TY  - CONF
AU  - Erić, Slavica
AU  - Jović, Milena
AU  - Zloh, Mire
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5009
AB  - Echinacea spp. have long history of use, dating from American natives. Among ten, three species (Echinacea purpurea (L.), Echinacea pallida (Nutt.) and Echinacea angustifolia (DC.)), are the most used, alone or in mixes, for treatment of various conditions, such are infections, cancers etc. Recently, it was shown that Echinacea spp. are effective in treatment of COVID 19, inhibiting progress of SARS CoV2 development. Due to availability of structures of certain number of chemical constituents of Echinacea spp. and 3D structures of possible targets included in processes of interaction, elucidation of its molecular mechanisms of action was performed by computational methods.
Three approaches for evaluation of molecular mechanisms of Echinacea spp. constituents (24 from Echinacea purpurea and 10 from other Echinacea spp.) for possible treatment of recent COVID 19 pandemia are presented. First, docking studies of Echinacea spp. constituents (34) were performed on three targets, according to literature as the most important for SARS CoV2 virus spread and development: SARS CoV2 spike protein and angiotensin converting enzyme (ACE2) receptor responsible for virus entry, as well as SARS-CoV-2 metalloproteinase Mpro as the most responsible in mediation of viral transcription and replication. Second, physicochemical properties and pharmacokinetic-related characterization (Lipinksi Rule of five) of Echinacea spp. constituents in conformation with minimum energy, were performed by Data Warrior program. Results show that 4/34 compounds have negative values of log P (hydrophilic), 6/34 showed negative results regarding selection by Rule of five, among which 5 significantly differ in H-bonding capacity, which indicates different properties for oral absorption and distribution within the organism, as well as mode of action. Drug likeness, calculated for fragments of 34 constituents, is scattered within 15 units of difference. Third, the probability of interaction of Echinacea spp. constituents with targets was estimated by use of SwissTarget Prediction program, based on query molecule showing activity on certain class of targets. Results showed that cannabinoid receptors (CNR) 1 and 2 (17 and 16 units) and peroxisome proliferatoractivated receptor gamma (PPARγ) (15 units) are the most preferable targets for interactions. Possible molecular mechanisms involved in evidented pharmacological records in treatment of COVID 19 by Ehinacea spp. were elucidated with regard of results of all three methods.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods
SP  - 33
EP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5009
ER  - 

@conference{
author = "Erić, Slavica and Jović, Milena and Zloh, Mire",
year = "2023",
abstract = "Echinacea spp. have long history of use, dating from American natives. Among ten, three species (Echinacea purpurea (L.), Echinacea pallida (Nutt.) and Echinacea angustifolia (DC.)), are the most used, alone or in mixes, for treatment of various conditions, such are infections, cancers etc. Recently, it was shown that Echinacea spp. are effective in treatment of COVID 19, inhibiting progress of SARS CoV2 development. Due to availability of structures of certain number of chemical constituents of Echinacea spp. and 3D structures of possible targets included in processes of interaction, elucidation of its molecular mechanisms of action was performed by computational methods.
Three approaches for evaluation of molecular mechanisms of Echinacea spp. constituents (24 from Echinacea purpurea and 10 from other Echinacea spp.) for possible treatment of recent COVID 19 pandemia are presented. First, docking studies of Echinacea spp. constituents (34) were performed on three targets, according to literature as the most important for SARS CoV2 virus spread and development: SARS CoV2 spike protein and angiotensin converting enzyme (ACE2) receptor responsible for virus entry, as well as SARS-CoV-2 metalloproteinase Mpro as the most responsible in mediation of viral transcription and replication. Second, physicochemical properties and pharmacokinetic-related characterization (Lipinksi Rule of five) of Echinacea spp. constituents in conformation with minimum energy, were performed by Data Warrior program. Results show that 4/34 compounds have negative values of log P (hydrophilic), 6/34 showed negative results regarding selection by Rule of five, among which 5 significantly differ in H-bonding capacity, which indicates different properties for oral absorption and distribution within the organism, as well as mode of action. Drug likeness, calculated for fragments of 34 constituents, is scattered within 15 units of difference. Third, the probability of interaction of Echinacea spp. constituents with targets was estimated by use of SwissTarget Prediction program, based on query molecule showing activity on certain class of targets. Results showed that cannabinoid receptors (CNR) 1 and 2 (17 and 16 units) and peroxisome proliferatoractivated receptor gamma (PPARγ) (15 units) are the most preferable targets for interactions. Possible molecular mechanisms involved in evidented pharmacological records in treatment of COVID 19 by Ehinacea spp. were elucidated with regard of results of all three methods.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods",
pages = "33-33",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5009"
}

Erić, S., Jović, M.,& Zloh, M.. (2023). Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 33-33.
https://hdl.handle.net/21.15107/rcub_farfar_5009

Erić S, Jović M, Zloh M. Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:33-33.
https://hdl.handle.net/21.15107/rcub_farfar_5009 .

Erić, Slavica, Jović, Milena, Zloh, Mire, "Elucidation of molecular mechanisms of activity of Echinacea spp. constituents for possible treatment of COVID 19 by computer-aided methods" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):33-33,
https://hdl.handle.net/21.15107/rcub_farfar_5009 .

TY  - JOUR
AU  - Ivković, Sanja
AU  - Major, Tamara
AU  - Mitić, Miloš
AU  - Lončarević-Vasiljković, Nataša
AU  - Jović, Milena
AU  - Adžić, Miroslav
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4078
AB  - The brain is the softest organ in the body, and any change in the mechanical properties of the tissue induces the activation of glial cells, astrocytes and microglia. Amyloid plaques, one of the main pathological features of Alzheimer's disease (AD), are substantially harder than the surrounding brain tissue and can activate astrocytes and microglia resulting in the glial engulfment of plaques. Durotaxis, a migratory preference towards stiffer tissue, is prompting microglia to form a mechanical barrier around plaques reducing amyloid β (Aβ) induced neurotoxicity. Mechanoreceptors are highly expressed in the brain, particularly in microglia. The large increase in the expression of the mechanoreceptor Piezo1 was observed in the brains from AD animal models and AD patients in plaque encompassing glia. Importantly, Piezo1 function is regulated via force-from–lipids through the lipid composition of the membrane and membranous incorporation of polyunsaturated fatty acids (PUFAs) can affect the function of Piezo1 altering mechanosensitive properties of the cell. On the other hand, PUFAs dietary supplementation can alter microglial polarization, the envelopment of amyloid plaques, and immune response and Piezo1 activity was implicated in the similar modulations of microglia behavior. Finally, PUFAs treatment is currently in use in medical trials as the therapy for sickle cell anemia, a disease linked with the mutations in Piezo1. Further studies are needed to elucidate the connection between PUFAs, Piezo1 expression, and microglia behavior in the AD brain. These findings could open new possibilities in harnessing microglia in AD and in developing novel therapeutic strategies.
PB  - Elsevier Inc.
T2  - Life Sciences
T1  - Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease
VL  - 297
DO  - 10.1016/j.lfs.2022.120470
ER  - 

@article{
author = "Ivković, Sanja and Major, Tamara and Mitić, Miloš and Lončarević-Vasiljković, Nataša and Jović, Milena and Adžić, Miroslav",
year = "2022",
abstract = "The brain is the softest organ in the body, and any change in the mechanical properties of the tissue induces the activation of glial cells, astrocytes and microglia. Amyloid plaques, one of the main pathological features of Alzheimer's disease (AD), are substantially harder than the surrounding brain tissue and can activate astrocytes and microglia resulting in the glial engulfment of plaques. Durotaxis, a migratory preference towards stiffer tissue, is prompting microglia to form a mechanical barrier around plaques reducing amyloid β (Aβ) induced neurotoxicity. Mechanoreceptors are highly expressed in the brain, particularly in microglia. The large increase in the expression of the mechanoreceptor Piezo1 was observed in the brains from AD animal models and AD patients in plaque encompassing glia. Importantly, Piezo1 function is regulated via force-from–lipids through the lipid composition of the membrane and membranous incorporation of polyunsaturated fatty acids (PUFAs) can affect the function of Piezo1 altering mechanosensitive properties of the cell. On the other hand, PUFAs dietary supplementation can alter microglial polarization, the envelopment of amyloid plaques, and immune response and Piezo1 activity was implicated in the similar modulations of microglia behavior. Finally, PUFAs treatment is currently in use in medical trials as the therapy for sickle cell anemia, a disease linked with the mutations in Piezo1. Further studies are needed to elucidate the connection between PUFAs, Piezo1 expression, and microglia behavior in the AD brain. These findings could open new possibilities in harnessing microglia in AD and in developing novel therapeutic strategies.",
publisher = "Elsevier Inc.",
journal = "Life Sciences",
title = "Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease",
volume = "297",
doi = "10.1016/j.lfs.2022.120470"
}

Ivković, S., Major, T., Mitić, M., Lončarević-Vasiljković, N., Jović, M.,& Adžić, M.. (2022). Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease. in Life Sciences
Elsevier Inc.., 297.
https://doi.org/10.1016/j.lfs.2022.120470

Ivković S, Major T, Mitić M, Lončarević-Vasiljković N, Jović M, Adžić M. Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease. in Life Sciences. 2022;297.
doi:10.1016/j.lfs.2022.120470 .

Ivković, Sanja, Major, Tamara, Mitić, Miloš, Lončarević-Vasiljković, Nataša, Jović, Milena, Adžić, Miroslav, "Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease" in Life Sciences, 297 (2022),
https://doi.org/10.1016/j.lfs.2022.120470 . .

TY  - JOUR
AU  - Stanojević, Ivan
AU  - Miller, Karolina
AU  - Kandolf-Sekulović, Lidija
AU  - Mijušković, Željko
AU  - Zolotarevska, Lidija
AU  - Jović, Milena
AU  - Gacević, Milomir
AU  - Đukić, Mirjana
AU  - Arsenijević, Nebojša
AU  - Vojvodić, Danilo
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2565
AB  - Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3(-), CD19(-), CD56(-)), HLA-DR-/low, CD11b(+) and CD33(+). Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI)  lt  12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI.
PB  - Oxford Univ Press, Oxford
T2  - International Immunology
T1  - A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma
VL  - 28
IS  - 2
SP  - 87
EP  - 97
DO  - 10.1093/intimm/dxv053
ER  - 

@article{
author = "Stanojević, Ivan and Miller, Karolina and Kandolf-Sekulović, Lidija and Mijušković, Željko and Zolotarevska, Lidija and Jović, Milena and Gacević, Milomir and Đukić, Mirjana and Arsenijević, Nebojša and Vojvodić, Danilo",
year = "2016",
abstract = "Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3(-), CD19(-), CD56(-)), HLA-DR-/low, CD11b(+) and CD33(+). Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI)  lt  12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Immunology",
title = "A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma",
volume = "28",
number = "2",
pages = "87-97",
doi = "10.1093/intimm/dxv053"
}

Stanojević, I., Miller, K., Kandolf-Sekulović, L., Mijušković, Ž., Zolotarevska, L., Jović, M., Gacević, M., Đukić, M., Arsenijević, N.,& Vojvodić, D.. (2016). A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma. in International Immunology
Oxford Univ Press, Oxford., 28(2), 87-97.
https://doi.org/10.1093/intimm/dxv053

Stanojević I, Miller K, Kandolf-Sekulović L, Mijušković Ž, Zolotarevska L, Jović M, Gacević M, Đukić M, Arsenijević N, Vojvodić D. A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma. in International Immunology. 2016;28(2):87-97.
doi:10.1093/intimm/dxv053 .

Stanojević, Ivan, Miller, Karolina, Kandolf-Sekulović, Lidija, Mijušković, Željko, Zolotarevska, Lidija, Jović, Milena, Gacević, Milomir, Đukić, Mirjana, Arsenijević, Nebojša, Vojvodić, Danilo, "A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma" in International Immunology, 28, no. 2 (2016):87-97,
https://doi.org/10.1093/intimm/dxv053 . .

TY  - JOUR
AU  - Jović, Milena
AU  - Cerović, Snežana
AU  - Zolotarevska, Lidija
AU  - Gačević, Milomir
AU  - Stanojević, Ivan
AU  - Miller, Karolina
AU  - Đukić, Mirjana
AU  - Saso, Luciano
AU  - Jauković, Ljiljana
AU  - Vojvodić, Danilo
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2634
AB  - Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of surviving + cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.
AB  - Uvod/Cilj. Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru (primarni tumor i metastatske promene) i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Metode. Nivo ekspresije survivina određivan je imunocitohistohemijski utumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicínu i Institutu za medicinska istraživanja na Vojnomedicinskoj akademiji, Beograd, Srbija. Rezultati. Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Ispoljavanje survivina i broj survivin pozitivnih ćelija u metastatskim lezijama bio je značajno udružen sa trajanjem intervala bez bolesti (disease free interval - DFI). Bolesnici sa visokim skorom ekspresije imali su skoro dvostruko kraći DFI u odnosu na one sa sla­bom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9 ± 7 vs 19 ± 13 meseci). Stepen prisustva tumor infltrišućih limfocita u tumorskom tkivu bio je značajno udružen sa koncetracijom survivina u serumu, sa najnižim prosečnim vrednostima detektovanim u uzorcima bolesnika sa najvećim stepenom infiltracije. Serumske koncentracije survivina bile su najveće u uzorcima bolesnika sa melanomom IA kliničkog stadijuma American Joint Commission on Cancer (AJCC), pT1a histološkog stadijuma, bolesnika čiji su tumori bili u horizontalnoj fazi rasta, bez znakova širenja limfohematogenim putem, sa najvećim brojem mitoza i koji su imali najmanji Clark indeks. Zaključak. Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno korelišu sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Određivanje survivina u tumorskom tkivu, kako u primarnom tumoru tako i u metastazama, od velikog je značaja u utvrđivanju trajanja DFI.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma
T1  - Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože
VL  - 73
IS  - 11
SP  - 1022
EP  - 1029
DO  - 10.2298/VSP150519119J
ER  - 

@article{
author = "Jović, Milena and Cerović, Snežana and Zolotarevska, Lidija and Gačević, Milomir and Stanojević, Ivan and Miller, Karolina and Đukić, Mirjana and Saso, Luciano and Jauković, Ljiljana and Vojvodić, Danilo",
year = "2016",
abstract = "Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of surviving + cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI., Uvod/Cilj. Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru (primarni tumor i metastatske promene) i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Metode. Nivo ekspresije survivina određivan je imunocitohistohemijski utumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicínu i Institutu za medicinska istraživanja na Vojnomedicinskoj akademiji, Beograd, Srbija. Rezultati. Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Ispoljavanje survivina i broj survivin pozitivnih ćelija u metastatskim lezijama bio je značajno udružen sa trajanjem intervala bez bolesti (disease free interval - DFI). Bolesnici sa visokim skorom ekspresije imali su skoro dvostruko kraći DFI u odnosu na one sa sla­bom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9 ± 7 vs 19 ± 13 meseci). Stepen prisustva tumor infltrišućih limfocita u tumorskom tkivu bio je značajno udružen sa koncetracijom survivina u serumu, sa najnižim prosečnim vrednostima detektovanim u uzorcima bolesnika sa najvećim stepenom infiltracije. Serumske koncentracije survivina bile su najveće u uzorcima bolesnika sa melanomom IA kliničkog stadijuma American Joint Commission on Cancer (AJCC), pT1a histološkog stadijuma, bolesnika čiji su tumori bili u horizontalnoj fazi rasta, bez znakova širenja limfohematogenim putem, sa najvećim brojem mitoza i koji su imali najmanji Clark indeks. Zaključak. Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno korelišu sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Određivanje survivina u tumorskom tkivu, kako u primarnom tumoru tako i u metastazama, od velikog je značaja u utvrđivanju trajanja DFI.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma, Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože",
volume = "73",
number = "11",
pages = "1022-1029",
doi = "10.2298/VSP150519119J"
}

Jović, M., Cerović, S., Zolotarevska, L., Gačević, M., Stanojević, I., Miller, K., Đukić, M., Saso, L., Jauković, L.,& Vojvodić, D.. (2016). Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 73(11), 1022-1029.
https://doi.org/10.2298/VSP150519119J

Jović M, Cerović S, Zolotarevska L, Gačević M, Stanojević I, Miller K, Đukić M, Saso L, Jauković L, Vojvodić D. Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma. in Vojnosanitetski pregled. 2016;73(11):1022-1029.
doi:10.2298/VSP150519119J .

Jović, Milena, Cerović, Snežana, Zolotarevska, Lidija, Gačević, Milomir, Stanojević, Ivan, Miller, Karolina, Đukić, Mirjana, Saso, Luciano, Jauković, Ljiljana, Vojvodić, Danilo, "Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma" in Vojnosanitetski pregled, 73, no. 11 (2016):1022-1029,
https://doi.org/10.2298/VSP150519119J . .

TY  - JOUR
AU  - Stefanović, Vladimir
AU  - Taso, Ervin
AU  - Petković-Ćurčin, Aleksandra
AU  - Đukić, Mirjana
AU  - Gardašević, Milka
AU  - Rakić, Mia
AU  - Xavier, Struillou
AU  - Jović, Milena
AU  - Miller, Karolina
AU  - Stanojević, Ivan
AU  - Vojvodić, Danilo
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2668
AB  - Background/Aim. Several cytokines and lymphokines (IL1β, ENA78, IL6, TNFα, IL8 and S100A8) are expressed during dental pulp inflammation. Analysis of gingival crevicular fluid (GCF) offers a non-invasive means of studying general host response in oral cavity. Although GCF levels of various mediators could reflect the state of inflammation both in dental pulp and gingiva adjacent to a tooth, GCF samples of those without significant gingivitis could be interpreted as reflection of pulpal process. The aim of this study was to investigate IL9 GCF values in patients with dental caries and to assess possible influence of various dental fillings materials on local IL9 production. Methods. The study group included 90 patients, aged 18-70, with inclusion and exclusion criteria in the prospective clinical study. Of the 6 types of material used for the restoration of prepared cavities, 3 were intended for temporary and 3 for definitive restoration. According to dental fillings weight, all the participants were divided into 3 groups: those with fillings lighter than 0.50 g, those with 0.50-1.00 g, and those with fillings heavier than 1.00 g. Samples were taken from gingival sulcus using the filter paper technique. Clinical parameters were determined by bleeding index, plaque index (Silness-Lou, 0-3), gingival index (0-3), and gingival sulcus depth. Cytokine concentrations were assessed using commercially available cytomix. Results. According to the weight of dental fillings, there was a clear decreament trend of IL9 values meaning that dental defects greater than 1.00 g of dental filling were associated with lower GCF IL9 concentration. The IL9 values correlated with the degree of gingival index and depth of gingival sulcus, being higher with more advanced gingivitis and more pronounced anatomical changes in the tooth edge. Different filling materials exerted various local IL9 responses. Zink polycarbonate cement and amalgam fillings induced a significant and long-lasting local IL9 decrement, while the use of Tetric EvoCeram and GMA-BISK significantly increased IL9 levels. Conclusion. The obtained results indicate that IL9 GCF could be regarded as a measure of odontoblasts' response to the extensity of dental caries. The type of material used for dental fillings could profoundly alter biological function of gingival and pulpal cells. Also, the results obtained in this study suggest that some materials could even enhance wound repair by modulating macrophage activation.
AB  - Uvod/Cilj. Jedan broj citokina i limfokina (IL1β, ENA78, IL6, TNFα, IL8 I S100A8) izlučuje se tokom upale zubne pulpe. Analiza gingivalne sulkusne tečnosti (gingival crevicular fluid - GCF) omogućava neinvazivno proučavanje opšteg odgovora pacijenta na lokalne promene u usnoj duplji. Iako nivoi GCF mogu da odražavaju stanje upale kako u zubnoj pulpi, tako i u gingivi susednog zuba, uzorci GCF zuba bez značajnijeg gingivitisa mogli bi se tumačiti kao pokazatelji procesa u pulpi. Cilj ovog istraživanja bio je da se ispitaju nivoi IL9 u GCF kod pacijenata sa zubnim karijesom i da se utvrdi eventualni uticaj različitih materijala za zubne ispune na lokalnu proizvodnju IL9. Metode. U studiju je bilo uključeno 90 pacijenata, starih od 18 do 70 godina, uz primenu kriterijuma za uključivanje/isključivanje za prospektivne kliničke studije. Od ukupno šest materijala za punjenje pripremljenih kaviteta, tri je korišćeno za privremenu i tri za trajnu ispunu. Prema težini zubnog ispuna, pacijenti su bili podeljeni na tri grupe: oni sa ispunama lakšim od 0,50 g, sa ispunama od 0,50 do 1,00 g i sa ispunama težim od 1,00 g. Uzorci su uzimani iz gingivalnog sulkusa primenom tehnike filter papira. Korišćeni klinički parametri bili su indeks krvarenja, plak indeks (Silness-Lou, 0-3), gingivalni indeks (0-3) i dubina gingivalnog sulkusa. Koncentracije citokina određene su komercijalnim citomiksom. Rezultati. Težina zubne ispune ukazivala je na tendenciju opadanja vrednosti IL9, što je značilo da je veće oštećenje zuba, sa zubnom ispunom težom od 1,00 g, praćeno nižom koncentracijom IL9 u GCF. Vrednosti IL9 bile su u korelaciji sa stepenom gingivalnog indeksa i dubinom gingivalnog sulkusa, pogotovu u poodmaklom gingivitisu i izraženijim anatomskim promenama ivica zuba. Različite ispune izazivale su različite lokalne sekrecije IL9. Cink-polikarbonatni cement i amalgamska ispuna izazvale su značajan i dugotrajan pad nivoa lokalnog IL9, dok je primena tetrik-evocerama i GMA-BISK znatno povisila nivoe IL9. Zaključak. Rezultati dobijeni u ovoj studiji ukazuju da se IL9 u GCF može koristiti kao mera za reakciju odontoblasta na veličinu karijesa. Tip zubne ispune može da promeni biološku funkciju ćelija gingive i pulpe. Rezultati ove studije, takođe, ukazuju i na to da neke vrste ispuna mogu čak da ubrzaju zarastanje rane modulacijom aktivnosti makrofaga.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Influence of dental filling material type on the concentration of interleukin 9 in the samples of gingival crevicular fluid
T1  - Uticaj tipa materijala za plombiranje zuba na koncentraciju interleukina 9 u uzorcima gingivalne sulkusne tečnosti
VL  - 73
IS  - 8
SP  - 728
EP  - 734
DO  - 10.2298/VSP140227054S
ER  - 

@article{
author = "Stefanović, Vladimir and Taso, Ervin and Petković-Ćurčin, Aleksandra and Đukić, Mirjana and Gardašević, Milka and Rakić, Mia and Xavier, Struillou and Jović, Milena and Miller, Karolina and Stanojević, Ivan and Vojvodić, Danilo",
year = "2016",
abstract = "Background/Aim. Several cytokines and lymphokines (IL1β, ENA78, IL6, TNFα, IL8 and S100A8) are expressed during dental pulp inflammation. Analysis of gingival crevicular fluid (GCF) offers a non-invasive means of studying general host response in oral cavity. Although GCF levels of various mediators could reflect the state of inflammation both in dental pulp and gingiva adjacent to a tooth, GCF samples of those without significant gingivitis could be interpreted as reflection of pulpal process. The aim of this study was to investigate IL9 GCF values in patients with dental caries and to assess possible influence of various dental fillings materials on local IL9 production. Methods. The study group included 90 patients, aged 18-70, with inclusion and exclusion criteria in the prospective clinical study. Of the 6 types of material used for the restoration of prepared cavities, 3 were intended for temporary and 3 for definitive restoration. According to dental fillings weight, all the participants were divided into 3 groups: those with fillings lighter than 0.50 g, those with 0.50-1.00 g, and those with fillings heavier than 1.00 g. Samples were taken from gingival sulcus using the filter paper technique. Clinical parameters were determined by bleeding index, plaque index (Silness-Lou, 0-3), gingival index (0-3), and gingival sulcus depth. Cytokine concentrations were assessed using commercially available cytomix. Results. According to the weight of dental fillings, there was a clear decreament trend of IL9 values meaning that dental defects greater than 1.00 g of dental filling were associated with lower GCF IL9 concentration. The IL9 values correlated with the degree of gingival index and depth of gingival sulcus, being higher with more advanced gingivitis and more pronounced anatomical changes in the tooth edge. Different filling materials exerted various local IL9 responses. Zink polycarbonate cement and amalgam fillings induced a significant and long-lasting local IL9 decrement, while the use of Tetric EvoCeram and GMA-BISK significantly increased IL9 levels. Conclusion. The obtained results indicate that IL9 GCF could be regarded as a measure of odontoblasts' response to the extensity of dental caries. The type of material used for dental fillings could profoundly alter biological function of gingival and pulpal cells. Also, the results obtained in this study suggest that some materials could even enhance wound repair by modulating macrophage activation., Uvod/Cilj. Jedan broj citokina i limfokina (IL1β, ENA78, IL6, TNFα, IL8 I S100A8) izlučuje se tokom upale zubne pulpe. Analiza gingivalne sulkusne tečnosti (gingival crevicular fluid - GCF) omogućava neinvazivno proučavanje opšteg odgovora pacijenta na lokalne promene u usnoj duplji. Iako nivoi GCF mogu da odražavaju stanje upale kako u zubnoj pulpi, tako i u gingivi susednog zuba, uzorci GCF zuba bez značajnijeg gingivitisa mogli bi se tumačiti kao pokazatelji procesa u pulpi. Cilj ovog istraživanja bio je da se ispitaju nivoi IL9 u GCF kod pacijenata sa zubnim karijesom i da se utvrdi eventualni uticaj različitih materijala za zubne ispune na lokalnu proizvodnju IL9. Metode. U studiju je bilo uključeno 90 pacijenata, starih od 18 do 70 godina, uz primenu kriterijuma za uključivanje/isključivanje za prospektivne kliničke studije. Od ukupno šest materijala za punjenje pripremljenih kaviteta, tri je korišćeno za privremenu i tri za trajnu ispunu. Prema težini zubnog ispuna, pacijenti su bili podeljeni na tri grupe: oni sa ispunama lakšim od 0,50 g, sa ispunama od 0,50 do 1,00 g i sa ispunama težim od 1,00 g. Uzorci su uzimani iz gingivalnog sulkusa primenom tehnike filter papira. Korišćeni klinički parametri bili su indeks krvarenja, plak indeks (Silness-Lou, 0-3), gingivalni indeks (0-3) i dubina gingivalnog sulkusa. Koncentracije citokina određene su komercijalnim citomiksom. Rezultati. Težina zubne ispune ukazivala je na tendenciju opadanja vrednosti IL9, što je značilo da je veće oštećenje zuba, sa zubnom ispunom težom od 1,00 g, praćeno nižom koncentracijom IL9 u GCF. Vrednosti IL9 bile su u korelaciji sa stepenom gingivalnog indeksa i dubinom gingivalnog sulkusa, pogotovu u poodmaklom gingivitisu i izraženijim anatomskim promenama ivica zuba. Različite ispune izazivale su različite lokalne sekrecije IL9. Cink-polikarbonatni cement i amalgamska ispuna izazvale su značajan i dugotrajan pad nivoa lokalnog IL9, dok je primena tetrik-evocerama i GMA-BISK znatno povisila nivoe IL9. Zaključak. Rezultati dobijeni u ovoj studiji ukazuju da se IL9 u GCF može koristiti kao mera za reakciju odontoblasta na veličinu karijesa. Tip zubne ispune može da promeni biološku funkciju ćelija gingive i pulpe. Rezultati ove studije, takođe, ukazuju i na to da neke vrste ispuna mogu čak da ubrzaju zarastanje rane modulacijom aktivnosti makrofaga.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Influence of dental filling material type on the concentration of interleukin 9 in the samples of gingival crevicular fluid, Uticaj tipa materijala za plombiranje zuba na koncentraciju interleukina 9 u uzorcima gingivalne sulkusne tečnosti",
volume = "73",
number = "8",
pages = "728-734",
doi = "10.2298/VSP140227054S"
}

Stefanović, V., Taso, E., Petković-Ćurčin, A., Đukić, M., Gardašević, M., Rakić, M., Xavier, S., Jović, M., Miller, K., Stanojević, I.,& Vojvodić, D.. (2016). Influence of dental filling material type on the concentration of interleukin 9 in the samples of gingival crevicular fluid. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 73(8), 728-734.
https://doi.org/10.2298/VSP140227054S

Stefanović V, Taso E, Petković-Ćurčin A, Đukić M, Gardašević M, Rakić M, Xavier S, Jović M, Miller K, Stanojević I, Vojvodić D. Influence of dental filling material type on the concentration of interleukin 9 in the samples of gingival crevicular fluid. in Vojnosanitetski pregled. 2016;73(8):728-734.
doi:10.2298/VSP140227054S .

Stefanović, Vladimir, Taso, Ervin, Petković-Ćurčin, Aleksandra, Đukić, Mirjana, Gardašević, Milka, Rakić, Mia, Xavier, Struillou, Jović, Milena, Miller, Karolina, Stanojević, Ivan, Vojvodić, Danilo, "Influence of dental filling material type on the concentration of interleukin 9 in the samples of gingival crevicular fluid" in Vojnosanitetski pregled, 73, no. 8 (2016):728-734,
https://doi.org/10.2298/VSP140227054S . .

TY  - JOUR
AU  - Karlicić, Vukoica
AU  - Vuković, Jelena
AU  - Stanojević, Ivan
AU  - Sotirović, Jelena
AU  - Perić, Alexandra
AU  - Jović, Milena
AU  - Cvijanović, Vlado
AU  - Đukić, Mirjana
AU  - Banović, Tatjana
AU  - Vojvodić, Danilo
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2641
AB  - Purpose: Advanced lung carcinoma is charasterized with fast disease progression. Interleukin (IL)10 and transforming growth factor (TGF)b1 are immunosuppressive mediators and their role in lung carcinoma pathogenesis and in the antitumor response has not yet been elucidated. The purpose of this study was to correlate IL10 and TGFb1 levels in the serum and lung tumor microcirculation with clinical stage, disease extent, histological features and TNM stage. Methods: The study included 41 lung cancer patients in clinical stage III and IV. Histological type was determined immunohistochemically, while tumor size, localization and dissemination were determined radiologically by multislice computerized tomography (MSCT). IL10 and TGFb1 levels were quantified with commercial flow cytometric test in serum and lung tumor microcirculation samples. Results: Non small cell lung cancer (NSCLC) patients had significantly elevated TGFb1 while small cell lung cancer (SCLC) patients had significantly increased IL10 in tumor microcirculation. IL10 was significantly elevated in patients with the largest tumors, as well as in patients with III clinical stage and without metastases, both in the serum and tumor microcirculation. TGFb1 was significantly increased in serum and tumor microcirculation in patients with larger tumors. We found significant correlation between these two immunosuppressive cytokines, IL10 and TGFbl, in tumor microcirculation but not in patient serum samples. Conclusion: IL10 and TGFb1 in systemic and tumor microcirculation are significantly associated with particular histological type of lung cancer, tumor size and degree of disease extent.
PB  - Balkan Union of Oncology (B.U.ON.)
T2  - Journal of BUON
T1  - Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma
VL  - 21
IS  - 5
SP  - 1210
EP  - 1218
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2641
ER  - 

@article{
author = "Karlicić, Vukoica and Vuković, Jelena and Stanojević, Ivan and Sotirović, Jelena and Perić, Alexandra and Jović, Milena and Cvijanović, Vlado and Đukić, Mirjana and Banović, Tatjana and Vojvodić, Danilo",
year = "2016",
abstract = "Purpose: Advanced lung carcinoma is charasterized with fast disease progression. Interleukin (IL)10 and transforming growth factor (TGF)b1 are immunosuppressive mediators and their role in lung carcinoma pathogenesis and in the antitumor response has not yet been elucidated. The purpose of this study was to correlate IL10 and TGFb1 levels in the serum and lung tumor microcirculation with clinical stage, disease extent, histological features and TNM stage. Methods: The study included 41 lung cancer patients in clinical stage III and IV. Histological type was determined immunohistochemically, while tumor size, localization and dissemination were determined radiologically by multislice computerized tomography (MSCT). IL10 and TGFb1 levels were quantified with commercial flow cytometric test in serum and lung tumor microcirculation samples. Results: Non small cell lung cancer (NSCLC) patients had significantly elevated TGFb1 while small cell lung cancer (SCLC) patients had significantly increased IL10 in tumor microcirculation. IL10 was significantly elevated in patients with the largest tumors, as well as in patients with III clinical stage and without metastases, both in the serum and tumor microcirculation. TGFb1 was significantly increased in serum and tumor microcirculation in patients with larger tumors. We found significant correlation between these two immunosuppressive cytokines, IL10 and TGFbl, in tumor microcirculation but not in patient serum samples. Conclusion: IL10 and TGFb1 in systemic and tumor microcirculation are significantly associated with particular histological type of lung cancer, tumor size and degree of disease extent.",
publisher = "Balkan Union of Oncology (B.U.ON.)",
journal = "Journal of BUON",
title = "Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma",
volume = "21",
number = "5",
pages = "1210-1218",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2641"
}

Karlicić, V., Vuković, J., Stanojević, I., Sotirović, J., Perić, A., Jović, M., Cvijanović, V., Đukić, M., Banović, T.,& Vojvodić, D.. (2016). Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma. in Journal of BUON
Balkan Union of Oncology (B.U.ON.)., 21(5), 1210-1218.
https://hdl.handle.net/21.15107/rcub_farfar_2641

Karlicić V, Vuković J, Stanojević I, Sotirović J, Perić A, Jović M, Cvijanović V, Đukić M, Banović T, Vojvodić D. Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma. in Journal of BUON. 2016;21(5):1210-1218.
https://hdl.handle.net/21.15107/rcub_farfar_2641 .

Karlicić, Vukoica, Vuković, Jelena, Stanojević, Ivan, Sotirović, Jelena, Perić, Alexandra, Jović, Milena, Cvijanović, Vlado, Đukić, Mirjana, Banović, Tatjana, Vojvodić, Danilo, "Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma" in Journal of BUON, 21, no. 5 (2016):1210-1218,
https://hdl.handle.net/21.15107/rcub_farfar_2641 .