Risultati per: Scoperto nuovo biomarker per il cancro al colon-retto

Stroke, Ahead of Print. Background:Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on MRI only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel MRI-based metric, infarct density, which leverages post-EVT apparent diffusion coefficient (ADC) as a marker of infarct severity.Methods:A retrospective cohort was derived from a single-center prospective EVT registry. Consecutive anterior circulation EVT patients were included from 2018-2019 who achieved successful reperfusion (mTICI ≥2b). MRI was performed 12-48 hours post-EVT and processed via RAPID to quantify FIV using the ADC

Stroke, Volume 56, Issue Suppl_1, Page ATP85-ATP85, February 1, 2025. Background and Purpose:Due to limitations associated with the symptom-based tools currently used for triage, up to 35% of strokes are missed at initial clinician contact in emergency medicine settings. As a result, there has been a decades-long push to identify blood biomarkers with utility for stroke recognition. Despite numerous studies reporting candidates with seemingly high levels of diagnostic performance, none have made their way into clinical use. It is possible this discrepancy is linked to translational limitations in how these prior biomarker discovery investigations have been designed and implemented. Thus, we performed a nontraditional systematic review and meta-analysis spanning 30 years of published acute stroke blood biomarker data in which we sought to explicitly quantify the effects of study design and reporting considerations on diagnostic performance estimates, and correct said estimates for such effects in order to provide better projections of how the candidate biomarkers that have been studied to date would perform in a true clinical use scenario.Methods and Results:A electronic database search was performed to identify previously reported human acute stroke blood biomarker investigations, which yielded 14,253 potential articles. 189 were included in our final analysis based on subsequent abstract and full-text screening. From each article, detailed methodological information for all reported diagnostic comparisons was manually extracted. Collectively, data from 705 different diagnostic comparisons involving 355 unique single analytes or multi-analyte panels were captured. The raw diagnostic performance estimates reported in the literature inferred that as high as 40% of previously investigated candidate biomarkers could be clinically useful for stroke recognition. However, multiple regression revealed that 47.2% of the variance in these diagnostic performance estimates could be attributed to a small number of confounding study design and reporting factors related to population sampling, timing of blood collection, blinding, and conflicts of interest. After using the model residuals to correct for these factors, not a single candidate biomarker displayed adequate evidence to suggest true clinical utility.Conclusions:Our results clarify the current state of the search for an acute stroke blood biomarker, and identify several translational limitations that need to addressed in future investigations if one is to be realized.

Stroke, Volume 56, Issue Suppl_1, Page ATP60-ATP60, February 1, 2025. Background:Due to limited diagnostic accuracy in the symptom-based tools currently used by paramedics, triage nurses, and emergency physicians, up to 35% of strokes are missed at initial clinician contact. As a result, there has been a push to identify blood biomarkers that could aid in stroke recognition at triage. There is evidence to suggest stroke is more frequently mistriaged in minority patients than White patients; to avoid perpetuating these disparities as stroke biomarkers move towards clinical use, it is important that involved investigations meaningfully account for race and ethnicity. However, it is unclear how commonly this occurs in practice.Purpose:This systematic review and meta-analysis aimed to quantify the degree that race and ethnicity information was reported in prior acute stroke blood biomarker investigations, and assess the effect of racial and ethnic heterogeneity on reported diagnostic performance.Methods:An electronic database search to identify published human acute stroke blood biomarker investigations yielded 14,253 articles. After abstract and full-text screening, 189 articles reporting 705 unique diagnostic comparisons were analyzed. For each diagnostic comparison, the reported primary diagnostic statistics were manually extracted, along with the racial and ethnic composition of the study sample if available. Diagnostic statistics were converted to a single diagnostic odds ratio, and race and ethnicity information was used to calculate a Gini diversity index value to represent the demographic heterogeneity of the sample.Results:Subject race or ethnicity was only described for 21.8% of diagnostic comparisons. For diagnostic comparisons reporting this information, study populations showed high homogeneity with median Gini diversity indices of 0.33 for race and 0 for ethnicity. We found a negative correlation between Gini diversity index for race and diagnostic odds ratio (Spearman’s rho= -0.17, p=0.14), indicating to some degree that that more homogenous study samples are more likely to produce higher diagnostic performance estimates.Conclusions:Findings from acute stroke biomarker investigations are at risk for poor generalizability to the diverse clinical populations that stroke triage serves. To reduce this risk, future work needs to address race and ethnicity more meaningfully in terms of both sampling methods and reporting.

Stroke, Volume 56, Issue Suppl_1, Page AWP230-AWP230, February 1, 2025. Hemorrhagic strokes (HS) are increasingly significant causes of disability and mortality worldwide, making the use of blood biomarkers for their diagnosis and prognosis critical. Inflammatory markers in peripheral blood reflect the body’s response to acute cerebrovascular incidents, and monitoring these during the acute phase of HS can provide valuable insights into disease progression and potential deterioration.This prospective observational study, conducted without medical intervention, involved 130 patients with clinically and instrumentally verified hemorrhagic strokes in the acute phase, all with hypertension, and a control group of 30 individuals without stroke, average age 60 years. Upon admission, patients were assessed for consciousness and neurological status using the FOUR and NIHSS scales. Blood samples for Glial Fibrillary Acidic Protein (GFAP), a marker of astroglial damage, were collected within the first 24-30 hours after onset and analyzed using ELISA. All patients also underwent CT and MRI brain scans.Statistical analysis was performed using multivariate linear regression and ROC analysis. The study found that GFAP levels were significantly higher in HS patients, particularly among those with fatal outcomes. Survivors had GFAP levels of 1.35 ng/mL, while deceased patients had levels of 1.94 ng/mL (p 50 mL. These findings were used to develop multivariate binary logistic regression models for predicting HS outcomes during the acute phase.The prognostic model, incorporating GFAP levels, FOUR and NIHSS scores, hematoma volume, perifocal edema, and midline structure shift, demonstrated a 95% sensitivity in determining fatal outcomes. GFAP, synthesized by astrocytes, plays a critical role in astrocyte differentiation, neuronal energy supply, blood-brain barrier formation, and reparative processes post-hemorrhage. Given its role as a marker of cellular damage and its regulatory function in brain repair, GFAP and other biomarkers should be employed to assess patient condition severity and guide the development of new therapeutic strategies for hemorrhagic strokes.

Stroke, Volume 56, Issue Suppl_1, Page ATP44-ATP44, February 1, 2025. Introduction:Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease (SVD) caused by amyloid β deposition. It is closely linked to Alzheimer’s disease (AD) and predisposes elderly patients to intracerebral hemorrhage and cognitive impairment. However, no effective serum biomarker has been established for early diagnosis or prediction of the disease progression. We discovered that a protein, “alpha1-Acid glycoprotein (α1-AGP),” is a potential serum biomarker for CAA.Methods:Proteins in serum samples from CAA patients (n = 10) who meet the modified Boston criteria by a classification of probable or possible and age-matched controls (n = 10) were analyzed exhaustively using two-dimensional differential gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF/MS). Afterward, each candidate was evaluated quantitatively using the ELISA (Enzyme-Linked Immunosorbent Assay) method.Results:Compared with the control group, the expression levels of 4 proteins (Hemopexin, Complement C9, C3, α1-AGP) were increased, and 1 protein (Apolipoprotein A-I) was decreased in the CAA group. We evaluated the expression levels of those 5 proteins by ELISA method and confirmed that the concentration of α1-AGP is significantly increased in the serum samples from the CAA group. Receiver Operatorating Characteristic curve analysis showed that the concentration of α1-AGP could clearly distinguish CAA or not. Moreover, we examined the association between the expression levels of those proteins and the MRI SVD burden (CAA-SVD score) in the same patient group and found a good correlation with α1-AGP (R squared is 0.779).Conclusion:Our results suggest that α1-AGP could be a novel serum protein biomarker for diagnosing CAA.

Stroke, Volume 56, Issue Suppl_1, Page ATP49-ATP49, February 1, 2025. Background:Small vessel cerebral vascular disease (sCVD) is common to older individuals, often asymptomatic, but associated with incident stroke and future mortality. Multiple mechanisms for sCVD have been postulated, all of which include injury to the neurovascular unit. Analysis of extracellular vesicles (EVs), important constituents of the intercellular communication pathway, may offer new ways to evaluate pathological processes of sCVD as well as serve as novel biomarkers or identify new avenues for therapy. This abstract summarizes work by our group to subtype EVs and measure cargo proteins from the various cell types of the neurovascular unit from a group of cognitively normal individuals with a spectrum of sCVD.Method:Study participants consisted of 14 individuals, 50 % female, 76+7 years of age, having 17.6+1.9 years of education. White matter hyperintensities varied from 0.73 – 38.8 cc. EV isolation used an Exodus ultrafiltration system on platelet depleted plasma. EVs were further fractionated into EV subtypes with resin-conjugated antibodies against cell type-specific markers. Five EV subtypes were isolated by two rounds of immunoprecipitation with the following markers: NCAM1/ATP1A3 (excitatory neuron EV), CD49f/LRP1 (astrocyte EV), CD11b/LCP1 (activated microglia EV), LAMP2/FTH1 (oligodendrocyte EV), CD31/CD146 (activated endothelial EV). Following isolation of EV subtypes, samples were characterized for purity and yield by nanoparticle tracking analysis, imaged for protein expression by super resolution microscopy, and sequenced for biomarker identification by quantitative proteomics.Results:Nanoparticle tracking analysis confirmed high yields of all 5 EV subtypes, > 2E9 EVs/mL, along with identical size and surface charge profiles. Super resolution microscopy showed consistent canonical EV marker distributions on all EVs while EV subtypes expressed unique markers based off their cell type of origin. Quantitative proteomics identified 400 unique and differentially expressed proteins present amongst the various EV subtypes as compared to mean plasma EVs concentrations. Protein abundance varied widely across EV subpopulations, indicating distinct protein profiles.Conclusion:Preliminary results confirm the potential for biomarker discovery from novel EV subpopulations through identification of differentially expressed cargo proteins from the neurovascular unit. Future work will associate these findings with sCVD phenotypes.

Il 25 Airc celebra 60 anni d’impegno, 141 milioni alla ricerca

Background
Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.

Objective
We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis.

Design
Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results.

Results
Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11+ epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer.

Conclusion
Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.

Studio, dieta anti cancro da cereali integrali e verdura

Studio, dieta anti cancro da cereali integrali e verdura

The prospect of avoiding an invasive colonoscopy has helped fuel interest around new less-invasive alternatives to colorectal cancer screenings, such as stool-based tests and cell-free blood-based DNA tests, which received approval from the US Food and Drug Administration (FDA) this past July. But traditional colonoscopies remain the best method for catching colorectal cancer early, according to a study published in the Annals of Internal Medicine.

Crollano titoli in Borsa delle aziende del settore

Crollano titoli in Borsa delle aziende del settore

Il programma viene esteso fino alla fascia 70-74 anni