Prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations on outcome in acute myeloid leukemia with normal karyotype

Mutacije u genima za izocitrat dehidrogenazu 1 i 2 (IDH1 i IDH2) su česte rekurentne molekularne promene kod akutne mijeloidne leukemije sa normalnim kariotipom (AMLNK). Uticaj IDH mutacija na kliničke karakteristike i ishod lečenja kod AML-NK su u velikoj meri istražene, ali samo nekoliko studija je pratilo ove mutacije u toku bolesti. Ciljevi: 1) Utvrđivanje učestalosti prisustva IDH1 i IDH2 mutacija kod bolesnika sa AMLNK; 2) Utvrđivanje uticaja prisustva IDH1 i IDH2 mutacija na učestalost i dužinu remisije, ukupno preživljavanje i povezanosti IDH1 i IDH2 mutacija i drugih prognostičkih markera: parametri krvne slike, biohemijski parametri, citološki tip bolesti, imunofenotipska i molekularno-genetska obeležja (FLT3 i NPM1 mutacije); 3) Utvrđivanje stabilnosti IDH1 i IDH2 mutacija u toku bolesti poređenjem uzoraka na početku bolesti sa uzorcima u toku kompletne remisije (KR), odnosno u recidivu bolesti. Materijal i metodologija istraživanja: Uzorci od 110 starijih de novo AML-NK bolesnika bili su ispitani na IDH1 i IDH2 mutaciju. Ispitana je njihova povezanost sa drugim prognostičkim markerima i ishodom lečenja. Pored toga, praćena je stabilnost ovih mutacija u KR i recidivu. Rezultati: IDH mutacije su nađene kod 25 (23%) bolesnika: IDH1 je imalo 8 (7%) bolesnika, svi od njih su imali IDHR132; IDH2 je imalo 17 (16%) bolesnika (15 IDHR140; 2 IDHR172). IDH+ bolesnici su imali viši broj trombocita (p=0.024), kao i veći procenat blasta u perifernoj krvi (p=0.031) u odnosu na IDH- bolesnike. IDH+ bolesnici su imali nižu stopu KR u poređenju sa IDH- bolesnicima (44% vs 60%, p=0.152), ali to nije bilo statistički značajno. Osim toga, IDH mutacije su imale samo neznatan uticaj na trajanje remisije bez bolesti (IDH+-12 meseci vs IDH--17 meseci; p=0.091), dok je ukupno preživljavanje (OS) IDH+ bolesnika bilo kraće u poređenju sa IDH- bolesnicima (2 vs 7 meseci; p=0.039). Nepovoljan uticaj IDH mutacije na OS je naročito bio očigledan kod bolesnika koji nisu imali NPM1 mutaciju (5 vs 12 meseci, p=0.050). IDH mutacije su ispitivane sekvencionalno kod 19 IDH+ bolesnika koji su bili živi posle indukcije...Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent recurrent molecular lesions in acute myeloid leukemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Aim: 1) To determine the frequency of presence of IDH1 and IDH2 mutations in patients with AML-NK; 2) To determine the effect of the presence of IDH1 and IDH2 mutations on duration of remission, overall survival and the association IDH1 and IDH2 mutations and other prognostic markers: blood parameters, the biochemical parameters, cytological disease type, immunophenotypic and molecular-genetic characteristics (FLT3 and NPM1 mutations); 3) To determine the stability IDH1 and IDH2 mutations in the course of the disease by comparing the samples at the start of the disease with samples during complete remission (CR), and in a relapse of the disease. Material and methodes: Samples from 110 adult de novo AML-NK patients were assessed for IDH1 and IDH2 mutations. Their association with other prognostic markers and outcome was analyzed. In addition, we monitored the stability of these mutations during CR and relapse. Results: IDH mutations were found in 25 (23%) patients: IDH1 in 8 (7%), all of them IDHR132; IDH2 in 17 (16%) patients (15 IDHR140; 2 IDHR172). IDH+ patients had higher platelet counts (p=0.024), as well as a higher percentage of peripheral blood blasts (p=0.031) than IDH- patients. They tended to have a lower CR rate compared to IDH- patients (44% vs 60%, p=0.152), but this was not statistically significant. Moreover, IDH mutations had only a slight impact on disease free survival (IDH+-12 months vs IDH--17 months; p=0.091), but overall survival (OS) of our IDH+ patients was shorter in comparison with IDH- patients (2 vs 7 months; p=0.039)..

Prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations on outcome in acute myeloid leukemia with normal karyotype

Mutacije u genima za izocitrat dehidrogenazu 1 i 2 (IDH1 i IDH2) su česte rekurentne molekularne promene kod akutne mijeloidne leukemije sa normalnim kariotipom (AMLNK). Uticaj IDH mutacija na kliničke karakteristike i ishod lečenja kod AML-NK su u velikoj meri istražene, ali samo nekoliko studija je pratilo ove mutacije u toku bolesti. Ciljevi: 1) Utvrđivanje učestalosti prisustva IDH1 i IDH2 mutacija kod bolesnika sa AMLNK; 2) Utvrđivanje uticaja prisustva IDH1 i IDH2 mutacija na učestalost i dužinu remisije, ukupno preživljavanje i povezanosti IDH1 i IDH2 mutacija i drugih prognostičkih markera: parametri krvne slike, biohemijski parametri, citološki tip bolesti, imunofenotipska i molekularno-genetska obeležja (FLT3 i NPM1 mutacije); 3) Utvrđivanje stabilnosti IDH1 i IDH2 mutacija u toku bolesti poređenjem uzoraka na početku bolesti sa uzorcima u toku kompletne remisije (KR), odnosno u recidivu bolesti. Materijal i metodologija istraživanja: Uzorci od 110 starijih de novo AML-NK bolesnika bili su ispitani na IDH1 i IDH2 mutaciju. Ispitana je njihova povezanost sa drugim prognostičkim markerima i ishodom lečenja. Pored toga, praćena je stabilnost ovih mutacija u KR i recidivu. Rezultati: IDH mutacije su nađene kod 25 (23%) bolesnika: IDH1 je imalo 8 (7%) bolesnika, svi od njih su imali IDHR132; IDH2 je imalo 17 (16%) bolesnika (15 IDHR140; 2 IDHR172). IDH+ bolesnici su imali viši broj trombocita (p=0.024), kao i veći procenat blasta u perifernoj krvi (p=0.031) u odnosu na IDH- bolesnike. IDH+ bolesnici su imali nižu stopu KR u poređenju sa IDH- bolesnicima (44% vs 60%, p=0.152), ali to nije bilo statistički značajno. Osim toga, IDH mutacije su imale samo neznatan uticaj na trajanje remisije bez bolesti (IDH+-12 meseci vs IDH--17 meseci; p=0.091), dok je ukupno preživljavanje (OS) IDH+ bolesnika bilo kraće u poređenju sa IDH- bolesnicima (2 vs 7 meseci; p=0.039). Nepovoljan uticaj IDH mutacije na OS je naročito bio očigledan kod bolesnika koji nisu imali NPM1 mutaciju (5 vs 12 meseci, p=0.050). IDH mutacije su ispitivane sekvencionalno kod 19 IDH+ bolesnika koji su bili živi posle indukcije...Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent recurrent molecular lesions in acute myeloid leukemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Aim: 1) To determine the frequency of presence of IDH1 and IDH2 mutations in patients with AML-NK; 2) To determine the effect of the presence of IDH1 and IDH2 mutations on duration of remission, overall survival and the association IDH1 and IDH2 mutations and other prognostic markers: blood parameters, the biochemical parameters, cytological disease type, immunophenotypic and molecular-genetic characteristics (FLT3 and NPM1 mutations); 3) To determine the stability IDH1 and IDH2 mutations in the course of the disease by comparing the samples at the start of the disease with samples during complete remission (CR), and in a relapse of the disease. Material and methodes: Samples from 110 adult de novo AML-NK patients were assessed for IDH1 and IDH2 mutations. Their association with other prognostic markers and outcome was analyzed. In addition, we monitored the stability of these mutations during CR and relapse. Results: IDH mutations were found in 25 (23%) patients: IDH1 in 8 (7%), all of them IDHR132; IDH2 in 17 (16%) patients (15 IDHR140; 2 IDHR172). IDH+ patients had higher platelet counts (p=0.024), as well as a higher percentage of peripheral blood blasts (p=0.031) than IDH- patients. They tended to have a lower CR rate compared to IDH- patients (44% vs 60%, p=0.152), but this was not statistically significant. Moreover, IDH mutations had only a slight impact on disease free survival (IDH+-12 months vs IDH--17 months; p=0.091), but overall survival (OS) of our IDH+ patients was shorter in comparison with IDH- patients (2 vs 7 months; p=0.039)..

Teacher training on application of historical method in teaching and professional development

Contemporary teaching of social sciences has a goal of transferring selected knowledge to students with as much of their active participation in the process of teaching as possible, primarily, through student activity while working with documents and sources of knowledge. It is necessary to provide students with minimal methodological training so that they would know how to critically assess original documents. A teacher trains students methodologically through work with selected examples, which requires basic knowledge of historical method and source criticism. it is assumed that students use acquired knowledge for later continuous professional development and self-education. With the aim of satisfying these needs, teachers of history and of other socio-humanistic sciences should be trained to apply the historical method and source criticism - written documents - to their teaching practice. The authors present main challenges of working with written sources. The paper rooted in the literature survey and the summary of experiences in teaching and researching history

Historians and modernity

Modernity investigates and explains the past, according to its standards and expectations. Historians are the researchers whose results are under the surveillance of the modern national ideology, current policies, institutions, and citizens. Everybody wants to monitor and evaluate, but they honestly do not help researchers and do not appreciate professionalism in the right way. The specificity of the past, its inaccessibility to direct research, lack and deficiency of the remains and sources of many research areas are objective obstacles to historical studies. It is undisputed that the outcomes of the research affects personality, knowledge, and ability of researchers, as well as their possible involvement. Impacts of ideology, politics, powerful groups, and individuals must not be neglected. The authors, based on the reference literature, research experiences, and reflections, tend to highlight some of these issues

Parliamentary elections in the srez of Berane in 1925 and 1927

During the second half of the 20s in the last century political circumstances in Berane and its narrow gravitational area were known by constant rivalry between two civil political parties where the National Radical Party and the Yugoslav Democratic Party as well as the new Independent Democratic Party that was formed after the split of the Yugoslav Democratic Party, were the most influential ones within the Serbian national corps. Some new party lists - the Association of Peasants and the Yugoslav Muslim Organization appeared for the first time during the elections in 1925 and 1927 while they were not part of the organized elections in the first half of the 20s. Moreover, the electoral struggles were also characterized by the appearance of 'factionary' party lists of candidates that were emphasized by certain local political leaders who were guided by their own ambitions, in spite of the orientation of the party headquarters especially among 'democrats'. The common characteristics of the elections in 1925 and 1927 were that they took part in the environment which did not have the developed tradition of political organizing, and then it was considered as the undeveloped agricultural area without economic, financial subjects or cultural institutions that could influence the content of campaign and the results of elections more seriously. In the area of district political parties that were active in the country competed with each other, while the individuals, who did not live in this area nor were even born in this region, were often members of these lists and had mandates. Furthermore, there was the separation of voters and also different lists from the same party were presented several times. The followers of Muhammad had recognizable profiled candidates and lists but it can be proved that religious differences were not the obstacle for becoming a candidate in the parties as well as in their common lists. The results of the elections in 1925 left Berane and its surrounding without 'its' Member of Parliament. Although Pavle Čubrović, the representative of the 'dissident list' of the Democratic Party, won the most votes, the fact that most voters elected the radicals' lists of candidates during the elections, decreased the importance of his result. However, two years later the result of the elections was completely different - the list of candidates of the Democratic Party won all three mandates for the Member of Parliament during the elections and therefore Čubrović became the Member of Parliament for the second time

Parlamentary elections in the District of Berane in 1920 and 1923

The lack of more significant political tradition due to the fact that Berane and the area of Donji Vasojevici were liberated from the Ottoman authorities in 1912, which lasted for many centuries, as well as the fact that only three years later a two-year period of AustroHungarian occupation took place, mainly predetermined the atmosphere of political life in the first years after Yugoslav unification in 1918. The underdevelopment of the party organizations and grouping based on denominational, tribal and even on belonging to some brotherhood, were characteristic for the beginnings of political subjects in Berane district. These were party organizations whose headquarters were settled in Belgrade, Sarajevo and Skopje and whose leaders were as in the case of other districts in the province, often resorted to emphasizing their candidature in them. There were also the individuals on the local political scene, mostly teachers or the civil servants, who were representatives of the party's ideas and programme in their surrounding and therefore also the incumbent candidates of their lists. During parliamentary elections in Berane in 1920 and 1923 the main political rivalry was between members of the radical and democratic party while it was characterised by fragmentation of the party namely emphasizing 'dissident' candidate list as the consequences of political ambitions of the individuals. Regarding the results of elections in 1920 and 1923, generally speaking, it can be said that during the first half of the 20s of the last century Democratic party dominated in Berane district. Berane got 'its' Member of the Parliament - 'a democrat' Pavle Cubrovic, PhD while in 1923 it no longer had its representative in the parliament. Namely, despite Cubrovic's triumph in Berane district, since his candidate list did not get enough votes in the first round of elections, the position of the Member of the Parliament 'escaped' him

Expression of β-Catenin Marker in Colorectal Cancer Cells after Treatment with Royal Jelly

The deregulation of a Wnt/β-catenin signal pathway is common in colorectal cancer, while β-catenin, its crucial component, is the target for the development of many anticancer therapies. Here, we showed that royal jelly, as a well-known beneficial natural product, can affect β-catenin at both the gene and protein level in HCT-116 colorectal cancer cell line. Our results indicate the effectiveness of royal jelly in targeting crucial markers responsible for the development and progression of cancer. Therefore, royal jelly presents a promising agent for the development of supplementary anticancer therapy

Expression of β-Catenin Marker in Colorectal Cancer Cells after Treatment with Royal Jelly

The deregulation of a Wnt/β-catenin signal pathway is common in colorectal cancer, while β-catenin, its crucial component, is the target for the development of many anticancer therapies. Here, we showed that royal jelly, as a well-known beneficial natural product, can affect β-catenin at both the gene and protein level in HCT-116 colorectal cancer cell line. Our results indicate the effectiveness of royal jelly in targeting crucial markers responsible for the development and progression of cancer. Therefore, royal jelly presents a promising agent for the development of supplementary anticancer therapy

Extract of Edible Mushroom Laetiporus sulphureus Affects the Redox Status and Motility of Colorectal and Cervical Cancer Cell Lines

Colorectal and cervical cancer are major health problems worldwide, and adjuvant therapy, which uses fungi, is considered valuable in cancer treatment. Herein, we evaluated effects of edible mushroom species Laetiporus sulphureus on the viability, redox status, and motility of two different cancer cell lines. Treatment induced oxidative stress and inhibition of migratory potential in both tested cell lines, showing cell selective activity and affecting HCT-116 and HeLa cells in a different manner. However, the presented effects of this mushroom should not be neglected in future studies, especially detailed studies on drug development