% confluent. Cells were then divided into two groups: treatment group and control group. The treatment group was treated with EGF 50 ng/mL. Cells were incubated with primary antibody rabbit polyclonal antibody anti-NIS, and then were followed with secondary-antibody goat polyclonal antibody to rabbit. Data from the observation were then assessed semi-quantitatively. Natrium/iodide symporter was seen to be expressed and distributed in the cytoplasm. Cells induced by EGF showed significant increase in NIS expression in cytoplasm and its distribution in cell membrane. It is concluded that the SKBR3 cells express NIS in cytoplasm and that EGF induction increases NIS expression and distribution in cell membrane. This finding leads to a potential ability of breast cancer cells to uptake and accumulate radioiodine. [MKB. 2016;48(1):15–8]Key words: Breast cancer, cell line SKBR-3, immunocytofluoresence, NIS expression DOI: 10.15395/mkb.v48n1.728

STUDI AWAL ESTIMASI DOSIS INTERNAL 177Lu-DOTA TRASTUZUMAB PADA MANUSIA BERBASIS UJI BIODISTRIBUSI PADA MENCIT

Jurnal Sains dan Teknologi Nuklir Indonesia Vol 16, No 2 (2015): Agustus 2015
Publisher : BATAN

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Abstract

ABSTRAK STUDI AWAL ESTIMASI DOSIS INTERNAL 177Lu-DOTA TRASTUZUMAB PADA MANUSIA BERBASIS UJI BIODISTRIBUSI PADA MENCIT. Radiofarmaka baru untuk pengobatan penyakit kanker payudara tipe HER-2, 177Lu-DOTA Trastuzumab, telah berhasil diproduksi oleh Pusat Teknologi Radioisotop dan Radiofarmaka (PTRR) BATAN. Demi keamanan produk dan keselamatan pasien, radiofarmaka baru tersebut perlu dilengkapi dengan data studi dosis internal yang dilakukan setelah uji praklinis pada hewan coba selesai. Oleh karena itu, studi ini bertujuan untuk melakukan estimasi dosis pada pasien yang dihitung berdasarkan data uji biodistribusi pada mencit. Studi Uji biodistribusi dilakukan pada 25 ekor mencit dan diamati biodistribusinya pada organ-organ, diantaranya otak, perut, usus, jantung , ginjal, hati, paru-paru, otot, tulang, limpa dan kandung kemih. Pengamatan cacahan organ dilakukan pada jam ke 1, 2, 3, 4, 24, 48 pasca injeksi radiofarmaka 177Lu DOTA-Trastuzumab sebesar 100mCi. Hasil yang diperoleh dari uji biodistribusi adalah % ID/gram organ tikus, kemudian dilakukan konversi perhitungan ke % ID/gram organ manusia. Untuk mengestimasi dosis ke manusia, hasil %ID/gram organ tersebut dipakai sebagai input pada software dosimetri internal OLINDA/EXM, dengan cara melakukan plotting %ID/gram versus waktu, yang akan menghasilkan residence time di masing-masing organ. Setelah residence time diperoleh, dosis internal radiasi pada masing-masing organ dan seluruh tubuh dapat diketahui. Hasil studi menunjukkan bahwa tiga  organ yang memiliki dosis internal tertinggi 177Lu DOTA Trastuzumab adalah : paru-paru, hati dan ovarium dengan dosis masing-masing 0,063; 0,046 dan 0,025 mSv/MBq. Disimpulkan bahwa hasil estimasi dosis internal radiasi total yang diperoleh manusia pada penyuntikan radiofarmaka 177Lu-DOTA Trastuzumab adalah 0.21 mSv/MBq. ABSTRACT   INTERNAL DOSE ESTIMATION OF 177Lu-DOTA TRASTUZUMAB IN HUMAN BASED ON THE BIODISTRIBUTION DATA OF MICE: A PRELIMINARY STUDY. A new radiopharmaceutical for treating Breast Cancer of HER-2 type, 177Lu DOTA-Trastuzumab, had been successfully produced by The Centre for Radioisotope and Radiopharmaceutical Technology-BATAN. With regard to the patient safety, the new drug development process need internal dosimetry data obtained of preclinical study in animal. Hence, this study has been objected to estimate the internal radiation dose in human by performing the biodistribution test in mice. In this study, the biodistribution test was done for 25 mice and sacrificed at 1, 2, 3, 4, 24, 48 hour after the injection of 177Lu DOTA-Trastuzumab. There were 11 organs, namely brain, stomach, intestine, heart, kidneys, liver, lungs, muscle, bone, spleen, and urinary bladder, have been investigated by observing the uptake in each organ during the proposed time. The result of biodistribution test then were being calculated into injection dose per gram human organ (%ID/gr). To estimate the internal dose in human, the data of % ID/gram in human need to be plotted to calculate the residence time which will be need as the input for OLINDA/EXM, a tool for calculating internal dosimetry in Nuclear Medicine fields. As a result, three organs that have been estimated receiving the highest internal radiation dose due to the administration of 177Lu DOTA Trastuzumab are: lungs, liver, and ovaries at approximately 0,063; 0,046 and 0,025 mSv/MBq respectively. To conclude, the total internal dose in human reference model due to the administration of 177Lu-DOTA Trastuzumab has been estimated to be 0,21 mSv/MBq.

Generalized Lymphadenopathy due to Chronic Lymphocytic Leukemia (CLL) : 18F-FDG PET Imaging

Journal of Medicine and Health Vol 1, No 3 (2016)
Publisher : Maranatha Christian University

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Abstract

Lymphadenopaty is a common clinical finding with a broad differential diagnosis, withCarcinoma of Unknown Primary (CUP) as one of it’s most common causes. Flourine-18 fluoro-2 deoxy glucose (18F- FDG) positron emission tomography (PET) is a Nuclear Medicinescintigraphy procedure commonly used to localize suspected a primary lesion by depicting ametabolic status. However, in the expertise of 18F FDG PET study, clinical finding andepidemiologic data must be considered to get a better conclusion. We describe 18F-FDG PETstudy in the presence of generalized lymphadenopathy due to chronic lymphocytic leukemia(CLL), a rare disease which is initially suspected of having CUP.Keywords: 18F-FDG PET, lymphadenopathy, lymphoma, leukemia