Search results for "ZOL"
showing 10 items of 4792 documents
Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug
2009
Abstract Introduction Aromatase, a member of the cytochrome P 450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1 H -1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor ( K i =11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1 H -1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide,…
Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools
2019
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…
Parthenolide induces superoxide anion production by stimulating EGF receptor in MDA-MB-231 breast cancer cells
2013
The sesquiterpene lactone parthenolide (PN) has recently attracted considerable attention because of its anti-microbial, anti-inflammatory and anticancer effects. However, the mechanism of its cytotoxic action on tumor cells remains scarcely defined. We recently provided evidence that the effect exerted by PN in MDA-MB-231 breast cancer cells was mediated by the production of reactive oxygen species (ROS). The present study shows that PN promoted the phosphorylation of EGF receptor (phospho-EGFR) at Tyr1173, an event which was observed already at 1 h of incubation with 25 µM PN and reached a peak at 8-16 h. This effect seemed to be a consequence of ROS production, because N-acetylcystein…
Rad51 and BRCA2 - New Molecular Targets for Sensitizing Glioma Cells to Alkylating Anticancer Drugs
2011
First line chemotherapeutics for brain tumors (malignant gliomas) are alkylating agents such as temozolomide and nimustine. Despite growing knowledge of how these agents work, patients suffering from this malignancy still face a dismal prognosis. Alkylating agents target DNA, forming the killing lesion O(6)-alkylguanine, which is converted into DNA double-strand breaks (DSBs) that trigger apoptosis. Here we assessed whether inhibiting repair of DSBs by homologous recombination (HR) or non-homologous end joining (NHEJ) is a reasonable strategy for sensitizing glioma cells to alkylating agents. For down-regulation of HR in glioma cells, we used an interference RNA (iRNA) approach targeting Ra…
Candida bloodstream infections in intensive care units: Analysis of the extended prevalence of infection in intensive care unit study
2011
Objectives: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. Design: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. Setting: EPIC II included 1265 intensive care units in 76 countries. Patients: Patients in partic…
Posaconazole against Candida glabrata with Variable Susceptibility to Fluconazole
2008
We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 microg/ml). POS MICs ranged from 64 microg/ml; POS MIC of 0.5 microg/ml). FLC significantly reduced the kidney burden of mice infected with the S strain (P = 0.0070) but not of those infected with the S-DD and R strains. POS was significantly effective against all three isolates at reducing the kidney fungal burden with respect to the controls (P ranging from 0.0003 to 0.029). In conclusion, our data suggest that POS may be a useful option in the …
The endocannabinoid N-arachidonoyldopamine (NADA) exerts neuroprotective effects after excitotoxic neuronal damage via cannabinoid receptor 1 (CB(1)).
2012
Endocannabinoids exert numerous effects in the CNS under physiological and pathological conditions. The aim of the present study was to examine whether the endocannabinoid N-arachidonoyldopamine (NADA) may protect neurons in excitotoxically lesioned organotypic hippocampal slice cultures (OHSC). OHSC were excitotoxically lesioned by application of N-methyl-d-aspartate (NMDA, 50 μM) for 4 h and subsequently treated with different NADA concentrations (0.1 pM-50 μM) alone or in combination with cannabinoid receptor antagonists. NADA protected dentate gyrus granule cells and caused a slight reduction in the number of microglial cells. The number of degenerated neurons significantly decreased be…
Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR- and BECLIN1-complex
2013
Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for Delta-9-Tetrahydrocannabinol in the central nervous system (CNS), mediating retrograde synaptic signaling of the endocannabinoid system. Beside its expression in various CNS regions, CB1 is ubiquituous in peripheral tissues, where it mediates, among other activities, the cell's energy homeostasis. We sought to examine the role of CB1 in the context of the evolutionarily conserved autophagic machinery, a main constituent of the regulation of the intracellular energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an elevated autophagic flux, while the expression of autophagy-related genes rema…
Synthesis and Characterization of Carbazole-Linked Porphyrin Tweezers
2015
Herein the synthesis, spectroscopic characterization, two-photon absorption and electrochemical properties of 3,6-disubstituted carbazole tweezers is reported. A dimer resulting from a Glaser homocoupling was isolated during a Sonogashira coupling reaction between a diethynyl-carbazole spacer and a 5-bromo-triarylporphyrin and the properties of this original compound were compared with the 3,6-disubstituted carbazole bisporphyrin tweezers. The dyads reported herein present a two-photon absorption maximum at 920 nm with two-photon absorption cross-section in the 1200 GM range. Despite a strong linear absorption in the Soret region and moderate fluorescence quantum yield, they both lead to a …
Reactions of electron-rich heterocycles with orthocarboxylic acid derivatives.11. Reactions of carbazole and 4-methoxycarbazole with triethyl orthofo…
1988
Carbazole (1a) and 4-methoxycarbazole (1b) can be regioselectively functionalized by reaction with triethyl orthoformate. Whereas the reaction of 1a with the ortho ester furnishes the amide acetal 2, the new carbazole derivatives 4–10 are formed, depending on the reaction conditions, in the electrophilic substitution of 1b. The products of this reaction sequence provide a contribution to studies on the mechanism of the transformation of 1b to tris-carbazolylmethane 5. Compound 5 represents a new, three-bladed propeller in the triheteroarylmethane series.