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Biomedical subjects

M J Cline

Publications and source records attributed to M J Cline.

At least 37 records · Page 2Linked to original sources
PubMed1988

A unique pattern of proto-oncogene abnormalities in ovarian adenocarcinomas.

Twelve cases of ovarian adenocarcinoma were studied for alterations in proto-oncogenes, and a unique pattern of altered ras proto-oncogenes was observed. Amplification of ras-Ki was found in three of seven ovarian tumors and amplification of ras-Ha in one of 12. In contrast, ras-Ha amplification was not found in any of the 334 other tumors and ras-Ki amplification was only seen in breast cancer at a frequency of 3%. Other proto-oncogenes altered in ovarian adenocarcinomas included c-myc and c-erbb-2. Proto-oncogene abnormalities were more frequent in aggressive tumors of high histologic grade.

Adenocarcinoma↗
PubMed1988

Alterations of class I HLA genes in human colon cancers.

Alterations of HLA class I genes were found in 3 of 12 human colon cancers. Rearrangements in HLA class I genes were observed in 2 cancers and amplification of HLA-coding genes was observed in 1 cancer. All 3 cancers were at an advanced stage. No examples of amplification or rearrangement in the HLA genes were found in 10 other tumours of diverse types. No alterations in the beta 2-microglobulin gene were observed in 22 human solid tumours included in this study. The association between alterations in HLA genes and proto-oncogenes in these tumours is discussed.

Adenocarcinoma↗
PubMed1988

Genetic and cytogenetic changes in acute lymphoblastic leukemia.

In recent years, a number of non-random chromosomal alterations have been identified in specific populations of acute lymphoblastic leukemic cells of either B-cell or T-cell lineage. The most frequently involved chromosomal sites are 1q, 4q, 6q, 7q, 8q, 9p, 9q, 10q, 11p, 12p, 14q, 19p and 22q. Genes located near frequent breakpoints include c-myc, c-abl and the genes for the T-cell alpha and beta receptors. In addition, approximately 20 other genes potentially involved in the leukemic process are located near less frequently encountered, but consistent, chromosomal breakpoints.

Chromosome Aberrations↗
PubMed1988

Amplification of human int-2 in breast cancers and squamous carcinomas.

Murine int-2 is one of the genetic loci implicated in the induction of mouse breast cancers by murine mammary tumor virus. An homologous gene has recently been identified in the human genome (Casey et al., 1986). The human int-2 locus was found to be amplified 7- to 25-fold in 4 of 46 infiltrating ductal breast cancers and 30- to 60-fold in 2 of 8 squamous carcinomas of the head and neck region, but not in other cancers. All of the involved tumors had metastasized to regional lymphatics at the time of analysis and five exhibited clinically aggressive behavior.

Breast Neoplasms↗
PubMed1987

Abnormalities of protooncogenes in non-small cell lung cancer. Correlations with tumor type and clinical characteristics.

Twenty-seven primary non-small cell (NSC) lung cancers were analyzed for alterations of protooncogenes by DNA hybridization techniques. Abnormalities were found in 56% of tumors including ten of 16 adenocarcinomas, three of nine squamous cell cancers and two of two larger cell cancers. Five protooncogenes were found to be commonly altered in tumors at frequencies between 12% and 60%. These were c-myc, c-myb, c-ras-Ha, c-erbB-1 and c-erb-B-2. Alterations in c-erbB-1 and c-erbB-2 correlated with histologic type of tumor and were more common in advanced cancers. Allelic deletions of c-ras-Ha or c-myb were frequently observed in primary tumors which recurred or progressed after surgery (five of six). Analysis of protooncogenes may provide insights into the pathogenesis of lung cancer and may aid in predicting clinical behavior.

Adenocarcinoma↗
PubMed1987

Association of multiple copies of the c-erbB-2 oncogene with spread of breast cancer.

Amplification of c-erbB-2 was at least three times more frequent in breast cancer than in most other types of carcinoma, and was not found in sarcomas or hematological malignancies. Amplification of c-erbB-2 was found in 15 of 86 primary breast cancers and in 3 of 12 secondary breast cancers. Amplification was more common in breast tumors of advanced stage, and in tumors which had metastasized to regional lymph nodes sites. Gene amplification was observed in 21% (4 of 19) of primary tumors which recurred within 3 years of mastectomy and in 6% (2 of 32) of nonrecurrent tumors.

Breast Neoplasms↗
PubMed1987

Cell type-specific expressions of c-ras gene products in the normal rat.

Expression of proteins encoded by the ras proto-oncogenes was examined immunohistochemically in formalin-fixed, paraffin-embedded tissues of the normal rat using anti-ras p21 antibodies generated against synthetic peptides. Cell type specific expressions of ras gene products were detected in distal tubules of kidney, megakaryocytes in spleen, neural cells in cerebrum, Purkinje cells in cerebellum, cells lining the pulmonary alveoli and cells in the epithelium of intestinal villi. Region specific expressions of the ras proteins were observed in spleen and thymus, where the ras proteins were detected in splenic nodules including germinal centers and thymic medulla, respectively. These findings suggest that the c-ras gene products in normal rat organs are expressed in specific cell-types within a tissue and may be associated with degree of cellular differentiation.

Animals↗
PubMed1987

Gene therapy: current status.

The bone marrow is the probable first target for gene therapy of genetic diseases. The candidate diseases are those involving mutant enzymes, such as adenosine deaminase. A consensus strategy has evolved utilizing RNA viral vectors to introduce new genes into marrow cells. Two major obstacles still preclude application of this technology to humans: extremely inefficient expression of a new gene in the host cell, and the lack of a convenient and clinically acceptable method of returning the genetically altered cells to the patient. Even before the technical problems of gene therapy have been solved, other technologies such as organ transplantation, are helping to ease the burden of many genetic diseases.

Bone Marrow↗
PubMed1987

Intranuclear uptake and persistence of biologically active DNA after electroporation of mammalian cells.

Radiolabeled or biologically functional DNA molecules were introduced into cells by electroporation in a variety of forms: double stranded circles, linearized double stranded fragments and single stranded circular molecules. Molecules rapidly entered cells after exposure to a high field-strength electric pulse and then redistributed between the cytoplasm and the nucleus. Maximal intranuclear levels approximated 10(4) molecules per cell. Introduced DNA persisted in a biologically active form with a half-life of 15-24 h. There was no evidence for biologically significant alteration of two double stranded gene sequences. Single stranded DNA molecules also retained biological activity.

Cell Transformation, Viral↗
PubMed1987

The role of proto-oncogenes in human cancer: implications for diagnosis and treatment.

Proto-oncogenes are normal genes which affect normal cell growth and proliferation, but which have the potential to contribute to cancer development if their expression is altered. A variety of events may activate proto-oncogenes and convert them from benign genes to cancer genes. These events include mutations of nucleic acid sequences, chromosomal rearrangements, and amplification of the number of genes. The observations that alterations in specific gene sequences frequently accompany neoplasia have provided the first insights into the pathogenesis of human cancer at the molecular level. These insights offer new opportunities for developing cancer diagnostics and therapeutics.

Gene Amplification↗
PubMed1987

Protooncogene abnormalities in colon cancers and adenomatous polyps.

To determine the frequency and clinical significance of oncogene abnormalities in colon cancer, deoxyribonucleic acids from 45 colon carcinomas and 15 benign adenomas were hybridized with 14 different protooncogene probes. Abnormalities of oncogenes were found in 22% of cancers at the time of resection. Amplification of c-myc or c-erbB-2 and allelic deletion of c-ras-Ha or c-myb were the most frequent abnormalities. The presence of altered oncogenes did not correlate with Dukes' stage, tumor progression, or patient survival after resection. One adenoma had an allelic deletion of the c-myb oncogene which was not seen in either the normal colon or an adjacent carcinoma. These data indicate that the spectrum of altered protooncogenes in colon carcinoma is similar to that of other adenocarcinomas, and that unstable oncogenes can be found before overt malignancy develops.

Adenocarcinoma↗
PubMed1987

Rearrangement of the p53 gene in human osteogenic sarcomas.

p53 is a 53-kDa nuclear protein that is associated with malignant transformation in several tumor model systems. In a survey of 134 human carcinomas, sarcomas, leukemias, and lymphomas obtained at surgery or from peripheral blood, we found rearrangements of the p53 gene only in osteogenic sarcomas (3 of 6 osteogenic sarcomas examined). Normal tissue from one of these patients had an unrearranged gene, indicating that the genetic abnormality in the tumor was acquired. Two of the sarcomas with rearranged genes expressed levels of p53 protein that were elevated relative to other tumors. Rearranged p53 genes were also found in human osteogenic sarcoma cell lines.

Cell Line↗
PubMed1987

Proto-oncogene abnormalities in human breast cancer: correlations with anatomic features and clinical course of disease.

DNAs from fifty-three primary breast cancers were hybridized with 16 different proto-oncogene or oncogene probes. Abnormalities of one or more of five proto-oncogenes were found in fifty-eight percent of tumors at the time of mastectomy. Amplification of c-myc and c-erbB-2, and allelic deletions of c-ras-Ha and c-myb were the most common abnormalities. The presence of altered proto-oncogenes correlated with clinical stage of the cancers. Fifteen of 43 evaluable tumors of stages I to III recurred, and four of five evaluable stage IV tumors progressed within 16 to 24 months of surgery. All but one of the cancers that recurred or progressed had detectably altered proto-oncogenes (P less than .001). Analysis of proto-oncogenes may have prognostic value in breast cancer.

Adult↗
PubMed1987

Specificity of proto-oncogene amplification in human malignant diseases.

DNAs from 253 fresh human tumors of 38 different types were hybridized with 17 different oncogene probes. The analysis demonstrated unique associations between amplification of specific oncogenes and specific types of tumors. In a large number of cases it was determined that amplified oncogenes occurred in 10 to 20% of tumors with the following specific associations: c-myc in adenocarcinomas, squamous carcinomas and sarcomas but not hematologic malignancies; c-erbB2 in adenocarcinomas, particularly breast cancers; c-erbB1 in squamous carcinomas; N-myc in neuroblastomas. A small number of cases suggested other specific associations: amplified c-myb in breast cancers; amplified c-ras-Ha and c-ras-Ki in ovarian carcinomas. In addition, there was a correlation between amplification of c-myc and the clinical stage of adenocarcinomas, and amplification of c-erbB2 and the clinical stage and lymph node involvement of breast cancers.

Carcinoma↗
PubMed1986

Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo.

There are two genes related to the viral erbB gene in the human genome. c-erbB-1 is the same as the gene for the epithelial-growth-factor (EGF) receptor, and c-erbB-2 encodes a receptor-like protein very similar to, but distinct from, the EGF receptor. Hybridisation analysis of DNA from 101 fresh human malignant tumours showed that the c-erbB-2 gene was amplified in 5 of 63 adenocarcinomas and none of 38 other types of tumours, whereas the c-erbB-1/EGF-receptor gene was amplified only in 1 of 8 squamous-cell carcinomas. Thus, the protein products of the amplified c-erbB-2 gene may have a role in the evolution of adenocarcinomas, as does the EGF receptor in some squamous-cell carcinomas.

Adenocarcinoma↗