Browsing by Subject "NEUTROPHILS"

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  • Koledova, Zuzana; Howard, Beatrice A.; Englund, Johanna; Bach, Karsten; Bentires-Alj, Mohammed; Gonzalez-Suarez, Eva (2018)
    The European Network for Breast Development and Cancer (ENBDC), a worldwide network (http://www.enbdc.org/), celebrated its tenth anniversary with a fantastic meeting last March 15-17, 2018 in Weggis with 76 attendees.
  • Tverring, Jonas; Vaara, Suvi T.; Fisher, Jane; Poukkanen, Meri; Pettila, Ville; Linder, Adam; FINNAKI Study Grp (2017)
    Background: Sepsis-related acute kidney injury (AKI) accounts for major morbidity and mortality among the critically ill. Heparin-binding protein (HBP)is a promising biomarker in predicting development and prognosis of severe sepsis and septic shock that has recently been proposed to be involved in the pathophysiology of AKI. The objective of this study was to investigate the added predictive value of measuring plasma HBP on admission to the intensive care unit (ICU) regarding the development of septic AKI. Methods: We included 601 patients with severe sepsis or septic shock from the prospective, observational FINNAKI study conducted in seventeen Finnish ICUs during a 5-month period (1 September 2011-1 February 2012). The main outcome measure was the development of KDIGO AKI stages 2-3 from 12 h after admission up to 5 days. Statistical analysis for the primary endpoint included construction of a clinical risk model, area under the receiver operating curve (ROC area), category-free net reclassification index (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence intervals (95% CI). Results: Out of 511 eligible patients, 101 (20%) reached the primary endpoint. The addition of plasma HBP to a clinical risk model significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk classification scores: cfNRI 62.0% (95% CI 40.5-82.4%) and IDI 0.053 (95% CI 0.029-0.075). Conclusions: Plasma HBP adds predictive value to known clinical risk factors in septic AKI. Further studies are warranted to compare the predictive performance of plasma HBP to other novel AKI biomarkers.
  • Chen, W.; Metsala, M.; Vaittinen, Olavi; Halonen, L. (2014)
  • Kaasinen, Mirjami; Hagström, Jaana; Mustonen, Harri; Sorsa, Timo; Sund, Malin; Haglund, Caj; Seppänen, Hanna (2022)
    Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002-2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan-Meier analysis while uni- and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69-17.93; p < 0.001) compared to a positive stain and low CRP level (
  • Hamdan, Firas; Ylösmäki, Erkko; Chiaro, Jacopo; Giannoula, Yvonne; Long, Maeve; Fusciello, Manlio; Feola, Sara; Martins, Beatriz; Feodoroff, Michaela; Antignani, Gabriella; Russo, Salvatore; Kari, Otto; Lee, Moon; Järvinen, Petrus; Nisen, Harry; Kreutzman, Anna; Leusen, Jeanette; Mustjoki, Satu; McWilliams, Thomas G.; Grönholm, Mikaela; Cerullo, Vincenzo (2021)
    Background Despite the success of immune checkpoint inhibitors against PD-L1 in the clinic, only a fraction of patients benefit from such therapy. A theoretical strategy to increase efficacy would be to arm such antibodies with Fc-mediated effector mechanisms. However, these effector mechanisms are inhibited or reduced due to toxicity issues since PD-L1 is not confined to the tumor and also expressed on healthy cells. To increase efficacy while minimizing toxicity, we designed an oncolytic adenovirus that secretes a cross-hybrid Fc-fusion peptide against PD-L1 able to elicit effector mechanisms of an IgG1 and also IgA1 consequently activating neutrophils, a population neglected by IgG1, in order to combine multiple effector mechanisms. Methods The cross-hybrid Fc-fusion peptide comprises of an Fc with the constant domains of an IgA1 and IgG1 which is connected to a PD-1 ectodomain via a GGGS linker and was cloned into an oncolytic adenovirus. We demonstrated that the oncolytic adenovirus was able to secrete the cross-hybrid Fc-fusion peptide able to bind to PD-L1 and activate multiple immune components enhancing tumor cytotoxicity in various cancer cell lines, in vivo and ex vivo renal-cell carcinoma patient-derived organoids. Results Using various techniques to measure cytotoxicity, the cross-hybrid Fc-fusion peptide expressed by the oncolytic adenovirus was shown to activate Fc-effector mechanisms of an IgA1 (neutrophil activation) as well as of an IgG1 (natural killer and complement activation). The activation of multiple effector mechanism simultaneously led to significantly increased tumor killing compared with FDA-approved PD-L1 checkpoint inhibitor (Atezolizumab), IgG1-PDL1 and IgA-PDL1 in various in vitro cell lines, in vivo models and ex vivo renal cell carcinoma organoids. Moreover, in vivo data demonstrated that Ad-Cab did not require CD8+ T cells, unlike conventional checkpoint inhibitors, since it was able to activate other effector populations. Conclusion Arming PD-L1 checkpoint inhibitors with Fc-effector mechanisms of both an IgA1 and an IgG1 can increase efficacy while maintaining safety by limiting expression to the tumor using oncolytic adenovirus. The increase in tumor killing is mostly attributed to the activation of multiple effector populations rather than activating a single effector population leading to significantly higher tumor killing.
  • Tracz, Joanna; Handschuh, Luiza; Lalowski, Maciej; Marczak, Lukasz; Kostka-Jeziorny, Katarzyna; Perek, Bartlomiej; Wanic-Kossowska, Maria; Podkowinska, Alina; Tykarski, Andrzej; Formanowicz, Dorota; Luczak, Magdalena (2021)
    A progressive loss of functional nephrons defines chronic kidney disease (CKD). Complications related to cardiovascular disease (CVD) are the principal causes of mortality in CKD; however, the acceleration of CVD in CKD remains unresolved. Our study used a complementary proteomic approach to assess mild and advanced CKD patients with different atherosclerosis stages and two groups of patients with different classical CVD progression but without renal dysfunction. We utilized a label-free approach based on LC-MS/MS and functional bioinformatic analyses to profile CKD and CVD leukocyte proteins. We revealed dysregulation of proteins involved in different phases of leukocytes' diapedesis process that is very pronounced in CKD's advanced stage. We also showed an upregulation of apoptosis-related proteins in CKD as compared to CVD. The differential abundance of selected proteins was validated by multiple reaction monitoring, ELISA, Western blotting, and at the mRNA level by ddPCR. An increased rate of apoptosis was then functionally confirmed on the cellular level. Hence, we suggest that the disturbances in leukocyte extravasation proteins may alter cell integrity and trigger cell death, as demonstrated by flow cytometry and microscopy analyses. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD018596.
  • Turunen, Antti; Kuuliala, Antti; Penttilä, Anne; Kaukonen, Kirsi-Maija; Mustonen, Harri; Pettilä, Ville; Puolakkainen, Pauli; Kylänpää, Leena; Kuuliala, Krista (2020)
    Activation of intracellular signaling pathways in circulating leukocytes represents an early step in systemic immune-inflammatory response occurring e.g. in acute pancreatitis (AP) and sepsis. Previously, we found aberrations in the phosphorylation of leukocyte signaling proteins in patients with sepsis or AP (measured
  • Hemilä, Harri (1992)
    The effect of vitamin C on the common cold has been the subject of several studies. These studies do not support a considerable decrease in the incidence of the common cold with supplemental vitamin C. However, vitamin C has consistently decreased the duration of cold episodes and the severity of symptoms. The benefits that have been observed in different studies show a large variation and, therefore, the clinical significance may not be clearly inferred from them. The biochemical explanation for the benefits may be based on the antioxidant property of vitamin C. In an infection, phagocytic leucocytes become activated and they produce oxidizing compounds which are released from the cell. By reacting with these oxidants, vitamin C may decrease the inflammatory effects caused by them. Scurvy, which is caused by a deficiency in vitamin C, is mostly attributed to the decreased synthesis of collagen. However, vitamin C also participates in several other reactions, such as the destruction of oxidizing substances. The common cold studies indicate that the amounts of vitamin C which safely protect from scurvy may still be too low to provide an efficient rate for other reactions, possibly antioxidant in nature, in infected people.
  • Hemilä, Harri; Herman, Zelek S (American College of Nutrition, 1995)
    In 1975 Thomas Chalmers analyzed the possible effect of vitamin C on the common cold by calculating the average difference in the duration of cold episodes in vitamin C and control groups in seven placebo-controlled studies. He found that episodes were 0.11 +/- 0.24 (SE) days shorter in the vitamin C groups and concluded that there was no valid evidence to indicate that vitamin C is beneficial in the treatment of the common cold. Chalmers' review has been extensively cited in scientific articles and monographs. However, other reviewers have concluded that vitamin C significantly alleviates the symptoms of the common cold. A careful analysis of Chalmers' review reveals serious shortcomings. For example, Chalmers did not consider the amount of vitamin C used in the studies and included in his meta-analysis was a study in which only 0.025-0.05 g/day of vitamin C was administered to the test subjects. For some studies Chalmers used values that are inconsistent with the original published results. Using data from the same studies, we calculated that vitamin C (1-6 g/day) decreased the duration of the cold episodes by 0.93 +/- 0.22 (SE) days; the relative decrease in the episode duration was 21%. The current notion that vitamin C has no effect on the common cold seems to be based in large part on a faulty review written two decades ago.