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Povzetek: Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60–70% of all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and non-specific ion receptor protein transporters TRPs. First, we found up-regulated CNR1, GPR55, and TRPV1 expression in glioma patient-derived tissue samples and cell lines compared with non-malignant brain samples. CNR1 and GPR55 did not correlate with glioma grade, whereas TRPV1 negatively correlated with grade and positively correlated with longer overall survival. This suggests a tumour-suppressor role of TRPV1. With respect to markers of GBM stem cells, preferred targets of therapy, TRPV1 and GPR55, but not CNR1, strongly correlated with different sets of stemness gene markers: NOTCH, OLIG2, CD9, TRIM28, and TUFM and CD15, SOX2, OCT4, and ID1, respectively. This is in line with the higher expression of TRPV1 and GPR55 genes in GSCs compared with differentiated GBM cells. Second, in a panel of patient-derived GSCs, we found that CBG and CBD exhibited the highest cytotoxicity at a molar ratio of 3:1. We suggest that this mixture should be tested in experimental animals and clinical studies, in which currently used Δ9-tetrahydrocannabinol (THC) is replaced with efficient and non-psychoactive CBG in adjuvant standard-of-care therapy.
Ključne besede: glioblastoma, glioma, cannabigerol, cannabidiol, cannabinoid receptors, stem cells
Objavljeno v DiRROS: 18.07.2024; Ogledov: 26; Prenosov: 16
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Povzetek: The major obstacle to the application of mesenchymal stromal cells (MSCs) in regenerative medicine is the expansion of the donor-derived cells in vitro to obtain high cell numbers in the shortest possible time. However, MSCs gradually undergo replicative senescence after a variable number of divisions that reduce their therapeutic efficacy, which needs to be determined before administration. The authors developed a fast and simple evaluation assay testing two senescence inducers, mitoxantrone (Mxt) and trichostatin A (TSA), to predict the onset of spontaneous replicative senescence of adipose-derived mesenchymal stromal cells (ASCs) and have confirmed the correlation between induced senescence and spontaneous replicative senescence in the assay using Mxt. This protocol facilitates the standardization of therapeutic ASCs and MSCs from other origins before application.
Ključne besede: adipose mesenchymal stromal (stem) cells (ASCs), cell longevity, induced senescence, mesenchymal stromal (stem) cells (MSCs), mitoxantrone, replicative senescence, trichostatin A
Objavljeno v DiRROS: 16.07.2024; Ogledov: 16; Prenosov: 17
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Povzetek: Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes. Materials and methods. In order to reach this aim, parental and invasive (INV) MDA-MB-231 (triple-negative), T47D (hormone receptor-positive), and Au565 (Her2-positive) breast carcinoma cells were used and their molecular phenotypes were compared using a proteomic approach. Results. Independently from breast cancer subtypes, INV cells have demonstrated fibroblast-like morphology accompanied by enhancement of invasive and migratory capacities, increased expression of cancer stem cell markers, and delayed tumor growth in in vivo animal models. However, the global proteomic analysis has highlighted that INV cells were different in protein expressions from the parental cells, and Her2-positive Au565-INV cells showed the most pronounced molecular differences compared to the triple-negative MDA-MB-231-INV and hormone receptor-positive T47D-INV cells. Although Au565-INV breast carcinoma cells possessed the highest number of deregulated proteins, they had the lowest overlapping in proteins commonly expressed in MDA-MB-231-INV and T47D-INV cells. Conclusions. We can conclude that hormone receptor-positive cells with increased invasiveness acquire the molecular characteristics of triple-negative breast cancer cells, whereas Her2-positive INV cells specifically changed their own molecular phenotype with very limited partaking in the involved pathways found in the MDA-MB-231-INV and T47D-INV cells. Since hormone receptor-positive invasive cells share their molecular properties with triple-negative breast cancer cells, we assume that these types of metastatic disease can be treated rather equally with an option to add anti-hormonal agents. In contrast, Her2-positive metastasis should be carefully evaluated for more effective therapeutic approaches which are distinct from the triple-negative and hormone-positive metastatic breast cancers.
Ključne besede: breast cancer, cancer stem cells, invasiveness, migration, metastasis
Objavljeno v DiRROS: 11.07.2024; Ogledov: 83; Prenosov: 16
Celotno besedilo (2,52 MB)

Povzetek: Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production.
Ključne besede: aerobic glycolysis, anaerobic glycolysis, angiogenesis, ATP synthesis, cancer cells, cancer stem cells, endothelial cells, energy metabolism, eye diseases, oxidative phosphorylation, pericytes, retina, Warburg effect
Objavljeno v DiRROS: 18.06.2024; Ogledov: 134; Prenosov: 79
Celotno besedilo (3,75 MB)
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Povzetek: We investigated micro-threaded stem taper surface and its impact on premature failures, aseptic loosening, and infection in cementless hip endoprostheses. Our study focused on the fretting, and crevice corrosion of micro-threaded tapers, as well as the characterization of the microstructure and surface properties of two new and three retrieved Zweymüller stem tapers. The retrieved samples were selected and examined based on the head–stem taper interface being the sole source of modularity with a metallic component, specifically between the Ti alloy taper stem and the ceramic head. To determine the surface chemistry and microstructures of both new and retrieved hip endoprostheses stem taper titanium alloy, scanning -electron microscopy (SEM) was employed for morphological and microstructural analyses. Energy dispersive spectroscopy (EDS) was utilized for characterizing chemical element distribution, and electron backscattered diffraction (EBSD) was used for phase analysis. The roughness of the micro-threated stem tapers from different manufacturers was investigated using an optical profilometer, with standard roughness parameters Ra (average surface roughness) and Rz (mean peak to valley height of the roughness profile) being measured. Electrochemical studies revealed no fretting corrosion in retrieved stem tapers with ceramic heads. Consequently, three retrieved tapers and two new ones for comparison underwent potentiodynamic measurements in Hank’s solution to determine the corrosion rate of new and retrieved stem taper surfaces. The results showed a low corrosion rate for both new and prematurely failed retrieved samples due to aseptic loosening. However, the corrosion rate was higher in infected and low-grade infected tapers. In conclusion, our study suggests that using ceramic heads reduces taper corrosion and subsequently decreases the incidence of premature failures in total hip arthroplasty.
Ključne besede: total hip arthroplasty, stem micro-threaded taper, taper surface morphology, microstructure, corrosion, Ti implant alloy
Objavljeno v DiRROS: 06.06.2024; Ogledov: 162; Prenosov: 139
Celotno besedilo (8,47 MB)
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