BACKGROUND The interleukin (IL)‐1‐IL‐6 network, the most potent cascade of pro‐inflammatory cytokines, plays an autocrine role in tumor growth. The IL‐1‐IL‐6 network is down‐regulated by a phased cytokine inhibitor IL‐1 receptor antagonist (ra) and an anti‐inflammatory cytokine IL‐10. The current study evaluated this down‐regulation system in colorectal carcinoma and its relation to the genetic alteration of tumor suppressor genes. METHODS Seventy‐four specimens of primary colorectal carcinoma and normal mucosa were collected to measure tissue concentrations of cytokines. Polymerase chain reaction amplification was performed to investigate the loss of heterozygosity of the microsatellite markers on chromosomes 17p and 18q. RESULTS The IL‐1ra/IL‐6 ratio in the carcinoma specimens was lower than ratios in adenomas and normal mucosae and decreased with disease progression. The IL‐1ra/IL‐6 ratio in early cancers tended to be lower than that in adenomas and normal mucosae. However, the tissue concentrations of IL‐1β and IL‐10 were not associated with any clinicopathologic parameters. The tissue IL‐1ra concentration correlated with that of IL‐6 only in adenomas and early cancers. Immunohistochemically, IL‐1ra and IL‐6 were localized in the tumor cytoplasm. A reduced tissue IL‐1ra/IL‐6 ratio in the carcinomas correlated with poor prognosis and was associated with the loss of heterozygosity of the microsatellite markers on chromosomes 18q. CONCLUSIONS There is an IL‐6‐IL‐1ra network system in colorectal tumors, but this system deteriorates with carcinogenesis and tumor growth. The deterioration of this network system was associated with the allelic loss of a portion of chromosome 18q, reflecting the genetic alteration of tumor suppressor genes. Cancer 2002;94:1584–92. © 2002 American Cancer Society. DOI 10.1002/cncr.10324

The serum HGF level may be a clinically significant tumor marker in patients with early-stage, as well as advanced-stage, gastric cancer. HGF elevation in early-stage patients may help us to predict the risk of lymph node metastasis of early gastric tumors, even of smaller tumor size. HGF may be a useful indicator for appropriate lymphadenectomy in early gastric cancer.

Hypothesis: Aging results in both decreased immunity to exogenous antigens and increased autoreactivity. We suggest that the increased autoreactivity against tumor-releasing cachectic cytokine and postsurgical hypercytokinemia are involved in the cause of increased morbidity and mortality in elderly patients with colorectal cancer. Design, Setting, and Patients: Eighty-three patients with colorectal cancer admitted to a university hospital were studied prospectively. Interventions: Surgical specimens of primary colorectal cancer were harvested and peripheral venous blood samples were obtained perioperatively. Main Outcome Measures: The tissue concentrations of interleukin (IL) 1␤ and IL-6 were determined. Serial determinations of serum concentrations of IL-6, IL-6 soluble receptor, and C-reactive protein were performed. Nutritional status was assessed by the creatinine height index. Results: The tumor IL-6 content was the independent factor that influenced the creatinine height index in the elderly patients, whereas Dukes classification was the only independent factor that influenced the creatinine height index in the younger patients. The elderly patients showed an exaggerated C-reactive protein response and increased IL-6 soluble receptor consumption independent of the tumor IL-6 content and postoperative IL-6 response. This immunologic disturbance was followed by a significant (P = .03) delay in the normalization of activated neutrophils, which seemed to be associated with postoperative fatal complications in the elderly patients. Conclusions: Autoreactivity against intrinsic IL-6 was increased and seemed to be associated with poor clinical outcomes in elderly patients. To prevent fatal complications, adequate nutritional support early in treatment and attenuation of the neutrophil-related hyperinflammatory sequence by controlling the IL-6 soluble receptor affinity should be advocated.