methylnitronitrosoguanidine and Carcinoma--Renal-Cell
methylnitronitrosoguanidine has been researched along with Carcinoma--Renal-Cell* in 3 studies
Reviews
1 review(s) available for methylnitronitrosoguanidine and Carcinoma--Renal-Cell
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Adjuvant therapy for renal cell carcinoma: past, present, and future.
At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials. Topics: Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Methylnitronitrosoguanidine; Molecular Targeted Therapy; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A | 2014 |
Other Studies
2 other study(ies) available for methylnitronitrosoguanidine and Carcinoma--Renal-Cell
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Renal cell carcinoma development in the rat independent of alterations at the VHL gene locus.
Germline alterations of the human von Hippel-Lindau (VHL) tumor suppressor gene predispose to renal cell carcinoma and a constellation of other tumor types found in VHL disease. This gene is also mutated or deleted in a high proportion of sporadic nonpapillary renal cell carcinomas. In the Eker rat model, spontaneous renal cell carcinoma develops with a high frequency. We therefore investigated the role of this tumor suppressor gene in the development of these hereditary rat tumors. By using reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis, the sequence of the rat VHL gene was determined over the portion of the gene homologous to regions where most mutations in the human VHL gene occur. The sequence homology was 90% and the amino-acid identity 99% between the rat and human genes. A developmental and tumor-specific pattern of expression for the VHL gene was found; a ubiquitous 3.2-kb transcript was expressed in all rat tissues examined (neonatal kidney, lung, liver, brain, heart, kidney, spleen, testis, and stomach), and an additional 4.5-kb transcript was expressed in neonatal kidney and cell lines derived from Eker rat renal cell carcinomas (ERC cell lines). To determine whether mutations in the VHL gene were involved in tumor development in the Eker model, RT-PCR, single-strand conformation polymorphism (SSCP) analysis, and direct sequencing were used to search for alterations in this gene in the ERC cell lines. Alterations in the VHL gene were not detected by SSCP, and these data were confirmed by direct sequencing. Transformed rat kidney epithelial cell lines derived from Fisher rats also expressed the VHL gene but like the ERC cell lines did not contain mutations in the VHL gene. These data indicate that in the rat, transformation of kidney epithelial cells and the development of solid, nonpapillary renal cell carcinoma can occur via pathways that are independent of alterations at the VHL gene locus. Topics: Animals; Animals, Newborn; Base Sequence; Blotting, Northern; Carcinoma, Renal Cell; Cell Line; DNA; Gene Expression; Genes, Tumor Suppressor; Humans; Kidney Neoplasms; Ligases; Mesothelin; Mesothelioma; Methylnitronitrosoguanidine; Mice; Molecular Sequence Data; Mutation; Organ Specificity; Polymerase Chain Reaction; Protein Biosynthesis; Proteins; Rats; Rats, Inbred F344; Rats, Mutant Strains; Sequence Homology, Nucleic Acid; Transcription, Genetic; Tumor Cells, Cultured; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Von Hippel-Lindau Tumor Suppressor Protein | 1996 |
Increased susceptibility to in vitro transformation of cells carrying the Eker tumor susceptibility mutation.
Rats carrying the Eker tumor susceptibility mutation are genetically predisposed to renal cell carcinoma. Rats heterozygous for the Eker mutation (Eker carriers) develop multiple bilateral renal cell carcinomas by the age of 1 year. Using an in vitro rat kidney epithelial (RKE) transformation assay developed in our laboratory, proximal tubule cells derived from known Eker rat carriers (+/ek) and non-carriers (+/+) were exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), to determine if cells derived from Eker carriers were more susceptible to in vitro transformation than cells derived from non-carrier animals. The percent transformation frequency following MNNG treatment was 7.5-fold higher in cells derived from carrier animals when compared to cells from non-carrier animals. This increased susceptibility to transformation due to inheritance of the Eker mutation is consistent with a predisposition resulting from inactivation of a tumor suppressor gene. The increased susceptibility of kidney epithelial cells carrying the Eker mutation may prove useful in the further development of the RKE transformation assay as a sensitive tool to identify potential renal carcinogens. In addition, because transformation frequency in the RKE assay measures a very early step in multistage transformation, these results also suggest that alterations (by Loss of Heterozygosity or mutation) at the Eker tumor susceptibility locus are an early event in the development of renal tumors in the rat. Topics: Animals; Carcinoma, Renal Cell; Cell Transformation, Neoplastic; Cocarcinogenesis; Epithelial Cells; Epithelium; Female; Kidney Neoplasms; Kidney Tubules; Male; Methylnitronitrosoguanidine; Mutation; Rats; Rats, Mutant Strains | 1994 |