TY  - JOUR
AU  - Živadinović, Milka
AU  - Andrić, Miroslav
AU  - Milošević, Verica
AU  - Manojlović-Stojanoski, Milica
AU  - Prokić, Branislav
AU  - Prokić, Bogomir
AU  - Dimić, Aleksandar
AU  - Ćalasan, Dejan
AU  - Brković, Božidar
PY  - 2016
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2082
AB  - Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm), which were grafted with autogenous bone and β-tricalcium phosphate (n = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p  lt  0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53%) compared with β-tricalcium phosphate (30%), (p  lt  0.030) and control (7%), (p  lt  0.000) groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p  lt  0.008). Conclusion. In the present study on the rabbit grafting model with induced diabetes mellitus type I, the effective bone regeneration of critical bone defects was obtained using autogenous bone graft.
AB  - Uvod/Cilj. Mehanizam otežanog zarastanja tkiva kod dijabetesa melitusa zasnovan je na različitim promenama funkcije na tkivnom i ćelijskom nivou, usled prisutnih mikro- i makrovaskularnih promena. Kao hronično metaboličko oboljenje sa vaskularnim komplikacijama, dijabetes melitus zahvata i proces koštane regeneracije. Terapijski postupci u okviru regeneracije kosti obuhvataju primenu autotransplantata sa oseoinduktivnim delovanjem i sintetskih osteokonduktivnih materijala, kao što je i β-trikalcijum fosfat. Cilj ovog rada bio je da se ispita kvantitet i kvalitet novoformiranog koštanog tkiva posle korišćenja autotransplantata kosti i β-trikalcijum fosfata, na modelu kritičnog defekta kalvarije kunića sa eksperimentalno izazvanim dijabetesom melitusom tipa I. Metode. U ovo istraživanje bilo je uključeno 8 kunića (soj Činičila), starosti 4 meseca, kod kojih je dijabetes melitus tipa I bio izazvan aloksanom. Kod svih životinja hirurški je urađen defekt kritičneveličine na kosti kalvarije (prečnika 12 mm), koji je popunjen autotransplantatom kosti i β-trikalcijum fosfatom (n = 4) ili je ostavljen da spontano zarasta kao kontrolni defekt (n = 4). Posle 4 nedelje, sve životinje su bile žrtvovane i koštani uzorci uzeti za histološku i histomorfometrijsku analizu. Pored deskriptivne histološke analize, urađena je i kvantitativna analiza novoformirane kosti, vezivnog tkiva i materijala za koštanu regeneraciju. Statistička analiza vršena je primenom Friedmanovog testa i post hock Vilkoksonovog neparametrijskog testa sa stepenom značajnosti od p  lt  0,05. Rezultati. Histološka analiza uzoraka kosti pokazala je prisustvo novoformirane kosti na periferiji defekta, dok je u centralom delu bilo prisutno vezivno tkivo, nezrelo koštano tkivo i dobro sjedinjeni neresorbovani materijal za regeneraciju kosti. Kontrolni uzorci nisu pokazali koštano zarastanje defekata. Značajno više novoformirane kosti bilo je prisutno u defektima regenerisanim autotransplantatom (53%) u poređenju sa kontrolnim defektima (7%), (p  lt  0,000) i defektima popunjenim β-trikalcijum fosfatom (30%), (p  lt  0,030). Takođe, značajna razlika uočena je i između grupe sa β-trikalcijum fosfatom i kontrolnim koštanim defektom (p  lt  0,008). Zaključak. Primena autotransplantata kosti značajno povećava uspešnost regeneracije kritičnih defekata kosti kalvarije kunića sa dijabetesom melitusom tipa I.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits
T1  - Histomorfometrijska analiza regeneracije kosti kod kunića sa dijabetesom melitusom posle primene autotransplantata kosti i beta-trikalcijum fosfata
VL  - 73
IS  - 12
SP  - 1132
EP  - 1138
DO  - 10.2298/VSP151125013Z
ER  - 

@article{
author = "Živadinović, Milka and Andrić, Miroslav and Milošević, Verica and Manojlović-Stojanoski, Milica and Prokić, Branislav and Prokić, Bogomir and Dimić, Aleksandar and Ćalasan, Dejan and Brković, Božidar",
year = "2016",
abstract = "Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm), which were grafted with autogenous bone and β-tricalcium phosphate (n = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p  lt  0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53%) compared with β-tricalcium phosphate (30%), (p  lt  0.030) and control (7%), (p  lt  0.000) groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p  lt  0.008). Conclusion. In the present study on the rabbit grafting model with induced diabetes mellitus type I, the effective bone regeneration of critical bone defects was obtained using autogenous bone graft., Uvod/Cilj. Mehanizam otežanog zarastanja tkiva kod dijabetesa melitusa zasnovan je na različitim promenama funkcije na tkivnom i ćelijskom nivou, usled prisutnih mikro- i makrovaskularnih promena. Kao hronično metaboličko oboljenje sa vaskularnim komplikacijama, dijabetes melitus zahvata i proces koštane regeneracije. Terapijski postupci u okviru regeneracije kosti obuhvataju primenu autotransplantata sa oseoinduktivnim delovanjem i sintetskih osteokonduktivnih materijala, kao što je i β-trikalcijum fosfat. Cilj ovog rada bio je da se ispita kvantitet i kvalitet novoformiranog koštanog tkiva posle korišćenja autotransplantata kosti i β-trikalcijum fosfata, na modelu kritičnog defekta kalvarije kunića sa eksperimentalno izazvanim dijabetesom melitusom tipa I. Metode. U ovo istraživanje bilo je uključeno 8 kunića (soj Činičila), starosti 4 meseca, kod kojih je dijabetes melitus tipa I bio izazvan aloksanom. Kod svih životinja hirurški je urađen defekt kritičneveličine na kosti kalvarije (prečnika 12 mm), koji je popunjen autotransplantatom kosti i β-trikalcijum fosfatom (n = 4) ili je ostavljen da spontano zarasta kao kontrolni defekt (n = 4). Posle 4 nedelje, sve životinje su bile žrtvovane i koštani uzorci uzeti za histološku i histomorfometrijsku analizu. Pored deskriptivne histološke analize, urađena je i kvantitativna analiza novoformirane kosti, vezivnog tkiva i materijala za koštanu regeneraciju. Statistička analiza vršena je primenom Friedmanovog testa i post hock Vilkoksonovog neparametrijskog testa sa stepenom značajnosti od p  lt  0,05. Rezultati. Histološka analiza uzoraka kosti pokazala je prisustvo novoformirane kosti na periferiji defekta, dok je u centralom delu bilo prisutno vezivno tkivo, nezrelo koštano tkivo i dobro sjedinjeni neresorbovani materijal za regeneraciju kosti. Kontrolni uzorci nisu pokazali koštano zarastanje defekata. Značajno više novoformirane kosti bilo je prisutno u defektima regenerisanim autotransplantatom (53%) u poređenju sa kontrolnim defektima (7%), (p  lt  0,000) i defektima popunjenim β-trikalcijum fosfatom (30%), (p  lt  0,030). Takođe, značajna razlika uočena je i između grupe sa β-trikalcijum fosfatom i kontrolnim koštanim defektom (p  lt  0,008). Zaključak. Primena autotransplantata kosti značajno povećava uspešnost regeneracije kritičnih defekata kosti kalvarije kunića sa dijabetesom melitusom tipa I.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits, Histomorfometrijska analiza regeneracije kosti kod kunića sa dijabetesom melitusom posle primene autotransplantata kosti i beta-trikalcijum fosfata",
volume = "73",
number = "12",
pages = "1132-1138",
doi = "10.2298/VSP151125013Z"
}

Živadinović, M., Andrić, M., Milošević, V., Manojlović-Stojanoski, M., Prokić, B., Prokić, B., Dimić, A., Ćalasan, D.,& Brković, B.. (2016). Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 73(12), 1132-1138.
https://doi.org/10.2298/VSP151125013Z

Živadinović M, Andrić M, Milošević V, Manojlović-Stojanoski M, Prokić B, Prokić B, Dimić A, Ćalasan D, Brković B. Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits. in Vojnosanitetski pregled. 2016;73(12):1132-1138.
doi:10.2298/VSP151125013Z .

Živadinović, Milka, Andrić, Miroslav, Milošević, Verica, Manojlović-Stojanoski, Milica, Prokić, Branislav, Prokić, Bogomir, Dimić, Aleksandar, Ćalasan, Dejan, Brković, Božidar, "Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits" in Vojnosanitetski pregled, 73, no. 12 (2016):1132-1138,
https://doi.org/10.2298/VSP151125013Z . .

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 . .