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Povzetek: This article presents the first results on shellfish toxicity in the Slovenian sea (Gulf of Trieste, Adriatic Sea) since the analytical methods for the detection of biotoxins (PSP, ASP, DSP and other lipophilic toxins) in bivalve molluscs were included in the national monitoring program in 2013. In addition to toxins, the composition and abundance of toxic phytoplankton and general environmental characteristics of the seawater (surface temperature and salinity) were also monitored. During the 2014–2019 study period, only lipophilic toxins were detected (78 positive tests out of 446 runs), of which okadaic acid (OA) predominated in 97% of cases, while dinophysistoxin-2 and yessotoxins only gave a positive result in one sampling event each. The number of samples that did not comply with the EC Regulation for the OA group was 17 or 3.8% of all tests performed, all of which took place from September to November, while a few positive OA tests were also recorded in December, April, and May. This toxicity pattern was consistent with the occurrence pattern of the five most common DSP-producing dinoflagellates, which was supported by the development of warm and thermohaline stratified waters: Dinophysis caudata, D. fortii, D. sacculus, D. tripos and Phalacroma rotundatum. The strong correlation (r = 0.611, p<0.001) between D. fortii, reaching abundances of up to 950 cells L−1, and OA suggests that D. fortii is the main cause of OA production in Slovenian waters. Strong interannual variations in OA and phytoplankton dynamics, exacerbated by the effects of anthropogenic impacts in this coastal ecosystem, reduce the predictability of toxicity events and require continuous and efficient monitoring. Our results also show that the introduction of the LC-MS/MS method for lipophilic toxins has improved the management of aquaculture activities, which was not as accurate based on mouse bioassays.
Ključne besede: biotoxins, okadaic acid, toxic phytoplankton, LC-MS/MS, toxicity, Adriatic Sea, hydrobiology, marine biology
Objavljeno v DiRROS: 19.06.2024; Ogledov: 94; Prenosov: 43
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Povzetek: Malignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known. Materials and methods The immunoassay and MTT assay were used to assess the concentration of secreted VEGF and cell viability after bevacizumab exposure. Metabolomic studies on cells were performed using high resolution magic angle spinning spectroscopy (HRMAS). Results mIDH1-U87 cells secreted VEGF (13 ng/mL). Regardless, bevacizumab had no cytotoxic effect, even after a 72h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (polyunsaturated fatty acids [PUFA], glycerophosphocholine, and phosphocholine). Conclusions In mIDH1-U87 cells, changes in glutamine group metabolites and lipids were identified as metabolic markers of bevacizumab treatment. These data support the possibility of a functional tricarboxylic acid cycle that runs in reductive manner, as a probable mechanism of action of bevacizumab in IDH1 mutated gliomas and propose a new target pathway for effective treatment of malignant gliomas.
Ključne besede: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer, idh1 mutation, malignant glioma, bevacizumab, metabolic fingerprint
Objavljeno v DiRROS: 11.06.2024; Ogledov: 62; Prenosov: 25
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Ključne besede: radiotherapy, adjuvant radiotherapy, cardiotoxicity, breast cancer
Objavljeno v DiRROS: 10.06.2024; Ogledov: 60; Prenosov: 22
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Povzetek: With introduction of immunotherapy (IT) into the treatment of advanced non-small-cell lung cancer (NSCLC), a need for predictive biomarker became apparent. Programmed death ligand 1 (PD-L1) protein expression is most widely explored predictive marker for response to IT. We assessed PD-L1 expression in tumor cells (TC) and immune cells (IC) of squamous-cell carcinoma (SCC) and adenocarcinoma (AC) patients. We obtained 54 surgically resected tumor specimens and assessed PD-L1 expression by immunohistochemistry after staining them with antibody SP142 (Ventana, USA). Clinicopathological characteristics were acquired from the hospital registry database. Results were analyzed according to cut-off values of % 5% and % 10% of PD-L1 expression on either TC or IC. 29 (54%) samples were AC and 25 (46%) were SCC. PD-L1 expression was significantly higher in TC of SCC compared to AC at both cut-off values (52% vs. 17%, p = 0.016 and 52% vs. 14%, p = 0.007, respectively) no difference in PD-L1 expression in IC of SCC and AC was found. In AC alone, PD-L1 expression was significantly higher in IC compared to TC at both cut-off values (72% vs. 17%, p < 0.001 and 41% vs. 14%, p = 0.008, respectively), while no significant difference between IC and TC PD-L1 expression was revealed in SCC. Our results suggest a significantly higher PD-L1 expression in TC of SCC compared to AC, regardless of the cut-off value. PD-L1 expression in IC is high in both histological subtypes of NSCLC, and adds significantly to the overall positivity of AC but not SCC.
Ključne besede: lung cancer, squamous-cell lung cancer, adenocarcinoma, tumor cells, immune cells, PD-L1 expression
Objavljeno v DiRROS: 31.05.2024; Ogledov: 155; Prenosov: 119
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Povzetek: The study was aimed to characterize tumor response after combined treatment employing electrochemotherapy with IL-12 gene electrotransfer in dogs with spontaneous mast cell tumors (MCT). Materials and methods. Eleven dogs with eleven MCTs were included in the study. Histological changes were investigated in biopsy specimens collected before the treatment (T0), and 4 (T1) and 8 weeks (T2) later. Cellular infiltrates were characterized immunohistochemically by using anti CD3, CD20, Foxp3 (Treg), CD68 and anti MHC-class II antibodies. Proliferation and anti-apoptotic activity of neoplastic cells were assessed using anti Ki-67 and Bcl-2 antibodies. Angiogenetic processes were investigated immunohistochemically by using anti Factor VIII and anti CD31 antibodies and micro vessel density quantification. Results. Histopathological examination of samples at T0 confirmed the diagnosis and the presence of scanty infiltrates consisted mainly of T-lymphocytes and macrophages. At T1 and T2 neoplastic cells were drastically reduced in 7/11 cases, small clusters of neoplastic cells were detected in 3/11 cases and 1/11 cases neoplastic cells were still evident. Proliferation activity of neoplastic cells was significantly reduced at T1 and T2 and expression of anti-apoptotic protein at T1. Microvessel density was drastically reduced in all samples after treatment. The number of T-lymphocytes increased at T1, although not significant, while Treg were significant higher at T1 and macrophages at T2. Conclusions. The combined electrochemotherapy and IL-12 gene electrotransfer effectively induced a cellular response against neoplastic cells characterized mainly by the recruitment of T-lymphocytes and macrophages and a fibrotic proliferation with reduction of microvessels.
Ključne besede: histopathology, interleukin-12, elektroporation, electrochemotherapy, immune cells
Objavljeno v DiRROS: 31.05.2024; Ogledov: 118; Prenosov: 82
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