Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Italy

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Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Italy

Authors

Publications

Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions

Keta, Otilija D.; Todorović, Danijela V.; Bulat, Tanja M.; Cirrone, Giuseppe Antonio Pablo; Romano, Francesco; Cuttone, Giacomo; Petrović, Ivan M.; Ristić-Fira, Aleksandra

(2017)

TY  - JOUR
AU  - Keta, Otilija D.
AU  - Todorović, Danijela V.
AU  - Bulat, Tanja M.
AU  - Cirrone, Giuseppe Antonio Pablo
AU  - Romano, Francesco
AU  - Cuttone, Giacomo
AU  - Petrović, Ivan M.
AU  - Ristić-Fira, Aleksandra
PY  - 2017
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/1573
AB  - The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons. When analyzing cell cycle distribution of both CRL5876 and HTB177 cells, it was noticed that therapeutic protons predominantly induced G1 arrest, while the cells after carbon ions were arrested in G2/M phase. The results illustrated that differences in the levels of phosphorylated H2AX, a double-strand break marker, exist after therapeutic proton and carbon ion irradiations. We also observed dose- and time-dependent increase in the p53 and p21 levels after applied irradiations. Carbon ions caused larger increase in the quantity of p53 and p21 compared to therapeutic protons. These results suggested that various repair mechanisms were induced in the treated cells. Considering the fact that we have not observed any distinct change in the Bax/Bcl-2 ratio following irradiations, it seemed that different types of cell death were involved in the response to the two types of irradiations that were applied.
T2  - Experimental Biology and Medicine
T1  - Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions
VL  - 242
IS  - 10
SP  - 1015
EP  - 1024
DO  - 10.1177/1535370216669611
ER  - 
@article{
author = "Keta, Otilija D. and Todorović, Danijela V. and Bulat, Tanja M. and Cirrone, Giuseppe Antonio Pablo and Romano, Francesco and Cuttone, Giacomo and Petrović, Ivan M. and Ristić-Fira, Aleksandra",
year = "2017",
url = "http://vinar.vin.bg.ac.rs/handle/123456789/1573",
abstract = "The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons. When analyzing cell cycle distribution of both CRL5876 and HTB177 cells, it was noticed that therapeutic protons predominantly induced G1 arrest, while the cells after carbon ions were arrested in G2/M phase. The results illustrated that differences in the levels of phosphorylated H2AX, a double-strand break marker, exist after therapeutic proton and carbon ion irradiations. We also observed dose- and time-dependent increase in the p53 and p21 levels after applied irradiations. Carbon ions caused larger increase in the quantity of p53 and p21 compared to therapeutic protons. These results suggested that various repair mechanisms were induced in the treated cells. Considering the fact that we have not observed any distinct change in the Bax/Bcl-2 ratio following irradiations, it seemed that different types of cell death were involved in the response to the two types of irradiations that were applied.",
journal = "Experimental Biology and Medicine",
title = "Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions",
volume = "242",
number = "10",
pages = "1015-1024",
doi = "10.1177/1535370216669611"
}
Keta, O. D., Todorović, D. V., Bulat, T. M., Cirrone, G. A. P., Romano, F., Cuttone, G., Petrović, I. M.,& Ristić-Fira, A. (2017). Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions.
Experimental Biology and Medicine, 242(10), 1015-1024.
https://doi.org/10.1177/1535370216669611
Keta OD, Todorović DV, Bulat TM, Cirrone GAP, Romano F, Cuttone G, Petrović IM, Ristić-Fira A. Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions. Experimental Biology and Medicine. 2017;242(10):1015-1024
Keta Otilija D., Todorović Danijela V., Bulat Tanja M., Cirrone Giuseppe Antonio Pablo, Romano Francesco, Cuttone Giacomo, Petrović Ivan M., Ristić-Fira Aleksandra, "Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions" Experimental Biology and Medicine, 242, no. 10 (2017):1015-1024,
https://doi.org/10.1177/1535370216669611 .
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Carbon ions of different linear energy transfer (LET) values induce apoptosis and G2 cell cycle arrest in radio-resistant melanoma cells

Žakula, Jelena; Korićanac, Lela; Keta, Otilija D.; Todorović, Danijela V.; Cirrone, Giuseppe Antonio Pablo; Romano, Francesco; Cuttone, Giacomo; Petrović, Ivan M.; Ristić-Fira, Aleksandra

(2016)

TY  - JOUR
AU  - Žakula, Jelena
AU  - Korićanac, Lela
AU  - Keta, Otilija D.
AU  - Todorović, Danijela V.
AU  - Cirrone, Giuseppe Antonio Pablo
AU  - Romano, Francesco
AU  - Cuttone, Giacomo
AU  - Petrović, Ivan M.
AU  - Ristić-Fira, Aleksandra
PY  - 2016
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/1290
AB  - Background and objectives: The main goal when treating malignancies with radiation is to deprive tumour cells of their reproductive potential. One approach is to induce tumour cell apoptosis. This study was conducted to evaluate the ability of carbon ions (C-12) to induce apoptosis and cell cycle arrest in human HTB140 melanoma cells. Methods: In this in vitro study, human melanoma HTB140 cells were irradiated with the 62 MeV/n carbon (C-12) ion beam, having two different linear energy transfer (LET) values: 197 and 382 keV/mu m. The dose range was 2 to 16 Gy. Cell viability was estimated by the sulforhodamine B assay seven days after irradiation. The cell cycle and apoptosis were evaluated 48 h after irradiation using flow cytometry. At the same time point, protein and gene expression of apoptotic regulators were estimated using the Western blot and q-PCR methods, respectively. Results: Cell viability experiments indicated strong anti-tumour effects of C-12 ions. The analysis of cell cycle showed that C-12 ions blocked HTB140 cells in G2 phase and induced the dose dependent increase of apoptosis. The maximum value of 21.8 per cent was attained after irradiation with LET of 197 keV/mu m at the dose level of 16 Gy. Pro-apoptotic effects of C-12 ions were confirmed by changes of key apoptotic molecules: the p53, Bax, Bcl-2, poly ADP ribose polymerase (PARP) as well as nuclear factor kappa B (NF kappa B). At the level of protein expression, the results indicated significant increases of p53, NF kappa B and Bax/Bcl-2 ratio and PARP cleavage. The Bax/Bcl-2 mRNA ratio was also increased, while no change was detected in the level of NF kappa B mRNA. Interpretation and conclusions: The present results indicated that anti-tumour effects of C-12 ions in human melanoma HTB140 cells were accomplished through induction of the mitochondrial apoptotic pathway as well as G2 arrest.
T2  - Indian Journal of Medical Research
T1  - Carbon ions of different linear energy transfer (LET) values induce apoptosis and G2 cell cycle arrest in radio-resistant melanoma cells
VL  - 143
SP  - 120
EP  - 128
DO  - 10.4103/0971-5916.191811
ER  - 
@article{
author = "Žakula, Jelena and Korićanac, Lela and Keta, Otilija D. and Todorović, Danijela V. and Cirrone, Giuseppe Antonio Pablo and Romano, Francesco and Cuttone, Giacomo and Petrović, Ivan M. and Ristić-Fira, Aleksandra",
year = "2016",
url = "http://vinar.vin.bg.ac.rs/handle/123456789/1290",
abstract = "Background and objectives: The main goal when treating malignancies with radiation is to deprive tumour cells of their reproductive potential. One approach is to induce tumour cell apoptosis. This study was conducted to evaluate the ability of carbon ions (C-12) to induce apoptosis and cell cycle arrest in human HTB140 melanoma cells. Methods: In this in vitro study, human melanoma HTB140 cells were irradiated with the 62 MeV/n carbon (C-12) ion beam, having two different linear energy transfer (LET) values: 197 and 382 keV/mu m. The dose range was 2 to 16 Gy. Cell viability was estimated by the sulforhodamine B assay seven days after irradiation. The cell cycle and apoptosis were evaluated 48 h after irradiation using flow cytometry. At the same time point, protein and gene expression of apoptotic regulators were estimated using the Western blot and q-PCR methods, respectively. Results: Cell viability experiments indicated strong anti-tumour effects of C-12 ions. The analysis of cell cycle showed that C-12 ions blocked HTB140 cells in G2 phase and induced the dose dependent increase of apoptosis. The maximum value of 21.8 per cent was attained after irradiation with LET of 197 keV/mu m at the dose level of 16 Gy. Pro-apoptotic effects of C-12 ions were confirmed by changes of key apoptotic molecules: the p53, Bax, Bcl-2, poly ADP ribose polymerase (PARP) as well as nuclear factor kappa B (NF kappa B). At the level of protein expression, the results indicated significant increases of p53, NF kappa B and Bax/Bcl-2 ratio and PARP cleavage. The Bax/Bcl-2 mRNA ratio was also increased, while no change was detected in the level of NF kappa B mRNA. Interpretation and conclusions: The present results indicated that anti-tumour effects of C-12 ions in human melanoma HTB140 cells were accomplished through induction of the mitochondrial apoptotic pathway as well as G2 arrest.",
journal = "Indian Journal of Medical Research",
title = "Carbon ions of different linear energy transfer (LET) values induce apoptosis and G2 cell cycle arrest in radio-resistant melanoma cells",
volume = "143",
pages = "120-128",
doi = "10.4103/0971-5916.191811"
}
Žakula, J., Korićanac, L., Keta, O. D., Todorović, D. V., Cirrone, G. A. P., Romano, F., Cuttone, G., Petrović, I. M.,& Ristić-Fira, A. (2016). Carbon ions of different linear energy transfer (LET) values induce apoptosis and G2 cell cycle arrest in radio-resistant melanoma cells.
Indian Journal of Medical Research, 143, 120-128.
https://doi.org/10.4103/0971-5916.191811
Žakula J, Korićanac L, Keta OD, Todorović DV, Cirrone GAP, Romano F, Cuttone G, Petrović IM, Ristić-Fira A. Carbon ions of different linear energy transfer (LET) values induce apoptosis and G2 cell cycle arrest in radio-resistant melanoma cells. Indian Journal of Medical Research. 2016;143:120-128
Žakula Jelena, Korićanac Lela, Keta Otilija D., Todorović Danijela V., Cirrone Giuseppe Antonio Pablo, Romano Francesco, Cuttone Giacomo, Petrović Ivan M., Ristić-Fira Aleksandra, "Carbon ions of different linear energy transfer (LET) values induce apoptosis and G2 cell cycle arrest in radio-resistant melanoma cells" Indian Journal of Medical Research, 143 (2016):120-128,
https://doi.org/10.4103/0971-5916.191811 .
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Radiosensitivity of human ovarian carcinoma and melanoma cells to gamma-rays and protons

Keta, Otilija D.; Todorović, Danijela V.; Popović, Nataša M.; Korićanac, Lela; Cuttone, Giacomo; Petrović, Ivan M.; Ristić-Fira, Aleksandra

(2014)

TY  - JOUR
AU  - Keta, Otilija D.
AU  - Todorović, Danijela V.
AU  - Popović, Nataša M.
AU  - Korićanac, Lela
AU  - Cuttone, Giacomo
AU  - Petrović, Ivan M.
AU  - Ristić-Fira, Aleksandra
PY  - 2014
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/5447
AB  - Introduction: Proton radiation offers physical advantages over conventional radiation. Radiosensitivity of human 59M ovarian cancer and HTB140 melanoma cells was investigated after exposure to gamma-rays and protons. Material and methods: Irradiations were performed in the middle of a 62 MeV therapeutic proton spread out Bragg peak with doses ranging from 2 to 16 Gy. The mean energy of protons was 34.88+/-2.15 MeV, corresponding to the linear energy transfer of 4.7+/-0.2 keV/mu m. Irradiations with gamma-rays were performed using the same doses. Viability, proliferation and survival were assessed 7 days after both types of irradiation while analyses of cell cycle and apoptosis were performed 48 h after irradiation. Results: Results showed that gamma-rays and protons reduced the number of viable cells for both cell lines, with stronger inactivation achieved after irradiation with protons. Surviving fractions for 59M were 0.91+/-0.01 for gamma-rays and 0.81+/-0.01 for protons, while those for HTB140 cells were 0.93+/-0.01 for gamma-rays and 0.86+/-0.01 for protons. Relative biological effectiveness of protons, being 2.47+/-0.22 for 59M and 2.08+/-0.36 for HTB140, indicated that protons provoked better cell elimination than gamma-rays. After proton irradiation proliferation capacity of the two cell lines was slightly higher as compared to gamma-rays. Proliferation was higher for 59M than for HTB140 cells after both types of irradiation. Induction of apoptosis and G2 arrest detected after proton irradiation were more prominent in 59M cells. Conclusions: The obtained results suggest that protons exert better antitumour effects on ovarian carcinoma and melanoma cells than gamma-rays. The dissimilar response of these cells to radiation is related to their different features.
T2  - Archives of Medical Science
T1  - Radiosensitivity of human ovarian carcinoma and melanoma cells to gamma-rays and protons
VL  - 10
IS  - 3
SP  - 578
EP  - 586
DO  - 10.5114/aoms.2014.43751
ER  - 
@article{
author = "Keta, Otilija D. and Todorović, Danijela V. and Popović, Nataša M. and Korićanac, Lela and Cuttone, Giacomo and Petrović, Ivan M. and Ristić-Fira, Aleksandra",
year = "2014",
url = "http://vinar.vin.bg.ac.rs/handle/123456789/5447",
abstract = "Introduction: Proton radiation offers physical advantages over conventional radiation. Radiosensitivity of human 59M ovarian cancer and HTB140 melanoma cells was investigated after exposure to gamma-rays and protons. Material and methods: Irradiations were performed in the middle of a 62 MeV therapeutic proton spread out Bragg peak with doses ranging from 2 to 16 Gy. The mean energy of protons was 34.88+/-2.15 MeV, corresponding to the linear energy transfer of 4.7+/-0.2 keV/mu m. Irradiations with gamma-rays were performed using the same doses. Viability, proliferation and survival were assessed 7 days after both types of irradiation while analyses of cell cycle and apoptosis were performed 48 h after irradiation. Results: Results showed that gamma-rays and protons reduced the number of viable cells for both cell lines, with stronger inactivation achieved after irradiation with protons. Surviving fractions for 59M were 0.91+/-0.01 for gamma-rays and 0.81+/-0.01 for protons, while those for HTB140 cells were 0.93+/-0.01 for gamma-rays and 0.86+/-0.01 for protons. Relative biological effectiveness of protons, being 2.47+/-0.22 for 59M and 2.08+/-0.36 for HTB140, indicated that protons provoked better cell elimination than gamma-rays. After proton irradiation proliferation capacity of the two cell lines was slightly higher as compared to gamma-rays. Proliferation was higher for 59M than for HTB140 cells after both types of irradiation. Induction of apoptosis and G2 arrest detected after proton irradiation were more prominent in 59M cells. Conclusions: The obtained results suggest that protons exert better antitumour effects on ovarian carcinoma and melanoma cells than gamma-rays. The dissimilar response of these cells to radiation is related to their different features.",
journal = "Archives of Medical Science",
title = "Radiosensitivity of human ovarian carcinoma and melanoma cells to gamma-rays and protons",
volume = "10",
number = "3",
pages = "578-586",
doi = "10.5114/aoms.2014.43751"
}
Keta, O. D., Todorović, D. V., Popović, N. M., Korićanac, L., Cuttone, G., Petrović, I. M.,& Ristić-Fira, A. (2014). Radiosensitivity of human ovarian carcinoma and melanoma cells to gamma-rays and protons.
Archives of Medical Science, 10(3), 578-586.
https://doi.org/10.5114/aoms.2014.43751
Keta OD, Todorović DV, Popović NM, Korićanac L, Cuttone G, Petrović IM, Ristić-Fira A. Radiosensitivity of human ovarian carcinoma and melanoma cells to gamma-rays and protons. Archives of Medical Science. 2014;10(3):578-586
Keta Otilija D., Todorović Danijela V., Popović Nataša M., Korićanac Lela, Cuttone Giacomo, Petrović Ivan M., Ristić-Fira Aleksandra, "Radiosensitivity of human ovarian carcinoma and melanoma cells to gamma-rays and protons" Archives of Medical Science, 10, no. 3 (2014):578-586,
https://doi.org/10.5114/aoms.2014.43751 .
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Response of Human HTB140 Melanoma Cells to Conventional Radiation and Hadrons

Ristić-Fira, Aleksandra; Todorović, Danijela V.; Žakula, Jelena; Keta, Otilija D.; Cirrone, Giuseppe Antonio Pablo; Cuttone, Giacomo; Petrović, Ivan M.

(2011)

TY  - JOUR
AU  - Ristić-Fira, Aleksandra
AU  - Todorović, Danijela V.
AU  - Žakula, Jelena
AU  - Keta, Otilija D.
AU  - Cirrone, Giuseppe Antonio Pablo
AU  - Cuttone, Giacomo
AU  - Petrović, Ivan M.
PY  - 2011
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/4537
AB  - Conventional radiotherapy with X-and gamma-rays is one of the common and effective treatments of cancer. High energy hadrons, i.e., charged particles like protons and (12)C ions, due to their specific physics and radiobiological advantages are increasingly used. In this study, effectiveness of different radiation types is evaluated on the radio-resistant human HTB140 melanoma cells. The cells were irradiated with gamma-rays, the 62 MeV protons at the Bragg peak and in the middle of the spread-out Bragg peak (SOBP), as well as with the 62 MeV/u (12)C ions. The doses ranged from 2 to 24 Gy. Cell survival and proliferation were assessed 7 days after irradiation, whereas apoptosis was evaluated after 48 h. The acquired results confirmed the high radio-resistance of cells, showing better effectiveness of protons than gamma-rays. The best efficiency was obtained with (12)C ions due to higher linear energy transfer. All analyzed radiation qualities reduced cell proliferation. The highest proliferation was detected for (12)C ions because of their large killing capacity followed by small induction of reparable lesions. This enabled unharmed cells to preserve proliferative activity. Irradiations with protons and (12)C ions revealed similar moderate pro-apoptotic ability that is in agreement with the level of cellular radio-resistance.
T2  - Physiological Research
T1  - Response of Human HTB140 Melanoma Cells to Conventional Radiation and Hadrons
VL  - 60
SP  - S129
EP  - S135
ER  - 
@article{
author = "Ristić-Fira, Aleksandra and Todorović, Danijela V. and Žakula, Jelena and Keta, Otilija D. and Cirrone, Giuseppe Antonio Pablo and Cuttone, Giacomo and Petrović, Ivan M.",
year = "2011",
url = "http://vinar.vin.bg.ac.rs/handle/123456789/4537",
abstract = "Conventional radiotherapy with X-and gamma-rays is one of the common and effective treatments of cancer. High energy hadrons, i.e., charged particles like protons and (12)C ions, due to their specific physics and radiobiological advantages are increasingly used. In this study, effectiveness of different radiation types is evaluated on the radio-resistant human HTB140 melanoma cells. The cells were irradiated with gamma-rays, the 62 MeV protons at the Bragg peak and in the middle of the spread-out Bragg peak (SOBP), as well as with the 62 MeV/u (12)C ions. The doses ranged from 2 to 24 Gy. Cell survival and proliferation were assessed 7 days after irradiation, whereas apoptosis was evaluated after 48 h. The acquired results confirmed the high radio-resistance of cells, showing better effectiveness of protons than gamma-rays. The best efficiency was obtained with (12)C ions due to higher linear energy transfer. All analyzed radiation qualities reduced cell proliferation. The highest proliferation was detected for (12)C ions because of their large killing capacity followed by small induction of reparable lesions. This enabled unharmed cells to preserve proliferative activity. Irradiations with protons and (12)C ions revealed similar moderate pro-apoptotic ability that is in agreement with the level of cellular radio-resistance.",
journal = "Physiological Research",
title = "Response of Human HTB140 Melanoma Cells to Conventional Radiation and Hadrons",
volume = "60",
pages = "S129-S135"
}
Ristić-Fira, A., Todorović, D. V., Žakula, J., Keta, O. D., Cirrone, G. A. P., Cuttone, G.,& Petrović, I. M. (2011). Response of Human HTB140 Melanoma Cells to Conventional Radiation and Hadrons.
Physiological Research, 60, S129-S135.
Ristić-Fira A, Todorović DV, Žakula J, Keta OD, Cirrone GAP, Cuttone G, Petrović IM. Response of Human HTB140 Melanoma Cells to Conventional Radiation and Hadrons. Physiological Research. 2011;60:S129-S135
Ristić-Fira Aleksandra, Todorović Danijela V., Žakula Jelena, Keta Otilija D., Cirrone Giuseppe Antonio Pablo, Cuttone Giacomo, Petrović Ivan M., "Response of Human HTB140 Melanoma Cells to Conventional Radiation and Hadrons" Physiological Research, 60 (2011):S129-S135
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