TY  - JOUR
AU  - Krajnović, Tamara
AU  - Pantelić, Nebojša Đ.
AU  - Wolf, Katharina
AU  - Eichhorn, Thomas
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Wessjohann, Ludger A.
AU  - Kaluđerović, Goran N.
PY  - 2022
UR  - https://www.mdpi.com/1996-1944/15/14/5028
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9320346
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5089
AB  - Xanthohumol (XN) and isoxanthohumol (IXN), prenylated flavonoids from Humulus lupulus, have been shown to possess antitumor/cancerprotective, antioxidant, antiinflammatory, and antiangiogenic properties. In this study, mesoporous silica (SBA-15) was loaded with different amounts of xanthohumol and isoxanthohumol and characterized by standard analytical methods. The anticancer potential of XN and IXN loaded into SBA-15 has been evaluated against malignant mouse melanoma B16F10 cells. When these cells were treated with SBA-15 containing xanthohumol, an increase of the activity correlated with a higher immobilization rate of XN was observed. Considering the amount of XN loaded into SBA-15 (calculated from TGA), an improved antitumor potential of XN was observed (IC50 = 10.8 ± 0.4 and 11.8 ± 0.5 µM for SBA-15|XN2 and SBA-15|XN3, respectively; vs. IC50 = 18.5 ± 1.5 µM for free XN). The main mechanism against tumor cells of immobilized XN includes inhibition of proliferation and autophagic cell death. The MC50 values for SBA-15 loaded with isoxanthohumol were over 300 µg/mL in all cases investigated.
PB  - Basel: MDPI
T2  - Materials (Basel, Switzerland)
T1  - Anticancer Potential of Xanthohumol and Isoxanthohumol Loaded into SBA-15 Mesoporous Silica Particles against B16F10 Melanoma Cells.
IS  - 14
VL  - 15
DO  - 10.3390/ma15145028
SP  - 5028
ER  - 

@article{
author = "Krajnović, Tamara and Pantelić, Nebojša Đ. and Wolf, Katharina and Eichhorn, Thomas and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Wessjohann, Ludger A. and Kaluđerović, Goran N.",
year = "2022",
abstract = "Xanthohumol (XN) and isoxanthohumol (IXN), prenylated flavonoids from Humulus lupulus, have been shown to possess antitumor/cancerprotective, antioxidant, antiinflammatory, and antiangiogenic properties. In this study, mesoporous silica (SBA-15) was loaded with different amounts of xanthohumol and isoxanthohumol and characterized by standard analytical methods. The anticancer potential of XN and IXN loaded into SBA-15 has been evaluated against malignant mouse melanoma B16F10 cells. When these cells were treated with SBA-15 containing xanthohumol, an increase of the activity correlated with a higher immobilization rate of XN was observed. Considering the amount of XN loaded into SBA-15 (calculated from TGA), an improved antitumor potential of XN was observed (IC50 = 10.8 ± 0.4 and 11.8 ± 0.5 µM for SBA-15|XN2 and SBA-15|XN3, respectively; vs. IC50 = 18.5 ± 1.5 µM for free XN). The main mechanism against tumor cells of immobilized XN includes inhibition of proliferation and autophagic cell death. The MC50 values for SBA-15 loaded with isoxanthohumol were over 300 µg/mL in all cases investigated.",
publisher = "Basel: MDPI",
journal = "Materials (Basel, Switzerland)",
title = "Anticancer Potential of Xanthohumol and Isoxanthohumol Loaded into SBA-15 Mesoporous Silica Particles against B16F10 Melanoma Cells.",
number = "14",
volume = "15",
doi = "10.3390/ma15145028",
pages = "5028"
}

Krajnović, T., Pantelić, N. Đ., Wolf, K., Eichhorn, T., Maksimović-Ivanić, D., Mijatović, S., Wessjohann, L. A.,& Kaluđerović, G. N.. (2022). Anticancer Potential of Xanthohumol and Isoxanthohumol Loaded into SBA-15 Mesoporous Silica Particles against B16F10 Melanoma Cells.. in Materials (Basel, Switzerland)
Basel: MDPI., 15(14), 5028.
https://doi.org/10.3390/ma15145028

Krajnović T, Pantelić NĐ, Wolf K, Eichhorn T, Maksimović-Ivanić D, Mijatović S, Wessjohann LA, Kaluđerović GN. Anticancer Potential of Xanthohumol and Isoxanthohumol Loaded into SBA-15 Mesoporous Silica Particles against B16F10 Melanoma Cells.. in Materials (Basel, Switzerland). 2022;15(14):5028.
doi:10.3390/ma15145028 .

Krajnović, Tamara, Pantelić, Nebojša Đ., Wolf, Katharina, Eichhorn, Thomas, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Wessjohann, Ludger A., Kaluđerović, Goran N., "Anticancer Potential of Xanthohumol and Isoxanthohumol Loaded into SBA-15 Mesoporous Silica Particles against B16F10 Melanoma Cells." in Materials (Basel, Switzerland), 15, no. 14 (2022):5028,
https://doi.org/10.3390/ma15145028 . .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Kaluđerović, Goran N.
AU  - Dunđerović, Duško
AU  - Mirkov, Ivana
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5291
AB  - A prenylflavonoid from hops, isoxanthohumol (IXN) is gaining a lot of attention
nowadays due to its broad spectrum of biological activities. This study aimed to investigate
its potential antimetastatic properties in vitro against the highly invasive melanoma
cell line B16-F10 and in a murine metastatic model in vivo, in the context of
independent action and interaction with chemotherapy. The treatment with IXN diminished
cell viability in a dose-dependent manner, which is a consequence of induced
combined cell death by autophagy and caspase-dependent apoptosis. Additionally, the
dividing potential of highly proliferative melanoma cells was dramatically affected by
IXN, and is in line with an abrogated clonogenic potential in the population of survived
cells, indicating changes in their metastatic features. Concordantly, IXN strongly diminished
cell metastatic features down-regulating adhesion, migration, and invasion
through disrupted integrin signaling. Separate application of IXN inhibited the development
of lung metastatic foci in tumor-challenged animals. Although IXN potentiated
the action of chemotherapeutic drug paclitaxel (PCT) in vitro, the concomitant
treatment of these two agents did not exert statistically significant suppression of lung
metastases formation. Nonetheless, the change in the regime of drugs’ application to
7-day treatment with IXN prior to PCT made the subtherapeutic dose of PCT effective,
indicating IXNs’ capacity to trigger the differentiation of B16-F10 cells toward a less
invasive phenotype, thus sensitizing them to chemotherapy. Along with histopathological
confirmation of changes in cell phenotype in metastases, this data underlines the
important impact of the differentiation process on chemotherapy efficacy. This study
represents the first proof of IXNs’ antimetastatic activity in vivo and significantly contributes
to the development of the differentiation therapy concept as a support in the
treatment of metastatic malignancies.
AB  - Пренилфлавоноид из хмеља, изоксантохумол (IXN) данас привлачи велику
пажњу због свог широког спектра биолошких активности. Ова студија је имала
за циљ да истражи његова потенцијална антиметастатска својства на високо ин-
вазивној ћелијској линији меланома B16-F10 in vitro и in vivo, у контексту њего-
вог самосталног деловања или у комбинацији са хемотерапијом. Третман IXN је
смањио вијабилитет ћелија меланома на дозно зависан начин, што је последица
индуковане комбиноване ћелијске смрти аутофагијом и апоптозом зависном од
каспаза. Поред тога, овај изофлаванон је снажно инхибирао деобу високо про-
лиферативних ћелија меланома као и клоногени потенцијал преживелих ћели-
ја, указујући на промене у њиховим метастатским карактеристикама. Сагласно
томе, IXN је супримирао процесе који дефинишу метастазирање као што су
ћелијска адхезија, миграција и инвазија, ометајући интегрински сигнални пут.
Примена IXN је инхибирала развој метастатских жаришта у плућима експери-
менталних животиња. Иако је IXN појачао дејство хемотерапеутика паклитаксе-
ла (PCT) in vitro, истовремени третман ова два агенса није довео до статистички
значајне супресије у формирању плућних метастаза. Са друге стране, промена
динамике давања агенаса у виду 7-дневног третмана животиња IXN пре апли-
кације PCT учинила је ефикасном субтерапеутску дозу PCT, што се може при-
писати његовом капацитету да диферентује B16-F10 ћелије ка мање инвазивном
фенотипу и тиме их сензитизује на хемотерапију. Уз хистопатолошку потврду
промене фенотипа ћелија у метастазама, овај податак указује на значајан до-
принос процеса диференцијације успешности исхода хемотерапије. Ова студија
представља први доказ антиметастатске активности IXN in vivo и значајно до-
приноси успостављању концепта диференцијационе терапије у подршци лечењу
метастатских малигнитета.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model
SP  - 152
EP  - 153
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5291
ER  - 

@conference{
author = "Krajnović, Tamara and Drača, Dijana and Kaluđerović, Goran N. and Dunđerović, Duško and Mirkov, Ivana and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela and Mijatović, Sanja",
year = "2022",
abstract = "A prenylflavonoid from hops, isoxanthohumol (IXN) is gaining a lot of attention
nowadays due to its broad spectrum of biological activities. This study aimed to investigate
its potential antimetastatic properties in vitro against the highly invasive melanoma
cell line B16-F10 and in a murine metastatic model in vivo, in the context of
independent action and interaction with chemotherapy. The treatment with IXN diminished
cell viability in a dose-dependent manner, which is a consequence of induced
combined cell death by autophagy and caspase-dependent apoptosis. Additionally, the
dividing potential of highly proliferative melanoma cells was dramatically affected by
IXN, and is in line with an abrogated clonogenic potential in the population of survived
cells, indicating changes in their metastatic features. Concordantly, IXN strongly diminished
cell metastatic features down-regulating adhesion, migration, and invasion
through disrupted integrin signaling. Separate application of IXN inhibited the development
of lung metastatic foci in tumor-challenged animals. Although IXN potentiated
the action of chemotherapeutic drug paclitaxel (PCT) in vitro, the concomitant
treatment of these two agents did not exert statistically significant suppression of lung
metastases formation. Nonetheless, the change in the regime of drugs’ application to
7-day treatment with IXN prior to PCT made the subtherapeutic dose of PCT effective,
indicating IXNs’ capacity to trigger the differentiation of B16-F10 cells toward a less
invasive phenotype, thus sensitizing them to chemotherapy. Along with histopathological
confirmation of changes in cell phenotype in metastases, this data underlines the
important impact of the differentiation process on chemotherapy efficacy. This study
represents the first proof of IXNs’ antimetastatic activity in vivo and significantly contributes
to the development of the differentiation therapy concept as a support in the
treatment of metastatic malignancies., Пренилфлавоноид из хмеља, изоксантохумол (IXN) данас привлачи велику
пажњу због свог широког спектра биолошких активности. Ова студија је имала
за циљ да истражи његова потенцијална антиметастатска својства на високо ин-
вазивној ћелијској линији меланома B16-F10 in vitro и in vivo, у контексту њего-
вог самосталног деловања или у комбинацији са хемотерапијом. Третман IXN је
смањио вијабилитет ћелија меланома на дозно зависан начин, што је последица
индуковане комбиноване ћелијске смрти аутофагијом и апоптозом зависном од
каспаза. Поред тога, овај изофлаванон је снажно инхибирао деобу високо про-
лиферативних ћелија меланома као и клоногени потенцијал преживелих ћели-
ја, указујући на промене у њиховим метастатским карактеристикама. Сагласно
томе, IXN је супримирао процесе који дефинишу метастазирање као што су
ћелијска адхезија, миграција и инвазија, ометајући интегрински сигнални пут.
Примена IXN је инхибирала развој метастатских жаришта у плућима експери-
менталних животиња. Иако је IXN појачао дејство хемотерапеутика паклитаксе-
ла (PCT) in vitro, истовремени третман ова два агенса није довео до статистички
значајне супресије у формирању плућних метастаза. Са друге стране, промена
динамике давања агенаса у виду 7-дневног третмана животиња IXN пре апли-
кације PCT учинила је ефикасном субтерапеутску дозу PCT, што се може при-
писати његовом капацитету да диферентује B16-F10 ћелије ка мање инвазивном
фенотипу и тиме их сензитизује на хемотерапију. Уз хистопатолошку потврду
промене фенотипа ћелија у метастазама, овај податак указује на значајан до-
принос процеса диференцијације успешности исхода хемотерапије. Ова студија
представља први доказ антиметастатске активности IXN in vivo и значајно до-
приноси успостављању концепта диференцијационе терапије у подршци лечењу
метастатских малигнитета.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model",
pages = "152-153",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5291"
}

Krajnović, T., Drača, D., Kaluđerović, G. N., Dunđerović, D., Mirkov, I., Wessjohann, L. A., Maksimović-Ivanić, D.,& Mijatović, S.. (2022). Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 152-153.
https://hdl.handle.net/21.15107/rcub_ibiss_5291

Krajnović T, Drača D, Kaluđerović GN, Dunđerović D, Mirkov I, Wessjohann LA, Maksimović-Ivanić D, Mijatović S. Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:152-153.
https://hdl.handle.net/21.15107/rcub_ibiss_5291 .

Krajnović, Tamara, Drača, Dijana, Kaluđerović, Goran N., Dunđerović, Duško, Mirkov, Ivana, Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, Mijatović, Sanja, "Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):152-153,
https://hdl.handle.net/21.15107/rcub_ibiss_5291 .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Wessjohann, Ludger A.
AU  - Kaluđerović, Goran N.
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5289
AB  - Prenylflavonoid from hops - xanthohumol (XN) has been shown to possess diverse biological properties, including strong anticancer activity. One of the possibilities for improving delivery and effectiveness of drugs is the use of mesoporous silica nanoparticles such as nontoxic SBA-15. The aim of this study was the evaluation of the in vitro anticancer potential of XN loaded with different amounts into SBA-15 particles against malignant mouse melanoma B16-F10 cells. Our data indicate that SBA-15 containing XN showed a loading rate–activity dependence. Importantly, immobilization of XN into SBA-15 preserved and even potentiated its antitumor potential, in comparison to its free form. Also, by loading into SBA-15 carrier, XNs’ anticancer mode of action converted from predominantly cytotoxic to cytostatic, resulting in a reduction of dividing potential. In addition, contrasting the previously observed apoptotic-inducing property of free XN, immobilized XN induced autophagic cell death that might be important for disabling tumor repopulation in response to apoptotic-induced cell proliferation, a mechanism often asscociated with therapy failure of advanced forms of cancer1.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Anticancer potential of xanthohumol loaded into SBA-15 mesoporous silica particles against B16-F10 cells
SP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5289
ER  - 

@conference{
author = "Krajnović, Tamara and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Wessjohann, Ludger A. and Kaluđerović, Goran N.",
year = "2022",
abstract = "Prenylflavonoid from hops - xanthohumol (XN) has been shown to possess diverse biological properties, including strong anticancer activity. One of the possibilities for improving delivery and effectiveness of drugs is the use of mesoporous silica nanoparticles such as nontoxic SBA-15. The aim of this study was the evaluation of the in vitro anticancer potential of XN loaded with different amounts into SBA-15 particles against malignant mouse melanoma B16-F10 cells. Our data indicate that SBA-15 containing XN showed a loading rate–activity dependence. Importantly, immobilization of XN into SBA-15 preserved and even potentiated its antitumor potential, in comparison to its free form. Also, by loading into SBA-15 carrier, XNs’ anticancer mode of action converted from predominantly cytotoxic to cytostatic, resulting in a reduction of dividing potential. In addition, contrasting the previously observed apoptotic-inducing property of free XN, immobilized XN induced autophagic cell death that might be important for disabling tumor repopulation in response to apoptotic-induced cell proliferation, a mechanism often asscociated with therapy failure of advanced forms of cancer1.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Anticancer potential of xanthohumol loaded into SBA-15 mesoporous silica particles against B16-F10 cells",
pages = "87",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5289"
}

Krajnović, T., Maksimović-Ivanić, D., Mijatović, S., Wessjohann, L. A.,& Kaluđerović, G. N.. (2022). Anticancer potential of xanthohumol loaded into SBA-15 mesoporous silica particles against B16-F10 cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 87.
https://hdl.handle.net/21.15107/rcub_ibiss_5289

Krajnović T, Maksimović-Ivanić D, Mijatović S, Wessjohann LA, Kaluđerović GN. Anticancer potential of xanthohumol loaded into SBA-15 mesoporous silica particles against B16-F10 cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:87.
https://hdl.handle.net/21.15107/rcub_ibiss_5289 .

Krajnović, Tamara, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Wessjohann, Ludger A., Kaluđerović, Goran N., "Anticancer potential of xanthohumol loaded into SBA-15 mesoporous silica particles against B16-F10 cells" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):87,
https://hdl.handle.net/21.15107/rcub_ibiss_5289 .

TY  - JOUR
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Kaluđerović, Goran N
AU  - Wessjohann, Ludger A
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3484
UR  - http://ar.iiarjournals.org/content/39/10/5403
AB  - BACKGROUND/AIM Tubugi-1 is a more stable and accessible synthetic counterpart of natural tubulysins. This study aimed to evaluate its cytotoxic potential against anaplastic human melanoma cells. MATERIALS AND METHODS The viability of A-375 cells was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assay. The type of cell death and proliferative rate were investigated using flow cytometry and fluorescent microscopy, while the molecular background was evaluated by western blot. RESULTS Tubugi-1 reduced the viability of A-375 cells, inducing massive micronucleation, followed by augmented expression of inhibitor of nuclear factor-κB and caspase-2, typical of a mitotic catastrophe. Disturbed proliferation and G2M block with prominent caspase activity, weakened the expression of B-cell lymphoma 2 and B-cell lymphoma 2-associated X transient up-regulation, coexisted with intensive autophagy. Specific inhibition of autophagy by chloroquine resulted in conversion from mitotic catastrophe to rapid apoptosis. CONCLUSION Multilevel anticancer action of tubugi-1 is extended by co-application of an autophagy inhibitor, giving a new dimension in further preclinical advancement of this potential agent.
T2  - Anticancer Research
T1  - Synthetic Tubulysin Derivative, Tubugi-1, Against Invasive Melanoma Cells: The Cell Death Triangle.
IS  - 10
VL  - 39
DO  - 10.21873/anticanres.13734
SP  - 5403
EP  - 5415
ER  - 

@article{
author = "Drača, Dijana and Mijatović, Sanja and Krajnović, Tamara and Kaluđerović, Goran N and Wessjohann, Ludger A and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "BACKGROUND/AIM Tubugi-1 is a more stable and accessible synthetic counterpart of natural tubulysins. This study aimed to evaluate its cytotoxic potential against anaplastic human melanoma cells. MATERIALS AND METHODS The viability of A-375 cells was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assay. The type of cell death and proliferative rate were investigated using flow cytometry and fluorescent microscopy, while the molecular background was evaluated by western blot. RESULTS Tubugi-1 reduced the viability of A-375 cells, inducing massive micronucleation, followed by augmented expression of inhibitor of nuclear factor-κB and caspase-2, typical of a mitotic catastrophe. Disturbed proliferation and G2M block with prominent caspase activity, weakened the expression of B-cell lymphoma 2 and B-cell lymphoma 2-associated X transient up-regulation, coexisted with intensive autophagy. Specific inhibition of autophagy by chloroquine resulted in conversion from mitotic catastrophe to rapid apoptosis. CONCLUSION Multilevel anticancer action of tubugi-1 is extended by co-application of an autophagy inhibitor, giving a new dimension in further preclinical advancement of this potential agent.",
journal = "Anticancer Research",
title = "Synthetic Tubulysin Derivative, Tubugi-1, Against Invasive Melanoma Cells: The Cell Death Triangle.",
number = "10",
volume = "39",
doi = "10.21873/anticanres.13734",
pages = "5403-5415"
}

Drača, D., Mijatović, S., Krajnović, T., Kaluđerović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2019). Synthetic Tubulysin Derivative, Tubugi-1, Against Invasive Melanoma Cells: The Cell Death Triangle.. in Anticancer Research, 39(10), 5403-5415.
https://doi.org/10.21873/anticanres.13734

Drača D, Mijatović S, Krajnović T, Kaluđerović GN, Wessjohann LA, Maksimović-Ivanić D. Synthetic Tubulysin Derivative, Tubugi-1, Against Invasive Melanoma Cells: The Cell Death Triangle.. in Anticancer Research. 2019;39(10):5403-5415.
doi:10.21873/anticanres.13734 .

Drača, Dijana, Mijatović, Sanja, Krajnović, Tamara, Kaluđerović, Goran N, Wessjohann, Ludger A, Maksimović-Ivanić, Danijela, "Synthetic Tubulysin Derivative, Tubugi-1, Against Invasive Melanoma Cells: The Cell Death Triangle." in Anticancer Research, 39, no. 10 (2019):5403-5415,
https://doi.org/10.21873/anticanres.13734 . .

TY  - JOUR
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Bogdanović Pristov, Jelena
AU  - Đukić, Tatjana
AU  - Kaluđerović, Goran N.
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0014482719302125?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3345
AB  - Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxel-treated animals. Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as M1. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward M1, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.
T2  - Experimental Cell Research
T1  - The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model
IS  - 2
VL  - 380
DO  - 10.1016/J.YEXCR.2019.04.028
SP  - 159
EP  - 170
ER  - 

@article{
author = "Drača, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Đukić, Tatjana and Kaluđerović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxel-treated animals. Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as M1. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward M1, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.",
journal = "Experimental Cell Research",
title = "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model",
number = "2",
volume = "380",
doi = "10.1016/J.YEXCR.2019.04.028",
pages = "159-170"
}

Drača, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Đukić, T., Kaluđerović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2019). The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research, 380(2), 159-170.
https://doi.org/10.1016/J.YEXCR.2019.04.028

Drača D, Mijatović S, Krajnović T, Bogdanović Pristov J, Đukić T, Kaluđerović GN, Wessjohann LA, Maksimović-Ivanić D. The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research. 2019;380(2):159-170.
doi:10.1016/J.YEXCR.2019.04.028 .

Drača, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Đukić, Tatjana, Kaluđerović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model" in Experimental Cell Research, 380, no. 2 (2019):159-170,
https://doi.org/10.1016/J.YEXCR.2019.04.028 . .

TY  - JOUR
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Kaluđerović, Goran
AU  - Dunđerović, Duško
AU  - Mirkov, Ivana
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0278691519302455?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3350
AB  - Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, gained increasing attention as a potential chemopreventive agent. In the present study, IXN antimetastatic potential in vitro against the highly invasive melanoma cell line B16-F10 and in vivo in a murine metastatic model was investigated. Melanoma cell viability was diminished in a dose-dependent manner following the treatment with IXN. This decrease was a consequence of autophagy and caspase-dependent apoptosis. Additionally, the dividing potential of highly proliferative melanoma cells was dramatically affected by this isoflavanone, which was in correlation with an abrogated cell colony forming potential, indicating changes in their metastatic features. Concordantly, IXN promoted strong suppression of the processes that define metastasis- cell adhesion, invasion, and migration. Further investigation at the molecular level revealed that the abolished metastatic potential of a melanoma subclone was due to disrupted integrin signaling. Importantly, these results were reaffirmed in vivo where IXN inhibited the development of lung metastatic foci in tumor-challenged animals. The results of the present study may highlight the beneficial effects of IXN on melanoma as the most aggressive type of skin cancer and will hopefully shed a light on the possible use of this prenylflavonoid in the treatment of metastatic malignancies.
T2  - Food and Chemical Toxicology
T1  - The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.
VL  - 129
DO  - 10.1016/j.fct.2019.04.046
SP  - 257
EP  - 268
ER  - 

@article{
author = "Krajnović, Tamara and Drača, Dijana and Kaluđerović, Goran and Dunđerović, Duško and Mirkov, Ivana and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela and Mijatović, Sanja",
year = "2019",
abstract = "Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, gained increasing attention as a potential chemopreventive agent. In the present study, IXN antimetastatic potential in vitro against the highly invasive melanoma cell line B16-F10 and in vivo in a murine metastatic model was investigated. Melanoma cell viability was diminished in a dose-dependent manner following the treatment with IXN. This decrease was a consequence of autophagy and caspase-dependent apoptosis. Additionally, the dividing potential of highly proliferative melanoma cells was dramatically affected by this isoflavanone, which was in correlation with an abrogated cell colony forming potential, indicating changes in their metastatic features. Concordantly, IXN promoted strong suppression of the processes that define metastasis- cell adhesion, invasion, and migration. Further investigation at the molecular level revealed that the abolished metastatic potential of a melanoma subclone was due to disrupted integrin signaling. Importantly, these results were reaffirmed in vivo where IXN inhibited the development of lung metastatic foci in tumor-challenged animals. The results of the present study may highlight the beneficial effects of IXN on melanoma as the most aggressive type of skin cancer and will hopefully shed a light on the possible use of this prenylflavonoid in the treatment of metastatic malignancies.",
journal = "Food and Chemical Toxicology",
title = "The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.",
volume = "129",
doi = "10.1016/j.fct.2019.04.046",
pages = "257-268"
}

Krajnović, T., Drača, D., Kaluđerović, G., Dunđerović, D., Mirkov, I., Wessjohann, L. A., Maksimović-Ivanić, D.,& Mijatović, S.. (2019). The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.. in Food and Chemical Toxicology, 129, 257-268.
https://doi.org/10.1016/j.fct.2019.04.046

Krajnović T, Drača D, Kaluđerović G, Dunđerović D, Mirkov I, Wessjohann LA, Maksimović-Ivanić D, Mijatović S. The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.. in Food and Chemical Toxicology. 2019;129:257-268.
doi:10.1016/j.fct.2019.04.046 .

Krajnović, Tamara, Drača, Dijana, Kaluđerović, Goran, Dunđerović, Duško, Mirkov, Ivana, Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, Mijatović, Sanja, "The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model." in Food and Chemical Toxicology, 129 (2019):257-268,
https://doi.org/10.1016/j.fct.2019.04.046 . .

TY  - JOUR
AU  - Krajnović, Tamara
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Drača, Dijana
AU  - Wolf, Katharina
AU  - Edeler, David
AU  - Wessjohann, Ludger A
AU  - Kaluđerović, Goran N
PY  - 2018
UR  - http://www.mdpi.com/2079-4991/8/5/322
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5977336
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3078
AB  - In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15|EO1⁻SBA-15|EO5: 8⁻36%) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in extremely acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27% of EO, while a constant activity for 32% and 36% of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15|EO3) does not disturb viability of peritoneal macrophages. SBA-15|EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of poly-(ADP-ribose)-polymerase (PARP) cleavage fragment. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.
T2  - Nanomaterials (Basel, Switzerland)
T1  - Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15.
IS  - 5
VL  - 8
DO  - 10.3390/nano8050322
SP  - 322
ER  - 

@article{
author = "Krajnović, Tamara and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Drača, Dijana and Wolf, Katharina and Edeler, David and Wessjohann, Ludger A and Kaluđerović, Goran N",
year = "2018",
abstract = "In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15|EO1⁻SBA-15|EO5: 8⁻36%) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in extremely acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27% of EO, while a constant activity for 32% and 36% of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15|EO3) does not disturb viability of peritoneal macrophages. SBA-15|EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of poly-(ADP-ribose)-polymerase (PARP) cleavage fragment. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.",
journal = "Nanomaterials (Basel, Switzerland)",
title = "Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15.",
number = "5",
volume = "8",
doi = "10.3390/nano8050322",
pages = "322"
}

Krajnović, T., Maksimović-Ivanić, D., Mijatović, S., Drača, D., Wolf, K., Edeler, D., Wessjohann, L. A.,& Kaluđerović, G. N.. (2018). Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15.. in Nanomaterials (Basel, Switzerland), 8(5), 322.
https://doi.org/10.3390/nano8050322

Krajnović T, Maksimović-Ivanić D, Mijatović S, Drača D, Wolf K, Edeler D, Wessjohann LA, Kaluđerović GN. Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15.. in Nanomaterials (Basel, Switzerland). 2018;8(5):322.
doi:10.3390/nano8050322 .

Krajnović, Tamara, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Drača, Dijana, Wolf, Katharina, Edeler, David, Wessjohann, Ludger A, Kaluđerović, Goran N, "Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15." in Nanomaterials (Basel, Switzerland), 8, no. 5 (2018):322,
https://doi.org/10.3390/nano8050322 . .

TY  - JOUR
AU  - Janković Tomanić, Milena
AU  - Todorović, Dajana
AU  - Stanivuković, Zoran
AU  - Perić Mataruga, Vesna
AU  - Wessjohann, Ludger A.
AU  - Kaluđerović, Goran N.
PY  - 2017
UR  - http://online.journals.tubitak.gov.tr/openDoiPdf.htm?mKodu=biy-1705-76
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2945
AB  - The study presented here aims to elucidate the effects of emodin (EO = 1,3,8-trihydroxy-6-methylanthraquinone) in its free form and when loaded into a mesoporous silica nanocarrier SBA-15 (→ SBA-15|EO) on the activities of the main antioxidative enzymes, superoxide dismutase, catalase, glutathione S-transferase, and glutathione reductase, in larvae of a polyphagous insect pest, the browntail moth Euproctis chrysorrhoea (L.). The results show that only SBA-15|EO upregulates the activities of the tested antioxidative enzymes. These results point to significant differences in the effectiveness of the compound in the free versus the loaded form.
PB  - Scientific and Technical Research Council of Turkey
T2  - Turkish Journal of Biology
T2  - Turkish Journal of Biology
T1  - Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae
IS  - 6
VL  - 41
DO  - 10.3906/biy-1705-76
SP  - 935
EP  - 942
ER  - 

@article{
author = "Janković Tomanić, Milena and Todorović, Dajana and Stanivuković, Zoran and Perić Mataruga, Vesna and Wessjohann, Ludger A. and Kaluđerović, Goran N.",
year = "2017",
abstract = "The study presented here aims to elucidate the effects of emodin (EO = 1,3,8-trihydroxy-6-methylanthraquinone) in its free form and when loaded into a mesoporous silica nanocarrier SBA-15 (→ SBA-15|EO) on the activities of the main antioxidative enzymes, superoxide dismutase, catalase, glutathione S-transferase, and glutathione reductase, in larvae of a polyphagous insect pest, the browntail moth Euproctis chrysorrhoea (L.). The results show that only SBA-15|EO upregulates the activities of the tested antioxidative enzymes. These results point to significant differences in the effectiveness of the compound in the free versus the loaded form.",
publisher = "Scientific and Technical Research Council of Turkey",
journal = "Turkish Journal of Biology, Turkish Journal of Biology",
title = "Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae",
number = "6",
volume = "41",
doi = "10.3906/biy-1705-76",
pages = "935-942"
}

Janković Tomanić, M., Todorović, D., Stanivuković, Z., Perić Mataruga, V., Wessjohann, L. A.,& Kaluđerović, G. N.. (2017). Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae. in Turkish Journal of Biology
Scientific and Technical Research Council of Turkey., 41(6), 935-942.
https://doi.org/10.3906/biy-1705-76

Janković Tomanić M, Todorović D, Stanivuković Z, Perić Mataruga V, Wessjohann LA, Kaluđerović GN. Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae. in Turkish Journal of Biology. 2017;41(6):935-942.
doi:10.3906/biy-1705-76 .

Janković Tomanić, Milena, Todorović, Dajana, Stanivuković, Zoran, Perić Mataruga, Vesna, Wessjohann, Ludger A., Kaluđerović, Goran N., "Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae" in Turkish Journal of Biology, 41, no. 6 (2017):935-942,
https://doi.org/10.3906/biy-1705-76 . .

TY  - JOUR
AU  - Krajnović, Tamara
AU  - Kaluđerović, Goran N
AU  - Wessjohann, Ludger A
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2016
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1043661816000189
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3306
AB  - Isoxanthohumol (IXN), a prenylated flavonoid from hops, exhibits diverse biological activities, e.g. antitumor, antiinflammatory, antioxidant and antiangiogenic. In this study, the effect of IXN is evaluated on two melanoma cell lines with dissimilar molecular background, B16 and A375. The treatment of both cell lines with IXN resulted in dose-dependent decrease of cell viability. Abolished viability was in correlation with changed morphology and loss of dividing potential indicating phenotypical alteration of both tested cell lines. While modified B16 cells underwent the process of non-classic differentiation followed by tyrosinase activity without enhancement of melanin content, inhibition of Notch 1, β-catenin and Oct-3/4 was observed in A375 cells indicating loss of their pluripotent characteristics. In parallel with this, distinct subpopulations in both cell cultures entered the process of programmed cell death-apoptosis in a caspase independent manner. The described changes in cultures upon exposure to IXN could be connected with the suppression of reactive oxygen (ROS) and nitrogen species (RNS) induced by the drug. Despite the differences in which IXN promoted modifications in the upper part of the PI3K/Akt and MEK-ERK signaling pathways between B16 and A375 cells, p70S6K and its target S6 protein in both types of melanoma cells, after transient activation, became inhibited. In addition to direct input of IXN on cell viability, this study for the first time shows that IXN strongly sensitizes melanoma cells to the treatment with paclitaxel in vivo, in concordance with data obtained in vitro on B16 cells as well as their highly invasive F10 subclone.
PB  - Academic Press
T2  - Pharmacological Research
T1  - Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo
VL  - 105
DO  - 10.1016/j.phrs.2016.01.011
SP  - 62
EP  - 73
ER  - 

@article{
author = "Krajnović, Tamara and Kaluđerović, Goran N and Wessjohann, Ludger A and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2016",
abstract = "Isoxanthohumol (IXN), a prenylated flavonoid from hops, exhibits diverse biological activities, e.g. antitumor, antiinflammatory, antioxidant and antiangiogenic. In this study, the effect of IXN is evaluated on two melanoma cell lines with dissimilar molecular background, B16 and A375. The treatment of both cell lines with IXN resulted in dose-dependent decrease of cell viability. Abolished viability was in correlation with changed morphology and loss of dividing potential indicating phenotypical alteration of both tested cell lines. While modified B16 cells underwent the process of non-classic differentiation followed by tyrosinase activity without enhancement of melanin content, inhibition of Notch 1, β-catenin and Oct-3/4 was observed in A375 cells indicating loss of their pluripotent characteristics. In parallel with this, distinct subpopulations in both cell cultures entered the process of programmed cell death-apoptosis in a caspase independent manner. The described changes in cultures upon exposure to IXN could be connected with the suppression of reactive oxygen (ROS) and nitrogen species (RNS) induced by the drug. Despite the differences in which IXN promoted modifications in the upper part of the PI3K/Akt and MEK-ERK signaling pathways between B16 and A375 cells, p70S6K and its target S6 protein in both types of melanoma cells, after transient activation, became inhibited. In addition to direct input of IXN on cell viability, this study for the first time shows that IXN strongly sensitizes melanoma cells to the treatment with paclitaxel in vivo, in concordance with data obtained in vitro on B16 cells as well as their highly invasive F10 subclone.",
publisher = "Academic Press",
journal = "Pharmacological Research",
title = "Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo",
volume = "105",
doi = "10.1016/j.phrs.2016.01.011",
pages = "62-73"
}

Krajnović, T., Kaluđerović, G. N., Wessjohann, L. A., Mijatović, S.,& Maksimović-Ivanić, D.. (2016). Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo. in Pharmacological Research
Academic Press., 105, 62-73.
https://doi.org/10.1016/j.phrs.2016.01.011

Krajnović T, Kaluđerović GN, Wessjohann LA, Mijatović S, Maksimović-Ivanić D. Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo. in Pharmacological Research. 2016;105:62-73.
doi:10.1016/j.phrs.2016.01.011 .

Krajnović, Tamara, Kaluđerović, Goran N, Wessjohann, Ludger A, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo" in Pharmacological Research, 105 (2016):62-73,
https://doi.org/10.1016/j.phrs.2016.01.011 . .