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ABSTRAK
Latar belakang: Diffuse large B-cell lymphoma DLBCL merupakan suatu entitas yang heterogen baik secara klinik maupun morfologik. Berdasarkan kriteria Hans melalui pemeriksaan imunohistokimia IHK CD10, Bcl-6 dan MUM1, DLBCL dikelompokkan menjadi 2 subtipe yaitu germinal center B-cell like GCB dan non-germinal center B-cell like non-GCB . Kesintasan subtipe GCB umumnya lebih baik daripada non-GCB, namun sebagian dapat berespon buruk. Penanda prognosis buruk c-Myc lebih sering ditemukan pada subtipe GCB, sedangkan infeksi EBV melalui NF-kB lebih sering ditemukan pada subtipe non-GCB. Penelitian ini bertujuan untuk mengetahui perbedaan ekspresi c-Myc dan EBV pada kedua subtipe DLBCL yang dapat berpengaruh pada kesintasan.Bahan dan cara: Penelitian ini menggunakan metode potong lintang, deskriptif analitik. Sampel terdiri atas 20 kasus untuk masing-masing subtipe. Dilakukan penilaian ulang diagnosis imunohistopatologik dari sediaan H E dan IHK sesuai kriteria Hans. Penilaian pulasan dilakukan oleh kedua pengamat dengan program ImageJ pada c-Myc dengan cut off ge; 60,4 dan EBV melalui EBER-ISH dengan nilai positivitas ge; 20 .Hasil: Hasil penilaian antar kedua pengamat menyimpulkan tidak ada perbedaan bermakna dengan p = 0,952. Ekspresi c-Myc tinggi secara bermakna lebih sering ditemukan pada subtipe GCB dibandingkan subtipe non-GCB p < 0,05 . Disisi lain EBV positif hanya ditemukan 4 kasus 10 dan cenderung lebih banyak pada subtipe non-GCB.Kesimpulan: DLBCL subtipe GCB lebih sering ditemukan ekspresi c-Myc tinggi, sedangkan infeksi EBV melalui NF-kB cenderung terdapat pada subtipe non-GCB. Positivitas c-Myc dan EBV ini diduga berkaitan dalam perbedaan kesintasan pada masing-masing subtipe DLBCL.

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ABSTRACT
"Background Diffuse large B cell lymphoma DLBCL is clinically and morphologically heterogeneous groups of lymphoma. Based on Han 39 s immunohistochemistry IHC features consists of CD10, Bcl 6 and MUM1, DLBCL are grouped into 2 subtypes the germinal center B cell like GCB and non germinal center B cell like non GCB . GCB subtype generally has been shown to have better survival than non GCB, while some may respond poorly. c Myc is a worse prognosis marker more commonly found among GCB subtype, meanwhile the EBV infection through NF kB pathway that mostly found among non GCB subtype. The study aims was analyzed the difference of c Myc and EBV expression in both subtypes which could predict survival.Methods This research used cross sectional method. The samples were consist of 20 cases for each DLBCL subtype. The slides were rediagnosed based on immunohistopathologic diagnosis from H E and IHC slides based on Han rsquo s criteria. c Myc immunostaining cut off ge 60,4 and EBV with Eptein Barr early RNA in situ hibridization cut off 20 which are assesed using ImageJ programe by two independent observers. Result The results between two observers showed no significant difference with p 0,952. Expression of high c Myc is found to be significantly higher in GCB subtype p 0,05 . Whereas EBV positive were only found in 4 cases 10 , mostly in non GCB subtype. Conclusion The expression c Myc is higher in GCB than non GCB subtype. While the EBV infection found among non GCB subtype. Positivity of c Myc and EBV is believed to affect differences in survival for each subtype DLBCL.

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Latar belakang: Kanker payudara merupakan kanker tersering dengan mortalitas kematian kelima tertinggi di dunia. Tamoksifen, terapi hormon lini pertama kanker payudara ditemukan kasus resisten pada sel kanker dengan ekspresi c-myc yang tinggi. C-myc adalah faktor transkripsi yang menginduksi proliferasi, diferensiasi, serta metastasis sel kanker. Penelitian terbaru telah menemukan lunasin, protein dari ekstrak kedelai yang dinilai memiliki berbagai efek antikanker. Tujuan penelitian ini adalah mengetahui apakah lunasin dapat menurunkan ekspresi protein c-myc pada sel kanker payudara. Metode: Desain penelitian adalah true-experimental laboratorium dengan sampel preparat jaringan kanker payudara tikus tersimpan. Kelompok sediaan terdiri kelompok normal, kontrol negatif, kontrol positif, terapi kombinasi (lunasin dan tamoksifen) dan lunasin. Jaringan diwarnai secara imunohistokimia dengan diaminobenzinidie (DAB) dan antibodi anti-c-myc. Sediaan dipotret dengan mikroskop cahaya perbesaran 400 kali sebanyak 5 lapang pandang secara acak. Hasil berupa H-score ekspresi c-myc yang dihitung menggunakan software ImageJ dengan plugin immunohistochemistry (IHC) Profiler. Hasil: Kelompok dengan indeks H-score tertinggi berurutan adalah kontrol negatif (174), terapi tamoksifen, (149,4), terapi lunasin (146,6), kombinasi (138,6), dan normal (129,4). Ekspresi c-myc pada seluruh kelompok berbeda signifikan dibandingkan dengan kontrol negatif. Perbandingan setiap dua kelompok juga berbeda signifikan kecuali antara kelompok kontrol positif dengan lunasin. Kesimpulan: Lunasin dari ekstrak kedelai menghambat ekspresi protein c-myc pada sel kanker payudara tikus yang diinduksi DMBA. Lunasin dan tamoksifen masing-masing mampu menurunkan ekspresi protein c-myc. Terapi kombinasi lunasin dan tamoksifen paling efektif menurunkan ekspresi c-myc sel kanker payudara ......Introduction: Breast cancer is the most prevalent and the fifth leading cause of death in the world. Tamoxifen, the first-line hormone therapy, which is found to be resistant to breast cancer cells with high c-myc expression. C-myc is a transcription factor that induces the proliferation, differentiation, and metastasis of cancer cells. Recent research has discovered lunasin, protein derived from soybean extract that have anticancer activities. The aim of this study was to determine whether lunasin can reduce c-myc protein expression in breast cancer. Method: The study design is a true-experimental laboratory with stored rat breast cancer tissue samples. The group was consisted of normal group, negative control, positive control, combination therapy (lunasin and tamoxifen) and lunasin. Tissues were stained with anti-c-myc adnd was photographed with a light microscope equipped with a 400x magnification camera with 5 fields of view at random. The result is an H-score of c-myc expression which is calculated using Image J software with the immunohistochemistry profiler plugin. Result: The groups with the highest H-score value to the lowest, respectively, are negative control (174), positive control (149,4), lunasin therapy (146,6), combination therapy (138,6), and normal (129,4). The C-myc expression in all groups is significantly different compared to the negative control. Conclusion: Lunasin inhibits the expression of c-myc protein in DMBA-induced rat breast cancer. Lunasin and tamoxifen are each able to reduce c-myc expression. The most effective way to reduce c-myc expression on breast cancer cells is combination therapy (lunasin and tamoxifen).

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Kanker kolorektal merupakan keganasan yang terbentuk melalui transformasi sel epitel yang menyusun lapisan mukosa dari bagian kolon dan rektum usus besar. Tingginya angka kasus baru di Indonesia menempatkan kanker kolorektal pada posisi keempat pada tingkatan kasus kanker paling umum di Indonesia. Gen c-MYC merupakan salah satu onkogen dalam tubuh manusia yang berperan penting dalam berbagai proses seluler. Potensi gen c-MYC dalam memicu karsinogenesis timbul ketika gen ini terderegulasi sehingga c-MYC berperan sebagai salah satu kandidat dalam studi ekspresi gen berbasis RNA dalam kasus kanker kolorektal. Molekul RNA berperan penting dalam proses ekspresi gen sehingga kerap digunakan sebagai biomarker dalam mengukur tingkat ekspresi suatu gen yang dapat dikuantifikasi menggunakan metode Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Tingkat ekspresi dari gen c-MYC kemudian dihitung berdasarkan nilai cycle threshold (Ct) menggunakan rumus Livak dan dilakukan uji statistik dengan bantuan perangkat lunak SPSS. Ekspresi gen dikatakan mengalami peningkatan atau upregulation apabila nilai 2-∆∆Ct > 1 sementara ekspresi gen dikatakan mengalami penurunan atau downregulation apabila nilai 2-∆∆Ct < 1. Hasil perhitungan tingkat ekspresi gen c-MYC dari sepuluh pasang sampel yang diperoleh dari sepuluh pasien kanker dari Rumah Sakit Cipto Mangunkusumo menunjukkan bahwa sebanyak 50% pasien menunjukkan terjadinya upregulation gen c-MYC sedangkan 40% pasien menunjukkan terjadinya downregulation gen c-MYC. Sementara itu, 10% dari pasien tidak menunjukkan adanya ekspresi gen c-MYC. Meski demikian, hasil uji Mann-Whitney menyimpulkan bahwa tidak terdapat perbedaan signifikan antara ekspresi gen c-MYC pada sampel jaringan normal dan kanker kolorektal yang diduga disebabkan oleh kurangnya sampel yang digunakan dalam penelitian. ......Colorectal cancer is a malignancy developed by cell transformation that occurs on the epithelium cells that forms the lining mucosa of the colon and rectum region of the large intestine. The rising number of new colorectal cancer cases in Indonesia makes it the fourth most common cancer in Indonesia. The c-MYC gene is one of the many oncogenes of the human body that affects cellular processes. Having the potential in inducing carcinogenesis when deregulated, the c-MYC gene is the perfect candidate for RNA-based gene expression study. RNA molecules play a big part on the overall gene expression process. Thus, it is commonly used as a biomarker to quantify gene expression levels using various methods, one of which is the Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). The expression of the c-MYC gene is calculated with the Livak formula towards the cycle threshold (Ct) value obtained which then the numbers are statistically analyzed using the help of the SPSS software. The gene expression can be considered as upregulated when the 2-∆∆Ct > 1 and can be considered as downregulated when the 2-∆∆Ct < 1. The c-MYC gene expression level result that are obtained from ten pairs of tissue sample from ten cancer patients of Dr. Cipto Mangunkusumo Hospital shows that 50% of the patients experience c-MYC upregulation while 40% of the patients experience downregulation of the c-MYC gene. The last 10% of the patients do not show any expression of the c-MYC gene. Despite the results, according to the statistical Mann-Whitney test, the data obtained does not show any significant difference between the c-MYC gene expression levels on normal and colorectal cancer tissues due to the small number of samples used.

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Background: According to WHO, breast cancer has the highest incidence rate among women. Breast cancer is caused by the uncontrolled growth of abnormal cells that form in breast tissue, triggered by the presence of cancer stem cells. The invasive properties of breast stem cells are closely related to the pluripotency of these cells. The pluripotency of a cell is closely related to the genes expressed. In this study, c-Myc gene expression was observed to determine the level of pluripotency of breast cancer stem cell fraction samples separated using the Magnetic Activated Cell Sorting (MACS) technique. Method: mRNA was obtained from 11 breast cancer stem cell samples which were fractionated using MACS. The expression of c-Myc in these cell fractions was analyzed using one step real time RT-PCR with SYBR Green ( Bioneer®) and electrophoresis. Results: Based on the experimental results, high level expression of c-Myc was present in the CD24-/44- cell fraction, while low level expression of the c-Myc gene was found in the CD24-/44+ cell fraction. Conclusions: The c-Myc gene is expressed in all breast cancer stem cell fractions. Looking at the c-Myc gene expression, higher levels of pluripotency can be found in the CD24-/44- cell fraction compared to CD24-/44+.

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Latar belakang: Data dari World Health Organization, Centers for Disease Control and Prevention dan Kementerian Kesehatan RI menunjukan bahwa kanker payudara merupakan kanker yang paling umum pada wanita. Penyembuhan kanker melalui berbagai cara telah banyak dilakukan, namun pertumbuhan kembali dari kanker telah banyak dilaporkan. Sel punca kanker diyakini berperan dalam pertumbuhan kanker maupun rekurensi setelah pengobatan. Berdasarkan beberapa riset, CD44+/CD24- sel punca kanker memiliki potensial yang tinggi untuk menimbulkan kanker. Beberapa gen memiliki peran sebagai faktor transkripsi yang berkontribusi dalam pertumbuhan kanker dan beberapa berperan juga dalam mempertahankan tingkat pluripotensi kanker. c-Myc merupakan salah satu gen yang mempertahankan iPS (induced pluripotent stem cells) bersama dengan KLF4, Oct4, SOX2 dan Nanog. Namun demikian, selama pertumbuhan kanker, lingkungan mikro dari kanker menjadi hipoksia. Berhubungan dengan ini, pengaruh hipoksia terhadap ekspresi gen yang berfungsi dalam pluripotensi masih belum jelas. Oleh karena itu, eksperimen ini menyelidiki ekspresi gen c-Myc dalam sel punca kanker yang diinduksi hipoksia. Metode: Sel punca kanker payudara CD44+/CD24- diinduksi oleh beberapa durasi hipoksia (0 jam, 0.5 jam, 4 jam, 6 jam dan 24 jam). Total RNA sel kemudian diekstraksi dan mRNA gen c-Myc diamplifikasi melalui one-step qRT-PCR. Ekspresi relative dari gen c-Myc dilakukan dengan formula Livak berdasarkan nilai Ct yang diperoleh dengan gen 18S. Sebagai kontrol, konfirmasi ekspresi gen c-Myc dikonfirmasi melalui elektroforesis. Hasil: Ekspresi c-Myc pada sampel sel punca kanker payudara CD44+/CD24- yang diinduksi hipoksia selama 0.5 jam sedikit mengalami peningkatan dibandingkan dengan sampel 0 jam walaupun tidak signifikan. Ekspresi c-Myc pada sampel yang diinduksi hipoksia selama 4, 6 dan 24 jam menurun dibandingkan sampel yang tidak diinduksi hipoksia. Kesimpulan: Ekspresi c-Myc pada sel punca kanker CD44+/CD24- yang digunakan dalam eksperimen ini cenderung menurun pada 3 durasi hipoksia yang berbeda (4 jam, 6 jam dan 24 jam) pada kondisi in vitro. ......Background: Data from World Health Organization, Centers for Disease Control and Prevention and Kementerian Kesehatan RI show that breast cancer is the most common cancer among women. Eradicating cancer through several treatments have been done but there are cases in which cancer relapse is reported. Cancer stem cells have been found to develop the cancer as well as play important role in cancer regrowth. According to some researches, CD44+/CD24- breast cancer stem cells potential to cancer development is high. Several genes which have role as transcription factors may contribute to cancer growth and some act to maintain the cancer stemness and pluripotency level. c-Myc is one gene which maintains iPS (induced pluripotent stem cells) along with KLF4, Oct4, SOX2 and Nanog. However, during the cancer growth the cancer microenvironment becomes hypoxic. In accordance to this, the effect of hypoxia towards the gene expression acting in cancer pluripotency was not yet clear. Therefore c-Myc expression in hypoxia-induced breast cancer stem cells was assessed in this research. Method: The CD44+/CD24- breast cancer stem cells (BCSCs) are induced by several hypoxia durations (0 hour, 0.5 hour, 4 hours, 6 hours and 24 hours) in hypoxia chamber. The mRNA of BCSCs is extracted through RNA isolation procedure. Following this, qRT-PCR procedure is done to amplify the mRNA. The Ct (cycle threshold) obtained from qRT-PCR are calculated using Livak formula to get the c-Myc relative expression from the samples. Ct of 18S is used to normalize the c-Myc Ct. Electrophoresis is done next to confirm the c-Myc expression. Results: c-Myc expression in 0.5 hour hypoxia induced CD44+/CD24- breast cancer stem cells sample is slightly high than in 0 hour hypoxia induced sample, even though the increase is not significant. Meanwhile, c-Myc expression in 4, 6 and 24 hours hypoxia induced samples are lower than 0 hour hypoxia induced sample. Conclusion: c-Myc expression from the breast cancer stem cell CD44+/CD24- samples used in this experiment tend to have gradual decrease during 3 different periods (0 hour, 0.5 hour, 4 hours, 6 hours and 24 hours) of hypoxia in vitro.

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ABSTRAK
Sel punca kanker adalah subpopulasi kecil sel kanker yang memiliki karakter stemness seperti halnya sel punca normal, antara lain self renewal dan ketahanan hidup yang tinggi sehingga dapat menyebabkan kekambuhan dan metastasis tumor. Pada saat ini, dilaporkan bahwa gen SOX2 dan c-Myc berperan penting dalam menginduksi sel punca progenitor dari sel fibroblast manusia dewasa. Oleh karena itu, kami berkeinginan untuk meneliti level RNA gen SOX2 dan c-Myc sel yang diperoleh dari jaringan kanker payudara dengan populasi sel punca kanker menggunakan metode reverse transcription-polymerase chain reaction (RT-PCR). Metode RT-PCR merupakan metode terpilih untuk mendeteksi jumlah mRNA dalam jumlah kecil namun metode ini memerlukan normalisasi agar pengukuran menjadi lebih akurat. Kami menormalisasi level RNA dengan menggunakan housekeeping gene PUM1 sebagai kontrol dalam. Hasilnya menunjukkan bahwa ekspresi gen SOX2 dan c-Myc meningkat sebanyak 1,47% -13,11% dan 27,37%- 37,77% setelah dinormalisasi yang mengindikasikan bahwa ekspresi PUM dan c-Myc meningkat pada sel punca kanker payudara.

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ABSTRACT
Cancer stem cells are a small subpopulation of cancer cells which has stemness characteristiclikenormalstemcells.someofthosecharacteristicsareself-renewal and high rate of survival that can cause tumor recurrence and metastasis. Recently.scientists reported that SOX2 and c-Myc genes are involved in induction of pluripotent stem cells from adult human fibroblast. Therefore, we intended to examine RNA level of SOX2 and c-Myc in cells that taken from breast cancer tissues with stem cells population using reverse transcription polymerase chain reaction (RT-PCR). Given the ability to detect very low abundance mRNA, reverse transcription-polymerase chain reaction is a complex technique that requires normalization to become more accurate. We normalize RNA level using housekeeping gene PUMl as internal control. Our result show that expression of SOX2 and c-Myc increase by 1,47%-13,11% and 27,37%- 37,77% after normalization whereas indicate S0X2 and c-Myc are rising up in breast cancer stem cells.

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protocol comm All-92 is ussed for therapy ALL at Dr.Sardjito General hospitl.....

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Efek lunasin sebagai anti-inflamasi, antioksidan, anti kanker dan anti metastasis telah lama diketahui. Lunasin melalui motif RGD pada strukturnya dapat berikatan dengan integrin dan menghambat jalur persinyalan FAK/Src/ERK/NFkB sehingga aktivasi NF-kB menurun. Hal ini akan menyebabkan penurunan aktifitas proliferasi dan peningkatan apoptosis. Penelitian ini bertujuan untuk mempelajari efek lunasin dalam menghambat karsinogenesis kolorektal dan mempelajari protein-protein yang terlibat dalam mekanisme tersebut. Penelitian ini menggunakan bahan biologi tersimpan (BBT) blok parafin jaringan kolon mencit BALB/c yang diinduksi AOM dan DSS yang terdiri dari 6 kelompok yaitu kelompok normal yang tidak diinduksi dan diberi perlakuan, kelompok kontrol negatif yang hanya diinduksi AOM dan DSS, kelompok kontrol positif yang diinduksi dan diberi aspirin, kelompok lunasin dosis rendah, sedang dan tinggi masing-masing yang diinduksi dan diberi lunasin 75, 150 dan 200 mg/BB. Jaringan kolon hewan diambil dan dilakuan pulasan hematoksilin eosin dan imunohistokimia untuk mengukur ekspresi Ki67, C-myc dan Bcl-2. Kuantifikasi ekspresi Ki67, C-myc dan Bcl-2 dari hasil pulasan imunohistokimia dilakukan dengan menggunakan metode H-score. Data H-score diolah dan dianalisa menggunakan uji statistik Kruskall Wallis. Ekspresi Ki67, C-myc dan Bcl-2 berbeda signifikan pada setiap kelompok (p=0,000). Lunasin dapat menurunkan ekspresi Ki67, C-myc dan Bcl-2 pada kolon model hewan karsinogenesis kolorektal yang diinduksi AOM dan DSS. ...... The effects of Lunasin as anti-inflammatory, antioxidant, anti-cancer and antimetastatic effects have long been known. Lunasin through the RGD motive on its structure can bind to integrins and inhibit the FAK/Src/ERK/NF-kB signaling pathway and supress NF-kB activation. It causes decreasing of proliferative activity and increasing of apoptosis. This study aims to study the effect of lunasin in inhibiting colorectal cancer carcinogenesis and investigate the proteins involved in this mechanism. This study used stored biological material (BBT), paraffin blocks, colon tissue of BALB/c mice induced by AOM and DSS which consisted of 6 groups, the normal group that was not induced and treated, the negative control group that was only induced by AOM and DSS, the positive control group. who were induced and given aspirin, the low, medium and high dose lunasin groups were induced and given lunacin 75, 150 and 200 mg/kgBW, respectively. Colon tissue was taken and stained with hematoxylin eosin and immunohistochemistry to measure the expression of Ki67, C-myc and Bcl-2. The quantification of Ki67, C-myc and Bcl-2 expressions from the results of immunohistochemical stains was done using the H-score method. The H-score data were processed and analyzed using the Kruskall Wallis statistical test. Expressions of Ki67, C-myc and Bcl-2 were significantly different in each group (p = 0.000). Lunasin can decrease the expression of Ki67, C-myc and Bcl-2 in colon animal models of AOM and DSS-induced colorectal cancer.

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Kanker payudara merupakan penyakit kanker yang berkembang dari jaringan epitel duktus dan kelenjar susu dalam payudara. Kanker payudara merupakan kanker dengan prevalensi tertinggi di dunia dan telah mengalami kenaikan jumlah kasus yang signifikan (16,6%) per tahun 2020 di Indonesia. Pengobatan dengan kemoterapi telah umum dilakukan namun dilaporkan memiliki banyak efek samping. Oleh karena itu, perlu dilakukan prediksi kemosensitivitas pada pasien sebelum obat diberikan. Prediksi kemosensitivitas dapat dilakukan dengan menggunakan kultur primer metode eksplan sebagai patient-derived model in vitro yang menggunakan sel primer langsung dari pasien dan dapat memprediksi respons klinis terhadap obat. Adanya ekspresi relatif gen c-Myc selaku oncogene addiction gene dapat menjadi biomarker potensial pada kultur eksplan setelah diberi perlakuan Doxorubicin. Pada penelitian ini, ekspresi c-Myc pada jaringan asal dan kultur eksplan serta pada kultur eksplan sebelum dan sesudah perlakuan diukur menggunakan metode semi kuantitatif RT-PCR dengan tahapan isolasi RNA, kuantifikasi, amplifikasi, dan visualisasi dengan elektroforesis. Kultur eksplan yang berhasil ditumbuhkan adalah sampel luminal A dan B. Sampel A menunjukkan migrasi sel hingga konfluensi 50%. Sementara uji viabilitas pada hasil kultur sampel B menunjukkan persentase viabilitas kultur non-treatment 60% dan treatment dosis 0,68 μM 41%. Hasil visualisasi elektroforesis tidak menunjukkan adanya ekspresi c-Myc di seluruh sampel. ......Breast cancer is a malignant tumor formacy on ductus epithelial tissue and mammary gland of the breast. The prevalence number of breast cancer is currently leading among other cancers in the world and significantly increasing especially in Indonesia (16,6% new cases in 2020). Treatment using chemotherapy agents is the most common option for patients but has many side effects. Chemosensitivity prediction using an in vitro model is recommended for more personalized treatment, and can be performed using primary culture (explant method) as an in vitro patient-derived model that uses primary cells directly from the patient and can predict pathological response to chemotherapy agents. c-Myc gene as an oncogene addiction gene can be a potential biomarker of explant cultures after being treated by Doxorubicin. In this study, c-Myc expression in fresh tissue and explant culture, also in culture prior to and after treatment, was measured using a semi quantitative RT-PCR method involving the process of RNA isolation, quantification, amplification, and visualization using electrophoresis. Luminal A and Luminal B samples of explant culture were successfully grown and harvested. A sample showed cell migration up to 50% confluency. Meanwhile, the viability test on the results of the B culture showed the viability percentage of non-treatment culture was 60% and 0,68 μM treatment dose culture 41%. The results of electrophoretic visualization consistently showed downregulation of c-Myc in the form of a very low expression in all samples.