IL-6 and IL-8 as Prognostic Factors in Peritoneal Fluid of Ovarian Cancer
Authors: Silva Rodrigues, Isac Souza; Martins-Filho, Agrimaldo; Micheli, Douglas Cobo; de Lima, Cid Almeida; Tavares-Murta, Beatriz Martins; Candido Murta, Eddie Fernando; Nomelini, Rosekeila Simoes
The objectives of the study were to analyze the dosage of a cytokine panel (IL2, IL5, IL6, IL8, IL10, and TNF-alpha) in the peritoneal fluid and relate the dosage of these cytokines to prognostic para- meters and survival in ovarian cancer. Peritoneal fluid was collected intraopera- tively from 29 patients with primary malignant ovarian neoplasia. Cytokine panel dosing was performed with ELISA. Comparisons of cytokines with prognostic factors were performed using the Wilcoxon-Mann-Whitney test. ROC curves were used to determine the cutoff value of NLR, PLR, and IL6. Univariate and multivariate analysis of disease-free survival (DFS) or overall survival (OS) were performed (Kaplan-Meier and Cox regression). The differences were considered significant when the value of p < .05. Higher levels of IL-6 were related to a neutrophil-lymphocyte ratio (NLR) >3.18 (p = .04), a platelet-lymphocyte ratio (PLR) >219.23 (p = .0051), CA-125 levels >35 U/mL (p = .0019), stage IIIC (p = .0203), and DFS <= 24 months (p = .0267). For IL-8, higher levels were related to PLR > 219.23 (p = .0426), and CA-125 >35 U/mL (p = .0292). In the univariate analysis, IL-6 levels >= 87.23 in peritoneal fluid had a relationship with shorter DFS at significance threshold (p = .05), and with a shorter OS (p = .039). Multivariate survival analysis proved that IL-6 level in the peritoneal fluid was an independent predictor of OS. Therefore, IL-6 and IL-8 in peritoneal lavage were related to poor prognostic factors. These cytokines may represent new biomarkers for ovarian cancer therapies.
Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers
BRAZILIAN JOURNAL OF INFECTIOUS DISEASES
Authors: Coelho, Antonio V. C.; de Moura, Ronald R.; Guimaraes, Rafael L.; Brandao, Lucas A. C.; Crovella, Sergio
Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated. Objective: To identify predictive genetic markers of immune response to ART. Methods: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure. Results: Male patients were overrepresented in non-responder group (p = 0.01). Non-responders also started with lower absolute CD4+ T cell counts (p <0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p = 0.04), rs1128503 (ABCB1) A allele (p = 0.03) and rs707265 (CYP2B6) A allele (p = 0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p =0.004) and rs4646437 (CYP3A4) A allele (p = 0.04). Conclusion: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response. (C) 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Espana, S.L.U.