0000000000264275
AUTHOR
Gloria Ganduscio
CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin
Summary Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless…
Choline PET/CT Features to Predict Survival Outcome in High Risk Prostate Cancer Restaging: A Preliminary Machine-Learning Radiomics Study
Background Radiomic features are increasingly utilized to evaluate tumor heterogeneity in PET imaging but to date its role has not been investigated for Cho-PET in prostate cancer. The potential application of radiomics features analysis using a machine-learning radiomics algorithm was evaluated to select 18F-Cho PET/CT imaging features to predict disease progression in PCa. Methods We retrospectively analyzed high-risk PCa patients who underwent restaging 18F-Cho PET/CT from November 2013 to May 2018. 18F-Cho PET/CT studies and related structures containing volumetric segmentations were imported in the "CGITA" toolbox to extract imaging features from each lesion. A Machine-learning model h…
Potential clinical value of quantitative fluorine-18-fluorodeoxyglucose-PET/computed tomography using a graph-based method analysis in evaluation of incidental lesions of gastrointestinal tract: correlation with endoscopic and histopathological findings.
Objectives To identify the clinical relevance of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with 18F-FDG PET/CT and to assess the potential benefit of using semiquantitative PET measures to discern malignant from benign lesions. Methods Forty-one patients who underwent F-FDG PET/CT scans during the oncologic follow-up, revealing abnormal incidental 18F-FDG accumulations in the GIT were included in this retrospective analysis. Incidental PET/CT findings were correlated with endoscopic and histological findings. Semiquantitative PET values (SUVmax, SUVmean, SULpeak, and TLG) were evaluated by using a new graph-based method. Two sample t-test analysis has been per…
Clinical and Prognostic Value of 18F-FDG-PET/CT in the Restaging Process of Recurrent Cutaneous Melanoma
Background: Several studies on 18F-FDG-PET/CT have investigated the prognostic role of this imaging modality in different tumors after treatment. Nevertheless, its role in restaging patients with recurrent CM still needs to be defined. Objective: The aim of this retrospective multicenter study was to evaluate the clinical and prognostic impact of 18F-FDG-PET/CT on the restaging process of cutaneous melanoma (CM) after surgery in patients with suspected distant recurrent disease or suspected metastatic progression disease. Materials and Methods: 74 patients surgically treated for CM underwent 18F-FDG-PET/CT for suspected distant recurrent disease or suspected metastatic progression disease.…
PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells
ObjectiveCancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy.DesignA collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional…