| 11091. |
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| 11092. |
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| 11093. |
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| 11094. |
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| 11095. |
- Lázaro-Ibáñez, Elisa, et al.
(författare)
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Distinct prostate cancer-related mRNA cargo in extracellular vesicle subsets from prostate cell lines
- 2017
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17:92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple types of extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs), are released by all cells constituting part of the cellular EV secretome. The bioactive cargo of EVs can be shuffled between cells and consists of lipids, metabolites, proteins, and nucleic acids, including multiple RNA species from non-coding RNAs to messenger RNAs (mRNAs). In this study, we hypothesized that the mRNA cargo of EVs could differ based on the EV cellular origin and subpopulation analyzed. Methods: We isolated MVs and EXOs from PC-3 and LNCaP prostate cancer cells by differential centrifugation and compared them to EVs derived from the benign PNT2 prostate cells. The relative mRNA levels of 84 prostate cancer-related genes were investigated and validated using quantitative reverse transcription PCR arrays. Results: Based on the mRNA abundance, MVs rather than EXOs were enriched in the analyzed transcripts, providing a snapshot of the tumor transcriptome. LNCaP MVs specifically contained significantly increased mRNA levels of NK3 Homeobox 1 (NKX3-1), transmembrane protease serine 2 (TMPRSS2), and tumor protein 53 (TP53) genes, whereas PC-3 MVs carried increased mRNA levels of several genes including, caveolin-2 (CAV2), glutathione S-transferase pi 1 (GSTP1), pescadillo ribosomal biogenesis factor 1 (PES1), calmodulin regulated spectrin associated protein 1 (CAMSAP1), zinc-finger protein 185 (ZNF185), and others compared to PNT2 MVs. Additionally, ETS variant 1 (ETV1) and fatty acid synthase (FASN) mRNAs identified in LNCaP-and PC-3-derived MVs highly correlated with prostate cancer progression. Conclusions: Our study provides new understandings of the variability of the mRNA cargo of MVs and EXOs from different cell lines despite same cancer origin, which is essential to better understand the the proportion of the cell transcriptome that can be detected within EVs and to evaluate their role in disease diagnosis.
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| 11096. |
- Lazzeroni, Marta, et al.
(författare)
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Evaluation of third treatment week as temporal window for assessing responsiveness on repeated FDG-PET scans in Non-Small Cell Lung Cancer patients
- 2018
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Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 46, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Early assessment of tumour response to treatment with repeated FDG-PET-CT imaging has potential for treatment adaptation but it is unclear what the optimal time window for this evaluation is. Previous studies indicate that changes in SUVmean and the effective radiosensitivity (alpha(eff), accounting for uptake variations and accumulated dose until the second FDG-PET-CT scan) are predictive of 2-year overall survival (OS) when imaging is performed before radiotherapy and during the second week. This study aims to investigate if multiple FDG-PET-derived quantities determined during the third treatment week have stronger predictive power.Methods: Twenty-eight lung cancer patients were imaged with FDG-PET-CT before radiotherapy (PET1) and during the third week (PET2). SUVmean, SUVmax, SUVpeak, MTV41%-50% (Metabolic Tumour Volume), TLG41%-50% (Total Lesion Glycolysis) in PET1 and PET2 and their change (), as well as average alpha(eff) (<(alpha)over bar >(eff)) and the negative fraction of alpha(eff) values (f(alpha eff) (< 0)) were determined. Correlations were sought between FDG-PET-derived quantities and OS with ROC analysis.Results: Neither SUVmean, SUVmax, SUVpeak in PET1 and PET2 (AUC = 0.5-0.6), nor their changes (AUC = 0.5-0.6) were significant for outcome prediction purposes. Lack of correlation with OS was also found for (alpha) over bar (eff) (AUC = 0.5) and f(alpha eff) (<) 0 (AUC = 0.5). Threshold-based quantities (MTV41%-50%, TLG41%-50%) and their changes had AUC= 0.5-0.7. P-values were in all cases >> 0.05.Conclusions: The poor OS predictive power of the quantities determined from repeated FDG-PET-CT images indicates that the third week of treatment might not be suitable for treatment response assessment. Comparatively, the second week during the treatment appears to be a better time window.
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| 11097. |
- Lazzeroni, Marta, et al.
(författare)
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Evolution of the hypoxic compartment on sequential oxygen partial pressure maps during radiochemotherapy in advanced head and neck cancer
- 2021
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier BV. - 2405-6316. ; 17, s. 100-105
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeLongitudinal Positron Emission Tomography (PET) with hypoxia-specific radiotracers allows monitoring the time evolution of regions of increased radioresistance and may become fundamental in determining the radiochemotherapy outcome in Head-and-Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the evolution of the hypoxic target volume on oxygen partial pressure maps (pO2-HTV) derived from 18FMISO-PET images acquired before and during radiochemotherapy and to uncover correlations between extent and severity of hypoxia and treatment outcome.Material and methods18FMISO-PET/CT images were acquired at three time points (before treatment start, in weeks two and five) for twenty-eight HNSCC patients treated with radiochemotherapy. The images were converted into pO2 maps and corresponding pO2-HTVs (pO2-HTV1, pO2-HTV2, pO2-HTV3) were contoured at 10 mmHg. Different parameters describing the pO2-HTV time evolution were considered, such as the percent and absolute difference between the pO2-HTVs (%HTVi,j and HTVi-HTVj with i,j = 1, 2, 3, respectively) and the slope of the linear regression curve fitting the pO2-HTVs in time. Correlations were sought between the pO2-HTV evolution parameters and loco-regional recurrence (LRR) using the Receiver Operating Characteristic method.ResultsThe Area Under the Curve values for %HTV1,2, HTV1-HTV2, HTV1-HTV3 and the slope of the pO2-HTV linear regression curve were 0.75 (p = 0.04), 0.73 (p = 0.02), 0.73 (p = 0.02) and 0.75 (p = 0.007), respectively. Other parameter combinations were not statistically significant.ConclusionsThe pO2-HTV evolution during radiochemotherapy showed predictive value for LRR. The changes in the tumour hypoxia during the first two treatment weeks may be used for adaptive personalized treatment approaches.
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| 11098. |
- Lazzeroni, Marta, et al.
(författare)
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Impact of Tumour Cell Infiltration on Treatment Outcome in Gamma Knife Radiosurgery : A Modelling Study
- 2019
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 39:4, s. 1675-1687
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-grade gliomas with a widespread infiltration beyond the lesion detectable on diagnostic images are increasingly treated with Gamma Knife (TM) Radiosurgery (GKRS). The aim of this study was to assess the cell infiltration impact on the GKRS outcome for invasive gliomas. Materials and Methods: Tumor cell distribution was predicted using a novel algorithm whose computations are iterated until they reach an agreement with histopathology results. Treatment plans with different combinations of dose prescription (20 Gy at 50%-20% isodose) and targets [Gross Tumour Volume (GTV), zone 1 with 100%-60% of the GTV cell density and zone 2 with 60%-0% of the GTV cell density] were evaluated using standard conformity indexes (CI) and radiobiological parameters. Results: Considerable differences in terms of tumor control probability were found between plans having similar CI but different targets. Conclusion: To account for tumor cell infiltration outside the target is of key importance in GKRS and a radiobiological evaluation should accompany well-established CI.
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| 11099. |
- Lazzeroni, Marta, et al.
(författare)
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Quantification of Tumor Oxygenation Based on FMISO PET : Influence of Location and Oxygen Level of the Well-Oxygenated Reference Region
- 2020
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Ingår i: Oxygen Transport to Tissue XLI. - Cham : Springer. - 9783030344597 - 9783030344610 ; 1232, s. 177-182
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Bokkapitel (refereegranskat)abstract
- Tumor hypoxia may play a fundamental role in determining the radiotherapy outcome for several cancer types. Functional imaging with hypoxia specific radiotracers offers a way to visualize and quantify regions of increased radioresistance, which may benefit from dose escalation strategies. Conversion of the uptake in positron emission tomography (PET) images into oxygenation maps offers a way to quantitatively characterize the microenvironment. However, normalization of the uptake with respect to a well-oxygenated reference volume (WOV), which should be properly selected, is necessary when using conversion functions. This study aims at assessing the sensitivity of quantifying tumor oxygenation based on 18F-fluoromisonidazole (FMISO) PET with respect to the choice of the location and the oxygenation level of the WOV in head and neck cancer patients. WOVs varying not only in shape and location but also with respect to the assigned pO2 level were considered. pO2 values other than the standard 60 mmHg were selected according to the specific tissue type included in the volume. For comparison, the volume which would be considered as hypoxic based on a tissue-to-muscle ratio equal to 1.4 was also delineated, as conventionally done in clinical practice. Hypoxia mapping strategies are found highly sensitive to selection of the location of well-oxygenated region, but also on its assigned oxygenation level, which is crucial for hypoxia-guided adaptive dose escalation strategies.
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| 11100. |
- Le Deley, Marie-Cécile, et al.
(författare)
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Cyclophosphamide Compared With Ifosfamide in Consolidation Treatment of Standard-Risk Ewing Sarcoma: Results of the Randomized Noninferiority Euro-EWING99-R1 Trial.
- 2014
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 32:23, s. 2440-2448
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Tidskriftsartikel (refereegranskat)abstract
- Relative efficacy and toxicity of cyclophosphamide compared with ifosfamide are debatable. The Euro-EWING99-R1 trial asked whether cyclophosphamide may replace ifosfamide in combination with vincristine and dactinomycin (vincristine, dactinomycin, and cyclophosphamide [VAC] v vincristine, dactinomycin, and ifosfamide [VAI]) after an intensive induction chemotherapy containing vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in standard-risk localized disease (NCT00020566).
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