12 research outputs found
Treatment of chronic myelogenous leukemia – current status and future prospects
Wprowadzenie imatynibu do terapii przewlekłej białaczki szpikowej (PBSz) można już z perspektywy ponad dekady ocenić jako jedno z przełomowych wydarzeń w leczeniu nowotworów i w historii onkologii. Drobnocząsteczkowy inhibitor swoiście hamujący aktywność onkogennej kinazy tyrozynowej BCR/ABL, odpowiedzialnej za transformację nowotworową komórki macierzystej krwiotworzenia, okazał się zaskakująco skuteczny u większości chorych i zrewolucjonizował terapię PBSz. Niestety znacząca grupa chorych z powodu wystąpienia oporności lub nietolerancji nie odnosi spodziewanych korzyści terapeutycznych, co powoduje, że jednym z głównych celów badań stało się poszukiwanie nowych, jeszcze skuteczniejszych leków. W ostatnich 5 latach do terapii wprowadzono inhibitory drugiej generacji (dasatynib, nilotynib, bosutynib), trwają badania kliniczne nad inhibitorami trzeciej generacji (np. ponatynib hamujący zmutowaną kinazę BCR/ABL z mutacją T315I) oraz inhibitorami allosterycznymi, które hamują kinazę w innym mechanizmie, nie wiążąc się z jej centrum aktywnym. Żaden z dotychczas badanych leków nie eliminuje macierzystych komórek białaczkowych będących źródłem choroby, dlatego obecnie uważa się, że leczenie musi być kontynuowane dożywotnio. Ponieważ celem dla terapii powinno być całkowite wyleczenie chorego i możliwość przerwania leczenia, trwają badania nad możliwością całkowitej eradykacji białaczki, przez zastosowanie terapii łączonych. Można mieć nadzieję, że tak jak sukces imatynibu w terapii PBSz wyznaczył nowy kierunek w onkologii, tak samo osiągnięcie celu w postaci całkowitego wyleczenia pomoże w znalezieniu skutecznej terapii w innych nowotworach.Introduction of imatinib to the treatment of chronic myelogenous leukemia (CML) more than a decade ago may be considered as one of the milestones in the history of cancer treatment and oncology. Small molecule inhibitor, which specifically inhibits BCR/ABL oncogenic tyrosine kinase, responsible for malignant transformation of hematopoietic stem cell proved to be unexpectedly effective in the majority of patients and has revolutionized CML therapy. Unfortunately, a significant group of patients develops resistance or is intolerant to the drug which necessitate search for new better drugs. In the last 5 years 2nd generation inhibitors have been approved (dasatinib, nilotinib and bosutinib), clinical trials are ongoing with 3rd generation inhibitors (among them ponatinib, active against BCR/ABL with T315I mutation) and allosteric inhibitors. None of the available drugs eliminates leukemia stem cells, which are the roots of the disease, therefore therapy must be continued indefinitely. Since ultimate goal is to cure the disease there are number of trials to eradicate the disease with combination therapies. We may expect that such like imatinib opened new therapeutic horizons in oncology, complete eradication of CML will help to find cure other cancers
Statins in prevention and therapy of cancer
Statyny, będące inhibitorami 3-hydroksy-3-metylo-glutarylo-koenzymu A (HMG-CoA), jednego z najważniejszych
enzymów szlaku syntezy cholesterolu, należą do grupy leków powszechnie stosowanych
w leczeniu hipercholesterolemii. Obecnie duże zainteresowanie wzbudza ich potencjalne działanie zapobiegające
powstawaniu nowotworu i zastosowanie w terapii chorób nowotworowych. Wyniki badań in vitro
i in vivo potwierdzają cytostatyczne i cytotoksyczne działanie statyn w stosunku do różnych linii komórek
nowotworowych. Ponadto statyny hamują waskularyzację w obrębie guza i zapobiegają przerzutom.
Obserwacje kliniczne nie potwierdzają w pełni wyników badań przedklinicznych. Dotychczas w próbach
randomizowanych nie potwierdzono wyników badań kliniczno-kontrolnych, w których wykazano znaczący
spadek ryzyka choroby nowotworowej u pacjentów przyjmujących statyny. Również kliniczne próby
wykorzystania statyn w terapii nie przyniosły oczekiwanego rezultatu. Niniejsza praca jest podsumowaniem
dotychczasowej wiedzy na temat możliwości zastosowania statyn w prewencji i terapii nowotworów,
a także prezentacją kierunków obecnie prowadzonych badań.Statins, inhibitors of one of the most important enzymes of cholesterol synthesis pathway - 3-hydroxy-3-
-methyl-glutharyl-coenzyme-A (HMG-CoA), are commonly used as cholesterol level reducing drugs.
Nowadays, more and more scientists take an interest of statins as potential both preventive and therapeutical
anticancer agents. In vitro and in vivo experiments showed cytotoxic and cytostatic effect of
statins in numerous cancer cell lines. Moreover, statins inhibit vascularisation in tumor and prevent metastasis.
Optimistic pre-clinical tests results are not completely confirmed by clinical observations. Very
promising results of clinical control trials showing a significant reduction of cancer risk in patients receiving
statins were not confirmed in randomized clinical trials so far. Clinical trials concerning statins in
anticancer therapy were not as successful as supposed. In this article we are trying to summarize current
knowledge about potential statins usage in cancer prevention and treatment
Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response
Clonal Evolution of Multiple Myeloma—Clinical and Diagnostic Implications
Plasma cell dyscrasias are a heterogeneous group of diseases characterized by the expansion of bone marrow plasma cells. Malignant transformation of plasma cells depends on the continuity of events resulting in a sequence of well-defined disease stages, from monoclonal gammopathy of undetermined significance (MGUS) through smoldering myeloma (SMM) to symptomatic multiple myeloma (MM). Evolution of a pre-malignant cell into a malignant cell, as well as further tumor progression, dissemination, and relapse, require development of multiple driver lesions conferring selective advantage of the dominant clone and allowing subsequent evolution under selective pressure of microenvironment and treatment. This process of natural selection facilitates tumor plasticity leading to the formation of genetically complex and heterogenous tumors that are notoriously difficult to treat. Better understanding of the mechanisms underlying tumor evolution in MM and identification of lesions driving the evolution from the premalignant clone is therefore a key to development of effective treatment and long-term disease control. Here, we review recent advances in clonal evolution patterns and genomic landscape dynamics of MM, focusing on their clinical implications
FoxP3 Tregs Response to Sublingual Allergen Specific Immunotherapy in Children Depends on the Manifestation of Allergy
Over the last decades allergic diseases has become a major health problem worldwide. The only specific treatment to date is allergen specific immunotherapy (ASIT). Although it was shown that ASIT generates allergen-tolerant T cells, detailed mechanism underlying its activity is still unclear and there is no reliable method to monitor its effectiveness. The aim of our study was to evaluate ASIT influence on the frequency of forkhead box P3 (FoxP3) Tregs in allergic children with various clinical manifestations. The relative number of FoxP3 Tregs in 32 blood samples from allergic children at baseline and/or after 1 year of ASIT was assessed by flow cytometry. In the entire studied group, the percentage of FoxP3 Tregs did not increase 1 year after ASIT. Nevertheless, the percentage of FoxP3 Tregs after ASIT significantly increased in children with respiratory allergy (conjunctivitis, asthma, and rhinitis) coexisting with nonrespiratory manifestations (food allergy and/or atopic dermatitis), whereas, in patients with respiratory allergy only, the percentage of FoxP3 Tregs decreased. To the best of our knowledge, this is the first report showing various differential FoxP3 Tregs response to ASIT in allergic children. FoxP3 Tregs number could be useful in treatment monitoring. Further studies are warranted to confirm these observations
P393: GENETIC CHARACTERISTICS OF PEDIATRIC B-OTHER ACUTE LYMPHOBLASTIC LEUKEMIA COHORT USING TARGETED RNA SEQUENCING
P656: NOVEL THIAZOLIDINEDIONE WITH HDAC INHIBITING PROPERTIES OPTIMIZED FOR CHRONIC MYELOID LEUKEMIA TREATMENT
PB2062: PAROXYSMAL NOCTURNAL HEMOGLOBINURIA SCREENING AFTER INTRODUCTION OF HIGH-SENSITIVITY DIAGNOSTICS – A SINGLE-CENTER 10-YEAR EXPERIENCE
Celiac antibodies in children with type 1 diabetes – A diagnostic validation study
Introduction: Autoimmune diseases, such as celiac disease (CD) and diabetes mellitus type 1, tend to co-occur within the same patient. The prevalence of CD in diabetic children is higher than in the general population, and is estimated to be 0.6–16.4%. The diagnosis of CD is based on histopathological examination and serological testing, however, these methods are still imperfect and new diagnostic algorithms should be considered. Aim: The aim of the study was to assess the diagnostic value of serological tests detecting antibodies against deamidated gliadin peptide, endomysium, tissue transglutaminase, neo-epitope tissue transglutaminase and to identify HLA-related genetic predisposition to CD in patients with type 1 diabetes mellitus (DM1). Methods: Autoantibodies were measured in the sera of 392 children suffering from DM1 aged 1–19 years old (mean 11.76 ± 4.14 years old). Additionally, PCR-based assessment of HLA DQ2/DQ8 genotyping was performed. Results: A positive result of at least one serological test was obtained from 81 children (20.66%). The sensitivity and specificity were 76.47% and 91.67% for anti-DGP IgA, 70.59% and 58.33% for IgG anti-DGP, respectively. A positive predictive value was 100% for the anti-TG IgA at cutoff levels of 5 and 10 times higher than upper limit of reference values. HLA DQ2 and/or DQ8 were found in 97.6% of examined children. Conclusions: Tests based on anti-TG IgA are more accurate for detecting CD in children with type 1 diabetes than anti-DGP IgA. A high percentage of diabetic children carry HLA alleles predisposing to CD, which indicates that genetic screening in this group of patients is not obligated