Search results for "Kinase inhibitor"
showing 10 items of 414 documents
Up-Regulation of leucocytes Genes Implicated in Telomere Dysfunction and Cellular Senescence Correlates with Depression and Anxiety Severity Scores
2012
BACKGROUND: Major depressive disorder (MDD) is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to eval…
Modulatory effects of the novel TrkB receptor agonist 7,8-dihydroxyflavone on synaptic transmission and intrinsic neuronal excitability in mouse visu…
2013
7,8-Dihydroxyflavone (7,8 DHF) is a new recently identified TrkB receptor agonist, which possesses a potent neurotrophic activity and shares many physiological properties with the neurotrophin "Brain Derived Neurotrophic Factor" (BDNF). However, its precise mechanism of action at the cellular level has not been clarified yet. In the present study we explored the effects of this agent on synaptic and intrinsic neuronal properties by performing whole-cell patch clamp recordings from layer 2/3 pyramidal neurons. Incubation of acute cortical slices with 7,8-DHF (20 µM) for 30 min caused a selective reduction in the strength of GABAergic inhibition. The amplitude of evoked inhibitory postsynapti…
Induction of apoptosis in human retinoblastoma cells by topoisomerase inhibitors
1998
PURPOSE:To examine the apoptotic effect induced in human retinoblastoma Y79 cells by camptothecin, etoposide, and amsacrine, to examine the effect of these drugs on the expression of many apoptosis-related modulators, and to test the antiapoptotic effect exerted by insulin-like growth factor-I (IGF-I). METHODS:Morphologic features of apoptosis were demonstrated using acridine orange- ethidium bromide staining and electron microscopy. DNA fragmentation was determined by means of an in situ cell detection procedure (TdT-dUTP terminal nick-end labeling [TUNEL]) or by electrophoresis on agarose gels and was quantified by enzyme-linked immunosorbent assay. The expression of apoptosis-related mod…
Novel 3-Azaindolyl-4-arylmaleimides Exhibiting Potent Antiangiogenic Efficacy, Protein Kinase Inhibition, and Antiproliferative Activity
2012
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.
Central role of IL-6 and MMP-1 for cross talk between human intestinal mast cells and human intestinal fibroblasts.
2012
Mast cells (MC) are key effector cells in allergic reactions but also involved in host defence, tissue remodeling, angiogenesis, and fibrogenesis. Here, we show that human intestinal fibroblasts (FB) suppress apoptosis in human intestinal MC dependent on IL-6. Intestinal FB produced IL-6 upon direct stimulation by intestinal MC in co-culture or by MC mediators such as TNF-α, IL-1β, tryptase or histamine. MC incubated with IL-6 survived for up to 3 weeks similar to MC co-cultured with FB and MC survival could be blocked by neutralizing anti-IL-6 Abs. Moreover, FB stimulated by MC mediators upregulated their expression of matrix metalloproteinase-1 (MMP-1), a key fibrolytic enzyme. Noteworthy…
A recommended practical approach to the management of target therapy and angiogenesis inhibitors cardiotoxicity: an opinion paper of the working grou…
2016
The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side-effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis. Moreover, other agents may be related to CTX induced by treatment. In this study, we review the g…
Neuronal cell cycle: the neuron itself and its circumstances.
2015
Neurons are usually regarded as postmitotic cells that undergo apoptosis in response to cell cycle reactivation. Nevertheless, recent evidence indicates the existence of a defined developmental program that induces DNA replication in specific populations of neurons, which remain in a tetraploid state for the rest of their adult life. Similarly, de novo neuronal tetraploidization has also been described in the adult brain as an early hallmark of neurodegeneration. The aim of this review is to integrate these recent developments in the context of cell cycle regulation and apoptotic cell death in neurons. We conclude that a variety of mechanisms exists in neuronal cells for G1/S and G2/M check…
JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation in CD8+ T Cells in Renal Cell Carcinoma Patients
2010
To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8(+) T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8(+) T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8(+) T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defe…
Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors
2022
Background: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, be-coming the standard of care of systemic therapy.Aim: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors.Methods: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients.Results: 422 (…
The role of Aurora-A inhibitors in cancer therapy
2007
Recently, new chemotherapy agents which target the non-structural components of mitosis have been developed. An important protein involved in several mitotic phases is the Aurora-A protein. By means of the phosphorylation of different substrates, Aurora-A regulates the correct development of the various phases of mitosis. The kinase activity of this protein makes Aurora-A an excellent candidate as an oncogene. The first data of Aurora-A involvement in cancer regarded the identification of Aurora-A overexpression in primary breast and colon tumour samples. With regard to the predictive role of Aurora-A, it has been shown that its overexpression disrupts the spindle checkpoint activated by pa…