Publications by authors named "Leena Tiainen"

5 Publications

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Lectin nanoparticle assays for detecting breast cancer-associated glycovariants of cancer antigen 15-3 (CA15-3) in human plasma.

PLoS One 2019 25;14(7):e0219480. Epub 2019 Jul 25.

Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland.

Cancer antigen 15-3 (CA15-3) is widely utilized for monitoring metastatic breast cancer (BC). However, its utility for early detection of breast cancer is severely limited due to poor clinical sensitivity and specificity. The glycosylation of CA15-3 is known to be affected by BC, and therefore it might offer a way to construct CA15-3 glycovariant assays with improved cancer specificity. To this end, we performed lectin-based glycoprofiling of BC-associated CA15-3. CA15-3 expressed by a BC cell line was immobilized on microtitration wells using an anti-CA15-3 antibody. The glycosylation of the immobilized CA15-3 was then detected by using lectins coated onto europium (III)-doped nanoparticles (Eu+3-NPs) and measuring the time-resolved fluorescence of Eu. Out of multiple lectin-Eu+3-NP preparations, wheat germ agglutinin (WGA) and macrophage galactose-type lectin (MGL) -Eu3+-NPs bound to the BC cell line-dericed CA15-3 glycovariants (CA15-3Lectin). To evaluate the clinical performance of these two lectin-based assays, plasma samples from metastatic BC patients (n = 53) and healthy age-matched women (n = 20).Plasma CA15-3Lectin measurements better distinguished metastatic BC patients from healthy controls than the conventional CA15-3 immunoassay. At 90% specificity, the clinical sensitivity of the assays was 66.0, 67.9 and 81.1% for the conventional CA15-3, CA15-3MGL and CA15-3WGA assays, respectively. Baseline CA15-3MGL and CA15-3WGA were correlated to conventional baseline CA15-3 levels (r = 0.68, p<0.001, r = 0.90, p>0.001, respectively). However, very low baseline CA15-3MGL levels ≤ 5 U/mL were common in this metastatic breast cancer patient population.In conclusion, the new CA15-3Lectin concept could considerably improve the clinical sensitivity of BC detection compared to the conventional CA15-3 immunoassays and should be validated further on a larger series of subjects with different cancer subtypes and stages.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219480PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658058PMC
February 2020

High baseline Tie1 level predicts poor survival in metastatic breast cancer.

BMC Cancer 2019 Jul 24;19(1):732. Epub 2019 Jul 24.

Department of Oncology, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, P.O. Box 100, FI-33014, Tampere, Finland.

Background: Angiopoietin growth factors (Angs) regulate angiogenesis and lymphangiogenesis by binding to the endothelial Tie2 receptor. Ang2 expression is elevated in tissue hypoxia and inflammation, which also induce cleavage of the extracellular domain of the orphan Tie1 receptor. Here we have examined if the concentrations of Ang2 and the soluble extracellular domain of Tie1 in patient plasma are associated with the prognosis of patients with metastatic breast cancer.

Methods: Plasma Tie1 and Ang2 levels were measured in metastatic breast cancer patients treated in a phase II trial with a taxane-bevacizumab combination chemotherapy in the first-line treatment setting. They were analyzed before treatment, after 6 weeks and 6 months of treatment, and at the final study visit. Using the median concentrations as cutoffs, Tie1 and Ang2 data were dichotomized into low and high concentration groups. Additionally, we analyzed Tie1 concentrations in plasma from 10 healthy women participating in a breast cancer primary prevention study.

Results: Plasma samples were available from 58 (89%) of the 65 patients treated in the trial. The baseline Tie1 levels of the healthy controls were significantly lower than those of the metastatic patients (p < 0.001). The overall survival of the patients with a high baseline Tie1 level was significantly shorter (multivariate HR 3.07, 95% CI 1.39-6.79, p = 0.005). Additionally, the progression-free survival was shorter for patients with a high baseline Tie1 level (multivariate HR 3.78, 95% CI 1.57-9.09, p = 0.003). In contrast, the baseline Ang2 levels had no prognostic impact in a multivariate Cox proportional hazard regression analysis. The combined analysis of baseline Tie1 and Ang2 levels revealed that patients with both high Tie1 and high Ang2 baseline levels had a significantly shorter overall survival than the patients with low baseline levels of both markers (multivariate HR for overall survival 4.32, 95% CI 1.44-12.94, p = 0.009).

Conclusions: This is the first study to demonstrate the prognostic value of baseline Tie1 plasma concentration in patients with metastatic breast cancer. Combined with the results of the Ang2 analyses, the patients with both high Tie1 and Ang2 levels before treatment had the poorest survival.

Trial Registration: Clinicaltrials.gov: NCT00979641, registration date 19-DEC-2008. The regional Ethics Committee: R08142M, registration date 18-NOV-2008.
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http://dx.doi.org/10.1186/s12885-019-5959-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657075PMC
July 2019

Low Plasma IL-8 Levels During Chemotherapy Are Predictive of Excellent Long-Term Survival in Metastatic Breast Cancer.

Clin Breast Cancer 2019 08 4;19(4):e522-e533. Epub 2019 Apr 4.

Department of Oncology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland.

Background: Interleukin (IL)-8 is a proinflammatory cytokine, and high levels of IL-8 are associated with poor prognosis in many malignancies. The objective of this study was to explore the clinical benefit of monitoring plasma IL-8 levels during breast cancer chemotherapy.

Patients And Methods: We conducted an exploratory analysis of several circulating proteins, including IL-8, in the plasma. Plasma samples were obtained from 58 metastatic breast cancer patients who took part in a prospective phase 2 first-line bevacizumab chemotherapy trial. Samples were analyzed before therapy, after 6 weeks and 6 months of treatment, and at the final study visit. On the basis of a trajectory analysis of the plasma IL-8 levels, the patients were divided into 3 trajectory groups.

Results: Plasma IL-8, IL-6, IL-18, matrix metalloproteinase (MMP)-2, MMP-9, YKL-40, resistin, and high-mobility group box 1 (HMGB1) concentrations were measured, and the most pronounced predictor of patient survival was IL-8. On the basis of the trajectory analysis of the IL-8 levels, the majority of patients (n = 35, 60%) belonged to trajectory group 1, and these patients had significantly lower IL-8 levels before and during the entire chemotherapy treatment period than did the patients in the other groups. Trajectory group 1 patients had significantly better overall survival compared to patients in trajectory group 2 (n = 17; age-adjusted HR = 2.45; 95% confidence interval, 1.21-5.97; P = .012) and 3 (n = 6; age-adjusted HR = 8.65; 95% confidence interval, 3.16-23.7; P < .001).

Conclusion: Low IL-8 levels during chemotherapy treatment might help identify patients with prolonged survival.
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http://dx.doi.org/10.1016/j.clbc.2019.03.006DOI Listing
August 2019

Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer.

Anticancer Res 2016 12;36(12):6431-6438

Department of Oncology, School of Medicine, University of Tampere, Tampere, Finland.

Aim: The study evaluated the efficacy of bevacizumab combined with a taxane-based treatment for advanced breast cancer.

Patients And Methods: In this non-randomized phase II study 65 patients received 10 mg/kg bevacizumab i.v. (days 1 and 15, q4w) plus either 50 mg/m docetaxel (days 1 and 15, q4w) or 90 mg/m paclitaxel (days 1,8 and 15, q4w) i.v. until disease progression, maximal response, unacceptable toxicity or the withdrawal of consent. Patients without progression continued bevacizumab at 15 mg/kg i.v. (q3w) alone, or with endocrine therapy. (NCT00979641).

Results: Progression-free survival was 11.3 months (95% confidence interval=9.7-16.0 months) and overall survival was 35.1 months (95% confidence interval=22.2-50.3 months). More than half of the patients (62%) responded at least partially. Bevacizumab-related serious adverse events occurred in 10.8% patients and one patient died because of gastrointestinal perforation.

Conclusion: Treating advanced breast cancer with a bevacizumab-containing regimen as the first-line cytotoxic treatment resulted in excellent response rates and long survival.
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http://dx.doi.org/10.21873/anticanres.11241DOI Listing
December 2016
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