We here describe the isolation, characterization, profile of lymphokine expression and T-cell-receptor gene rearrangement pattern of 444P.3, a CD3+ CD4+ CD8- 4B4+ interleukin-2 (IL-2)-dependent clone derived from the malignant ascites of a patient with renal cell cancer.
In three cases of bladder cancer c-ras mutations were found, at codons 13 and 61 of c-Ha-ras and at codon 61 of c-Ki-ras, while no mutation was found in kidney cancer.
On the other hand, tumor cells were characterized by loss of der(3), supporting the hypothesis that loss of a specific 3p segment is associated with the development of renal cancer.
On the other hand, tumor cells were characterized by loss of der(3), supporting the hypothesis that loss of a specific 3p segment is associated with the development of renal cancer.
Two criteria suggest that primary multidrug resistance in human adenocarcinomas of the kidney results, at least in part, from expression of the mdr1 gene: (1) mdr1 mRNA levels are elevated in four unselected kidney adenocarcinoma cell lines that show a multidrug-resistant phenotype; and (2) multidrug resistance in these kidney cancer cell lines is reversed by verapamil and quinidine, agents known to reverse mdr1-associated drug resistance in cell lines selected for multidrug resistance in vitro.
Two criteria suggest that primary multidrug resistance in human adenocarcinomas of the kidney results, at least in part, from expression of the mdr1 gene: (1) mdr1 mRNA levels are elevated in four unselected kidney adenocarcinoma cell lines that show a multidrug-resistant phenotype; and (2) multidrug resistance in these kidney cancer cell lines is reversed by verapamil and quinidine, agents known to reverse mdr1-associated drug resistance in cell lines selected for multidrug resistance in vitro.
On average, the level of expression of Nm23 mRNA in short-term cultures of benign proximal renal tubular cells was found to be similar to the level seen in renal cancer cell lines.
Expression of NAD(P)H:quinone oxidoreductase and glutathione S-transferases alpha and pi in human renal cell carcinoma and in kidney cancer-derived cell lines.
These results suggest that, while the primary disease gene for kidney cancer appears to be on chromosome 3, abnormalities of p53 are common and may be involved in the progression of this malignancy.
However, the methylation change is the only one of the 17p abnormalities which occurs at a high incidence in early-stage renal cancers (hypermethylation, 50%; 17p allelic loss, 13%; p53 mutations, 0%).
Summarizing these results, it seems unlikely that p53 gene alterations will serve as an important new factor for the clinical prognosis of patients with renal-cell cancer.