25 research outputs found
Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci
We have recently shown that radiotherapy may not only be a successful local and regional treatment
but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the
role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with
MSC + radiotherapy (RT). The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were:
44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5%
in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover,
the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the
mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor
growth delay and metastasis control after treatment. Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in
the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that
exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors
with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used
in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the
control of tumor growth and metastasis.This work was supported by CNPq, Conselho Nacional de
Desenvolvimento Científico e Tecnológico – Brasil, Junta de Andalucía,
project of Excellence from Junta de Andalucía P12-CTS-383 to FJO, Spanish
Ministry of Economy and Competitiveness SAF2015-70520-R to FJO and
JMRdA, RTICC RD12/0036/0026 and CIBER Cáncer ISCIII CB16/12/00421 to
FJO
Formaldehyde and Epigenetic Alterations: MicroRNA Changes in the Nasal Epithelium of Nonhuman Primates
Background: Formaldehyde is an air pollutant present in both indoor and outdoor atmospheres. Because of its ubiquitous nature, it is imperative to understand the mechanisms underlying formaldehyde-induced toxicity and carcinogenicity. MicroRNAs (miRNAs) can influence disease caused by environmental exposures, yet miRNAs are understudied in relation to formaldehyde. Our previous investigation demonstrated that formaldehyde exposure in human lung cells caused disruptions in miRNA expression profiles in vitro. Objectives: Using an in vivo model, we set out to test the hypothesis that formaldehyde inhalation exposure significantly alters miRNA expression profiles within the nasal epithelium of nonhuman primates. Methods: Cynomolgus macaques were exposed by inhalation to approximately 0, 2, or 6 ppm formaldehyde for 6 hr/day for 2 consecutive days. Small RNAs were extracted from nasal samples and assessed for genome-wide miRNA expression levels. Transcriptional targets of formaldehyde-altered miRNAs were computationally predicted, analyzed at the systems level, and assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Results: Expression analysis revealed that 3 and 13 miRNAs were dysregulated in response to 2 and 6 ppm formaldehyde, respectively. Transcriptional targets of the miRNA with the greatest increase (miR-125b) and decrease (miR-142-3p) in expression were predicted and analyzed at the systems level. Enrichment was identified for miR-125b targeting genes involved in apoptosis signaling. The apoptosis-related targets were functionally tested using RT-PCR, where all targets showed decreased expression in formaldehyde-exposed samples. Conclusions: Formaldehyde exposure significantly disrupts miRNA expression profiles within the nasal epithelium, and these alterations likely influence apoptosis signaling
Synthesis, DFT calculations, linear and nonlinear optical properties of binuclear phthalocyanine gallium chloride
10.1007/s00894-005-0043-5Journal of Molecular Modeling125543-550JMMO