15 research outputs found
Prognostic Significance of mTOR Expression in Recurrence Following Hepatic Metastasectomy in Colorectal Cancer
No full textSurgery is one of the most effective treatment methods for liver metastases developing from primary colorectal cancer (CRC). Despite the widespread application of surgical approaches, recurrence rates remain substantial. Although chemotherapy is frequently employed, the supporting evidence for its efficacy in this context remains inconclusive. In the present study, we aimed to identify potential predictors of post-metastasectomy recurrence by analyzing clinical, pathological, and molecular features of both primary colorectal tumors and their corresponding hepatic metastases. Specifically, we evaluated the expression of epithelial–mesenchymal transition (EMT) markers, cancer stem cell (CSC) markers, and selected oncogenic mRNAs (RAS, mTOR, and CMYC) in tissue samples from 84 patients. RAS and CMYC are well-known proto-oncogenes involved in cell proliferation and survival, while mTOR functions as a central regulator of cell growth and metabolism. Following liver metastasectomy, intra-hepatic recurrence was observed in 40.5% of the cases. Among the molecular markers analyzed, the EMT transcription factor SNAIL—which plays a critical role in cancer cell invasion and metastasis—and mTOR exhibited significantly elevated expression in metastatic lesions from patients who experienced recurrence. While SNAIL expression did not show a clear association with the time to recurrence, increased mTOR expression in metastatic liver tissue was significantly associated with both shorter recurrence-free survival and diminished overall survival (p < 0.001). Results showed that mTOR expression levels could be a clinically relevant predictive indicator of remnant liver recurrence. In patients with liver metastases, the use of mTOR inhibitors may be considered after hepatic metastasectomy
Olea europaea Leaf Phenolics Oleuropein, Hydroxytyrosol, Tyrosol, and Rutin Induce Apoptosis and Additionally Affect Temozolomide against Glioblastoma: In Particular, Oleuropein Inhibits Spheroid Growth by Attenuating Stem-like Cell Phenotype
No full textThe effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy
Olea europaea leaf extract decreases tumour size by affecting the LncRNA expression status in glioblastoma 3D cell cultures
No full textIntroduction: Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide (TMZ) is a chemotherapy drug used in the treatment of GB. Despite treatment with TMZ, the prognosis of GB is poor. This study aimed to demonstrate the ability of Olea europaea leaf extract (OLE) alone and in combination with TMZ to suppress tumour aggressiveness by evaluating long non-coding RNA (LncRNA) and cancer stem cell (CSC) markers in GB cells using a three-dimensional (3D) model. Methods: The Real-time PCR (RT-PCR) method was used to determine the effects of OLE on LncRNA and CSC markers associated with tumour aggressiveness. To explore the effect of OLE on tumour size, a 3D model was developed. Results: It was found that OLE suppressed tumour aggressiveness with inhibited the MALAT1, SOX2 and NANOG ( p < 0.05). OLE + TMZ also inhibited MALAT1, LOXL1-AS1, PVT1 and H19 ( p < 0.05) and OCT4, NANOG, SOX2 and CD133 ( p < 0.05). In addition, to reduce tumour aggressiveness in a 3D cell culture, the use of OLE and OLE + TMZ has been supported (47.11-fold, p < 0.0001 and 18.04-fold, p < 0.0001, respectively). Conclusion: OLE may be a potential therapeutic agent that can be used in the treatment of GB, as it has been shown to reduce tumour size and increase the effect of TMZ
Inhibitory Effects of Olea europaea Leaf Extract on Mesenchymal Transition Mechanism in Glioblastoma Cells
No full textBackground: Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current treatment methods, the survival rate of patients is very low. Therefore, there is a need to develop new therapeutic agents. The migration and invasion capacity of GB cells is related to mesenchymal transition (MT) mechanism. Materials and Methods: The effect of OLE on MT was determined by analysis of the Twist, Snail, Zeb1, N-cadherin and E-cadherin genes in the EMT mechanism. The effect of OLE on cell migration was determined by wound healing test. Results: 2 mg/ml OLE reduced Twist, Snail, Zeb1 and N-cadherin expression and the combination of OLE + TMZ (2 mg/ml OLE + 350 mM TMZ) increased E-cadherin and reduced Twist, Zeb1 and N-cadherin. In addition, co-treatment with OLE increased TMZ-induced anti-invasion properties thought suppressing transcription factors of MT mechanism. Conclusion: OLE can enhance the anti-MT activities of TMZ against GB and provide strong evidence that combined treatment with OLE and TMZ has the potential to be an effective alternative approach in GB therapy
Frequency of azole resistance in clinical and environmental strains of Aspergillus fumigatus in Turkey: a multicentre study
No full textObjectives Aspergillus fumigatus causes several diseases in humans and azole resistance in A. fumigatus strains is an important issue. The aim of this multicentre epidemiological study was to investigate the prevalence of azole resistance in clinical and environmental A. fumigatus isolates in Turkey. Methods Twenty-one centres participated in this study from 1 May 2018 to 1 October 2019. One participant from each centre was asked to collect environmental and clinical A. fumigatus isolates. Azole resistance was screened for using EUCAST agar screening methodology (EUCAST E.DEF 10.1) and was confirmed by the EUCAST E.DEF 9.3 reference microdilution method. Isolates with a phenotypic resistance pattern were sequenced for the cyp51A gene and microsatellite genotyping was used to determine the genetic relationships between the resistant strains. Results In total, resistance was found in 1.3% of the strains that were isolated from environmental samples and 3.3% of the strains that were isolated from clinical samples. Mutations in the cyp51A gene were detected in 9 (47.4%) of the 19 azole-resistant isolates, all of which were found to be TR34/L98H mutations. Microsatellite genotyping clearly differentiated the strains with the TR34/L98H mutation in the cyp51A gene from the strains with no mutation in this gene. Conclusions The rate of observed azole resistance of A. fumigatus isolates was low in this study, but the fact that more than half of the examined strains had the wild-type cyp51A gene supports the idea that other mechanisms of resistance are gradually increasing.Bursa Uludag University Scientific Research Projects Commission [QUAP[T]-2015-5]; Ener Private Health Service CompanyThis work was partly supported by Bursa Uludag University Scientific Research Projects Commission (QUAP[T]-2015-5) and Ener Private Health Service Company
Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release
No full textGlioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) coreshell nanofiber webs were encapsulated with OL (PLA(OL)), rutin (PLA(rutin)), and TMZ (PLA(TMZ)) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core -shell structures with an average diameter between 133 +/- 30.7-139 +/- 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLA(OL) and PLA(TMZ) suppressed GB cell viability with a controlled release that increased over 120 h, while PLA(rutin) caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nanowebs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.100/2000 The Council of Higher Education (CoHE)2211-C priority areas PhD program scholarshi
Coexistence of MACC1 and NM23-H1 dysregulation and tumor budding promise early prognostic evidence for recurrence risk of early-stage colon cancer
No full textOlea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro
No full textOverexpression of the Long Noncoding RNA HomeoboxA Transcript at the Distal Tip Predicts Poor Prognosis in a KRAS-Independent Manner in Periampullary Region Tumors
No full textLong noncoding RNA MALAT1 may be a prognostic biomarker in IDH1/2 wild-type primary glioblastomas
No full textPrimary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most primary GBs are IDH wild-type. Recent studies have shown that the long noncoding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is associated with aggressive tumor phenotypes in different cancers. Our aim was to clarify the prognostic significance of MALAT1 in IDH1/2 wild-type primary GB tumors. We analyzed IDH1/2 mutation status in 75 patients with primary GB by DNA sequencing. The expression of MALAT1 was detected in the 75 primary GB tissues and 5 normal brain tissues using reverse transcription quantitative PCR (RT-qPCR). The associations between MALAT1 expression, IDH1/2 mutation status, and clinicopathological variables of patients were determined. IDH1 (R132H) mutation was observed in 5/75 primary GBs. IDH2 (R172H) mutation was not detected in any of our cases. MALAT1 expression was significantly upregulated in primary GB vs. normal brain tissues (p = 0.025). Increased MALAT1 expression in IDH1/2 wild-type primary GBs correlated with patient age and tumor localization (p = 0.032 and p = 0.025, respectively). A multivariate analysis showed that high MALAT1 expression was an unfavorable prognostic factor for overall survival (p = 0.034) in IDH1/2 wild-type primary GBs. High MALAT1 expression may have a prognostic role in primary GBs independent of IDH mutations
