ObjectiveCharacterization of altered expression of selected transcripts linked to inflammation in the peripheral blood of sporadic amyotrophic lateral sclerosis (sALS) patients at early stage of disease to increase knowledge about peripheral inflammatory response in sALS.MethodsRNA expression levels of 45 genes were assessed by RT-qPCR in 22 sALS cases in parallel with 13 age-matched controls. Clinical and serum parameters were assessed at the same time.ResultsUpregulation of genes coding for factors involved in leukocyte extravasation (ITGB2, INPP5D, SELL, and ICAM1) and extracellular matrix remodeling (MMP9 and TIMP2), as well as downregulation of certain chemokines (CCL5 and CXC5R), anti-inflammatory cytokines (IL10, TGFB2, and IL10RA), pro-inflammatory cytokines (IL-6), and T-cell regulators (CD2 and TRBC1) was found in sALS cases independently of gender, clinical symptoms at onset (spinal, respiratory, or bulbar), progression, peripheral leukocyte number, and integrity of RNA. MMP9 levels positively correlated with age, whereas CCR5, CCL5, and TRBC1 negatively correlated with age in sALS but not in controls. Relatively higher TNFA expression levels correlate with higher creatinine kinase protein levels in plasma.ConclusionPresent findings show early inflammatory responses characterized by upregulation of factors enabling extravasation of leukocytes and extracellular matrix remodeling in blood in sALS cases, in addition to increased TNFA levels paralleling skeletal muscle damage.
CAR<0.15 was 65%, whereas for patients with CAR!0.15 was 46% (p < 0.01). In the univariate analysis, the following were prognostic factors for OS: CAR (p ¼ 0.02), tumor downstaging (p ¼ 0.05) and pCR (p ¼ 0.03). In the multivariate analysis, tumor downstaging (HR 0.23, 95% CI 0.06-0.91, p ¼ 0.04) and low CAR (HR 0.09, 95% CI 0.01-8.8, p ¼ 0.03) maintained a positive impact on OS. Conclusion: According to these data, CAR was an independent prognostic factor for OS. It is a promising and innovative prognostic marker in several pathologies, among them esophageal cancer. However, CAR needs validation in prospective multicentric studies.chemoradiation in esophageal squamous-cell carcinoma: latin/paclitaxel versus cisplatin/5
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