Biomedical subjects

Z Ronai

Publications and source records attributed to Z Ronai.

116 records · Page 7Linked to original sources

PubMed1992

ras oncogene detection in pre-neoplastic lesions: possible applications for diagnosis and prevention.

The development of methodologies for the early detection of genetic mutations is an important issue in the prevention and treatment of malignancy. Current knowledge of the association of specific genetic alterations with the development of certain types of tumors enables us to approach the early detection of cancer long before histologic or pathologic evidence indicates the development of neoplastic tumor growth. The identification of genetic alterations as biological markers allows for early diagnosis, which in turn may dictate a particular regimen of treatment to prevent subsequent tumor development. This commentary presents an evaluation of the current status of procedures for the early detection of mutations in the ras oncogene family and their relevance to diagnosis and prevention of neoplastic disease.

Alleles↗

PubMed1991

Dietary N-3 fatty acids do not affect induction of Ha-ras mutations in mammary glands of NMU-treated rats.

The purpose of this study was to determine whether dietary n-3 polyunsaturates (PUFA) can affect the frequency of N-nitrosomethylurea (NMU)-induced Ha-ras mutations in virgin female F344 rat mammary glands. Two groups of 15 rats each were fed isocaloric diets containing either 23% w/w corn oil or corn oil plus menhaden oil (1:1) at starting 14 d before NMU administration (day 50 of age) and continuing for 13 wk. Mammary gland samples were taken serially at 3, 5, 9, and 13 wk post-NMU treatment. Total cellular DNA was isolated and analyzed by a newly devised enriched amplification procedure that involves predigestion of normal Ha-ras alleles at codon 12, amplification of the mutant alleles, and restriction fragment length polymorphism analysis. Selective amplification enabled the detection of Ha-ras mutations as early as 3 wk post-NMU treatment. Approximately 40-50% of all glands and 75% of all rats tested had the Ha-ras codon 12 mutation. No significant differences were found between the two dietary groups at any time point, indicating that the mammary tumor-inhibiting effect of n-3 PUFA is probably not exerted at the level of the Ha-ras activation step in NMU tumorigenesis.

Animals↗

PubMed1991

Rapid and sensitive nonradioactive detection of mutant K-ras genes via 'enriched' PCR amplification.

We have developed a rapid and highly sensitive nonradioactive method for the detection of a mutant codon 12 human c-K-ras allele in the presence of as many as 10(4) copies of the wild type codon 12 allele. This sensitivity is achieved by selective polymerase chain reaction (PCR) amplification of mutant K-ras gene sequences employing a two stage procedure. The first stage entails the amplification of both K-ras mutant and wild type codon 12 sequences, followed by a selective restriction enzyme digestion of only wild type sequences. The second stage involves a subsequent amplification of undigested amplified fragments, enriched in mutant codon 12 sequences. These products are subject to restriction length polymorphism analysis for the detection of point mutations at codon 12. This technique is rapid, nonradioactive, and eliminates the need for either oligonucleotide hybridization or DNA sequencing. Variations of this selective amplification procedure may prove promising for the detection of specific point mutations in heterogenous cell populations.

Adenocarcinoma↗

PubMed1990

Polyoma DNA replication dependent upon growth condition of SEWA sarcoma cells.

Extrachromosomal replication of viral DNA sequences has been observed in transformed as well as in normal cells following "stress"-inducing treatments. To explore the effect of growth conditions on the ability to support such replication, we analyzed SEWA sarcoma cells that grew subcutaneously or as ascites tumors in vivo as well as cell lines that were established from each of these tumors. The replicative form of polyoma DNA sequences was observed in SEWA tumors grown in ascites fluids but not in cells maintained as solid tumors. Polyoma DNA replication was found in ascites-derived cells that were adapted to grow in culture, only when the cultured cells are stimulated with UV irradiation. Immunoprecipitation of T antigens enabled detection of large T antigen only in the ascites-derived cells. The mechanisms that may regulate this phenomenon and the possible role large T may play in different growth conditions of SEWA cells are discussed.

Animals↗

PubMed1986

Serial circulating immune complex values and development of metastatic disease in breast cancer and malignant melanoma patients.

A polyethylene glycol precipitation technique was used to determine the levels of circulating immune complexes (CIC) in breast cancer and melanoma patients. All patients in the study had undergone surgery and were free of distant metastatic disease. CIC were measured at two to four time intervals, of 3 to 6 months each, over an average follow-up period of 13.5 months (range 7-20 months). In both groups of patients, metastatic disease developed with a higher frequency in patients who had undetectable CIC levels throughout the follow-up period or had become negative at the time metastases were discovered.

Antigen-Antibody Complex↗

PubMed1986

(Auto)antibodies in human breast cancer sera against antigens associated with breast cancer cells, detected by immunoblotting.

Sera of patients with breast cancer (as well as control normal sera and sera of patients with ovarian cancer or melanoma) were screened for the presence of antibodies against antigens expressed by the MDA breast cancer cell line. The techniques employed were radioimmunoassay with radioiodinated protein A and immunodotting with peroxidase-conjugated anti-human immunoglobulin antibodies. Sera reacting strongly by immunodotting were subsequently tested against antigens of the MDA and T47D cell lines in immunoblotting experiments. Both the breast cancer and the control sera yielded highly complex band patterns, which varied from serum to serum. The cancer sera differed from the normal sera, however, as they produced in most cases one or several bands that were distinctly stronger than the others. One of the strong bands, in fact a doublet of approximately 50 kilodaltons (kd), was produced preferentially (although not exclusively) when breast cancer sera were reacted with T47D cell membrane antigens. Absorption of selected sera with normal tissue or MDA antigens abolished or greatly reduced the intensity of some of the bands. It is concluded that, with the possible exception of the 50-kd band, most (probably all) of the bands seen in immunoblots resulted from the binding of autoantibodies to normal antigens expressed by the breast cancer cell lines. The main difference between cancer and normal sera would seem to be an increased content of autoantibodies in cancer, the specificity of these autoantibodies varying, however, from serum to serum.

Antigens, Neoplasm↗

PubMed1983

Anti-red blood cell autoantibodies induced in rat by Plasmodium berghei infection bind to a cross-reacting determinant present also in other cell types.

It has been previously shown that rats injected with red blood cells (RBC) infected with Plasmodium berghei make autoantibodies reacting with normal rat RBC as demonstrated by a staphylococcal protein A binding assay. In this study, the serum of the infected rats was found to contain also antibodies to several other types of rat cells (lymphoid, liver, and kidney cells and brain tissue) as well as against RBC and lymphoid cells of mice and sheep, but not of man. Rat, mouse, and sheep RBC and rat and mouse lymphocytes absorbed completely the antibodies to rat RBC, suggesting that a single, cross-reacting determinant might be involved in these reactions.

Absorption↗

PubMed1981

Autoantibodies to red blood cells in rats infected with Plasmodium berghei.

A radio-iodinated Protein A (125SPA) binding assay was used to identify autoantibodies to red blood cells (RBC's) in sera of rats infected with Plasmodium berghei. Sera taken from rats at various times after infection were reacted with washed, normal RBC's, then the RBC's were washed and treated with 125SPA. The bound radioactivity was taken as a measure of the amount of Ig attached to the RBC's membranes. Using this test, anti-RBC autoantibodies were detected in rat sera as early as 5 days after infection. The level of the autoantibodies rose to a maximum at 12 to 14 days, at which time parasitemia was also maximal, then declined sharply. Autoantibodies were still detectable at 21 days after infection. Red blood cells from infected rats had readily detectable, membrane-bound Ig, as shown by their capacity to bind 125SPA directly. The amount of this Ig rose and fell in a fashion closely paralleling course of parasitemia.

Animals↗