TY  - JOUR
AU  - Milosevic, Zorica
AU  - Tanić, Nikola
AU  - Banković, Jasna Z.
AU  - Stankovic, Tijana
AU  - Buta, Marko
AU  - Lavrnic, Dragana
AU  - Milovanovic, Zorka
AU  - Pupic, Gordana
AU  - Stojković Burić, Sonja
AU  - Milinkovic, Vedrana
AU  - Ito, Yasuhiro
AU  - Džodić, Radan R.
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2290
AB  - Multiple cancers represent 2.42\% of all human cancers and are mainly
   double or triple cancers. Many possible causes of multiple malignancies
   have been reported such as genetic alterations, exposure to anti-cancer
   chemotherapy, radiotherapy, immunosuppressive therapy and reduced
   immunologic response. We report a female patient with multiple sclerosis
   and quadruple cancers of different embryological origin. Patient was
   diagnosed with stage III (T3, N1a, MO) medullary thyroid carcinoma
   (MTC), multicentric micropapillary thyroid carcinoma, scapular and
   lumbar melanomas (Clark II, Breslow II), and lobular invasive breast
   carcinoma (T1a, NO, MO). All tumors present in our patient except
   micropapillary thyroid carcinomas were investigated for gene alterations
   known to have a key role in cancer promotion and progression. Tumor
   samples were screened for the p16 alterations (loss of heterozygosity
   and homozygous deletions), loss of heterozygosity of PTEN, p53
   alterations (mutational status and loss of heterozygosity) and
   mutational status of RET, HRAS and KRAS. Each type of tumor investigated
   had specific pattern of analyzed genetic alterations. The most prominent
   genetic changes were mutual alterations in PTEN and p53 tumor
   suppressors present in breast cancer and two melanomas. These
   co-alterations could be crucial for promoting development of multiple
   malignancies. Moreover the insertion in 4th codon of HRAS gene was
   common for all tumor types investigated. It represents frameshift
   mutation introducing stop codon at position 5 which prevents synthesis
   of a full-length protein. Since the inactivated RAS enhances sensitivity
   to tamoxifen and radiotherapy this genetic alteration could be
   considered as a good prognostic factor for this patient.
T2  - International Journal of Clinical and Experimental Pathology
T1  - Genetic alterations in quadruple malignancies of a patient with multiple
 sclerosis: their role in malignancy development and response to therapy
IS  - 4
VL  - 7
SP  - 1826
EP  - 1833
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2290
ER  - 

@article{
author = "Milosevic, Zorica and Tanić, Nikola and Banković, Jasna Z. and Stankovic, Tijana and Buta, Marko and Lavrnic, Dragana and Milovanovic, Zorka and Pupic, Gordana and Stojković Burić, Sonja and Milinkovic, Vedrana and Ito, Yasuhiro and Džodić, Radan R.",
year = "2014",
abstract = "Multiple cancers represent 2.42\% of all human cancers and are mainly
   double or triple cancers. Many possible causes of multiple malignancies
   have been reported such as genetic alterations, exposure to anti-cancer
   chemotherapy, radiotherapy, immunosuppressive therapy and reduced
   immunologic response. We report a female patient with multiple sclerosis
   and quadruple cancers of different embryological origin. Patient was
   diagnosed with stage III (T3, N1a, MO) medullary thyroid carcinoma
   (MTC), multicentric micropapillary thyroid carcinoma, scapular and
   lumbar melanomas (Clark II, Breslow II), and lobular invasive breast
   carcinoma (T1a, NO, MO). All tumors present in our patient except
   micropapillary thyroid carcinomas were investigated for gene alterations
   known to have a key role in cancer promotion and progression. Tumor
   samples were screened for the p16 alterations (loss of heterozygosity
   and homozygous deletions), loss of heterozygosity of PTEN, p53
   alterations (mutational status and loss of heterozygosity) and
   mutational status of RET, HRAS and KRAS. Each type of tumor investigated
   had specific pattern of analyzed genetic alterations. The most prominent
   genetic changes were mutual alterations in PTEN and p53 tumor
   suppressors present in breast cancer and two melanomas. These
   co-alterations could be crucial for promoting development of multiple
   malignancies. Moreover the insertion in 4th codon of HRAS gene was
   common for all tumor types investigated. It represents frameshift
   mutation introducing stop codon at position 5 which prevents synthesis
   of a full-length protein. Since the inactivated RAS enhances sensitivity
   to tamoxifen and radiotherapy this genetic alteration could be
   considered as a good prognostic factor for this patient.",
journal = "International Journal of Clinical and Experimental Pathology",
title = "Genetic alterations in quadruple malignancies of a patient with multiple
 sclerosis: their role in malignancy development and response to therapy",
number = "4",
volume = "7",
pages = "1826-1833",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2290"
}

Milosevic, Z., Tanić, N., Banković, J. Z., Stankovic, T., Buta, M., Lavrnic, D., Milovanovic, Z., Pupic, G., Stojković Burić, S., Milinkovic, V., Ito, Y.,& Džodić, R. R.. (2014). Genetic alterations in quadruple malignancies of a patient with multiple
 sclerosis: their role in malignancy development and response to therapy. in International Journal of Clinical and Experimental Pathology, 7(4), 1826-1833.
https://hdl.handle.net/21.15107/rcub_ibiss_2290

Milosevic Z, Tanić N, Banković JZ, Stankovic T, Buta M, Lavrnic D, Milovanovic Z, Pupic G, Stojković Burić S, Milinkovic V, Ito Y, Džodić RR. Genetic alterations in quadruple malignancies of a patient with multiple
 sclerosis: their role in malignancy development and response to therapy. in International Journal of Clinical and Experimental Pathology. 2014;7(4):1826-1833.
https://hdl.handle.net/21.15107/rcub_ibiss_2290 .

Milosevic, Zorica, Tanić, Nikola, Banković, Jasna Z., Stankovic, Tijana, Buta, Marko, Lavrnic, Dragana, Milovanovic, Zorka, Pupic, Gordana, Stojković Burić, Sonja, Milinkovic, Vedrana, Ito, Yasuhiro, Džodić, Radan R., "Genetic alterations in quadruple malignancies of a patient with multiple
 sclerosis: their role in malignancy development and response to therapy" in International Journal of Clinical and Experimental Pathology, 7, no. 4 (2014):1826-1833,
https://hdl.handle.net/21.15107/rcub_ibiss_2290 .

TY  - JOUR
AU  - Martinovic, Katarina M. Mirjacic
AU  - Babovic, Nada Lj.
AU  - Džodić, Radan R.
AU  - Jurisic, Vladimir B.
AU  - Tanić, Nikola
AU  - Konjevic, Gordana M.
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2187
AB  - Although natural killer (NK) cells play an important antitumor role,
   melanoma cells may affect their effector functions. In this study, we
   analyzed the expression of various receptors and effector molecules in
   NK cells and their subsets in metastatic melanoma (MM) patients compared
   with healthy controls (HCs). In HC and MM patients, we analyzed NK cell
   activity using a chromium release assay and the expression of CD107a
   degranulation marker, activating NKG2D, NKp46, DNAM-1, and inhibitory
   CD158a and CD158b receptors, IL-12R beta 1, IL-12R beta 2, intracellular
   interferon (IFN)-gamma, perforin, and STAT-1 in CD3-CD56 + NK cells, and
   cytotoxic CD3-CD56 dim and immunoregulatory CD3-CD56 bright subsets by
   flow cytometry. MM patients compared with HC not only had significantly
   decreased NK cell activity, lower expression of CD107a, and impaired
   IFN-gamma production but also had decreased expression of activating
   NKG2D, NKp46, and DNAM-1 receptors, which was followed by lower
   expression of perforin, STAT-1, and both IL-12R subunits in NK cells. In
   MM patients only, there was a positive correlation between NKG2D
   expression and degranulation capacity, as well as IFN-gamma production
   in NK cells. Analysis of the expression of various parameters of NK cell
   effector functions between MM patients with different localization of
   distant metastases showed that patients in the unfavorable M1c subclass
   had decreased expression of NKG2D and NKp46 on NK cells compared with
   patients in the M1a + b group. Downregulated NKG2D, NKp46, and DNAM-1
   receptors associated with impaired NK cell effector function are
   important biomarkers of advanced disease with a poor prognosis in
   melanoma patients. (C) 2014 Wolters Kluwer Health vertical bar
   Lippincott Williams \& Wilkins.
T2  - Melanoma Research
T1  - Decreased expression of NKG2D, NKp46, DNAM-1 receptors, and
 intracellular perforin and STAT-1 effector molecules in NK cells and
 their dim and bright subsets in metastatic melanoma patients
IS  - 4
VL  - 24
DO  - 10.1097/CMR.0000000000000072
SP  - 295
EP  - 304
ER  - 

@article{
author = "Martinovic, Katarina M. Mirjacic and Babovic, Nada Lj. and Džodić, Radan R. and Jurisic, Vladimir B. and Tanić, Nikola and Konjevic, Gordana M.",
year = "2014",
abstract = "Although natural killer (NK) cells play an important antitumor role,
   melanoma cells may affect their effector functions. In this study, we
   analyzed the expression of various receptors and effector molecules in
   NK cells and their subsets in metastatic melanoma (MM) patients compared
   with healthy controls (HCs). In HC and MM patients, we analyzed NK cell
   activity using a chromium release assay and the expression of CD107a
   degranulation marker, activating NKG2D, NKp46, DNAM-1, and inhibitory
   CD158a and CD158b receptors, IL-12R beta 1, IL-12R beta 2, intracellular
   interferon (IFN)-gamma, perforin, and STAT-1 in CD3-CD56 + NK cells, and
   cytotoxic CD3-CD56 dim and immunoregulatory CD3-CD56 bright subsets by
   flow cytometry. MM patients compared with HC not only had significantly
   decreased NK cell activity, lower expression of CD107a, and impaired
   IFN-gamma production but also had decreased expression of activating
   NKG2D, NKp46, and DNAM-1 receptors, which was followed by lower
   expression of perforin, STAT-1, and both IL-12R subunits in NK cells. In
   MM patients only, there was a positive correlation between NKG2D
   expression and degranulation capacity, as well as IFN-gamma production
   in NK cells. Analysis of the expression of various parameters of NK cell
   effector functions between MM patients with different localization of
   distant metastases showed that patients in the unfavorable M1c subclass
   had decreased expression of NKG2D and NKp46 on NK cells compared with
   patients in the M1a + b group. Downregulated NKG2D, NKp46, and DNAM-1
   receptors associated with impaired NK cell effector function are
   important biomarkers of advanced disease with a poor prognosis in
   melanoma patients. (C) 2014 Wolters Kluwer Health vertical bar
   Lippincott Williams \& Wilkins.",
journal = "Melanoma Research",
title = "Decreased expression of NKG2D, NKp46, DNAM-1 receptors, and
 intracellular perforin and STAT-1 effector molecules in NK cells and
 their dim and bright subsets in metastatic melanoma patients",
number = "4",
volume = "24",
doi = "10.1097/CMR.0000000000000072",
pages = "295-304"
}

Martinovic, K. M. M., Babovic, N. Lj., Džodić, R. R., Jurisic, V. B., Tanić, N.,& Konjevic, G. M.. (2014). Decreased expression of NKG2D, NKp46, DNAM-1 receptors, and
 intracellular perforin and STAT-1 effector molecules in NK cells and
 their dim and bright subsets in metastatic melanoma patients. in Melanoma Research, 24(4), 295-304.
https://doi.org/10.1097/CMR.0000000000000072

Martinovic KMM, Babovic NL, Džodić RR, Jurisic VB, Tanić N, Konjevic GM. Decreased expression of NKG2D, NKp46, DNAM-1 receptors, and
 intracellular perforin and STAT-1 effector molecules in NK cells and
 their dim and bright subsets in metastatic melanoma patients. in Melanoma Research. 2014;24(4):295-304.
doi:10.1097/CMR.0000000000000072 .

Martinovic, Katarina M. Mirjacic, Babovic, Nada Lj., Džodić, Radan R., Jurisic, Vladimir B., Tanić, Nikola, Konjevic, Gordana M., "Decreased expression of NKG2D, NKp46, DNAM-1 receptors, and
 intracellular perforin and STAT-1 effector molecules in NK cells and
 their dim and bright subsets in metastatic melanoma patients" in Melanoma Research, 24, no. 4 (2014):295-304,
https://doi.org/10.1097/CMR.0000000000000072 . .

TY  - JOUR
AU  - Milosevic, Zorica
AU  - Pešić, Milica
AU  - Stankovic, Tijana
AU  - Dinić, Jelena
AU  - Milovanovic, Zorka
AU  - Stojsic, Jelena
AU  - Džodić, Radan R.
AU  - Tanić, Nikola
AU  - Banković, Jasna Z.
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2133
AB  - Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive and
   chemoresistant tumor with dismal prognosis. Most ATCs harbor mutations
   that activate RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. Therefore, we
   investigated and correlated the expression of phosphatase and tensin
   homolog, pERK, and pAKT proteins as well as mutations of BRAF, RAS, and
   p53 genes in samples of patients with ATC. Furthermore, we evaluated the
   potential of inhibition of these pathways on chemosensitization of ATC
   using 2 thyroid carcinoma cell lines (FRO and SW1736). Our results
   revealed a negative correlation between the activity of RAS-MAPK-ERK and
   PI3K-AKT-mTOR pathways in samples of patients. To be specific, the
   PI3K-AKT-mTOR pathway was suppressed in patients with activated NRAS or
   high pERK expression. In vitro results suggest that the inhibition of
   either RAS-MAPK-ERK or PI3K-AKT-mTOR components may confer sensitivity
   of thyroid cancer cells to classic chemotherapeutics. This may form a
   basis for the development of novel genetic-based therapeutic approach
   for this cancer type.
T2  - Translational Research
T1  - Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to
 chemosensitize anaplastic thyroid carcinoma
IS  - 5
VL  - 164
DO  - 10.1016/j.trsl.2014.06.005
SP  - 411
EP  - 423
ER  - 

@article{
author = "Milosevic, Zorica and Pešić, Milica and Stankovic, Tijana and Dinić, Jelena and Milovanovic, Zorka and Stojsic, Jelena and Džodić, Radan R. and Tanić, Nikola and Banković, Jasna Z.",
year = "2014",
abstract = "Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive and
   chemoresistant tumor with dismal prognosis. Most ATCs harbor mutations
   that activate RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. Therefore, we
   investigated and correlated the expression of phosphatase and tensin
   homolog, pERK, and pAKT proteins as well as mutations of BRAF, RAS, and
   p53 genes in samples of patients with ATC. Furthermore, we evaluated the
   potential of inhibition of these pathways on chemosensitization of ATC
   using 2 thyroid carcinoma cell lines (FRO and SW1736). Our results
   revealed a negative correlation between the activity of RAS-MAPK-ERK and
   PI3K-AKT-mTOR pathways in samples of patients. To be specific, the
   PI3K-AKT-mTOR pathway was suppressed in patients with activated NRAS or
   high pERK expression. In vitro results suggest that the inhibition of
   either RAS-MAPK-ERK or PI3K-AKT-mTOR components may confer sensitivity
   of thyroid cancer cells to classic chemotherapeutics. This may form a
   basis for the development of novel genetic-based therapeutic approach
   for this cancer type.",
journal = "Translational Research",
title = "Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to
 chemosensitize anaplastic thyroid carcinoma",
number = "5",
volume = "164",
doi = "10.1016/j.trsl.2014.06.005",
pages = "411-423"
}

Milosevic, Z., Pešić, M., Stankovic, T., Dinić, J., Milovanovic, Z., Stojsic, J., Džodić, R. R., Tanić, N.,& Banković, J. Z.. (2014). Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to
 chemosensitize anaplastic thyroid carcinoma. in Translational Research, 164(5), 411-423.
https://doi.org/10.1016/j.trsl.2014.06.005

Milosevic Z, Pešić M, Stankovic T, Dinić J, Milovanovic Z, Stojsic J, Džodić RR, Tanić N, Banković JZ. Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to
 chemosensitize anaplastic thyroid carcinoma. in Translational Research. 2014;164(5):411-423.
doi:10.1016/j.trsl.2014.06.005 .

Milosevic, Zorica, Pešić, Milica, Stankovic, Tijana, Dinić, Jelena, Milovanovic, Zorka, Stojsic, Jelena, Džodić, Radan R., Tanić, Nikola, Banković, Jasna Z., "Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to
 chemosensitize anaplastic thyroid carcinoma" in Translational Research, 164, no. 5 (2014):411-423,
https://doi.org/10.1016/j.trsl.2014.06.005 . .

TY  - JOUR
AU  - Tanić, Nikola T
AU  - Milovanović, Zorka
AU  - Tanić, Nasta
AU  - Džodić, Radan R.
AU  - Juranić, Zorica D
AU  - Susnjar, Snezana
AU  - Plesinac-Karapandžić, Vesna
AU  - Tatić, Svetislav B
AU  - Dramicanin, Tatjana
AU  - Davidović, Radoslav
AU  - Dimitrijević, Bogomir B.
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1100
AB  - Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.
T2  - Cancer Biology & Therapy
T1  - The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients
IS  - 12
VL  - 13
SP  - 55
EP  - 1174
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1100
ER  - 

@article{
author = "Tanić, Nikola T and Milovanović, Zorka and Tanić, Nasta and Džodić, Radan R. and Juranić, Zorica D and Susnjar, Snezana and Plesinac-Karapandžić, Vesna and Tatić, Svetislav B and Dramicanin, Tatjana and Davidović, Radoslav and Dimitrijević, Bogomir B.",
year = "2012",
abstract = "Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.",
journal = "Cancer Biology & Therapy",
title = "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients",
number = "12",
volume = "13",
pages = "55-1174",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1100"
}

Tanić, N. T., Milovanović, Z., Tanić, N., Džodić, R. R., Juranić, Z. D., Susnjar, S., Plesinac-Karapandžić, V., Tatić, S. B., Dramicanin, T., Davidović, R.,& Dimitrijević, B. B.. (2012). The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology & Therapy, 13(12), 55-1174.
https://hdl.handle.net/21.15107/rcub_ibiss_1100

Tanić NT, Milovanović Z, Tanić N, Džodić RR, Juranić ZD, Susnjar S, Plesinac-Karapandžić V, Tatić SB, Dramicanin T, Davidović R, Dimitrijević BB. The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology & Therapy. 2012;13(12):55-1174.
https://hdl.handle.net/21.15107/rcub_ibiss_1100 .

Tanić, Nikola T, Milovanović, Zorka, Tanić, Nasta, Džodić, Radan R., Juranić, Zorica D, Susnjar, Snezana, Plesinac-Karapandžić, Vesna, Tatić, Svetislav B, Dramicanin, Tatjana, Davidović, Radoslav, Dimitrijević, Bogomir B., "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients" in Cancer Biology & Therapy, 13, no. 12 (2012):55-1174,
https://hdl.handle.net/21.15107/rcub_ibiss_1100 .