New primary non-breast malignancies after breast cancer: ten years single institution follow-up

Background and Purpose: Breast cancer is the most common cancer in Croatian women. Due to improved diagnostic and treatment options women with breast cancer now live longer, which increases their risk of developing new primary malignancies. The aim of this study was to establish incidence of new primary non-breast malignancies after breast cancer diagnosis. Material and Methods: In the study cohort that included 215 consecutive patients treated for early breast cancer at University Hospital Center Zagreb, Croatia, 12 patients (5.58%) have developed new primary non-breast malignancy within nearly ten year follow-up. Results: Although the majority of studies found gynecological cancers to be the most common cancer site of new primary non-breast malignancies after breast cancer diagnosis, in our study most patients developed colorectal cancer. Conclusion: This is particularly interesting if you take into account that after breast cancer colorectal cancer is the second most common cancer in Croatian women. In order to stratify the risk for the development of new primary tumors it is necessary to further investigate the interaction of various factors that are thought to influence the evolvement of tumors

THE CONSEQUENCE OF THE COVID CRISIS ON INTERNATIONAL BUSINESS AND COUNTRIES\u27 TRADE POLICIES

Međunarodno poslovanje, kao ključni nositelj nacionalne konkurentnosti odnosi se na svaku situaciju u kojoj proizvodnja ili distribucija robe ili usluga prelazi državne granice, uz termin se lako vezuje globalizacija - pomak ka više međuovisnoj i integriranijoj globalnoj ekonomiji koja zapravo stvara veće mogućnosti za međunarodno poslovanje. Globalizacija kao takva se tako može odvijati u uvjetima tržišta, gdje trgovinske barijere padaju, a preferencije kupaca se mijenjaju. To se može vidjeti na primjerima proizvodnje, gdje tvrtka može lako nabavljati robu i usluge iz drugih zemalja. Dakle, vanjskotrgovinsko poslovanje obuhvaća čitav niz prekograničnih razmjena robe, usluga ili resursa između dvije ili više nacija. No, vanjskotrgovinsko poslovanje, bez obzira na globalizacijske napore, mogu poremetiti krize, koje opet zahtijevaju i poseban makroekonomski okvir, odnosno trgovinsku politiku kako bi se iz istih što bezbolnije izašlo. Gospodarska kriza izazvana korona virusom Covid-19 jedinstvena je u dosadašnjoj ekonomskoj povijesti po načinu i brzini nastanka, globalnom obuhvatu i posljedicama. Nesumnjivo je da će zbog jedinstvenog načina nastanka, mehanizama i dubokih posljedica, ova kriza biti veliki izazov za ekonomsku znanost i struku. U ovom radu dat ćemo pregled kako je COVID-19 kriza utjecala na međunarodno poslovanje i trgovinske politike.International business, as a key carrier of national competitiveness, refers to any situation in which the production or distribution of goods or services crosses state borders, with the term easily associated with globalization - a shift towards a more interdependent and more integrated global economy that actually creates greater opportunities for international business. Globalization as such can thus take place in market conditions, where trade barriers fall, and customer preferences change. Thus, foreign trade involves a whole range of cross-border exchanges of goods, services or resources between two or more nations. However, foreign trade, regardless of globalization efforts, can disrupt crises, which again require a special macroeconomical framework, that is, trade policy in order to get out of them as painlessly as possible. The economic crisis caused by the Covid-19 corona virus is unique in its economic history so far in terms of manner and speed of occurrence, global coverage and consequences. Undoubtedly, due to the unique way of emergence, mechanisms and profound consequences, this crisis will be a great challenge for economic science and the profession. In this paper we will give an overview of how the COVID-19 crisis has affected international business and trade policies

Hypoxia in solid tumors: biological responses to hypoxia and implications on therapy and prognosis

Tumor development, promotion and ability to spread depend greatly on tumor microenvironment. Rapid growth accompanied by inadequate angiogenesis is the reason why most solid tumors contain hypoxic regions. Activation of hypoxia signaling pathways stimulates neoangiogenesis, alters tumor metabolism, promotes a more aggressive tumor behavior and significantly affects its responsiveness to therapy. Growing amount of evidence suggest that hypoxia induces transcription of tumor promoting genes leading to increased tumor cell proliferation and metastatic potential. Improved understanding of molecular pathways will enable establishment of useful prognostic and predictive factors, along with more effective treatment options

Hypoxia in solid tumors: biological responses to hypoxia and implications on therapy and prognosis

Tumor development, promotion and ability to spread depend greatly on tumor microenvironment. Rapid growth accompanied by inadequate angiogenesis is the reason why most solid tumors contain hypoxic regions. Activation of hypoxia signaling pathways stimulates neoangiogenesis, alters tumor metabolism, promotes a more aggressive tumor behavior and significantly affects its responsiveness to therapy. Growing amount of evidence suggest that hypoxia induces transcription of tumor promoting genes leading to increased tumor cell proliferation and metastatic potential. Improved understanding of molecular pathways will enable establishment of useful prognostic and predictive factors, along with more effective treatment options

NEW PRIMARY MALIGNANCIES AFTER BREAST CANCER DIAGNOSIS: INTERPLAY OF GENETICS, RISK FACTORS AND TREATMENT MODALITIES

Značajan napredak u ranom otkrivanju i kvalitetnije liječenje oboljelih rezultirali su činjenicom da u najrazvijenijim zemljama gotovo 90% žena s dijagnozom raka dojke preživi duže od 5 godina nakon dijagnoze i liječenja. Kod jedne od dvadeset žena oboljelih od raka dojke unutar 10 godina od postavljanja dijagnoze razvit će se novi primarni tumor čije sijelo nije dojka. Mutacije gena BRCA 1 i 2, RAD51C, MMR, p53, CDKN2A te 113insArg povezuju se s povećanim rizikom od razvoja raka dojke i drugih zloćudnih tumora. Čini se da i modalitet liječenja utječe na povećanje rizika od razvoja novoga zloćudnog tumora. Tako je nakon radioterapije primijećen povećan rizik za tkiva koja primaju višu dozu zračenja, osobito kod mlađih bolesnica, desetak godina nakon zračenja. Nađena je povećana incidencija leukemije i mijelodisplastičnog sindroma nakon liječenja kemoterapijom u odnosu na opću populaciju, ali smanjen rizik od razvoja zloćudnih tumora ostalih sijela. Odranije poznat povećan rizik od razvoja raka endometrija nakon hormonske terapije tamoksifenom potvrđen je i u novijim studijama. Mehanizam nastanka novih primarnih zloćudnih tumora nije potpuno razjašnjen. Koliki udio u tome imaju zajednički nasljedni čimbenici, mogući zajednički okolišni rizični čimbenici ili neželjene nuspojave specifičnog onkološkog liječenja tek se treba otkriti.Significant advances in early breast cancer detection and increased quality of care within developed countries resulted in longer than five years survival in almost 90% of women diagnosed and treated for breast cancer. One in twenty women diagnosed with breast cancer will develop a new primary non-breast malignancy within 10 years from initial diagnosis. Mutations in BRCA 1 i 2, RAD51C, MMR, p53, CDKN2A and 113insArg genes are linked with increased risk of breast cancer and other cancer sites. It seems that treatment modalities also play significant role in development of new primary malignancies. Tissues that receive higher doses of radiation during radiotherapy of breast cancer are under increased risk of developing new primary tumor, especially in younger women, ten years after the treatment. Chemotherapy may cause higher incidence of leukemia and myelodysplastic syndrome but lower overall risk for development of other malignancies. Connection between tamoxifen therapy and increased risk of endometrial cancer is well known and confirmed also in recent studies. The true mechanism of cancer development is still unclear. Significance of hereditary factors, possible common environmental risk factors or unwanted side effects of the specific anticancer treatments are yet to be discovered

Determinants of thyroid volume in healthy young adults of Dalmatia

Background and purpose: The aim of this study was to investigate thyroid volume (TV) and its determinants in healthy young adults without present or previous thyroid disease. Materials and methods: The study was performed in a sample of 145 healthy young participants aged 19-29 years, living in an iodine-sufficient area of Dalmatia. Dimensions of the thyroid gland were obtained by ultrasound and used to determine TV. Anthropometric data was collected, and measurements of serum TSH, fT4, Tg, TgAb, and TPOAb levels were determined. Correlations between TV and other continuous variables were determined using the Pearson correlation test, while multivariate linear regression analysis was used to determine the associations of the potential predictors for the TV. Results: TV in men was larger than in women (p=3.53x10-8) and was positively correlated with anthropometric measurements, with the highest correlation coefficient for height (r=0.53, p=6.36x10-12), then body surface area, BSA (r=0.48, p=1.68x10-9), weight (r=0.43, p=8.28x10-8) and body mass index, BMI (r=0.17, p=0.04). Age and cigarette smoking did not appear to be significantly associated with TV (p=0.13 and p=0.95, respectively). Univariate analysis showed TV correlated with fT4 plasma levels (r=0.35, 1.73x10-5), while multivariate analysis showed height and fT4 levels to be important parameters with a significant role in TV. Conclusions: We confirmed previously observed association of TV with sex and anthropometric parameters and reported a significant correlation between TV and fT4 levels. Furthermore, fT4 levels and height were found to be the important parameters for predicting TV.</p

The peptide hormone hepcidin: the main regulator of iron metabolism

Hepcidin je peptidni hormon i glavni je re- gulator metabolizma željeza. Otkriven je u humanom serumu i urinu 2000. godine i nazvan je LEAP-1 (engl. Liver Expressed Antimicrobial Protein). Nedugo nakon toga znanstvenici su pod vodstvom Tomasa Ganze u potrazi za antimikrobnim peptidima otkrili peptid povezan s upalom i nazvali ga “hepcidin”. Otkrili su da se sintetizira u jetri i da ima antimikrobna svojstva. Najveći broj istraživanja o djelovanju i regulaciji izlučivanja hepcidina učinjen je na mišjim modelima kada je ustanovljeno da se sinteza i izlučivanje hepcidina u miševa povećava u stanjima s povišenim količinama željeza u serumu i upalnim stanjima. Određivanje hepcidina u krvi i ostalim tjelesnim tekućinama određuje se imunološkim testovima s antihepcidinskim protutijelima - ELISA (prema engl. enzyme-linked immunosorbent assay) i masenom spektrometrijom. Koncentracije hepcidina u serumu određene masenom spektometrijom i koncentracije određene ELISA metodom dobro koreliraju. Imunološki testovi najtočnije mjere niske vrijednosti hepcidina, a masena spektrometrija točnije mjeri aktivnu formu hepcidina. Poremećaji u ekspresiji hepcidina javljaju se kod mnogih bolesti kao što su: anemija prouzročena kroničnim sistemskim bolestima, sideropenične anemije, maligne bolesti, hereditarne hemokromatoze i stanja s neefektivnom eritropoezom. Stoga mjerenje koncentracije hepcidina ima veliko značenje u dijagnostici i liječenju stanja u kojima je narušena ravnoteža željeza u organizmu. Napredak u razumijevanju uloge hepcidina u kontroli homeostaze željeza dovodi do novih mogućnosti liječenja u stanjima sa sniženim ili povišenim razinama željeza u organizmu. Hepcidin je nedavno identificiran kao akutno fazni protein s antimikrobnom i regulatornom funkcijom željeza. Mnogi su istra- živači pokazali interes za razvoj dijagnostičkog testa za mjerenje hepcidina u pasa. Ciljevi njihovog istraživanja bili su kloniranje i sekvenciranje gena psećeg hepcidina i prikupljanje preliminarnih podataka o pojavi hepcidina u pasa. Filogenetska analiza pokazala je da je humani hepcidin bio sličniji hepcidinu pasa nego hepcidinu glodavaca. U pasa, kao i u ljudi, hepcidin se najviše sinetitiza u jetri, a nešto slabije u bubrezima i plućnom tkivu pasa. Rezultat ovog istraživanja uspostavio je osnovu za buduća istraživanja psećeg hepcidina. Autori navode da psi mogu biti dobar model za istraživanje uloge hepcidina u ljudi.Hepcidin is a peptide hormone and the main regulator of iron metabolism in the body. It was discovered in human serum and urine in 2000 and named liver expressed antimicrobial protein-1 (LEAP-1). Research of antimicrobial peptides in relation to inflammatory response was conducted by Tomas Ganz. He named the protein hepcidin as it is produced by the liver and also has antimicrobial properties. The mouse model has been used in numerous studies on the role of hepcidin and its excretion regulation. It has also been shown that the synthesis of hepcidin is greatly stimulated by inflammation or iron overload. Hepcidin detection in serum and other body fluids is performed by the ELISA assay and mass spectrometry. The hepcidin concentrations in plasma measured by ELISA and by mass spectrometry are in correlation. ELISA assay is the most favourable method for the detection and measurement of hepcidin in low concentrations in fluids, whereas mass spectrometry is a more suitable measurement method for the active form of hepcidin. Chronic anaemia, sideropenic anaemia, malignant diseases, hereditary hemochromatosis, and ineffective erythropoiesis can all disrupt hepcidin secretion. Therefore, hepcidin concentrations may have significant relevance in the diagnosis and treatment of iron imbalance. Improving the knowledge of the role of hepcidin in iron haemostasis can lead to new treatment possibilities in cases of increased or decreased iron concentrations. Hepcidin has recently been identified as an acute phase protein with antimicrobial and iron regulatory roles. Many researchers have contributed to the development of diagnostic testing to assess canine hepcidin concentrations, with research focusing on cloning and sequencing the genes that regulate canine hepcidin production. Phylogenetic studies have revealed that human hepcidin is more similar to canine than murine hepcidin. In dogs, as in humans, hepcidin is predominantly produced in the liver. In dogs, it has been detected in kidneys and in the lungs. Based on this review article, a new foundation has been laid for novel research of canine hepcidin. The dog could serve as a suitable model to elucidate the role of human hepcidin

The structure–activity relationship and computational studies of 1,3-thiazole derivatives as cholinesterase inhibitors with anti-inflammatory activity

In our previous research, some screened 1,3-thiazole fragments were found to be potent by inhibiting LPS-induced TNF$\alpha$ and IL-8 release with IC50 values in the $\mu$M range without cytotoxic activity. In the current study, 1,3-thiazole fragments were further investigated as potent cholinesterase inhibitors prompted by the previously documented anti-inflammatory effect of AChE inhibitors. Molecular docking enabled insight into stabilizing interactions between the selected thiazoles and the active site of AChE and BChE. According to these experimental results, the cholinesterase inhibitory and anti-inflammatory activity of 1,3-thiazoles were correlated and confirmed that the same compounds inhibited LPS-stimulated TNF$\alpha$ cytokine production in PBMCs and enzymes cholinesterases