Browsing by Author "Llorente, Alicia"

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    Detection of circulating miRNAs : comparative analysis of extracellular vesicle-incorporated miRNAs and cell-free miRNAs in whole plasma of prostate cancer patients
    (2017-11-09) Endzelinš, Edgars; Berger, Andreas; Melne, Vita; Bajo-Santos, Cristina; Sobolevska, Kristlne; Abols, Arturs; Rodriguez, Marta; Šantare, Daiga; Rudnickiha, Anastasija; Lietuvietis, Vilnis; Llorente, Alicia; Line, Aija; Rīga Stradiņš University
    Background: Circulating cell-free miRNAs have emerged as promising minimally-invasive biomarkers for early detection, prognosis and monitoring of cancer. They can exist in the bloodstream incorporated into extracellular vesicles (EVs) and ribonucleoprotein complexes. However, it is still debated if EVs contain biologically meaningful amounts of miRNAs and may provide a better source of miRNA biomarkers than whole plasma. The aim of this study was to systematically compare the diagnostic potential of prostate cancer-associated miRNAs in whole plasma and in plasma EVs. Methods: RNA was isolated from whole plasma and plasma EV samples from a well characterised cohort of 50 patient with prostate cancer (PC) and 22 patients with benign prostatic hyperplasia (BPH). Nine miRNAs known to have a diagnostic potential for PC in cell-free blood were quantified by RT-qPCR and the relative quantities were compared between patients with PC and BPH and between PC patients with Gleason score ≥ 8 and ≤6. Results: Only a small fraction of the total cell-free miRNA was recovered from the plasma EVs, however the EV-incorporated and whole plasma cell-free miRNA profiles were clearly different. Four of the miRNAs analysed showed a diagnostic potential in our patient cohort. MiR-375 could differentiate between PC and BPH patients when analysed in the whole plasma, while miR-200c-3p and miR-21-5p performed better when analysed in plasma EVs. EV-incorporated but not whole plasma Let-7a-5p level could distinguish PC patients with Gleason score ≥ 8 vs ≤6. Conclusions: This study demonstrates that for some miRNA biomarkers EVs provide a more consistent source of RNA than whole plasma, while other miRNAs show better diagnostic performance when tested in the whole plasma.
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    Diagnostic, prognostic and predictive value of cell-free miRNAs in prostate cancer : A systematic review
    (2016-05-18) Endzeliņš, Edgars; Melne, Vita; Kalniņa, Zane; Lietuvietis, Vilnis; Riekstiņa, Una; Llorente, Alicia; Line, Aija; Rīga Stradiņš University
    Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolent disease. Treatment outcome and management of prostate cancer could be improved by the development of non-invasive biomarker assays that aid in increasing the sensitivity and specificity of prostate cancer screening, help to distinguish aggressive from indolent disease and guide therapeutic decisions. Prostate cancer cells release miRNAs into the bloodstream, where they exist incorporated into ribonucleoprotein complexes or extracellular vesicles. Later, cell-free miRNAs have been found in various other biofluids. The initial RNA sequencing studies suggested that most of the circulating cell-free miRNAs in healthy individuals are derived from blood cells, while specific disease-associated miRNA signatures may appear in the circulation of patients affected with various diseases, including cancer. This raised a hope that cell-free miRNAs may serve as non-invasive biomarkers for prostate cancer. Indeed, a number of cell-free miRNAs that potentially may serve as diagnostic, prognostic or predictive biomarkers have been discovered in blood or other biofluids of prostate cancer patients and need to be validated in appropriately designed longitudinal studies and clinical trials. In this review, we systematically summarise studies investigating cell-free miRNAs in biofluids of prostate cancer patients and discuss the utility of the identified biomarkers in various clinical scenarios. Furthermore, we discuss the possible mechanisms of miRNA release into biofluids and outline the biological questions and technical challenges that have arisen from these studies.
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    The Effect of High-Intensity Interval Training on Quality of Life and Incidence of Chemotherapy Side Effects in Women With Breast Cancer
    (2024-01-01) Kļaviņa, Aija; Cešeiko, Rūdolfs; Čampa, Mārtiņš; Jermoļenko, Grēta Frančeska; Eglītis, Kristaps; Llorente, Alicia; Linē, Aija; Latvian Academy of Sport Education (LASE); Rīga Stradiņš University
    UNLABELLED Women with breast cancer (BC) experience multiple symptoms related to neoadjuvant chemotherapy (NAC) treatment that impair their functioning and quality of life (QoL). This study aimed to explore the effect of high-intensity aerobic interval training (HIIT) on quality of life and NAC side effects in women with BC. METHODS 56 patients (48.56 (7.84) years, range 35-64 years) diagnosed locally advanced (stage II-III) ER + BC receiving doxorubicin/cyclophosphamide-based NAC were randomly assigned to the HIIT group and a control group (CG) for 6 months. The HIIT group performed 2 to 3 HIIT sessions per week according to the study protocol (4 × 4 minutes at 85%-95% peak heart rate (HR)). The CG followed the standard of care instructions by the oncologists. To assess the QoL participants completed the EORTC QLQ-C30 with the additional BC module of QLQ BR-23. Weekly self-reports on NAC side effects were collected through online survey. RESULTS Study data were analyzed for 37 participants (nHIIT = 17, nCON = 20) who reported at least 14 (60%) weeks. HIIT was effective to reduce BC symptom scale outcomes (ES = 0.113, P = .048), and alleviate systemic therapy side effects (ES = 0.154, P = .020) and cancer related symptoms (ES = 0.124, P = .038). The most common side effect participants experienced at least 1 to 4 days/week was pain (average 50.9% and 56.8% for HIIT and CG, respectively), followed by sleep disturbances (average 50.9% and 49.9%, respectively). About 31% in both groups experienced sleep disturbances 5 to 7 days/week. The NAC induced physical, social and fatigue side effects had significantly lower incidence in HIIT group, while psychological side effects were significantly more common in training group. CONCLUSIONS HIIT is an effective physical exercise program to maintain higher quality of life and help to reduce some of NAC induced side effects for women with BC.
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    From sweat to hope : The role of exercise-induced extracellular vesicles in cancer prevention and treatment
    (2024-08) Llorente, Alicia; Brokāne, Agnese; Mlynska, Agata; Puurand, Marju; Sagini, Krizia; Folkmane, Signe; Hjorth, Marit; Martin-Gracia, Beatriz; Romero, Silvana; Skorinkina, Diana; Čampa, Mārtiņš; Cešeiko, Rūdolfs; Romanchikova, Nadezhda; Kļaviņa, Aija; Käämbre, Tuuli; Linē, Aija; Rīga Stradiņš University; Latvian Academy of Sport Education (LASE)
    The benefits of regular physical exercise on cancer prevention, as well as reducing fatigue, treatment side effects and recurrence, and improving quality of life and overall survival of cancer patients, are increasingly recognised. Initial studies showed that the concentration of extracellular vesicles (EVs) increases during physical activity and that EVs carry biologically active cargo. These EVs are released by blood cells, skeletal muscle and other organs involved in exercise, thus suggesting that EVs may mediate tissue crosstalk during exercise. This possibility triggered a great interest in the study of the roles of EVs in systemic adaptation to exercise and in their potential applications in the prevention and treatment of various diseases, including cancer. This review presents studies exploring the concentration and molecular cargo of EVs released during exercise. Furthermore, we discuss putative stimuli that may trigger EV release from various cell types, the biological functions and the impact of exercise-induced EVs on cancer development and progression. Understanding the interplay between exercise, EVs, and cancer biology may offer insights into novel therapeutic strategies and preventive measures for cancer.
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    Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies
    (2023-02-03) Bajo-Santos, Cristina; Brokāne, Agnese; Zayakin, Pawel; Endzeliņš, Edgars; Soboļevska, Kristīne; Belovs, Alberts; Jansons, Juris; Sperga, Māris; Llorente, Alicia; Radoviča-Spalviņa, Ilze; Lietuvietis, Vilnis; Linē, Aija; Rīga Stradiņš University
    Introduction: Extracellular vesicles (EVs) have emerged as a very attractive source of cancer- derived RNA biomarkers for the early detection, prognosis and monitoring of various cancers, including prostate cancer (PC). However, biofluids contain a mixture of EVs released from a variety of tissues and the fraction of total EVs that are derived from PC tissue is not known. Moreover, the optimal biofluid—plasma or urine—that is more suitable for the detection of EV- enclosed RNA biomarkers is not yet clear. Methodology: In the current study, we performed RNA sequencing analysis of plasma and urinary EVs collected before and after radical prostatectomy, and matched tumor and normal prostate tissues of 10 patients with prostate cancer. Results and Discussion: The most abundant RNA biotypes in EVs were miRNA, piRNA, tRNA, lncRNA, rRNA and mRNA. To identify putative cancer-derived RNA biomarkers, we searched for RNAs that were overexpressed in tumor as compared to normal tissues, present in the pre-operation EVs and decreased in the post-operation EVs in each RNA biotype. The levels of 63 mRNAs, 3 lncRNAs, 2 miRNAs and 1 piRNA were significantly increased in the tumors and decreased in the post-operation urinary EVs, thus suggesting that these RNAs mainly originate from PC tissue. No such RNA biomarkers were identified in plasma EVs. This suggests that the fraction of PC-derived EVs in urine is larger than in plasma and allows the detection and tracking of PC-derived RNAs.