Risultati per: Nanotubi di DNA per terapie contro i tumori del cervello

In an observational study, outcomes were similar to those from a first round.

Andreoni (Simit): “Caso australiano eccezionale. Parassiti nuova minaccia”

Andreoni:’Caso australiano eccezionale.Parassiti nuova minaccia’

Un tumor board vede impegnati numerosi specialisti dell’Aou

La carenza associata a un maggiore rischio di decesso

Introduction
In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076, NCT04288999).

Methods and analysis
JCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801. Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy). Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue–agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points.

Ethics and dissemination
The study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration.

Studio Sapienza-Cnr-Gemelli pubblicato su Nature Communications

Elementi a quattro filamenti anziché i due della classica doppia elica

Circulation, Ahead of Print. BACKGROUND:The major cytosolic DNA sensor GMP-AMP synthase (cGAS) has emerged as a key mediator of inflammation that underlies cardiovascular disease. On interaction with double-stranded DNA, cGAS generates the second messenger 2′,3′-cyclic GMP-AMP (cGAMP) that directly binds to and activates the stimulator of interferon genes, which in turn leads to enhanced expression of genes encoding interferons and proinflammatory cytokines. Here, we show that cGAMP generated by cGAS also directly activates PKGI (cGMP-dependent protein kinase 1), a mechanism that underlies crosstalk between inflammation and blood pressure regulation.METHODS:The ability of cGAS and cGAMP to activate PKGI was assessed using molecular, cellular, and biochemical analyses, and in myography experiments, as well. The release of cGAMP from the endothelium was measured using an ELISA, and its uptake into the vascular smooth muscle was assessed using molecular and biochemical approaches, including the identification and targeting of specific cGAMP transporters. The blood pressure of wild-type and cGAS–/–mice was assessed using implanted telemetry probes. cGAS was activated by in vivo transfection with G3-YSD or mice were made septic by administration of lipopolysaccharide.RESULTS:The detection of cytosolic DNA by cGAS within the vascular endothelium leads to formation of cGAMP that was found to be actively extruded by MRP1 (multidrug resistance protein 1). Once exported, this cGAMP is then imported into neighboring vascular smooth muscle cells through the volume-regulated anion channel, where it can directly activate PKGI. The activation of PKGI by cGAMP mediates vasorelaxation that is dependent on the activity of MRP1 and volume-regulated anion channel, but independent of the canonical nitric oxide pathway. This mechanism of PKGI activation mediates lowering of blood pressure and contributes to hypotension and tissue hypoperfusion during sepsis.CONCLUSIONS:The activation of PKGI by cGAMP enables the coupling of blood pressure to cytosolic DNA sensing by cGAS, which plays a key role during sepsis by mediating hypotension and tissue hypoperfusion.

Studio italiano sull’evoluzione di uno delle più aggressive e diffuse neoplasie cerebrali

Studiata l’evoluzione del glioblastoma in un modello animale

Cresce del 50% il pericolo per il collo dell’utero

Presentato alla Camera studio, ‘riduce del 70% il rischio’

To the Editor A recent study showed pretransplant persistence of FLT3 internal tandem duplication (FLT3-ITD) and NPM1 variants in adults with acute myeloid leukemia (AML) to be an effective predictor of posttransplant relapse. We have several observations about this study.

In Reply We thank Dr Khaire and colleagues for their interest in our study, and for their agreement that the study provides strong evidence that the detection of persistent FLT3-ITD or NPM1 variants in the blood samples of adults during first remission from AML prior to allogeneic transplant is associated with increased posttransplant relapse and death, compared with those testing negative.