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
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Метаподаци
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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previously demonstrated that SFN (1) and PA-MSHA (unpublished data) dysregulated 13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 G...ene 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/PathvaiBr...ovser/#/) 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.
Извор:
Arhiv za farmaciju, 2022, 72, 4 suplement, S607-S608Издавач:
- Savez farmaceutskih udruženja Srbije (SFUS)
Финансирање / пројекти:
- Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije kroz međunarodni istraživačko-razvojni projekat između Republike Srbije i NR Kine: „Povećanje efikasnosti terapije karcinoma kombinacijom CAR-T ćelija ili PD-1/PD- L1 inhibitora pomoću imunomodulatora” (451-03-1203/2021-09).
Напомена:
- VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd
Институција/група
PharmacyTY - 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 .