Project description:TFEB has been recently reported to be a key molecule for lysosomal regulation. Renal cell carcinoma (RCC) with t(6;11) (p21;q12) is known to be the only tumor in which TFEB is upregulated. Transcriptome analysis using a whole-genome expression array and pathway analysis using upregulated genes in tumor tissue revealed that the lysosome-associated pathways were significantly deregulated. Total RNA was extracted from non-tumor and tumor in patient of renal cell carcinoma with t(6;11) (p21;q12) and subjected to gene expression microarray analysis.
Project description:TFEB has been recently reported to be a key molecule for lysosomal regulation. Renal cell carcinoma (RCC) with t(6;11) (p21;q12) is known to be the only tumor in which TFEB is upregulated. Transcriptome analysis using a whole-genome expression array and pathway analysis using upregulated genes in tumor tissue revealed that the lysosome-associated pathways were significantly deregulated.
Project description:We established patient-derived organoids and monolayer culture cells from the salivary gland cancer cases. To compare the RNA profiles of primary culture cells (Organoids and monolayer culture cells) and their parental tumors, we isolated total RNA from 2 cases of the salivary gland cancer and performed transcriptome sequencing for the organoids, monolayer culture cells, and their parental tumors of both cases. Case 6 is a case of adenoid cystic carcinoma and Case 11 is a case of salivary duct carcinoma.
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.
Project description:We report a case of a 55 years old women who present a ALK associated renal cell carcinoma, with 3p deletion and measling of TFE3 expression. With CGH analysis and FISH we identify the rearrangment of ALK with TPM3
Project description:the dataset contains RNA bam files of Renal Cell Carcinoma patients, which belongs to "An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors"
Project description:MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy. Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis.
Project description:Both N6-methyladenosine (m6A) mediates RNA fates and ubiquitin mediates protein fates play an important role in either physiology or pathology including cancer, yet how long noncoding RNAs (lncRNAs) are involved in a link of molecular fate between m6A and ubiquitin remains unknown. Here, we reveal a role for a lncRNA Downregulated RNA in Cancer (DRAIC) to suppress tumor growth and metastasis in clear cell Renal Carcinoma (ccRCC). Mechanistically, DRAIC physically interacts with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and enhances its protein stability by blocking E3 ligase F-box protein 11 (FBXO11)-mediated ubiquitin and proteasome-dependent degradation. Subsequently, hnRNPA2B1 destabilizes m6A modified-type 1 insulin-like growth factor receptor (IGF1R) to lead to inhibition of ccRCC progression. Moreover, four m6A modification sites of IGF1R are identified and results in its mRNA degradation. Collectively, our findings reveal that DRAIC/hnRNPA2B1 axis regulates IGF1R mRNA expression in an m6A-dependent manner and highlights an important mechanism of IGF1R fate. These findings shed light on DRAIC/hnRNPA2B1/FBXO11/IGF1R axis as potential therapeutic targets in ccRCC and build a link of molecular fate between m6A-modified RNA and ubiquitin-modified protein.
Project description:Both N6-methyladenosine (m6A) mediates RNA fates and ubiquitin mediates protein fates play an important role in either physiology or pathology including cancer, yet how long noncoding RNAs (lncRNAs) are involved in a link of molecular fate between m6A and ubiquitin remains unknown. Here, we reveal a role for a lncRNA Downregulated RNA in Cancer (DRAIC) to suppress tumor growth and metastasis in clear cell Renal Carcinoma (ccRCC). Mechanistically, DRAIC physically interacts with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and enhances its protein stability by blocking E3 ligase F-box protein 11 (FBXO11)-mediated ubiquitin and proteasome-dependent degradation. Subsequently, hnRNPA2B1 destabilizes m6A modified-type 1 insulin-like growth factor receptor (IGF1R) to lead to inhibition of ccRCC progression. Moreover, four m6A modification sites of IGF1R are identified and results in its mRNA degradation. Collectively, our findings reveal that DRAIC/hnRNPA2B1 axis regulates IGF1R mRNA expression in an m6A-dependent manner and highlights an important mechanism of IGF1R fate. These findings shed light on DRAIC/hnRNPA2B1/FBXO11/IGF1R axis as potential therapeutic targets in ccRCC and build a link of molecular fate between m6A-modified RNA and ubiquitin-modified protein.