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Biomedical subjects

T Kiyama

Publications and source records attributed to T Kiyama.

At least 55 records · Page 3Linked to original sources
PubMed1990

Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice.

Thirty-two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF-positive surgical specimens and one (6%) of the 16 EGF-negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

Adenocarcinoma↗
PubMed1990

The correlation of epidermal growth factor with invasion and metastasis in human gastric cancer.

We examined the localization of epidermal growth factor (EGF) in 185 specimens of primary human gastric cancer using the avidin-biotin peroxidase complex immunohistochemical method on formalin-fixed paraffin-embedded sections. Thirty-four per cent of the gastric cancer specimens were positive for EGF, which was mainly located in the cytoplasm of the cancer cells and occasionally in the stromal cells, but was not detected in non-cancerous gastric epithelium. Moreover, the presence of EGF in gastric cancer was correlated with gastric wall invasion and lymph node metastasis. EGF was found more often in advanced cancers than in early ones (p less than 0.01), and also more often in cancers with lymph node metastasis than in those without (p less than 0.05). The five-year survival of patients with EGF-positive tumors was worse than that of patients with EGF-negative tumors (p less than 0.05). The presence of EGF in human gastric cancer may thus represent higher malignant potential.

Epidermal Growth Factor↗
PubMed1990

Changes in serum and tissue carcinoembryonic antigen with growth of a human gastric cancer xenograft in nude mice.

We established a human gastric cancer xenograft which, when inoculated into nude mice, showed a positive correlation between tumor growth and the serum level of carcinoembryonic antigen (CEA). Serum CEA levels in the mice rose continuously with increasing tumor weight after inoculation, showing a correlation coefficient of 0.96. A positive correlation was also observed between the tissue CEA level and tumor weight, the former increasing along with the latter. Furthermore, the level of serum CEA closely paralleled that of tissue CEA. The serum CEA level fell after tumor extirpation, with a half-life of approximately 86 h. These results suggest that the elevation of serum CEA is attributable to the gain in tumor weight as well as the increase of CEA production in the tumor tissue. Thus, human gastric cancer xenografts in nude mice are a good model for examining the biological role of CEA.

Adenocarcinoma↗
PubMed1989

Contrasting actions of estradiol on the growth of human gastric cancer xenografts in nude mice.

The effects of estradiol on the growth of six human gastric xenografts in nude mice were studied and diverse effects were found, including one case of stimulation, two of inhibition and three of unchanged condition. Neither the histological features of the original tumor nor the estrogen-binding capacity seemed to be related to the response to estradiol. It is concluded that the growth of human gastric cancer can be modulated by estradiol.

Animals↗
PubMed1989

[Combination therapy with etoposide, adriamycin and cisplatin in advanced primary and recurrent gastric cancer].

Fourteen patients with advanced gastric cancer consisting of seven primary cases and seven recurrent cases were treated with the combination of etoposide, adriamycin and cisplatin (EAP). One of the primary cases (14%) and three of the recurrent cases (43%) responded to the therapy, but a high incidence of toxicities including leukopenia, thrombocytopenia, alopecia, nausea and vomiting was observed. It is concluded that EAP therapy can be useful in the treatment of advanced gastric cancer if countermeasures to the toxicities of these drugs are considered.

Adenocarcinoma↗
PubMed1988

Simultaneous gastric cancer in monozygotic twins.

Monozygotic twins developed gastric cancers that were found almost simultaneously. A 47-year-old man complained of nausea and vomiting; an upper gastrointestinal series and endoscopy revealed advanced gastric cancer invading the serosa. Palliative subtotal gastrectomy was performed. In his asymptomatic twin a gastric polyp was detected during a screening examination, and this was observed for 2 years. After the former twin had undergone surgery, the latter twin was given a detailed endoscopic examination, and biopsy revealed gastric cancer limited to within the mucosa. Curative subtotal gastrectomy was performed. The noncancerous gastric mucosa of the former twin showed severe intestinal metaplasia, but that in the latter showed only spotty metaplasia. They had lived together for 40 years, but the former was a heavy smoker and drank alcohol, while the latter did not. These differences in taste might have contributed to the observed difference in intestinal metaplasia, which indicates chronic mucosal damage.

Adenocarcinoma↗
PubMedDate not supplied

Effect of matrix metalloproteinase inhibition on colonic anastomotic healing in rats.

Wound strength depends on the balance between collagen synthesis and degradation; however, the role of collagen breakdown in wound healing is still not well understood. We investigated the role of matrix metalloproteinases in wound healing by using BE16627B, a matrix metalloproteinase inhibitor. Identical surgical procedures consisting of a colonic anastomosis (single-layer, inverted) and implantation of an osmotic pump in the back were performed in male Sprague-Dawley rats weighing 270 to 290 grams. The animals were randomly assigned to receive either BE16627B (n = 10) dissolved in dimethylsulfoxide and diluted with ethylene glycol at a dosage of 2.4 mg/rat/day for 3 days or the vehicle solution alone (n = 11). The solutions were administered through the surgically implanted osmotic pumps. The animals were killed 4 days after surgery, and the colonic bursting pressure (mm Hg) and hydroxyproline concentration (microg/mg wet tissue, index of collagen) were measured. The administration of BE16627B enhanced colonic anastomotic healing, as measured by the increase in the colonic bursting pressure (160 +/- 12 vs. 125 +/- 7 mm Hg; P < 0.05) and the increase in the soluble fraction of collagen (0.27 +/- 0.01 vs. 0.21 +/- 0.01 microg/mg wet tissue; P < 0.01) in the anastomosis. Histologic examination of the tissue revealed that the use of BE16627B resulted in the preservation of the multilayered colonic structure and increased the network of collagen between both ends of the colon in the thickening submucosal layer. These findings demonstrate that the inhibition of matrix metalloproteinase activity influences colonic anastomotic healing, indicating a potential mechanism for enhancing anastomotic healing.

Anastomosis, Surgical↗
PubMedDate not supplied

Effect of nutritional route on colonic anastomotic healing in the rat.

Although early enteral feeding has been shown to benefit cutaneous healing when compared to parenteral feeding, the effect of the route of nutritional support in gastrointestinal anastomotic healing has not been defined. The aim of the present study was to determine whether the route of nutritional support influences colonic anastomotic healing. Twenty male Sprague-Dawley rats weighing 270 to 290 grams underwent identical surgical manipulation consisting of central venous catheterization, gastrostomy insertion, and distal colonic anastomosis (single-layer, inverted). Identical nutrient infusates composed of 4.25% amino acids, 25% dextrose, and vitamins were administered, with half the animals receiving the infusions via the gastrostomy and the other half via the venous catheter. Animals were killed 5 days after surgery. There were no differences in nutritional parameters between the parenterally and enterally fed groups. Colonic anastomotic bursting pressure was significantly higher in the enterally fed group (180 +/- 6 vs. 150 +/- 11 mm Hg; P <0.01). The measured insoluble collagen and total protein content in anastomotic tissue were enhanced in the enterally supported group. The fraction of soluble (newly synthesized) collagen did not differ between the two groups. The data demonstrate that the route of nutrient administration influences colonic anastomotic healing. The preservation of colonic structural collagen in the enteral group may improve the ability of the gut to hold sutures and thus enhance anastomotic healing.

Amino Acids↗
PubMedDate not supplied

Expression and function of inducible nitric oxide synthase during rat colon anastomotic healing.

Nitric oxide plays a significant but incompletely understood role in fibroblast function and cutaneous wound collagen synthesis; however, the participation of inducible nitric oxide synthase (iNOS) in gastrointestinal anastomotic healing has not been studied. Male Sprague-Dawley rats underwent single-layer left colonic anastomosis. Animals were killed at 24-hour intervals postoperatively and the anastomosis was excised. Parallel uninjured colon tissue samples were also analyzed. Reverse transcriptase-polymerase chain reaction confirmed the absence of iNOS messenger RNA in control colon and expression of the gene in anastomotic tissue on all study days. Northern hybridization demonstrated maximal iNOS messenger RNA transcription on day 1 with decreased levels on days 3 and 5. iNOS enzyme activity, measured biochemically by the conversion of [(3) H-arginine to [(3) H]-citrulline ex vivo, was also maximal on day 1 (7.35 +/- 1.34 pmol/mg protein/min [+/- standard error of the mean], n = 10) and decreased on days 3 (4.37 +/- 2.32 pmol/mg protein/min; n = 6) and 5 (2.80 +/- 0.92 pmol/mg protein/min; n = 6). Immunohistochemical staining demonstrated that (1) iNOS expression is confined to a discrete cell population in the region of the anastomosis containing inflammatory cells; (2) those cells assume a highly conserved position on the luminal edge of the proliferating scar; and (3) the iNOS-expressing cells are present throughout the fibroplastic phase of healing. To functionally assess the role of iNOS in colonic healing, rats were treated with a continuous intravenous infusion of S-methylisothiourea (a selective inhibitor of iNOS) at a dosage of 200 mg/kg/day for 5 days after anastomosis. There was a significantly reduced anastomotic bursting pressure in rats treated with the inhibitor as compared to rats treated with intravenous normal saline solution (108.4 +/- 13.2 mm Hg vs. 148.4 +/- 10.3 mm Hg; P <0.05). These results suggest that iNOS gene expression is induced during colonic anastomotic healing, that it is present through all phases of healing but is maximal through the inflammatory phase, and that iNOS activity is required for optimal anastomotic healing.

Anastomosis, Surgical↗