National Science Fund of Bulgaria

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National Science Fund of Bulgaria

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New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors

Podolski-Renić, Ana; Dinić, Jelena; Stanković, Tijana; Tsakovska, Ivanka; Pajeva, Ilza; Tuccinardi, Tiziano; Botta, Lorenzo; Schenone, Silvia; Pešić, Milica

(Basel: MDPI, 2021)

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Tsakovska, Ivanka
AU  - Pajeva, Ilza
AU  - Tuccinardi, Tiziano
AU  - Botta, Lorenzo
AU  - Schenone, Silvia
AU  - Pešić, Milica
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/21/5308
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4631
AB  - Tyrosine kinase inhibitors (TKIs) often interact with the multidrug resistant (MDR) phenotype of cancer cells. In some cases, TKIs increase the susceptibility of MDR cancer cells to chemotherapy. As the overexpression of membrane transporter P‐glycoprotein (P‐gp) is the most com-mon alteration in MDR cancer cells, we investigated the effects of TKI pyrazolo[3,4‐d]pyrimidines on P‐gp inhibition in two cellular models comprising sensitive and corresponding MDR cancer cells (human non‐small cell lung carcinoma and colorectal adenocarcinoma). Tested TKIs showed collateral sensitivity by inducing stronger inhibition of MDR cancer cell line viability. Moreover, TKIs directly interacted with P‐gp and inhibited its ATPase activity. Their potential P‐gp binding site was proposed by molecular docking simulations. TKIs reversed resistance to doxorubicin and paclitaxel in a concentration‐dependent manner. The expression studies excluded the indirect effect of TKIs on P‐gp through regulation of its expression. A kinetics study showed that TKIs decreased P‐gp activity and this effect was sustained for seven days in both MDR models. Therefore, pyrazolo[3,4‐d]pyrimidines with potential for reversing P‐gp‐mediated MDR even in prolonged treatments can be considered a new therapeutic strategy for overcoming cancer MDR.
PB  - Basel: MDPI
T2  - Cancers
T1  - New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors
IS  - 21
VL  - 13
DO  - 10.3390/cancers13215308
SP  - 5308
ER  - 
@article{
author = "Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Tsakovska, Ivanka and Pajeva, Ilza and Tuccinardi, Tiziano and Botta, Lorenzo and Schenone, Silvia and Pešić, Milica",
year = "2021",
abstract = "Tyrosine kinase inhibitors (TKIs) often interact with the multidrug resistant (MDR) phenotype of cancer cells. In some cases, TKIs increase the susceptibility of MDR cancer cells to chemotherapy. As the overexpression of membrane transporter P‐glycoprotein (P‐gp) is the most com-mon alteration in MDR cancer cells, we investigated the effects of TKI pyrazolo[3,4‐d]pyrimidines on P‐gp inhibition in two cellular models comprising sensitive and corresponding MDR cancer cells (human non‐small cell lung carcinoma and colorectal adenocarcinoma). Tested TKIs showed collateral sensitivity by inducing stronger inhibition of MDR cancer cell line viability. Moreover, TKIs directly interacted with P‐gp and inhibited its ATPase activity. Their potential P‐gp binding site was proposed by molecular docking simulations. TKIs reversed resistance to doxorubicin and paclitaxel in a concentration‐dependent manner. The expression studies excluded the indirect effect of TKIs on P‐gp through regulation of its expression. A kinetics study showed that TKIs decreased P‐gp activity and this effect was sustained for seven days in both MDR models. Therefore, pyrazolo[3,4‐d]pyrimidines with potential for reversing P‐gp‐mediated MDR even in prolonged treatments can be considered a new therapeutic strategy for overcoming cancer MDR.",
publisher = "Basel: MDPI",
journal = "Cancers",
title = "New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors",
number = "21",
volume = "13",
doi = "10.3390/cancers13215308",
pages = "5308"
}
Podolski-Renić, A., Dinić, J., Stanković, T., Tsakovska, I., Pajeva, I., Tuccinardi, T., Botta, L., Schenone, S.,& Pešić, M.. (2021). New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors. in Cancers
Basel: MDPI., 13(21), 5308.
https://doi.org/10.3390/cancers13215308
Podolski-Renić A, Dinić J, Stanković T, Tsakovska I, Pajeva I, Tuccinardi T, Botta L, Schenone S, Pešić M. New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors. in Cancers. 2021;13(21):5308.
doi:10.3390/cancers13215308 .
Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Tsakovska, Ivanka, Pajeva, Ilza, Tuccinardi, Tiziano, Botta, Lorenzo, Schenone, Silvia, Pešić, Milica, "New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors" in Cancers, 13, no. 21 (2021):5308,
https://doi.org/10.3390/cancers13215308 . .
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Pilot Application of ‘Invasive Alien Species in Europe’ Smartphone App in the Danube Region

Trichkova, Teodora; Paunović, Momir; Cogălniceanu, Dan; Schade, Sven; Todorov, Milcho; Tomov, Rumen; Stănescu, Florina; Botev, Ivan; López-Cañizares, Celia; Gervasini, Eugenio; Hubenov, Zdravko; Ignatov, Kostadin; Kenderov, Marian; Marinković, Nikola; Mitton, Irena; Preda, Cristina; Spinelli, Fabiano Antonio; Tsiamis, Konstantinos; Cardoso, Ana Cristina

(Basel: MDPI, 2021)

TY  - JOUR
AU  - Trichkova, Teodora
AU  - Paunović, Momir
AU  - Cogălniceanu, Dan
AU  - Schade, Sven
AU  - Todorov, Milcho
AU  - Tomov, Rumen
AU  - Stănescu, Florina
AU  - Botev, Ivan
AU  - López-Cañizares, Celia
AU  - Gervasini, Eugenio
AU  - Hubenov, Zdravko
AU  - Ignatov, Kostadin
AU  - Kenderov, Marian
AU  - Marinković, Nikola
AU  - Mitton, Irena
AU  - Preda, Cristina
AU  - Spinelli, Fabiano Antonio
AU  - Tsiamis, Konstantinos
AU  - Cardoso, Ana Cristina
PY  - 2021
UR  - https://www.mdpi.com/2073-4441/13/21/2952
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4644
AB  - The present pilot study tested and validated the use of the ‘Invasive Alien Species in Europe’ smartphone app (IASapp) in the Lower Danube Region. The study was conducted in three stages: (1) Testing the effectiveness of the app in Bulgaria, Romania and Serbia by organizing information and field testing campaigns; (2) Improving and extending the functionality of the app and developing a list of the invasive alien species (IAS) of concern to the Danube River Basin (DRB); and (3) Testing the updated app during the Joint Danube Survey 4 campaign. Overall, 13 campaigns were carried out, during which seven aquatic IAS of EU concern and nine IAS relevant to the DRB were recorded. Currently, the developed new functionality of IASapp allows the recording of 64 IAS of DRB concern. The updated IASapp has an important role in increasing public awareness on IAS issues, as well as in enlarging the participation and output of citizen science in the IAS early detection, monitoring and reporting in the DRB. Therefore, the constant communication with existing stakeholder groups and establishment of new citizen science groups is crucial for increasing the effectiveness of using the IASapp in the Danube Region and tackling the IAS issues.
PB  - Basel: MDPI
T2  - Water
T1  - Pilot Application of ‘Invasive Alien Species in Europe’ Smartphone App in the Danube Region
IS  - 21
VL  - 13
DO  - 10.3390/w13212952
SP  - 2952
ER  - 
@article{
author = "Trichkova, Teodora and Paunović, Momir and Cogălniceanu, Dan and Schade, Sven and Todorov, Milcho and Tomov, Rumen and Stănescu, Florina and Botev, Ivan and López-Cañizares, Celia and Gervasini, Eugenio and Hubenov, Zdravko and Ignatov, Kostadin and Kenderov, Marian and Marinković, Nikola and Mitton, Irena and Preda, Cristina and Spinelli, Fabiano Antonio and Tsiamis, Konstantinos and Cardoso, Ana Cristina",
year = "2021",
abstract = "The present pilot study tested and validated the use of the ‘Invasive Alien Species in Europe’ smartphone app (IASapp) in the Lower Danube Region. The study was conducted in three stages: (1) Testing the effectiveness of the app in Bulgaria, Romania and Serbia by organizing information and field testing campaigns; (2) Improving and extending the functionality of the app and developing a list of the invasive alien species (IAS) of concern to the Danube River Basin (DRB); and (3) Testing the updated app during the Joint Danube Survey 4 campaign. Overall, 13 campaigns were carried out, during which seven aquatic IAS of EU concern and nine IAS relevant to the DRB were recorded. Currently, the developed new functionality of IASapp allows the recording of 64 IAS of DRB concern. The updated IASapp has an important role in increasing public awareness on IAS issues, as well as in enlarging the participation and output of citizen science in the IAS early detection, monitoring and reporting in the DRB. Therefore, the constant communication with existing stakeholder groups and establishment of new citizen science groups is crucial for increasing the effectiveness of using the IASapp in the Danube Region and tackling the IAS issues.",
publisher = "Basel: MDPI",
journal = "Water",
title = "Pilot Application of ‘Invasive Alien Species in Europe’ Smartphone App in the Danube Region",
number = "21",
volume = "13",
doi = "10.3390/w13212952",
pages = "2952"
}
Trichkova, T., Paunović, M., Cogălniceanu, D., Schade, S., Todorov, M., Tomov, R., Stănescu, F., Botev, I., López-Cañizares, C., Gervasini, E., Hubenov, Z., Ignatov, K., Kenderov, M., Marinković, N., Mitton, I., Preda, C., Spinelli, F. A., Tsiamis, K.,& Cardoso, A. C.. (2021). Pilot Application of ‘Invasive Alien Species in Europe’ Smartphone App in the Danube Region. in Water
Basel: MDPI., 13(21), 2952.
https://doi.org/10.3390/w13212952
Trichkova T, Paunović M, Cogălniceanu D, Schade S, Todorov M, Tomov R, Stănescu F, Botev I, López-Cañizares C, Gervasini E, Hubenov Z, Ignatov K, Kenderov M, Marinković N, Mitton I, Preda C, Spinelli FA, Tsiamis K, Cardoso AC. Pilot Application of ‘Invasive Alien Species in Europe’ Smartphone App in the Danube Region. in Water. 2021;13(21):2952.
doi:10.3390/w13212952 .
Trichkova, Teodora, Paunović, Momir, Cogălniceanu, Dan, Schade, Sven, Todorov, Milcho, Tomov, Rumen, Stănescu, Florina, Botev, Ivan, López-Cañizares, Celia, Gervasini, Eugenio, Hubenov, Zdravko, Ignatov, Kostadin, Kenderov, Marian, Marinković, Nikola, Mitton, Irena, Preda, Cristina, Spinelli, Fabiano Antonio, Tsiamis, Konstantinos, Cardoso, Ana Cristina, "Pilot Application of ‘Invasive Alien Species in Europe’ Smartphone App in the Danube Region" in Water, 13, no. 21 (2021):2952,
https://doi.org/10.3390/w13212952 . .
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