We examined the ratio of neutrophils to lymphocytes (N/L ratio) in the peripheral blood in patients with colorectal cancer. The ability to produce active oxygen and phagocytosis of neutrophils, G-CSF, sIL-2R and IAP (immunosuppressive acidic protein) were also measured. The N/L ratios were significantly higher in the advanced stages of cancer than in normal controls. The ability to produce active oxygen in the terminal stage was 33% lower than in the control group. The G-CSF levels had no relationship with the neutrophil counts. IAP levels increased with cancer stage, and were inversely related to the ability to produce active oxygen. The IAP levels correlated well with the sIL-2R levels and the N/L ratio. These findings suggest that the ability to produce active oxygen, N/L ratio and IAP reflect anticancer mechanisms and that they may be useful when considering treatment or prognosis of patients with advanced stages of cancer.

We studied the antithyroid action of cigarette smoking products (nicotine, cotinine, and thiocyanate) in the physiological culture system of porcine thyroid follicles. Iodide uptake, iodine organification, de novo thyroid hormone formation, and iodide efflux were measured in the presence of 0–200 μmol/l nicotine, cotinine, or potassium thiocyanate. Nicotine and cotinine did not inhibit iodide transport or thyroid hormone formation. Thiocyanate concentrations equivalent to serum levels of smokers showed three independent antithyroid actions: (i) inhibition of iodide transport, (ii) inhibition of iodine organification, and (iii) increased iodide efflux. Inhibition of iodide transport by thiocyanate was competitive with iodide and independent of TSH concentration. Thiocyanate did not inhibit TSH mediated cAMP production or Na+K+ATPase activity, a sodium pump for iodide transport. When 50 μmol/l thiocyanate was added 2 h after incubation with iodide or when 1 μmol/l thiocyanate was added from the beginning of incubation, iodine organification was inhibited without changing iodide transport. De novo thyroid hormone formation was clearly inhibited by 50 μmol/l thiocyanate. Thiocyanate increased iodide efflux although the degrees of iodide efflux by 10 μmol/l and 100 μmol/l thiocyanate did not differ significantly. In summary, thiocyanate, a product of smoking, has three independent antithyroid activities. The data of iodide transport kinetics suggest that thiocyanate can be an antithyroid agent particularly in iodine deficiency.

Levels of serum sIL-2R (soluble interleukin-2 receptor) reflect the total amount of activated T lymphocytes in tumor infiltrating lymphocytes of cancer tissues and metastatic organs, because a part of alpha-chain of IL-2R is released into the bloodstream on the attachment of IL-2 (interleukin-2) to its specific IL-2R membrane. In most malignant diseases, elevated levels of serum sIL-2R are found, compare to normal control. Serum sIL-2R is a useful parameter for evaluating the disease stage and monitoring the disease progression during the post-treatment follow-up, though it is not an organ-specific parameter.

In this study, we quantitatively measured glycogen levels in tissue samples obtained from tumors, regions adjacent to tumor, and regions of normal colorectum to determine whether the levels were related to cell cycle and cancer growth. Glycogen levels were analyzed in relation to histopathological factors, (tumor size and stage of disease) and cell cycle progression. The glycogen level was found to be highest in the cancer tissue, lower in normal tissue, and lowest in the adjacent tissue. The difference in glycogen level between the cancer tissue and the other two regions was significant (P < 0.05). There was a negative correlation between glycogen level and tumor size, but it was not significant. The level of glycogen in cancer tissues decreased as the stage of the disease progressed, but a significant difference was not found between stages. There was a negative correlation between the glycogen level and the proliferation index. There was a positive correlation between the glycogen level and the proportion of cancer cells in G1 phase, while there was a negative correlation with S and G2M phases. Glycogen levels were highest in cancers with a high proportion of cells in G1, and decreased with progression to S phase. It may be that glycogen is utilized in the progression to S phase, and the cancer tissues are supplied with glycogen from the tumors themselves as well as their adjacent tissues. Cancer growth may be inhibited by artificial control of the glycogen level in the G1 phase of cancer cells.

The significance of superoxide dismutase (SOD) activity in colorectal cancer tissue was determined from the aspect of the antioxidant defense system. SOD activity and thiobarbituric acid reactive substance were measured in the tumor, in tissues adjacent to the tumor, and in regions that appeared normal, and the results were analyzed in terms of various histopathological factors (stage of disease, depth of invasion, venous invasion, etc.). DNA ploidy pattern and cell proliferation in cancer tissue were also measured, and the results analyzed in relation to SOD activity. SOD activity in cancer tissue was higher than in the other two regions. SOD activity in cancer tissue increased with the progression of stage, and changed with the depth of invasion. There was a significant difference in SOD activity between patients with venous invasion and those in whom this was absent. Stepwise regression analysis suggested that venous invasion was the most significant factor influencing SOD activity. The proliferation index was high in cancer tissue with low SOD activity. The incidence of aneuploidy was high in cancer with high SOD activity, whereas the incidence of diploidy was high in cancer with low SOD activity. These results suggest that elucidation of the antioxidant system in cancer tissue can provide us with a better strategy for cancer treatment.

Lithium has been reported to alter thyroid function and cause goiter in some patients. To explain the mechanism of lithium action in the thyroid gland, we studied the effect of lithium on thyroid function and cell growth in FRTL-5 rat thyroid cells and on de novo thyroid hormone formation in primary cultures of porcine thyroid follicles. TSH-induced iodide uptake was suppressed at 2 mM lithium in both FRTL-5 cells and porcine follicles. In porcine thyroid follicles, iodide uptake stimulated by 8-bromo-cAMP, iodine organification, and de novo thyroid hormone formation were also reduced by lithium; however, 2 mM lithium did not inhibit TSH-induced cAMP production. In FRTL-5 cells, lithium also inhibited forskolin-stimulated iodide uptake. These results suggested that lithium exerts its effect at a step involving cAMP signal transduction rather than inhibiting cAMP production. In both FRTL-5 thyroid cells and porcine follicles, lithium enhanced cell growth in basal states (lacking TSH) and with TSH treatment. In porcine thyroid cells, the protein kinase C activator, tetradecanoyl phorbol-13-acetate, increased cell growth, and lithium had an additive effect with tetradecanoyl phorbol-13-acetate on cell growth. To examine the possibility that the action of lithium was mediated by the protein kinase C pathway, porcine cells were incubated with lithium and H7, a selective protein kinase C inhibitor. Lithium-induced cell growth was suppressed to the basal level by H7. These results suggest that lithium exerts its growth-promoting effect through the protein kinase C system.

We report a case of heterochronic adrenal metastasis from colorectal carcinoma in a 51-year-old woman. A left adrenal metastasis was found by computed tomography and magnetic resonance imaging 8 months after an anterior resection for advanced rectal carcinoma, and a left hepatectomy for a solitary liver metastasis. The level of serum carcinoembryonic antigen was still within the normal range. A left adrenalectomy was performed, and histopathological examination revealed adenocarcinoma, compatible with the rectal carcinoma resected 8 months earlier. The patient died of lung metastases 6 months after the adrenalectomy. A review of autopsy series in the world literature revealed that adrenal metastasis from colorectal cancer is not rare. Therefore, the possibility of adrenal metastasis should be considered in the follow-up of patients after primary surgery for colorectal cancer, even though the liver and lung are the main metastatic sites.

The mechanism of progression of appendicitis has not been clarified. We examined tissue superoxide dismutase (SOD) activity, thiobarbituric acid reactive substance (TBARS), and the localization of Cu, Zn-SOD in 56 inflamed appendices in relation to histopathological classification. There was a significant difference in SOD activity between catarrhal appendix and phlegmonous and gangrenous appendix (2.3 +/- 0.1 vs 5.0 +/- 0.2 and 4.6 +/- 0.6 units/mg protein, respectively P < 0.05). TBARS value was highest in gangrenous appendix, being significantly different from the levels in the other two types (0.47 +/- 0.04 vs 0.19 +/- 0.01 n mol/mg protein, in catarrhal and 0.20 +/- 0.02, in phlegmonous appendix P < 0.05). Positive staining for Cu, Zn-SOD was demonstrated in 64% of catarrhal appendices, 96% of phlegmonous appendices, and 75% of gangrenous appendices, and intense positive staining was recognized in 9%, 28%, and 40% of these appendices, respectively. These results indicated that active oxygen influences the degree of inflammation in phlegmonous and gangrenous appendicitis. Gangrenous appendicitis and the other two types of appendicitis seemed to be different entities.