TY  - JOUR
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Lakić, Iva
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Drakulić, Dunja R.
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10173
AB  - A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.
T2  - International Journal of Molecular Sciences
T1  - The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats
VL  - 23
IS  - 4
SP  - 2395
DO  - 10.3390/ijms23042395
ER  - 

@article{
author = "Đurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pejić, Snežana and Todorović, Ana and Drakulić, Dunja R. and Stanković, Sanja and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2022",
abstract = "A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.",
journal = "International Journal of Molecular Sciences",
title = "The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats",
volume = "23",
number = "4",
pages = "2395",
doi = "10.3390/ijms23042395"
}

Đurašević, S., Ružičić, A., Lakić, I., Tosti, T., Đurović, S., Glumac, S., Pejić, S., Todorović, A., Drakulić, D. R., Stanković, S., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2022). The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences, 23(4), 2395.
https://doi.org/10.3390/ijms23042395

Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pejić S, Todorović A, Drakulić DR, Stanković S, Jasnić N, Đorđević J, Todorović Z. The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences. 2022;23(4):2395.
doi:10.3390/ijms23042395 .

Đurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pejić, Snežana, Todorović, Ana, Drakulić, Dunja R., Stanković, Sanja, Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats" in International Journal of Molecular Sciences, 23, no. 4 (2022):2395,
https://doi.org/10.3390/ijms23042395 . .

TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Jovanović, Svetlana P.
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir S.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9980
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death
VL  - 177
SP  - 167
EP  - 180
DO  - 10.1016/j.freeradbiomed.2021.10.025
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović-Marković, Biljana and Jovanović, Svetlana P. and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir S.",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death",
volume = "177",
pages = "167-180",
doi = "10.1016/j.freeradbiomed.2021.10.025"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Marković, Z., Todorović-Marković, B., Jovanović, S. P., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O., Vuković, I., Harhaji-Trajković, L.,& Trajković, V. S.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine, 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zogović N, Mirčić A, Marković Z, Todorović-Marković B, Jovanović SP, Kleut D, Mojović M, Nakarada Đ, Marković O, Vuković I, Harhaji-Trajković L, Trajković VS. Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović-Marković, Biljana, Jovanović, Svetlana P., Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir S., "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Pejić, Snežana
AU  - Grigorov, Ilijana
AU  - Nikolić, Gorana
AU  - Mitić-Ćulafić, Dragana
AU  - Dragićević, Milan
AU  - Đorđević, Jelena
AU  - Todorović Vukotić, Nevena
AU  - Đorđević, Neda O.
AU  - Todorović, Ana
AU  - Drakulić, Dunja R.
AU  - Veljković, Filip M.
AU  - Pajović, Snežana B.
AU  - Todorović, Zoran
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9831
AB  - Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.
T2  - Antioxidants
T1  - Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes
VL  - 10
IS  - 6
SP  - 911
DO  - 10.3390/antiox10060911
ER  - 

@article{
author = "Đurašević, Siniša and Pejić, Snežana and Grigorov, Ilijana and Nikolić, Gorana and Mitić-Ćulafić, Dragana and Dragićević, Milan and Đorđević, Jelena and Todorović Vukotić, Nevena and Đorđević, Neda O. and Todorović, Ana and Drakulić, Dunja R. and Veljković, Filip M. and Pajović, Snežana B. and Todorović, Zoran",
year = "2021",
abstract = "Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.",
journal = "Antioxidants",
title = "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes",
volume = "10",
number = "6",
pages = "911",
doi = "10.3390/antiox10060911"
}

Đurašević, S., Pejić, S., Grigorov, I., Nikolić, G., Mitić-Ćulafić, D., Dragićević, M., Đorđević, J., Todorović Vukotić, N., Đorđević, N. O., Todorović, A., Drakulić, D. R., Veljković, F. M., Pajović, S. B.,& Todorović, Z.. (2021). Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants, 10(6), 911.
https://doi.org/10.3390/antiox10060911

Đurašević S, Pejić S, Grigorov I, Nikolić G, Mitić-Ćulafić D, Dragićević M, Đorđević J, Todorović Vukotić N, Đorđević NO, Todorović A, Drakulić DR, Veljković FM, Pajović SB, Todorović Z. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants. 2021;10(6):911.
doi:10.3390/antiox10060911 .

Đurašević, Siniša, Pejić, Snežana, Grigorov, Ilijana, Nikolić, Gorana, Mitić-Ćulafić, Dragana, Dragićević, Milan, Đorđević, Jelena, Todorović Vukotić, Nevena, Đorđević, Neda O., Todorović, Ana, Drakulić, Dunja R., Veljković, Filip M., Pajović, Snežana B., Todorović, Zoran, "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes" in Antioxidants, 10, no. 6 (2021):911,
https://doi.org/10.3390/antiox10060911 . .

TY  - JOUR
AU  - Glumac, Sofija
AU  - Davidović, Radoslav S.
AU  - Dožić, Branko
AU  - Hinić, Sasa
AU  - Pavlović, Ivan
AU  - Drakulić, Dunja R.
AU  - Todorović, Ana
AU  - Medojević Pavlović, Maja
AU  - Radojević-Škodrić, Sanja
AU  - Baralić, Ivana
AU  - Sopta, Jelena
AU  - Pejić, Snežana
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9887
AB  - Rhabdomyosarcoma (RMS) is a highly malignant cancer and is the most common soft tissue sarcoma in children and adolescents, but it is rare in adults (<1% of all adult malignancies). Altered expression and molecular abnormalities of cell-cycle-regulatory proteins are one of the most prominent features in RMS. Therefore, we evaluated the expression of cyclin-dependent kinase inhibitors p57 and p16, as well as p16 methylation status, along with clinicopathological characteristics and overall survival (OS) in RMS patients. This analysis was conducted on 23 pediatric and 44 adult patients. There was a male predominance in both groups and extremities were the most frequent tumor site. In adults, alveolar and pleomorphic types were almost equally represented. The majority of pediatric tumors were low grade, whereas, in adults, only one patient had a low-grade tumor. Seven pediatric (30.43%) and eight adult (18.18%) patients had a low p16 expression. The analysis of methylation status of the p16 promoter showed the presence of methylated allele only in one sample with pleomorphic histology. Six (26.1%) pediatric and 15 (34.1%) adult patients had low p57 expression, while in 17 (73.9%) pediatric and 29 (65.9%) adult patients it was assessed as high. Ninetyone percent of the pediatric patients and 32.6% of adults were alive at the end of the observational period. In adults, significant associations were found between OS and age (P = 0.020), gender (P = 0.027), tumor size (P < 0.001), lymph node status (P < 0.001), presence of metastases (P = 0.015), and p57 expression (P = 0.039). Stratification by histological type showed the correlation of low p57 expression (P = 0.030) and worse OS of patients with alveolar RMS. Univariate analysis identified age > 50 yrs. (HR 2.447), tumors > 5 cm (HR 21.31), involvement of regional lymph nodes (HR 3.96), the presence of metastases (HR 2.53), and low p57 expression (HR 2.11) as predictors of lower OS. Tumor size, regional lymph nodes involvement, and metastases were the independent predictors after multivariate analysis, while p57 did not predict OS in an independent way. In summary, although p57 was not confirmed to be an independent predictor of OS, our results indicate that its low expression may be the marker of aggressive phenotype and poor prognosis in adult RMS patients. Also, our findings suggest that epigenetic inactivation of p16 is not important in the pathogenesis of rhabdomyosarcoma.
T2  - Pathology - Research and Practice
T1  - Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma
VL  - 225
SP  - 153558
DO  - 10.1016/j.prp.2021.153558
ER  - 

@article{
author = "Glumac, Sofija and Davidović, Radoslav S. and Dožić, Branko and Hinić, Sasa and Pavlović, Ivan and Drakulić, Dunja R. and Todorović, Ana and Medojević Pavlović, Maja and Radojević-Škodrić, Sanja and Baralić, Ivana and Sopta, Jelena and Pejić, Snežana",
year = "2021",
abstract = "Rhabdomyosarcoma (RMS) is a highly malignant cancer and is the most common soft tissue sarcoma in children and adolescents, but it is rare in adults (<1% of all adult malignancies). Altered expression and molecular abnormalities of cell-cycle-regulatory proteins are one of the most prominent features in RMS. Therefore, we evaluated the expression of cyclin-dependent kinase inhibitors p57 and p16, as well as p16 methylation status, along with clinicopathological characteristics and overall survival (OS) in RMS patients. This analysis was conducted on 23 pediatric and 44 adult patients. There was a male predominance in both groups and extremities were the most frequent tumor site. In adults, alveolar and pleomorphic types were almost equally represented. The majority of pediatric tumors were low grade, whereas, in adults, only one patient had a low-grade tumor. Seven pediatric (30.43%) and eight adult (18.18%) patients had a low p16 expression. The analysis of methylation status of the p16 promoter showed the presence of methylated allele only in one sample with pleomorphic histology. Six (26.1%) pediatric and 15 (34.1%) adult patients had low p57 expression, while in 17 (73.9%) pediatric and 29 (65.9%) adult patients it was assessed as high. Ninetyone percent of the pediatric patients and 32.6% of adults were alive at the end of the observational period. In adults, significant associations were found between OS and age (P = 0.020), gender (P = 0.027), tumor size (P < 0.001), lymph node status (P < 0.001), presence of metastases (P = 0.015), and p57 expression (P = 0.039). Stratification by histological type showed the correlation of low p57 expression (P = 0.030) and worse OS of patients with alveolar RMS. Univariate analysis identified age > 50 yrs. (HR 2.447), tumors > 5 cm (HR 21.31), involvement of regional lymph nodes (HR 3.96), the presence of metastases (HR 2.53), and low p57 expression (HR 2.11) as predictors of lower OS. Tumor size, regional lymph nodes involvement, and metastases were the independent predictors after multivariate analysis, while p57 did not predict OS in an independent way. In summary, although p57 was not confirmed to be an independent predictor of OS, our results indicate that its low expression may be the marker of aggressive phenotype and poor prognosis in adult RMS patients. Also, our findings suggest that epigenetic inactivation of p16 is not important in the pathogenesis of rhabdomyosarcoma.",
journal = "Pathology - Research and Practice",
title = "Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma",
volume = "225",
pages = "153558",
doi = "10.1016/j.prp.2021.153558"
}

Glumac, S., Davidović, R. S., Dožić, B., Hinić, S., Pavlović, I., Drakulić, D. R., Todorović, A., Medojević Pavlović, M., Radojević-Škodrić, S., Baralić, I., Sopta, J.,& Pejić, S.. (2021). Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma. in Pathology - Research and Practice, 225, 153558.
https://doi.org/10.1016/j.prp.2021.153558

Glumac S, Davidović RS, Dožić B, Hinić S, Pavlović I, Drakulić DR, Todorović A, Medojević Pavlović M, Radojević-Škodrić S, Baralić I, Sopta J, Pejić S. Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma. in Pathology - Research and Practice. 2021;225:153558.
doi:10.1016/j.prp.2021.153558 .

Glumac, Sofija, Davidović, Radoslav S., Dožić, Branko, Hinić, Sasa, Pavlović, Ivan, Drakulić, Dunja R., Todorović, Ana, Medojević Pavlović, Maja, Radojević-Škodrić, Sanja, Baralić, Ivana, Sopta, Jelena, Pejić, Snežana, "Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma" in Pathology - Research and Practice, 225 (2021):153558,
https://doi.org/10.1016/j.prp.2021.153558 . .

TY  - JOUR
AU  - Isaković, Anđelka M.
AU  - Čolović, Mirjana B.
AU  - Ma, Tian
AU  - Ma, Xiang
AU  - Jeremić, Marija
AU  - Gerić, Marko
AU  - Gajski, Goran
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9952
AB  - Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
T2  - JBIC Journal of Biological Inorganic Chemistry
T1  - Selected polyoxopalladates as promising and selective antitumor drug candidates
VL  - 26
IS  - 8
SP  - 957
EP  - 971
DO  - 10.1007/s00775-021-01905-4
ER  - 

@article{
author = "Isaković, Anđelka M. and Čolović, Mirjana B. and Ma, Tian and Ma, Xiang and Jeremić, Marija and Gerić, Marko and Gajski, Goran and Misirlić-Denčić, Sonja and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2021",
abstract = "Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.",
journal = "JBIC Journal of Biological Inorganic Chemistry",
title = "Selected polyoxopalladates as promising and selective antitumor drug candidates",
volume = "26",
number = "8",
pages = "957-971",
doi = "10.1007/s00775-021-01905-4"
}

Isaković, A. M., Čolović, M. B., Ma, T., Ma, X., Jeremić, M., Gerić, M., Gajski, G., Misirlić-Denčić, S., Kortz, U.,& Krstić, D. Z.. (2021). Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry, 26(8), 957-971.
https://doi.org/10.1007/s00775-021-01905-4

Isaković AM, Čolović MB, Ma T, Ma X, Jeremić M, Gerić M, Gajski G, Misirlić-Denčić S, Kortz U, Krstić DZ. Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry. 2021;26(8):957-971.
doi:10.1007/s00775-021-01905-4 .

Isaković, Anđelka M., Čolović, Mirjana B., Ma, Tian, Ma, Xiang, Jeremić, Marija, Gerić, Marko, Gajski, Goran, Misirlić-Denčić, Sonja, Kortz, Ulrich, Krstić, Danijela Z., "Selected polyoxopalladates as promising and selective antitumor drug candidates" in JBIC Journal of Biological Inorganic Chemistry, 26, no. 8 (2021):957-971,
https://doi.org/10.1007/s00775-021-01905-4 . .