Ontology highlight
ABSTRACT:
PROVIDER: PRJNA493178 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7903883.fastq.gz | Fastqsanger.gz | |||
| SRR7903884.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The clinical response to sunitinib in advanced renal-cell carcinoma (RCC) is frequently limited in magnitude and duration due to drug resistance, but the underlying mechanisms remain elusive. To discover mechanisms of resistance, we developed drug-resistant cell lines and have their gene expressions profiled and compared. Results provide insight into the molecular mechanisms underlying sunitinib-resistance.
2016-09-30 | GSE69535 | 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.
2024-09-02 | BIOMD0000000908 | BioModels
Project description:Renal cell carcinoma (RCC) represents about 2-3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC with good or intermediate prognosis. However, about one third of metastatic RCC patients do not respond to sunitinib, leading to disease progression. Here we aim to find and characterize proteins associated with poor sunitinib response in a pilot proteomics study. 16 RCC tumors from patients responding (8) vs. non-responding (8) to sunitinib in 3 months after treatment initiation, together with their adjacent non-cancerous tissues, were analyzed using data independent acquisition mass spectrometry. Proteomics analysis quantified 1996 protein groups (q<0.01) and revealed 27 proteins deregulated between tumors non-responding vs. responding to sunitinib, representing a pattern of deregulated proteins potentially contributing to sunitinib resistance. Gene set enrichment analysis showed up-regulation of epithelial-to-mesenchymal transition with transgelin as one of the most significantly abundant protein. Transgelin expression was silenced by CRISPR/Cas9 and RNA interference, and the cells with reduced transgelin level exhibited significantly slower proliferation. Our data indicate that transgelin is an essential protein supporting RCC cell proliferation which could contribute to intrinsic sunitinib resistance.
2021-11-03 | PXD027065 | Pride
Project description:To investigate the function FUS in the regulation of sunitinib-resistance， we used lentiviral transduction to knock down FUS expression in the sunitinib-resistant RCC cells.
2023-03-31 | GSE226245 | GEO
Project description:Recently, immune checkpoint inhibitors (ICIs) have been approved as first line and second-line therapies for individuals with advanced renal cell carcinoma (RCC) who developed a resistance to anti-angiogenic therapies. It remains unknown how ICIs efficacy is affected by the development of resistance to anti-angiogenic inhibitors. Thus, our goal is to evaluate transcriptomic and metabolic effects after ICI therapy of sunitinib-resistant RCC and compare the efficacy of ICIs between naïve and sunitinib-resistant RCC.
2025-01-01 | GSE216495 | GEO
Project description:Sunitinib is a TKI inhibitor used for managing metastatic renal cell carcinoma (RCC). However, chronic sunitinib treatment in RCC usually results in the development of drug resistance via alternating phosphorylation dynamics. On the other hand, 17-beta-estradiol, or estrogen, has been demonstrated to repress RCC growth partly through regulating cell signallings. To investigate how estrogen can repress sunibitinib-resistant RCC growth and its the possible mechanism of action related protein phosphorylation, a label-free quantitative phosphoproteomics study is performed.
2020-08-07 | PXD011020 | Pride
Project description:The tyrosine kinase inhibitor sunitinib is an effective first-line treatment for patients with advanced renal cell carcinoma (RCC). Hypothesizing that a functional read-out by mass spectrometry-based (phospho, p-)proteomics will identify predictive biomarkers for treatment outcome of sunitinib, tumor tissues of 26 RCC patients were analyzed. Eight patients were primary resistant (RES) and 18 sensitive (SENS).
2024-01-26 | PXD043514 | Pride
Project description:VHL mutations are the most common tumorigenic lesions in clear cell renal cell carcinoma (ccRCC) and result in continued activation of the HIF/VEGF pathway and uncontrolled cancer progression. Receptor tyrosine kinase (RTK) inhibitors such as sunitinib have been demonstrated to target tumorigenic signaling pathways, delay tumor progression and improve patient prognosis in metastatic renal cell carcinoma (mRCC). Although several mechanisms of sunitinib resistance have been reported, the solutions to overcome this resistance remain still unclear. In our study, we found that increased expression of YB1 (Y box binding protein 1, a multidrug resistance associated protein) and EphA2 (a member of erythropoietin-producing hepatocellular (Eph) receptors, belonging to the RTK family) mediated sunitinib resistance and mRCC exhibited a large phenotypic dependence on YB1 and EphA2. In addition, our findings confirm that YB1 promotes the invasion, metastasis and sunitinib resistance of ccRCC by regulating the EphA2 signaling pathway. Furthermore, pharmacological inhibition of EphA2 through the small molecule inhibitor ALW-II-41-27 reduced the proliferation of sunitinib-resistant tumor cells and suppressed tumor growth in vivo and restored the sensitivity of sunitinib-resistant tumor cells to sunitinib in vitro and in vivo. Mechanistically, YB1 increases the protein levels of EphA2 by maintaining the protein stabilization of EphA2 through inhibiting the proteasomal degradation pathway. Collectively, our findings provide the theoretical rationale that ccRCC metastasis and RTK-directed therapeutic resistance could be prospectively and purposefully targeted.
2020-05-28 | GSE151336 | GEO
Project description:Generation of a new library of targeted mass spectrometry assays for accurate protein quantification in malignant and normal kidney tissue. Aliquots of primary tumor tissue lysates from 86 patients with initially localized renal cell carcinoma (RCC), 75 patients with metastatic RCC treated with sunitinib or pazopanib in the first line and 17 adjacent normal tissues treated at Masaryk Memorial Cancer Institute (MMCI) in Brno, Czech Republic, or University Hospital Pilsen (UHP), Czech Republic, were used to generate the spectral library. Two previously published datasets (dataset A and B) and two newly generated RCC datasets (dataset C and D) were analyzed using the newly generated library showing increased number of quantified peptides and proteins, depending on the size of the library and LC-MS/MS instrumentation. This PRIDE project also includes quantitative analysis results for all four datasets and raw files for dataset C and D. Dataset A is characterized in DOI: 10.1038/nm.3807. It consists of 18 samples from 9 RCC patients involving one cancer and non-cancerous sample per patient. Dataset B is characterized in DOI: 10.3390/biomedicines9091145. It consists of 16 tumor samples and 16 adjacent normal tissues from 16 mRCC patients treated at Masaryk Memorial Cancer Institute (MMCI) in Brno, Czech Republic. Dataset C involves only tumor tissues from dataset B. Half of them responded to sunitinib treatment in the first line three months after treatment initiation and half did not. Dataset D involves 16 RCC patients treated at University Hospital Pilsen (UHP), Czech Republic. All were localized at the time of initial diagnosis, half of the tumors developed distant metastasis in five years after the diagnosis.
2022-01-03 | PXD028411 | Pride
Project description:Despite sunitinib contributes to prolong the progression-free survival of metastatic renal cell carcinoma significantly, the universal presence of resistance limits the initial response rate and restricts durable responses. The mechanisms involved in sunitinib resistance vary and need further investigation. We found lncRNA CCAT1 overexpressed in sunitinib resistant cells while declined in the parental cells. Moreover, lncRNA CCAT1 increased significantly in samples with resistance to sunitinib compared to those with responses to sunitinib. Impoverishment of CCAT1 suppressed cell growth and colony formation while triggered apoptosis. Inversely, the ectopic expression of c-Myc reversed the inhibition of cell growth and enhancement of apoptosis by sh-CCAT1. We also verified that anti-apoptosis protein Bcl-2 and Mcl-1 decreased along with the deregulation of CCAT1, whereas the expression of Bcl-2 and Mcl-1 restored in cells those were transfected sh-CCAT1 and c-Myc simultaneously. Apart from the in vitro experiments, we demonstrated that knockdown of CCAT1 boosted response to sunitinib by performing sunitinib-resistant ACHN mouse models. Briefly, lncRNA CCAT1 conferred renal cell carcinoma resistance to sunitinib in a c-Myc-dependent manner, providing novel target for improvement of sunitinib therapy.
2020-03-15 | GSE146305 | GEO