Renal cell carcinoma characterized

Tremoiada, L, Magni, F., Valsecchi, C., Sarto, C., Mocarelli, P., Perego, R., Cordani, N., Favini, P., Galli Kienle, M., Sanchez, J. C., et al. (2005). Characterization of heat shock protein 27 phosphorylation sites in renal cell carcinoma. Proteomics 5, 788-795. 

Naito, S., Kanamori, T. and Hisano, S. (1982). Human renal cell carcinoma establishment and characterization of two new cell lines. J. Urol. 128, 1117-1121. 

Three interleukins (ILs) are in use for renal cell carcinoma and malignant melanoma (IL-2), cutaneous T-cell lymphoma (denileukin), and thrombocytopenia associated with cancer chemotherapy (IL-11). These interleukins are protein products that can cause substantial multiorgan toxicity, especially cardiovascular, and limit their full clinical usefulness, which characterizes most interleukins. Denileukin is a fusion protein of IL-2 and diphtheria toxin (Table 9). 

IL-2 has been used in the treatment of sohd tumors such as metastatic melanoma, metastatic renal cell carcinoma, and colorectal carcinoma. Interleukin-2 infusions are associated with significant dose-dependent toxicity characterized by fevers, malaise, nausea, vomiting, diarrhea, hepatic dysfunction, pulmonary edema, somnolence, confusion, dysrhythmias, myocardial infarction, hematopoietic suppression, and renal insufficiency [10]. IL-2 has a short serum half-life of 6-10 min and a clearance of 30-60 min after bolus intravenously infusion [11]. Resultant toxicity is generally transient and reversible. It is possible that IL-2 induced renal failure only occurs in the setting of profound hypotension, prior volume depletion, concurrent administration of potentially nephrotoxic drugs, or the presence of underlying renal disease. 

Polycythemia is characterized by an increase in the number, and in the hemoglobin content, of circulating red cells. In patients who have chronic anoxia from impaired pulmonary ventilation or congenital or acquired heart disease, the increase in plasma erythropoietin leads to secondary polycythemia. Some renal cell carcinomas, hepatocarcinomas, and other tumors, which produce physiologically inappropriate amounts of erythropoietin, may also cause secondary polycythemia. Conversely, anemia can result from renal insufficiency and from chronic disorders that depress erythropoietin production. In polycythemia vera (primary polycythemia), which is a malignancy of erythrocyte stem cells of unknown cause, erythropoietin levels are normal or depressed. 

Eurge KA, Dykema K, Petillo D, et al. Combining diffetential expression, chromosomal and pathway analyses fot the molecular characterization of renal cell carcinoma. Can Urol Assoc J. 2007 1 S21. 

Induction of iNOS in human cell types and tissues has been difficult to characterize. Although multiple cell types in humans can be induced to express iNOS mRNA, the degree of activation is less robust than that seen in rodent cells. In vivo evidence of the relevance of iNOS in health and disease is provided by the work of Hibbs et al. (1992). IL-2 chemotherapy for malignant melanoma and renal cell carcinoma produces a septic-shock-like state that is associated with activation of the L-arginine-NO signaling pathway. Why cells derived from rodents and humans differ in their responsiveness is not clear. A working hypothesis is that the promoter for human iNOS is under tighter transcriptional control and/or less active compared to that in the mouse or the rat. 

Selection of a number of cases from patient subsets in a given microarray slide is amenable to statistical modeling to enhance analysis of results. Different microarrays can be constructed to answer different scientific questions. The microarrays can also be produced from archival material, using paraffin blocks of already characterized tumors with clinical follow-up. This would provide a rapid evaluation of clinically well-characterized tumors. The viability of this approach has been tested with prostate carcinomas, renal cell carcinomas, and other tumors (5,6). 

Von Hippel-Lindau disease (VHL) is an autosomal dominant condition secondary to an alteration in a tumor suppressor gene on chromosome 3. It has incomplete penetrance and is characterized by hemangioblastomas in the retina, CNS, renal cell carcinoma, endolymphatic sac tumors, pheochro-mocytomas, papillary cystadenoma of the epididymis, angiomas of the liver and kidney, cysts of the liver, kidney and epididymis, and pulmonary arteriovenous shunts (Fig. 4.18a-c). In the pancreas, VHL may have multiple presentations, the most common being the presence of multiple small pancreatic cysts with calcifications in 40% of cases. Serous cystad-enomas, solid nonfunctional islet cell tumors, and adenocarcinoma are less common (Richard et al. 2004). 

Hyper-vascular tumors such as islet cell tumors and certain hyper-vascular (renal cell carcinoma) metastases will often appear hyper-attenuating on the pancreatic phase which allows for better characterization of these tumors (Fig. 3.11). 

Most renal masses can be characterized with high accuracy by noninvasive imaging alone, and a sohd non-fat-containing or complex renal mass should be considered a renal cell carcinoma until proven otherwise. Metas-tases to the kidney are usually small and multifocal or perinephric. Lymphomatous involvement of the kidneys also usually occurs in the setting of disseminated disease and is characterized by typical CT patterns like multiple small masses, spread from retroperitoneal disease, diffuse infiltration, and perinephric encasement. In a study by Lechevallier et al. (2000), CT-guided renal biopsy of 63 patients had an overall accuracy of 89%. Biopsy material was not sufficient for analysis in 15 patients (21%). Unsuccessful biopsy was related to lesion size biopsy was unsuccessful in 11 of 30 tumors (37%) of 3 cm or less, versus 4 of 43 (9%) of tumors greater than 3 cm. 

KIM-1 is a type I cell membrane glycoprotein which contains, in its extracellular portion, a six-cysteine immunoglobulin-like domain, two N-glycosylation sites, and a T/SP-rich domain characteristic of mucin-like O-glycosylated proteins. The ectodomain of KlM-1 is shed from cells in vitro and in vivo into the urine in rodents and humans after proximal tubular kidney injury or in patients with renal cell carcinoma. KlM-1 confers on epithelial cells the ability to recognize and phagocytose dead cells that are present in the postischemic kidney and contribute to the obstmction of the tubule lumen that characterizes acute kidney injiuy. In... 

T. Cancer, G. Atlas, Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499 (2013) 43-49. 

Acute exposure to unleaded gasoline and a variety of light hydrocarbons present in gasoline produces a nephropathy in male rats characterized by (1) an excessive accumulation of protein (hyaline droplets) in epithelial cells of proximal tubule, (2) accumulation of casts at the corticomedullary junction, and (3) evidence of mild tubular regeneration. This nephropathy only occurs in male rats female rats and mice do not show any renal pathology. A number of chemicals present in unleaded petrol when tested alone have been shown to produce nephropathy and, in particular 2,2,4-trimethylpentane and decalin have been used as model compounds. Certain other industrial chemicals (1,4-dichlorobenzene and isophorone), natural products (o-limonene), and pharmaceuticals (levamisole) also produce this male-rat-specific nephropathy. Chronic exposure of male rats to unleaded petrol, 1,4-dichlorobenzene, isophorone, or o-limonene ultimately leads to the induction of a low incidence of renal adenomas and carcinomas. 

Matsuda M, Osafune M, Nakano E, Kotake T, Sonoda T, Watanabe S, Hada T, Okashi T, Higashino K, Yamamura Y, Abe T. Characterization of an established cell line from human renal carcinoma. Cancer Res 1979 39 4694-4699. 

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