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ABSTRACT:
PROVIDER: PRJNA170718 | ENA |
REPOSITORIES: ENA
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Project description:In order to clarify the molecular mechanism involved in renal carcinogenesis, and identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes.
2012-07-16 | GSE39364 | 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:Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. To better understand the biology of this tumor, we analyze the miRNA expression profiles of a set of CCPRCC by microarrays.
2017-02-28 | GSE95385 | GEO
Project description:In order to clarify the molecular mechanism involved in renal carcinogenesis, and identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes. Tissue samples of surgically-resected clear cell renal cell carcinoma (ccRCC) and their corresponding clinical information were obtained from patients with written informed consent. The total of 15 cancer patients (6 women and 9 men; median age, 66; range, 36-75 years) that had been confirmed histologically as ccRCC were selected for this study. Two to three pieces of cancer tissue had been taken from each patient at the time of radical nephrectomy. Normal tissue had been obtained from the distant region from cancer area in the resected kidney tissue. These samples were immediately embedded in TissueTek OCT compound (Sakura, Tokyo, Japan), frozen, and stored at -80°C. The frozen tissues were sliced into 8-μm sections using a cryostat (Sakura) and then stained with H&E for histological examination. We used LMM technology to collect pure populations of ccRCC cells as well as non-cancerous renal cortex. A mixture of normal renal cortex cells in kidney tissues from 11 patients was prepared as a universal control. Experiments were performed using 6 sets of slides (slide set 1-6 corresponding to ID_REF 1-27648).
2012-07-15 | E-GEOD-39364 | biostudies-arrayexpress
Project description:Aberrant DNA methylation is common in cancer. To associate DNA methylation with gene function, we performed RNAseq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients. To quantify 5mC and 5hmC level in each CG site at genome-wide level, we performed BS-seq and TAB-seq upon tumor tissue and matched normal tissues of two ccRCC (clear cell renal cell carcinoma) patients, respectively. mRNA profiles of tumor and matched normal tissues from two ccRCC patients were generated by deep sequencing, using Hiseq 2000. Single-nucleotide-resolution, whole-genome, 5mC and 5hmC profiles of tumor and matched normal tissues from two ccRCC (clear cell renal cell carcinoma) patients were generated by deep sequencing, using Hiseq 2000.
2016-02-29 | E-GEOD-63183 | biostudies-arrayexpress
Project description:Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinomas (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC.
2014-11-06 | GSE63002 | GEO
Project description:Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinomas (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC.
2014-11-06 | GSE63001 | GEO
Project description:Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinomas (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC.
2014-11-06 | GSE63000 | GEO
Project description:Identifying mRNA targets of microRNA in clear cell renal cell carcinoma
| PRJNA116271 | ENA
Project description:The ubiquitin proteasome system governs a wide spectrum of cellular events and offers therapeutic opportunities for pharmacological intervention in cancer treatment. Renal clear cell carcinoma represents the predominant histological subtype and accounts for the majority of cancer death related to kidney malignancies. Through a systematic survey in the association of human ubiquitin-specific proteases with patient prognosis of renal clear cell carcinoma and subsequent phenotypic validation, we uncovered the tumor-promoting role of USP35. Biochemical characterizations confirmed the stabilizing effects of USP35 towards multiple members of the IAP family in an enzymatic activity-dependent manner. USP35 silencing led to reduced expression levels of IAP proteins, which were accompanied with increased cellular apoptosis. Further transcriptomic analysis revealed that USP35 knockdown altered expression levels of NRF2 downstream transcripts, which were conferred by compromised NRF2 abundance. USP35 functions to maintain NRF2 levels by catalyzing its deubiquitylation and thus antagonizing degradation. NRF2 reduction imposed by USP35 silencing rendered renal clear cell carcinoma cells increased sensitivity to ferroptosis induction. Finally, induced USP35 knockdown markedly attenuated xenograft formation of renal clear cell carcinoma in nude mice. Hence, our findings identify a number of USP35 substrates and reveal the protecting role of USP35 against both apoptosis and ferroptosis in renal clear cell carcinoma.
2023-06-17 | GSE216154 | GEO