Pre-symptomatic diagnostics of medullary thyroid carcinoma using r-DNA methods

Razlikovanje sporadičnog i nasljednog medularnog karcinoma štitnjače od velikog je kliničkog značenja kako zbog razlike u prognozi, tako i potrebe za presimptomatskom dijagnostikom i genskim savjetovanjem u potonjem slučaju. Nasljedne mutacije proto-onkogena ret dovode do nastanka sindroma multiple endokrine neoplazije tipa 2. Somatske točkaste mutacije ovog gena prisutne su u sporadičnim medularnim karcinomima štitnjače. Metode molekularne medicine omogućuju genetičke analize kojima se potvrđuje ili isključuje prisustvo nasljedne mutacije. Ujedno omogućuju i presimptomatsko otkrivanje bolesti u zdravih ljudi.The distinction of sporadic from inherited medullary thyroid carcinomas (MTCs) is of clinical importance because of the differences in prognosis and the need for family screening for genetic counselling required in the latter. Germline mutations in the ret proto-oncogene are associated with multiple endocrine neoplasia type 2. Somatic point mutations in the same gene are identified in a subset of sporadically occurring MTCs. The methods of molecular medicine are suitable to distinguish heritable from non-heritable MTCs and identify asymptomatic individuals at risk

Pre-symptomatic diagnostics of medullary thyroid carcinoma using r-DNA methods

Razlikovanje sporadičnog i nasljednog medularnog karcinoma štitnjače od velikog je kliničkog značenja kako zbog razlike u prognozi, tako i potrebe za presimptomatskom dijagnostikom i genskim savjetovanjem u potonjem slučaju. Nasljedne mutacije proto-onkogena ret dovode do nastanka sindroma multiple endokrine neoplazije tipa 2. Somatske točkaste mutacije ovog gena prisutne su u sporadičnim medularnim karcinomima štitnjače. Metode molekularne medicine omogućuju genetičke analize kojima se potvrđuje ili isključuje prisustvo nasljedne mutacije. Ujedno omogućuju i presimptomatsko otkrivanje bolesti u zdravih ljudi.The distinction of sporadic from inherited medullary thyroid carcinomas (MTCs) is of clinical importance because of the differences in prognosis and the need for family screening for genetic counselling required in the latter. Germline mutations in the ret proto-oncogene are associated with multiple endocrine neoplasia type 2. Somatic point mutations in the same gene are identified in a subset of sporadically occurring MTCs. The methods of molecular medicine are suitable to distinguish heritable from non-heritable MTCs and identify asymptomatic individuals at risk

Epigenetics and major depression disorder

Veliki depresivni poremećaj (MDD, od engl. Major Depressive Disorder) jedan je od najčešćih psihosomatskih poremećaja, sa snažnom tendencijom porasta broja oboljelih. Do 2020. godine mogao bi postati drugi najveći zdravstveni svjetski problem. Uzroci nastanaka bolesti, kao i klinička slika, vrlo su složeni. Ovakva složenost posljedica je aktivnosti velikog broja gena, od kojih svaki „pridonosi“ nastanku i izražaju bolesti s relativno malim udjelom. Sve veći broj rezultata mnogih studija upućuje na važnost epigenetičkih mehanizama regulacije aktivnosti gena, kao poveznicu bioloških i drugih čimbenika koji se povezuju s nastankom depresije. Većina istraživanja pokazuje uzročno-posljedičnu vezu između različitih bioloških i psihosocijalnih čimbenika, s jedne strane, te međuovisne promjene obrazaca metilacije/demetilacije molekule DNK i promjene koda histona, s druge strane. Sve je više podataka o značajnoj ulozi različitih nekodirajućih molekula RNK u nastanku depresivnog poremećaja. Konačno, pokazalo se da mnogi antidepresivi djeluju na epigenom. Ovaj učinak otvara potpuno novo poglavlje u razumijevanju patogeneze i epigenetičke podloge liječenja depresivnog poremećaja.Major Depressive Disorder (MDD) represents one of the most common psychosomatic disorders with a pronounced increasing incidence. It is expected to become the number two major world health problem by 2020. The causes of MDD as well as its clinical features are very complex. The probable reason for such complexity relates to a large number of genes, being involved in a condition where each gene makes only a minor contribution to the MDD etiology and clinic phenotypes. An increasing number of studies published during last decade have pointed out the importance of epigenetic regulatory mechanisms in affecting gene activity as well as constituting a possible link between biological and other factors related to MDD. Most of the studies have shown causality between different, MDD related biological and psycho-social factors. They have also described mutually controlled processes involved in the regulation of DNA methylation and establishment of histone code. There is a growing body of evidence on the significant role of non-coding RNA molecules in the ethiopathogenesis of MDD. Finally, it was shown that many antidepressive agents exert much influence on the epigenome. Such activity opens a new chapter in understanding the MDD pathogenesis and the basis for epigenome-reshaping related therapy

Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning

Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal disease that spreads quickly. However, currently available biomarkers cannot precisely predict the course of a disease, and novel strategies are needed to guide prostate cancer management. Amino acids serve numerous roles in cancers, among which are energy production, building block reservoirs, maintenance of redox homeostasis, epigenetic regulation, immune system modulation and resistance to therapy. In this article, by using The Cancer Genome Atlas (TCGA) data, we found that the expression of amino acid metabolism-related genes is highly aberrant in prostate cancer, which holds potential to be exploited in biomarker design or in treatment strategies. This change in expression is especially evident for catabolism genes and transporters from the solute carrier family. Furthermore, by using recursive partitioning, we confirmed that the Gleason score is strongly prognostic for progression-free survival. However, the expression of the genes SERINC3 (phosphatidylserine and sphingolipids generation) and CSAD (hypotaurine generation) can refine prognosis for high and low Gleason scores, respectively. Therefore, our results hold potential for novel prostate cancer progression biomarkers

Epigenetics and gene physiology

Za razliku od genomike, koja se temelji na proučavanju građe – anatomije gena, epigenomika se temelji na izučavanju nasljednih varijacija u aktivnosti gena, dakle njihovoj fiziologiji. Osnovni epigenetički procesi, regulatori aktivnosti gena su metilacija molekule DNA i post translacijske modifikacije histona. Ova dva procesa međusobno se nadopunjuju pri čemu stvaraju epigenetičku mrežu događaja koja u konačnici regulira aktivnost pojedinih gena. Uspostava određenog tipa epigenetičke mreže ovisi o anatomiji gena i njegovog promotora te stalnom međudjelovanju egzogenih i endogenih čimbenika koji dovode do stvaranja karakterističnog epigenetičkog biljega. Sve se više uviđa važnost reverzibilnosti uspostave i uklanjanja epigenetičkih molekularnih biljega u svim, a naročito u zloćudnim bolestima. Istraživanja u području epigenomike, primjene novih, epigenomskih pristupa u liječenju, a posebno u području razvoja “pametnih”, epigenetičkih lijekova, u uzlaznoj su putanji koja još uvijek nije dosegla svoj zenit.Epigenetics is focused on gene physiology, analyzing inherited variations in gene expression, while genomics is focused on gene anatomy, analyzing gene structure. DNA methylation and histone post-translational modifications are the basic epigentic mechanisms regulating gene activity. These two processes complement each other, creating an epigenetic network of events which regulates specifi c gene activity. Establishing a particular type of epigenetic network depends on the anatomy of both the gene and its promoter, as well as the permanent interaction of exogenic and endogenic factors, which result in a particular epigenetic mark. As a result of new data, the importance of epigenetic marks as a reversible process, is becoming increasingly relevant to disease development, especially for cancer. One looks forward to the promise, still to be fully realized, of research in epigenetics, including new approaches to therapy and the development of “smart” epigenetic drugs