The plasma level of human DNA was determined by the dot-hybridization method using human Alu-family DNA as a probe in 45 patients with primary lung cancer, 54 patients with benign pulmonary diseases, and 59 healthy controls. The mean plasma DNA level was significantly higher in the patients with lung cancer than that in the patients with benign pulmonary diseases or in healthy controls. The mean plasma DNA level in the patients with benign pulmonary diseases was also significantly higher than that in healthy controls. There was no significant difference in mean plasma DNA level in each histologic type of lung cancer. The plasma DNA level was elevated above the cut-off level of 80 ng/ml in 71% of the patients with lung cancer, 37% of the patients with benign pulmonary diseases and none of the healthy controls. The serum CEA was positive in 38% of the patients with lung cancer and thus when plasma DNA and serum CEA were used in combination, 78% of the cases with lung cancer could be detected by these two markers. In the patients with lung cancer who responded to treatment, the plasma DNA levels were significantly decreased after treatment, while its levels were elevated in the patients whose treatment was unsuccessful. These findings indicate that plasma DNA may be a useful marker in patients with lung cancer.

DNA content of 369 rectal cancers was measured by flow cytometry. One hundred and four (28.2%) were diploid, 252 (68.3%) were aneuploid and 13 (3.5%) were tetraploid. Diploid cancers were associated with an improved 5 year survival (p less than 0.001) and were more likely to be diagnosed at an early stage. However DNA content did not confer independent prognostic information in a Cox model based on four discrete pathological variables. Patients were classified by a new system of prognostic grouping and those with a very good or a very poor outlook were removed leaving 137 prognostic group 3 patients. No further substratification of this group by DNA content or by four additional pathological variables could be achieved. As the new prognostic system is not improved by the additional of ploidy, routine adoption of flow cytometry in the assessment of rectal cancer can not be recommended.

This study was carried out to investigate whether there is any difference of biological characteristics between a gastric cancer cell line (KATOIII) and another cell line derived from liver metastasis of the same cell line (KATOIII-H2). The liver metastasis was produced by intrasplenic injection of the fluid containing of KATOIII in nude mouse and new cell line was established using the cells of metastatic site. The results are as follows. 1) Inoculation of KATOIII-H2 into the spleen produced liver metastases in all of the experimental animals, whereas the same procedure with KATOIII produced metastasis only in 30% of the animals. 2) KATOIII-H2 exhibited more prominent platelet-aggregating activity than KATOIII. 3) There is no difference between two cell lines on doubling time, histological findings of the xenografts and chromosomal number. 4) DNA index of KATOIII-H2 is lower than KATOIII and the trisomy in NO. 20 chromosome of KATOIII-H2 was noted. The results indicate that metastatic potential is different between two cell lines and this fact is probably in a part because of the different platelet-aggregating activity of each cell line.

Analysis of the nuclear DNA content from paraffin-embedded specimens using flow cytometry was performed on 86 patients in squamous cell carcinoma of the lung. There were no relationships between the site of tumor origin and the nuclear DNA content or the survival of the patients. The frequency of DNA aneuploidy was 74.4% among tumors, and it significantly (p less than 0.05) increased with advanced stage. The patients with DNA aneuploidy were significantly (p less than 0.01) less favorable prognosed than those with DNA diploidy. Similar results were demonstrated in patients of absolute or relative curative resections. These results indicate that DNA aneuploidy is of higher grade malignant intensity than DNA diploidy in squamous cell carcinoma of the lung. In patients with absolute or relative curative resection, DNA aneuploid tumors occurred much more often in distant metastasis. In conclusion, there were no relationships between the site of tumor origin and the biological features or the prognosis of patients in squamous carcinoma of the lung. DNA ploidy pattern is related to relapse and prognosis of the tumors. If the DNA ploidy pattern of patients on whom absolute curative resection was performed is DNA aneuploidy, adjuvant therapy should be strongly performed and carefully followed up as long as possible.

Polymerase chain reaction (PCR) is a novel tool for the in vitro amplification of DNA segments up to several kb. Repeated cycles of DNA synthesis by heat-stable Taq DNA polymerase enables to obtain more than 10(5) copies of the target sequence. Recently its enormous attitude of amplification has been applied for the detection of tumor-specific gene alterations. Examples include the detection of point mutation of RAS oncogenes at codons 12, 13, and 61 and the detection of minimal residual neoplastic cells in patients in complete clinical remission. Among many kinds of tumor specific gene translocations, BCR-ABL gene in t(9;22)(q34;q11) and BCL-2-IgH gene in t(14:18)(q32;q21) have been successfully PCR-amplified around their fused regions. In lymphoid malignancies gene rearrangements of T cell receptor chain or immunoglobulin heavy chain can be used as clonal markers for leukemic cells. PCR technique permits the detection of leukemia DNA at dilution of 10(-4) to 10(-6). Although further investigation of patients' follow-up in large scale is needed, this technique seems to hold promise for the monitoring of residual neoplastic cells.

Oncogenic potential of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) which are both associated with occurrence of cervical cancer and the mechanism of oncogenesis by these viruses were investigated by transformation experiments in vitro. The results were obtained as follows. 1) HSV-2 induced neoplastic transformation of normal diploid cells is a multistep process. Cervical cancer associated antigen AG-4 is encoded within the specific region of HSV-2 DNA which converts immortalized cells to tumorigenic lines. 2) Tumor cells express cellular oncogene at a final stage of neoplastic transformation induced by HSV-2 and "hit and run" theory is applicable to oncogenesis of this virus. 3) Complete carcinogenesis can be mediated by HPV-16 or HPV-18 DNA under collaboration with other cofactors such as HSV-2. 4) It is suggested that neoplastic transformation induced by HPV-18 DNA is based on "hit and run" oncogenesis. 5) HPV-16 or HPV-18 DNA can immortalize primary diploid cells and convert them to fully tumorigenic phenotype by repeating cell passage. 6) It has been experimentally proved that the difference in transforming potential exists between HPV 6/11 and HPV 16/18. 7) Amplification and overexpression of c-myc oncogene was detected in transformed cells obtained by HPV-16 transfection. While overexpression of c-myc was detected in transformed cells induced by HPV-18 DNA, but no amplification was observed. On the other hand, detection of HPV, DNA and amplification or overexpression of protooncogenes was performed in cervical intraepithelial neoplasias (CIN) and invasive cervical carcinomas. The results were summarized as follows. 1) HPV DNA was detected in approximately 70% of a population with CIN by in situ hybridization. CIN II showed the highest incidence of positive HPV DNA (91%), and the positive ratio decreased in CIN III (56%). 2) Immunohistochemical study of paraffin-embedded specimens with monoclonal antibodies to oncogene products revealed that only some of cervical invasive carcinomas expressed c-myc protein, ras p21 or EGFR. 3) HPV DNA was detected in 46% of invasive cervical carcinomas by Southern blot hybridization. The percentage of patients with positive results for HPV 16/18 was 29%. However, it increased up to 58% by use of polymerase chain reaction (PCR), suggesting that there are many cervical cancer tissues in which a number of cells lack viral DNA. 4) Northern blot hybridization analysis revealed overexpression of c-myc mRNA in 30% of cervical invasive carcinomas although amplification of c-myc oncogene was detected in only one of invasive carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

To elucidate the cell biological significance of ras oncogene, the expression of ras-p21 was analyzed in 53 cases of liver tissues including 34 cases of hepatocellular carcinoma (HCC), by using immunohistochemical method. In result, 22 (65%) cases of 34 HCC and 34 (79%) cases of 43 liver cirrhosis were positive for p21, whereas all of chronic hepatitis and normal livers were negative. Especially, comparative study between the expression of p21 and clinicopathological background of HCC revealed that p21 was prominently expressed in well differentiated form, nodular type, small liver cancer, and the cases showing AFP levels below 400 ng/ml. From these results, it was indicated that ras oncogene might play an important role in malignant transformation of hepatocytes or differentiation of HCC.