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Simultaneous Integrated Boost Preoperative Radiotherapy for Rectum Cancer

ABSTRACT: The investigators propose a randomized non-inferiority trial that compares preoperative Fluoro Uracil (FU)-based chemoradiotherapy to radiotherapy with a simultaneous integrated boost. In patients with T3-4 rectal cancer, the latter approach is considered preferential with regard to toxicity and cost. The metabolic response of the tumor, as assessed by 18F-2-Fluoro-2-Deoxyglucose-Positron Emission tomography (18F-FDG PET) or PET-CT, will be used as a surrogate marker of cause specific outcome

DISEASE(S): Rectal Neoplasms,Colorectal Cancer,Colorectal Neoplasms,Rectal Cancer

PROVIDER: 2096816 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Functional Genomics and Molecular Imaging of Liver Disease and Cancer

Project description:<p>Molecular imaging with 18F-fluorocholine PET/CT reveals two distinct imaging phenotypes for hepatocellular carcinoma (HCC) as a potential source of non-invasive insight into its molecular heterogeneity. Using gene set enrichment analyses, we found 18F-fluorocholine-avid tumors to be significantly enriched by genes comprising a subset of previously published HCC-related gene signatures. Significant gene sets included those from existing molecular classification systems for HCC as well as gene signatures predictive of clinical outcomes after tumor resection. PET/CT imaging using 18F-fluorocholine might therefore provide surrogate information about tumor molecular characteristics and prognosis in HCC.</p>

| phs001784 | dbGaP

STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [18F]FLT PET imaging

Project description:Type I interferons (IFNs) are critical effectors of emerging cancer immunotherapies designed to activate pattern recognition receptors (PRRs). A challenge in the clinical translation of these new immuno-modulatory agents is the lack of pharmacodynamic biomarkers indicative of increased intratumoral IFN signaling following PRR activation. Positron emission tomography (PET) imaging enables the visualization of tissue metabolic activity but whether IFN signaling-induced alterations in tumor cell metabolism can be detected using PET has not been investigated. We found that IFN signaling augments pancreatic ductal adenocarcinoma (PDAC) cell nucleotide metabolism via transcriptional induction of metabolism-associated genes including thymidine phosphorylase (TYMP). TYMP catalyzes the first step in the catabolism of thymidine which competitively inhibits intratumoral accumulation of the nucleoside analog PET probe [18F]-fluorothymidine ([18F]FLT). Accordingly, IFN treatment stimulates cancer cell [18F]FLT uptake in the presence of thymidine and this effect is dependent on TYMP expression. In vivo, genetic activation of stimulator of interferon genes (STING), a PRR widely expressed in PDAC, enhances the [18F]FLT avidity of xenograft tumors. Treatment with a small molecule STING agonist triggers IFN signaling-dependent TYMP expression in PDAC cells and enhances both subcutaneous and orthotopic tumor [18F]FLT uptake in vivo following systemic treatment. These findings indicate that [18F]FLT accumulation in tumors is sensitive to IFN signaling and that [18F]FLT PET may serve as a novel pharmacodynamic biomarker for PRR agonist-based immunotherapies in PDAC and possibly other malignancies characterized by elevated STING expression.

2021-08-30 | GSE178901 | GEO

Evaluation of Metabolic Activity of Liver Metastases by FDG-PET Scanning

Project description:The purpose of this study is to evaluate the effect of primary tumor resection on the metabolic activity of metastases in patients with a colorectal primary tumor and synchronous liver metastases by positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D-glucose (FDG-PET) scanning.

| 2018360 | ecrin-mdr-crc

Expression profile of Ewing sarcoma

Project description:The expression profile in Ewing tumors was analyzed and correlated with glucose uptake (SUVmax) measured in 18F-FDG-PET imaging

2022-11-29 | GSE218758 | GEO

68Ga-FAPI PET imaging assesses tumor immunity and guides TGF-β inhibition to sensitize metastatic colorectal cancer to immunotherapy

Project description:BACKGROUND. Improving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor β (TGF-β) inhibitor that targets cancer associated fibroblasts (CAFs) is promising to enhance efficacy of cancer immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy. METHODS. We measure CAFs in vivo using gallium 68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) for PET/CT imaging to guide TGF-β inhibition and sensitize metastatic colorectal cancer (CRC) to immunotherapy. A total of 131 patients with metastatic CRC underwent 68Ga-FAPI and 18F-fludeoxyglucose (18F-FDG) PET/CT imaging. Fourteen patients underwent surgery after the imaging. Relationship between uptake of 68Ga-FAPI and tumor immunity was analyzed. Mouse cohorts of metastatic CRC were treated with TGF-β receptor (TGF-βR) inhibitor combined with KN046 which blocks PD-L1 and CTLA4, followed with 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses. RESULTS. Patients with metastatic CRC demonstrated high uptakes of 68Ga-FAPI, along with suppressive tumor immunity and poor prognosis. TGF-βR inhibitor enhanced tumor infiltrating T cells and significantly sensitized metastatic CRC to KN046. 68Ga-FAPI PET/CT imaging accurately monitored the dynamical changes of CAFs and tumor response to combined TGF-βR inhibitor with immunotherapy. CONCLUSION. 68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to stratify and guide patients with CRC for precise TGF-β inhibition plus immunotherapy, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.

2023-12-19 | GSE247303 | GEO

Glucose metabolic profiles evaluated by PET associated with molecular characteristic landscape of gastric cancer

Project description:Although FDG-PET is widely used in cancer, its role in gastric cancer (GC) is still controversial due to variable [18F]fluorodeoxyglucose ([18F]FDG) uptake. Here, we investigate the molecular landscape of GC and its association with glucose metabolic profiles noninvasively evaluated by [18F]FDG PET. Based on a genetic signature, PETscore, representing [18F]FDG avidity, was developed by imaging data acquired from thirty patient-derived xenografts (PDX). Five genes, PLS1, PYY, HBQ1, SLC6A5, NAT16, were identified for the PETscore, which was validated in independent cohorts by qRT-PCR and RNA-sequencing. By applying the PETscore on the Cancer Genome Atlas (TCGA), a significant association between glucose uptake and tumor mutational burden as well as genomic alterations was identified in GC. Our findings suggest that molecular characteristics are underlying the diverse metabolic profiles of GC. Diverse glucose metabolic profiles may apply to precise diagnostic and therapeutic approaches for GC.

2022-04-05 | GSE164961 | GEO

Glucose partitioning in the bone marrow micro-environment in acute myeloid leukaemia [bulk RNA-seq]

Project description:We used a positron emission tomography (PET) tracer 18F fluorodeoxyglucose ([18F]-FDG) and transcriptomic analysis to detect glucose uptake by cells in the bone marrow micro-environment with an MLL-AF9-induced mouse model. Leukaemic cells had the greatest glucose uptake. To determine whether glucose uptake is driven by intrinsic demand, we applied RNA-seq of sorted leukaemia cells (GFP+) and bone marrow micro-environment myeloid cells (GFP-CD11b+) from the MLL-AF9 transduced mouse model.

2023-04-14 | GSE227581 | GEO

Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis

Project description:Analysis of transcriptional differences between HIV infected persons with evidence of latent tuberculosis (TB) infection by Quantiferon Gold-in-tube, with and without evidence of subclinical TB disease on FDG-PET/CT scan. Tuberculosis is classically divided into two clinical states: latent infection and active disease. One-quarter of the global population is considered latently infected but diagnostic tests poorly predict the small proportion that will progress to disease. We recruited 35 asymptomatic, HIV-1 infected adults with latent TB by current diagnostic criteria, who underwent [18F]-fluoro-2-deoxy-D-glucose positron emission/computed tomography; ten had pulmonary abnormalities consistent with subclinical disease and were significantly more likely to progress. As positive control, we recruited 15 HIV-1 infected adults with symptomatic microbiologically confirmed active pulmonary TB, age, sex and CD4 matched to the 35 participants undergoing FDG-PET/CT. By whole-blood transcriptomic profiling we characterised 82-transcripts distinguishing those with subclinical pathology from those without. Transcripts representing the classical complement pathway were overabundant in both subclinical and active TB. We have demonstrated that latent TB is not a homogenous condition and defined a distinct high-risk subgroup with evidence of subclinical disease. These findings point the way to the future development of more predictive diagnostic tests.

2018-01-01 | GSE69581 | GEO

Transcriptome of human white and brown adipose tissue biopsies

Project description:We analyzed coding transcript abundance in paired biopsies of white and brown adipose tissue obtained from the supraclavicular region of 15 healthy subjects. In a prior experiment measuring 18F-deoxyglucose uptake by PET-CT, 9 subjects displayed active brown fat and 6 did not.

2018-07-06 | GSE113764 | GEO

mRNA therapy restores ureagenesis and corrects glutathione metabolism in argininosuccinic aciduria

Project description:Argininosuccinate lyase (ASL) is a key enzyme integral to the hepatic urea cycle which is required for ammonia detoxification, and the citrulline-nitric oxide (NO) cycle for NO production. ASL deficient patients present with argininosuccinic aciduria (ASA), an inherited metabolic disease with hyperammonaemia and a chronic systemic phenotype with neurocognitive impairment and chronic liver disease. ASL deficiency as an inherited model of systemic NO deficiency, shows enhanced nitrosative and oxidative stress. Here, we describe the dysregulation of glutathione biosynthesis and upstream cysteine utilization in ASL-deficient patients and mice using targeted metabolomics and in vivo positron emission tomography (PET) imaging using (S)-4-(3-18F-fluoropropyl)-L-glutamate ([18F]FSPG). Upregulation of cysteine metabolism contrasted with glutathione depletion and down-regulated antioxidant pathways. hASL mRNA encapsulated in lipid nanoparticles corrected and rescued the neonatal and adult Asl-deficient mouse phenotypes, respectively, enhancing ureagenesis and glutathione metabolism and ameliorating chronic liver disease. We further present [18F]FSPG PET as a novel non-invasive diagnostic tool to assess liver disease and therapeutic efficacy in ASA. These findings support clinical translation of mRNA therapy for ASA.

2023-01-31 | GSE222874 | GEO

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