Search results for "Farm"
showing 10 items of 3554 documents
Histone deacetylase inhibition modulates deoxyribonucleotide pools and enhances the antitumor effects of the ribonucleotide reductase inhibitor 3’-C-…
2011
Histone deacetylase (HDAC) inhibitors are a new class of epigenetic agents that were reported to enhance the cytotoxic effects of classical anticancer drugs through multiple mechanisms. However, which of the possible drug combinations would be the most effective and clinically useful are to be determined. We treated the HL60 and NB4 promyelocytic leukaemia cells with a combination of the ribonucleotide reductase (RR) inhibitor 3'-C-methyladenosine (3'-Me-Ado) and several hydroxamic acid-derived HDAC inhibitors, including two recently synthesized molecules, MC1864 and MC1879, and the reference compound trichostatin A (TSA). The results showed significant growth inhibitory and apoptotic syner…
Patterns of Innate or Acquired Resistance to Anticancer Drugs: Our Experience to Overcome It
2021
Drug resistance, which is often of a multiple type, can be defined as the ability of cancer cells to obtain resistance to both conventional and novel chemotherapy agents. It remains a major problem to solve in cancer therapy. The mechanisms of resistance are multifactorial, and in our cellular models of acute myeloid leukemia, hepatocellular carcinoma, and triple-negative breast cancer, it involves the NF-κB pathway. In our opinion, multitarget molecules can be considered as privileged compounds capable of attacking and reversing the resistant phenotype. In the phenomena of both innate and acquired drug resistance that we have been studying since 1998 to today and up to 2016 under the guida…
STAT5 and STAT5 Inhibitors in Hematological Malignancies
2019
The JAK-STAT pathway is an important physiologic regulator of different cellular functions including proliferation, apoptosis, differentiation, and immunological responses. Out of six different STAT proteins, STAT5 plays its main role in hematopoiesis and constitutive STAT5 activation seems to be a key event in the pathogenesis of several hematological malignancies. This has led many researchers to develop compounds capable of inhibiting STAT5 activation or interfering with its functions. Several anti-STAT5 molecules have shown potent STAT5 inhibitory activity in vitro. However, compared to the large amount of clinical studies with JAK inhibitors that are currently widely used in the clini…
The new iodoacetamidobenzofuran derivative TR120 decreases STAT5 expression and induces antitumor effects in imatinib-sensitive and imatinib-resistan…
2013
The identification of novel compounds modulating the expression/activity of molecular targets downstream to BCR-ABL could be a new approach in the treatment of chronic myeloid leukemias (CMLs) resistant to imatinib or other BCR-ABL-targeted molecules. Recently, we synthesized a new class of substituted 2-(3,4,5-trimethoxybenzoyl)-2-N,N-dimethylamino-benzo[b]furans, and among these 3-iodoacetylamino-6-methoxybenzofuran-2-yl(3,5-trimethoxyphenyl)methanone (TR120) showed marked cytotoxic activity in BCR-ABL-expressing cells. Interestingly, TR120 was more potent than imatinib in cell growth inhibition and apoptosis induction in both BCR-ABL-expressing K562 and KCL22 cells. Moreover, it showed a…
Evaluation of [1,2]oxazolo[5,4-e]isoindoles in lymphoma cells
2020
Anti-tubulin agents are important chemotherapeutics. Combretastatin A-4 (CA-4) emerged as lead compound for the design of new tubulin-binding agents. Its analogues 4,5-diarylisoxazoles, containing the [1,2]oxazole ring as linker of two aryl moieties, displayed higher antitubulin activity than CA-4. [1,2]oxazolo[5,4-e]isoindoles also gave excellent results reducing cell growth of NCI-60 tumor cell lines and diffuse malignant peritoneal mesothelioma (DMPM) cells. Selected derivatives showed in vivo antitumor activity at well-tolerated doses in a DMPM xenograft model. [1,2]oxazolo[5,4-e]isoindoles were screened in four lymphoma histotypes: germinal center B-cell and activated diffuse large B c…
2-Triazenoazaindoles: Α novel class of triazenes inducing transcriptional down-regulation of EGFR and HER-2 in human pancreatic cancer cells
2012
Pancreatic cancer is a complex malignancy arising from the accumulation of genetic and epigenetic defects in the affected cells. Standard chemotherapy for patients with advanced disease shows only modest effects and is associated with considerable toxicity. Overexpression or aberrant activation of members of the epidermal growth factor receptor tyrosine kinase family, which includes EGFR and HER-2, occurs frequently and is associated with multiple drug resistance and decreased patient survival. In this study, we have investigated the therapeutic potential of AS104, a novel compound of the triazene class, with potential inhibitory effects on EGFR. We found that treatment of cells with AS104 …
Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells
2008
Resistance to imatinib mesylate is an emergent problem in the treatment of Bcr-Abl expressing myelogenous leukemias and additional therapeutic strategies are required. We observed that galangin, a non-toxic, naturally occurring flavonoid was effective as anti-proliferative, and apoptotic agent in Bcr-Abl expressing K562 and KCL22 cells and in imatinib mesylate resistant K562-R and KCL22-R cells. Galangin induced an arrest of cells in G0–G1phase of cell cycle and a decrease in pRb, cdk4, cdk1, cycline B levels; moreover, it was able to induce a monocytic differentiation of leukemic Bcr-Abl+ cells. Of note, galangin caused a decrease in Bcl-2 levels and markedly increased the apoptotic activi…
Candida ģints sēņu jutības pret antifungālajiem līdzekļiem noteikšana
2015
Bakalaura darbs tika izstrādāts LU Medicīnas fakultātē Mg. Sc. biol. Ivetas Līdumas vadībā. Bakalaura darbā ir analizēta Mikobakterioloģiskajā laboratorijā identificēto no klīniskajiem paraugiem izdalīto raugveida sēņu dati, ka arī pētīta sēņu paraugu jutība, pret antifungālajiem līdzekļiem (amfotericīnu B, itrakonazolu, flukonazolu). Sēņu sugas tika identificētas izmantojot mikroskopisko analīzi, ka arī veicot uzsējumus uz BBL™ CHROMagar™ barotnes. Lai noteiktu antifungālo jutību tika izmantota standartizēta disku difūzijas metode, izmantojot CLSI noteiktos kritērijus, kā arī lietojot E-testus tika noteikta MIC (minimālā inhibējošā koncentrācija). Jutība pret antifungālajiem līdzekļiem tik…
Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats
2013
Increasing evidence focuses on acetaldehyde (ACD) as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking and relapse behaviour. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioural equivalent of compulsive drug use despite adverse consequences. The aim of this study was thus to characterize…
Disabilità e dolore: il caso della cannabis terapeutica. Fisionomia e limiti del diritto alla cura nel decreto del Ministero della Salute 9 novembre …
2022
Il contributo illustra l’originale struttura del mercato della cannabis terapeutica, ricostruendo la legislazione italiana in materia, di cui si mette in luce la dubbia compatibilità con i principi di libera circolazione e di concorrenza. La specialità del settore è comunemente giustificata alla luce delle esigenze di salute pubblica, dell’ordine pubblico e della pubblica sicurezza la cui tutela è sottesa anche ai più recenti interventi normativi: specialità che non consente tuttavia di giudicare la regolazione della cannabis terapeutica conforme all’interpretazione consolidata degli articoli 49, 52, 56, 106 T.f.Ue e alla altrettanto stabile giurisprudenza della Corte costituzionale italia…