Homo sapiens
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PROVIDER: PRJNA321029 | ENA |
REPOSITORIES: ENA
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Project description:Global cellular biological processes governed by MET amplification
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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.
2024-09-02 | BIOMD0000000908 | BioModels
Project description:Understanding the biological processes of clear cell renal carcinoma carcinogenesis: an integrative multi-omics approach.
| PRJNA1120468 | ENA
Project description:The lack of effective treatment optionsfor advanced non-clear cell renal cell carcinoma (NCCRCC) is a critical unmet clinical need. Applying a high throughput drug screen to multiple human kidney cancer cells, weidentified the combination of the VEGFR-MET inhibitor cabozantinib and the SRC inhibitor dasatinib acted synergistically in cells to markedly reduce cell viability. Importantly, the combination was well tolerated and caused tumor regression in vivo. Transcriptional and phosphoproteomic profilingrevealed that the combination converged to downregulate the MAPK-ERK signaling pathway, a result not predicted by single agent analysis alone. Correspondingly, the addition of a MEK inhibitor synergized with either dasatinib or cabozantinibto increase its efficacy. This study, by employing approved, clinically relevant drugs provides the rationale for the design of effective combination treatments in NCCRCC that can be rapidly translated to the clinic.
2021-04-02 | GSE171358 | GEO
Project description:This study uses a drug called dasatinib to produce an anti-cancer effect called large granular lymphocyte cellular expansion. Large granular lymphocytes are blood cells known as natural killer cells that remove cancer cells. Researchers think that dasatinib may cause large granular lymphocyte expansion to happen in patients who have received a blood stem cell transplant (SCT) between 3 to 15 months after the SCT. In this research study, researchers want to find how well dasatinib can be tolerated, the best dose to take of dasatinib and how to estimate how often large granular lymphocytic cellular expansion happens at the best dose of dasatinib.
| 2128801 | ecrin-mdr-crc
Project description:This study uses a drug called dasatinib to produce an anti-cancer effect called large granular lymphocyte cellular expansion. Large granular lymphocytes are blood cells known as natural killer cells that remove cancer cells. Researchers think that dasatinib may cause large granular lymphocyte expansion to happen in patients who have received a blood stem cell transplant (SCT) between 3 to 15 months after the blood SCT. In this research study, researchers want to find how well dasatinib can be tolerated, the best dose to take of dasatinib and to estimate how often large granular lymphocytic cellular expansion happens at the best dose of dasatinib.
| 2126216 | ecrin-mdr-crc
Project description:We investigated the changes in gene expression accompanying the development and progression of kidney cancer using 31,500 element complementary DNA arrays. We measured expression profiles for paired neoplastic and non-cancerous renal epithelium samples from 37 individuals. Using an experimental design optimized for factoring out technological and biological noise, and an adapted statistical test, we find 1738 differentially expressed cDNAs with an expected number of 6 false positives. Functional annotation of these genes provided views of the changes in the activities of specific biological pathways in renal cancer. Cell adhesion, signal transduction, and nucleotide metabolism were among the biological processes with a large proportion of genes overexpressed in renal cell carcinoma. Downregulated pathways in the kidney tumor cells included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Our expression profiling data uncover gene expression changes shared with other epithelial tumors, as well as a unique signature for renal cell carcinoma. Expression data for the differentially expressed cDNAs are available in the web supplement (http://www.dkfz-heidelberg.de/abt0840/whuber/rcc). Keywords = renal clear cell carcinoma, kidney Keywords: other
2001-07-19 | GSE3 | GEO
Project description:Cellular and molecular characterization of renal cell carcinoma
| PRJNA671296 | ENA
Project description:Cellular and molecular characterization of renal cell carcinoma
| PRJNA671297 | ENA
Project description:Global transcriptional analysis of renal cell carcinoma cells.
| PRJDB8377 | ENA