Browsing by Subject "MARKER"

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  • Kashani-Sabet, Mohammed; Sagebiel, Richard W.; Joensuu, Heikki; Miller, James R. (2013)
  • Kaipio, Katja; Chen, Ping; Roering, Pia; Huhtinen, Kaisa; Mikkonen, Piia; Östling, Päivi; Lehtinen, Laura; Mansuri, Naziha; Korpela, Taina; Potdar, Swapnil; Hynninen, Johanna; Auranen, Annika; Grénman, Seija; Wennerberg, Krister; Hautaniemi, Sampsa; Carpén, Olli (2020)
    Poor chemotherapy response remains a major treatment challenge for high-grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient-derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment-naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment-naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment-naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K-mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K-mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment-naive tumours. EGFR, mTOR-PI3K and aurora kinase inhibitors are candidates for targeting this cell population. (c) 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
  • Koulaouzidis, Anastasios; Sipponen, Taina; Nemeth, Artur; Makins, Richard; Kopylov, Uri; Nadler, Moshe; Giannakou, Andry; Yung, Diana E.; Johansson, Gabriele Wurm; Bartzis, Leonidas; Thorlacius, Henrik; Seidman, Ernest G.; Eliakim, Rami; Plevris, John N.; Toth, Ervin (2016)
    Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images. Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels. Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months. Overall, correlation between FC and LS was weak (r (s): 0.232, P <0.001). When two clinically significant FC thresholds (100 and 250 mu g/g) were examined, the r (s) between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS a parts per thousand yen 135) or negative (LS <135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 mu g/g with sensitivity 0.59 and specificity 0.41. Limitations: Retrospective design. LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level a parts per thousand yen 76 mu g/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup.
  • Lundberg, Marie; Renkonen, Suvi; Haglund, Caj; Mattila, Petri S.; Leivo, Ilmo; Hagstrom, Jaana; Makitie, Antti A. (2016)
    Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC. Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations. Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other. Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997-2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry. Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T- and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found.
  • Strandberg, Timo E.; Levinson, Susan L.; DiNubile, Mark J.; Jyväkorpi, Satu; Kivimäki, Mika (2022)
    Background Biomarkers are needed for frailty, a common phenotype often associated with muscle loss in older people. Plasma gelsolin (pGSN) is a protein largely synthesized and secreted by skeletal muscle. Aims To investigate whether pGSN could be a biomarker of the frailty phenotype and predict mortality. Methods A homogenous cohort of males (born 1919-1934, baseline n = 3490) has been followed since the 1960s. In 2010/11, frailty phenotypes by modified Fried criteria were assessed. pGSN was measured in a convenience subset (n = 469, mean age 83) and re-measured in survivors (n = 127) in 2017. Mortality through December 31, 2018 was retrieved from national registers. Regression models were used for analyses. Results Of 469 males, 152 (32.4%) were robust, 284 (60.6%) prefrail, and 33 (7.0%) frail in 2010/11. There was a graded (p = 0.018) association between pGSN (mean 58.1 ug/mL, SD 9.3) and frailty. After multivariable adjustment, higher pGSN levels were associated with lower odds of having contemporaneous phenotypic prefrailty (OR per 1 SD 0.73, 95% CI 0.58-0.92) and frailty (OR per 1 SD 0.70, 95% CI 0.44-1.11). By 2018, 179 males (38.2%) had died, and higher baseline pGSN predicted a lower 7-year mortality rate (HR per 1 SD 0.85, 95% CI 0.72-1.00). pGSN concentrations in 2010/11 and 2017 were correlated (n = 127, r = 0.34, p < 0.001). Discussion Higher baseline pGSN concentrations were associated with a persistently robust phenotype and lower mortality rate over 7 years in a cohort of octogenarian males with high socioeconomic status and may be a promising laboratory biomarker for the development of a frailty phenotype.
  • Sääksjärvi, Katri; Lehto, Elviira; Lehto, Reetta; Suhonen, Eira; Leppänen, Marja; Michels, Nathalie; Saha, Mari; Ray, Carola; Vepsäläinen, Henna; Pajulahti, Riikka; Heiman-Lindh, Anu; Sainio, Taina; Erkkola, Maijaliisa; Roos, Eva; Sajaniemi, Nina (2021)
    Associations between hair cortisol concentration (HCC), diurnal salivary cortisol (sCort) and alpha-amylase (sAA), and temperament dimensions were examined among 3-6-year-old Finnish children (n = 833). Children's hair samples were collected at preschool, while parents collected five saliva samples from children during one weekend day and completed a questionnaire assessing child's temperament dimensions i.e. surgency, negative affectivity, and effortful control (HCC, n = 677; AUCg of sAA, n = 380; AUCg of sCort, n = 302; temperament dimensions, n = 751). In linear regression analysis, diurnal sCort associated positively with HCC, the association persisting after adjustments (beta 0.31, 95% CI 0.20-0.42). In logistic regression analysis, increasing scores in effortful control associated with higher likelihood of having high HCC (OR 1.47, 95% CI 1.07-2.03), the association slightly attenuating to non-significant after adjustments. Otherwise, no clear indication for associations between temperament and stress-related biomarkers were found.
  • Slik, Khadija; Turkki, Riku; Carpen, Olli; Kurki, Samu; Korkeila, Eija; Sundström, Jari; Pellinen, Teijo (2019)
    Current risk factors in stage II colorectal carcinoma are insufficient to guide treatment decisions. Loss of CDX2 has been shown to associate with poor clinical outcome and predict benefit for adjuvant chemotherapy in stage II and III colorectal carcinoma. The prognostic relevance of CDX2 in stage II disease has not been sufficiently validated, especially in relation to clinical risk factors, such as microsatellite instability (MSI) status, BRAF mutation status, and tumor budding. In this study, we evaluated the protein expression of CDX2 in tumor center and front areas in a tissue microarrays material of stage II colorectal carcinoma patients (n=232). CDX2 expression showed a partial or total loss in respective areas in 8.6% and 10.9% of patient cases. Patients with loss of CDX2 had shorter disease-specific survival when scored independently either in tumor center or tumor front areas (log rank P=0.012; P=0.012). Loss of CDX2 predicted survival independently of other stage II risk factors, such as MSI status and BRAF mutation status, pT class, and tumor budding (hazard ratio=5.96, 95% confidence interval=1.55-22.95; hazard ratio=3.70, 95% confidence interval=1.30-10.56). Importantly, CDX2 loss predicted inferior survival only in patients with microsatellite stable, but not with MSI-high phenotype. Interestingly, CDX2 loss associated with low E-cadherin expression, tight junction disruption, and high expression of ezrin protein. The work demonstrates that loss of CDX2 is an independent risk factor of poor disease-specific survival in stage II colorectal carcinoma. Furthermore, the study suggests that CDX2 loss is linked with epithelial-to-mesenchymal transition independently of tumor budding.
  • Hewetson, Michael; Sykes, Ben William; Hallowell, Gayle Davina; Tulamo, Riitta-Mari (2017)
    Background: Equine gastric ulcer syndrome (EGUS) is common in adult horses, particularly those involved in performance disciplines. Currently, detection of EGUS by gastroscopy is the only reliable ante mortem method for definitive diagnosis; however it is unsuitable as a screening test because it is expensive, time consuming, and is not readily available to most veterinarians. Sucrose permeability testing represents a simple, economical alternative to gastroscopy for screening purposes, and the feasibility of this approach in the horse has been previously reported. The aim of this study was to determine the diagnostic accuracy of blood sucrose as a screening test for EGUS in a large group of adult horses with and without naturally occurring gastric disease. Results: One hundred and one adult horses with or without naturally occurring gastric ulceration were studied. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL), glandular lesions (GDL), squamous lesions (SQL), and clinically significant lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using receiver operator characteristics (ROC) curves and calculating the area under the curve (AUC). For each lesion type, sucrose concentration in blood was compared to gastroscopy, as the gold standard, and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Ulcer grading was performed blindly by one observer; and the results were validated by comparing them with that of two other observers, and calculating the level of agreement. Cut-off values were selected manually to optimize Se. The prevalence of GL, GDL, SQL, and CSL was 83, 70, 53 and 58% respectively. At the selected cut-offs, Se ranged from 51 to 79% and Sp ranged from 43 to 72%, depending upon the lesion type and time of sampling. Conclusions: Blood sucrose is neither a sensitive or specific test for detecting EGUS in this population of adult horses with naturally occurring gastric ulceration. Further studies aimed at evaluating the performance characteristics of the test in different study populations are warranted. Given the limitations of endoscopy, due consideration should also be given to alternative methods for comparison of blood sucrose with a gold standard.
  • Almangush, Alhadi; Youssef, Omar; Pirinen, Matti; Sundström, Jari; Leivo, Ilmo; Mäkitie, Antti A. (2019)
    Tumour budding has emerged as a promising prognostic marker in many cancers. We systematically reviewed all studies that evaluated tumour budding in diagnostic biopsies. We conducted a systematic review of PubMed, MEDLINE, Scopus, Web of Science and Cochrane library for all articles that have assessed tumour budding in diagnostic (i.e. pretreatment or pre-operative) biopsies of any tumour type. Two independent researchers screened the retrieved studies, removed duplicates, excluded irrelevant studies and extracted data from the eligible studies. A total of 13 reports comprising 11 cohorts were found to have studied tumour budding in diagnostic biopsies. All these reports showed that evaluation of tumour budding in diagnostic biopsies was easily applicable. A strong association was observed between tumour budding score in diagnostic biopsies and corresponding surgical samples. Evaluation of tumour budding in diagnostic biopsies had a significant prognostic value for lymph node metastasis and patient survival. In all studies, tumour budding was a valuable marker of tumour aggressiveness and can be evaluated in technically satisfactory diagnostic biopsies. Thus, the assessment of tumour budding seems to identify the behaviour of cancer, and therefore to facilitate treatment planning.
  • Yalgin, Cagri; Rovenko, Bohdana; Andjelkovic, Ana; Neefjes, Margot; Oymak, Burak; Dufour, Eric; Hietakangas, Ville; Jacobs, Howard T. (2020)
    Dopaminergic (DA) neurons have been implicated as key targets in neurological disorders, notably those involving locomotor impairment, and are considered to be highly vulnerable to mitochondrial dysfunction, a common feature of such diseases. Here we investigated a Drosophila model of locomotor disorders in which functional impairment is brought about by pan-neuronal RNAi knockdown of subunit COX7A of cytochrome oxidase (COX). Despite minimal neuronal loss by apoptosis, the expression and activity of tyrosine hydroxylase was decreased by half. Surprisingly, COX7A knockdown specifically targeted to DA neurons did not produce locomotor defect. Instead, using various drivers, we found that COX7A knockdown in specific groups of cholinergic and glutamatergic neurons underlay the phenotype. Based on our main finding, the vulnerability of DA neurons to mitochondrial dysfunction as a cause of impaired locomotion in other organisms, including mammals, warrants detailed investigation.
  • Hukkinen, Maria; Pakarinen, Mikko Petteri; Merras-Salmio, Laura; Koivusalo, Antti; Rintala, Risto; Kolho, Kaija-Leena (2016)
    Background: Fecal calprotectin (FC) correlates with endoscopic recurrence of Crohn's disease (CD) in adults but has not been studied among children postoperatively. We aimed to analyze whether FC relates with postoperative CD recurrence in children. Methods: Altogether 51 postoperative endoscopies and FC measurements from 22 patients having undergone surgery for CD at age Results: Ileocecal resection (n = 15), small bowel resection (n = 6), or left hemicolectomy (n = 1) was performed at median age of 15.1 (interquartile range 14.4-17.6) years. Following surgery, FC decreased significantly (659 vs. 103 mu g/g, p = 0.001). During median follow-up of 5.7 (4.2-7.7) years, either endoscopic or histological recurrence occurred in 17 patients (77%). FC > 139 mu g/g at time of endoscopy or FC increase of 79 mu g/g compared to first postoperative value was suggestive of endoscopic recurrence (Rutgeerts score i2-i4), while FC > 101 mu g/g or increase of 21 mu g/g indicated histological recurrence. Best accuracy for prediction of recurrence was obtained by combining FC at endoscopy and the postoperative increase of FC. The corresponding AUROC values were 0.74 (95% 0.58-0.89) for endoscopic recurrence whereas 0.81 (95% CI 0.67-0.95) for histological recurrence. Conclusion: FC is a useful surrogate marker of postoperative recurrence also in pediatric CD patients. (C) 2016 Elsevier Inc. All rights reserved.
  • Pesonen, Eero; Passov, Arie; Salminen, Ulla-Stina; Ilmakunnas, Minna; Vento, Antti; Aittomäki, Juha; Andersson, Sture; Schramko, Alexey (2019)
    Background. Heparin binding protein (HBP) is released from neutrophilic secretory vesicles upon neutrophil adhesion on the endothelium. HBP mediates capillary hyperpermeability experimentally. In sepsis, HBP predicts organ dysfunction. Cardiopulmonary bypass induces neutrophil activation and hyperpermeability. We hypothesized that in cardiopulmonary bypass, HBP is released in the reperfused coronary circulation concomitantly with neutrophil adhesion. Methods. In 30 patients undergoing aortic valve replacement, concomitant blood samples were drawn from the coronary sinus and arterial line before aortic cross-clamping and 5 minutes after reperfusion to calculate transcoronary differences. Plasma HBP concentrations, neutrophil markers lactoferrin and myeloperoxidase, myocardial injury marker heart-type fatty acid binding protein, and leukocyte differential counts were measured. Results. Arterial HBP was 4.1 ng/mL (interquartile range [IQR], 3.6 to 5.3 ng/mL) preoperatively and 150.0 ng/mL (IQR, 108.2 to 188.6 ng/mL) after aortic declamping. HBP increased 39-fold, lactoferrin 16-fold, and myeloperoxidase fourfold during cardiopulmonary bypass. Before cardiopulmonary bypass, there were marginal transcoronary differences in HBP (1.4 ng/mL; IQR, -0.4 to 3.6 ng/mL; p = 0.001) and heart-type fatty acid binding protein (0.4 ng/mL; IQR, -0.04 to 3.5 ng/mL; p = 0.001) but not in the other indicators. During reperfusion, transcoronary HBP release (6.4 ng/mL; IQR, 1.8 to 13.7; ng/mL; p <0.001) was observed concomitantly with transcoronary neutrophil sequestration (-0.14 3 109/L; IQR, -0.28 to 0.01 3 109/L; p = 0.001) and transcoronary heart-type fatty acid binding protein release (6.9 ng/mL; IQR, 3.0 to 25.8 ng/mL; p <0.001). There were no transcoronary differences in lactoferrin or myeloperoxidase during reperfusion. Conclusions. Cardiopulmonary bypass results in substantial increase in circulating HBP. HBP is also released from the reperfused coronary circulation concomitantly with coronary neutrophil adhesion and myocardial injury. HBP may be one candidate for a humoral factor mediating capillary leak in cardiopulmonary bypass. (C) 2019 by The Society of Thoracic Surgeons
  • Algars, Annika; Avoranta, Tuulia; Osterlund, Pia; Lintunen, Minnamaija; Sundstrom, Jari; Jokilehto, Terhi; Ristimaki, Ari; Ristamaki, Raija; Carpen, Olli (2014)
  • Sidoroff, Marianne; Karikoski, Riitta; Raivio, Taneli; Savilahti, Erkki; Kolho, Kaija-Leena (2010)
  • Kaprio, Tuomas; Sariola, Hannu; Linder, Nina; Lundin, Johan; Kere, Juha; Haglund, Caj; Wedenoja, Satu (2021)
    Trophoblast-specific expression of human leukocyte antigen-G (HLA-G) induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal carcinoma (CRC) using the MEM-G/1 antibody and a tissue microarray series of CRC tumors (n = 317). HLA-G expression appeared in 20% of the tumors and showed high intratumoral heterogeneity. HLA-G positivity was associated with better differentiation (p = 0.002) and non-mucinous histology (p = 0.008). However, HLA-G expression alone showed no prognostic value: 5-years disease-specific survival among patients with HLA-G expression was 68.9% (95% CI: 62.7%-75.0%) compared to 74.8% (95% CI: 63.2%-86.3%) among those without expression. These results support a modulatory role of HLA-G in CRC.
  • Tervahartiala, Minna; Taimen, Pekka; Mirtti, Tuomas; Koskinen, Ilmari; Ecke, Thorsten; Jalkanen, Sirpa; Bostrom, Peter J. (2017)
    Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of patients to chemotherapy that are likely to respond to the treatment. To date, there are no validated molecular markers or baseline clinical characteristics to identify these patients. Different inflammatory markers, including tumor associated macrophages with their plastic pro-tumorigenic and anti-tumorigenic functions, have extensively been under interests as potential prognostic and predictive biomarkers in different cancer types. In this immunohistochemical study we evaluated the predictive roles of three immunological markers, CD68, MAC387, and CLEVER-1, in response to NAC and outcome of BC. 41% of the patients had a complete response (pT0N0) to NAC. Basic clinicopathological variables did not predict response to NAC. In contrast, MAC387(+) cells and CLEVER-1(+) macrophages associated with poor NAC response, while CLEVER-1(+) vessels associated with more favourable response to NAC. Higher counts of CLEVER-1+ macrophages associated with poorer overall survival and CD68(+) macrophages seem to have an independent prognostic value in BC patients treated with NAC. Our findings point out that CD68, MAC387, and CLEVER-1 may be useful prognostic and predictive markers in BC.
  • Jian, Ching; Kanerva, Sonja; Qadri, Sami; Yki-Järvinen, Hannele; Salonen, Anne (2022)
    Commercially available ELISAs for zonulin (pre-haptoglobin 2), a protein with tight junction regulatory activity in the epithelia, were recently shown to recognize other proteins that are structurally and functionally related to zonulin, termed zonulin family peptides (ZFPs). With little or no information about the identity and property of ZFPs, various commercial zonulin ELISA kits are widely utilized in research as a marker of intestinal permeability. Bacterial exposure is a known trigger for the secretion of zonulin, but it remains unclear whether distinct bacteria differ in their capability to stimulate zonulin secretion. We hypothesized that ZFPs are similar to zonulin regarding response to bacterial exposure and aimed to compare the effects of non-pathogenic, Gram-negative bacteria (Escherichia coli RY13 and E. coli K12 DH5α) and probiotic, Gram-positive bacteria (Lactobacillus rhamnosus GG and Bifidobacterium bifidum) on ZFP secretion in an in vitro model. Additionally, utilizing samples from human clinical trials, we correlated circulating levels of ZFPs to the gut bacteria and determined the presence of ZFPs in various human tissues. Unexpectedly, we found that the ZFPs quantified by the widely used IDK® Zonulin ELISA kits are specifically triggered by the exposure to live Lactobacillus rhamnosus GG in HT-29 cells, associated with absolute abundances of intestinal Lactobacillus and Bifidobacterium in adults, and are copious in the small intestine but undetectable in the liver or adipose tissue. These characteristics appear to be different from zonulin and highlight the need for further characterization of ZFPs recognized by commercially available and widely used “zonulin” ELISAs.
  • Gordin, Daniel; Saraheimo, Markku; Tuomikangas, Jaana; Soro-Paavonen, Aino; Forsblom, Carol; Paavonen, Karri Jorma Antero; Steckel-Hamann, Birgit; Vandenhende, Francois; Nicolaou, Loizos; Pavo, Imre; Koivisto, Veikko; Groop, Per-Henrik (2016)
    Context: Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease. Objective: The objective of the study was to determine whether postprandial hyperglycemia affects arterial function in T2D. Design: Asingle-center, open-label study of three groups of men were studied: 1) T2D patients with albuminuria (n = 22), 2) T2D patients without albuminuria (n = 24), and 3) nondiabetic controls (n = 25). Patients were randomized to a two-period crossover study schedule, ingesting breakfast, with or without insulin lispro (to induce low or high postprandial glycemia). Main Outcome Measures: Arterial stiffness was assessed by calculating pulse wave velocity (PWV) and augmentation index using applanation tonometry, and endothelial dysfunction was assessed using peripheral arterial tonometry, 30 minutes before breakfast and up to 240 minutes after breakfast. Results: At baseline, arterial stiffness was increased in patients. When adjusted for age and body mass index, in a combined group of patients with and without albuminuria, brachial PWV was higher during low (P = .032) and high (P = .038) postprandial glycemia vs controls. These differences were driven by the albuminuria group vs controls during low (P = .014) and high (P = .018) postprandial glycemia. No differences were observed in aortic PWV, augmentation index, or peripheral arterial tonometry ratio between patients and controls. Endothelin-1 and IL-6 were higher, and superoxide dismutase was lower, during postprandial hyperglycemia in T2D patients vs controls. Conclusions: In patients with T2D and albuminuria, brachial PWV was higher under postprandial hyperglycemic conditions, relative to controls. These data suggest that hyperglycemia induces an increase in stiffness of intermediate-sized arteries. We found no changes in other parts of the arterial bed.
  • Soovares, Piret; Pasanen, Annukka; Butzow, Ralf; Lassus, Heini (2017)
    Objective. Our aim was to study the expression of L1CAM in endometrioid and clear cell ovarian carcinomas and to evaluate its correlation with clinical parameters and patient prognosis. Methods. Tissue microarray-based immunohistochemical analysis of L1CAM expression was performed in 249 endometrioid and 140 clear cell ovarian carcinomas. Concurrent endometrial carcinoma was found in 57 of these patients. Results. L1CAM expression was found in 15% of endometrioid and 23% of clear cell ovarian carcinomas. L1CAM expression was strongly associated with poor disease-specific overall survival and poor disease-free survival in endometrioid (p <0.0001, p = 0.0005), but not in clear cell ovarian carcinomas. Significant association of L1CAM expression with poor overall survival was observed in grade 1-2 carcinomas (p <0.0001), but not in grade 3 tumors. In endometrioid ovarian carcinomas, L1CAM expression was associated with aggressive tumor characteristics, such as higher grade and stage, and incomplete response to primary therapy. However, L1CAM expression was not an independent prognostic factor for overall or disease-free survival. Of the 57 patients with concurrent endometrial carcinoma L1CAM positivity was found in 4 cases both in the ovarian and endometrial tumors, and in 3 cases only in the endometrial tumor. All these seven patients with L1CAM positive tumors had poor outcome. Conclusions. L1CAM expression could serve as a biomarker for predicting clinical outcome and response to therapy in patients with endometrioid ovarian carcinoma, but not in clear cell carcinomas. L1CAM positivity also predicts poor outcome in patients with concurrent endometrioid ovarian and endometrial carcinomas. (C) 2017 Elsevier Inc. All rights reserved.
  • Rakkolainen, Ilmari; Elmasry, Moustafa; Steinvall, Ingrid; Vuola, Jyrki (2018)
    B-type natriuretic peptide has shown promising results as a biomarker for acute kidney injury in general intensive care patients. It may also indirectly reflect fluid balance of the circulation. Among burn patients, it has been observed to indicate excessive fluid resuscitation and organ dysfunction, although its clinical use to indicate acute kidney injury or guide fluid resuscitation has not been validated. The aim of this study was to evaluate whether the N-terminal pro-brain natriuretic peptide values are related to the amount of fluids given after severe burn injury and whether it can act as a novel biomarker for acute kidney injury in these patients. Nineteen consecutive burn patients were included. Plasma N-terminal pro-brain natriuretic peptide was measured daily during 1 week from admission. Other variables such as laboratory values and intravenous infusions were also recorded. The association between acute kidney injury and N-terminal pro-brain natriuretic peptide values was analyzed with a multivariable panel regression model, adjusted for burned total body surface area, age, body mass index, and laboratory values. N-terminal pro-brain natriuretic peptide values varied between single patients, and even more between the patients who developed acute kidney injury. Older age, lower body mass index, and cumulative infusions were independently associated with higher N-terminal pro-brain natriuretic peptide values, whereas acute kidney injury was not. N-terminal pro-brain natriuretic peptide values correlated with cumulative infusions given during the first week. The authors could not validate the role of N-terminal probrain natriuretic peptide as a biomarker for acute kidney injury in burns.