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Low-dose whole liver hyperfractionated radiation in diffuse liver metastasis of breast and colorectal cancer, application of low-dose hyper-radiosensitivity theory

ABSTRACT: Interventions: Case series:Radiotherapy Primary outcome(s): size of lesion of liver metastasis Study Design: Case series

DISEASE(S): Diffuse Liver Metastasis Of Breast Or Colorectal Cancer

PROVIDER: 2671194 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Prophylactical Low Dose Whole-Liver Irradiation Inhibited Colorectal Liver Metastasis by Regulating Hepatic Niche in Mice.

Project description:BackgroundThe liver is the most common target for metastatic colorectal cancer. Changes of the local hepatic niche due to hepatic diseases such as cirrhosis decrease the incidence of colorectal cancer liver metastasis. Hepatic niche heterogeneity could influence the risk of hepatic metastasis.Materials and methodsWe simulated changes of the hepatic niche via prophylactical liver irradiation with a safe dose of 6 Gy. GEO dataset and GO analysis revealed a difference in the expression of matrix metalloproteinase 1 (MMP1) in primary colorectal cancer versus liver metastasis, as well as synchronous versus metachronous liver metastasis. Western blotting, Immunofluorescence and qRT-PCR were conducted to measure protein expressions, location and RNA expressions. Colony formation, wound-healing, transwell assays experiments were performed to determine the malignant biological properties of colorectal cancer cells. shRNA transfection was used to conduct stable transfected cell lines.ResultsTissue inhibitor of metalloproteinases 1 (TIMP1) expression was significantly higher in metastases lesions than primary tumors. In vivo, TIMP1 expression in the hepatic niche increased after a safe dose of 6 Gy irradiation, along with MMP1 decreased, leading to collagen fiber deposition and impairment of hepatic microcirculation. In vitro, irradiated hepatic stellate cells-conditioned media reduced the migration and clone formation ability of colon cancer cells SW480 and HCT116. Low TIMP1 expression in hepatic stellate cells reduced tumor cell invasion and migration.ConclusionProphylactical 6 Gy whole-liver irradiation could inhibit colorectal cancer liver metastasis by regulating TIMP1/MMP1 balance in the hepatic niche before liver metastatic lesion formed.

| S-EPMC7455754 | biostudies-literature

Clinical research for the application of DWI, ctDNA to predict the outcomes after liver tumor alblation

Project description:Interventions: Case series:microwave ablation Primary outcome(s): ctDNA Study Design: Single arm

| 2689023 | ecrin-mdr-crc

Neurobehavioral effects of acute low-dose whole-body irradiation.

Project description:Radiation exposure has multiple effects on the brain, behavior and cognitive functions. It has been reported that high-dose (>20 Gy) radiation-induced behavior and cognitive aberration partly associated with severe tissue destruction. Low-dose (<3 Gy) exposure can occur in radiological disasters and cerebral endovascular treatment. However, only a few reports analyzed behavior and cognitive functions after low-dose irradiation. This study was undertaken to assess the relationship between brain neurochemistry and behavioral disruption in irradiated mice. The irradiated mice (0.5 Gy, 1 Gy and 3 Gy) were tested for alteration in their normal behavior over 10 days. A serotonin (5-HT), Dopamine, gamma-Aminobutyric acid (GABA) and cortisol analysis was carried out in blood, hippocampus, amygdala and whole brain tissue. There was a significant decline in the exploratory activity of mice exposed to 3 Gy and 1 Gy radiation in an open field test. We observed a significant short-term memory loss in 3 Gy and 1 Gy irradiated mice in Y-Maze. Mice exposed to 1 Gy and 3 Gy radiation exhibited increased anxiety in an elevated plus maze (EPM). The increased anxiety and memory loss patterns were also seen in 0.5 Gy irradiated mice, but the results were not statistically significant. In this study we observed that neurotransmitters are significantly altered after irradiation, but the neuronal cells in the hippocampus were not significantly affected. This study suggests that the low-dose radiation-induced cognitive impairment may be associated with the neurochemical in low-dose irradiation and unlike the high-dose scenario might not be directly related to the morphological changes in the brain.

| S-EPMC8438260 | biostudies-literature

Application of personalized plasma ctDNA detection in dynamic monitoring of recurrence after resection of colorectal cancer liver metastases.

Project description:Interventions: Case series:closely follow-up after blood collection Primary outcome(s): RFS Study Design: Sequential

| 2696089 | ecrin-mdr-crc

Project description:cefepime-zidebactam case series

| PRJNA1174875 | ENA

Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow.

Project description:Results are presented of a feasibility study of three-dimensional X-ray tomographic mammography utilising in-line phase contrast. Experiments were performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic phantom and a mastectomy sample containing a malignant lesion were used to study the reconstructed image quality as a function of different image processing operations. Detailed evaluation and optimization of image reconstruction workflows have been carried out using combinations of several advanced computed tomography algorithms with different pre-processing and post-processing steps. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. A number of objective image quality indices have been applied for quantitative evaluation of the results, and these were compared with subjective assessments of the same images by three experienced radiologists and one pathologist. The outcomes of this study provide practical guidelines for the optimization of image processing workflows in synchrotron-based phase-contrast mammo-tomography.

| S-EPMC4541534 | biostudies-other

Clinical application of CT-guided percutaneous microwave ablation for the treatment of lung metastasis from colorectal cancer

Project description:Interventions: Case series:microwave ablation Primary outcome(s): Local tumor response;survival Study Design: Case series

| 2671120 | ecrin-mdr-crc

Wide-scale transcriptome disturbance underlies liver and kidney pathology from chronic ultra low dose Roundup exposure

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-09-04 | E-GEOD-66060 | biostudies-arrayexpress

Application of SNP-array for the detection of genomic rearrangements responsible for sindromic mental retardation of unknown cause

Project description:Developmental delay/intellectual disability (DD/ID)affects 2% of our population. However, mostpatients are often leftwithout aspecific diagnosis,with thecorresponding consequences for the patientsand their families. The application of microarray technology in the study of patients with DD/ID allows whole-genome analysis with a high resolutionand performance. Here we present the results of a case included in a series of 246 patients with DD/ID, as part of the screening of the genetic causes responsible for their phenotype.

2014-10-17 | GSE62438 | GEO

Low and High Dose Progestins Elicit Distinct Breast Cancer Biology

Project description:An incomplete understanding of dose-dependent progesterone receptor (PR) biology has led to the suboptimal exploitation of PR as a therapeutic target. While hormone replacement therapies (HRT) containing low-doses of synthetic progestogens (progestins) have been associated with an increased risk of breast cancer, high-dose progestin therapies have beneficial therapeutic effects in some patients with breast cancer. Herein we report that PR subcellular localization, post-trans3lational modifications, stability, chromatin binding, responsive gene expression and downstream biology differ considerably as a function of progestin concentration. Dose-dependent transcriptional profiling revealed that different concentrations of progestin elicit classic sigmoidal and/or biphasic gene induction at distinct target gene sets. Notably, when compared to high doses of progestin, low-dose treatments lead to minimal nuclear translocation of PR while supporting robust induction of a subset of target genes, indicating that PR occupancy has a complex relationship to target gene induction. Interestingly, high but not low-dose progestin treatments lead to increased phosphorylation at Ser294 and is associated with higher receptor turnover. Furthermore, while low-dose treatments stimulate cell proliferation, high-dose treatments do not result in significant cell cycle progression to S phase. Similar biphasic and sigmoidal patterns of gene induction were observed in human breast tumor explants treated with various concentrations of progestin, underscoring the need to fine tune the dosage of PR-targeting therapies. Given the wide range of medical applications of PR target therapy, our discovery of distinct dose-dependent PR biology may have important clinical implications.

2020-06-13 | GSE99986 | GEO

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