Molecular characterization of thyroid gland tumors:biological and clinical aspects

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Molecular characterization of thyroid gland tumors:biological and clinical aspects (en)
Молекуларна карактеризација тумора штитасте жлезде: биолошки и клинички аспекти (sr)
Molekularna karakterizacija tumora štitaste žlezde: biološki i klinički aspekti (sr_RS)
Authors

Publications

GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro

Soković Bajić, Svetlana; Đokić, Jelena; Dinić, Miroslav; Tomić, Sergej; Popović, Nikola; Brdarić, Emilija; Golić, Nataša; Tolinački, Maja

(Nature Publishing Group, London, 2020)

TY  - JOUR
AU  - Soković Bajić, Svetlana
AU  - Đokić, Jelena
AU  - Dinić, Miroslav
AU  - Tomić, Sergej
AU  - Popović, Nikola
AU  - Brdarić, Emilija
AU  - Golić, Nataša
AU  - Tolinački, Maja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1318
AB  - The characterization of mechanisms involved in the positive effects of probiotic bacteria in various pathophysiological conditions is a prerogative for their safe and efficient application in biomedicine. We have investigated the immunological effects of live bacteria-free supernatant collected from GABA-producing Lactobacillus brevis BGZLS10-17 on Concanavalin A-stimulated mesenteric lymph node cells (MLNC), an in vitro model of activated immune cells. We have shown that GABA containing and GABA-free supernatant of Lactobacillus brevis BGZLS10-17 have strong immunoregulatory effects on MLNC. Further, GABA produced by this strain exhibit additional inhibitory effects on proliferation, IFN-gamma and IL-17 production by MLNC, and the expression of MHCII and CD80 on antigen presenting cells. At the other hand, GABA-containing supernatants displayed the strongest stimulatory effects on the expression of immunoregulatory molecules, such as Foxp3(+), IL-10, TGF-beta, CTLA4 and SIRP-alpha. By looking for the mechanisms of actions, we found that supernatants produced by BGZLS10-17 induce autophagy in different MLNC, such as CD4(+) and CD8(+) T lymphocytes, NK and NKT cells, as well as antigen presenting cells. Further, we showed that the stimulation of Foxp3(+), IL-10 and TGF-beta expression by BGZLS10-17 produced GABA is completely mediated by the induction of ATG5 dependent autophagy, and that other molecules in the supernatants display GABA-, ATG5-, Foxp3(+)-, IL-10- and TGF-beta- independent, immunoregulatory effects.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro
SP  - 1347
VL  - 10
DO  - 10.1038/s41598-020-58177-2
ER  - 
@article{
author = "Soković Bajić, Svetlana and Đokić, Jelena and Dinić, Miroslav and Tomić, Sergej and Popović, Nikola and Brdarić, Emilija and Golić, Nataša and Tolinački, Maja",
year = "2020",
abstract = "The characterization of mechanisms involved in the positive effects of probiotic bacteria in various pathophysiological conditions is a prerogative for their safe and efficient application in biomedicine. We have investigated the immunological effects of live bacteria-free supernatant collected from GABA-producing Lactobacillus brevis BGZLS10-17 on Concanavalin A-stimulated mesenteric lymph node cells (MLNC), an in vitro model of activated immune cells. We have shown that GABA containing and GABA-free supernatant of Lactobacillus brevis BGZLS10-17 have strong immunoregulatory effects on MLNC. Further, GABA produced by this strain exhibit additional inhibitory effects on proliferation, IFN-gamma and IL-17 production by MLNC, and the expression of MHCII and CD80 on antigen presenting cells. At the other hand, GABA-containing supernatants displayed the strongest stimulatory effects on the expression of immunoregulatory molecules, such as Foxp3(+), IL-10, TGF-beta, CTLA4 and SIRP-alpha. By looking for the mechanisms of actions, we found that supernatants produced by BGZLS10-17 induce autophagy in different MLNC, such as CD4(+) and CD8(+) T lymphocytes, NK and NKT cells, as well as antigen presenting cells. Further, we showed that the stimulation of Foxp3(+), IL-10 and TGF-beta expression by BGZLS10-17 produced GABA is completely mediated by the induction of ATG5 dependent autophagy, and that other molecules in the supernatants display GABA-, ATG5-, Foxp3(+)-, IL-10- and TGF-beta- independent, immunoregulatory effects.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro",
pages = "1347",
volume = "10",
doi = "10.1038/s41598-020-58177-2"
}
Soković Bajić, S., Đokić, J., Dinić, M., Tomić, S., Popović, N., Brdarić, E., Golić, N.,& Tolinački, M.. (2020). GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro. in Scientific Reports
Nature Publishing Group, London., 10, 1347.
https://doi.org/10.1038/s41598-020-58177-2
Soković Bajić S, Đokić J, Dinić M, Tomić S, Popović N, Brdarić E, Golić N, Tolinački M. GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro. in Scientific Reports. 2020;10:1347.
doi:10.1038/s41598-020-58177-2 .
Soković Bajić, Svetlana, Đokić, Jelena, Dinić, Miroslav, Tomić, Sergej, Popović, Nikola, Brdarić, Emilija, Golić, Nataša, Tolinački, Maja, "GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro" in Scientific Reports, 10 (2020):1347,
https://doi.org/10.1038/s41598-020-58177-2 . .
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Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation

Bartolome, Aleksandar; Bošković, Srđan; Paunović, Ivan; Bozić, Vesna; Cvejić, Dubravka

(Wiley-Blackwell, Hoboken, 2016)

TY  - JOUR
AU  - Bartolome, Aleksandar
AU  - Bošković, Srđan
AU  - Paunović, Ivan
AU  - Bozić, Vesna
AU  - Cvejić, Dubravka
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/987
AB  - Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p  lt  0.001), pT status (p  lt  0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients.
PB  - Wiley-Blackwell, Hoboken
T2  - APMIS
T1  - Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation
EP  - 277
IS  - 4
SP  - 271
VL  - 124
DO  - 10.1111/apm.12505
ER  - 
@article{
author = "Bartolome, Aleksandar and Bošković, Srđan and Paunović, Ivan and Bozić, Vesna and Cvejić, Dubravka",
year = "2016",
abstract = "Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p  lt  0.001), pT status (p  lt  0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "APMIS",
title = "Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation",
pages = "277-271",
number = "4",
volume = "124",
doi = "10.1111/apm.12505"
}
Bartolome, A., Bošković, S., Paunović, I., Bozić, V.,& Cvejić, D.. (2016). Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation. in APMIS
Wiley-Blackwell, Hoboken., 124(4), 271-277.
https://doi.org/10.1111/apm.12505
Bartolome A, Bošković S, Paunović I, Bozić V, Cvejić D. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation. in APMIS. 2016;124(4):271-277.
doi:10.1111/apm.12505 .
Bartolome, Aleksandar, Bošković, Srđan, Paunović, Ivan, Bozić, Vesna, Cvejić, Dubravka, "Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation" in APMIS, 124, no. 4 (2016):271-277,
https://doi.org/10.1111/apm.12505 . .
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Malignant Risk Stratification of Thyroid FNA Specimens With Indeterminate Cytology Based on Molecular Testing

Paskas, Svetlana; Janković, Jelena; Zivaljević, Vladan; Tatić, Svetislav; Bozić, Vesna; Nikolić, Aleksandra; Radojković, Dragica; Savin, Svetlana; Cvejić, Dubravka

(Wiley, Hoboken, 2015)

TY  - JOUR
AU  - Paskas, Svetlana
AU  - Janković, Jelena
AU  - Zivaljević, Vladan
AU  - Tatić, Svetislav
AU  - Bozić, Vesna
AU  - Nikolić, Aleksandra
AU  - Radojković, Dragica
AU  - Savin, Svetlana
AU  - Cvejić, Dubravka
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/827
AB  - BACKGROUND: Fine-needle aspiration (FNA) has been employed for many years for examining thyroid nodules, and the cytology of aspirates is the primary determinant for whether thyroidectomy is indicated. Fifteen to thirty percent of thyroid nodules, not being clearly benign or malignant, fall into an indeterminate category. The main goals of molecular diagnostics for thyroid nodules are to prevent unnecessary surgery in patients with benign nodules and to stop patients with malignant nodules from being subjected to repeated operations. METHODS: This study was designed to evaluate the diagnostic utility of 4 markers in thyroid FNA cytology via testing for the BRAF V600E mutation and the expression of microRNA-221, microRNA-222, and galectin-3 protein in FNA samples with indeterminate cytology. RESULTS: A predictor model distinguishing benign samples from malignant samples on the basis of the 4 aforementioned markers was formulated. This decision model provided a sensitivity of 73.5%, a specificity of 89.8%, and a diagnostic accuracy of 75.7%. The positive predictive value was 80.6%, and the negative predictive value was 85.5%; this suggested that the prediction had good reliability. CONCLUSIONS: One hundred twenty FNA samples were examined, and 62 nodules were classified as benign with the proposed diagnostic algorithm. This resulted in a reduction of the initial 120 patients to 58 and thus decreased by half the number of persons undergoing surgery.
PB  - Wiley, Hoboken
T2  - Cancer Cytopathology
T1  - Malignant Risk Stratification of Thyroid FNA Specimens With Indeterminate Cytology Based on Molecular Testing
EP  - 479
IS  - 8
SP  - 471
VL  - 123
DO  - 10.1002/cncy.21554
ER  - 
@article{
author = "Paskas, Svetlana and Janković, Jelena and Zivaljević, Vladan and Tatić, Svetislav and Bozić, Vesna and Nikolić, Aleksandra and Radojković, Dragica and Savin, Svetlana and Cvejić, Dubravka",
year = "2015",
abstract = "BACKGROUND: Fine-needle aspiration (FNA) has been employed for many years for examining thyroid nodules, and the cytology of aspirates is the primary determinant for whether thyroidectomy is indicated. Fifteen to thirty percent of thyroid nodules, not being clearly benign or malignant, fall into an indeterminate category. The main goals of molecular diagnostics for thyroid nodules are to prevent unnecessary surgery in patients with benign nodules and to stop patients with malignant nodules from being subjected to repeated operations. METHODS: This study was designed to evaluate the diagnostic utility of 4 markers in thyroid FNA cytology via testing for the BRAF V600E mutation and the expression of microRNA-221, microRNA-222, and galectin-3 protein in FNA samples with indeterminate cytology. RESULTS: A predictor model distinguishing benign samples from malignant samples on the basis of the 4 aforementioned markers was formulated. This decision model provided a sensitivity of 73.5%, a specificity of 89.8%, and a diagnostic accuracy of 75.7%. The positive predictive value was 80.6%, and the negative predictive value was 85.5%; this suggested that the prediction had good reliability. CONCLUSIONS: One hundred twenty FNA samples were examined, and 62 nodules were classified as benign with the proposed diagnostic algorithm. This resulted in a reduction of the initial 120 patients to 58 and thus decreased by half the number of persons undergoing surgery.",
publisher = "Wiley, Hoboken",
journal = "Cancer Cytopathology",
title = "Malignant Risk Stratification of Thyroid FNA Specimens With Indeterminate Cytology Based on Molecular Testing",
pages = "479-471",
number = "8",
volume = "123",
doi = "10.1002/cncy.21554"
}
Paskas, S., Janković, J., Zivaljević, V., Tatić, S., Bozić, V., Nikolić, A., Radojković, D., Savin, S.,& Cvejić, D.. (2015). Malignant Risk Stratification of Thyroid FNA Specimens With Indeterminate Cytology Based on Molecular Testing. in Cancer Cytopathology
Wiley, Hoboken., 123(8), 471-479.
https://doi.org/10.1002/cncy.21554
Paskas S, Janković J, Zivaljević V, Tatić S, Bozić V, Nikolić A, Radojković D, Savin S, Cvejić D. Malignant Risk Stratification of Thyroid FNA Specimens With Indeterminate Cytology Based on Molecular Testing. in Cancer Cytopathology. 2015;123(8):471-479.
doi:10.1002/cncy.21554 .
Paskas, Svetlana, Janković, Jelena, Zivaljević, Vladan, Tatić, Svetislav, Bozić, Vesna, Nikolić, Aleksandra, Radojković, Dragica, Savin, Svetlana, Cvejić, Dubravka, "Malignant Risk Stratification of Thyroid FNA Specimens With Indeterminate Cytology Based on Molecular Testing" in Cancer Cytopathology, 123, no. 8 (2015):471-479,
https://doi.org/10.1002/cncy.21554 . .
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