D J | University of Belgrade, School of Medicine (original) (raw)

Papers by D J

Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial ear... more Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial early events in carcinogenesis is the induction of genomic instability and mutator phenotype. We investigated genomic instability in 30 patients with non-small-cell lung cancer (NSCLC) by comparing DNA fingerprints of paired tumor and normal tissues using arbitrarily primed polymerase chain reaction (AP-PCR). Selected 21 DNA bands with altered mobility were isolated from polyacrylamide gels, cloned and sequenced. Obtained sequences were submitted to homology search in GenBank database which revealed the following genes: TSPAN14, CDH12, RDH10, CYP4Z1, KIR, E2F4, PHACTR3, PHF20, PRAME family member and SLC2A13. Following the identification of these genes we examined their relation to the clinicopathological parameters and survival of the patients. Our study revealed that genetic alterations of TSPAN14, SLC2A13 and PHF20 appeared prevalently in tumors of grade 1, stage I suggesting that structural changes of these genes could play a role in NSCLC promotion. Contrary to this CYP4Z1, KIR and RDH10 were prevalently mutated in tumors of grade 3, stage III suggesting that they could play a role in NSCLC progression. E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in NSCLC geneses. In conclusion, our study revealed altered genes previously not described in regard to this type of cancer.

Srpski arhiv za celokupno lekarstvo, 2008

Uvod U Sr bi ji ima do sta oso ba obo le lih od pne u mo kok ne pne u mo ni je. Kod oso ba sta ri... more Uvod U Sr bi ji ima do sta oso ba obo le lih od pne u mo kok ne pne u mo ni je. Kod oso ba sta ri jih od 65 go di na, imu no kompro mi to va nih i bo le sni ka s ko mor bi di te ti ma kao što su hro nič na op struk tiv na bo lest plu ća i kon ge stiv na in sufi ci jen ci ja sr ca po sto ji naj ve ći ri zik za na sta nak pne u mo kok ne pne u mo ni je. Većina bo le sni ka se le či em pi rij ski, iako se če sto pred vi di či we ni ca da Strep to coc cus pne u mo ni ae mo že bi ti re zi sten tan na iza bra ne an ti bi ot ske le kove. Tro ško vi za bol nič ko i am bu lant no le če we bo le sni ka s ovim obo qe wem ve o ma su vi so ki. Vak ci na ci ja ri zič nih bo le sni ka od raz vo ja bo le sti iza zva nih sa Strep to coc cus pne u mo ni ae u Sr bi ji vr ši se pri me nom pne u mo kok ne po li saha rid ne vak ci ne pre ma kli nič kim in di ka ci ja ma. Ta čan broj vak ci ni sa nih i uku pan broj re gi stro va nih bo le sni ka i da qe ni je po znat, ali je si gur no da je neo prav da no ma li. Ciq rada Ciq ra da je bio da se to kom jed no go di šweg pe ri o da is pi ta ju broj i osnov ne od li ke oso ba bol nič ki leče nih od pne u mo ni je, vr sta uzroč ni ka in fek ci je, pri me we ni an ti bi ot ski le ko vi, tra ja we i tro ško vi bol nič kog leče wa u Insti tu tu za pluć ne bo le sti i tu ber ku lo zu Kliničkog cen tra Sr bi je u Be o gra du. Metod rada Re tro spek tiv no su ana li zi ra ni me di cin ski po da ci bo le sni ka le če nih od pne u mo ni je to kom 2006. godi ne u Insti tu tu za pluć ne bo le sti i tu ber ku lo zu Kliničkog cen tra Sr bi je u Be o gra du. Rezultati To kom po sma tra nog jed no go di šweg pe ri o da bol nič ki je le če no 290 bo le sni ka, od če ga je uzroč nik in fekci je po tvr đen kod 116 (40%). Bol nič ko le če we je u pro se ku tra ja lo 12 da na, a tro ško vi le če wa po bo le sni ku bi li su 32.031,74 di na ra (402,42 evra). Tro ško vi le če wa po bo le sni ku s op štom i in ten ziv nom ne gom bi li su 18.290,01 di nar (229,78 evra). Di stri bu tiv na ce na po je di nač ne vak ci ne "Pne u mo 23" u Sr bi ji bez po re za bi la je 746,90 di na ra (9,38 evra). Zakqučak Pne u mo kok na pne u mo ni ja je zna ča jan me di cin ski i eko nom ski pro blem za zdrav stve ni si stem Sr bi je. Prime na an tip ne u mo kok ne vak ci ne mo že bi ti ko ri sna u sma we wu ukup nih tro ško va le če wa od pne u mo kok ne in fek ci je.

Srpski arhiv za celokupno lekarstvo, 2003

1. In sti tut za kar di o va sku lar ne bo le sti, Kli niè ki cen tar Sr bi je, Be o grad; 2. In ... more 1. In sti tut za kar di o va sku lar ne bo le sti, Kli niè ki cen tar Sr bi je, Be o grad; 2. In sti tut za pluae ne bo le sti i tu ber ku lo zu, Kli niè ki cen tar Sr bi je, Be o grad KRATAK SADRŽAJ: Pri mar ni se mi no mi me di ja sti nu ma su ret ki i mo gu aee fa tal ni tu mo ri. Oni mo gu uzro ko va ti kompre si ju ili in va zi ju okol nih struk tu ra, ali da ti i udaqe ne me ta sta ze. Pri ka zan je re dak slu èaj me di ja sti nal nog se mi no ma ko ji je uzro ko vao di rekt nu in tra ka vi tar nu in va zi ju de sne pret ko mo re i pro ši rio se u le vu pret ko moru. Dva de set dvo go dišwi mla diae je ho spi ta li zo van zbog bo la na desnoj strani grudnog koša, kašqa, disp ne ja, febril no sti i oto ka de sne ru ke. Te go be su se ja vi le me sec da na pre ho spi ta li za ci je. Rend ge no gra fi jom grudi na ðe na je ve li ka ma sa u predwem me di ja sti nu mu de sno. Eho kar di o graf skim pre gle dom je ot kri ve na kom pre si ja de sne pret ko mo re tu mor skom ma som ko ja je isto vre me no in fil tri sa la wen zid. Takoðe su na ðe ni po li po id na ma sa u levoj pret ko mo ri u bli zi ni uš aea de snih pluae nih ve na i pe ri kard ni iz liv. Per ku ta nom bi op si jom je utvr ðe no da se ra di o se mi no mu. Pre ma do sa dašwim sa znawi ma, sli èan pri kaz ni je ob ja vqen u na šoj me di cin skoj li te ra tu ri. Kquè ne re èi: se mi nom, me di ja sti num.

Palliative & supportive care, Jan 2, 2015

Under conditions in which palliative care has not yet become part of clinical practice, the diffe... more Under conditions in which palliative care has not yet become part of clinical practice, the differences in palliative care needs between patients with cancer and other life-limiting diseases can yield knowledge that will be very valuable for future planning. The aim of our investigation was to compare health-related quality of life (HRQoL) for patients with end-stage chronic obstructive pulmonary disease (COPD) and those with non-small-cell lung cancer (NSCLC) in Belgrade, Serbia. We also evaluated the influence of demographic, socioeconomic, and clinical factors on HRQoL for both patient groups. This cross-sectional study included 100 NSCLC patients (stages IIIb and IV) and 100 patients with stage IV COPD. Measures included the SF-36 questionnaire, the EORTC QLQ-C30, the St. George's Respiratory Questionnaire, and the Beck Depression Inventory (BDI). Associations of demographic, socioeconomic, and clinical factors with QoL were examined using linear regression analyses. The COP...

American journal of respiratory and critical care medicine, Jan 6, 2015

To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene ... more To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1726 German sarcoidosis cases and 5482 controls were genotyped for 128,705 SNPs using the Illumina Immunochip for the screening step. The remaining 3955 cases, 7514 controls and 684 parents of affected offspring were used for validation and replication of 44 candidate and 2 established risk SNPs. Four novel susceptibility loci were identified with genome-wide significance in the European case control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1) and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA-region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA DPB...

Clinics in Chest Medicine, 2008

Sarcoidosis is an inflammatory granulomatous disease that is characterized by diverse organ syste... more Sarcoidosis is an inflammatory granulomatous disease that is characterized by diverse organ system manifestations, a variable clinical course, and a predilection for affecting relatively young adults worldwide. Abnormalities on chest radiographs are detected in 85% to 95% of patients who have sarcoidosis. Approximately 20% to 50% of patients who have sarcoidosis present with respiratory symptoms, including dyspnea, cough, chest pain, and tightness of the chest. The clinical course and manifestations of pulmonary sarcoidosis are protean: spontaneous remission occurs in approximately two thirds of patients; up to 30% of patients have chronic course of the lung disease, resulting in progressive, (sometimes life-threatening) loss of lung function. Morbidity that correlates to sarcoidosis occurs in 1% to 4% of patients.

Lung Cancer, 2010

Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial ear... more Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial early events in carcinogenesis is the induction of genomic instability and mutator phenotype. We investigated genomic instability in 30 patients with non-small-cell lung cancer (NSCLC) by comparing DNA fingerprints of paired tumor and normal tissues using arbitrarily primed polymerase chain reaction (AP-PCR). Selected 21 DNA bands with altered mobility were isolated from polyacrylamide gels, cloned and sequenced. Obtained sequences were submitted to homology search in GenBank database which revealed the following genes: TSPAN14, CDH12, RDH10, CYP4Z1, KIR, E2F4, PHACTR3, PHF20, PRAME family member and SLC2A13. Following the identification of these genes we examined their relation to the clinicopathological parameters and survival of the patients. Our study revealed that genetic alterations of TSPAN14, SLC2A13 and PHF20 appeared prevalently in tumors of grade 1, stage I suggesting that structural changes of these genes could play a role in NSCLC promotion. Contrary to this CYP4Z1, KIR and RDH10 were prevalently mutated in tumors of grade 3, stage III suggesting that they could play a role in NSCLC progression. E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in NSCLC geneses. In conclusion, our study revealed altered genes previously not described in regard to this type of cancer.

Vojnosanitetski pregled, 2014

Endobronchial tuberculosis (EBTB) is a specific type of pulmonary tuberculosis which often affect... more Endobronchial tuberculosis (EBTB) is a specific type of pulmonary tuberculosis which often affect the tracheobronchial tree, and can be microbiologically and/or pathohistologically confirmed. The aim of the study was to determine the clinical features and diagnostic aspects of EBTB. This retrospective study was conducted at the Clinic for Lung Diseases, Clinical Center of Serbia, Belgrade, from January 1997 to December 2007. All patients with EBTB confirmed by bronchoscopy with biopsy during a study period were analysed. Data included the patient's medical history, a physical exam, chest X-ray, mycobacterial analysis of sputum samples, endoscopic types and patohistological confirmation. In the study, 57.6% of the patients were males. The most frequent symptoms were cough (71.2%), malaise (54.20%), fever (49.2%), weight loss (40.7%), and hemoptysis (13.60%). Most of the patients were diagnosed within 30 days of symptoms onset. Sputum examination showed acid-fast bacilli in 31.4% of the patients, while sputum culture for tuberculosis bacilli were positive in 55.9% of the patients. The most common radiographic localization was in the upper lung lobes (63.5%). Cavities were present in 60.4% of the patients. The most common endoscopic subtype determined by bronchoscopy were nonspecific bronchitis (39.9%) and edematous-hyperemic subtype (36.4%). EBTB was more frequent among men, and among people in their fifties in our country. Detailed bronchoscopic examination, correlated with clinical and laboratory findings, will improve diagnostic rate and provide timely therapy.

Journal of Thoracic Oncology, 2007

The group consists of 58 pts (30 females and 28 males), the average age of 48 ys (17 - 75). 57 of... more The group consists of 58 pts (30 females and 28 males), the average age of 48 ys (17 - 75). 57 of them underwent operation: lobectomy in 34pts (58.6.%), pneumonectomy in 11pts(19%), atypical resection in 9pts (15.5%), bilobectomy in 3pts (5.2%). Hystologic finding of typical ...

Journal of Thoracic Oncology, 2007

The aim of the survey was to estimate some aspects of health system concerning malignant diseases... more The aim of the survey was to estimate some aspects of health system concerning malignant diseases, preferably lung cancer, in Serbia. The survey (face to face) on public opinion comprised 1023 persons-represantative sample, 171 cancer patients (pts)-majority with ...

Nature, 2015

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human c... more We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial ear... more Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial early events in carcinogenesis is the induction of genomic instability and mutator phenotype. We investigated genomic instability in 30 patients with non-small-cell lung cancer (NSCLC) by comparing DNA fingerprints of paired tumor and normal tissues using arbitrarily primed polymerase chain reaction (AP-PCR). Selected 21 DNA bands with altered mobility were isolated from polyacrylamide gels, cloned and sequenced. Obtained sequences were submitted to homology search in GenBank database which revealed the following genes: TSPAN14, CDH12, RDH10, CYP4Z1, KIR, E2F4, PHACTR3, PHF20, PRAME family member and SLC2A13. Following the identification of these genes we examined their relation to the clinicopathological parameters and survival of the patients. Our study revealed that genetic alterations of TSPAN14, SLC2A13 and PHF20 appeared prevalently in tumors of grade 1, stage I suggesting that structural changes of these genes could play a role in NSCLC promotion. Contrary to this CYP4Z1, KIR and RDH10 were prevalently mutated in tumors of grade 3, stage III suggesting that they could play a role in NSCLC progression. E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in NSCLC geneses. In conclusion, our study revealed altered genes previously not described in regard to this type of cancer.

Srpski arhiv za celokupno lekarstvo, 2008

Uvod U Sr bi ji ima do sta oso ba obo le lih od pne u mo kok ne pne u mo ni je. Kod oso ba sta ri... more Uvod U Sr bi ji ima do sta oso ba obo le lih od pne u mo kok ne pne u mo ni je. Kod oso ba sta ri jih od 65 go di na, imu no kompro mi to va nih i bo le sni ka s ko mor bi di te ti ma kao što su hro nič na op struk tiv na bo lest plu ća i kon ge stiv na in sufi ci jen ci ja sr ca po sto ji naj ve ći ri zik za na sta nak pne u mo kok ne pne u mo ni je. Većina bo le sni ka se le či em pi rij ski, iako se če sto pred vi di či we ni ca da Strep to coc cus pne u mo ni ae mo že bi ti re zi sten tan na iza bra ne an ti bi ot ske le kove. Tro ško vi za bol nič ko i am bu lant no le če we bo le sni ka s ovim obo qe wem ve o ma su vi so ki. Vak ci na ci ja ri zič nih bo le sni ka od raz vo ja bo le sti iza zva nih sa Strep to coc cus pne u mo ni ae u Sr bi ji vr ši se pri me nom pne u mo kok ne po li saha rid ne vak ci ne pre ma kli nič kim in di ka ci ja ma. Ta čan broj vak ci ni sa nih i uku pan broj re gi stro va nih bo le sni ka i da qe ni je po znat, ali je si gur no da je neo prav da no ma li. Ciq rada Ciq ra da je bio da se to kom jed no go di šweg pe ri o da is pi ta ju broj i osnov ne od li ke oso ba bol nič ki leče nih od pne u mo ni je, vr sta uzroč ni ka in fek ci je, pri me we ni an ti bi ot ski le ko vi, tra ja we i tro ško vi bol nič kog leče wa u Insti tu tu za pluć ne bo le sti i tu ber ku lo zu Kliničkog cen tra Sr bi je u Be o gra du. Metod rada Re tro spek tiv no su ana li zi ra ni me di cin ski po da ci bo le sni ka le če nih od pne u mo ni je to kom 2006. godi ne u Insti tu tu za pluć ne bo le sti i tu ber ku lo zu Kliničkog cen tra Sr bi je u Be o gra du. Rezultati To kom po sma tra nog jed no go di šweg pe ri o da bol nič ki je le če no 290 bo le sni ka, od če ga je uzroč nik in fekci je po tvr đen kod 116 (40%). Bol nič ko le če we je u pro se ku tra ja lo 12 da na, a tro ško vi le če wa po bo le sni ku bi li su 32.031,74 di na ra (402,42 evra). Tro ško vi le če wa po bo le sni ku s op štom i in ten ziv nom ne gom bi li su 18.290,01 di nar (229,78 evra). Di stri bu tiv na ce na po je di nač ne vak ci ne "Pne u mo 23" u Sr bi ji bez po re za bi la je 746,90 di na ra (9,38 evra). Zakqučak Pne u mo kok na pne u mo ni ja je zna ča jan me di cin ski i eko nom ski pro blem za zdrav stve ni si stem Sr bi je. Prime na an tip ne u mo kok ne vak ci ne mo že bi ti ko ri sna u sma we wu ukup nih tro ško va le če wa od pne u mo kok ne in fek ci je.

Srpski arhiv za celokupno lekarstvo, 2003

1. In sti tut za kar di o va sku lar ne bo le sti, Kli niè ki cen tar Sr bi je, Be o grad; 2. In ... more 1. In sti tut za kar di o va sku lar ne bo le sti, Kli niè ki cen tar Sr bi je, Be o grad; 2. In sti tut za pluae ne bo le sti i tu ber ku lo zu, Kli niè ki cen tar Sr bi je, Be o grad KRATAK SADRŽAJ: Pri mar ni se mi no mi me di ja sti nu ma su ret ki i mo gu aee fa tal ni tu mo ri. Oni mo gu uzro ko va ti kompre si ju ili in va zi ju okol nih struk tu ra, ali da ti i udaqe ne me ta sta ze. Pri ka zan je re dak slu èaj me di ja sti nal nog se mi no ma ko ji je uzro ko vao di rekt nu in tra ka vi tar nu in va zi ju de sne pret ko mo re i pro ši rio se u le vu pret ko moru. Dva de set dvo go dišwi mla diae je ho spi ta li zo van zbog bo la na desnoj strani grudnog koša, kašqa, disp ne ja, febril no sti i oto ka de sne ru ke. Te go be su se ja vi le me sec da na pre ho spi ta li za ci je. Rend ge no gra fi jom grudi na ðe na je ve li ka ma sa u predwem me di ja sti nu mu de sno. Eho kar di o graf skim pre gle dom je ot kri ve na kom pre si ja de sne pret ko mo re tu mor skom ma som ko ja je isto vre me no in fil tri sa la wen zid. Takoðe su na ðe ni po li po id na ma sa u levoj pret ko mo ri u bli zi ni uš aea de snih pluae nih ve na i pe ri kard ni iz liv. Per ku ta nom bi op si jom je utvr ðe no da se ra di o se mi no mu. Pre ma do sa dašwim sa znawi ma, sli èan pri kaz ni je ob ja vqen u na šoj me di cin skoj li te ra tu ri. Kquè ne re èi: se mi nom, me di ja sti num.

Palliative & supportive care, Jan 2, 2015

Under conditions in which palliative care has not yet become part of clinical practice, the diffe... more Under conditions in which palliative care has not yet become part of clinical practice, the differences in palliative care needs between patients with cancer and other life-limiting diseases can yield knowledge that will be very valuable for future planning. The aim of our investigation was to compare health-related quality of life (HRQoL) for patients with end-stage chronic obstructive pulmonary disease (COPD) and those with non-small-cell lung cancer (NSCLC) in Belgrade, Serbia. We also evaluated the influence of demographic, socioeconomic, and clinical factors on HRQoL for both patient groups. This cross-sectional study included 100 NSCLC patients (stages IIIb and IV) and 100 patients with stage IV COPD. Measures included the SF-36 questionnaire, the EORTC QLQ-C30, the St. George's Respiratory Questionnaire, and the Beck Depression Inventory (BDI). Associations of demographic, socioeconomic, and clinical factors with QoL were examined using linear regression analyses. The COP...

American journal of respiratory and critical care medicine, Jan 6, 2015

To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene ... more To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1726 German sarcoidosis cases and 5482 controls were genotyped for 128,705 SNPs using the Illumina Immunochip for the screening step. The remaining 3955 cases, 7514 controls and 684 parents of affected offspring were used for validation and replication of 44 candidate and 2 established risk SNPs. Four novel susceptibility loci were identified with genome-wide significance in the European case control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1) and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA-region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA DPB...

Clinics in Chest Medicine, 2008

Sarcoidosis is an inflammatory granulomatous disease that is characterized by diverse organ syste... more Sarcoidosis is an inflammatory granulomatous disease that is characterized by diverse organ system manifestations, a variable clinical course, and a predilection for affecting relatively young adults worldwide. Abnormalities on chest radiographs are detected in 85% to 95% of patients who have sarcoidosis. Approximately 20% to 50% of patients who have sarcoidosis present with respiratory symptoms, including dyspnea, cough, chest pain, and tightness of the chest. The clinical course and manifestations of pulmonary sarcoidosis are protean: spontaneous remission occurs in approximately two thirds of patients; up to 30% of patients have chronic course of the lung disease, resulting in progressive, (sometimes life-threatening) loss of lung function. Morbidity that correlates to sarcoidosis occurs in 1% to 4% of patients.

Lung Cancer, 2010

Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial ear... more Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial early events in carcinogenesis is the induction of genomic instability and mutator phenotype. We investigated genomic instability in 30 patients with non-small-cell lung cancer (NSCLC) by comparing DNA fingerprints of paired tumor and normal tissues using arbitrarily primed polymerase chain reaction (AP-PCR). Selected 21 DNA bands with altered mobility were isolated from polyacrylamide gels, cloned and sequenced. Obtained sequences were submitted to homology search in GenBank database which revealed the following genes: TSPAN14, CDH12, RDH10, CYP4Z1, KIR, E2F4, PHACTR3, PHF20, PRAME family member and SLC2A13. Following the identification of these genes we examined their relation to the clinicopathological parameters and survival of the patients. Our study revealed that genetic alterations of TSPAN14, SLC2A13 and PHF20 appeared prevalently in tumors of grade 1, stage I suggesting that structural changes of these genes could play a role in NSCLC promotion. Contrary to this CYP4Z1, KIR and RDH10 were prevalently mutated in tumors of grade 3, stage III suggesting that they could play a role in NSCLC progression. E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in NSCLC geneses. In conclusion, our study revealed altered genes previously not described in regard to this type of cancer.

Vojnosanitetski pregled, 2014

Endobronchial tuberculosis (EBTB) is a specific type of pulmonary tuberculosis which often affect... more Endobronchial tuberculosis (EBTB) is a specific type of pulmonary tuberculosis which often affect the tracheobronchial tree, and can be microbiologically and/or pathohistologically confirmed. The aim of the study was to determine the clinical features and diagnostic aspects of EBTB. This retrospective study was conducted at the Clinic for Lung Diseases, Clinical Center of Serbia, Belgrade, from January 1997 to December 2007. All patients with EBTB confirmed by bronchoscopy with biopsy during a study period were analysed. Data included the patient's medical history, a physical exam, chest X-ray, mycobacterial analysis of sputum samples, endoscopic types and patohistological confirmation. In the study, 57.6% of the patients were males. The most frequent symptoms were cough (71.2%), malaise (54.20%), fever (49.2%), weight loss (40.7%), and hemoptysis (13.60%). Most of the patients were diagnosed within 30 days of symptoms onset. Sputum examination showed acid-fast bacilli in 31.4% of the patients, while sputum culture for tuberculosis bacilli were positive in 55.9% of the patients. The most common radiographic localization was in the upper lung lobes (63.5%). Cavities were present in 60.4% of the patients. The most common endoscopic subtype determined by bronchoscopy were nonspecific bronchitis (39.9%) and edematous-hyperemic subtype (36.4%). EBTB was more frequent among men, and among people in their fifties in our country. Detailed bronchoscopic examination, correlated with clinical and laboratory findings, will improve diagnostic rate and provide timely therapy.

Journal of Thoracic Oncology, 2007

The group consists of 58 pts (30 females and 28 males), the average age of 48 ys (17 - 75). 57 of... more The group consists of 58 pts (30 females and 28 males), the average age of 48 ys (17 - 75). 57 of them underwent operation: lobectomy in 34pts (58.6.%), pneumonectomy in 11pts(19%), atypical resection in 9pts (15.5%), bilobectomy in 3pts (5.2%). Hystologic finding of typical ...

Journal of Thoracic Oncology, 2007

The aim of the survey was to estimate some aspects of health system concerning malignant diseases... more The aim of the survey was to estimate some aspects of health system concerning malignant diseases, preferably lung cancer, in Serbia. The survey (face to face) on public opinion comprised 1023 persons-represantative sample, 171 cancer patients (pts)-majority with ...

Nature, 2015

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human c... more We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.