TY  - JOUR
AU  - Eljabo, Najib
AU  - Nikolić, Nadja
AU  - Čarkić, Jelena
AU  - Jelovac, Drago
AU  - Lazarević, M.
AU  - Tanić, Nasta
AU  - Milašin, Jelena
PY  - 2018
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2301
AB  - Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a high rate of recurrence and metastasis, which could be explained by the presence of molecular alterations in seemingly normal tumour margins and the entire oral mucosa. The aims of this study were (1) to assess the presence of gene amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2) to evaluate the possibility of using these alterations as prognostic markers. c-Myc and HER2 genes were quantified by means of real-time PCR (qPCR), and p14 and p16 methylation status was determined by methylation-specific PCR (MSP PCR). All tissues examined exhibited molecular alterations in various proportions. Tumour tissues, as expected, showed the highest prevalence of alterations, while oral mucosa showed the lowest. Multiple alterations (co-alterations) in tumours and tumour margins were significantly more frequent than in unaffected oral mucosa (P  lt  0.001 and P = 0.027, respectively). HER2 amplification in margin tissue (P  lt  0.001) and swabs (P = 0.013), as well as the existence of three co-alterations in margins (P = 0.001) and macroscopically unaffected oral mucosa (P  lt  0.001) were correlated with shorter disease-specific survival.
PB  - Churchill Livingstone, Edinburgh
T2  - International Journal of Oral & Maxillofacial Surgery
T1  - Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer
VL  - 47
IS  - 8
SP  - 976
EP  - 982
DO  - 10.1016/j.ijom.2018.01.020
ER  - 

@article{
author = "Eljabo, Najib and Nikolić, Nadja and Čarkić, Jelena and Jelovac, Drago and Lazarević, M. and Tanić, Nasta and Milašin, Jelena",
year = "2018",
abstract = "Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a high rate of recurrence and metastasis, which could be explained by the presence of molecular alterations in seemingly normal tumour margins and the entire oral mucosa. The aims of this study were (1) to assess the presence of gene amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2) to evaluate the possibility of using these alterations as prognostic markers. c-Myc and HER2 genes were quantified by means of real-time PCR (qPCR), and p14 and p16 methylation status was determined by methylation-specific PCR (MSP PCR). All tissues examined exhibited molecular alterations in various proportions. Tumour tissues, as expected, showed the highest prevalence of alterations, while oral mucosa showed the lowest. Multiple alterations (co-alterations) in tumours and tumour margins were significantly more frequent than in unaffected oral mucosa (P  lt  0.001 and P = 0.027, respectively). HER2 amplification in margin tissue (P  lt  0.001) and swabs (P = 0.013), as well as the existence of three co-alterations in margins (P = 0.001) and macroscopically unaffected oral mucosa (P  lt  0.001) were correlated with shorter disease-specific survival.",
publisher = "Churchill Livingstone, Edinburgh",
journal = "International Journal of Oral & Maxillofacial Surgery",
title = "Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer",
volume = "47",
number = "8",
pages = "976-982",
doi = "10.1016/j.ijom.2018.01.020"
}

Eljabo, N., Nikolić, N., Čarkić, J., Jelovac, D., Lazarević, M., Tanić, N.,& Milašin, J.. (2018). Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer. in International Journal of Oral & Maxillofacial Surgery
Churchill Livingstone, Edinburgh., 47(8), 976-982.
https://doi.org/10.1016/j.ijom.2018.01.020

Eljabo N, Nikolić N, Čarkić J, Jelovac D, Lazarević M, Tanić N, Milašin J. Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer. in International Journal of Oral & Maxillofacial Surgery. 2018;47(8):976-982.
doi:10.1016/j.ijom.2018.01.020 .

Eljabo, Najib, Nikolić, Nadja, Čarkić, Jelena, Jelovac, Drago, Lazarević, M., Tanić, Nasta, Milašin, Jelena, "Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer" in International Journal of Oral & Maxillofacial Surgery, 47, no. 8 (2018):976-982,
https://doi.org/10.1016/j.ijom.2018.01.020 . .

TY  - JOUR
AU  - Nikolić, Nadja
AU  - Čarkić, Jelena
AU  - Ilic-Dimitrijević, Ivana
AU  - Eljabo, Najib
AU  - Radunović, Milena
AU  - Aničić, Boban
AU  - Tanić, Nasta
AU  - Falk, Markus
AU  - Milašin, Jelena
PY  - 2018
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2317
AB  - Objective. To investigate the prevalence of p16(INK4) (a), p14(ARF), tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. Study design. DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing. Results. The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P  lt  .001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P  lt  .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively). Conclusions. Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters.
PB  - Elsevier Science Inc, New York
T2  - Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology
T1  - P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population
VL  - 125
IS  - 1
SP  - 52
EP  - 58
DO  - 10.1016/j.oooo.2017.09.013
ER  - 

@article{
author = "Nikolić, Nadja and Čarkić, Jelena and Ilic-Dimitrijević, Ivana and Eljabo, Najib and Radunović, Milena and Aničić, Boban and Tanić, Nasta and Falk, Markus and Milašin, Jelena",
year = "2018",
abstract = "Objective. To investigate the prevalence of p16(INK4) (a), p14(ARF), tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. Study design. DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing. Results. The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P  lt  .001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P  lt  .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively). Conclusions. Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters.",
publisher = "Elsevier Science Inc, New York",
journal = "Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology",
title = "P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population",
volume = "125",
number = "1",
pages = "52-58",
doi = "10.1016/j.oooo.2017.09.013"
}

Nikolić, N., Čarkić, J., Ilic-Dimitrijević, I., Eljabo, N., Radunović, M., Aničić, B., Tanić, N., Falk, M.,& Milašin, J.. (2018). P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population. in Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology
Elsevier Science Inc, New York., 125(1), 52-58.
https://doi.org/10.1016/j.oooo.2017.09.013

Nikolić N, Čarkić J, Ilic-Dimitrijević I, Eljabo N, Radunović M, Aničić B, Tanić N, Falk M, Milašin J. P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population. in Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology. 2018;125(1):52-58.
doi:10.1016/j.oooo.2017.09.013 .

Nikolić, Nadja, Čarkić, Jelena, Ilic-Dimitrijević, Ivana, Eljabo, Najib, Radunović, Milena, Aničić, Boban, Tanić, Nasta, Falk, Markus, Milašin, Jelena, "P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population" in Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, 125, no. 1 (2018):52-58,
https://doi.org/10.1016/j.oooo.2017.09.013 . .

TY  - JOUR
AU  - Nikolić, Nadja
AU  - Aničić, Boban
AU  - Čarkić, Jelena
AU  - Simonović, Jelena
AU  - Toljić, Boško
AU  - Tanić, Nasta
AU  - Tepavčević, Zvezdana
AU  - Vukadinović, Miroslav
AU  - Konstantinović, Vitomir
AU  - Milašin, Jelena
PY  - 2015
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2019
AB  - Objectives: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. Materials and Methods: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. Results: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P = 0.00), and significantly decreased in comparison to the carcinoma group (P = 0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P = 0.044 and P = 0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P = 0.013). Conclusion: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and Pl4(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Archives of Oral Biology
T1  - High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors
VL  - 60
IS  - 11
SP  - 1662
EP  - 1666
DO  - 10.1016/j.archoralbio.2015.08.011
ER  - 

@article{
author = "Nikolić, Nadja and Aničić, Boban and Čarkić, Jelena and Simonović, Jelena and Toljić, Boško and Tanić, Nasta and Tepavčević, Zvezdana and Vukadinović, Miroslav and Konstantinović, Vitomir and Milašin, Jelena",
year = "2015",
abstract = "Objectives: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. Materials and Methods: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. Results: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P = 0.00), and significantly decreased in comparison to the carcinoma group (P = 0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P = 0.044 and P = 0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P = 0.013). Conclusion: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and Pl4(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Archives of Oral Biology",
title = "High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors",
volume = "60",
number = "11",
pages = "1662-1666",
doi = "10.1016/j.archoralbio.2015.08.011"
}

Nikolić, N., Aničić, B., Čarkić, J., Simonović, J., Toljić, B., Tanić, N., Tepavčević, Z., Vukadinović, M., Konstantinović, V.,& Milašin, J.. (2015). High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors. in Archives of Oral Biology
Pergamon-Elsevier Science Ltd, Oxford., 60(11), 1662-1666.
https://doi.org/10.1016/j.archoralbio.2015.08.011

Nikolić N, Aničić B, Čarkić J, Simonović J, Toljić B, Tanić N, Tepavčević Z, Vukadinović M, Konstantinović V, Milašin J. High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors. in Archives of Oral Biology. 2015;60(11):1662-1666.
doi:10.1016/j.archoralbio.2015.08.011 .

Nikolić, Nadja, Aničić, Boban, Čarkić, Jelena, Simonović, Jelena, Toljić, Boško, Tanić, Nasta, Tepavčević, Zvezdana, Vukadinović, Miroslav, Konstantinović, Vitomir, Milašin, Jelena, "High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors" in Archives of Oral Biology, 60, no. 11 (2015):1662-1666,
https://doi.org/10.1016/j.archoralbio.2015.08.011 . .

TY  - JOUR
AU  - Roganović, Jelena
AU  - Đukić, Ljiljana
AU  - Kršljak, Elena
AU  - Tanić, Nasta
AU  - Stojić, Dragica
PY  - 2015
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1963
AB  - ObjectivesThe influence of experimental diabetes (alloxan, 100mgkg(-1)) was studied on rabbit parotid gland function. Material and MethodsCarbachol-induced parotid secretion in vivo, and in vitro quantification of inducible nitric oxide synthase (iNOS) mRNA expression, by real-time RT-PCR, and activity of superoxide dismutase (SOD) and total antioxidant capacity (TAC) in commercial colorimetric assays were measured in parotid glands of non-diabetic and diabetic rabbits. ResultsCarbachol-induced dose-dependent increase in parotid secretion significantly reduced in diabetic rabbits. Functional studies in the presence of muscarinic receptor and nitric oxide synthase (NOS) antagonists revealed that in M-3 receptor-mediated carbachol secretion, nitric oxide, deriving mainly from neuronal NOS (nNOS) in control, and iNOS in diabetic rabbits, was involved. Also, upregulation of iNOS mRNA expression and enhanced SOD activity and TAC were detected in diabetic glands. ConclusionsOur data suggest that decreased M-3 receptor-mediated parotid secretion in diabetic rabbits appears to be due to alterations in NO signaling, mainly due to iNOS induction, accompanied by elevated antioxidant response.
PB  - Wiley, Hoboken
T2  - Oral Diseases
T1  - Reduced muscarinic parotid secretion is underlain by impaired NO signaling in diabetic rabbits
VL  - 21
IS  - 5
SP  - 634
EP  - 640
DO  - 10.1111/odi.12327
ER  - 

@article{
author = "Roganović, Jelena and Đukić, Ljiljana and Kršljak, Elena and Tanić, Nasta and Stojić, Dragica",
year = "2015",
abstract = "ObjectivesThe influence of experimental diabetes (alloxan, 100mgkg(-1)) was studied on rabbit parotid gland function. Material and MethodsCarbachol-induced parotid secretion in vivo, and in vitro quantification of inducible nitric oxide synthase (iNOS) mRNA expression, by real-time RT-PCR, and activity of superoxide dismutase (SOD) and total antioxidant capacity (TAC) in commercial colorimetric assays were measured in parotid glands of non-diabetic and diabetic rabbits. ResultsCarbachol-induced dose-dependent increase in parotid secretion significantly reduced in diabetic rabbits. Functional studies in the presence of muscarinic receptor and nitric oxide synthase (NOS) antagonists revealed that in M-3 receptor-mediated carbachol secretion, nitric oxide, deriving mainly from neuronal NOS (nNOS) in control, and iNOS in diabetic rabbits, was involved. Also, upregulation of iNOS mRNA expression and enhanced SOD activity and TAC were detected in diabetic glands. ConclusionsOur data suggest that decreased M-3 receptor-mediated parotid secretion in diabetic rabbits appears to be due to alterations in NO signaling, mainly due to iNOS induction, accompanied by elevated antioxidant response.",
publisher = "Wiley, Hoboken",
journal = "Oral Diseases",
title = "Reduced muscarinic parotid secretion is underlain by impaired NO signaling in diabetic rabbits",
volume = "21",
number = "5",
pages = "634-640",
doi = "10.1111/odi.12327"
}

Roganović, J., Đukić, L., Kršljak, E., Tanić, N.,& Stojić, D.. (2015). Reduced muscarinic parotid secretion is underlain by impaired NO signaling in diabetic rabbits. in Oral Diseases
Wiley, Hoboken., 21(5), 634-640.
https://doi.org/10.1111/odi.12327

Roganović J, Đukić L, Kršljak E, Tanić N, Stojić D. Reduced muscarinic parotid secretion is underlain by impaired NO signaling in diabetic rabbits. in Oral Diseases. 2015;21(5):634-640.
doi:10.1111/odi.12327 .

Roganović, Jelena, Đukić, Ljiljana, Kršljak, Elena, Tanić, Nasta, Stojić, Dragica, "Reduced muscarinic parotid secretion is underlain by impaired NO signaling in diabetic rabbits" in Oral Diseases, 21, no. 5 (2015):634-640,
https://doi.org/10.1111/odi.12327 . .

TY  - JOUR
AU  - Tanić, Nasta
AU  - Milašin, Jelena
AU  - Dramićanin, Tatjana
AU  - Bošković, Maja
AU  - Vukadinović, Miroslav
AU  - Milošević, Verica
AU  - Tanić, Nikola
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1780
AB  - Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. Therefore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycDI in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycDI and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours.
AB  - Uvod: Skvamocelularni karcinomi glave i vrata (HNSCC) uključujući i skvamocelularni karcinom usne duplje (OSCC) ubrajaju se u šest najčešćih tipova humanih maligniteta. Uprkos značajnim napredcima u hirurškom i terapijskom tretmanu, stopa petogodišnjeg preživljavanja kod ovog tipa maligniteta nije značajnije popravljena. Upravo zato, definisanje pouzdanih molekularnih markera progresije kod OSSC predstavlja apsolutni prioritetet. Metode: Amplifikacioni status c-myc, cycD1 i EGFR gena određen je pomoću eseja za detekciju broja genskih kopija, aktivacija H-ras onkogena i inaktivacija TP53 tumor supresora određena je PCR-SSCP mutacionom analizom, a hipermetilacija promotora p16 i MGMT gena je ispitana metil specifičnim PCR-om (MSP). Rezultati: Amplifikacija c-myc onkogena detektovana je kod 56,7%, cycD1 onkogena kod 20%, a EGFR onkogena kod 16,7% analiziranih oralnih skvamocelularnih carcinoma. Istovremeno, mutaciona aktivacija H-ras onkogena detektovana je kod 33,3% ispitanih uzoraka. Amplifikovani c-myc, statistički značajno korelira sa gradusom 2 OSCC. Posebno intrigantan je bio nalaz po kom se onkogene aktivacije u EGFR i H-ras genu međusobno isključuju. Hipermetilacija promotora p16 gena detektovana je kod 30%, a MGMT kod 13,3% analiziranih uzoraka. Ko-alteracije cycDI i p16 gena nisu zapažene ni u jednom od analiziranih uzoraka. Inaktivacija TP53 gena detektovana je kod 56,7% uzoraka i utvrđeno je da statistički značajno korelira sa gradusom 2 i statusom 2 OSCC. Pored ovoga, utvrđeno je da statistički značajan broj uzoraka gradusa 2, sa aktiviranim TP53 genom ima istovremeno aktiviran i c-myc onkogen. Zaključak: TP53, najčešće mutirani gen u oralnim karcinomima, ostaje za sada i najpouzdaniji marker progresije kod OSCC. Obzirom na detektovani sinergizam između TP53 i c-myc gena, možemo reći da su istovremene promene u ova dva gena još pouzdaniji pokazatelj progresije OSSC iz gradusa 1 u gradus 2.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - TP53 and c-myc Co-alterations: A hallmark of oral cancer progression
T1  - Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma
VL  - 32
IS  - 4
SP  - 380
EP  - 388
DO  - 10.2478/jomb-2014-0009
ER  - 

@article{
author = "Tanić, Nasta and Milašin, Jelena and Dramićanin, Tatjana and Bošković, Maja and Vukadinović, Miroslav and Milošević, Verica and Tanić, Nikola",
year = "2013",
abstract = "Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. Therefore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycDI in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycDI and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours., Uvod: Skvamocelularni karcinomi glave i vrata (HNSCC) uključujući i skvamocelularni karcinom usne duplje (OSCC) ubrajaju se u šest najčešćih tipova humanih maligniteta. Uprkos značajnim napredcima u hirurškom i terapijskom tretmanu, stopa petogodišnjeg preživljavanja kod ovog tipa maligniteta nije značajnije popravljena. Upravo zato, definisanje pouzdanih molekularnih markera progresije kod OSSC predstavlja apsolutni prioritetet. Metode: Amplifikacioni status c-myc, cycD1 i EGFR gena određen je pomoću eseja za detekciju broja genskih kopija, aktivacija H-ras onkogena i inaktivacija TP53 tumor supresora određena je PCR-SSCP mutacionom analizom, a hipermetilacija promotora p16 i MGMT gena je ispitana metil specifičnim PCR-om (MSP). Rezultati: Amplifikacija c-myc onkogena detektovana je kod 56,7%, cycD1 onkogena kod 20%, a EGFR onkogena kod 16,7% analiziranih oralnih skvamocelularnih carcinoma. Istovremeno, mutaciona aktivacija H-ras onkogena detektovana je kod 33,3% ispitanih uzoraka. Amplifikovani c-myc, statistički značajno korelira sa gradusom 2 OSCC. Posebno intrigantan je bio nalaz po kom se onkogene aktivacije u EGFR i H-ras genu međusobno isključuju. Hipermetilacija promotora p16 gena detektovana je kod 30%, a MGMT kod 13,3% analiziranih uzoraka. Ko-alteracije cycDI i p16 gena nisu zapažene ni u jednom od analiziranih uzoraka. Inaktivacija TP53 gena detektovana je kod 56,7% uzoraka i utvrđeno je da statistički značajno korelira sa gradusom 2 i statusom 2 OSCC. Pored ovoga, utvrđeno je da statistički značajan broj uzoraka gradusa 2, sa aktiviranim TP53 genom ima istovremeno aktiviran i c-myc onkogen. Zaključak: TP53, najčešće mutirani gen u oralnim karcinomima, ostaje za sada i najpouzdaniji marker progresije kod OSCC. Obzirom na detektovani sinergizam između TP53 i c-myc gena, možemo reći da su istovremene promene u ova dva gena još pouzdaniji pokazatelj progresije OSSC iz gradusa 1 u gradus 2.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "TP53 and c-myc Co-alterations: A hallmark of oral cancer progression, Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma",
volume = "32",
number = "4",
pages = "380-388",
doi = "10.2478/jomb-2014-0009"
}

Tanić, N., Milašin, J., Dramićanin, T., Bošković, M., Vukadinović, M., Milošević, V.,& Tanić, N.. (2013). TP53 and c-myc Co-alterations: A hallmark of oral cancer progression. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 32(4), 380-388.
https://doi.org/10.2478/jomb-2014-0009

Tanić N, Milašin J, Dramićanin T, Bošković M, Vukadinović M, Milošević V, Tanić N. TP53 and c-myc Co-alterations: A hallmark of oral cancer progression. in Journal of Medical Biochemistry. 2013;32(4):380-388.
doi:10.2478/jomb-2014-0009 .

Tanić, Nasta, Milašin, Jelena, Dramićanin, Tatjana, Bošković, Maja, Vukadinović, Miroslav, Milošević, Verica, Tanić, Nikola, "TP53 and c-myc Co-alterations: A hallmark of oral cancer progression" in Journal of Medical Biochemistry, 32, no. 4 (2013):380-388,
https://doi.org/10.2478/jomb-2014-0009 . .

TY  - JOUR
AU  - Roganović, Jelena
AU  - Radenković, Miroslav
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Petrović, Nina
AU  - Stojić, Dragica
PY  - 2011
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1625
AB  - The aim of this study was to assess the effect of type 1 diabetes mellitus (induced by a single intravenous injection of 100 mg kg(-1) of alloxan) on acetylcholine (ACh)-induced relaxation in isolated rabbit parotid gland feeding artery. Isometric force measurements and quantification of inducible nitric oxide synthase (iNOS) mRNA by real-time RT-PCR were made in parotid artery rings from diabetic and control rabbits. Acetylcholine induced concentration- and endothelium-dependent vasorelaxation that was significantly decreased in parotid artery rings from diabetic rabbits. Schild analysis of the ACh vasorelaxant effect, in the presence of selective muscarinic receptor antagonists, revealed involvement of the M-3 receptor subtype in parotid artery rings from both control and diabetic rabbits, with no change in antagonist affinity constants. The inhibitory effects of indomethacin, a non-selective inhibitor of cyclooxygenase, and of high potassium, an inhibitor of hyperpolarization, on ACh vasorelaxation were increased. The effect of N-G-nitro-L-arginine, a non-selective inhibitor of NOS, was decreased in diabetes. S-methylisothiourea, a selective inhibitor of iNOS, significantly reduced ACh vasorelaxation only in parotid artery rings from diabetic rabbits. Also, up-regulation of iNOS mRNA expression was detected in parotid artery rings from diabetic rabbits. These results suggest that in parotid artery rings from diabetic rabbits, impaired endothelium-dependent vasorelaxation to ACh appears to be caused by the loss of a nitric oxide-mediated component and increased iNOS expression, and is unlikely to be caused by a change at the M-3 receptor level.
PB  - Wiley, Hoboken
T2  - European Journal of Oral Sciences
T1  - Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit
VL  - 119
IS  - 5
SP  - 352
EP  - 360
DO  - 10.1111/j.1600-0722.2011.00851.x
ER  - 

@article{
author = "Roganović, Jelena and Radenković, Miroslav and Tanić, Nikola and Tanić, Nasta and Petrović, Nina and Stojić, Dragica",
year = "2011",
abstract = "The aim of this study was to assess the effect of type 1 diabetes mellitus (induced by a single intravenous injection of 100 mg kg(-1) of alloxan) on acetylcholine (ACh)-induced relaxation in isolated rabbit parotid gland feeding artery. Isometric force measurements and quantification of inducible nitric oxide synthase (iNOS) mRNA by real-time RT-PCR were made in parotid artery rings from diabetic and control rabbits. Acetylcholine induced concentration- and endothelium-dependent vasorelaxation that was significantly decreased in parotid artery rings from diabetic rabbits. Schild analysis of the ACh vasorelaxant effect, in the presence of selective muscarinic receptor antagonists, revealed involvement of the M-3 receptor subtype in parotid artery rings from both control and diabetic rabbits, with no change in antagonist affinity constants. The inhibitory effects of indomethacin, a non-selective inhibitor of cyclooxygenase, and of high potassium, an inhibitor of hyperpolarization, on ACh vasorelaxation were increased. The effect of N-G-nitro-L-arginine, a non-selective inhibitor of NOS, was decreased in diabetes. S-methylisothiourea, a selective inhibitor of iNOS, significantly reduced ACh vasorelaxation only in parotid artery rings from diabetic rabbits. Also, up-regulation of iNOS mRNA expression was detected in parotid artery rings from diabetic rabbits. These results suggest that in parotid artery rings from diabetic rabbits, impaired endothelium-dependent vasorelaxation to ACh appears to be caused by the loss of a nitric oxide-mediated component and increased iNOS expression, and is unlikely to be caused by a change at the M-3 receptor level.",
publisher = "Wiley, Hoboken",
journal = "European Journal of Oral Sciences",
title = "Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit",
volume = "119",
number = "5",
pages = "352-360",
doi = "10.1111/j.1600-0722.2011.00851.x"
}

Roganović, J., Radenković, M., Tanić, N., Tanić, N., Petrović, N.,& Stojić, D.. (2011). Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit. in European Journal of Oral Sciences
Wiley, Hoboken., 119(5), 352-360.
https://doi.org/10.1111/j.1600-0722.2011.00851.x

Roganović J, Radenković M, Tanić N, Tanić N, Petrović N, Stojić D. Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit. in European Journal of Oral Sciences. 2011;119(5):352-360.
doi:10.1111/j.1600-0722.2011.00851.x .

Roganović, Jelena, Radenković, Miroslav, Tanić, Nikola, Tanić, Nasta, Petrović, Nina, Stojić, Dragica, "Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit" in European Journal of Oral Sciences, 119, no. 5 (2011):352-360,
https://doi.org/10.1111/j.1600-0722.2011.00851.x . .

TY  - JOUR
AU  - Tanić, Nasta
AU  - Tanić, Nikola
AU  - Milašin, Jelena
AU  - Vukadinović, Miroslav
AU  - Dimitrijević, Bogomir
PY  - 2009
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1483
AB  - Leukoplakias, clinically identifiable premalignant lesions, often precede oral squamous cell carcinoma (OSCC). Identification of leukoplakias that have the potential for transformation to malignancy is a key clinical problem. The aim of this study was to assess genomic instability, and to detect tumor-specific genomic alterations, in leukoplakias. Genomic instability was analyzed by comparing the DNA fingerprints of 32 leukoplakias with those of paired normal tissue. In addition, the mutational status of the p53 gene was analyzed using polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) and polymerase chain reaction-heteroduplex DNA (PCR-HET), and the mutations were subsequently confirmed by DNA sequencing. Moderate-to-significant genomic instability was detected in all leukoplakias analysed. Nine unique amplicons, present in leukoplakias but not in normal tissue, were retrieved and successfully characterized. The p53 gene was mutated in 40.6% of patients. Four patients with moderate instability and mutated p53 developed OSCC. The data obtained in this study support and concretize the thesis that premalignant lesions possess many of the alterations found in cancer before the development of a malignant phenotype. Inactivation or mutation of the p53 tumor-suppressor might be an early event contributing to genomic instability and increasing the risk of malignant transformation.
PB  - Wiley, Hoboken
T2  - European Journal of Oral Sciences
T1  - Genomic instability and tumor-specific DNA alterations in oral leukoplakias
VL  - 117
IS  - 3
SP  - 231
EP  - 237
DO  - 10.1111/j.1600-0722.2009.00624.x
ER  - 

@article{
author = "Tanić, Nasta and Tanić, Nikola and Milašin, Jelena and Vukadinović, Miroslav and Dimitrijević, Bogomir",
year = "2009",
abstract = "Leukoplakias, clinically identifiable premalignant lesions, often precede oral squamous cell carcinoma (OSCC). Identification of leukoplakias that have the potential for transformation to malignancy is a key clinical problem. The aim of this study was to assess genomic instability, and to detect tumor-specific genomic alterations, in leukoplakias. Genomic instability was analyzed by comparing the DNA fingerprints of 32 leukoplakias with those of paired normal tissue. In addition, the mutational status of the p53 gene was analyzed using polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) and polymerase chain reaction-heteroduplex DNA (PCR-HET), and the mutations were subsequently confirmed by DNA sequencing. Moderate-to-significant genomic instability was detected in all leukoplakias analysed. Nine unique amplicons, present in leukoplakias but not in normal tissue, were retrieved and successfully characterized. The p53 gene was mutated in 40.6% of patients. Four patients with moderate instability and mutated p53 developed OSCC. The data obtained in this study support and concretize the thesis that premalignant lesions possess many of the alterations found in cancer before the development of a malignant phenotype. Inactivation or mutation of the p53 tumor-suppressor might be an early event contributing to genomic instability and increasing the risk of malignant transformation.",
publisher = "Wiley, Hoboken",
journal = "European Journal of Oral Sciences",
title = "Genomic instability and tumor-specific DNA alterations in oral leukoplakias",
volume = "117",
number = "3",
pages = "231-237",
doi = "10.1111/j.1600-0722.2009.00624.x"
}

Tanić, N., Tanić, N., Milašin, J., Vukadinović, M.,& Dimitrijević, B.. (2009). Genomic instability and tumor-specific DNA alterations in oral leukoplakias. in European Journal of Oral Sciences
Wiley, Hoboken., 117(3), 231-237.
https://doi.org/10.1111/j.1600-0722.2009.00624.x

Tanić N, Tanić N, Milašin J, Vukadinović M, Dimitrijević B. Genomic instability and tumor-specific DNA alterations in oral leukoplakias. in European Journal of Oral Sciences. 2009;117(3):231-237.
doi:10.1111/j.1600-0722.2009.00624.x .

Tanić, Nasta, Tanić, Nikola, Milašin, Jelena, Vukadinović, Miroslav, Dimitrijević, Bogomir, "Genomic instability and tumor-specific DNA alterations in oral leukoplakias" in European Journal of Oral Sciences, 117, no. 3 (2009):231-237,
https://doi.org/10.1111/j.1600-0722.2009.00624.x . .