The influence of lovastatin on thrombomodulin gene expression in vascular endothelial cells--in vitro study.

OBJECTIVEStatins reduce lipids concentration in blood. The latest investigations show they also improved the function of vascular endothelial cells (ECs). Thrombomodulin (TM) is particularly important marker of ECs activity. We investigated the in vitro effect of lovastatin on the expression level of TM gene.METHODS AND RESULTSECs were incubated for 24 h in culture medium including lovastatin in 3 concentrations: 0.1, 1.0, 10.0 mol/l. The mRNA level of TM increased in correlation with rising concentrations of lovastatin to 600 % vs. control group.CONCLUSIONSTM is essential antithrombotic factor in endothelial cells. Lovastatin significantly raises thrombomodulin gene expression. It is important characteristics of this medicine, which prevents cardiovascular events

The influence of lovastatin on thrombomodulin gene expression in vascular endothelial cells--in vitro study.

<strong>OBJECTIVE</strong><br />Statins reduce lipids concentration in blood. The latest investigations show they also improved the function of vascular endothelial cells (ECs). Thrombomodulin (TM) is particularly important marker of ECs activity. We investigated the in vitro effect of lovastatin on the expression level of TM gene.<br /><br /><strong>METHODS AND RESULTS</strong><br />ECs were incubated for 24 h in culture medium including lovastatin in 3 concentrations: 0.1, 1.0, 10.0 mol/l. The mRNA level of TM increased in correlation with rising concentrations of lovastatin to 600 % vs. control group.<br /><br /><strong>CONCLUSIONS</strong><br />TM is essential antithrombotic factor in endothelial cells. Lovastatin significantly raises thrombomodulin gene expression. It is important characteristics of this medicine, which prevents cardiovascular events.<br /><br /&gt

Molecular diagnostic tests for thrombophilia in patients referred to genetic counseling clinic because due to recurrent pregnancy failure. One center’s experience.

The loss of three or more subsequent pregnancies before the end of the 22nd week is observed in 0.4–1% of women. Despite great advances in medicine, the causes of pregnancy failure (miscarriages, missed abortions and stillbirths), and the birth of a child or children with congenital abnormalities, are still not determined precisely. The aim: The purpose of the research was to determine the association of polymorphisms and mutations of coagulation factors II and V genes, as well as methylenetethrahydrofolate reductase (MTHFR) gene polymorphism, with the course of pregnancy and the type of reproductive failure. Methods: The research was performed in a group of 116 women referred to the Genetic Outpatient Clinic of the NCU SM in Bydgoszcz between 2009–2010 due to reproductive failures. The molecular tests for thrombophilia, i.e. mutation of the factor V Leiden, prothrombin gene mutation 20210G>A, and MTHFR polymorphism 677C>T were done in all patients. Results: The Leiden mutation was found in 8 women (homozygotic in 2 of them) and prothrombin gene mutation in 3. 85 women had the heterozygotic MTHFR polymorphism, while 24 the homozygotic one. Coexistence of the Leiden mutation and the MTHFR polymorphism was found in 3 patients with history of miscarriages. Conclusions: 1. The presence of the mutations that promote thrombophilia in the genes responsible for the foliate metabolism and for the plasma coagulation is often associated with pregnancy failures and may be their basic cause in some cases. 2. The percentage of women with pregnancy failures being heterozygotes (73.3%), homozygotes (20.7%) or both (94%) of the MTHFR gene 677C>T polymorphism is statistically significantly higher than the highest prevalence of these changes in the general population (55, 13%, and 68%, respectively). 3. The factor V gene Leiden mutation is associated mainly with recurrent spontaneous abortions. In the present study it was found only in the group of women with both early and late miscarriages

Prognostic significance of BCR-ABL rearrangement in childhood acute lymphoblastic leukemia

B a c k g r o u n d. Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. Presence of adverse risk factors determines risk group stratification in this disease. O b j e c t i v e. The aim of study was the analysis of results of therapy and role of prognostic risk factors in treatment of childhood ALL in kujawsko-pomorskie region in 1995-2010. P a t i e n t s a n d m e t h o d s. During this period, ALL was diagnosed in 223 patients. With respect to time period and therapy protocol, the patients were divided into two groups: group 1 A/B (1995-2002) and group 2 (2002- 2010). Probability of overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were analyzed. Uni- and multivariate analyzes for risk factors were performed. R e s u l t s. Over the analyzed 17-year period, OS has increased from 77.9% in group 1A and 73.7% in group 1B to 86.2% in group 2. Results of RFS and EFS have also increased during this time. The death rate has decreased from 26% in group 1A and 26.3% in group 1B to 10.2% in group 2. The most important adverse prognostic risk factors during the first period included involvement of liver, spleen, lymph nodes as well as poor response to initial therapy, while during the second period the most important independent risk factor was BCR-ABL rearrangement in lymphoblasts. C o n c l u s i o n s. The most important independent prognostic risk factors in pediatric ALL include advanced disease, BCR-ABL rearrangement, and initial response to therapy. These factors are used for stratification to treatment groups, intensification of therapy and hematopoietic stem cell transplantation.W s t ę p. Ostra białaczka limfoblastyczna (ALL) jest najczęstszym nowotworem wieku dziecięcego. W tej chorobie obecność czynników ryzyka decyduje o stratyfikacji pacjentów do grup ryzyka. C e l p r a c y. Analiza wyników terapii i roli czynników prognostycznych w ALL u dzieci w regionie kujawsko-pomorskim w latach 1995-2010. P a c j e n c i  i  m e t o d y k a. Analizą objęto 223 dzieci, które podzielono na 2 grupy w zależności od okresu terapii i stosowanych protokołów leczenia: grupa 1A/B (1995-2002) i grupa 2 (2002-2010). Wyznaczono prawdopodobieństwo przeżycia wolnego od zdarzeń (pEFS), prawdopodobieństwo przeżycia (pOS) i prawdopodobieństwa przeżycia wolnego od wznowy (pRFS). Przeprowadzono analizę jedno- i wielowariantową czynników ryzyka niepowodzenia terapii. Wy n i k i. W analizowanym okresie 17 lat, OS wzrosło od 77,9% w grupie 1A i 73,7% w grupie 1B do 86,2% w grupie 2. Wyniki RFS i EFS również uległy poprawie. W tym czasie odsetek zgonów obniżył się z 26% w grupie 1A i 26,3% w grupie 1B do 10,2% w grupie 2. W analizie czynników ryzyka wykazano, że w pierwszym analizowanym okresie zajęcie wątroby, śledziony i węzłów chłonnych oraz niekorzystna początkowa odpowiedź na terapię były związane z gorszymi ostatecznymi wynikami terapii, natomiast w drugim okresie czasu najsilniejszym niezależnym niekorzystnym czynnikiem rokowniczym była obecność rearanżacji BCR-ABL w limfoblastach. Wn i o s k i. Najważniejszymi czynnikami prognostycznymi w ALL u dzieci są: zaawansowanie choroby, odpowiedź na leczenie oraz obecność rearanżacji BCR-ABL, które są podstawą stratyfikacji do grup ryzyka, intensyfikacji leczenia w grupach wysokiego ryzyka oraz kwalifikacji do przeszczepiania komórek krwiotwórczych

Znaczenie prognostyczne rearanżacji BCR-ABL w ostrej białaczce limfoblastycznej u dzieci

B a c k g r o u n d . Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. Presence of adverse risk factors determines risk group stratification in this disease.O b j e c t i v e . The aim of study was the analysis of results of therapy and role of prognostic risk factors in treatment of childhood ALL in kujawsko-pomorskie region in 1995-2010.P a t i e n t s a n d m e t h o d s . During this period, ALL was diagnosed in 223 patients. With respect to time period and therapy protocol, the patients were divided into two groups: group 1 A/B (1995-2002) and group 2 (2002- 2010). Probability of overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were analyzed. Uni- and multivariate analyzes for risk factors were performed.R e s u l t s . Over the analyzed 17-year period, OS has increased from 77.9% in group 1A and 73.7% in group 1B to 86.2% in group 2. Results of RFS and EFS have also increased during this time. The death rate has decreased from 26% in group 1A and 26.3% in group 1B to 10.2% in group 2. The most important adverse prognostic risk factors during the first period included involvement of liver, spleen, lymph nodes as well as poor response to initial therapy, while during the second period the most important independent risk factor was BCR-ABL rearrangement in lymphoblasts.C o n c l u s i o n s . The most important independent prognostic risk factors in pediatric ALL include advanced disease, BCR-ABL rearrangement, and initial response to therapy. These factors are used for stratification to treatment groups, intensification of therapy and hematopoietic stem cell transplantation.W s t ę p . Ostra białaczka limfoblastyczna (ALL) jest najczęstszym nowotworem wieku dziecięcego. W tej chorobie obecność czynników ryzyka decyduje o stratyfikacji pacjentów do grup ryzyka.C e l p r a c y . Analiza wyników terapii i roli czynników prognostycznych w ALL u dzieci w regionie kujawsko-pomorskim w latach 1995-2010.P a c j e n c i  i  m e t o d y k a . Analizą objęto 223 dzieci, które podzielono na 2 grupy w zależności od okresu terapii i stosowanych protokołów leczenia: grupa 1A/B (1995-2002) i grupa 2 (2002-2010). Wyznaczono prawdopodobieństwo przeżycia wolnego od zdarzeń (pEFS), prawdopodobieństwo przeżycia (pOS) i prawdopodobieństwa przeżycia wolnego od wznowy (pRFS). Przeprowadzono analizę jedno- i wielowariantową czynników ryzyka niepowodzenia terapii.Wy n i k i . W analizowanym okresie 17 lat, OS wzrosło od 77,9% w grupie 1A i 73,7% w grupie 1B do 86,2% w grupie 2. Wyniki RFS i EFS również uległy poprawie. W tym czasie odsetek zgonów obniżył się z 26% w grupie 1A i 26,3% w grupie 1B do 10,2% w grupie 2. W analizie czynników ryzyka wykazano, że w pierwszym analizowanym okresie zajęcie wątroby, śledziony i węzłów chłonnych oraz niekorzystna początkowa odpowiedź na terapię były związane z gorszymi ostatecznymi wynikami terapii, natomiast w drugim okresie czasu najsilniejszym niezależnym niekorzystnym czynnikiem rokowniczym była obecność rearanżacji BCR-ABL w limfoblastach.Wn i o s k i . Najważniejszymi czynnikami prognostycznymi w ALL u dzieci są: zaawansowanie choroby, odpowiedź na leczenie oraz obecność rearanżacji BCR-ABL, które są podstawą stratyfikacji do grup ryzyka, intensyfikacji leczenia w grupach wysokiego ryzyka oraz kwalifikacji do przeszczepiania komórek krwiotwórczych