Yukimasa Suzuki

Cell Adhesion Molecule Expression by Vascular Endothelial Cells as an Immune/Inflammatory Reaction in Human Colon Carcinoma

The cell adhesion of inflammatory cells to vascular endothelial cells is an important process in the recruitment of inflammatory cells to the site. In cancer tissue, infiltration of inflammatory cells has been suggested to be a mechanism of host resistance. To clarify this infiltration mechanism, we investigated cell adhesion molecule expression (E‐selectin, P‐selectin, and ICAM‐1) in vascular endothelial cells by immunohistochemistry in colon carcinoma. Venules distributed along the invasive margin expressed E‐ and P‐selectins and ICAM‐1. These phenotypical features are identical to those of endothelial cells observed in active inflammatory lesions, and the vessels can, therefore, be designated as immunologically activated vessels. Nevertheless, the majority of blood vessels within the tumor lacked immunoreactivity for all these adhesion molecules and, therefore, could be designated as immunologically inactive vessels. Granulocytes, lymphocytes and macrophages, bearing the counter‐receptors of these adhesion molecules, were more densely distributed along the invasive margin. In contrast, few inflammatory cells were present within the tumor. In conclusion, the present study has demonstrated the phenotypical heterogeneity of tumor vessels; those for inflammatory cell infiltration to the tumor and those for the nutrient supply to the tumor.

Intercellular adhesion molecule-1 expression by macrophages in human gastrointestinal carcinoma: Possible roles as host immune/inflammatory reaction

Tumor‐associated macrophages (TAM) are one of the factors which modulate the carcinoma progression. The present study described immunohistochemical expression of intercellular adhesion molecule‐1 (ICAM‐1) in stromal cells in human gastrointestinal carcinoma identifying the cell types by immunoelectron microscopy. In colon and gastric carcinomas, ICAM‐1‐positive cells were mostly stromal cells, and major cell types were identified as macrophages and fibroblasts by immunoelectron microscopy. Macrophages were characterized by their ovoid shape, cytoplasmic projections, abundant vacuoles, phagocytosis, and paucity of rough endoplasmic reticulum. Fibroblasts contained stacks of rough endoplasmic reticulum. Macrophages were major cells among ICAM‐1‐positive cells along the invasive margin, while fibroblasts were predominant in the stroma within carcinoma in colon and intestinal‐type gastric carcinomas. Lymphocytes positive for lymphocyte function associated antigen (LFA‐1), a counter‐receptor of ICAM‐1, were densely distributed along the invasive margin, and sparsely in the stroma within carcinoma. In diffuse‐type gastric carcinoma, most macrophages were dendriticshaped and negative for ICAM‐1. Our study suggests that the invasive margin is an area similar to active inflammation, where the antigen presenting cells (macrophages) and lymphocytes may interact via the ICAM‐1/LFA‐1 adhesion.

Enhanced Expression of Lipocortin - 1 as a New Immunosuppressive Protein in Cancer Patients and Its Influence on Reduced In Vitro Peripheral Blood Lymphocyte Response to Mitogens

To clarify the mechanism of immunosuppression in cancer-bearing hosts, the expression of lipocortin-1 (LC1), a new immunosuppressant, and its effects on the in vitro mitogen responsiveness of peripheral blood mononuclear cells (PBMC) were investigated in cancer patients. Immunohistochemical studies showed LC1 expression in the cytoplasm of inflammatory cells morphologically recognized as a macrophage lineage, infiltrating the tumor interstices of gastric cancer. LC1 protein was detected in the ascitic fluid from gastric cancer patients using Western blot analysis. LC1 expression in PBMC was studied using a fluorescence-activated cell sorter (FACScan), which revealed that the percentage of CD14 and LC1 double positive cells was much greater in cancer patients than in healthy individuals. The proliferative response of PBMC by concanavalin A (ConA) stimulation was significantly suppressed in patients with advanced cancer, while the intact mitogen responsiveness in healthy individuals was inhibited when recombinant LC1 was added to the cultures. A similar inhibitory effect was induced by adding the supernatant of cancerous ascites or spleen cell cultures derived from advanced cancer patients. These inhibitory effects were eliminated, and the suppressed mitogen responsiveness in cancer patients recovered to the control level of healthy individuals when anti-LCI antibody was added to the cultures. These findings indicate that LC1 is produced and expressed in cancer patients, and deeply involved in the immunosuppressive mechanism of tumor-bearing hosts.

Histological Grade of Malignancy of Colorectal Carcinoma with Hematogenous Metastasis after Curative Resection.

大腸癌の血行性転移再発の組織学的予知因子の検索を行った.進行大腸癌の治癒切除症例で, 術後の血行性転移再発症例 (A群) 25例, 非再発症例 (B群) 32例の合計57例を対象とし, 浸潤に伴う, より低い分化程度への形態変化の有無, 癌深部での先進部における低分化腺癌の要素 (以下, por compo.) の有無, 粘液成分 (以下, muc compo.) の有無の点より検討した.形態変化は, A群では25例中16例64.0%にみられ, B群の32例中8例25.0%に比べ有意に高頻度であった.またpor compo-もA群では21例84.0%にみられ, B群の13例40.6%に比べ有意に高頻度であった.しかし, muc compo-に関しては両群間に有意差を認めなかった.以上より, 癌組織内で浸潤につれ低い分化形態への形態変化を認める症例, 特に癌先進部において低分化腺癌の要素を認める症例は, 血行性転移再発の可能性が高く, 組織学的予知因子となるものと考えられた.

Intraperitoneal Administration of Recombinant Interleukin-2 (rIL-2) Against Peritoneal Dissemination of Gastric Cancer

Postoperative intraperitoneal (i.p.) daily administration of recombinant interleukin 2 (rIL-2) was performed in gastric cancer patients with or without peritoneal metastasis. A remarkable increase in NK activity as well as LAK activity in peritoneal exudate cells (PEC) was observed during the treatment, and cytological examinations revealed a disappearance of malignant cells in peritoneal effusions or intraperitoneal washings in either patient examined. Preventive effects against peritoneal metastasis were achieved in 2 out of 4 patients receiving i.p. rIL-2. However, this treatment could not lead to a clinical efficacy in patients with peritonitis carcinomatosa.