Browsing by Subject "biomarkers"

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  • Räisänen, Ismo T.; Heikkinen, Anna Maria; Pakbaznejad Esmaeili, Elmira; Tervahartiala, Taina; Pajukanta, Riitta; Silbereisen, Angelika; Bostanci, Nagihan; Sorsa, Timo (2019)
    Background This cross-sectional study aims to investigate if a point-of-care (PoC) test of active matrix metalloproteinase-8 (aMMP-8) predicts levels of inflammation amplifier triggering receptor expressed on myeloid cells-1 (TREM-1) and its putative ligand the neutrophil peptidoglycan recognition protein 1 (PGLYRP1) in saliva. Methods Forty-seven adolescents, aged 15 to 17 years, were tested with aMMP-8 PoC test, which was followed by a full-mouth clinical examination of the assessment of periodontal, mucosal, and oral health. TREM-1 and PGLYRP1 levels were analyzed by ELISA. The immunofluorometric assay (IFMA) specific for aMMP-8 was used as the reference method. Results Fourteen saliva samples out of a total of 47 showed positivity for aMMP-8 PoC test. Both the TREM-1 and the aMMP-8 (IFMA) levels were significantly elevated among the aMMP-8 PoC test positives compared with the PoC test negatives (P <0.05). Moreover, aMMP-8 levels assessed by IFMA showed a strong positive correlation with TREM-1 levels in saliva (r = 0.777, P <0.001). The number of sites with a probing depth of >= 4 mm was significantly lower among the adolescents that had a negative aMMP-8 PoC test result, and TREM-1 levels <75 pg/mL (P <0.05). In contrast, adolescents with a positive aMMP-8 PoC test result (i.e., elevated aMMP-8 levels) together with elevated TREM-1 levels had a significantly higher number of periodontal pockets with >= 4 mm (P <0.001). Conclusion The present study validated usability of aMMP-8 PoC test for predicting "proinflammatory" salivary profile and periodontal health status in adolescents.
  • Sorsa, Timo; Alassiri, Saeed; Grigoriadis, Andreas; Räisänen, Ismo T.; Pärnänen, Pirjo; Nwhator, Solomon O.; Gieselmann, Dirk-Rolf; Sakellari, Dimitra (2020)
    The aim of this study was to investigate the utility of incorporating active matrix metalloproteinase-8 (aMMP-8) as a biomarker into the new periodontitis classification system (stage/grade) presented in 2018. This study included 150 Greek adults aged 25-78, of whom 74 were men and 76 women. Participants were tested with an aMMP-8 point-of-care mouthrinse test, after which a full-mouth clinical examination was performed to assess their periodontal and oral health. The aMMP-8 levels in mouthrinse were significantly lower among healthy patients compared with patients in more severe periodontitis stages and grades (Kruskal-Wallis test and Dunn-Bonferroni test for pairwise post-hoc comparisons; p <0.01 and p <0.05, respectively). Furthermore, aMMP-8 levels were less correlated with plaque levels than bleeding on probing (BOP) (Spearman's rho = 0.269, p <0.001; Spearman's rho = 0.586, p <0.001); respectively). Thus, aMMP-8 was more robust to the confounding effects of oral hygiene than traditional periodontal parameter bleeding on probing. The aMMP-8 point-of-care mouthrinse test can be utilized as an adjunctive and preventive diagnostic tool to identify periodontal disease, classified by stage and grade, and ongoing periodontal breakdown chairside in clinical practice in only 5 min. Overall, integrating aMMP-8 into the new periodontitis classification system seems beneficial.
  • Posti, Jussi P.; Takala, Riikka S. K.; Raj, Rahul; Luoto, Teemu M.; Azurmendi, Leire; Lagerstedt, Linnea; Mohammadian, Mehrbod; Hossain, Iftakher; Gill, Jessica; Frantzen, Janek; van Gils, Mark; Hutchinson, Peter J.; Katila, Ari J.; Koivikko, Pia; Maanpää, Henna-Riikka; Menon, David K.; Newcombe, Virginia F.; Tallus, Jussi; Blennow, Kaj; Tenovuo, Olli; Zetterberg, Henrik; Sanchez, Jean-Charles (2020)
    Background: Blood biomarkers may enhance outcome prediction performance of head computed tomography scores in traumatic brain injury (TBI). Objective: To investigate whether admission levels of eight different protein biomarkers can improve the outcome prediction performance of the Helsinki computed tomography score (HCTS) without clinical covariates in TBI. Materials and methods: Eighty-two patients with computed tomography positive TBIs were included in this study. Plasma levels of beta-amyloid isoforms 1-40 (A beta 40) and 1-42 (A beta 42), glial fibrillary acidic protein, heart fatty acid-binding protein, interleukin 10 (IL-10), neurofilament light, S100 calcium-binding protein B, and total tau were measured within 24 h from admission. The patients were divided into favorable (Glasgow Outcome Scale-Extended 5-8, n = 49) and unfavorable (Glasgow Outcome Scale-Extended 1-4, n = 33) groups. The outcome was assessed 6-12 months after injury. An optimal predictive panel was investigated with the sensitivity set at 90-100%. Results: The HCTS alone yielded a sensitivity of 97.0% (95% CI: 90.9-100) and specificity of 22.4% (95% CI: 10.2-32.7) and partial area under the curve of the receiver operating characteristic of 2.5% (95% CI: 1.1-4.7), in discriminating patients with favorable and unfavorable outcomes. The threshold to detect a patient with unfavorable outcome was an HCTS > 1. The three best individually performing biomarkers in outcome prediction were A beta 40, A beta 42, and neurofilament light. The optimal panel included IL-10, A beta 40, and the HCTS reaching a partial area under the curve of the receiver operating characteristic of 3.4% (95% CI: 1.7-6.2) with a sensitivity of 90.9% (95% CI: 81.8-100) and specificity of 59.2% (95% CI: 40.8-69.4). Conclusion: Admission plasma levels of IL-10 and A beta 40 significantly improve the prognostication ability of the HCTS after TBI.
  • Lähteenmäki, Hanna; Umeizudike, Kehinde A.; Heikkinen, Anna Maria; Räisänen, Ismo T.; Rathnayake, Nilminie; Johannsen, Gunnar; Tervahartiala, Taina; Nwhator, Solomon O.; Sorsa, Timo (2020)
    This communication article addresses currently available rapid non-invasive methods to screen and detect periodontitis and dental peri-implantitis. In this regard, oral fluid biomarkers have been researched extensively but self-reported oral health (SROH)-questionnaires have also been developed. Both alternatives may offer a quick and easy way to screen and detect diseased patients. Active matrix metalloproteinase (aMMP-8) is one of the most validated biomarkers for screening and detecting periodontal breakdown related to periodontitis and peri-implantitis and monitoring their treatment effects revealing successful, less- and non-successful treatment results. Currently available aMMP-8 lateral-flow technologies allow this kind of analysis, as demonstrated here, to be conducted quantitatively online and real-time as point-of-care/chairside testing in dental and even medical care settings. In this study, an aMMP-8 peri-implant sulcular fluid point-of-care-test diagnosed peri-implantitis and healthy implants far more accurately than bleeding-on-probing or the other biomarkers, such as polymorphonuclear (PMN)/neutrophil elastase, myeloperoxidase and MMP-9. Although, SROH-questionnaires allow screening in similar settings but they lack the information about the current disease activity of periodontitis and peri-implantitis, which is of essential value in periodontal diagnostics and treatment monitoring. Thus, both methods can be considered as adjunct methods for periodontitis and peri-implant diagnostics, but the value of oral fluid biomarkers analysis does not seem to be substitutable.
  • Räisänen, Ismo T.; Lähteenmäki, Hanna; Gupta, Shipra; Grigoriadis, Andreas; Sahni, Vaibhav; Suojanen, Juho; Seppänen, Hanna; Tervahartiala, Taina; Sakellari, Dimitra; Sorsa, Timo (2021)
    The aim of this cross-sectional study is to propose an efficient strategy based on biomarkers adjunct with an interview/questionnaire covering risk factors for periodontitis for the identification of undiagnosed periodontitis by medical professionals. Active matrix metalloproteinase (aMMP)-8 levels in mouthrinse were analyzed by a point-of-care (PoC)/chairside lateral-flow immunotest, and salivary total MMP-8, total MMP-9 and calprotectin levels were analyzed by enzyme-linked immunosorbent assays (ELISAs) and active MMP-9 by gelatin zymography for 149 Greek patients. Patients underwent a full-mouth oral health examination for diagnosis according to the 2018 classification system of periodontal diseases. In addition, patient characteristics (risk factors: age, gender, education level, smoking and body mass index) were recorded. Receiver operating curve (ROC) analysis indicated better diagnostic precision to identify undiagnosed periodontitis for oral fluid biomarkers in adjunct with an interview/questionnaire compared with a plain questionnaire (i.e., risk factors): aMMP-8 AUC (95% confidence interval) = 0.834 (0.761-0.906), total MMP-8 = 0.800 (0.722-0.878), active MMP-9 = 0.787 (0.704-0.870), total MMP-9 = 0.773 (0.687-0.858) and calprotectin = 0.773 (0.687-0.858) vs. questionnaire = 0.764 (0.676-0.851). The findings of this study suggest that oral fluid biomarker analysis, such as a rapid aMMP-8 PoC immunotest, could be used as an adjunct to an interview/questionnaire to improve the precision of timely identification of asymptomatic, undiagnosed periodontitis patients by medical professionals. This strategy appears to be viable for referring patients to a dentist for diagnosis and treatment need assessment.
  • Fedirko, Veronika; Jenab, Mazda; Meplan, Catherine; Jones, Jeb S.; Zhu, Wanzhe; Schomburg, Lutz; Siddiq, Afshan; Hybsier, Sandra; Overvad, Kim; Tjonneland, Anne; Omichessan, Hanane; Perduca, Vittorio; Boutron-Ruault, Marie-Christine; Kuehn, Tilman; Katzke, Verena; Aleksandrova, Krasimira; Trichopoulou, Antonia; Karakatsani, Anna; Kotanidou, Anastasia; Tumino, Rosario; Panico, Salvatore; Masala, Giovanna; Agnoli, Claudia; Naccarati, Alessio; Bueno-de-Mesquita, Bas; Vermeulen, Roel C. H.; Weiderpass, Elisabete; Skeie, Guri; Nost, Therese Haugdahl; Lujan-Barroso, Leila; Ramon Quiros, J.; Maria Huerta, Jose; Rodriguez-Barranco, Miguel; Barricarte, Aurelio; Gylling, Bjoern; Harlid, Sophia; Bradbury, Kathryn E.; Wareham, Nick; Khaw, Kay-Tee; Gunter, Marc; Murphy, Neil; Freisling, Heinz; Tsilidis, Kostas; Aune, Dagfinn; Riboli, Elio; Hesketh, John E.; Hughes, David J. (2019)
    Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (P-ACT = 0.10; P-ACT significance threshold was P <0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.
  • Almangush, Alhadi; Leivo, Ilmo; Makitie, Antti A. (2021)
    Oral squamous cell carcinoma (OSCC) forms a major health problem in many countries. For several decades the management of OSCC consisted of surgery with or without radiotherapy or chemoradiotherapy. Aiming to increase survival rate, recent research has underlined the significance of harnessing the immune response in treatment of many cancers. The promising finding of checkpoint inhibitors as a weapon for targeting metastatic melanoma was a key event in the development of immunotherapy. Furthermore, clinical trials have recently proven inhibitor of PD-1 for treatment of recurrent/metastatic head and neck cancer. However, some challenges (including patient selection) are presented in the era of immunotherapy. In this mini-review we discuss the emergence of immunotherapy for OSCC and the recently introduced biomarkers of this therapeutic strategy. Immune biomarkers and their prognostic perspectives for selecting patients who may benefit from immunotherapy are addressed. In addition, possible use of such biomarkers to assess the response to this new treatment modality of OSCC will also be discussed.
  • Prasad, Marianne; Takkinen, Hanna-Mari; Uusitalo, Liisa; Tapanainen, Heli; Ovaskainen, Marja-Leena; Alfthan, Georg; Erlund, Iris; Ahonen, Suvi; Åkerlund, Mari; Toppari, Jorma; Ilonen, Jorma; Knip, Mikael; Veijola, Riitta; Virtanen, Suvi M. (2018)
    Fruit and vegetable intake has been associated with a reduced risk of many chronic diseases. These foods are the main dietary source of carotenoids. The aim of the present study was to evaluate the associations between dietary intake and serum concentrations of alpha- and beta-carotene in a sample of young Finnish children from the population-based birth cohort of the Type 1 Diabetes Prediction and Prevention (DIPP) Study. The current analysis comprised 3-day food records and serum samples from 207 children aged 1, 2 and 3 years. Spearman and partial correlations, as well as a cross-classification analyses, were used to assess the relationship between dietary intake and the corresponding biomarkers. Serum concentrations of alpha- and beta-carotene were significantly higher among the 1-year-old compared to the 3-year-old children. Dietary intakes of alpha- and beta-carotene correlated significantly with their respective serum concentrations in all age groups, the association being highest at the age of 1 year (alpha-carotene r = 0.48; p <0.001 and beta-carotene r = 0.47; p <0.001), and lowest at the age of 3 years (alpha-carotene r = 0.44; p <0.001 and beta-carotene r = 0.30; p <0.001). A cross-classification showed that 72-81% of the participants were correctly classified to the same or adjacent quartile, when comparing the reported dietary intakes and the concentrations of the corresponding carotenoid in serum. The 3-day food record seems to be reasonably valid in the assessment of root vegetable consumption among young Finnish children. Root vegetables were the main dietary source of both carotenoids in all age groups. The high consumption of commercial baby foods among the 1-year-old children was reflected in the relatively high dietary intake and serum concentration of both carotenoids.
  • Lindström, Linda (Helsingin yliopisto, 2020)
    Background: Cardiovascular (CVD) risk factors and several biomarkers have been linked to phenotypic frailty but the data is inconsistent, especially in oldest-old men. Purpose: To examine the association of frailty phenotype and different clinical and laboratory parameters in a cohort of older men. Methods: The Helsinki Businessmen Study (HBS) -cohort consists of men with high socioeconomic status (born 1919-1934, original n=3490). Their health status and CVD risk factors have been followed up since the 1960s and the clinical-epidemiological, longitudinal study is still ongoing. In 2017/2018 a random subcohort of community-dwelling survivors (n=232) was assessed. A postal questionnaire was sent to the men and they were invited to a study visit including clinical and laboratory examinations. Phenotypic frailty was identified according to the Fried physical phenotype criteria (nonfrail, prefrail or frail). SPSS software was used for statistical analyses. Results: Phenotypic frailty could be assessed in surviving 130 participants. Of them, 31%, 54% and 15% were nonfrail, prefrail, frail, respectively. Median ages were 86, 87 and 87.5 years. Frailty was associated with lower levels of systolic blood pressure, peak expiratory flow (PEF), total cholesterol, HDL cholesterol, and an increase in β2 microglobulin levels. Compared to nonfrail men, β2 microglobulin was 0.5 mg/L higher in the prefrail and frail subgroups (median [IQ range] 2.50 [0.8], 3.10 [1.5], 3.0 [2.6] mg/L, p=0.024). PEF, in turn, decreased with increasing frailty status (440 [80], 410 [160], 350 [160] L/min, p=0,013). Conclusions: β2 microglobulin can be considered an interesting candidate for a biomarker of frailty. As a simple clinical measurement, PEF may be a quick and inexpensive way to assess physical frailty in older adults. Further study on these matters is encouraged.
  • Stewart, Juhani A.; Koistinen, Riitta; Lempiäinen, Anna; Hotakainen, Kristina; Salminen, Ulla-Stina; Vakkuri, Anne; Wennervirta, Johanna; Stenman, Ulf-Hakan; Koistinen, Hannu (2020)
    The concentrations of several diagnostic markers have been found to increase dramatically in critically ill patients with a severe disturbance of normal physiological homeostasis, without indication of the diseases they are normally associated with. To prevent false diagnoses and inappropriate treatments of critically ill patients, it is important that the markers aiding the selection of second-line treatments are evaluated in such patients and not only in the healthy population and patients with diseases the markers are associated with. The levels of trypsinogen isoenzymes, the trypsin inhibitor serine peptidase inhibitor Kazal type 1 (SPINK1), hCG and hCG beta, which are used as pancreatitis and cancer markers, were analyzed by immunoassays from serum samples of 17 adult patients who have undergone surgery of the ascending aorta during hypothermic circulatory arrest (HCA) with optional selective cerebral perfusion. Highly elevated levels of trypsinogen-1, -2 and -3, SPINK1 and hCG beta were observed in patients after HCA. This was accompanied by increased concentrations of S100 beta and NSE. In conclusion, this study highlights the importance of critically evaluating the markers used for aiding selection of second line of treatments in critically ill patients.
  • Ndika, Joseph; Airaksinen, Liisa; Suojalehto, Hille; Karisola, Piia; Fyhrquist, Nanna; Puustinen, Anne; Alenius, Harri (2017)
    Background: Seasonal allergic rhinitis (SAR) caused by intermittent exposure to seasonal pollen causes itching, nasal congestion, and repeated sneezing, with profound effects on quality of life, work productivity, and school performance. Although both the genotype and environmental factors can contribute to the immunologic basis of allergic reactions, the molecular underpinnings associated with the pathogenesis of allergic rhinitis are not entirely clear. Methods: To address these questions, nasal epithelial brushings were collected from 29 patients with SAR and 31 control subjects during and after the pollen season. We then implemented an orbitrap-based, bottom-up, label-free quantitative proteomics approach, followed by multivariate analyses to identify differentially abundant (DA) proteins among the 4 sample groups. Results: We identified a total of 133 DA proteins for which the most significantly overrepresented functional category was found to be interferon 1 signaling. Two proteins, cystatin 1 and myeloblastin, the former of which protects against protease activity of allergens and the latter with a role in epithelial barrier function, were DA in patients with SAR and control subjects, irrespective of season. Moreover, interferon-inducible protein with tetratricopeptide repeats 1, cystatin 1, and interferon-inducible protein with tetratricopeptide repeats 3 were found to be differentially regulated between patients with SAR and control subjects, with inverse abundance dynamics during the transition from fall to spring. Conclusion: We identified type 1 interferon-regulated proteins as biomarkers in patients with SAR, potentially playing an important role in its pathogenesis. Moreover, when compared with patients with SAR, healthy subjects exhibit an antagonistic proteomic response across seasons, which might prove to be a therapeutic target for disease prevention.
  • Sikorski, Vilbert; Karjalainen, Pasi; Blokhina, Daria; Oksaharju, Kati; Khan, Jahangir; Katayama, Shintaro; Rajala, Helena; Suihko, Satu; Tuohinen, Suvi Sirkku; Teittinen, Kari; Nummi, Annu; Nykänen, Antti; Eskin, Arda; Stark, Christoffer; Biancari, Fausto; Kiss, Jan; Simpanen, Jarmo; Ropponen, Jussi O; Lemström, Karl; Savinainen, Kimmo; Lalowski, Maciej; Kaarne, Markku; Jormalainen, Mikko; Elomaa, Outi; Koivisto, Pertti; Raivio, Peter; Bäckström, Pia; Dahlbacka, Sebastian; Syrjälä, Simo; Vainikka, Tiina; Vähäsilta, Tommi; Tuncbag, Nurcan; Karelson, Mati; Mervaala, Eero; Juvonen, Tatu; Laine, Mika; Laurikka, Jari; Vento, Antti; Kankuri, Esko (2021)
    Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.
  • Schuster, Romina; Strehse, Jennifer S.; Ahvo, Aino; Turja, Raisa; Maser, Edmund; Bickmeyer, Ulf; Lehtonen, Kari K.; Brenner, Matthias (Elsevier, 2021)
    Marine Environmental Research 167 (2021), 105264
    Baltic mussels (Mytilus spp.) were exposed to the explosive trinitrotoluene (TNT) for 96 h (0.31–10.0 mg/L) and 21 d (0.31–2.5 mg/L). Bioaccumulation of TNT and its degradation products (2- and 4-ADNT) as well as biological effects ranging from the gene and cellular levels to behaviour were investigated. Although no mortality occurred in the concentration range tested, uptake and metabolism of TNT and responses in antioxidant enzymes and histochemical biomarkers were observed already at the lowest concentrations. The characteristic shell closure behaviour of bivalves at trigger concentrations led to complex exposure patterns and non-linear responses to the exposure concentrations. Conclusively, exposure to TNT exerts biomarker reponses in mussels already at 0.31 mg/L while effects are recorded also after a prolonged exposure although no mortality occurs. Finally, more attention should be paid on shell closure of bivalves in exposure studies since it plays a marked role in definining toxicity threshold levels.
  • Salminen, Liina; Gidwani, Kamlesh; Grenman, Seija; Carpen, Olli; Hietanen, Sakari; Pettersson, Kim; Huhtinen, Kaisa; Hynninen, Johanna (2020)
    Objective Human epididymis protein 4 (HE4) is a validated, complementary biomarker to cancer antigen 125 (CA125) for high grade serous ovarian carcinoma (HGSC). Currently, there are insufficient data on the utility of longitudinal HE4 measurement during HGSC treatment and follow up. We set to provide a comprehensive analysis on the kinetics and prognostic performance of HE4 with serial measurements during HGSC treatment and follow up. Methods This prospective study included 143 patients with advanced HGSC ( identifier: NCT01276574). Serum CA125 and HE4 were measured at baseline, before each cycle of chemotherapy and during follow up until first progression. Baseline biomarker values were compared to the tumor load assessed during surgery and to residual disease. Biomarker nadir values and concentrations at progression were correlated to survival. Results The baseline HE4 concentration distinguished patients with a high tumor load from patients with a low tumor load assessed during surgery (p
  • Santti, Kirsi; Ihalainen, Hanna; Ronty, Mikko; Boehling, Tom; Karlsson, Christina; Haglund, Caj; Tarkkanen, Maija; Blomqvist, Carl (2018)
    Background and Objectives: Desmoid tumors are soft-tissue tumors originating from myofibroblasts with a tendency to recur after surgery. High expression of proliferation markers is associated with shortened progression-free and/or overall survival in many neoplasms, including soft-tissue sarcomas. We investigated the prognostic role of cyclin A and Ki67 in desmoid tumors by immunohistochemistry. Methods: The study included 76 patients with desmoid tumor operated at Helsinki University Hospital between 1987 and 2011. A tissue micro array (TMA) was constructed and the TMA sections were immunostained with cyclin A and Ki67 antibodies. A computer-assisted image analysis was performed. Results: Cyclin A expression was evaluable in 74 and Ki67 in 70 patients. Cyclin A immunopositivity varied from 0% to 9.9%, with a mean of 1.9%. Cyclin A expression correlated significantly with Ki67. Cyclin A expression was associated with recurrence-free survival (HR 1.9, 95% CI = 1.1-3.2, P = .02), as were positive margin (HR 6.0, 95% CI = 1.6-22.5, P = .008) and extremity location (HR 5.3, 95% CI = 1.7-16.8, P = 0.005). Ki67 immunopositivity varied from 0.33% to 13.8%, with a mean of 4.6%, but had no significant prognostic impact (HR 1.1, P = .2). Conclusions: Our study indicates that cyclin A may be a new prognostic biomarker in surgically treated desmoid tumors.
  • Kasurinen, Aaro (Helsingin yliopisto, 2018)
    Matriksin metalloproteinaasit ovat endopeptidaaseja, joilla on monipuolisia biokemiallisia ominaisuuksia. Ne voivat edistää syövän invaasiota ja metastasointia hajottamalla soluväliainetta. Korkea matriksin metalloproteinaasi 14 (MMP-14) ilmentyvyys mahasyöpäpotilaiden kudosnäytteissä on aiemmin todettu liittyvän huonoon ennusteeseen ja metastaasien läsnäoloon. Tavoitteenamme oli tutkia seerumin MMP-14 pitoisuuden merkitystä ennusteellisena tekijänä mahasyövässä. Aineisto sisälsi 240 Helsingin seudun yliopistollisessa keskussairaalassa vuosien 2000 ja 2009 välillä leikattua mahasyöpäpotilasta. Määritimme seerumin MMP-14 pitoisuudet enzyme-linked immunosorbent assay (ELISA) -menetelmällä. Tutkimme yhteyksiä seerumin MMP-14 pitoisuuden ja kliinispatologisten muuttujien välillä Mann-Whitney U ja Kruskal-Wallis testien avulla. Elossaolokuvaajat muodostettiin Kaplan-Meier menetelmää käyttäen. Korkea seerumin MMP-14 pitoisuus liittyi III-IV asteen tauteihin (p = 0.029) ja elinmetastaasien läsnäoloon (p = 0.022). Matalan seerumin MMP-14 pitoisuuden omaavien potilaiden tautispesifinen 5-vuotiselossaolo oli 49.2 % (95 % confidence interval [CI] 45.5-52.9), kun taas korkean seerumin MMP-14 pitoisuuden omaavilla se oli 22.1 % (95 % CI 15.2-29.0; p = 0.001). Korkea seerumin MMP-14 pitoisuus liittyi huonoon ennusteeseen histologisesti intestinaalista syöpää sairastavien potilaiden keskuudessa (hazard ratio [HR] 3.54; 95 % CI 1.51-8.33; p = 0.004), mutta ei diffuusia syöpää sairastavien potilaiden keskuudessa. Korkea seerumin MMP-14 pitoisuus osoittautui itsenäiseksi ennusteelliseksi tekijäksi monimuuttaja-analyysissä (HR 1.55; 95 % CI 1.02-2.35; p = 0.040). Tämä tutkimus osoittaa, ensimmäistä kertaa, että korkea seerumin MMP-14 pitoisuus mahasyövässä liittyy huonoon ennusteeseen ja metastaasien läsnäoloon.
  • CardShock Investigators; Hongisto, Mari; Kataja, Anu; Tarvasmäki, Tuukka; Holopainen, Anu; Javanainen, Tuija; Jurkko, Raija; Jäntti, Toni; Kimmoun, Antoine; Levy, Bruno; Mebazaa, Alexandre; Pulkki, Kari; Sionis, Alessandro; Tolppanen, Heli; Wollert, Kai C.; Harjola, Veli-Pekka; Lassus, Johan (2019)
    Background: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS). Methods and Results: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-15(0h) level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P=.002). Adding GDF-15(12h) >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality. Conclusions: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS.
  • Limoges, Audrey; Ribeiro, Sofia; Weckström, Kaarina; Heikkila, Maija; Zamelczyk, Katarzyna; Andersen, Thorbjorn J.; Tallberg, Petra; Masse, Guillaume; Rysgaard, Soren; Norgaard-Pedersen, Niels; Seidenkrantz, Marit-Solveig (2018)
    The eastern north coast of Greenland is considered to be highly sensitive to the ongoing Arctic warming, but there is a general lack of data on modern conditions and in particular on the modern distribution of climate and environmental proxies to provide a baseline and context for studies on past variability. Here we present a detailed investigation of 11 biogenic proxies preserved in surface sediments from the remote High Arctic Wandel Sea shelf, the entrance to the Independence, Hagen, and Danmark fjords. The composition of organic matter (organic carbon, C:N ratios, C-13, N-15, biogenic silica, and IP25) and microfossil assemblages revealed an overall low primary production dominated by benthic diatoms, especially at the shallow sites. While the benthic and planktic foraminiferal assemblages underline the intrusion of chilled Atlantic waters into the deeper parts of the study area, the distribution of organic-walled dinoflagellate cysts is controlled by the local bathymetry and sea ice conditions. The distribution of the dinoflagellate cyst Polarella glacialis matches that of seasonal sea ice and the specific biomarker IP25, highlighting the potential of this species for paleo sea ice studies. The information inferred from our multiproxy study has important implications for the interpretation of the biogenic-proxy signal preserved in sediments from circum-Arctic fjords and shelf regions and can serve as a baseline for future studies. This is the first study of its kind in this area.
  • Kuang, Alan; Erlund, Iris; Herder, Christian; Westerhuis, Johan A.; Tuomilehto, Jaakko; Cornelis, Marilyn C. (2018)
    Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry-mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p <0.05 and q <0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p <0.05 and q > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.
  • Tikkanen, Emmi; Minicocci, Ilenia; Hällfors, Jenni; Di Costanzo, Alessia; D'Erasmo, Laura; Poggiogalle, Eleonora; Donini, Lorenzo Maria; Wurtz, Peter; Jauhiainen, Matti; Olkkonen, Vesa M.; Arca, Marcello (2019)
    Objective- Loss-of-function (LOF) variants in the ANGPTL3 (angiopoietin-like protein 3) have been associated with low levels of plasma lipoproteins and decreased coronary artery disease risk. We aimed to determine detailed metabolic effects of genetically induced ANGPTL3 deficiency in fasting and postprandial state. Approach and Results- We studied individuals carrying S17X LOF mutation in ANGPTL3 (6 homozygous and 32 heterozygous carriers) and 38 noncarriers. Nuclear magnetic resonance metabolomics was used to quantify 225 circulating metabolic measures. We compared metabolic differences between LOF carriers and noncarriers in fasting state and after a high-fat meal. In fasting, ANGPTL3 deficiency was characterized by similar extent of reductions in LDL (low-density lipoprotein) cholesterol (0.74 SD units lower concentration per LOF allele [95% CI, 0.42-1.06]) as observed for many TRL (triglyceride-rich lipoprotein) measures, including VLDL (very-low-density lipoprotein) cholesterol (0.75 [95% CI, 0.45-1.05]). Within most lipoprotein subclasses, absolute levels of cholesterol were decreased more than triglycerides, resulting in the relative proportion of cholesterol being reduced within TRLs and their remnants. Further, beta-hydroxybutyrate was elevated (0.55 [95% CI, 0.21-0.89]). Homozygous ANGPTL3 LOF carriers showed essentially no postprandial increase in TRLs and fatty acids, without evidence for adverse compensatory metabolic effects. Conclusions- In addition to overall triglyceride- and LDL cholesterol-lowering effects, ANGPTL3 deficiency results in reduction of cholesterol proportion within TRLs and their remnants. Further, ANGPTL3 LOF carriers had elevated ketone body production, suggesting enhanced hepatic fatty acid beta-oxidation. The detailed metabolic profile in human knockouts of ANGPTL3 reinforces inactivation of ANGPTL3 as a promising therapeutic target for decreasing cardiovascular risk.