E-TABM-90
Ontology highlight
ABSTRACT:
PROVIDER: E-TABM-90 | ExpressionAtlas | 2015-07-29
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:The majority of patients tolerate radiotherapy well, but some of them suffer from severe side effects. To find genes possibly predictive for radiosensitivity, mRNA profiles were generated before and 6 h after in vitro irradiation with 5 Gy. We analyzed lymphocytes from four head and neck and eight breast cancer patients with strong acute radiation toxicity and from 12 matching normal reacting patients in a blind study. In peripheral blood lymphocytes of all patients, 153 genes were identified which were statistically significantly altered by a fold change of more than 50% by irradiation. Pathway analysis revealed genes involved in p53 signalling, cell cycle control and apoptosis in response to radiation in primary lymphocytes. In these cells, a set of 67 radiation-induced genes was identified capable of differentiating between severe radiosensitive and normal reacting patients. More than one third of such classifying genes belong to the group of apoptosis or cell cycle regulating genes. Total RNA obtained from lymphocytes of cancer patients with strong acute radiation toxicity and from matching normal reacting patients were compared 6 hours after in vitro irradiation with 5 Gy.
2012-09-06 | E-GEOD-40640 | biostudies-arrayexpress
Project description:Peripheral blood lymphocytes from a total of 57 patients were immortalized with Epstein-Barr virus. Fourteen radiation-therapy patients suffered unusual levels of radiation toxicity (RadS). Thirteen radiation-therapy patients with limited toxicity (RadC) were enrolled as controls. Fifteen patients diagnosed with skin cancer before age 40 (SkCa) were used as a second group of controls. Fifteen healthy subjects without any history of cancer (NoCa) were matched to the skin cancer patients and used as a third group of controls. Cells were exposed to mock treatment (Mock), ultra-violet radiation (UV), or ionizing radiation (IR). For UV radiation treatment, cells were exposed to 10 J/m^2 and harvested for RNA 24 hours later. For IR treatment, cells were exposed to 5 Gy of IR and harvested for RNA 4 hours later. For example, RadS1-Mock refers to cells from radiation sensitive patient 1 exposed to mock treatment. The published manuscript (PNAS 101:6634, 2004) can be found at http://www.pnas.org/cgi/doi/10.1073/pnas.0307761101; Data were analyzed with Affymetrix MAS version 4.0. Normalization â?? A reference data set was generated by averaging the expression of each gene over all data sets. The data for each hybridization were compared with the reference data set in a cube root scatter plot. A linear least-squares fit to the cube root scatter plot was then used to normalize each hybridization.
2007-08-05 | E-GEOD-1725 | biostudies-arrayexpress
Project description:Purpose: Severe late normal tissue damage limits radiotherapy treatment regimens. This study aims to validate γ-H2AX foci decay ratios and induced expression levels of DNA double strand break (DSB) repair genes, found in a retrospective study, as possible predictors for late radiation toxicity. Methods and Materials: Prospectively, decay ratios (initial/residual γ-H2AX foci numbers) and genome-wide expression profiles were examined in ex vivo irradiated lymphocytes of 198 prostate cancer patients. All patients were followed ≥2 years after radiotherapy, clinical characteristics were assembled and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. Results: No clinical factors were correlated with late radiation toxicity. Analysis of γ-H2AX foci uncovered a negative correlation between the foci decay ratio and toxicity grade. Significantly smaller decay ratios were found in grade≥3 compared to grade 0 patients (p=0.02), indicating less efficient DNA-DSB repair in radio-sensitive patients. Moreover, utilizing a foci decay ratio threshold determined in our previous retrospective study correctly classified 23 of the 28 grade≥3 patients (sensitivity, 82%) and 9 of the 14 grade 0 patients (specificity, 64%). Grade of toxicity also correlated with a reduced induction of the homologous recombination (HR) repair gene-set. The difference in average fold induction of the HR gene-set was most pronounced between grade 0 and grade≥3 patients (p=0.008). Conclusions: Reduced responsiveness of HR repair genes to irradiation and inefficient DSB repair correlate with an increased risk of late radiation toxicity. Using a decay ratio classifier, we could correctly classify 82% of the patients with grade≥3 toxicity. Additional studies are required to further optimize and validate the foci decay assay and to assess its predictive value for late radiation toxicity in patients prostate cancer
2017-01-30 | GSE85570 | GEO
Project description:Mathematical modeling of regulatory T cell effects on renal cell carcinoma treatment
Lisette dePillis 1, , Trevor Caldwell 2, , Elizabeth Sarapata 2, and Heather Williams 2,
1.
Department of Mathematics, Harvey Mudd College, Claremont, CA 91711
2.
Harvey Mudd College, Claremont, CA 91711, United States, United States, United States
Abstract
We present a mathematical model to study the effects of the regulatory T cells (Treg) on Renal Cell Carcinoma (RCC) treatment with sunitinib. The drug sunitinib inhibits the natural self-regulation of the immune system, allowing the effector components of the immune system to function for longer periods of time. This mathematical model builds upon our non-linear ODE model by de Pillis et al. (2009) [13] to incorporate sunitinib treatment, regulatory T cell dynamics, and RCC-specific parameters. The model also elucidates the roles of certain RCC-specific parameters in determining key differences between in silico patients whose immune profiles allowed them to respond well to sunitinib treatment, and those whose profiles did not.
Simulations from our model are able to produce results that reflect clinical outcomes to sunitinib treatment such as: (1) sunitinib treatments following standard protocols led to improved tumor control (over no treatment) in about 40% of patients; (2) sunitinib treatments at double the standard dose led to a greater response rate in about 15% the patient population; (3) simulations of patient response indicated improved responses to sunitinib treatment when the patient's immune strength scaling and the immune system strength coefficients parameters were low, allowing for a slightly stronger natural immune response.
Keywords: Renal cell carcinoma, mathematical modeling., sunitinib, immune system, regulatory T cells.
2020-01-06 | BIOMD0000000908 | BioModels
Project description:Peripheral blood lymphocytes from a total of 57 patients were immortalized with Epstein-Barr virus. Fourteen radiation-therapy patients suffered unusual levels of radiation toxicity (RadS). Thirteen radiation-therapy patients with limited toxicity (RadC) were enrolled as controls. Fifteen patients diagnosed with skin cancer before age 40 (SkCa) were used as a second group of controls. Fifteen healthy subjects without any history of cancer (NoCa) were matched to the skin cancer patients and used as a third group of controls. Cells were exposed to mock treatment (Mock), ultra-violet radiation (UV), or ionizing radiation (IR). For UV radiation treatment, cells were exposed to 10 J/m^2 and harvested for RNA 24 hours later. For IR treatment, cells were exposed to 5 Gy of IR and harvested for RNA 4 hours later. For example, RadS1-Mock refers to cells from radiation sensitive patient 1 exposed to mock treatment. The published manuscript (PNAS 101:6634, 2004) can be found at http://www.pnas.org/cgi/doi/10.1073/pnas.0307761101 Data were analyzed with Affymetrix MAS version 4.0. Normalization – A reference data set was generated by averaging the expression of each gene over all data sets. The data for each hybridization were compared with the reference data set in a cube root scatter plot. A linear least-squares fit to the cube root scatter plot was then used to normalize each hybridization. Keywords = Gene expression in lymphoid cells of cancer patients Keywords: repeat sample
2004-09-06 | GSE1725 | GEO
Project description:Study goal is to disclose features of gene expressio profile of non-cancerous liver-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas and tumor-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas. Keywords: gene expression profile, non-cancerous liver-infiltrating lymphocytes, tumor-infiltrating lymphocytes, type C hepatitis, hepatocellular carcinoma Non-cancerous liver-infiltrating lymphocytes were obtained by laser capture microdissection from surgically resected liver tissues of 12 type C hepatitis patients with hepatocellular carcinoma. The mRNA was amplified and expression profile was comprehensively analyzed with reference RNA using oligo-DNA chip. Tumor-infiltrating lymphocytes were obtained by laser capture microdissection from surgically resected cancer tissues of 12 type C hepatitis patients with hepatocellular carcinoma. The mRNA was amplified and expression profile was comprehensively analyzed with reference RNA using oligo-DNA chip.
2010-06-25 | E-GEOD-10461 | biostudies-arrayexpress
Project description:Prostate cancer is the second most occurring cancer in men worldwide, and with the advances made with screening for prostate-specific antigen, it has been prone to early diagnosis and over-treatment. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. The model includes pathways such as androgen receptor, MAPK, Wnt, NFkB, PI3K/AKT, MAPK, mTOR, SHH, the cell cycle, the epithelial-mesenchymal transition (EMT), apoptosis and DNA damage pathways. The final model accounts for 133 nodes and 449 edges. We applied a methodology to personalise this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients, using TCGA and GDSC datasets.
2022-06-22 | MODEL2106070001 | BioModels
Project description:The majority of patients tolerate radiotherapy well, but some of them suffer from severe side effects. To find genes possibly predictive for radiosensitivity, mRNA profiles were generated before and 6 h after in vitro irradiation with 5 Gy. We analyzed lymphocytes from four head and neck and eight breast cancer patients with strong acute radiation toxicity and from 12 matching normal reacting patients in a blind study. In peripheral blood lymphocytes of all patients, 153 genes were identified which were statistically significantly altered by a fold change of more than 50% by irradiation. Pathway analysis revealed genes involved in p53 signalling, cell cycle control and apoptosis in response to radiation in primary lymphocytes. In these cells, a set of 67 radiation-induced genes was identified capable of differentiating between severe radiosensitive and normal reacting patients. More than one third of such classifying genes belong to the group of apoptosis or cell cycle regulating genes.
2012-09-06 | GSE40640 | GEO
Project description:Post-operative radiation therapy (PORT) is the standard treatment for patients with head and neck squamous cell carcinoma (HNSCC) having adverse pathological features. Despite PORT, many patients develop relapse causing morbidity and mortality. These specimens are from a high-risk cohort of such patients treated by PORT and are being used to develop gene signatures for therapeutic response.
2022-03-16 | GSE67614 | GEO
Project description:The aim of this study was to assess the relationship between gene expression profiles of ex vivo 2 Gy radiated lymphocytes and the development of acute and late toxicity due to hyperfractionated dose-escalation radiation therapy schedule in patientes with advanced breast cancer. The gene expression profiles of ex vivo non-radiated lymphocytes were also examined. Keywords: Toxicity grade analysis. Twelve patients were analyzed. No replicates of each patient was assesed. Human RNA universal control (Stratagene) was used as reference.
2010-05-18 | E-GEOD-15341 | biostudies-arrayexpress