[A Case of Resection of T2N0 Colon Cancer with Synchronous Solitary Lung Metastasis].

A 73-year-old man was referred to our hospital for anemia. He underwent a colonoscopy; a 15-mm Ip polyp and a 30- mm type 1 lesion were found in the sigmoid colon. Pathological examination results indicated a well-differentiated adenocarcinoma. Thoracic computed tomography(CT)revealed a mass lesion 12 mm in diameter in the left lung lobe. The patient underwent a laparoscopic sigmoidectomy and D3 lymph node dissection and was discharged in a good condition. He then underwent a diagnostic-therapeutic segmental pulmonary resection for the pulmonary mass. Postoperative pathological findings indicated pT1b(SM), ly0, v0 and pT2(MP), ly1, v1, pN0 for the 2 lesions of the colon. The pulmonary mass was diagnosed as a metastatic adenocarcinoma based on immunostaining examination(CK7: negative, CK20: positive, TTF-1: negative, and CDX-2: positive). The patient is currently under follow-up as an outpatient without recurrence.

Hemophagocytic syndrome in ileum-origin B-cell lymphoma.

A 56 year-old-man was admitted due to upper abdominal tumor and was diagnosed as having stage IVb diffuse B-cell malignant lymphoma that originally developed in the terminal ileum. The first and the second administrations of CHOP (cyclophosphamide, 750 mg/m(2); adriamycin, 50 mg/m(2); vincristine, 1.4 mg/m(2); and prednisolone, 100 mg/day) therapy were effective; however, the third course of therapy was postponed because of an episode of massive hematochezia. After this episode, lymph nodes began to enlarge and progressive pancytopenia occurred. Bone marrow smear showed the proliferation of reactive histiocytic cells which phagocytized red blood cells, white blood cells, and platelets. B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) was diagnosed. This case is extremely rare because: (1) LAHS occurred in an ileum-origin B-cell lymphoma, and (2) LAHS developed during an interval after chemotherapy.

Overexpression of the thrombospondin 2 (TSP2) gene modulated by the matrix metalloproteinase family expression and production in human colon carcinoma cell line.

Thrombospondin 2 (TSP2) is an extracellular matrix glycoprotein involved in tumor progression and angiogenesis. We evaluated whether overexpression of the TSP2 gene show an alteration of various genes by cDNA arrays in the colon carcinoma cell line SW480. The transformants with the human TSP2 gene overexpression showed a down-regulation of matrix metalloproteinase 2 (MMP2) and MMP9 in comparison to those with vector-control. Protein production of MMP2 and MMP9 decreased in the transformants overexpressing the TSP2 gene. Conversely, the SW480 transformants showed up-regulation of MMP12 and MMP17. These results suggested that the TSP2 gene is a multifunctional modulator of remodeling tissue in which matrix degradation is required.

Unique properties of 189 amino acid isoform of vascular endothelial growth factor in tumorigenesis.

The 189 amino acid isoform of vascular endothelial growth factor (VEGF189) has been shown to be more strongly associated with the cell membrane than other isoforms of human VEGF (VEGF121, VEGF165). To analyze the biological activities of these VEGF isoforms on tumor growth, we transfected human VEGF121, VEGF165 or VEGF189 cDNA into the human colon cancer cell line SW-480, and established several clones overexpressing these VEGF isoforms. The total amounts of VEGF protein in the culture supernatants of the VEGF189-transfectants were less than those of VEGF121 and VEGF165-transfectants. These transfectants showed no significant differences in growth in culture. Nevertheless, the rate of in vivo tumor growth of VEGF189-transfectants was faster than or equivalent to that of VEGF121-transfectants, while the VEGF165-transfectant showed the greatest enhancement of tumor growth. The protein levels of VEGF were markedly increased only in the VEGF189-transfectants cultured in the presence of heparin. The enhanced in vivo tumor growth of VEGF189-transfectants can be partly explained by the cell-associated features of VEGF189 molecules. The VEGF189 molecule, which is strongly bound to the cell surface, has unique properties and high potential in local angiogenesis and tumor growth in the cancer inductive microenvironment.

Angiopoietin-1 and vascular endothelial growth factor expression in human esophageal cancer.

Angiopoietin-1 (Ang-1) has been shown to act as an angiogenic promoter in embryonic angiogenesis by promoting vascular branching, pericyte recruitment and endothelial survival. Ang-1 expression has not been examined in human esophageal cancer. We examined Ang-1 and vascular endothelial growth factor (VEGF) gene expression in tumors from 45 esophageal cancer patients who underwent surgical resection. Forty (88.9%) of the 45 esophageal cancers revealed Ang-1 gene expression. VEGF121, VEGF165 and VEGF189 isoforms were detected in 93.3 (42/45), 55.6 (25/45) and 26.7% (12/45) of the cases, respectively. Ang-1 gene expression was significantly correlated with VEGF121 and VEGF165 gene expression (P=0.0289 and P=0.0127, respectively, Fisher's test). The results suggest that Ang-1 is associated with neovascularization in the cancer stroma through VEGF net-works in esophageal cancer.

Ribozyme mediated suppression of vascular endothelial growth factor gene expression enhances matrix metalloproteinase 1 expression in a human hepatocellular carcinoma cell line.

The levels of expression of various genes were altered in cellular transformants with manipulation of expression of single genes. Vascular endothelial growth factor A (VEGF-A) is a key molecule for tumor progression, although it is unclear how VEGF-A expression regulates various genes. Multiple gene expression levels were evaluated using cDNA arrays in a human hepatocellular carcinoma cell line (HLF) with suppression of the VEGF-A gene by anti-VEGF-A ribozyme (alphaVRz). The ribozyme-mediated suppression of VEGF-A gene solely up-regulated matrix metalloproteinase 1 (MMP1) gene level in HLF/alphaVRz. Levels of expression of other members of MMP family or tissue inhibitors of MMPs did not show any alteration. These results suggested that intracellular suppression of VEGF-A gene was specifically linked to up-regulation of MMP1 in human hepatocellular carcinoma cells.

Human thrombospondin 2 inhibits proliferation of microvascular endothelial cells.

This study was performed to characterize human thrombospondin 2 (TSP2). TSP2 has recently attracted attention as an endogenous negative regulator of angiogenesis in tumorigenesis. We cloned and transfected human TSP2 cDNA into the human colon cancer cell line SW-480. Stable transfectants (TSP2-1, TSP2-6) overexpressing TSP2 were established. Growth characteristics of TSP2-transfectants were investigated in vitro and in vivo. TSP2-transfectants showed similar growth properties to vector-transfectants and wild-type SW-480 cells. The overexpression of transfected human TSP2 cDNA did not affect proliferation of SW-480 cells. When the conditioned media of TSP2-transfectants were added to cultures of bovine pulmonary microvascular endothelial cells (BPMEC), the BPMEC proliferation was significantly inhibited. These results suggested that human TSP2 is a potential inhibitor of angiogenesis.