View clinical trials related to Neoplasms, Adipose Tissue.
Filter by:The aim of this project is to study the presence of cancer-associated adipocytes in oesogastric cancers and their possible links with myosteatosis. This research project has a retrospective component, the aim of which is to analyse the body component based on imaging in patients with oesogastric neoplasia in order to determine the incidence of myosteatosis and to study the relationship with oncological and prognostic data. The second part of the project is prospective and will collect biological material (skeletal muscle, adipose tissue, tumour, blood) for histological, molecular and genomic analyses and will analyse muscle function in patients with oesogastric cancer. It will address the role of adipocytes in the tumour microenvironment of oesogastric cancer, focusing on their interactions with the observed muscle myosteatosis and prognosis. In the future, it will help to identify signalling pathways, targets and patients who could benefit from appropriate treatment.
The study participant has been diagnosed with non-rhabdomyosarcoma (NRSTS). Primary Objectives Intermediate-Risk - To estimate the 3-year event-free survival for intermediate-risk patients treated with ifosfamide, doxorubicin, pazopanib, surgery, and maintenance pazopanib, with or without RT. - To characterize the pharmacokinetics of pazopanib and doxorubicin in combination with ifosfamide in intermediate-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and pazopanib and doxorubicin pharmacokinetics. High-Risk - To estimate the maximum tolerated dose (MTD) and/or the recommended phase 2 dosage (RP2D) of selinexor in combination with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib in high-risk participants. - To characterize the pharmacokinetics of selinexor, pazopanib and doxorubicin in combination with ifosfamide in high-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and selinexor, pazopanib and doxorubicin pharmacokinetics. Secondary Objectives - To estimate the cumulative incidence of primary site local failure and distant metastasis-free, disease-free, event-free, and overall survival in participants treated on the risk-based treatment strategy defined in this protocol. - To define and describe the CTCAE Grade 3 or higher toxicities, and specific grade 1-2 toxicities, in low- and intermediate-risk participants. - To study the association between radiation dosimetry in participants receiving radiation therapy and the incidence and type of dosimetric local failure, normal adjacent tissue exposure, and musculoskeletal toxicity. - To evaluate the objective response rate (complete and partial response) after 3 cycles for high-risk patients receiving the combination of selinexor with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib. - To assess the relationship between the pharmacogenetic variation in drug-metabolizing enzymes or drug transporters and the pharmacokinetics of selinexor, pazopanib, and doxorubicin in intermediate- or high-risk patients. Exploratory Objectives - To explore the correlation between radiographic response, pathologic response, survival, and toxicity, and tumor molecular characteristics, as assessed through next-generation sequencing (NGS), including whole genome sequencing (WGS), whole exome sequencing (WES), and RNA sequencing (RNAseq). - To explore the feasibility of determining DNA mutational signatures and homologous repair deficiency status in primary tumor samples and to explore the correlation between these molecular findings and the radiographic response, survival, and toxicity of patients treated on this protocol. - To explore the feasibility of obtaining DNA methylation profiling on pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to assess the correlation with this and pathologic diagnosis, tumor control, and survival outcomes where feasible. - To explore the feasibility of obtaining high resolution single-cell RNA sequencing of pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to characterize the longitudinal changes in tumor heterogeneity and tumor microenvironment. - To explore the feasibility of identifying characteristic alterations in non-rhabdomyosarcoma soft tissue sarcoma in cell-free DNA (cfDNA) in blood as a non-invasive method of detecting and tracking changes during therapy, and to assess the correlation of cfDNA and mutations in tumor samples. - To describe cardiovascular and musculoskeletal health, cardiopulmonary fitness among children and young adults with NRSTS treated on this protocol. - To investigate the potential prognostic value of serum cardiac biomarkers (high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro B-type natriuretic peptide (NT-Pro-BNP), serial electrocardiograms (EKGs), and serial echocardiograms in patients receiving ifosfamide, doxorubicin, and pazopanib, with or without selinexor. - To define the rates of near-complete pathologic response (>90% necrosis) and change in FDG PET maximum standard uptake value (SUVmax) from baseline to week 13 in intermediate risk patients with initially unresectable tumors treated with induction pazopanib, ifosfamide, and doxorubicin, and to correlate this change with tumor control and survival outcomes. - To determine the number of high-risk patients initially judged unresectable at diagnosis that are able to undergo primary tumor resection after treatment with ifosfamide, doxorubicin, selinexor, and pazopanib. - To identify the frequency with which assessment of volumes of interest (VOIs) of target lesions would alter RECIST response assessment compared with standard linear measurements.
The main objective of this project is to identify a new non-invasive biological test for the diagnosis of LPS by measuring circulating serine levels. The current gold standard is the detection of Mdm2 amplification by the FISH.
The obesity epidemic has resulted in an exponential increase in obesity-related disorders including type 2 diabetes, dyslipidemia and cardiovascular disease. The associated morbidity and mortality have major consequences both at an individual as well as on the socioeconomical level. Thus, the development of novel therapies aimed at reducing the development of obesity is highly warranted. Brown adipose tissue (BAT) recently emerged as a novel player in energy expenditure in humans as it combusts fatty acids towards heat. Interestingly, obese subjects have less BAT as compared to lean subjects and activation of BAT by means of intermittent cold exposure reduces fat mass. Therefore, BAT is considered a promising novel target to reduce obesity and associated disorders. As cold exposure is not the most desired therapeutic strategy for humans, current pre-clinical research focuses on pharmacological activation of BAT. Interestingly, the investigators have recently shown that central agonism of the receptor for the incretin hormone glucacon-like peptide-1 (GLP-1) results in activation of BAT in mice. One of the currently used anti-diabetic drugs that enhances GLP-1 availability is Sitagliptin (STG). Interestingly, STG also reduces body weight and plasma triglyceride (TG) levels in type 2 diabetes mellitus (T2DM) patients. The mechanism underlying these beneficial metabolic effects is currently unknown. The investigators hypothesize that STG enhances BAT activation, thereby increasing energy expenditure and combustion of TG-derived fatty acids, resulting in lowering of plasma TG levels and body weight. To this end, the investigators will perform a randomized double-blinded placebo-controlled study in which 30 male Dutch Caucasian adults aged 35-50 years with moderate obesity and pre-diabetes are included. Subjects will be treated for 12 weeks with STG or placebo. Before and after treatment, the investigators will determine BAT volume and total BAT activity via cold-induced 18F-FDG PET-CT scans, resting energy expenditure via indirect calorimetry using ventilated hoods, body weight, and body composition via DEXA scan. Furthermore, before and after treatment, blood samples will be taken to measure plasma lipids, glucose and insulin levels. This study will offer valuable novel insight in the effects of pharmacological activation of BAT in human obese subjects.