Biomedical subjects

E Gabrielson

Publications and source records attributed to E Gabrielson.

42 records · Page 3Linked to original sources

PubMed1994

Homozygous deletion on chromosome 9p and loss of heterozygosity on 9q, 6p, and 6q in primary human small cell lung cancer.

We analyzed the pattern of allelic loss in 33 primary human small cell lung cancers (SCLCs) using highly informative microsatellite markers on chromosomes 2p, 3p, 5q, 6, 9, 13q, and 17p. Nineteen of these tumors (58%) displayed loss of heterozygosity on chromosome 9. Fourteen SCLCs demonstrated loss of heterozygosity for all informative markers on both chromosomal arms; two tumors demonstrated partial loss on chromosome 9p. In one tumor, a multiplex polymerase chain reaction assay disclosed a homozygous deletion at 9p21-22 including the markers IFN-alpha, D9S126, and D9S171. Two SCLCs retained all informative markers on 9p but showed allelic loss of the entire 9q arm, while one case had a partial loss of proximal 9q extending into all of 9p. Analysis of other chromosomal arms showed loss of heterozygosity on 3p (93%), 5q (75%), 6p (46%), 6q (47%), 13q (75%), and 17p (93%). It was necessary to test multiple markers at several loci because of the frequent expression of microsatellite instability that confounded our mapping efforts in SCLCs with replication errors. This study demonstrates the frequent loss of a suppressor gene locus on chromosome 9p21-22 and identifies novel suppressor loci on 6p, 6q, and 9q in primary SCLC.

Adult↗

PubMed1994

Frequent microsatellite instability in primary small cell lung cancer.

Alterations in microsatellite sequences characterize hereditary nonpolyposis colorectal cancer. This microsatellite instability is due in some kindreds to a germline mutation of the mismatch repair gene hMSH2 on chromosome 2p. Although microsatellite alterations have been reported in other hereditary nonpolyposis colorectal cancer-associated tumors including endometrial and gastric cancers, such changes were not detected in most other major neoplasms. We found that 15 of 33 (45%) primary small cell lung cancers, tumors not found in the hereditary nonpolyposis colorectal cancer syndrome, displayed alterations of microsatellite loci which consisted of deletions or expansions of (CA)n dinucleotide repeats. In 8 of these 15 neoplasms, microsatellite instability was detected in more than 10% of all tested alleles. However, small cell lung cancers that revealed instability contained widespread allelic loss and had a uniformly poor prognosis. These results expand considerably the known spectrum of tumors with microsatellite instability.

Adult↗

PubMed1994

Frequent loss of chromosome 9 in human primary non-small cell lung cancer.

We analyzed the pattern of allelic loss on chromosome 9 in 40 primary human non-small cell lung cancers including 16 squamous cell, 18 adeno-, and 6 large cell carcinomas. Using 24 polymorphic microsatellite markers spanning chromosome 9, we found that 27 of 40 (67.5%) of these neoplasms displayed loss of heterozygosity (LOH) on chromosome 9. Most tumors showed LOH for all informative markers on both chromosomal arms, whereas five tumors demonstrated partial LOH on chromosome 9. In four of these tumors, allelic loss was limited to the 9p arm, whereas in the remaining specimen, LOH extended from 9p21-22 to terminal 9q. These five tumors delineate a minimal area of loss at 9p21-22, which includes a previously defined tumor suppressor gene locus. We have identified a distinct region of loss on chromosome 9p commonly involved in non-small cell lung cancer tumorigenesis.

Aged↗

PubMed1994

Oxidant stress responses in human pleural mesothelial cells exposed to asbestos.

The generation of oxidants is a proposed mechanism of cell injury by asbestos fibers. To determine whether human pleural mesothelial cells (HMC) respond to asbestos and active oxygen species (AOS) by induction of antioxidant enzymes, cells obtained from pleural effusion were exposed to crocidolite or chrysotile asbestos or xanthine/xanthine oxidase (X/XO), a chemical-generating system of AOS. Gene expression of manganese-containing superoxide dismutase (MnSOD) and heme oxygenase (HO), endogenous enzymes involved in cell defense against oxidant stresses, was then determined. Dosage-dependent increases in steady-state mRNA levels of MnSOD and HO were observed in HMC exposed to asbestos or X/XO. However, increases in gene expression of MnSOD or HO did not occur in HMC after exposure to particulates such as polystyrene beads or riebeckite, the nonfibrous analog of crocidolite asbestos. Comparative experiments with human adult lung fibroblasts (HAL) showed less striking increases in mRNA levels of MnSOD and HO in response to asbestos, but steady-state mRNA levels for HO were increased more than fivefold in response to X/XO. To determine whether increases in mRNA levels of MnSOD were translated into protein, Western blot analyses were performed on HMC and HAL cells exposed to asbestos or X/XO. Slight increases in MnSOD immunoreactive protein were observed in HMC in response to both agents. In contrast, X/XO caused striking elevations in MnSOD protein levels in HAL cells. These results suggest that certain antioxidant enzymes are inducible in HMC after exposure to asbestos and other oxidants.

Asbestos, Crocidolite↗

PubMed1985

In vitro studies of human lung carcinogenesis.

Advances in the methodology to culture normal human lung cells have provided opportunities to investigate fundamental problems in biomedical research, including the mechanism(s) of carcinogenesis. Using the strategy schematically shown in Figure 1, we have initiated studies of the effects of carcinogens on the normal progenitor cells of the human cancers caused by these carcinogens. Extended lifespans and aneuploidy were found after exposure of mesothelial cells to asbestos and bronchial epithelial cells to nickel sulfate. These abnormal cells may be considered to be preneoplastic and at an intermediate position in the multistage process of carcinogenesis. Human bronchial epithelial cells can also be employed to investigate the role of specific oncogenes in carcinogenesis and tumor progression. Using the protoplast fusion method for high frequency gene transfection, vHa-ras oncogene initiates a cascade of events in the normal human bronchial cells leading to their apparent immortality, aneuploidy, and tumorigenicity in athymic nude mice. These results suggest that oncogenes may play an important role in human carcinogenesis.

Animals↗

PubMed1981

Two-dimensional electrophoresis of human-CHO cell hybrids containing human chromosome 11.

Two-dimensional electrophoresis-electrofocusing with polyacrylamide gels is described in which the pattern of peptide spots obtained from hybrid cells of CHO containing the single human chromosome 11 are compared with those from the hybrid which has undergone reversion so as to lose this chromosome. At least eight distinct spots unique to the cell containing chromosome 11 have been located on the electrophoretogram. Experiments are described demonstrating applicability of the method to hybrids containing specific deletion mutants of chromosome 11, an approach which makes possible regional mapping of the loci responsible for specific peptides. The methodology appears applicable to study of gene expression under the influence of hormones and other agents and to the comparison of normal and disease situations.

Animals↗