No abstract

The efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines such as UFT and 5'-DFUR may not be as great for patients with a tumor positive for MMP-9 having a greater risk to postoperative recurrence.

Nude mice have been used to grow subcutis (s.c.) growing human colorectal tumors, but these tumors rarely metastasize. This is a problem for studies into the biological behavior of metastatic subpopulations of human colorectal cancers. We have followed the evolution of the parental line and of a variant of human colon carcinoma KM12 cells, that were both tumorigenic, following implantation into the s.c. or cecal' wall of nude mice. The tumors growing s.c. did not produce visceral metastases, whereas the cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. However, the incidence of liver metastases was different between the parental cell line KM12C cells and the in vivo selected cell line KM12SM cells after orthotopic inoculation. The morphological findings of KM12 cells proliferating in a monolayered sheet revealed that these two cell lines consisted of various cell populations. These results suggest that in the orthotopic colon cancer models, liver metastasis is defined by difference in subpopulations of metastatic phenotypes to the liver with early dominance of its growth in the implanted organ. As a result, our new model using orthotopic implantation of KM12SM cells, which produce a 50% incidence of liver metastasis, can help to provide a technique to study the biological behavior of metastatic subpopulations of human colon cancers.Key words metastatic animal model, human colon carcinoma, orthotopic implantation, liver metastasis, lung metastasis, mesenteric lymph node metastasis Received for publication December 15,1997C orresponding address and reprint requests to: Yutaka Ogata,

Summary:We have evaluated the degree of MMP-9 and TIMP-1 messenger RNA (mRNA) expressions according to cell types in tumor tissues, and evaluated the implication of balance between the MMP-9 mRNA and the TIMP-1 mRNA expression in liver metastasis using orthotopicimplanted colon cancer in nude mouse, and also in 47 patients with colorectal cancer. The grade of MMP-9 or TIMP-1 mRNA expression was classified into 4 categories according to positive cell ratio. A higher grade of MMP-9 mRNA expression in tumor cells was correlated with liver metastasis in the experimental colon cancer, but was not statistically correlated in the clinical colorectal cancer. In contrast, the expression of TIMP-1 mRNA in the stromal cells of human colorectal cancer was correlated with liver metastasis. In both experimental and clinical colorectal cancer, a balance between the expression of MMP-9 mRNA and that of TIMP-1 mRNA was correlated with the occurrence of liver metastasis. The imbalance of MMP-9 dominance in tumor cells was implicated in liver metastasis. However, there was no significant relationship between the incidence of liver metastasis and the expression patterns of MMP-9 and TIMP-1 mRNA in the stromal cells. These results suggest that the balance between the expressions of MMP-9 and TIMP-1 in the tumor cells is more closely related to tumor biological behavior rather than the balance in the stromal cells.

A 41-year-old man with Cronkhite-Canada syndrome presented with multiple juvenile polyps with hyperplastic and adenomatous changes throughout his stomach and entire colorectum. Dysgeusia was recognized and the degree of hypoproteinemia was remarkable. A barium enema study and colonofiberscopy also revealed an advanced cancer in the rectum. Chronic hepatitis B and membranous glomerulonephritis were also present. It was difficult to design a conservative protocol using steroids for the treatment of protein-loosing enteropathy because the patient was a hepatitis B virus carrier. As a result, a subtotal colectomy while preserving the cecum with cecorectal anastomosis was performed. Pathologically, the ulcerated rectal tumor was a moderately differentiated adenocarcinoma with invasion into the muscularis propria. Most polyps showed cystically dilated glands without dysplasia or edematous stroma with inflammatory cell infiltration. A few polyps were juvenile-type polyps with adenoma components. Although no remarkable improvement was observed in the hypoproteinemia postoperatively, an alpha1-antitrypsin clearance test showed a significant decrease in protein loss from the gastrointestinal tract, which was only about one third of the loss seen preoperatively. These findings lead us to conclude that when improvement using conservative treatment can be neither obtained nor is expected, then the use of surgery should be considered when treating patients with Cronkhite-Canada syndrome.