TY  - CONF
AU  - Đukić-Ćosić, Danijela
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4485
AB  - Malignant diseases world incidence is constantly increasing and it is assumed that
combining immunomodulators with immunotherapy would improve cancer therapy
effectiveness. We present a research-development project of international cooperation with
the People's Republic of China entitled "Increasing the effectiveness of cancer
immunotherapy with a combination of CAR-T cells or PD-1/PD-L1 inhibitors using
immunomodulators", led by Faculty of Pharmacy, University of Belgrade. Sulforaphane
(SFN), isothiocyanate from cabbage vegetables, and a type of inactivated bacterium
Pseudomonas aeruginosa (PA-MSHA) have been recognized as immunomodulators with high
immune system stimulating potential, i.e. antitumor effect. However, there are few data on
their individual safe use, and no data on the potential side/harmful effects of their
combination, especially in patients with malignant diseases and significant immune system
impairment. The Chinese team is investigating the effectiveness of improving
immunotherapy with combination of immunomodulators, with their first published results
proving SFN positive effect when administered with CAR-T cells (1), while Serbian team aims
to examine toxicological profiles of single and/or combined SFN and PA MSHA, in silico, in
vitro and in vivo on two experimental models - zebrafish and rat. The project will specifically
examine adverse effects potential of single and/or combined use of the tested
immunomodulators or lack of their efficacy in cancer patients, especially colon cancer. The
first in silico results of the Serbian team indicated benefit/risk of SFN in patients with colon
cancer depending on individual genes expression and identified gene set which change may
indicate a positive or negative effect of immunomodulators (2).
AB  - Incidenca malignih oboljenja u svetu je u stalnom porastu i pretpostavlja se da bi
kombinacija imunomodulatora sa imunoterapijom poboljšala efikasnost terapije kod
pacijenata obolelih od raka. Ovaj rad prezentuje istraživačko-razvojni projekat međunarodne
saradnje sa NR Kinom pod nazivom „Povećanje efikasnosti imunoterapije karcinoma
kombinacijom CAR-T ćelija ili PD-1/PD-L1 inhibitora pomoću imunomodulatora” čiji je
nosilac Farmaceutski fakultet Univerziteta u Beogradu. Sulforafan (SFN), izotiocijanat iz
kupusastog povrća, i vrsta inaktivisane bakterije Pseudomonas aeruginosa (PA-MSHA)
prepoznati su kao imunomodulatori sa velikim stimulativnim potencijalom imunskog
sistema, odnosno antitumorskim efektom. Međutim, malo je podataka o njihovoj
pojedinačnoj bezbednoj primeni, dok nema podataka o potencijalnim neželjenim i štetnim
efektima njihove kombinovane primene, posebno kod pacijenata obolelih od malignih bolesti
sa značajno narušenim imunskim sistemom. Kineski tim ispituje efikasnost poboljašanja
imunoterapije kombinacijom sa imunomodulatorima, pri čemu je njihovim prvim
publikovanim rezultatima dokazano pozitivno dejstvo SFN kada se primenjuje sa CAR-T
ćelijama (1), dok je zadatak srpskog tima da ispita toksikolški profile pojedinačne ili
kombinovane primene SFN i PA-MSHA in silico, in vitro i in vivo na dva eksperimentalna
modela – zebrica i pacova. Projekat će posebno ispitati potencijal za pojavu štetnih efekata
pojedinačne i/ili kombinovane primene ispitivanih imunomodulatora ili pak izostanak
efikasnosti terapije kod pacijenata sa rakom, posebno rakom debelog creva. Prvi in silico
rezultati srpskog istraživačkog tima ukazuju da korist ili rizik primene SFN kod pacijenata sa
rakom debelog creva zavisi od ekspresije pojedinih gena kod pacijenta i identifikuje setove
gena čija promena može ukazati na pozitivan ili čak negativan efekat primene
imunomodulatora (2).
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Toxicological aspect of immunomodulators: friend or foe in increasing the effectiveness of cancer immunotherapy
T1  - Toksikološki aspekt imunomodulatora: prijatelj ili neprijatelj u povećanju efikasnosti imunoterapije karcinoma
VL  - 72
IS  - 4 suplement
SP  - S167
EP  - S168
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4485
ER  - 

@conference{
author = "Đukić-Ćosić, Danijela",
year = "2022",
abstract = "Malignant diseases world incidence is constantly increasing and it is assumed that
combining immunomodulators with immunotherapy would improve cancer therapy
effectiveness. We present a research-development project of international cooperation with
the People's Republic of China entitled "Increasing the effectiveness of cancer
immunotherapy with a combination of CAR-T cells or PD-1/PD-L1 inhibitors using
immunomodulators", led by Faculty of Pharmacy, University of Belgrade. Sulforaphane
(SFN), isothiocyanate from cabbage vegetables, and a type of inactivated bacterium
Pseudomonas aeruginosa (PA-MSHA) have been recognized as immunomodulators with high
immune system stimulating potential, i.e. antitumor effect. However, there are few data on
their individual safe use, and no data on the potential side/harmful effects of their
combination, especially in patients with malignant diseases and significant immune system
impairment. The Chinese team is investigating the effectiveness of improving
immunotherapy with combination of immunomodulators, with their first published results
proving SFN positive effect when administered with CAR-T cells (1), while Serbian team aims
to examine toxicological profiles of single and/or combined SFN and PA MSHA, in silico, in
vitro and in vivo on two experimental models - zebrafish and rat. The project will specifically
examine adverse effects potential of single and/or combined use of the tested
immunomodulators or lack of their efficacy in cancer patients, especially colon cancer. The
first in silico results of the Serbian team indicated benefit/risk of SFN in patients with colon
cancer depending on individual genes expression and identified gene set which change may
indicate a positive or negative effect of immunomodulators (2)., Incidenca malignih oboljenja u svetu je u stalnom porastu i pretpostavlja se da bi
kombinacija imunomodulatora sa imunoterapijom poboljšala efikasnost terapije kod
pacijenata obolelih od raka. Ovaj rad prezentuje istraživačko-razvojni projekat međunarodne
saradnje sa NR Kinom pod nazivom „Povećanje efikasnosti imunoterapije karcinoma
kombinacijom CAR-T ćelija ili PD-1/PD-L1 inhibitora pomoću imunomodulatora” čiji je
nosilac Farmaceutski fakultet Univerziteta u Beogradu. Sulforafan (SFN), izotiocijanat iz
kupusastog povrća, i vrsta inaktivisane bakterije Pseudomonas aeruginosa (PA-MSHA)
prepoznati su kao imunomodulatori sa velikim stimulativnim potencijalom imunskog
sistema, odnosno antitumorskim efektom. Međutim, malo je podataka o njihovoj
pojedinačnoj bezbednoj primeni, dok nema podataka o potencijalnim neželjenim i štetnim
efektima njihove kombinovane primene, posebno kod pacijenata obolelih od malignih bolesti
sa značajno narušenim imunskim sistemom. Kineski tim ispituje efikasnost poboljašanja
imunoterapije kombinacijom sa imunomodulatorima, pri čemu je njihovim prvim
publikovanim rezultatima dokazano pozitivno dejstvo SFN kada se primenjuje sa CAR-T
ćelijama (1), dok je zadatak srpskog tima da ispita toksikolški profile pojedinačne ili
kombinovane primene SFN i PA-MSHA in silico, in vitro i in vivo na dva eksperimentalna
modela – zebrica i pacova. Projekat će posebno ispitati potencijal za pojavu štetnih efekata
pojedinačne i/ili kombinovane primene ispitivanih imunomodulatora ili pak izostanak
efikasnosti terapije kod pacijenata sa rakom, posebno rakom debelog creva. Prvi in silico
rezultati srpskog istraživačkog tima ukazuju da korist ili rizik primene SFN kod pacijenata sa
rakom debelog creva zavisi od ekspresije pojedinih gena kod pacijenta i identifikuje setove
gena čija promena može ukazati na pozitivan ili čak negativan efekat primene
imunomodulatora (2).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Toxicological aspect of immunomodulators: friend or foe in increasing the effectiveness of cancer immunotherapy, Toksikološki aspekt imunomodulatora: prijatelj ili neprijatelj u povećanju efikasnosti imunoterapije karcinoma",
volume = "72",
number = "4 suplement",
pages = "S167-S168",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4485"
}

Đukić-Ćosić, D.. (2022). Toxicological aspect of immunomodulators: friend or foe in increasing the effectiveness of cancer immunotherapy. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S167-S168.
https://hdl.handle.net/21.15107/rcub_farfar_4485

Đukić-Ćosić D. Toxicological aspect of immunomodulators: friend or foe in increasing the effectiveness of cancer immunotherapy. in Arhiv za farmaciju. 2022;72(4 suplement):S167-S168.
https://hdl.handle.net/21.15107/rcub_farfar_4485 .

Đukić-Ćosić, Danijela, "Toxicological aspect of immunomodulators: friend or foe in increasing the effectiveness of cancer immunotherapy" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S167-S168,
https://hdl.handle.net/21.15107/rcub_farfar_4485 .

TY  - CONF
AU  - Božić, Dragica
AU  - Baralić, Katarina
AU  - Živančević, Katarina
AU  - Đukić-Ćosić, Danijela
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4641
AB  - Sulforaphane (SFN) and Pseudomonas aeruginosa – mannose sensitive hemagglutinin
(PA-MSHA) are known immune modulators with shown anti-tumor characteristics and
ability to inhibit the growth and progression of cancer cells. However, the benefit/risk ratio
of their combinational use is not fully explained and needs further investigation. Thus, this
study aims to understand the potential of the given therapy mixture to induce side/toxic
effects in cancer patients. With the help of in-depth in silico toxicogenomics analysis, we have
previously demonstrated that SFN (1) and PA-MSHA (unpublished data) dysregulated 13
and 64 genes in cancer patients, among which 5 and 16 were repressed, while 8 and 48 were
induced by the given molecule, respectively. A total of 21 downregulated and 56 upregulated
genes were analyzed with computational tools such as ToppGene ToppFun
(https://toppgene.cchmc.org/)
and REACTOME (https://reactome.org/PathwayBrowser/#/) to determine the most
important Gene Ontology terms and molecular pathways influenced by SFN/PA-MSHA
combination. As expected, this therapy approach can lead to dysregulation of cell cycle and
p53 signalling pathway, but also acute kidney failure. On the other hand, the set of SFN/PA-
MSHA upregulated genes were enriched for leukocyte activation, positive regulation of cell
population proliferation, TNF and other cytokines signalling pathways, as well as
inflammatory diseases such as psoriasis, ulcerative colitis, or Crohn disease. Thus, the
combinational treatment of the given immune modulators might have the potential to cause
severe adverse outcomes and should be used with caution in cancer patients with renal
insufficiency or immune diseases.
AB  - Sulforafan (SFN) i Pseudomonas aeruginosa – hemaglutinin osetljiv na manozu (PA-
MSHA) su imunomodulatori koji ispoljavaju antitumorske osobine i mogu da inhibiraju rast i
progresiju ćelija raka. Međutim, odnos korist/rizik njihove kombinovane upotrebe nije u
potpunosti razjašnjen zbog čega je potrebno detaljnije ispitati farmakološko-toksikološki
profil ovakve kombinacije. Stoga, ova studija ima za cilj da razjasni potencijal kombinovane
primene SFN/PA-MSHA da izazove neželjene/toksične efekte kod pacijenata obolelih od
raka. Uz pomoć detaljne in silico tokiskogenomske analize podataka, prethodno smo pokazali
da SFN (1) i PA-MSHA (nepublikovani podaci) utiču na ekspresiju 13 i 64 gena, među kojima
je 5 i 16 inhibirano, dok je 8 i 48 indukovano datim molekulima, redom. Ukupno 21
inaktiviran gen i 56 gena čija je ekspresija stimulisana analizirano je pomoću računarskih
alata kao što su ToppGene ToppFun (https://toppgene.cchmc.org/) i REACTOME
(https://reactome.org/PathvaiBrovser/#/) kako bi bile utvrđene najznačajnije molekularne
funkcije, biološke procese i molekularne puteve na koje utiče kombinacija SFN/PA-MSHA.
Kao što je i očekivano, ovakav terapijski pristup može dovesti do disregulacije ćelijskog
ciklusa i signalnog puta p53, ali i do akutnog zapaljenja bubrega. S druge strane, skup
aktiviranih SFN/PA-MSHA gena je uključen u aktivaciju leukocita, pozitivnu regulaciju
proliferacije ćelija, TNF i druge signalne puteve citokina, ali i inflamatorne bolesti kao što su
psorijaza, ulcerozni kolitis ili Kronova bolest. Stoga, kombinovani tretman ispitivanih
imunomodulatora može imati potencijal da izazove ozbiljne neželjene ishode zbog čega ga
treba sa oprezom koristiti kod pacijenata sa bubrežnom insuficijencijom ili postojećim
imunološkim oboljenjima.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Toxic potential of combined sulforaphane/Pseudomonas aeruginosa mannose sensitive hemagglutinin treatment in cancer patients
T1  - Toksični potencijal kombinovane primene sulforafana i pseudomonas aeruginosa ‐ hemaglutinin osetljiv na manozu kod pacijenata obolelih od raka
VL  - 72
IS  - 4 suplement
SP  - S607
EP  - S608
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4641
ER  - 

@conference{
author = "Božić, Dragica and Baralić, Katarina and Živančević, Katarina and Đukić-Ćosić, Danijela",
year = "2022",
abstract = "Sulforaphane (SFN) and Pseudomonas aeruginosa – mannose sensitive hemagglutinin
(PA-MSHA) are known immune modulators with shown anti-tumor characteristics and
ability to inhibit the growth and progression of cancer cells. However, the benefit/risk ratio
of their combinational use is not fully explained and needs further investigation. Thus, this
study aims to understand the potential of the given therapy mixture to induce side/toxic
effects in cancer patients. With the help of in-depth in silico toxicogenomics analysis, we have
previously demonstrated that SFN (1) and PA-MSHA (unpublished data) dysregulated 13
and 64 genes in cancer patients, among which 5 and 16 were repressed, while 8 and 48 were
induced by the given molecule, respectively. A total of 21 downregulated and 56 upregulated
genes were analyzed with computational tools such as ToppGene ToppFun
(https://toppgene.cchmc.org/)
and REACTOME (https://reactome.org/PathwayBrowser/#/) to determine the most
important Gene Ontology terms and molecular pathways influenced by SFN/PA-MSHA
combination. As expected, this therapy approach can lead to dysregulation of cell cycle and
p53 signalling pathway, but also acute kidney failure. On the other hand, the set of SFN/PA-
MSHA upregulated genes were enriched for leukocyte activation, positive regulation of cell
population proliferation, TNF and other cytokines signalling pathways, as well as
inflammatory diseases such as psoriasis, ulcerative colitis, or Crohn disease. Thus, the
combinational treatment of the given immune modulators might have the potential to cause
severe adverse outcomes and should be used with caution in cancer patients with renal
insufficiency or immune diseases., Sulforafan (SFN) i Pseudomonas aeruginosa – hemaglutinin osetljiv na manozu (PA-
MSHA) su imunomodulatori koji ispoljavaju antitumorske osobine i mogu da inhibiraju rast i
progresiju ćelija raka. Međutim, odnos korist/rizik njihove kombinovane upotrebe nije u
potpunosti razjašnjen zbog čega je potrebno detaljnije ispitati farmakološko-toksikološki
profil ovakve kombinacije. Stoga, ova studija ima za cilj da razjasni potencijal kombinovane
primene SFN/PA-MSHA da izazove neželjene/toksične efekte kod pacijenata obolelih od
raka. Uz pomoć detaljne in silico tokiskogenomske analize podataka, prethodno smo pokazali
da SFN (1) i PA-MSHA (nepublikovani podaci) utiču na ekspresiju 13 i 64 gena, među kojima
je 5 i 16 inhibirano, dok je 8 i 48 indukovano datim molekulima, redom. Ukupno 21
inaktiviran gen i 56 gena čija je ekspresija stimulisana analizirano je pomoću računarskih
alata kao što su ToppGene ToppFun (https://toppgene.cchmc.org/) i REACTOME
(https://reactome.org/PathvaiBrovser/#/) kako bi bile utvrđene najznačajnije molekularne
funkcije, biološke procese i molekularne puteve na koje utiče kombinacija SFN/PA-MSHA.
Kao što je i očekivano, ovakav terapijski pristup može dovesti do disregulacije ćelijskog
ciklusa i signalnog puta p53, ali i do akutnog zapaljenja bubrega. S druge strane, skup
aktiviranih SFN/PA-MSHA gena je uključen u aktivaciju leukocita, pozitivnu regulaciju
proliferacije ćelija, TNF i druge signalne puteve citokina, ali i inflamatorne bolesti kao što su
psorijaza, ulcerozni kolitis ili Kronova bolest. Stoga, kombinovani tretman ispitivanih
imunomodulatora može imati potencijal da izazove ozbiljne neželjene ishode zbog čega ga
treba sa oprezom koristiti kod pacijenata sa bubrežnom insuficijencijom ili postojećim
imunološkim oboljenjima.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Toxic potential of combined sulforaphane/Pseudomonas aeruginosa mannose sensitive hemagglutinin treatment in cancer patients, Toksični potencijal kombinovane primene sulforafana i pseudomonas aeruginosa ‐ hemaglutinin osetljiv na manozu kod pacijenata obolelih od raka",
volume = "72",
number = "4 suplement",
pages = "S607-S608",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4641"
}

Božić, D., Baralić, K., Živančević, K.,& Đukić-Ćosić, D.. (2022). Toxic potential of combined sulforaphane/Pseudomonas aeruginosa mannose sensitive hemagglutinin treatment in cancer patients. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S607-S608.
https://hdl.handle.net/21.15107/rcub_farfar_4641

Božić D, Baralić K, Živančević K, Đukić-Ćosić D. Toxic potential of combined sulforaphane/Pseudomonas aeruginosa mannose sensitive hemagglutinin treatment in cancer patients. in Arhiv za farmaciju. 2022;72(4 suplement):S607-S608.
https://hdl.handle.net/21.15107/rcub_farfar_4641 .

Božić, Dragica, Baralić, Katarina, Živančević, Katarina, Đukić-Ćosić, Danijela, "Toxic potential of combined sulforaphane/Pseudomonas aeruginosa mannose sensitive hemagglutinin treatment in cancer patients" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S607-S608,
https://hdl.handle.net/21.15107/rcub_farfar_4641 .