TY  - JOUR
AU  - Trivanović, Drenka
AU  - Mojsilović, Slavko
AU  - Bogosavljević, Nikola
AU  - Jurišić, Vladimir
AU  - Jauković, Aleksandra
PY  - 2024
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1460
AB  - Among multiple hemostasis components, platelets hyperactivity plays major roles in cancer progression by providing surface and internal components for intercellular crosstalk as well as by behaving like immune cells. Since platelets participate and regulate immunity in homeostatic and disease states, we assumed that revealing platelets profile might help in conceiving novel anti-cancer immune-based strategies. The goal of this review is to compile and discuss the most recent reports on the nature of cancer-associated platelets and their interference with immunotherapy. An increasing number of studies have emphasized active communication between cancer cells and platelets, with platelets promoting cancer cell survival, growth, and metastasis. The anti-cancer potential of platelet-directed therapy has been intensively investigated, and anti-platelet agents may prevent cancer progression and improve the survival of cancer patients. Platelets can (i) reduce antitumor activity; (ii) support immunoregulatory cells and factors generation; (iii) underpin metastasis and, (iv) interfere with immunotherapy by expressing ligands of immune checkpoint receptors. Mediators produced by tumor cell-induced platelet activation support vein thrombosis, constrain anti-tumor T- and natural killer cell response, while contributing to extravasation of tumor cells, metastatic potential, and neovascularization within the tumor. Recent studies showed that attenuation of immunothrombosis, modulation of platelets and their factors have a good perspective in immunotherapy optimization. Particularly, blockade of intra-tumoral platelet-associated programmed death-ligand 1 might promote anti-tumor T cell-induced cytotoxicity. Collectively, these findings suggest that platelets might represent the source of relevant cancer staging biomarkers, as well as promising targets and carriers in immunotherapeutic approaches for combating cancer.
PB  - Neoplasia Press, Inc.
T2  - Translational Oncology
T2  - Translational OncologyTranslational Oncology
T1  - Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development
SP  - 101871
VL  - 40
DO  - 10.1016/j.tranon.2023.101871
ER  - 

@article{
author = "Trivanović, Drenka and Mojsilović, Slavko and Bogosavljević, Nikola and Jurišić, Vladimir and Jauković, Aleksandra",
year = "2024",
abstract = "Among multiple hemostasis components, platelets hyperactivity plays major roles in cancer progression by providing surface and internal components for intercellular crosstalk as well as by behaving like immune cells. Since platelets participate and regulate immunity in homeostatic and disease states, we assumed that revealing platelets profile might help in conceiving novel anti-cancer immune-based strategies. The goal of this review is to compile and discuss the most recent reports on the nature of cancer-associated platelets and their interference with immunotherapy. An increasing number of studies have emphasized active communication between cancer cells and platelets, with platelets promoting cancer cell survival, growth, and metastasis. The anti-cancer potential of platelet-directed therapy has been intensively investigated, and anti-platelet agents may prevent cancer progression and improve the survival of cancer patients. Platelets can (i) reduce antitumor activity; (ii) support immunoregulatory cells and factors generation; (iii) underpin metastasis and, (iv) interfere with immunotherapy by expressing ligands of immune checkpoint receptors. Mediators produced by tumor cell-induced platelet activation support vein thrombosis, constrain anti-tumor T- and natural killer cell response, while contributing to extravasation of tumor cells, metastatic potential, and neovascularization within the tumor. Recent studies showed that attenuation of immunothrombosis, modulation of platelets and their factors have a good perspective in immunotherapy optimization. Particularly, blockade of intra-tumoral platelet-associated programmed death-ligand 1 might promote anti-tumor T cell-induced cytotoxicity. Collectively, these findings suggest that platelets might represent the source of relevant cancer staging biomarkers, as well as promising targets and carriers in immunotherapeutic approaches for combating cancer.",
publisher = "Neoplasia Press, Inc.",
journal = "Translational Oncology, Translational OncologyTranslational Oncology",
title = "Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development",
pages = "101871",
volume = "40",
doi = "10.1016/j.tranon.2023.101871"
}

Trivanović, D., Mojsilović, S., Bogosavljević, N., Jurišić, V.,& Jauković, A.. (2024). Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development. in Translational Oncology
Neoplasia Press, Inc.., 40, 101871.
https://doi.org/10.1016/j.tranon.2023.101871

Trivanović D, Mojsilović S, Bogosavljević N, Jurišić V, Jauković A. Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development. in Translational Oncology. 2024;40:101871.
doi:10.1016/j.tranon.2023.101871 .

Trivanović, Drenka, Mojsilović, Slavko, Bogosavljević, Nikola, Jurišić, Vladimir, Jauković, Aleksandra, "Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development" in Translational Oncology, 40 (2024):101871,
https://doi.org/10.1016/j.tranon.2023.101871 . .

TY  - CONF
AU  - Trivanović, Drenka
AU  - Vujačić, Marko
AU  - Arsić, Aleksandra
AU  - Bogosavljević, Nikola
AU  - Kovačić, Marijana
AU  - Drvenica, Ivana
AU  - Mojsilović, Slavko
AU  - Baščarević, Zoran
AU  - Bugarski, Diana
AU  - Jauković, Aleksandra
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1408
AB  - Bone marrow (BM) adipose tissue (BMAT) has been described as lipotoxic factor with negative impacts on skeletal system regeneration and repair. As BMAT undergoes metabolic and cellular 
adaptations with age and disease, we assumed that investigation of BMAT-associated lipid profile and cellularity at different skeletal locations in osteoarthritis (OA) patients might contribute to understanding of lipid involvement in OA development and progression.Acetabular and femoral BM, and femoral subcutaneous adipose tissue (fSAT) were obtained from 
matched patients (n=11, 5 women, 6 men; age: 65±11 years; BMI: 27.89±4.42 kg/m2) undergoing hip arthroplasty surgery (Ethical approval I-97/11). BM, BMAT and fSAT were explored at the levels of total lipids, fatty acids, and cells, by using thin layer and gas chromatography and ex vivo cellular 24734039, 2023, S3, Downloaded from https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbm4.10738 by Readcube (Labtiva Inc.), Wiley Online Library on [23/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License assays. Statistical significance was estimated by non-parametric tests and Spearman’s rank correlation (r) was calculated.BMAT content was significantly higher in femoral (0.262±0.088 mL/g) than in acetabular BM (0.063±0.051 mL/g) (n=11, p=0.016). Negative associations with BMI of patients were found for femoral BM (r=-0.783, p=0.017, n=11) and BMAT (n=9, r=-1.000, p=0.017) tissue cellularity. 
Additionally, femoral BMAT cellularity declined with age (r=-0.675, n=10, p=0.037). Total lipid analyses revealed significantly lower triglyceride content in femoral than in acetabular BMAT and fSAT. Frequency of saturated palmitic, myristic and stearic acids were higher in femoral than in acetabular BMAT and fSAT, where palmitoleic, linoleic, oleic acids were more dominant. BMAT associated compartments from both locations host lower frequency of non-hematopoietic CD45- neutral lipid-loaded cells when compared to BM. This associated with higher incidence of clonogenic mesenchymal stromal (stem) cells in acetabular (0.032± 0.04%) and femoral (0.021± 0.028%) BMATs and fSAT (0.031 ± 0.016%) than in their BM counterparts.
Collectively, our results indicate that the lipid profiles of hip BMAT impose significantly different BM microenvironments and distribution of cells with regenerative potential in OA patients.
PB  - American Society for Bone and Mineral Research
C3  - JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool
T1  - Lipid and cellular profiles of acetabular and femoral bone marrow adipose tissues are distinct in hip osteoarthritis patients
IS  - 3
SP  - P140
VL  - 7
UR  - https://hdl.handle.net/21.15107/rcub_rimi_1408
ER  - 

@conference{
author = "Trivanović, Drenka and Vujačić, Marko and Arsić, Aleksandra and Bogosavljević, Nikola and Kovačić, Marijana and Drvenica, Ivana and Mojsilović, Slavko and Baščarević, Zoran and Bugarski, Diana and Jauković, Aleksandra",
year = "2023",
abstract = "Bone marrow (BM) adipose tissue (BMAT) has been described as lipotoxic factor with negative impacts on skeletal system regeneration and repair. As BMAT undergoes metabolic and cellular 
adaptations with age and disease, we assumed that investigation of BMAT-associated lipid profile and cellularity at different skeletal locations in osteoarthritis (OA) patients might contribute to understanding of lipid involvement in OA development and progression.Acetabular and femoral BM, and femoral subcutaneous adipose tissue (fSAT) were obtained from 
matched patients (n=11, 5 women, 6 men; age: 65±11 years; BMI: 27.89±4.42 kg/m2) undergoing hip arthroplasty surgery (Ethical approval I-97/11). BM, BMAT and fSAT were explored at the levels of total lipids, fatty acids, and cells, by using thin layer and gas chromatography and ex vivo cellular 24734039, 2023, S3, Downloaded from https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbm4.10738 by Readcube (Labtiva Inc.), Wiley Online Library on [23/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License assays. Statistical significance was estimated by non-parametric tests and Spearman’s rank correlation (r) was calculated.BMAT content was significantly higher in femoral (0.262±0.088 mL/g) than in acetabular BM (0.063±0.051 mL/g) (n=11, p=0.016). Negative associations with BMI of patients were found for femoral BM (r=-0.783, p=0.017, n=11) and BMAT (n=9, r=-1.000, p=0.017) tissue cellularity. 
Additionally, femoral BMAT cellularity declined with age (r=-0.675, n=10, p=0.037). Total lipid analyses revealed significantly lower triglyceride content in femoral than in acetabular BMAT and fSAT. Frequency of saturated palmitic, myristic and stearic acids were higher in femoral than in acetabular BMAT and fSAT, where palmitoleic, linoleic, oleic acids were more dominant. BMAT associated compartments from both locations host lower frequency of non-hematopoietic CD45- neutral lipid-loaded cells when compared to BM. This associated with higher incidence of clonogenic mesenchymal stromal (stem) cells in acetabular (0.032± 0.04%) and femoral (0.021± 0.028%) BMATs and fSAT (0.031 ± 0.016%) than in their BM counterparts.
Collectively, our results indicate that the lipid profiles of hip BMAT impose significantly different BM microenvironments and distribution of cells with regenerative potential in OA patients.",
publisher = "American Society for Bone and Mineral Research",
journal = "JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool",
title = "Lipid and cellular profiles of acetabular and femoral bone marrow adipose tissues are distinct in hip osteoarthritis patients",
number = "3",
pages = "P140",
volume = "7",
url = "https://hdl.handle.net/21.15107/rcub_rimi_1408"
}

Trivanović, D., Vujačić, M., Arsić, A., Bogosavljević, N., Kovačić, M., Drvenica, I., Mojsilović, S., Baščarević, Z., Bugarski, D.,& Jauković, A.. (2023). Lipid and cellular profiles of acetabular and femoral bone marrow adipose tissues are distinct in hip osteoarthritis patients. in JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool
American Society for Bone and Mineral Research., 7(3), P140.
https://hdl.handle.net/21.15107/rcub_rimi_1408

Trivanović D, Vujačić M, Arsić A, Bogosavljević N, Kovačić M, Drvenica I, Mojsilović S, Baščarević Z, Bugarski D, Jauković A. Lipid and cellular profiles of acetabular and femoral bone marrow adipose tissues are distinct in hip osteoarthritis patients. in JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool. 2023;7(3):P140.
https://hdl.handle.net/21.15107/rcub_rimi_1408 .

Trivanović, Drenka, Vujačić, Marko, Arsić, Aleksandra, Bogosavljević, Nikola, Kovačić, Marijana, Drvenica, Ivana, Mojsilović, Slavko, Baščarević, Zoran, Bugarski, Diana, Jauković, Aleksandra, "Lipid and cellular profiles of acetabular and femoral bone marrow adipose tissues are distinct in hip osteoarthritis patients" in JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool, 7, no. 3 (2023):P140,
https://hdl.handle.net/21.15107/rcub_rimi_1408 .

TY  - CONF
AU  - Trivanović, Drenka
AU  - Okić Đorđević, Ivana
AU  - Živanović, Milena
AU  - Vujačić, Marko
AU  - Bogosavljević, Nikola
AU  - Bugarski, Diana
AU  - Jauković, Aleksandra
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1409
AB  - Aging and disease-induced adipogenesis in skeletal system has been described as detrimental process for bone tissue metabolism. Dynamic of adipogenic program is controlled by microenvironmental factors and activity of bone marrow (BM) mesenchymal stromal (stem) cells (MSC)s. As different skeletal locations are not affected by extrinsic factors in same manner, we assumed that marrow adipogenic program can be distinct in acetabular (aMSCs) and femoral MSCs (fMSCs). Here, we compared expanded aMSCs and fMSCs from matched patients undergoing hip arthroplasty (n=6, Ethical approval I-97/11). Cellular and molecular assays were performed to investigate differences in MSC features. Statistical significance was estimated by ANOVA. Results showed that adipogenic stimuli triggered stronger adipogenesis in fMSCs when compared to acetabular counterparts (p=0.036). Tissue non-specific alkaline phosphatase (TNAP) activity and protein expression was higher in fMSCs than in aMSCs, along with significantly higher TNAP levels detected in mitochondrial-enriched fraction proteins in fMSCs. Stronger expression of mitochondrial electron transport chain (ETC) proteins, supercomplexes I and V was found in fMSCs than in aMSCs. This coincided with increased β-galactosidase and total intracellular reactive oxygen species (ROS) production in fMSCs. Lipid droplet accumulation was followed by upregulated tissue beta-galactosidase and TNAP activities, expression of glyceraldehyde 3-phosphate dehydrogenase 24734039, 2023, S3, Downloaded from https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbm4.10738 by Readcube (Labtiva Inc.), Wiley Online Library on [23/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License (GAPDH), in parallel with stimulated ROS and mitochondrial superoxide production in both MSCs. Presence of fatty acid oxidation (FAO) inhibitor etomoxir increased gene expression of fatty acid binding protein (Fabp)4, while decreased protein and gene expression of GAPDH in both populations. Although etomoxir supported adipogenic differentiation and β-galactosidase activity in aMSCs only, TNAP activity and ROS content stayed unaltered.These results indicate that mitochondrial pathways required for energy production, ETC and FAO are bone-specific, and differently affect marrow adipogenesis in acetabular and femoral regions. Further elucidation of marrow adipogenesis can contribute to development of pharmacologic strategies to support skeletal and metabolic health.
PB  - American Society for Bone and Mineral Research
C3  - JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool
T1  - Region-specific differences of marrow adipogenesis in mesenchymal stromal (stem) cells of human acetabulum and femur: involvement of fatty acid oxidation
IS  - 3
SP  - P141
VL  - 7
UR  - https://hdl.handle.net/21.15107/rcub_rimi_1409
ER  - 

@conference{
author = "Trivanović, Drenka and Okić Đorđević, Ivana and Živanović, Milena and Vujačić, Marko and Bogosavljević, Nikola and Bugarski, Diana and Jauković, Aleksandra",
year = "2023",
abstract = "Aging and disease-induced adipogenesis in skeletal system has been described as detrimental process for bone tissue metabolism. Dynamic of adipogenic program is controlled by microenvironmental factors and activity of bone marrow (BM) mesenchymal stromal (stem) cells (MSC)s. As different skeletal locations are not affected by extrinsic factors in same manner, we assumed that marrow adipogenic program can be distinct in acetabular (aMSCs) and femoral MSCs (fMSCs). Here, we compared expanded aMSCs and fMSCs from matched patients undergoing hip arthroplasty (n=6, Ethical approval I-97/11). Cellular and molecular assays were performed to investigate differences in MSC features. Statistical significance was estimated by ANOVA. Results showed that adipogenic stimuli triggered stronger adipogenesis in fMSCs when compared to acetabular counterparts (p=0.036). Tissue non-specific alkaline phosphatase (TNAP) activity and protein expression was higher in fMSCs than in aMSCs, along with significantly higher TNAP levels detected in mitochondrial-enriched fraction proteins in fMSCs. Stronger expression of mitochondrial electron transport chain (ETC) proteins, supercomplexes I and V was found in fMSCs than in aMSCs. This coincided with increased β-galactosidase and total intracellular reactive oxygen species (ROS) production in fMSCs. Lipid droplet accumulation was followed by upregulated tissue beta-galactosidase and TNAP activities, expression of glyceraldehyde 3-phosphate dehydrogenase 24734039, 2023, S3, Downloaded from https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbm4.10738 by Readcube (Labtiva Inc.), Wiley Online Library on [23/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License (GAPDH), in parallel with stimulated ROS and mitochondrial superoxide production in both MSCs. Presence of fatty acid oxidation (FAO) inhibitor etomoxir increased gene expression of fatty acid binding protein (Fabp)4, while decreased protein and gene expression of GAPDH in both populations. Although etomoxir supported adipogenic differentiation and β-galactosidase activity in aMSCs only, TNAP activity and ROS content stayed unaltered.These results indicate that mitochondrial pathways required for energy production, ETC and FAO are bone-specific, and differently affect marrow adipogenesis in acetabular and femoral regions. Further elucidation of marrow adipogenesis can contribute to development of pharmacologic strategies to support skeletal and metabolic health.",
publisher = "American Society for Bone and Mineral Research",
journal = "JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool",
title = "Region-specific differences of marrow adipogenesis in mesenchymal stromal (stem) cells of human acetabulum and femur: involvement of fatty acid oxidation",
number = "3",
pages = "P141",
volume = "7",
url = "https://hdl.handle.net/21.15107/rcub_rimi_1409"
}

Trivanović, D., Okić Đorđević, I., Živanović, M., Vujačić, M., Bogosavljević, N., Bugarski, D.,& Jauković, A.. (2023). Region-specific differences of marrow adipogenesis in mesenchymal stromal (stem) cells of human acetabulum and femur: involvement of fatty acid oxidation. in JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool
American Society for Bone and Mineral Research., 7(3), P141.
https://hdl.handle.net/21.15107/rcub_rimi_1409

Trivanović D, Okić Đorđević I, Živanović M, Vujačić M, Bogosavljević N, Bugarski D, Jauković A. Region-specific differences of marrow adipogenesis in mesenchymal stromal (stem) cells of human acetabulum and femur: involvement of fatty acid oxidation. in JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool. 2023;7(3):P141.
https://hdl.handle.net/21.15107/rcub_rimi_1409 .

Trivanović, Drenka, Okić Đorđević, Ivana, Živanović, Milena, Vujačić, Marko, Bogosavljević, Nikola, Bugarski, Diana, Jauković, Aleksandra, "Region-specific differences of marrow adipogenesis in mesenchymal stromal (stem) cells of human acetabulum and femur: involvement of fatty acid oxidation" in JBMR PlusVolume 7: Abstracts of the 50th ECTS Congress featuring BRS Annual Meeting, 15-18 April 2023, Liverpool, 7, no. 3 (2023):P141,
https://hdl.handle.net/21.15107/rcub_rimi_1409 .