Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges

Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges

Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy

Therapy of chronic lymphocytic leukemia (CLL) - from past to present

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in Western European countries. This disease occurs mainly in adult population at an age of over 50 years, more commonly in men. Many years of research have shown that CLL is a disease with a very diverse clinical course and variable sensitivity to treatment. Therefore, in each case of newly diagnosed CLL, the clinical stage, prognostic factors and individualized therapeutic goals should be precisely defined before the treatment initiation. Recent 50 years have been a period of significant development in the treatment of proliferative diseases of the hematopoietic and lymphatic systems. Along with dynamic development of molecular biology techniques, several new specific prognostic markers have been investigated and introduced, allowing better stratification of patients and more accurate direction of the therapy. A lot of effort has gone into searching for the next prognostic factors which allow to determine better probable life span and to implement the successful treatment. Furthermore, many preclinical and clinical studies continually extend the list of effective anticancer drugs, including these for CLL treatment. Increasingly, in addition to standard cytostatics, drugs with more selective mechanisms of action are being tested in monotherapy and new combinations. Considering the historical aspects, only a few anticancer drugs were available 50 years ago. In addition, they mainly presented the one mechanism of action directed at nucleic acids. Today, the list of effective drugs is significantly longer. In addition to typical cytostatics, it also contains drugs with selective mechanisms of action, affecting the cell life processes, their subcellular structures, signaling from outside and inside the cell, surface antigens, as well as drugs that act on the microenvironment of cancer cells and their vascularization. The aim of this paper was to show the historical background in the therapy of leukemia and summarize the current knowledge in CLL biology and treatments. The manuscript is focused on the clinical course of the disease, the main risk factors and mainly, on the available treatment strategies.Przewlekła białaczka limfocytowa (PBL) jest najczęściej występującą postacią białaczki w krajach Europy Zachodniej. Jest to choroba dotycząca przede wszystkim osób powyżej 50 roku życia, częściej mężczyzn niż kobiet. Wieloletnie badania wykazały, że PBL jest chorobą o bardzo zróżnicowanym przebiegu klinicznym i zmiennej wrażliwości na zastosowane leczenie. W związku z powyższym, w każdym przypadku nowo zdiagnozowanej PBL, przed rozpoczęciem leczenia, należy precyzyjnie określić stadium zaawansowania klinicznego, czynniki prognostyczne oraz cele terapeutyczne zindywidualizowane dla danego pacjenta. Ostatnie 50 lat to okres istotnego postępu w leczeniu chorób rozrostowych układu krwiotwórczego i chłonnego. Wraz z dynamicznym rozwojem technik biologii molekularnej pojawiły się nowe, specyficzne czynniki prognostyczne, umożliwiające lepszą stratyfikację chorych oraz dokładniejsze określenie dalszego kierunku terapii. W dalszym ciągu prowadzone są prace nad kolejnymi czynnikami umożliwiającymi określenie długości przeżycia pacjenta oraz szans powodzenia terapii. Jednocześnie prowadzone badania przedkliniczne i kliniczne wydłużają listę bardziej skutecznych leków przeciwnowotworowych, znajdujących swoje zastosowanie również w PBL. Coraz częściej obok standardowych cytostatyków pojawiają się leki o bardziej swoistym mechanizmie działania, zarówno w monoterapii, jak i w nowych połączeniach. Celem pracy było przedstawienie rysu historycznego w zakresie terapii białaczek i przegląd dotychczasowej wiedzy na temat charakterystyki i terapii PBL. W artykule zwrócono szczególną uwagę na przebieg choroby, czynniki ryzyka oraz stosowane obecnie strategie leczenia