The relationship between interleukin-6 and C-reactive protein in patients with benign and malignant prostate disease.
Ontology highlight
ABSTRACT:
SUBMITTER: McArdle PA
PROVIDER: S-EPMC2410056 | biostudies-other | 2004 Nov
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundBoth benign prostatic hyperplasia (BPH) and sarcopenic obesity (SO) are common conditions among older adult/adults males. The prevalent lifestyle associated with SO is a significant risk factor for the development of BPH. Therefore, we investigated the causal relationship between SO factors and BPH.MethodThe instrumental variables for SO factors were selected using the inverse variance-weighted method, which served as the primary approach for Mendelian randomization analysis to assess the causal effect based on summary data derived from genome-wide association studies of BPH.ResultThe increase in BMR (OR = 1.248; 95% CI = (1.087, 1.432); P = 0.002) and ALM (OR = 1.126; 95% CI = (1.032, 1.228); P = 0.008) was found to be associated with an elevated risk of BPH. However, no genetic causality between fat-free mass distribution, muscle mass distribution, and BPH was observed.ConclusionOur findings indicate that a genetic causal association between BMR, ALM and BPH. BMR and ALM are risk factors for BPH. The decrease in BMR and ALM signified the onset and progression of SO, thus SO is a protective factor for BPH.
| S-EPMC10663947 | biostudies-literature
Project description:We enrolled 33 patients with COVID-19 (23 men and 10 women; age 59 ± 15; males, n = 23; females, n = 10) admitted to the Department of Infectious Diseases of Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" of Reggio Calabria, Italy, between March and May 2020. Whole blood samples were collected before the start of therapeutic treatment using all virus spread containment measures. Sample preparation protocols were designed in order to minimize operators direct specimen's manipulation. On univariate analysis, circulating levels of CRP were strongly and inversely related to CD3+ (rho = -0.77, p < 0.001), CD3+4+ (rho = -0.74, p < 0.001), and CD3+8+ (rho = -0.66, p = 0.001) implying that the shared variances between absolute values T cells and CRP ranged from 44 to 59%. Of note, the strength of these associations was higher in patients with relatively lower (below the median value) white blood cells (WBC) as compared to those with WBC above the median value. CRP also correlated with NK bright (rho = -0.56, p = 0.005) but failed to be related with CD19+ (rho = -0.38, p = 0.07), CD4+/CD8+ ratio (rho = 0.03, p = 0.89), CD16+ CD56+ (rho = -0.18, p = 0.43), and NKdim (rho = -0.15, p = 0.49). Lymphocyte subsets alteration monitoring in COVID-19 positive patients may be a valid aid to control treatment efficacy of therapy and to choose better clinical approach. In particular, the negative correlation between CD3+, CD3+CD4+, CD3+CD8+ T cells values and CRP could be a useful tool to predict patient's response to therapy, particularly in patients with relatively lower WBC.
| S-EPMC8013919 | biostudies-literature
Project description:We have examined the role of a novel cytokine, interleukin-27 (IL-27), in mediating interactions between prostate cancer and bone. IL-27 is the most recently characterized member of the family of heterodimeric IL-12-related cytokines and has shown promise in halting tumor growth and mediating tumor regression in several cancer models, including prostate cancer. Prostate cancer is frequently associated with metastases to the bone, where the tumor induces a vicious cycle of communication with osteoblasts and osteoclasts to induce bone lesions, which are a significant cause of pain and skeletal-related events for patients, including a high fracture risk. We describe our findings in the effects of IL-27 gene delivery on prostate cancer cells, osteoblasts, and osteoclasts at different stages of differentiation. We applied the IL-27 gene delivery protocol in vivo utilizing sonoporation (sonodelivery) with the goal of treating and reducing the growth of prostate cancer at a bone metastatic site in vivo. We used a new model of immune-competent prostate adenocarcinoma and characterized the tumor growth reduction, gene expression, and effector cellular profiles. Our results suggest that IL-27 can be effective in reducing tumor growth, can help normalize bone structure, and can promote enhanced accumulation of effector cells in prostate tumors. These results are promising, because they are relevant to developing a novel IL-27-based strategy that can treat both the tumor and the bone, by using this simple and effective sonodelivery method for treating prostate tumor bone metastases.
| S-EPMC3868392 | biostudies-literature
Project description:The human BCL6 gene, which is involved in the pathogenesis of certain human lymphomas, encodes a transcriptional repressor that is needed for germinal center B cell development and T follicular helper cell differentiation. Our goal was to identify BCL6 target genes using a cell system in which BCL6 repressive effects are inhibited followed by subtractive hybridization, and we detected the RUVBL1 (Pontin, TIP49) gene as a potential target of BCL6 repression. Here we show that the BCL6 protein significantly represses RUVBL1 transcription (6.8-fold). Knockdown of endogenous BCL6 in a human B cell lymphoma line leads to significant upregulation of RUVBL1, and there is an inverse expression pattern between the BCL6 and RUVBL1 proteins in certain human lymphomas. RUVBL1 is part of the AAA+ superfamily and participates in multiple processes, including gene transcription regulation, chromatin remodeling, and DNA repair, which, if dysregulated, may promote lymphoma development. A further understanding of the relationship between RUVBL1 and BCL6 should improve our understanding of the pathogenesis of human lymphomas.
| S-EPMC4822715 | biostudies-literature
Project description:Background To promote ideal cardiovascular health, the American Heart Association recommends adhering to Life's Simple 7 (LS7)-achieving healthy targets for body mass index, physical activity, dietary intake, blood pressure, fasting plasma glucose, and cholesterol, along with smoking abstinence. Poorer achievement of LS7 (lower score) has been associated with the development of hypertension and cardiovascular disease. However, less is known about the associations between LS7 and specific biomarkers linked to cardiovascular health: aldosterone, CRP (C-reactive protein), and IL-6 (interleukin-6). Methods and Results We analyzed 379 individuals (age 18-66 years) from the HyperPATH (International Hypertensive Pathotype), who were maintained on ≥200 mEq of sodium daily for 1 week. We calculated a 14-point summative LS7 score according to participants' baseline data. Based on the range of LS7 score in this population (3-14), we classified participants as "inadequate" (3-6), "average" (7-10), and "optimal" (11-14). Regression analyses found that a higher LS7 score group was associated with lower levels of serum and urinary aldosterone (Ptrend<0.001 and Ptrend=0.001, respectively), lower plasma renin activity (Ptrend<0.001), and a blunted increase in serum aldosterone with angiotensin II infusion (Ptrend=0.023). Being in the "optimal" LS7 score group was associated with lower serum CRP (Ptrend=0.001) and IL-6 (Ptrend=0.001). Conclusions A higher LS7 score was associated with a lower activity of the renin-angiotensin-aldosterone system and lower levels of the inflammatory markers CRP and IL-6. These findings offer a possible link between ideal cardiovascular health targets and biomarkers known to play a central role in the development of cardiovascular disease.
| S-EPMC10227293 | biostudies-literature
Project description:Background & aimsThere is evidence that immune dysfunction precedes symptoms of inflammatory bowel disease (IBD) by several years. Characterization of preclinical systemic inflammation could contribute to the understanding of the biology of IBD and, ultimately, facilitate development of strategies for early disease detection and intervention. We evaluated associations between circulating levels of interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP) and diagnosis of incident Crohn's disease (CD) or ulcerative colitis (UC).MethodsWe conducted a nested case-control study of participants enrolled in 2 population-based, nationwide, prospective cohort studies (the Nurses' Health Study and the Nurses' Health Study II). We analyzed blood specimens, collected before diagnosis, from 83 persons with CD, 90 persons with UC, and 344 matched individuals without IBD (control subjects). Plasma levels of hsCRP and IL6 were measured. We investigated associations between each inflammatory marker and IBD risk using multivariable logistic regression models to adjust for potential confounding exposures.ResultsCompared with the lowest quintile of IL6 level, the highest quintile was associated with an odds ratio (OR) of 4.68 (95% confidence interval, 1.91-11.46) for CD (Ptrend < .001) and an OR of 3.43 (95% confidence interval, 1.44-8.15) for UC (Ptrend = .004). The highest quintile of hsCRP level, compared with the lowest quintile, was associated with an OR of 2.82 (95% confidence interval, 1.15-6.87) for CD (Ptrend = .019) and an OR of 1.79 (95% confidence interval, 0.80-3.99) for UC (Ptrend = .015).ConclusionsPlasma levels of IL6 and hsCRP before diagnosis are associated with risk of incident CD and UC. Subclinical levels of systemic inflammation may be a feature of an early disease state that precedes the development of symptomatic IBD.
| S-EPMC4875875 | biostudies-literature
Project description:Interleukin-6 (IL-6) and C-reactive protein (CRP) are elevated in prostate cancer patients, but the role of prediagnostic levels of these inflammatory mediators on prostate cancer outcomes is unclear. We undertook a large, prospective case-control study to evaluate the relation between prediagnostic levels of IL-6 and CRP and prostate cancer incidence and mortality. We also investigated the role of the IL-6 (-174 G/C) polymorphism in relation to circulating levels of IL-6 and CRP, as well as cancer risk and mortality. We used unconditional logistic regression that adjusted for matching factors to analyze prostate cancer risk. For analyses of prostate cancer mortality, we conducted survival analyses in cases. Because of the strong link between inflammatory markers and body mass index (BMI), we assessed interactions between BMI and plasma levels on prostate cancer outcomes. Neither IL-6 nor CRP plasma levels varied significantly by IL-6 genotype. Genotype was not associated with prostate cancer risk or survival. Though neither IL-6 nor CRP was associated with prostate cancer incidence overall, we observed a statistically significant interaction between IL-6 and BMI on prostate cancer incidence (p(interaction) < 0.01). Increasing IL-6 levels were positively associated with risk in healthy weight men, but inversely associated with risk in overweight men. Further, prediagnostic IL-6 was associated with time to prostate cancer progression/death among healthy weight prostate cancer cases (p(trend) = 0.02). Adjusted hazard ratios were 1.73 (95% CI: 0.86, 3.51) comparing the highest to lowest IL-6 level. Our study suggests that IL-6 may potentially be involved in the development or progression of prostate cancer.
| S-EPMC2667697 | biostudies-literature
Project description:Intra-tumor heterogeneity (ITH) has been studied at the morphologic, genomic, and transcriptomic level, but not proteomic level. Recent advances in mass spectrometric (MS) proteome quantification techniques, exemplified by SWATH-MS, a massively parallel targeting method, now also support precise quantitative proteomic comparisons across multiple samples, thus identifying molecular and implied functional differences. Here we used SWATH-MS to analyze the proteome profiles of a set of fresh-frozen prostate tissue samples derived from radical prostatectomy specimens. A high confidence set of 1,906 proteins were consistently quantified across 60 biopsy-level tissue samples from three prostatectomy patients, each consisting of 1.0 mm punch biopsies from histologically malignant (acinar and ductal adenocarcinoma) and matching benign prostatic hyperplasia tissues. The quantitative protein profiles allowed independent quantification of the degree of intra-tumor heterogeneity for each protein in benign and malignant tissues. We found that while majority of the proteins showed comparably low intra-tumor variability, 122 proteins were highly variable in malignant and/or matching benign tissues. We observed that proteins that varied between patients or tissue types also tended to be highly variable within prostate tissues, suggesting that these variability patterns will be a critical selection criterion in future protein biomarker studies. The data also permitted investigation of the heterogeneity of multiple biochemical pathways. The high variability of several of the pathways, including Glypican-1 network, alpha-linolenic acid metabolism and celecoxib pathway, explained contradictory results regarding them in the literature. In conclusion, we demonstrated a methodology for investigating proteomic intra-tumor heterogeneity from biopsy-level tissue samples, and quantified the degree of intra-tumor heterogeneity of 1,906 proteins in prostate tumors. The method and data presented here have advanced our understanding of tumor biology and offered critical insights for future biomarker development.
2018-08-13 | PXD003497 | Pride
Project description:Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7-CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates. Furthermore, there were differences between the prostate conditions regarding the percentage of T-cells expressing several activation markers and co-inhibitory receptors. In conclusion, many prostate-infiltrating T-cells express co-inhibitory receptors PD-1 and LAG-3, regardless of prostate condition. Despite the observed increase in counts and percentages of PD-1+ T-cells in PC, the concomitant demonstration of high percentage of PD-1+ T-cells in control prostates suggests that PD-1 may play a role in controlling the homeostasis of the prostate rather than in contributing to PC-associated immune-suppression. Thus, PD-1 may not be a good candidate for checkpoint blockade in PC and these data are relevant for evaluation of clinical trials and in designing future immunotherapeutic approaches of PC.
| S-EPMC5601136 | biostudies-literature
Project description:BackgroundProstate cancer is a major health concern in aging men. Paralleling an aging society, prostate cancer prevalence increases emphasizing the need for efficient diagnostic algorithms.MethodsRetrospectively, 106 prostate tissue samples from 48 patients (mean age, [Formula: see text] years) were included in the study. Patients suffered from prostate cancer (n = 38) or benign prostatic hyperplasia (n = 10) and were treated with radical prostatectomy or Holmium laser enucleation of the prostate, respectively. We constructed tissue microarrays (TMAs) comprising representative malignant (n = 38) and benign (n = 68) tissue cores. TMAs were processed to histological slides, stained, digitized and assessed for the applicability of machine learning strategies and open-source tools in diagnosis of prostate cancer. We applied the software QuPath to extract features for shape, stain intensity, and texture of TMA cores for three stainings, H&E, ERG, and PIN-4. Three machine learning algorithms, neural network (NN), support vector machines (SVM), and random forest (RF), were trained and cross-validated with 100 Monte Carlo random splits into 70% training set and 30% test set. We determined AUC values for single color channels, with and without optimization of hyperparameters by exhaustive grid search. We applied recursive feature elimination to feature sets of multiple color transforms.ResultsMean AUC was above 0.80. PIN-4 stainings yielded higher AUC than H&E and ERG. For PIN-4 with the color transform saturation, NN, RF, and SVM revealed AUC of [Formula: see text], [Formula: see text], and [Formula: see text], respectively. Optimization of hyperparameters improved the AUC only slightly by 0.01. For H&E, feature selection resulted in no increase of AUC but to an increase of 0.02-0.06 for ERG and PIN-4.ConclusionsAutomated pipelines may be able to discriminate with high accuracy between malignant and benign tissue. We found PIN-4 staining best suited for classification. Further bioinformatic analysis of larger data sets would be crucial to evaluate the reliability of automated classification methods for clinical practice and to evaluate potential discrimination of aggressiveness of cancer to pave the way to automatic precision medicine.
| S-EPMC9809030 | biostudies-literature