Biomedical subjects

Haruo Ohtani

Publications and source records attributed to Haruo Ohtani.

23 records · Page 2Linked to original sources

PubMed2002

Gene therapy for pancreatic cancer using an adenovirus vector encoding soluble flt-1 vascular endothelial growth factor receptor.

INTRODUCTION: Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. The soluble form of flt-1 VEGF receptor inhibits VEGF activity in a dominant-negative manner. AIM: This study demonstrated the regional tumor suppression effect of adenovirus-mediated soluble flt-1 in human pancreatic cancer cells. METHODOLOGY: The VEGF expression level was examined in nine cell lines. Panc-1 and PK-8 were used as lower- and higher-VEGF-producing cell lines, respectively. The in vitro proliferation of cancer cells infected with adenovirus vectors encoding soluble flt-1 (Adsflt) and control vectors (AdLacZ) was not different. To assess the in vivo tumor growth suppression, cancer cells were inoculated subcutaneously in SCID mice. Adsflt, AdLacZ, or vehicle was injected directly into the tumors. The early process of tumor angiogenesis in a dorsal skinfold chamber was monitored by intravital microscopy. RESULTS: In both Panc-1 cells and PK-8 cells, the tumor growth of the Adsflt-treated group was significantly suppressed. The microvessel density, revealed by CD31 immunostaining, was also significantly lower in the Adsflt-treated group. Apoptosis index was higher in the Adsflt group. Immunofluorescence staining revealed the expression of VEGF not only in cancer cells but also in tumor stromal cells. Wild-type cells and AdLacZ-infected cells prompted strong tumor angiogenesis, whereas Adsflt-infected cells failed to exert such an effect. CONCLUSION: These results indicate that antiangiogenic gene therapy using soluble flt-1 might be an effective approach for pancreatic cancer treatment.

Adenoviridae↗

PubMed2002

Close association between Fas ligand (FasL; CD95L)-positive tumor-associated macrophages and apoptotic cancer cells along invasive margin of colorectal carcinoma: a proposal on tumor-host interactions.

Anti-tumor immune responses are considered to be one of the key host reactions in human colorectal cancer, with T cells as important effector cells. For the induction of tumor-specific immunity, processing of cancer cells and priming of T cells by antigen-presenting cells are important. The present study was designed to clarify the relationship between Fas ligand (FasL; CD95L) expression and apoptotic cancer cells. Immunohistochemistry using frozen sections taken from 58 patients with colorectal cancer revealed that stromal cells composed mainly of tumor-associated macrophages expressed FasL, leaving cancer cells negative for FasL. These macrophages were abundantly distributed along the invasive margin. In situ hybridization revealed that these macrophages as well as cancer cells expressed FasL mRNA, whereas macrophages in the normal colon mucosa rarely expressed FasL. Apoptotic cancer cells recognized by monoclonal antibody M30 CytoDEATH were localized not only in cancer cell nests, but also in the stroma along the invasive margin showing a dissociated pattern, which was particularly evident in the areas of FasL+ macrophages. Furthermore, these macrophages, phenotypically similar to dendritic cells, occasionally contained M30+ apoptotic cancer cells in the cytoplasm. Clinicopathologic analyses in 123 cases revealed 1) a positive correlation between the degree of dissociated M30+ apoptotic cancer cells and the number of macrophages along the invasive margin and 2) an inverse association between the degree of dissociated M30+ apoptotic cancer cells and the occurrence of hematogenous metastasis after surgical resection of the primary tumor. In conclusion, the present study shows the importance of FasL+ activated macrophages as one of the host defense mechanisms against cancer cell spread in human colorectal cancer.

Aged↗

PubMed2002

CXC chemokine receptor 1 (CXCR1) is expressed mainly by neutrophils in inflamed gut and stomach tissues.

CXC chemokine receptor 1 (CXCR1) is one of the important receptors for CXC chemokines with ELR motif, of which interleukin 8 (IL-8; CXCL8) is representative. To identify the cell type(s) of CXCR1-expressing cells in inflamed stomach and gut tissues, we performed immunoperoxidase method using pre-fixed frozen sections. In chronic gastritis associated with Helicobacter pylori infection (7 cases), CXCR1 was positive in neutrophils (polymorphonuclear leucocytes) in the lamina propria near the neck region and those in pit abscess. In ulcerative colitis (6 cases) and Crohn's disease (5 cases), CXCR1 was sporadically expressed by neutrophils in the mucosa, and particularly CXCR1+ neutrophils were abundantly distributed in inflammatory granulation tissue in ulcer base. Double staining confirmed co-localization of CXCR1 and neutrophil elastase. Neither CD3+ T lymphocytes nor CD68+ macrophages were positive for CXCR1. Immunoelectron microscopy confirmed the cell surface localization of CXCR1. Neutrophils protect the host from microbial pathogens. However, they also cause damages to host tissues in chronic inflammation. Therefore, our study underscores the importance of CXCR1 expression in inflammatory processes.

Colitis, Ulcerative↗

PubMedDate not supplied

Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease.

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is selectively expressed in the endothelial cells of intestinal mucosa and gut-associated lymphoid tissue (GALT). Engagement of MAdCAM-1 to its ligand, integrin alpha4beta7, on lymphocytes is associated with the homing of gut-associated lymphocytes to normal gastrointestinal tract and inflammation sites. The present study was designed to elucidate differences between Crohn's disease (CrD) and ulcerative colitis (UC) from the expression patterns of MAdCAM-1. Samples were taken from 40 patients with CrD and 24 patients with UC at surgical resection. Using frozen sections, immunohistochemistry was performed for MAdCAM-1, E-selectin and CD34. MAdCAM-1+ venules were abundant in inflamed mucosa in both UC and CrD. In contrast, clear differences were noted between UC and CrD in the inflammatory area in the ulcer base, that is, MAdCAM-1+ venules were more abundant in CrD than in UC (P < 0.001), while E-selectin was expressed equally in these venules in both diseases. Furthermore, CrD was characterized by the occurrence of MAdCAM-1+ venules in deeper layers of the intestinal tissue, mainly in lymphoid aggregates. Our data indicated more extensive expression of MAdCAM-1 in CrD, which could contribute not only to mucosal inflammation, but also to transmural inflammation in CrD.

Adult↗

PubMedDate not supplied

Osteosarcoma arising in the breast.

We report on a 49-year-old woman with osteosarcoma arising in the breast. She had undergone two consecutive excision biopsies for right breast tumors at ages 40 and 42 years. The tumors were diagnosed as a fibroadenoma and a benign phyllodes tumor, respectively. At age 46 years, she noticed a gradually enlarging mass in the same breast. After 3 years, at age 49 years, total mastectomy was performed. The tumor occupied the entire breast and measured 12x9x8.5 cm. The tumor cells were spindle-shaped and pleomorphic, with large, irregular nuclei and distinct nucleoli. Many tumor cells had characteristics of osteoblastic and chondroblastic elements producing osteoid, osseous, and cartilaginous intracellular substances. Pathologic mitoses and apoptotic cells were frequent. Neoplastic cells had infiltrated the skin. Blood and lymph vessel invasion was present. Tumor cells expressed vimentin, osteopontin, vascular endothelial growth factor, CD10, and alkaline phosphatase, but did not express keratin. Chemotherapy was not effective. The patient died of multiple pulmonary metastases 9 months after mastectomy.

Adult↗