TY  - JOUR
AU  - Todorović, Lidija
AU  - Stamenković, Gorana
AU  - Vučetić-Tadić, Biljana
AU  - Umezawa, Kazuo
AU  - Božović, Ana M.
AU  - Yamashita, Shunichi
AU  - Stanojević, Boban
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9413
AB  - The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.
T2  - Archives of Biological Sciences
T1  - Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2
VL  - 73
IS  - 1
SP  - 31
EP  - 38
DO  - 10.2298/ABS201010055T
ER  - 

@article{
author = "Todorović, Lidija and Stamenković, Gorana and Vučetić-Tadić, Biljana and Umezawa, Kazuo and Božović, Ana M. and Yamashita, Shunichi and Stanojević, Boban",
year = "2021",
abstract = "The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.",
journal = "Archives of Biological Sciences",
title = "Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2",
volume = "73",
number = "1",
pages = "31-38",
doi = "10.2298/ABS201010055T"
}

Todorović, L., Stamenković, G., Vučetić-Tadić, B., Umezawa, K., Božović, A. M., Yamashita, S.,& Stanojević, B.. (2021). Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2. in Archives of Biological Sciences, 73(1), 31-38.
https://doi.org/10.2298/ABS201010055T

Todorović L, Stamenković G, Vučetić-Tadić B, Umezawa K, Božović AM, Yamashita S, Stanojević B. Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2. in Archives of Biological Sciences. 2021;73(1):31-38.
doi:10.2298/ABS201010055T .

Todorović, Lidija, Stamenković, Gorana, Vučetić-Tadić, Biljana, Umezawa, Kazuo, Božović, Ana M., Yamashita, Shunichi, Stanojević, Boban, "Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2" in Archives of Biological Sciences, 73, no. 1 (2021):31-38,
https://doi.org/10.2298/ABS201010055T . .

TY  - JOUR
AU  - Stanojević, Boban
AU  - Saenko, Vladimir
AU  - Todorović, Lidija
AU  - Petrović, Nina
AU  - Nikolić, Dragan
AU  - Živaljević, Vladan R.
AU  - Paunović, Ivan R.
AU  - Nakashima, Masahiro
AU  - Yamashita, Shunichi
AU  - Džodić, Radan R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/340
AB  - Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR=5.78, 95% CI 3.17-10.53, P LT 0.0001), classical papillary morphology of the tumor (OR=2.92, 95% CI 1.33-6.44, P=0.008) and multifocality (OR=1.96, 95% CI 1.06-3.62, P=0.031). In disease-free survival analysis, low VHL expression had marginal significance (P=0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.
T2  - PLOS One
T1  - Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma
VL  - 9
IS  - 12
DO  - 10.1371/journal.pone.0114511
ER  - 

@article{
author = "Stanojević, Boban and Saenko, Vladimir and Todorović, Lidija and Petrović, Nina and Nikolić, Dragan and Živaljević, Vladan R. and Paunović, Ivan R. and Nakashima, Masahiro and Yamashita, Shunichi and Džodić, Radan R.",
year = "2014",
abstract = "Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR=5.78, 95% CI 3.17-10.53, P LT 0.0001), classical papillary morphology of the tumor (OR=2.92, 95% CI 1.33-6.44, P=0.008) and multifocality (OR=1.96, 95% CI 1.06-3.62, P=0.031). In disease-free survival analysis, low VHL expression had marginal significance (P=0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.",
journal = "PLOS One",
title = "Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma",
volume = "9",
number = "12",
doi = "10.1371/journal.pone.0114511"
}

Stanojević, B., Saenko, V., Todorović, L., Petrović, N., Nikolić, D., Živaljević, V. R., Paunović, I. R., Nakashima, M., Yamashita, S.,& Džodić, R. R.. (2014). Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma. in PLOS One, 9(12).
https://doi.org/10.1371/journal.pone.0114511

Stanojević B, Saenko V, Todorović L, Petrović N, Nikolić D, Živaljević VR, Paunović IR, Nakashima M, Yamashita S, Džodić RR. Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma. in PLOS One. 2014;9(12).
doi:10.1371/journal.pone.0114511 .

Stanojević, Boban, Saenko, Vladimir, Todorović, Lidija, Petrović, Nina, Nikolić, Dragan, Živaljević, Vladan R., Paunović, Ivan R., Nakashima, Masahiro, Yamashita, Shunichi, Džodić, Radan R., "Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma" in PLOS One, 9, no. 12 (2014),
https://doi.org/10.1371/journal.pone.0114511 . .