19 research outputs found
COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase
MicroRNA-mediated drug resistance in breast cancer
Chemoresistance is one of the major hurdles to overcome for the successful treatment of breast cancer. At present, there are several mechanisms proposed to explain drug resistance to chemotherapeutic agents, including decreased intracellular drug concentrations, mediated by drug transporters and metabolic enzymes; impaired cellular responses that affect cell cycle arrest, apoptosis, and DNA repair; the induction of signaling pathways that promote the progression of cancer cell populations; perturbations in DNA methylation and histone modifications; and alterations in the availability of drug targets. Both genetic and epigenetic theories have been put forward to explain the mechanisms of drug resistance. Recently, a small non-coding class of RNAs, known as microRNAs, has been identified as master regulators of key genes implicated in mechanisms of chemoresistance. This article reviews the role of microRNAs in regulating chemoresistance and highlights potential therapeutic targets for reversing miRNA-mediated drug resistance. In the future, microRNA-based treatments, in combination with traditional chemotherapy, may be a new strategy for the clinical management of drug-resistant breast cancers
Recommended from our members
Tuning electronic correlations in transition metal pnictides: Chemistry beyond the valence count
The effects of electron-electron correlations on the low-energy electronic structure and their relationship with unconventional superconductivity are central aspects in the research on iron-based pnictide superconductors. Here we use soft x-ray angle-resolved photoemission spectroscopy to study how electronic correlations evolve in different chemically substituted iron pnictides. We find that correlations are intrinsically related to the effective filling of the correlated orbitals, rather than to the filling obtained by valence counting. Combined density functional theory and dynamical mean-field theory calculations capture these effects, reproducing the experimentally observed trend in the correlation strength. The occupation-driven trend in the electronic correlation reported in our paper supports and extends the recently proposed connection between cuprate and pnictide phase diagrams
Invasive Africanized honeybees change the structure of native pollination networks in Brazil
Structural analysis of N-glycans in medaka gut exposed to silver and titanium dioxide nanoparticles
Arsenic induced apoptosis in malignant melanoma cells is enhanced by menadione through ROS generation, p38 signaling and p53 activation
Introduction Resistance to apoptosis is a prominent feature
of melanoma. Pharmacological concentration of
arsenic in combination with a widely known oxidant,
menadione was explored in this study to synergistically
sensitize malignant melanoma cells to apoptosis. The
molecular mechanism of apoptosis and the signalingpathways
involved were thoroughly investigated.
Materials methods and results Menadione synergized
NaAsO2 to significantly increase ROS generation and
facilitate the major apoptotic signaling events: alteration of
mitochondrial membrane potential, cytochrome c release
and anti-apoptotic protein Bcl-2 down-regulation and
subsequent activation of caspase-9 and caspase-3 followed
by poly-ADP-ribose polymerase-1 cleavage. Antioxidant
N-acetyl-L-cysteine antagonized these events. Investigation
of the signaling-pathway revealed significant suppression
of AP-1 activity but not NF-jB upon NaAsO2 and menadione
application. An increase in p38 phosphorylation and
p53 protein expression did also dictate the apoptotic
response. Suppression of p38 activation with SB203580
and inhibition of p53 expression by siRNA attenuated
apoptosis. Transfection of p53, in p53 null HCT cells
augmented the apoptotic events. Moreover, the treatment
also led to tumor size reduction in BALB/c mice developed
by intra-dermal B16 mouse melanoma cell injection;however, it had no detectable pro-proliferative or proapoptotic
effect on non-tumor keratinocytes, normal
fibroblasts or PBMC.
Conclusion This study thus provides an insight into
innovative mechanisms of melanoma sensitization, a
proper cure against which is still elusive. Taken together,
our data also provides the first evidence of arsenic activity
accentuation by menadione through modulation of specific
signaling-pathways