Imunohistokemijska izraženost pd-l1 u solidnim tumorima

Recent clinical trials have demonstrated that it is possible to induce durable remission in several tumors (non-small cell lung cancer (NSCLC), melanoma, squamous cancer of head and neck, renal cell carcinoma, Hodgkin lymphoma, colorectal cancer) by blocking the PD-1/PD-L1 (programmed death-1/programmed death-ligand 1) axis with anti-PD-1 or anti-PD-L1 antibodies and that an objective clinical response was closely associated with immunohistochemical PD-L1expression in tumor cells. Because immunohistochemistry is widely accepted and used method for PD-L1 assessment it is important to defi ne criteria for selecting patients who are candidates for immunotherapy and can benefi t from it.Posljednjih godina klinička istraživanja su pokazala da je moguće postići trajniju remisiju kod nekoliko vrsta solidnih tumora (karcinom pluća ne-malih stanica (NSCLC), melanom, pločasti karcinom glave i vrata, renalni karcinom, urotelni karcinom, Hodgkin limfom, kolorektalni karcinom) blokirajući aktivaciju PD-1/PD-L1 (engl. programmed death- 1/programmed death-ligand 1) signalnog puta primjenjujući anti-PD-1 i anti-PD-L1 protutijela. Učinak terapije usko je povezan s izraženošću PD-L1 u tumorskim stanicama. Iako su mehanizmi kojima tumorske stanice izražavaju PD-L1 dobro poznati, studije su do sada pokazale da samo manji broj pacijenata može imati koristi od PD-1/PD-L1 imunoterapije, vezano uz izraženost PD-L1 na tumorskim stanicama. Stoga je važno odrediti kriterije za odabir pacijenata koji mogu imati koristi od imunoterapije

E‑cadherin and NEDD9 expression in primary colorectal cancer, metastatic lymph nodes and liver metastases

In Croatia, colorectal cancer mortality rates in males are the third highest in Europe, after Hungary and Slovakia. The results for females rank Croatia in second place after Hungary. According to previous studies, the loss of E-cadherin expression and the higher expression of neural precursor cell-expressed developmentally downregulated 9 (NEDD9) are associated with a worse prognosis. The aim of the present study was to analyze the immunohistochemical expression of NEDD9 and E-cadherin as markers of metastatic potential using a tissue microarray. This retrospective study included 40 previously untreated patients, including 23 males and 17 females with a median age of 64.5 years (range 38-84), with colorectal cancer and synchronous liver metastases that underwent simultaneous colorectal and hepatic resection between January 1st 2006 and December 31st 2013, in the Clinical Hospital Center Sestre Milosrdnice (Zagreb, Croatia). The most frequent tumor stage was T3, while the most frequent nodal stage was N1. Microvascular invasion was present in 37.5% of patients, while perineural invasion was observed in 30% of patients. The immunohistochemical staining index of E-cadherin was highly positive in 87.5% samples of colorectal cancer, 67.7% of lymph nodes and 77.5% of liver metastases. In the primary tumor, highly positive NEDD9 expression was identified in 22.5% of patients. In lymph nodes, it was identified in 35.5% of patients, while in the liver, it was identified in 30% of patients. Significant positive correlations were observed between the percentage of positive lymph nodes and the immunohistochemical staining index of E-cadherin (ρ=0.372; P=0.039) and NEDD9 (ρ=0.451; P=0.011) in lymph nodes. After the conclusion of the study, 55% of the patients succumbed. No significant differences in survival rates were identified regarding the expression of E-cadherin and NEDD9 in the primary tumor, metastatic lymph nodes and liver metastases. Due to the small sample size and the negative results obtained, further research is required to implement these parameters as prognostic factors

Frequency of tuberculosis at autopsies in a large hospital in Zagreb, Croatia: a 10-year retrospective study

Aim To assess the frequency and forms of pulmonary tuberculosis at autopsy in a high-traffic hospital in the capital city of a country with a low tuberculosis incidence. Methods We performed a retrospective search of autopsy data from the period 2000 to 2009 at Sestre Milosrdnice University Hospital Center, Zagreb, Croatia. We also examined patients’ records and histological slides. Results Of 3479 autopsies, we identified 61 tuberculosis cases, corresponding to a frequency of 1.8%. Active tuberculosis was found in 33 cases (54%), 23 of which (70%) were male. Of the 33 active cases, 25 (76%) were clinically unrecognized and 19 (76%) of these were male. Conclusion Clinically undiagnosed tuberculosis accounted for a substantial proportion of active tuberculosis cases diagnosed at autopsy. Autopsy data may be an important complement to epidemiological data on tuberculosis frequency

Dobne i spolne razlike u oštećenju genoma između pretpubertetskih i odraslih miševa nakon izlaganja ionizirajućemu zračenju

The mechanisms that lead to sex and age differences in biological responses to exposure to ionising radiation and related health risks have still not been investigated to a satisfactory extent. The significance of sex hormones in the aetiology of radiogenic cancer types requires a better understanding of the mechanisms involved, especially during organism development. The aim of this study was to show age and sex differences in genome damage between prepubertal and adult mice after single exposure to gamma radiation. Genome damage was measured 24 h, 48 h, and 72 h after exposure of 3-week and 12-week old BALB/CJ mice to 8 Gy of gamma radiation using an in vivo micronucleus assay. There was a significantly higher genome damage in prepubertal than in adult animals of both sexes for all sampling times. Irradiation caused a higher frequency of micronuclei in males of both age groups. Our study confirms sex differences in the susceptibility to effects of ionising radiation in mice and is the first to show that such a difference occurs already at prepubertal age.Mehanizmi koji uzrokuju spolne i dobne razlike u biološkim odgovorima na izloženost ionizirajućemu zračenju i s tim u vezi zdravstvene rizike još nisu dovoljno ispitani. Kako bi se spoznao značaj spolnih hormona u etiologiji zračenjem izazvanih vrsta tumora, potrebno je bolje poznavanje mehanizama koji su uključeni u taj proces, osobito tijekom razvojne faze organizma. Cilj ovoga istraživanja bio je prikazati dobne i spolne razlike u oštećenju genoma između pretpubertetskih i odraslih miševa nakon jednokratnoga izlaganja gama-zračenju. Primjenom in vivo mikronukleus-testa izmjereno je oštećenje genoma nastalo 24 sata, 48 sati i 72 sata nakon izlaganja BALB/CJ miševa, starih tri tjedna i dvanaest tjedana, dozi gama zračenja od 8 Gy. U svim vremenskim točkama mjerenja uočeno je značajnije veće oštećenje genoma u pretpubertetskih u odnosu na odrasle jedinke obaju spolova. Zračenje je uzrokovalo veću učestalost mikronukleusa u muških jedinki u objema dobnim skupinama. Dobiveni rezultati potvrđuju postojanje spolnih razlika u osjetljivosti na učinke ionizirajućega zračenja u miševa, a ovo je prvo istraživanje rezultati kojega pokazuju da do takvih razlika dolazi već u pretpubertetskoj dobi

THE IMPORTANCE OF ANTENATAL ULTRASOUND SCREENING FOR CONGENITAL OSTEOCHONDRODYSPLASIA – TWO CASE REPORTS

Osteohondrodisplazije velika su skupina rijetkih genskih bolesti karakterizirana poremećajem rasta i razvoja hrskavice i kosti. Često su povezane s malformacijama drugih organskih sustava. Mogu se podijeliti na letalne i neletalne skeletne displazije. Tanatoforična displazija jedna je od najčešćih letalnih skeletnih displazija s učestalošću pojavljivanja od 0,69 na 10.000 porođaja, dok je heterozigotna ahondrodisplazija među najčešćim neletalnim displazijama s učestalošću od 0,15 na 10.000 porođaja. Prikazat ćemo dva novorođenčeta s osteohondrodisplazijom. Prvi je prikaz letalne osteohondrodisplazije kod novorođenčeta 41-godišnje višerotkinje koja je u 33. tjednu nekontrolirane trudnoće došla u našu Kliniku zbog započetog porođaja. Drugi je prikaz neletalne osteohondrodisplazije u novorođenčeta 31-godišnje višerotkinje kod kojeg se od 30. tjedna trudnoće prate kraće kosti udova.Osteochondrodysplasias comprise a large, genetically heterogeneous group of disorders characterized by abnormalities of cartilage and bone growth. They are often associated with abnormalities in other organ systems. They are classified as lethal or non-lethal skeletal dysplasias. Thanatophoric dysplasia is the most common form of lethal skeletal dysplasia with an incidence of 0.69 per 10.000 births. Heterozygous achondroplasia is the most common non-lethal dysplasia with an incidence of 0.15 per 10.000 births. We will present two cases of skeletal dysplasia. The first case is the case of lethal osteochondrodysplasia in the fetus of a 41-year-old multiparous woman, who came to our hospital in active preterm labor, in the 33th week of uncontrolled pregnancy. The second case is the case of non-lethal osteochondrodysplasia in the fetus of a 31-year-old multiparous woman. The fetal short femur length was detected in the 30th week of pregnancy

Imunohistokemijska izraženost NEDD9, gamma-katenina i e-kadherina u adenokarcinomu gušterače [Immunohistochemical expression of NEDD9, gamma catenin and e-cadherin in pancreatic adenocarcinoma]

Early metastasis is a hallmark of pancreatic ductal adenocarcinoma and is responsible for more than 90% of pancreatic cancer deaths. Since patient outcome is not reliably predicted using pathological factors (tumor stage, differentiation, resection margin status) alone, markers of tumor behaviour are needed. A few candidates are NEDD 9 (HEF-1/CAS-L), recently identified as a key protein in tumor cell proliferation and migration as well as e-cadherin and gamma-catenin known as important adhesion molecules responsible for maintaining cell-cell adhesion. Changes in their functioning reflect invasive properties of cancer cells. The study objective was to assess changes in the expression of e-cadherin, gamma-catenin and NEDD9 proteins in pancreatic ductal adenocarcinoma in correlation with clinicopathological parameters. Sixty-one patients with pancreatic ductal adenocarcinoma were analyzed in relation to gender, histological malignancy grade and stage and lymph node involvement. Intensity of immunohistochemical staining as well as the percent of positive tumor cells were analyzed in tissue samples. Reduced expression of e-cadherin and gamma-catenin were observed in pancreatic ductal adenocarcinoma, while expression of NEDD9 was increased in pancreatic adenocarcinoma samples. The statistical analysis showed positive correlations of reduced e-cadherin and gamma-catenin expression in tumor (rho=0,370, P<0,001) as well as positive correlations between e-cadherin expression and patient survival (rho=0,267, P=0,038) meaning that patients with tumors that had perserved e-cadherin expression had longer survival time. The statistical analysis showed negative correlation of e-cadherin expression and tumor grade (rho=-0,364, P=0,004) meaning that high grade tumors more often had reduced expression of e-cadherin. Our study indicates strong correlation of reduced e-cadherin expression with gamma-catenin expression, tumor grade and patient surviv

The Relationship between Strain, Anger and Internet Aggression

Agresija na internetu se u literaturi proučava u okviru različitih teorija. Jedna od tih teorija je i generalna teorija stresa (Agnew, 1992), prema kojoj stresni događaji kod pojedinca izazivaju neugodne emocije, ponajprije ljutnju, a koje često rezultiraju uključivanjem pojedinca u činjenje agresije. Iako u literaturi postoje istraživanja koja proučavaju agresiju na internetu u okviru generalne teorije stresa, ona su relativno malobrojna. Štoviše, u hrvatskoj literaturi, koliko je poznato autorici ovog diplomskog rada, ne postoje istraživanja koja su proučavala agresiju na internetu u okviru ove teorije. Stoga je cilj istraživanja bio proučiti odnos između stresa, ljutnje i činjenja agresije na internetu na uzorku hrvatskih adolescenata. Istraživanje je provedeno u rujnu 2020. godine u dvije srednje škole s područja Dubrovnika. U njemu je sudjelovalo 158 sudionika, od čega 75 učenica i 83 učenika u dobi između 14 i 18 godina. Podatci su prikupljeni mjerama samoprocjene doživljavanja školskog stresa, ljutnje te činjenja i doživljavanja agresije na internetu. Rezultati medijacijske analize su pokazali da doživljavanje stresa nije značajan izravni prediktor činjenja agresije na internetu. Također, ljutnja se pokazala značajnim medijatorom odnosa između stresa i činjenja agresije na internetu. Pri tome je izraženiji stres predviđao izraženiju ljutnju, a izraženija ljutnja je predvidjela učestalije činjenje agresije na internetu. Ovaj rad ima teorijske implikacije, u vidu provjere postavki generalne teorije stresa u predviđanju agresije na internetu. Također, ima i praktične implikacije, jer pruža smjernice za prevencijske i intervencijske strategije za smanjivanje agresije na internetu.In literature, Internet aggression is studied within the framework of various theories. One of these theories is the General Strain Theory (Agnew, 1992), according to which stressful events cause negative emotions, primarily anger, which often result in Internet aggression. There are relatively few studies that studied Internet aggression within the General Strain Theory. Moreover, as far as the author of this thesis is aware, there are no studies that have studied Internet aggression within this theory in Croatia. Therefore, the aim of this study was to examine the relationship between strain, anger and Internet aggression on a sample of Croatian adolescents. The research was conducted in two high schools from Dubrovnik area during September, 2020. It involved 158 participants, of which 75 female and 83 male high school students 14-18 years of age. The participants completed self-assessment scales assessing school strain, anger, cyber-aggression and cyber-victimization. The results of mediation analysis showed that experiencing strain was not a significant direct predictor of Internet aggression. The results also showed that anger acts as a significant mediator between strain and Internet aggression, in a way that greater strain predicted greater anger and greater anger predicted greater incidence of Internet aggression. The current study has theoretical implications, in a way that it reviews postulations of the General Strain Theory in predicting Internet aggression. It also has practical implications, such as providing guidelines for prevention and intervention strategies to reduce Internet aggression

Immunohistochemical expression of NEDD9, gamma catenin and e-cadherin in pancreatic adenocarcinoma

Pankreatični duktalni adenokarcinom je najčešći tip karcinoma gušterače i čini oko 85% svih malignih tumora tog organa. Glavno obilježje mu je rana pojava metastaza. Duktalni adenokarcinom gušterače se češće pojavljuje u muškaraca (1,6:1), a većina bolesnika je starije dobi, između 60 i 80 godina. Preživljenje tih bolesnika je nisko. U potrazi za biljezima koji bi mogli biti bolji prognostički markeri ili nuditi eventalnu mogućnost razvoja specifičnog lijeka, analizirali smo imunohistokemijsku izraženost E-kadherina, gamma-katenina i NEDD9 na uzorcima adenokarcinoma gušterače. Hipoteza ovog istraživanja je da adenokarcinomi gušterače pokazuju pojačanu izraženost NEDD9 u odnosu na normalne stanice duktusa gušterače, dok je izraženost gamma-katenina i e-kadherina smanjena u stanicama karcinoma u odnosu na normalno tkivo. Analizirani uzorci gušterače s karcinomom predstavljaju arhivski materijal dobiven nakon totalne ili parcijalne pankreatektomije i histološki potvrđene dijagnoze duktalnog adenokarcinoma gušterače na Kliničkom zavodu za patologiju „Ljudevit Jurak” KBC „Sestre milosrdnice” u Zagrebu. Analizirano je 61 uzorak normalnog tkiva gušterače te 61 uzorak duktalnog adenokarcinoma gušterače bolesnika kod kojih je napravljena parcijalna ili totalna pankreatektomija između 1. siječnja 2000. i 31. prosinca 2012. Statističkom analizom rezultata je nađena fokalno izgubljena reakcija i slabiji intenzitet reakcije na e-kadherin u svim analiziranim uzorcima adenokarcinoma gušterače, kao i slabiji intenzitet reakcije na gamma-katenin u većini uzoraka adenokarcinoma gušterače te jača imunohistokemijska izraženost NEDD9 u odnosu na normalno tkivo gušterače (X2 test; P<0,05). Spearmanovim testom statistički značajne pozitivne korelacije zabilježene su između ekspresije gamma-katenina i e-kadherina u karcinomu (rho=0,370, P<0,001) što znači da su uzorci adenokarcinoma gušterače sa slabijom izraženošću e-kadherina pokazivali i slabiju izraženost gamma-katenina. Pozitivna korelacija zabilježena je u dužini praćenja i ekspresiji e-kadherina u karcinomu (rho=0,267, P=0,038) čime je utvrđeno da su duže preživljenje imali bolesnici s karcinomom koji je imunohistokemijski pokazivao jaču izraženost e-kadherina. Statistički značajna negativna korelacija pronađena je između gradusa karcinoma i izraženosti e-kadherina u karcinomu (rho=-0,364, P=0,004) što upućuje da je veći gradus karcinoma povezan s nižim intenzitetom reakcije na e-kadherin. Dobiveni rezultati ovog istraživanja ukazuju na statistički značajnu povezanost slabije imunohistokemijske izraženosti e-kadherina u adenokarcinomima gušterače s višim gradusom. Također, ukazuju na povezanost gubitka adhezijskih molekula e-kadherina i gamma-katenina te njihovu ulogu u progresiji adenokarcinoma gušterače. Iako postoji pojačana izraženost molekule NEDD9 u karcinomu u odnosu na normalno tkivo, u ovom istraživanju nije dokazana njena povezanost s drugim analiziranim molekulama niti s prognostički važnim pokazateljima kao što su stupanj i gradus karcinoma te zahvaćenost limfnih čvorova. Za razliku od NEDD9, gubitak izraženosti e-kadherina pokazao se kao samostalan progostički pokazatelj preživljenja bolesnika.Early metastasis is a hallmark of pancreatic ductal adenocarcinoma and is responsible for more than 90% of pancreatic cancer deaths. Since patient outcome is not reliably predicted using pathological factors (tumor stage, differentiation, resection margin status) alone, markers of tumor behaviour are needed. A few candidates are NEDD 9 (HEF-1/CAS-L), recently identified as a key protein in tumor cell proliferation and migration as well as e-cadherin and gamma-catenin known as important adhesion molecules responsible for maintaining cell-cell adhesion. Changes in their functioning reflect invasive properties of cancer cells. The study objective was to assess changes in the expression of e-cadherin, gamma-catenin and NEDD9 proteins in pancreatic ductal adenocarcinoma in correlation with clinicopathological parameters. Sixty-one patients with pancreatic ductal adenocarcinoma were analyzed in relation to gender, histological malignancy grade and stage and lymph node involvement. Intensity of immunohistochemical staining as well as the percent of positive tumor cells were analyzed in tissue samples. Reduced expression of e-cadherin and gamma-catenin were observed in pancreatic ductal adenocarcinoma, while expression of NEDD9 was increased in pancreatic adenocarcinoma samples. The statistical analysis showed positive correlations of reduced e-cadherin and gamma-catenin expression in tumor (rho=0,370, P<0,001) as well as positive correlations between e-cadherin expression and patient survival (rho=0,267, P=0,038) meaning that patients with tumors that had perserved e-cadherin expression had longer survival time. The statistical analysis showed negative correlation of e-cadherin expression and tumor grade (rho=-0,364, P=0,004) meaning that high grade tumors more often had reduced expression of e-cadherin. Our study indicates strong correlation of reduced e-cadherin expression with gamma-catenin expression, tumor grade and patient surviv

Immunohistochemical expression of NEDD9, gamma catenin and e-cadherin in pancreatic adenocarcinoma

Pankreatični duktalni adenokarcinom je najčešći tip karcinoma gušterače i čini oko 85% svih malignih tumora tog organa. Glavno obilježje mu je rana pojava metastaza. Duktalni adenokarcinom gušterače se češće pojavljuje u muškaraca (1,6:1), a većina bolesnika je starije dobi, između 60 i 80 godina. Preživljenje tih bolesnika je nisko. U potrazi za biljezima koji bi mogli biti bolji prognostički markeri ili nuditi eventalnu mogućnost razvoja specifičnog lijeka, analizirali smo imunohistokemijsku izraženost E-kadherina, gamma-katenina i NEDD9 na uzorcima adenokarcinoma gušterače. Hipoteza ovog istraživanja je da adenokarcinomi gušterače pokazuju pojačanu izraženost NEDD9 u odnosu na normalne stanice duktusa gušterače, dok je izraženost gamma-katenina i e-kadherina smanjena u stanicama karcinoma u odnosu na normalno tkivo. Analizirani uzorci gušterače s karcinomom predstavljaju arhivski materijal dobiven nakon totalne ili parcijalne pankreatektomije i histološki potvrđene dijagnoze duktalnog adenokarcinoma gušterače na Kliničkom zavodu za patologiju „Ljudevit Jurak” KBC „Sestre milosrdnice” u Zagrebu. Analizirano je 61 uzorak normalnog tkiva gušterače te 61 uzorak duktalnog adenokarcinoma gušterače bolesnika kod kojih je napravljena parcijalna ili totalna pankreatektomija između 1. siječnja 2000. i 31. prosinca 2012. Statističkom analizom rezultata je nađena fokalno izgubljena reakcija i slabiji intenzitet reakcije na e-kadherin u svim analiziranim uzorcima adenokarcinoma gušterače, kao i slabiji intenzitet reakcije na gamma-katenin u većini uzoraka adenokarcinoma gušterače te jača imunohistokemijska izraženost NEDD9 u odnosu na normalno tkivo gušterače (X2 test; P<0,05). Spearmanovim testom statistički značajne pozitivne korelacije zabilježene su između ekspresije gamma-katenina i e-kadherina u karcinomu (rho=0,370, P<0,001) što znači da su uzorci adenokarcinoma gušterače sa slabijom izraženošću e-kadherina pokazivali i slabiju izraženost gamma-katenina. Pozitivna korelacija zabilježena je u dužini praćenja i ekspresiji e-kadherina u karcinomu (rho=0,267, P=0,038) čime je utvrđeno da su duže preživljenje imali bolesnici s karcinomom koji je imunohistokemijski pokazivao jaču izraženost e-kadherina. Statistički značajna negativna korelacija pronađena je između gradusa karcinoma i izraženosti e-kadherina u karcinomu (rho=-0,364, P=0,004) što upućuje da je veći gradus karcinoma povezan s nižim intenzitetom reakcije na e-kadherin. Dobiveni rezultati ovog istraživanja ukazuju na statistički značajnu povezanost slabije imunohistokemijske izraženosti e-kadherina u adenokarcinomima gušterače s višim gradusom. Također, ukazuju na povezanost gubitka adhezijskih molekula e-kadherina i gamma-katenina te njihovu ulogu u progresiji adenokarcinoma gušterače. Iako postoji pojačana izraženost molekule NEDD9 u karcinomu u odnosu na normalno tkivo, u ovom istraživanju nije dokazana njena povezanost s drugim analiziranim molekulama niti s prognostički važnim pokazateljima kao što su stupanj i gradus karcinoma te zahvaćenost limfnih čvorova. Za razliku od NEDD9, gubitak izraženosti e-kadherina pokazao se kao samostalan progostički pokazatelj preživljenja bolesnika.Early metastasis is a hallmark of pancreatic ductal adenocarcinoma and is responsible for more than 90% of pancreatic cancer deaths. Since patient outcome is not reliably predicted using pathological factors (tumor stage, differentiation, resection margin status) alone, markers of tumor behaviour are needed. A few candidates are NEDD 9 (HEF-1/CAS-L), recently identified as a key protein in tumor cell proliferation and migration as well as e-cadherin and gamma-catenin known as important adhesion molecules responsible for maintaining cell-cell adhesion. Changes in their functioning reflect invasive properties of cancer cells. The study objective was to assess changes in the expression of e-cadherin, gamma-catenin and NEDD9 proteins in pancreatic ductal adenocarcinoma in correlation with clinicopathological parameters. Sixty-one patients with pancreatic ductal adenocarcinoma were analyzed in relation to gender, histological malignancy grade and stage and lymph node involvement. Intensity of immunohistochemical staining as well as the percent of positive tumor cells were analyzed in tissue samples. Reduced expression of e-cadherin and gamma-catenin were observed in pancreatic ductal adenocarcinoma, while expression of NEDD9 was increased in pancreatic adenocarcinoma samples. The statistical analysis showed positive correlations of reduced e-cadherin and gamma-catenin expression in tumor (rho=0,370, P<0,001) as well as positive correlations between e-cadherin expression and patient survival (rho=0,267, P=0,038) meaning that patients with tumors that had perserved e-cadherin expression had longer survival time. The statistical analysis showed negative correlation of e-cadherin expression and tumor grade (rho=-0,364, P=0,004) meaning that high grade tumors more often had reduced expression of e-cadherin. Our study indicates strong correlation of reduced e-cadherin expression with gamma-catenin expression, tumor grade and patient surviv