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Initiation and elongation factor co-expression correlates with recurrence and survival in epithelial ovarian cancer
Monika Sobočan, Daniela Brunialti, S Sprung, Christoph Schatz, Jure Knez, Rajko Kavalar, Iztok Takač, Johannes Haybaeck, 2022, izvirni znanstveni članek

Opis: High grade epithelial ovarian cancer (EOC) represents a diagnostic and therapeutic challenge due to its aggressive features and short recurrence free survival (RFS) after primary treatment. Novel targets to inform our understanding of the EOC carcinogenesis in the translational machinery can provide us with independent prognostic markers and provide drugable targets. We have identified candidate eukaryotic initiation factors (eIF) and eukaryotic elongation factors (eEF) in the translational machinery for differential expression in EOC through in-silico analysis. We present the analysis of 150 ovarian tissue microarray (TMA) samples on the expression of the translational markers eIF2α, eIF2G, eIF5 (eIF5A and eIF5B), eIF6 and eEF1A1. All translational markers were differentially expressed among non-neoplastic ovarian samples and tumour samples (borderline tumours and EOC). In EOC, expression of eIF5A was found to be significantly correlated with recurrence free survival (RFS) and expression of eIF2G and eEF1A1 with overall survival (OS). Expression correlation among factor subunits showed that the correlation of eEF1A1, eIF2G, EIF2α and eIF5A were significantly interconnected. eIF5A was also correlated with eIF5B and eIF6. Our study demonstrates that EOCs have different translational profile compared to benign ovarian tissue and that eIF5A is a central dysregulated factor of the translation machinery.
Ključne besede: epithelial ovarian cancer, initiation and elongation factor, translational markers
Objavljeno v DKUM: 12.12.2024; Ogledov: 0; Prenosov: 2
.pdf Celotno besedilo (1,70 MB)
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3.
Changes in the extracellular matrix in endometrial and cervical cancer : a systematic review
Tjaša Padežnik, Anja Oleksy, Andrej Cokan, Iztok Takač, Monika Sobočan, 2023, pregledni znanstveni članek

Opis: Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.
Ključne besede: extracellular matrix, endometrial cancer, cervical cancer
Objavljeno v DKUM: 02.12.2024; Ogledov: 0; Prenosov: 0
.pdf Celotno besedilo (688,98 KB)
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4.
Isoform-level transcriptome analysis of peripheral blood mononuclear cells from breast cancer patients identifies a disease-associated RASGEF1A isoform
Helena Sabina Čelešnik, Mario Gorenjak, Martina Krušič, Bojana Crnobrnja, Monika Sobočan, Iztok Takač, Darja Arko, Uroš Potočnik, 2024, izvirni znanstveni članek

Opis: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.
Ključne besede: breast cancer, peripheral blood, isoform-level RNA-seq, RASGEF1A ENST00000374459, ctDNA, Ki-67
Objavljeno v DKUM: 26.11.2024; Ogledov: 0; Prenosov: 3
.pdf Celotno besedilo (1,52 MB)
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5.
Translational regulation in hepatocellular carcinogenesis
Suzana Bračič Tomažič, Christoph Schatz, Johannes Haybaeck, 2021, pregledni znanstveni članek

Opis: The mortality of hepatocellular carcinoma (HCC) is distributed unevenly worldwide. One of the major causes is hepatitis B or hepatitis C virus infection and the development and progression of liver cirrhosis. The carcinogenesis of HCC is among others regulated via the mTOR (mechanistic target of rapamycin) signaling pathway and represents a possible method of targeted treatment. The aim of our article was to address the most recent clinical advances and findings of basic studies on the mTOR signaling pathway and the involved factors. Risk factors play a key role in dysregulation of the signaling pathway, where both mTORCs are upregulated and protein synthesis is altered. eIFs and, to a lesser extent, eEFs play an essential role in this process. Whether the factor will be upregulated or downregulated, among others, depends on hepatitis B/C virus infection. The amount of a particular factor in a patient sample lets us know whether HCC recurrence will occur, what is the likelihood of chemoresistance, and what outcome is predicted for patients with an increased value. Our analysis shows that in addition to mTOR, eIF3, eIF4, and eIF5 play an important role, as they can serve as biomarkers for non- and virus-related HCC.
Ključne besede: mTOR, virus related HCC, non-virus related HCC, cancer, translation initiation, liver
Objavljeno v DKUM: 18.10.2024; Ogledov: 0; Prenosov: 2
.pdf Celotno besedilo (4,21 MB)
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6.
Robotic versus laparoscopic surgery for colorectal cancer : a case-control study
Jan Grosek, Jurij Aleš Košir, Primož Sever, Vanja Erčulj, Aleš Tomažič, 2021, izvirni znanstveni članek

Opis: Background: Robotic resections represent a novel approach to treatment of colorectal cancer. The aim of our study was to critically assess the implementation of robotic colorectal surgical program at our institution and to compare it to the established laparoscopically assisted surgery. Patients and methods: A retrospective case-control study was designed to compare outcomes of consecutively operated patients who underwent elective laparoscopic or robotic colorectal resections at a tertiary academic centre from 2019 to 2020. The associations between patient characteristics, type of operation, operation duration, conversions, duration of hospitalization, complications and number of harvested lymph nodes were assessed by using univariate logistic regression analysis. Results: A total of 83 operations met inclusion criteria, 46 robotic and 37 laparoscopic resections, respectively. The groups were comparable regarding the patient and operative characteristics. The operative time was longer in the robotic group (p < 0.001), with fewer conversions to open surgery (p = 0.004), with less patients in need of transfusions (p = 0.004) and lower reoperation rate (p = 0.026). There was no significant difference between the length of stay (p = 0.17), the number of harvested lymph nodes (p = 0.24) and the overall complications (p = 0.58). Conclusions: The short-term results of robotic colorectal resections were comparable to the laparoscopically assisted operations with fewer conversions to open surgery, fewer blood transfusions and lower reoperation rate in the robotic group.
Ključne besede: robotic surgery, laparoscopic surgery, minimally invasive surgery, colorectal cancer
Objavljeno v DKUM: 14.08.2024; Ogledov: 94; Prenosov: 4
.pdf Celotno besedilo (263,06 KB)
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7.
Stability analysis of the singular points and Hopf bifurcations of a tumor growth control model
Dániel András Drexler, Ilona Nagy, Valery Romanovski, 2024, izvirni znanstveni članek

Opis: We carry out qualitative analysis of a fourth-order tumor growth control model using ordinary differential equations. We show that the system has one positive equilibrium point, and its stability is independent of the feedback gain. Using a Lyapunov function method, we prove that there exist realistic parameter values for which the systems admit limit cycle oscillations due to a supercritical Hopf bifurcation. The time evolution of the state variables is also represented.
Ključne besede: bifurcation, cancer therapy, limit cycle, singular point, tumor therapy, tumor control
Objavljeno v DKUM: 12.08.2024; Ogledov: 73; Prenosov: 6
.pdf Celotno besedilo (2,44 MB)

8.
Novel methacrylate-based multilayer nanofilms with incorporated FePt-based nanoparticles and the anticancer drug 5-fluorouracil for skin cancer treatment
Kristijan Skok, Tanja Zidarič, Kristjan Orthaber, Matevž Pristovnik, Nina Kostevšek, Kristina Žužek Rožman, Sašo Šturm, Lidija Gradišnik, Uroš Maver, Tina Maver, 2022, izvirni znanstveni članek

Opis: Despite medical advances, skin-associated disorders continue to pose a unique challenge to physicians worldwide. Skin cancer is one of the most common forms of cancer, with more than one million new cases reported each year. Currently, surgical excision is its primary treatment; however, this can be impractical or even contradictory in certain situations. An interesting potential alternative could lie in topical treatment solutions. The goal of our study was to develop novel multilayer nanofilms consisting of a combination of polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA), sodium deoxycholate (NaDOC) with incorporated superparamagnetic iron–platinum nanoparticles (FePt NPs), and the potent anticancer drug (5-fluorouracil), for theranostic skin cancer treatment. All multilayer systems were prepared by spin-coating and characterised by atomic force microscopy, infrared spectroscopy, and contact angle measurement. The magnetic properties of the incorporated FePt NPs were evaluated using magnetisation measurement, while their size was determined using transmission electron microscopy (TEM). Drug release performance was tested in vitro, and formulation safety was evaluated on human-skin-derived fibroblasts. Finally, the efficacy for skin cancer treatment was tested on our own basal-cell carcinoma cell line.
Ključne besede: nanomaterials, bimodal therapy, topical skin treatmen, magnetic nanoparticles, thin films, skin cancer, methacrylates
Objavljeno v DKUM: 04.07.2024; Ogledov: 98; Prenosov: 16
.pdf Celotno besedilo (5,33 MB)
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9.
Psychometric properties of the Slovenian version of the Cancer Survivors' Unmet Needs (CaSUN-SL) measure in post-treatment cancer survivors
Špela Miroševič, Polona Selič-Zupančič, Judith B. Prins, Vesna Homar, Zalika Klemenc-Ketiš, 2022, izvirni znanstveni članek

Opis: Background: As the number of cancer survivors is growing, valid instruments for assessing cancer survivors' needs are required. Thus, the aim of this study was to translate and validate the Cancer Survivors Unmet Needs (CaSUN) scale. Methods: Cancer survivors were recruited from 30 family medicine practices and separated into two samples (sample 1, n = 147; sample 2, n = 148). Factor structure was explored with an exploratory analysis in sample 1 and determined with a confirmatory analysis in sample 2. Psychometric properties were assessed with internal consistency, test-retest reliability and construct validity. Results: A translation and cultural adaptation of the CaSUN scale resulted in 34 items being included in the final version. The factor structure confirmed the five-factors solution of the CaSUN-SL. Cronbach's alpha was 0.94 for the CaSUN-SL and ranged from 0.71-0.88 for specific domains. Test-retest reliability showed moderate-high stability over time. The CaSUN-SL significantly and positively correlated with anxiety (r = 0.49), depression (r = 0.44), health-related quality of life (r = 0.36), and negatively with self-perceived health (r = - 0.36) and resilience (r = - 0.47), which confirms the construct validity. In addition, we found a significant correlation between unmet needs and age (r = - 0.29), gender (r = 0.14), cancer stage (r = 0.20), cancer type (r = 0.19), and time since treatment (r = - 0.20). Conclusions: Results indicate that CaSUN-SL is a valid and reliable measure to assess the Slovenian cancer survivors' unmet, met and total needs and can be used for further prospective studies.
Ključne besede: Cancer survivors, needs assessment, psychometrics, anxiety, depression, quality of life, cancer, survivol, psychometrics
Objavljeno v DKUM: 27.06.2024; Ogledov: 130; Prenosov: 15
.pdf Celotno besedilo (993,82 KB)
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10.
Factors associated with a high level of unmet needs and their prevalence in the breast cancer survivors 1–5 years after post local treatment and (neo)adjuvant chemotherapy during the COVID-19 : a cross-sectional study
Špela Miroševič, Judith B. Prins, Simona Borštnar, Nikola Bešić, Vesna Homar, Polona Selič-Zupančič, Andreja Cirila Škufca Smrdel, Zalika Klemenc-Ketiš, 2022, izvirni znanstveni članek

Opis: Objective: To assess the prevalence of unmet needs in post-treatment breast cancer survivors and identify sociodemographic, clinical, and psychosocial variables associated with reported unmet needs during the COVID-19 pandemic. Materials and methods: In this cross-sectional study, 430 post-treatment breast cancer survivors, ranging between 1 and 5 years after the procedure, completed the Cancer Survivors’ Unmet Needs (CaSUN) questionnaire from September 2021 and January 2022. The multivariate logistic analysis identified factors associated with at least one reported unmet need in the total CaSUN scale and specific domains. Results: A total of 67% of survivors reported at least one unmet need. The most frequently reported unmet needs were the lack of accessible hospital parking (43%) and recurrence concerns (39.5%). The majority of reported unmet needs relate to comprehensive care (44%), followed by the psychological and emotional support domain (35.3%). Younger age (OR = 0.95, 95% CI = 0.92–0.99; p < 0.001), three or more comorbidities (OR = 0.27, 95% CI = 0.11–0.71, p < 0.01), a lower quality of life (OR = 0.06, 95% CI = 0.01–0.47, p < 0.01) and low resilience (OR = 0.95, 95% CI = 0.93–0.99) were associated with a high level of unmet needs in the multivariate regression model. Results are presented for factors associated with a high level of unmet needs for comprehensive cancer care and psychological and emotional support domain. Conclusion: A high prevalence found in our study could be attributed to the COVID-19 pandemic, where patients may have missed adequate follow-up care, although comparing to studies done in non-pandemic time is difficult. Family physicians should be more attentive toward younger cancer survivors and those with more comorbidities as both characteristics can be easily recognized in the family practice.
Ključne besede: breast cancer, cancer survivors (MeSH term), needs assessment [MeSH], fear of cancer recurrence, quality of life, psycho-oncology, COVID-19, chemotherapy, unmet needs
Objavljeno v DKUM: 27.06.2024; Ogledov: 129; Prenosov: 4
.pdf Celotno besedilo (621,32 KB)
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