Renal cell carcinoma

Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, responsible for approximately 90–95% of cases. RCC occurrence shows a male predominance over women with a ratio of 1.5:1. RCC most commonly occurs between 6th and 7th decade of life. Initial treatment is most commonly either partial or complete removal of the affected kidney(s). Where the cancer has not metastasised (spread to other organs) or burrowed deeper into the tissues of the kidney, the five-year survival rate is 65–90%, but this is lowered considerably when the cancer has spread. The body is remarkably good at hiding the symptoms and as a result people with RCC often have advanced disease by the time it is discovered. The initial symptoms of RCC often include blood in the urine (occurring in 40% of affected persons at the time they first

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Yap1 Activation Enables Bypass of Oncogenic Kras Addiction in Pancreatic Cancer

Shan Jiang, Anguraj Sadanandam

Activating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible Kras(G12D) driven mouse model of PDAC has established a critical role for sustained Kras(G12D) expression in tumor maintenance, providing a model to determine the potential for and the underlying mechanisms of Kras(G12D)-independent PDAC recurrence. Here, we show that some tumors undergo spontaneous relapse and are devoid of Kras(G12D) expression and downstream canonical MAPK signaling and instead acquire amplification and overexpression of the transcriptional coactivator Yap1. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving Kras(G12D)-independent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models, portend a novel mechanism of escape from oncogenic Kras addiction in PDAC.

Cell Press2014

Role of Bicaudal-C in Left-Right Axis Formation and Kidney Morphogenesis

Charlotte Maisonneuve

The KH domain RNA binding protein Bicaudal-C is known to play a role in anterior-posterior (AP) patterning in Drosophila by acting on oskar mRNA. In mammals, its expression is induced at late gastrulation in the mesodermal layer of the ventral node. Renal cysts arise in mice and frogs lacking Bicaudal-C. Polycystic diseases and left-right (LR) axis malformations are frequently linked to cilia defects. However, a role for BicC in cilia function has not been demonstrated. Here, I report that targeted inactivation of BicC confirms a role in inducing polycystic kidney disease (PKD). In addition, this targeted mutation was found to randomize left-right (LR) asymmetry by disrupting the planar alignment of motile cilia required for cilia-driven fluid flow. Furthermore, depending on its SAM domain, BicC can uncouple Dvl2 signaling from the canonical Wnt pathway, which has been implicated in antagonizing planar cell polarity (PCP). The SAM domain is shown to concentrate BicC in cytoplasmic structures harboring RNA-processing bodies (P-bodies) and Dvl2. P-bodies are implicated degrading target mRNAs that are silenced by microRNAs. These results suggest a model whereby BicC links the orientation of cilia to PCP, possibly by regulating RNA silencing in P-bodies. In the kidney, BicC is localized in proximal tubules. The cystic phenotype is accompanied by increased levels of cAMP and of Adcy6 protein. BicC is proposed to inhibit target mRNA at the translation-initiation stage by regulating the assembly of miRNP/P-bodies.

EPFL2010

Gene Expression Profile of Peripheral Blood Lymphocytes from Renal Cell Carcinoma Patients Treated with IL-2, Interferon-α and Dendritic Cell Vaccine

Benita Wolf

Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma (mRCC) who received combined treatment with IL-2, interferon-?-2a and dendritic cell vaccine. We examined gene expression, cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry (FCM). Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors (HD). PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and T(REG)-cell activation pathways, which was also reflected in lymphocyte subset distribution. Overall, PBL gene expression post-treatment (POST) was not significantly different than pre-treatment (PRE). Nevertheless, treatment related changes in gene expression (post-treatment minus pre-treatment) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding (R) patients compared to non-responding (NR) patients. In addition, we observed down-regulation of T(REG)-cell pathways post-treatment in R vs. NR patients. While exploratory in nature, this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy. This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC.

Public Library of Science2012

Kidney cancer

Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, lump in the abdomen, or back pain. Fever, weig

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A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have

Cancer

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spr

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