MyMedR

Displaying all 7 publications

Abstract:

Sort:

Fulltext Influence of out-of-field photon beam radiotherapy to the cancer cell survival

Raizulnasuha Ab Rashid, Nurhikmah Azam, Norhayati Dollah, Wan Nordiana W Abd Rahman

Jurnal Sains Nuklear Malaysia, 2018;30(2):47-56.
MyJurnal

The purpose of the study was to determine the effect of out-of-field photon beams radiotherapy to the cancer cell survival. In this study, HeLa and T24 cancer cells were irradiated with 6 MV and 10 MV photon beams in two different conditions, one with intercellular communication with the in-field cell and one without the communication. Cells survival was determined by clonogenic assay. In the presence of intercellular communication, the cell death was increased which indicate the presence of radiation induced bystander effects (RIBE). The effects were also dependent on the cell types and photon energy where the HeLa cells exhibit less survival compares to T24 cells and the effects were prominent at higher photon energy. This study demonstrates that the out-of-field cells in conjunction with RIBE plays important roles in the cells response towards megavoltage photon beam radiation therapy.

Matched MeSH terms: Bystander Effect
An evaluation of novel real-time technology as a tool for measurement of radiobiological and radiation-induced bystander effects

Ibahim MJ, Crosbie JC, Paiva P, Yang Y, Zaitseva M, Rogers PA

Radiat Environ Biophys, 2016 May;55(2):185-94.
PMID: 26994995 DOI: 10.1007/s00411-016-0641-x

The xCELLigence real-time cell impedance system uses a non-invasive and label-free method to create a cell index that is a composite measure of cell proliferation. The aim of this study was to evaluate xCELLigence against clonogenic assay (gold standard) for measuring radiobiological effects and radiation-induced bystander effects (RIBE). A radiobiological study was conducted by irradiating EMT6.5, 4T1.2 and NMUMG cell lines with different radiation doses, while a RIBE study was done using transfer of conditioned media (CM) harvested from donor to the same type of recipient cell (EMT6.5, 4T1.2, NMUMG, HACAT and SW48). CM was harvested using two protocols which differed in the dose chosen and the exposure to the recipient cells. Results showed that xCELLigence measured a radiobiological effect which correlated with the clonogenic assay. For the RIBE study, no statistically significant differences were observed between xCELLigence or clonogenic survival in control or recipient cells incubated with CM in protocol one. However, there was a significant increase in cell index slope using CM from EMT-6.5 cells irradiated at 7.5 Gy compared with the control group under the second protocol. No other evidence of RIBE was detected by either xCELLigence or clonogenic assay. In conclusion, xCELLigence methods can measure radiobiological effects and the results correlate with clonogenic assay. We observed a lack of RIBE in all tested cell lines with the clonogenic assay; however, we observed a RIBE effect in EMT6.5 cells under one particular protocol that showed RIBE is cell type dependent, is not universally observed and can be detected in different assays.

Matched MeSH terms: Bystander Effect/radiation effects*
Enhanced DNA double-strand break repair of microbeam targeted A549 lung carcinoma cells by adjacent WI38 normal lung fibroblast cells via bi-directional signaling

Kobayashi A, Tengku Ahmad TAF, Autsavapromporn N, Oikawa M, Homma-Takeda S, Furusawa Y, et al.

Mutat Res, 2017 10;803-805:1-8.
PMID: 28689138 DOI: 10.1016/j.mrfmmm.2017.06.006

Understanding the mechanisms underlying the radiation-induced bystander effect (RIBE) and bi-directional signaling between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to cancer radiotherapy. The present study investigated propagation of RIBE signals between human lung carcinoma A549 cells and normal lung fibroblast WI38 cells in bystander cells, either directly or indirectly contacting irradiated A549 cells. We prepared A549-GFP/WI38 co-cultures and A549-GFP/A549 co-cultures, in which A549-GFP cells stably expressing H2BGFP were co-cultured with either A549 cells or WI38 cells, respectively. Using the SPICE-NIRS microbeam, only the A549-GFP cells were irradiated with 500 protons per cell. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured for up to 24h post-irradiation in three categories of cells: (1) "targeted"/irradiated A549-GFP cells; (2) "neighboring"/non-irradiated cells directly contacting the "targeted" cells; and (3) "distant"/non-irradiated cells, which were not in direct contact with the "targeted" cells. We found that DSB repair in targeted A549-GFP cells was enhanced by co-cultured WI38 cells. The bystander response in A549-GFP/A549 cell co-cultures, as marked by γ-H2AX levels at 8h post-irradiation, showed a decrease to non-irradiated control level when approaching 24h, while the neighboring/distant bystander WI38 cells in A549-GFP/WI38 co-cultures was maintained at a similar level until 24h post-irradiation. Surprisingly, distant A549-GFP cells in A549-GFP/WI38 co-cultures showed time dependency similar to bystander WI38 cells, but not to distant cells in A549-GFP/A549 co-cultures. These observations indicate that γ-H2AX was induced in WI38 cells as a result of RIBE. WI38 cells were not only involved in rescue of targeted A549, but also in the modification of RIBE against distant A549-GFP cells. The present results demonstrate that radiation-induced bi-directional signaling had extended a profound influence on cellular sensitivity to radiation as well as the sensitivity to RIBE.

Matched MeSH terms: Bystander Effect/radiation effects*
Emerging Role of Secondary Bystander Effects Induced by Fractionated Proton Microbeam Radiation

Autsavapromporn N, Liu C, Kobayashi A, Ahmad TAFT, Oikawa M, Dukaew N, et al.

Radiat Res, 2019 02;191(2):211-216.
PMID: 30526323 DOI: 10.1667/RR15155.1

Increased understanding of radiation-induced secondary bystander effect (RISBE) is relevant to radiation therapy since it likely contributes to normal tissue injury and tumor recurrence, subsequently resulting in treatment failure. In this work, we developed a simple method based on proton microbeam radiation and a transwell insert co-culture system to elucidate the RISBE between irradiated human lung cancer cells and nonirradiated human normal cells. A549 lung cancer cells received a single dose or fractionated doses of proton microbeam radiation to generate the primary bystander cells. These cells were then seeded on the top of the insert with secondary bystander WI-38 normal cells growing underneath in the presence or absence of gap junction intercellular communication (GJIC) inhibitor, 18-α-glycyrrhetnic acid (AGA). Cells were co-cultured before harvesting and assayed for micronuclei formation. The results of this work showed that fractionated doses of protons caused less DNA damage in the secondary bystander WI-38 cells compared to a single radiation dose, where the means differ by 20%. However, the damaging effect in the secondary bystander normal cells could be eliminated when treated with AGA. This novel work reflects our effort to demonstrate that GJIC plays a major role in the RISBE generated from the primary bystander cancer cells.

Matched MeSH terms: Bystander Effect/radiation effects*
Fulltext Bystander Effect Induced in Breast Cancer (MCF-7) and Human Osteoblast Cell Lines (hFOB 1.19) with HDR-Brachytherapy

Zainudin Nh M, R A, W N R

J Biomed Phys Eng, 2020 Jun;10(3):319-328.
PMID: 32637376 DOI: 10.31661/jbpe.v0i0.1135

Background: Radiation induced bystander effects (RIBEs) occurs in unirradiated cells exhibiting indirect biological effect as a consequence of signals from other irradiated cells in the population.
Objective: In this study, bystander effects in MCF-7 breast cancer cells and hFOB 1.19 normal osteoblast cells irradiated with gamma emitting HDR Brachytherapy Ir-192 source were investigated.
Material and Methods: In this in-vitro study, bystander effect stimulation was conducted using medium transfer technique of irradiated cells to the non-irradiated bystander cells. Cell viability, reactive oxygen species (ROS) generation and colony forming assay was employed to evaluate the effect.
Results: Results indicate that the exposure to the medium irradiated MCF-7 induced significant bystander killing and decreased the survival fraction of bystander MCF-7 and hFOB from 1.19 to 81.70 % and 65.44 %, respectively. A significant decrease in survival fraction was observed for hFOB 1.19 bystander cells (p < 0.05). We found that the rate of hFOB 1.19 cell growth significantly decreases to 85.5% when added with media from irradiated cells. The ROS levels of bystander cells for both cell lines were observed to have an increase even after 4 h of treatment. Our results suggest the presence of bystander effects in unirradiated cells exposed to the irradiated medium.
Conclusion: These data provide evidence that irradiated MCF-7 breast cancer cells can induce bystander death in unirradiated MCF-7 and hFOB 1.19 bystander cells. Increase in cell death could also be mediated by the ROS generation during the irradiation with HDR brachytherapy.

Matched MeSH terms: Bystander Effect
BYSTANDER WI-38 CELLS MODULATE DNA DOUBLE-STRAND BREAK REPAIR IN MICROBEAM-TARGETED A549 CELLS THROUGH GAP JUNCTION INTERCELLULAR COMMUNICATION

Kobayashi A, Autsavapromporn N, Ahmad TAFT, Oikawa M, Homma-Takeda S, Furusawa Y, et al.

Radiat Prot Dosimetry, 2019 May 01;183(1-2):142-146.
PMID: 30535060 DOI: 10.1093/rpd/ncy249

Bi-directional signaling involved in radiation-induced bystander effect (RIBE) between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to radiation cancer therapy. Using the SPICE-NIRS microbeam, we delivered 500 protons to A549-GFP lung carcinoma cells, stably expressing H2B-GFP, which were co-cultured with normal WI-38 cells. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured up to 24-h post-irradiation in both targeted and bystander cells. As a result, inhibition of gap junction intercellular communication (GJIC) attenuated DSB repair in targeted A549-GFP cells, and suppressed RIBE in bystander WI-38 cells but not in distant A549-GFP cells. This suggests that GJIC plays a two-way role through propagating DNA damage effect between carcinoma to normal cells and reversing the bystander signaling, also called 'rescue effect' from bystander cells to irradiated cells, to enhance the DSB repair in targeted cells.

Matched MeSH terms: Bystander Effect/radiation effects
Characteristics and outcomes of young adults who suffered an out-of-hospital cardiac arrest (OHCA)

Chia MY, Lu QS, Rahman NH, Doctor NE, Nishiuchi T, Leong BS, et al.

Resuscitation, 2017 02;111:34-40.
PMID: 27923113 DOI: 10.1016/j.resuscitation.2016.11.019

BACKGROUND: There is paucity of data examining the incidence and outcomes of young OHCA adults. The aim of this study is to determine the outcomes and characteristics of young adults who suffered an OHCA and identify factors that are associated with favourable neurologic outcomes.
METHODS: All EMS-attended OHCA adults between the ages of 16 and 35 years in the Pan-Asian Resuscitation Outcomes Study (PAROS) registry were analysed. The primary outcome was favourable neurologic outcome (Cerebral Performance Category 1 or 2) at hospital discharge or at 30th day post OHCA if not discharged. Regression analysis was performed to identify factors associated with favourable neurologic outcomes.
RESULTS: 66,780 OHCAs were collected between January 2009 and December 2013; 3244 young OHCAs had resuscitation attempted by emergency medical services (EMS). 56.8% of patients had unwitnessed arrest; 47.9% were of traumatic etiology. 17.2% of patients (95% CI: 15.9-18.5%) had return of spontaneous circulation; 7.8% (95% CI: 6.9-8.8%) survived to one month; 4.6% (95% CI: 4.0-5.4%) survived with favourable neurologic outcomes. Factors associated with favourable neurologic outcomes include witnessed arrest (adjusted RR=2.42, p-value<0.0001), bystander CPR (adjusted RR=1.57, p-value=0.004), first arrest shockable rhythm (adjusted RR=27.24, p-value<0.0001), and cardiac etiology (adjusted RR=3.99, p-value<0.0001).
CONCLUSIONS: OHCA among young adults are not uncommon. Traumatic OHCA, occurring most frequently in young adults had dismal prognosis. First arrest rhythms of VF/VT/unknown shockable rhythm, cardiac etiology, bystander-witnessed arrest, and bystander CPR were associated with favourable neurological outcomes. The results of the study would be useful for planning preventive and interventional strategies, improving EMS, and guiding future research.

Matched MeSH terms: Bystander Effect