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- 1. RECENT RESEARCH 2018-2022 NOOR NABILAH BINTI TALIK SISIN (BELLE) PhD (Radiation Biology) 2021 Master (Biomedicine) 2017 Bachelor (Biomedical Science) 2014 1
- 2. Clinic al beam s Metallic nanoparticles Conventiona l drug Natural compound 2 Radio- biological effects RADIOSENSITIZATION EFFECTS OF SEVERAL COMPOUNDS ON CANCER CELL LINES
- 3. INVESTIGATED COMPOUNDS Metallic nanoparticles •Bi2O3 •Schiff-based Fe •Schiff-based Cu •Schiff-based Mn Conventional drug •Cisplatin Natural compound •Baicalein-rich fraction 3
- 4. CELL CULTUTRE 2D Monolayer cell lines MCF-7 breast cancer cells MDA-MB-231 breast cancer cells HCT 116 colon cancer cells NIH/3T3 normal fibroblast cells 4 2D Monolayer cell lines Hep G2 liver cancer cells HeLa cervical cancer cells L929 normal connective tissue
- 5. CELLS IRRADIATION SET UP 5
- 6. CLINICAL BEAMS Photon beam Electron beam Brachytherapy: microSelectron HDR 192Ir Proton beam 6 Hospital Universiti Sains Malaysia (HUSM) HUSM HUSM Hyogo Ion Beam Medical Centre, Japan
- 8. BIOLOGICAL ASSAYS Cell viability (Prestoblue assay) ROS (DCFH-DA assay) Uptake/Cellular localization (Microscopy) 8
- 9. BIOLOGICAL ASSAYS Clonogenic assay Apoptosis/ Cell cycle assay (flow cytometry) Subcellular changes (Raman micro- spectroscopy) 9
- 12. WAN NORDIANA RAHMAN research team (Universiti Sains Malaysia) 12
- 13. OTHER RESEARCH ACTIVITIES Synchrotron-based FTIR microspectroscopy beamline (BL4.1) Enzyme-linked immunosorbent assay (ELISA) Genotyping, gel electrophoresis Synchrotron Light Research Institute, Thailand, 2018 Universiti Sains Malaysia, 2019 International Research Center for Medical Sciences, Japan,
- 14. 14 OTHER RESEARCH ACTIVITIES Histopathology Immunostaining, 3D ex-vivo imging (confocal microscope) International Research Center for Medical Sciences, Japan, 2017 International Islamic University Malaysia, 2014
- 15. RECENT RESEARCH 2018-2022 NOOR NABILAH BINTI TALIK SISIN (BELLE) PhD (Radiation Biology) 2021 Master (Biomedicine) 2017 Bachelor (Biomedical Science) 2014 15
Editor's Notes
- So, my name is Noor Nabilah, but you can call me Belle. I am from Malaysia, located near Singapore, Indonesia, Brunei and Thailand. As you know, I graduated in Radiation Biology and also in Biomedical Science.
- My recent research since in my doctoral study was on the topic of…. The investigated compounds consist of several types such as … which were treated on several cell lines and irradiated using clinical radiotherapy beams at hospital. After that, the radiobiological effects were observed.
- until now, I have been involved in the project that combined these 3 types of components, …., to see which combination is the most effective radiosensitizer for radiotherapy. As side projects, I also examined the effects of the Schiff-based iron, copper and manganese NPs.
- So, the investigated compounds would be tested on the several types of cell lines first. Recently, we only used these 4 cell lines… but I also had experience in culturing HepG2, HeLa and L929 cells. I am proficient in the monolayer cell cultures, but I am also confident that I can handle culturing spheroid or organoid cells.
- Here’s how we irradiated the cells and compounds, in the flask, plates and also PCR tubes. There would be water equivalent phantom above and below the samples.
- Here are the clinical beams that we used in the hospital in Malaysia, and Japan; the ….
- I’ll briefly show again the flow of what I did previously. First, the cells were treated with the compounds. Then, the we tested the cytotoxicities of the compounds using prestoblue assay, ROS and also the cellular uptake of the compounds. After that, we irradiated the cells and measured the radiobiological effects on the survival fractions, ROS, apoptosis and Raman spectra.
- Precisely, these are the biological assays that I have conducted previously. We used 96 wells plates and microplate reader for the cell viability and ROS measurement. Fot the localization of the compounds into the cells, we used crystal violet dye and microscopy.
- In addition, we also used clonogenic assay, flow cytometry for ROS and cell cycle testing, as well as Raman microspectroscopy to investigated the subcellular changes.
- Here are the publications with me as the first authors, from the year 2019 to 2022.
- The research that had been presented are all conducted with Dr. Rahman research team, from Universiti Sains Malaysia.
- Besides that, I also had the opportunities to joined several short courses and project that involved the ….
- Table lists the summary of the SER values from the individual component treatments. 1) Across all the RT sources, the highest SER value of 2.24 was measured up from the MCF-7 cells treated with Cis and electron beam irradiation. 2) It is also observed that only the photon beam irradiation would cause radiosensitization enhancement in normal cells, in comparison to the brachytherapy and electron beam therapy. 3) Furthermore, only the SER value yielded from normal cells for brachytherapy was lower than the value of 1, which suggested the treatment did not sensitize the normal cell line and the selectivity of individual treatments towards breast cancer cells for the brachytherapy source. Overall, it is predicted that the presence of BiONPs would increase the effective atomic numbers, absorption probabilities and radiation scattering (Ovsyannikov et al., 2015; Taha et al., 2018). Meanwhile, Cis is an effective radiosensitizer but could cause nephrotoxicity. Thus, we evaluated another option of non-toxic radiosensitizer, the BRF 4) Overall data concluded that BRF could sensitize all 3 cells when irradiated with photon beams. The results may be compelled by the suppression of HIF, which blocked the cellular transcription activity, as well as induced apoptosis and DNA damages. 5) On the other hand, BRF was found to provide radioprotection towards all 3 cell lines from brachytherapy irradiation. It was known that, natural extracts and compounds would have antioxidative properties, which could lead to the radioprotective effect. BRF might able to execute its function as an antioxidant that would prevail over the irradiation-induced oxidative stress, which was caused by the low energy released by the brachytherapy source. Overall, it was found that Cis is the most excellent individual radiosensitizer, followed by BiONPs and BRF. ================================== the role of Cis as a radiosensitizer in CRT also had been evaluated in several cell lines. The high sensitization enhancement by Cis for electron beam may be induced by the interactions between the Cis and electrons, leading to the cleavage of chlorine atom of the Cis compound, and bonding of the product to the cellular DNA (Kopyra et al., 2009). A combination of Cis and irradiation in breast cancer cells would activate the upregulation of microRNA-200 family expressions, which increased the ROS production, and indirectly would amplify the cellular apoptosis as well as autophagic cell deaths.
- This is the SER values from the combination treatments The highest SER of 4.29 was observed owing to the treatment of the BC combination on MCF-7 cells. The same pattern of radiosensitization effects could be seen in MCF-7 and MDA-MB-231 cell lines, in which the of BC was higher than BCB and BB combinations. The values signify that the BC combination could be an excellent radiosensitizer for breast cancer cells as it only caused a moderate negative effect on normal cells. 2) In comparison to the BC combination, the BCB combination treatment had incited the highest cell deaths in NIH normal cells. It showed that the BCB combination is the least preferred to be used as the radiosensitizer. The BB combination also is not a good radiosensitizer option as it elicited approximately the same sensitization effect level on both cancer and normal cells. In the present study, only a low concentration of Cis was used to lessen the drug effect and emphasized the impact of BiONPs and irradiation. Consequently, any sensitization process which transpired in cells could be due to the dynamism of BiONPs, while being boosted by Cis and irradiation.
- Apoptosis is highly related to radiosensitization. Based on the statistical test, the total apoptosis of the control cells were significantly boosted from the 14 hours to 40 hours post-brachytherapy For the BC-treated cells, the percentage of early apoptosis was notably higher than that of late apoptotic cells, for both 14- and 40-hours post-irradiation incubation periods. It showed that early apoptosis dominated the process. This situation may be due to the presence of bismuth-based NPs, influenced by the Bcl2/Bax signaling pathways, which were known as the apoptosis biomarkers. After the brachytherapy sessions in MCF-7, it was suggested that there were reduction of the Bcl2 while up-regulation of the pro-apoptotic Bax expressions. RAP80 is one of the DNA-damage response (DDR) protein, which might be reduced after the RT and promoted the apoptotic pathway (Jin et al., 2019; Mok and Henderson, 2012). 2) In this study, it was verified that the BiONPs did not enter the nucleus. Thus, maybe the BiONPs was not the leading cause of the apoptosis. Apoptosis induction could be founded by the radiation or the presence of the Cis in the cells, which involved the regulation of several genes and proteins such as
- Onto the analysis by raman spectroscopy… The biochemical alterations spectra for control and treatment groups ranged from 400 to 1700 cm-1 . 2) But here we would emphasized only on 3 highest vibration detected.
- Apoptosis is highly related to radiosensitization. Based on the statistical test, the total apoptosis of the control cells were significantly boosted from the 14 hours to 40 hours post-brachytherapy For the BC-treated cells, the percentage of early apoptosis was notably higher than that of late apoptotic cells, for both 14- and 40-hours post-irradiation incubation periods. It showed that early apoptosis dominated the process. This situation may be due to the presence of bismuth-based NPs, influenced by the Bcl2/Bax signaling pathways, which were known as the apoptosis biomarkers. After the brachytherapy sessions in MCF-7, it was suggested that there were reduction of the Bcl2 while up-regulation of the pro-apoptotic Bax expressions. RAP80 is one of the DNA-damage response (DDR) protein, which might be reduced after the RT and promoted the apoptotic pathway (Jin et al., 2019; Mok and Henderson, 2012). 2) In this study, it was verified that the BiONPs did not enter the nucleus. Thus, maybe the BiONPs was not the leading cause of the apoptosis. Apoptosis induction could be founded by the radiation or the presence of the Cis in the cells, which involved the regulation of several genes and proteins such as