48,300 research outputs found
Potent Apoptotic Response Induced by Chloroacetamidine Anthrathiophenediones in Bladder Cancer Cells.
No full textWe previously found that two neighboring G-quadruplexes behave as a molecular switch controlling the expression of HRAS (Cogoi, S.; Schekotikhin, A. E.; Xodo, L. E. Nucl. Acids Res. 2014, DOI: 10.1093/nar/gku574). In this study we have designed anthrathiophenediones with two hloroacetamidine-containing side chains (CATDs) as G-quadruplex binders and have examined their anticancer activity in T24 bladder cancer cells bearing mutant HRAS and in T24 xenografts. The designed CATDs (3a−e), bearing alkyl side chains of different length, penetrate T24 cancer cells more than their analogues with guanidine-containing side chains. The lead compounds 3a and 3c inhibit HRAS expression, metabolic activity, and colony formation in T24 cancer cells. They also activate a strong apoptotic response, as indicated by PARP-1, caspases 3/7, and annexin V/propidium iodide assays.
Apoptosis occurs under conditions where cyclin D1 is down-regulated and the cell cycle arrested in G2 phase. Finally, compound 3a inhibits the growth of T24 xenografts and increases the median survival time of nude mice
Potent Apoptotic Response Induced by Chloroacetamidine Anthrathiophenediones in Bladder Cancer Cells
No full textWe previously found that two neighboring
G-quadruplexes behave
as a molecular switch controlling the expression of <i>HRAS</i> (Cogoi, S.; Schekotikhin, A. E.; Xodo, L. E. Nucl.
Acids Res. 2014, DOI: 10.1093/nar/gku574). In this study we have designed anthrathiophenediones
with two chloroacetamidine-containing side chains (CATDs) as G-quadruplex
binders and have examined their anticancer activity in T24 bladder
cancer cells bearing mutant <i>HRAS</i> and in T24 xenografts.
The designed CATDs (<b>3a</b>–<b>e</b>), bearing
alkyl side chains of different length, penetrate T24 cancer cells
more than their analogues with guanidine-containing side chains. The
lead compounds <b>3a</b> and <b>3c</b> inhibit <i>HRAS</i> expression, metabolic activity, and colony formation
in T24 cancer cells. They also activate a strong apoptotic response,
as indicated by PARP-1, caspases 3/7, and annexin V/propidium iodide
assays. Apoptosis occurs under conditions where cyclin D1 is down-regulated
and the cell cycle arrested in G2 phase. Finally, compound <b>3a</b> inhibits the growth of T24 xenografts and increases the median survival
time of nude mice
Role of RKIP in the tumor response to photooxidative damage
No full textThe Raf-kinase inhibitor protein (RKIP) plays a role in the regulation of different processes, through its interaction with several signaling pathways. These pathways include the mitogen activated protein kinase (MAPK), nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), G protein-coupled receptors (GPCR) and glycogen synthase kinase 3 beta (GSK 3β). RKIP negatively affects tumor survival and proliferation, acting as a metastasis suppressor. Moreover, RKIP overexpression has been reported to reverse tumor chemo/immuno/radio-resistance and support the anticancer host immuno-surveillance. The aim of this work is to evaluate the role of RKIP in cancer cells during a photooxidative damage induced by photodynamic therapy (PDT). PDT treatment is based on three components: a photosensitizer, light and oxygen. Their combined action produces singlet oxygen (1O2) and/or reactive oxygen species (ROS) leading to an oxidative insult in tumor cells. Dependently on the PDT dose, the response of tumor cells can have a double outcome: stimulation of tumor cell proliferation with a low PDT dose (IC50), or tumor growth arrest in the case of a high PDT dose (IC50). We evaluated RKIP expression within its complex network, correlating with other factors involved in the tumor response to oxidative stress. We found a link between the expression of RKIP and NF-κB, MAPK, Snail and Nrf2 according to the type of the oxidative insult. In the presence of low PDT, RKIP is downregulated, while NF-κB, Snail and Nrf2 are upregulated: an expression profile that stimulates tumor proliferation and resistance. Conversely, RKIP is overexpressed in the case of high PDT, thus allowing an arrest of tumor growth.Considering that many antitumor drugs develop ROS/RNS causing disease recurrence and drug resistance, RKIP could be a good prognostic marker to follow patients' response to anticancer therapies
Il lampo dell'aforisma nella pedagogia di Giuseppe Acone
No full textLa persona considerata nella sua eccedenza ontologica e l'educazione, pensata e progettata come ultima narrazione capace di resistere al sirenico canto della Stimmung del post, costituiscono l'infrastruttura teorica e lo sfondo ermeneutico dell'intero volum
The ROS-KRAS-Nrf2 axis in the control of the redox homeostasis and the intersection with survival-apoptosis pathways: Implications for photodynamic therapy
No full textThe central role of creatine and polyamines in fetal growth restriction
No full textPlacental insufficiency often correlates with fetal growth restriction (FGR), a condition that has both short- and long-term effects on the health of the newborn. In our study, we analyzed placental tissue from infants with FGR and from infants classified as small for gestational age (SGA) or appropriate for gestational age (AGA), performing comprehensive analyses that included transcriptomics and metabolomics. By examining villus tissue biopsies and 3D trophoblast organoids, we identified significant metabolic changes in placentas associated with FGR. These changes include adaptations to reduced oxygen levels and modifications in arginine metabolism, particularly within the polyamine and creatine phosphate synthesis pathways. Specifically, we found that placentas with FGR utilize arginine to produce phosphocreatine, a crucial energy reservoir for ATP production that is essential for maintaining trophoblast function. In addition, we found polyamine insufficiency in FGR placentas due to increased SAT1 expression. SAT1 facilitates the acetylation and subsequent elimination of spermine and spermidine from trophoblasts, resulting in a deficit of polyamines that cannot be compensated by arginine or polyamine supplementation alone, unless SAT1 expression is suppressed. Our study contributes significantly to the understanding of metabolic adaptations associated with placental dysfunction and provides valuable insights into potential therapeutic opportunities for the future
Tatuaggio e piercing: conoscenze nei giovani di una possibile trasmissione di patologie infettive
No full textOBIETTIVI: La presenza di piercing e tatuaggio è un fenomeno frequente
nella popolazione. In Italia non esistono molti dati relativi a prevalenza,
atteggiamenti verso tali pratiche, conseguenze sanitarie e sociali. Lo studio
si propone di valutare la distribuzione del fenomeno e la percezione del
rischio infettivo in un campione di studenti di diverse tipologie di scuole
superiori, residenti nelle sette province Venete.
MATERIALI: È stato utilizzato un questionario anonimo, auto-somministrato,
distribuito nell’anno scolastico 2007-2008, contente domande su:
caratteristiche socio-demografiche, livello di scolarizzazione familiare,
presenza di piercing e tatuaggio (P&T) e relativo atteggiamento personale,
conoscenza di possibili malattie correlate, importanza della scelta
dell’operatore.
RIASSUNTO: Sono stati compilati correttamente 4320 questionari (95,5%):
34,7% maschi e 65,3% femmine (età media 17?1,7 anni). Rispettivamente
il 20,2% e il e il 6,4% ha sperimentato il P&T (principalmente per motivi
estetici), mentre ne è molto attratto rispettivamente il 46,7% e il 57,4%. La
maggioranza degli intervistati (81,6%) ritiene sia possibile contrarre
un’infezione, anche se circa il 40% pensa di non poter contrarre patologie
gravi (AIDS, Epatiti e Sifilide). Il livello di istruzione familiare non correla
con tale percezione. L’88,0% preferisce rivolgersi per P&T ad operatori
qualificati. In caso di ipotetica infezione il 79,4% ricorrerebbe all’intervento
sanitario, ma quando questa si è verificata solo il 37,0% l’ha fatto. Il
ricorso alla prestazione sanitaria in caso di ipotetica o reale infezione
correla con un livello di istruzione familiare elevato (laurea).
CONCLUSIONI: La prevalenza di piercing e tatuaggio rilevata è simile a
quella riferita da altri studi e aumenta con l’età. Emerge l’insufficiente
consapevolezza dei rischi per la salute: è necessario rinforzare e attuare
precocemente interventi di informazione ed educazione sanitaria diretti a
studenti, docenti e genitori. Fondamentale la formazione degli operatori
riguardo a: norme igieniche, legislazione vigente, informazione del cliente
e verifica della sua maggiore età
Bystander effect in photosensitized prostate cancer cells with a different grade of malignancy: The role of nitric oxide
No full textPhotodynamic therapy (PDT) is a therapeutic modality based on the simultaneous action of three elements: photosensitizer, light and oxygen. This triad generates singlet oxygen and reactive oxygen species that can reduce the mass of a tumor. PDT is also able to stimulate iNOS, the enzyme that generates nitric oxide (NO). The role of NO in PDT-treated cancer cells has been investigated in several studies. They showed that low iNOS/NO levels stimulate signaling pathways that promote tumor survival, while high iNOS/NO levels arrest tumor growth. There is increasing evidence that ROS/RNS control both proliferation and migration of cells in the vicinity of PDT-treated tumor cells (so-called bystander cells). In this work, we addressed the question of how NO, which is generated by weak PDT, affects bystander cells. We used a conditioned medium: medium of PDT-treated tumor cells containing the stressors produced by the cells was added to untreated cells mimicking the neighboring bystander cells to investigate whether the conditioned medium affects cell proliferation. We found that low-level NO in prostate cancer cells affects the bystander tumor cells in a manner that depends on their malignancy grade
Widespread presence in mammals and high binding specificity of a nuclear protein that recognizes the single-stranded (CCCTAA)n telomeric motif.
No full text- …
