DNA polymerase-alpha as a putative early relapse marker in non-small cell lung cancer: an immunohistochemical study
Article Abstract:
As is the case for most malignant tumors, a better survival rates for lung cancer are associated with early diagnosis. For patients with no signs of tumor spread to the local lymph nodes, the five-year disease-free survival from non-small cell lung cancer is about 70 percent. However, little is known about the factors that distinguish the 70 percent who survive from the 30 percent who succumb, despite early diagnosis and treatment. The rapidly reproducing cells of a malignant tumor must be manufacturing DNA at an increased rate. Therefore, the enzymes necessary for DNA replication are likely to be present in tumor cells in greater amounts. One such enzyme is DNA polymerase alpha (POL-alpha). A study was conducted to determine if POL-alpha might provide insight into the biological behavior of lung cancers in different patients. A total of 72 patients with non-small cell lung cancer were studied. Many of these patients died soon after surgery or underwent only palliative surgery. Such patients were excluded, and only patients with a reasonable chance of long-term survival were included in the analysis. Using specific antibodies against microscopic sections of the surgical specimens, it was found that 17 percent of all the specimens were positive for POL-alpha. Normal tissue contains POL-alpha, therefore, a 'positive' indication was considered to be more than 5 percent of the cells staining with the specific antibody. Of 43 patients who underwent a complete surgical resection of the cancer, the three-year survival rate was 42 percent for the patients with POL-alpha-positive cancers and 81 percent for the patients with negative cancers. The favorable prognosis associated with POL-alpha-negative tumor was even more striking if only the patients without lymph node metastases were considered. Among the node-negative patients with negative POL-alpha findings, the three-year disease-free survival rate was 100 percent. These results suggest that POL-alpha may be a useful marker of the patients more susceptible to early relapse and disease progression. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1991
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Oncogene expression in the liver tissue of patients with nonneoplastic liver disease
Article Abstract:
The discovery of oncogenes, the genes in cancer-causing viruses responsible for the transformation of normal cells, rapidly led to the observation of proto-oncogenes. Indeed, the distinction between proto-oncogenes, the cellular equivalent of oncogenes found in healthy cells, and pathologic oncogenes is often blurred; now the normal cellular genes are frequently called "oncogenes" as well. A great deal of research has focused upon the changes which occur in proto-oncogenes in a number of human cancers. Less emphasis has been placed, however, on the role of proto-oncogenes in the normal function of healthy cells. Since proto-oncogenes are believed to play an important role in the regulation of cell proliferation, the activity of such genes might be expected to increase in regenerating tissue in which much cell replication is taking place. This possibility was examined in 66 patients with hepatitis or cirrhosis, liver diseases which are not cancerous, but which involve the regeneration of liver tissue. Four other cases, including diabetes and/or obesity, were also examined. Techniques of molecular biology were used to detect the activity of nine separate cellular oncogenes; seven of these nine could not be detected in any specimen. The expression of the c-fos gene was faintly detected in only a few specimens. Curiously, however, the activity of the c-K-ras cellular oncogene was increased in all specimens. The cellular oncogene ras has been shown to have increased expression in a number of different tumors. The results of the present study indicate that the expression of ras should not be thought of as a strictly pathological event, but rather that ras expression can be an essential part of liver cell function as well. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1991
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DNA alterations at proto-oncogene loci and their clinical significance in operable non-small cell lung cancer
Article Abstract:
Lung cancer is the leading cause of cancer death among men in industrialized countries. Despite improvements in treatment, the five-year survival rate of all cancers of the lung is less than 15 percent. Operable non-small cell lung cancer has the best prognosis, and several factors have been identified which contribute to a favorable outcome. However, some patients die within two years of apparently successful surgery of early non-small cell lung cancer. Clearly, additional prognostic indicators are required. Since the so-called proto-oncogenes of human cells are thought to be involved both in normal cell replication and the development of cancer, the DNA makeup of several proto-oncogenes was determined from tumor specimens obtained from 54 patients with operable non-small cell lung cancer. Seven different proto-oncogenes were examined: c-raf-1, three members of the myc family, and three members of the ras family. Changes in the copy number of c-raf-1, c-myc, and Ha-ras were observed in seven tumor specimens. Although the malignant tumors in which these genetic alterations were identified should have, by all appearances, had a good prognosis, six of the seven patients relapsed within an average disease-free interval of 6.5 months. This study shows that a significant correlation exists between alterations in proto-oncogenes and relapse within a year of surgery for non-small cell lung cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1990
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