Analysis of metastatic spread and growth of tumor cells in mice with depressed natural killer activity by anti-asialo GMl antibody or anticancer agents

Summary The mechanism of artificial and spontaneous metastases of tumor was analyzed in B16 melanoma cells and C57BL/6 mice by using anti-asialo GM1 antibody and anticancer agents. Single administrations of 500 g anti-asialo GM1 antibody resulted in significantly decreased NK activity in spleen cells of C57BL/6 mice, lasting 10 days from the day following administration. Treatment with anti-asialo GM1 antibody never decreased the function of T lymphocytes measured by blastogenesis with phytohemagglutinin or T cell growth factor. The tumoricidal functions of activated macrophages but not of resident macrophages were decreased by in vivo treatment with anti-asialo GM1 antibody.The anti-asialo GM1 antibody was evaluated in terms of the enhancing effect on pulmonary metastases with regard to the timing of administration. Treatment with anti-asialo GM1 antibody 1 day before or on the day of tumor inoculation resulted in a substantial increase in the number of artificial pulmonary metastases. In the experimental system of spontaneous metastases, anti-asialo GM1 antibody most effectively increased the number of pulmonary metastases when administered 1–2 weeks before the removal of primary tumor, when the tumor cells are thought to be released into blood circulation from the primary site. In addition, accelerated growth of transplanted tumors at the primary site was observed in mice treated with anti-asialo GM1 antibody. These results strongly suggest that anti-asialo GM1 antibody enhances the incidence of in vivo tumor metastases and the growth of transplanted tumor mainly by suppressing the function of NK cells.The maximum effective dose (MED) of mitomycin C or its derivative (M-83) suppressed NK activity significantly, and pretreatment with these anticancer agents enhanced the growth of the artificial pulmonary and liver metastases. In contrast, the MED of cDDP showed no effect on the NK activity or the numbers of pulmonary and liver metastases. These results indicate that the depression of NK activity induced by chemotherapy results in the promotion of metastatic disease.From these studies it can be concluded that NK cells have a key role in the control of metastases of malignant disease, and that support of NK activity is very important for the prevention of metastases.     

False negative cases of F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in small lung cancer less than 3 cm in size]

A considerable number of false negative cases in FDG-PET were seen in small-cell lung cancer, despite the usefulness of this imaging modality. We investigated the correlation between FDG-PET results and the clinicopathological findings in small lung cancers less than 3 cm in size. Fifty-one consecutive cases of surgically resected small lung cancers scanned preoperatively by FDG-PET was assessed. The medical records of each case were reviewed for the maximum tumor size in the CT findings, histology, grade of differentiation, lymphatic and vascular invasion, pleural invasion, lymph node stage, serum level of carcinoembryonic antigen (CEA), and CT findings. All of the 5 cases (4 adenocarcinomas, 1 small-cell carcinoma) less than 1 cm in size were false negatives. In the 46 cases 1-3 cm in size (34 adenocarcinomas, 9 squamous sell carcinomas, 2 large sell carcinomas, 1 small cell carcinoma), false negative results were seen in 8 of 15 cases of well-differentiated adenocarcinoma (53%). In the 8 false negative cases, 1 (13%) lymphatic vessel invasion (ly), 0 (0%) vascular vessel invasion (v), 0 (0%) pleural invasion (p), 0 (0%) lymph node metastasis, 0 (0%) high serum level of CEA, and 5 (63%) cases showing ground-glass opacity on CT were observed. There were significant differences in the factors ly, v, CEA, and CT findings between the 8 false-negative cases and the 26 true positive cases with adenocarcinoma (p < 0.01-0.05). Lung cancers < 1 cm in size cannot be detected in FDG-PET. Adenocarcinomas of the lung 1-3 cm in size with false negatives in FDG-PET showed significantly less invasiveness than the true positives.     

Serum Surfactant Protein A Levels in Healthy Individuals Are Increased in Smokers

Serum levels of surfactant protein A (SP-A) were studied in 237 healthy subjects in relation to sex, age, and smoking habits. SP-A values in male smokers were significantly higher than those in male nonsmokers (p < 0.001). The amount of cigarette smoking did not correlate significantly with SP-A values, however. SP-A values in young nonsmoking males and females were somewhat lower than those in older, but without significant difference. No significant difference in values was found between the sexes. We conclude that (1) smoking increases serum levels of SP-A, and (2) SP-A serum levels are not affected by age and sex. Accepted for publication: 6 March 1998     

DIFFUSE MALIGNANT PERICARDIAL MESOTHELIOMA

A 67 year-old male case of pericardial mesothelioma is reported. The diagnosis was established by the gross appearance at autopsy and its his-tological findings. The tumor arising from the anterior epicardium of the right half of the heart was located within the pericardial sac, and displaced and compressed the heart to the posterior direction. Histologically, large areas of the tumor were composed of spindle-shaped malignant cells which were arranged in interlacing bundles. The other areas showed the presence of tubular structures and ill-defined solid nests. Distant metastasis was found only in a small focus of the 8th vertebral bone marrow composed of spindle-shaped cells. A meticulous search failed to find any tumor in other organs. Based on these findings, the tumor was diagnosed as diffuse malignant mesothelioma of biphasic type. ACTA PATHOL. JPN. 35 : 1475–1481, 1985.     

Bronchial dilatation due to broncholithiasis mimicking lung abscess]

A 61-year-old man who had been treated for pneumonia several times was examined because radiographs and computed tomograms disclosed a mass-like shadow associated with a cavity in the left lingular segment. The lesion was resected by video-assisted thoracoscopic surgery because it was suspected of being a lung abscess that had caused repeated episodes of inflammation. The resected specimen revealed a severely dilated peripheral bronchus due to broncholithiasis. It is often difficult to diagnose a lesion as broncholithiasis on the basis of secondary changes or calcification without bronchoscopic data. We emphasize that broncholithiasis should be suspected when a shadow resembling a lung abscess associated with symptoms of recurrent infection is found.     

KL-6 and CEA levels in epithelial lining fluid microsamples predict response to gefitinib in patients with advanced non-small cell lung cancer

Background and objective: Both Krebs von den Lungen‐6 (KL‐6) and carcinoembryonic antigen (CEA) are known to be tumour markers in non‐small cell lung cancer (NSCLC). The aim of the present study was to assess whether or not intrabronchial epithelial lining fluid (ELF) levels of these markers predicted tumour response better than serum levels in patients with advanced NSCLC treated with gefitinib. Methods: ELF samples were obtained both from near the tumour and from the contralateral lung using a bronchoscopic microsampling technique, before and 2 weeks after the start of gefitinib treatment. Serum samples were taken concurrently. Among the 22 patients enrolled in the study, 14 (64%) showed partial responses or stabilization of disease with gefitinib treatment (treatment responders), while 8 (36%) showed progression of disease (treatment non‐responders), 4 weeks after the start of treatment. Results: ELF KL‐6 levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.011), whereas there was a marginal increase in the treatment non‐responders group (P = 0.049). ELF CEA levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.004), whereas there was no significant change in the treatment non‐responders group. For both markers, neither the serum levels nor the levels in contralateral ELF showed any significant changes in either group of patients. Conclusions: Both KL‐6 and CEA levels in ELF near the tumour predicted tumour response in NSCLC patients treated with gefitinib, whereas serum levels did not.