[Human tumor sensitivity to 5-fluorouracil influenced by dihydropyrimidine dehydrogenase mRNA in the tumor].
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Animals↗
Biomedical subjects
M Kitajima
Publications and source records attributed to M Kitajima.
Rebamipide attenuates gastric microcirculatory disturbances in the early period after thermal injury in rats.
In our previous study we showed that rebamipide attenuated gastric erosions and active oxygen species released only from the gastric mucosa and not from circulating leukocytes after thermal injury. This study was designed to examine whether rebamipide affects the potential of active oxygen generation from circulating leukocytes, and attenuates microcirculatory disturbance caused by thermal injury to skin. Rats were anesthetized and a 30% full skin-thickness dorsal burn was inflicted. Microvascular images and leukocytes were observed using in vivo microscopy. Endothelial damage was assessed by monastral blue B deposits. Active oxygen species were measured by the chemiluminescence method. Rebamipide (100 mg/kg) decreased leukocyte rolling and monastral blue B deposits in venules but did not improve arteriolar contractions 15 min after thermal injury. These results suggest that rebamipide preserves gastric microcirculation possibly through inhibition of leukocyte adhesion and endothelial damage caused by thermal injury to skin.
Alanine↗
[Ischemic disease of the intestine].
With the remarkable progress in diagnostic techniques, the recent increase in the incidence of arteriosclerosis and the gradually aging population, a great deal of attention is now being focused on intestinal ischemia and this disease has come to be regarded as one of the clinically important pathological conditions. From the clinic aspect, special attention should be directed to the artery which is involved in intestinal ischemia. Furthermore acute superior mesenteric arterial ischemia (SMA ischemia), ischemic colitis, non-occlusive mesenteric ischemia (NOMI) require serious attentions. Few specific findings of these pathological conditions can be obtained in general examinations, therefore angiography is the most useful technique for making difinitive diagnoses. SMA ischemia and NOMI are progressive diseases and their prognoses are poor. The progress of ischemic colitis is gradual and the conservative therapy consisting of fasting, drip infusion and antibiotic administration is generally effective in treating this disease.
Acute Disease↗
[Prognostic factors of esophageal cancer].
A number of molecules involved in the process of invasion and metastasis of cancer cells have been demonstrated as a biological prognostic parameter. In esophageal cancer, overexpression of the oncogenes (c-erbB, int-2/hst-1/cyclin D1, MDM2), altered expression of suppressor genes (p 16, DCC), and abnormal expression of adhesion molecules (E-cadherin, alpha-catenin) has been reported as markers of high malignant potential. Proliferation markers (Ki-67, AgNORs, PCNA) and angiogenetic factors (intratumoral microvessel density, VEGF) are also related to the prognosis of the patients with various cancers including esophageal cancer. Prognostic significance of p53 is still controversial. In addition to the clinicopathological parameters, combination of these biological markers would be important to predict the clinical outcome of the cases and to establish an individualized strategy of the treatment of each case according to the biological behavior of the cancer cells.
Cell Division↗
Characteristics of Helicobacter pylori strains isolated from patients with different gastric diseases.
The pathogenesis of chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis is considered to be related to infection by Helicobacter pylori. The purpose of this study was to investigate the characteristics of H. pylori strains isolated from patients with various gastric diseases. Fifty strains of H. pylori were clinically isolated at Keio University Hospital and were assessed for (i) vacuolating cytotoxin (VT) production, by cytotoxic assay using rabbit kidney (RK) 13 cells; (ii) the expression of cytotoxin associated gene (cagA), by polymerase chain reaction; and (iii) motility on a semi-solid plate. Positivity for VT production by H. pylori strains isolated from patients with chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, was 100%, 89%, 92%, 100%, and 60%, respectively. There was no significant difference in the incidence of positivity for cagA among the strains isolated from different gastric diseases. Swarming distances, which indicate motility of H. pylori strains, were 12.7, 13.2, 12.8, 16.6 and 9.2mm in strains from chronic gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and remnant gastritis, respectively, with H. pylori isolated from remnant gastritis showing significantly less motility than H. pylori isolates from other diseases. There were no significant differences in VT production and cagA positivity among the H. pylori strains.
Animals↗
[Does incidence of carcinoma of the esophagogastric junction increase?].
The incidence of carcinoma of the esophagogastric junction was evaluated based on data from the Japanese Esophageal Cancer Registry during the periods 1976-1994 and the Japanese Gastric Cancer Registry during 1963-1989. Although the number of cases of carcinoma of the esophagogastric junction had increased, the incidence was evaluated to have decreased. On the other hand, there are some reports that the incidence of carcinoma of the esophagogastric junction and the cardia have increased in the USA and western European countries. The trend is controversial and it is necessary to evaluate the location of lesions accurately. Possible explanations for the increasing trend etc. therefore are smoking and alcohol intake, Helicobacter pylori infection, hiatal hernia. To determine the incidence of carcinoma of the esophagogastric junction more reliably, the nationwide cancer registry program should continue.
Esophageal Neoplasms↗
An Endoscopic Observation of Intraductal Papillary Lesion.
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Journal Article↗
Molecular Targeting for Epidermal Growth Factor Receptor Expressed on Breast Cancer Cells by Human Fusion Protein.
Recombinant human ribonuclease 1 (RNase 1) was chemically linked to recombinant human epidermal growth factor (EGF). The cytotoxicity of this conjugate was assayed using MTT assay. The EGF-RNase conjugate showed dose-dependent cytotoxicity against breast and squamous cell carcinomas overexpressing the EGF receptor (EGFR). The cytotoxicity of the conjugate correlated positively with the level of EGFR expression by each cell line. These results suggest that the EGF-RNase conjugate is a more effective anticancer agent with less immunogenicity and toxicity than conventional chimeric breast cancer toxins.
Journal Article↗
The Role of Contrast-Enhanced High Resolution MRI in the Surgical Planning of Breast Cancer.
The role of contrast-enhanced high resolution MRI for planning surgery in breast cancer was evaluated. Of 72 patients examined, 57 patients had invasive ductal carcinoma, 2 had mucinous carcinoma, 1 had medullary carcinoma, 7 had invasive lobular carcinoma, 2 had ductal carcinoma in situ (DCIS) and 3 had Paget's disease. A 1.5 T Signa imager (GE Medical Systems, Milwaukee, WI) was used with a dedicated breast coil. The pulse sequence based on RARE(rapid acquisition with relaxation enhancement) was used with a fat suppression technique. After examining both breasts, the affected breast alone was examined with Gd enhancement. Linear and/or spotty enhancement on MRI was considered to suggest DCIS or intraductal spread in the area surrounding the invasive cancer. Of 72 patients, 50 showed linear and/or spotty enhancement on MRI and 41 of those 50 patients had DCIS or intraductal spread. In contrast, 22 of 72 patients were considered to have little or no intraductal spread on MRI and 17 of the 22 patients had no or little intraductal spread on pathological examination. The sensitivity, specificity and accuracy for detecting intraductal spread on MRI were 89%, 82% and 81%, respectively. Discrepancies in the estimated extent of intraductal spread were less than 2 cm in 90% of the patients according to pathological mapping. High resolution MRI was considered useful in detecting intraductal spread and in estimating its extent, however, larger study using precise correlation with pathology is necessary.
Journal Article↗
Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/reperfusion injury.
BACKGROUND: Oxygen-derived free radicals (FRs) are critical mediators of ischemia/reperfusion injury. Inflammatory cytokines have been shown to play important roles in tissue injury. To examine the relationship between FRs and interleukin-1 (IL-1) in hepatic ischemia/reperfusion injury, we used interleukin-1 receptor antagonist (IL-1ra) to block endogenous IL-1 production in a rat model of hepatic ischemia/reperfusion. METHODS: Female SD rats were subjected to 30 min of hepatic ischemia followed by reperfusion. The animals were divided into two groups, control group and IL-1ra-treated group, according to the rinse solution. In both groups, FR production, histological changes, and interactions between leukocytes and endothelial cells were analyzed in the course of reperfusion. RESULTS: In the control group, production of FRs increased significantly after 60 min of reperfusion. After 60 and 180 min of reperfusion, histological examination showed atrophy and degeneration of hepatocytes. Hepatic microcirculation demonstrated a marked increase in the number of leukocytes adherent to endothelial cells and of injured cells after reperfusion. In the IL-1ra-treated group, IL-1ra pretreatment markedly reduced FR production after 60 min of reperfusion, the number of leukocytes adherent to endothelial cells, and tissue injury. CONCLUSION: These data clearly show an important role for IL-1 in the induction of FR production, leukocyte adhesion, and tissue injury after hepatic ischemia/reperfusion injury.
Animals↗
Efficacy of intraportal infusion of prostaglandin E1 to improve the hepatic blood flow and graft viability in porcine liver transplantation.
BACKGROUND: Prostaglandin E1 (PGE1) has been reported to have a protective effect in experimental and clinical models of liver damage. The aim of this study was to elucidate the effects of the intraportal infusion of PGE1 on hepatic blood flow and graft viability after orthotopic liver transplantation in pigs. METHODS: First, the hepatic arterial flow (HAF), portal venous flow (PVF), and liver tissue blood flow (LTBF) were measured during the continuous intravenous or intraportal infusion of PGE1. Second, two groups of pigs underwent orthotopic liver transplantation: group A, untreated controls; and group B, animals that received intraportal PGE1 for 2 hr after vascular reconstruction of the allograft. Changes in HAF, PVF, LTBF, and hepatic function were measured. RESULTS: The intraportal infusion of PGE1 significantly increased HAF and had no effect on blood pressure, PVF, or LTBF. In group B, HAF and LTBF increased significantly with time. In group A, HAF remained unchanged and a decrease in LTBF was observed. Group B exhibited a higher arterial ketone body ratio and a greater bile flow compared with group A. A significant elevation in serum glutamic oxaloacetic transaminase concentration was observed in group A, but not in group B. CONCLUSIONS: This study demonstrates that the intraportal infusion of PGE1 improves hepatic allograft blood flow, predominantly through an effect on HAF, and may improve graft viability after orthotopic liver transplantation.
Alprostadil↗
Active oxidants mediate IFN-alpha-induced microvascular alterations in rat mesentery.
The present study was designed to investigate the influences of IFN-alpha on the microcirculatory hemodynamics. The mesenteric microcirculation of male Wistar rats was observed through an intravital fluorescence microscopic system. The leukocyte behavior, RBC velocity, and albumin leakage were monitored simultaneously before and after a continuous infusion of IFN-alpha. In other rats, the oxidant-sensitive fluorescence probe dihydrorhodamine-123 (DHR) fluorescence was observed in the same set up. Administration of IFN-alpha increased the number of adherent and emigrated leukocytes and decreased the RBC velocity in mesenteric venules. Oxidative stress indicated by DHR fluorescence was exacerbated in microvessels of IFN-alpha-treated rats. Following the leukocyte recruitment and oxidative stress, an exaggerated albumin leakage was observed. Thrombus formation in venules and hemorrhage along venules were frequently observed in rats treated with IFN-alpha. N,N'-dimethylthiourea, a scavenger of hydrogen peroxide and a hydroxyl radical, largely prevented these microvascular responses. Pretreatment of rats with mAb directed against either CD18 or ICAM-1 also attenuated the IFN-alpha-induced microvascular alterations. It is concluded, therefore, that a high concentration of IFN-alpha stimulates CD18/ICAM-1-dependent adhesive interactions with endothelial cells and oxidant production of leukocytes, which leads to microcirculatory derangements characterized by decreased barrier function and reduced anticoagulant activity of venular endothelial cells.
Animals↗
Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat.
The inflammatory cytokines interleukin (IL) 1 and tumor necrosis factor (TNF) may play an important role in hepatic ischemia-reperfusion (I/R) injury. To study the role of IL-1 in hepatic I-R injury, we investigated the effect of pretreatment with IL-1 receptor antagonist (IL-1ra) on the production of IL-1, TNF, histological findings in the liver, and the survival rate for 7 days. Rats were subjected to 90 min of partial liver warm ischemia by clamping the vessels of the left and middle lobes. In the IL-1ra-treated group, IL-1ra was given 5 min before liver ischemia was induced. IL-1alpha and TNF levels were determined in blood and liver at 0, 30, 90, and 180 min after reperfusion. In a second experiment to determine the effect of IL-1ra pretreatment on survival rate, after 90 min of partial liver ischemia, the right lateral and caudate lobes were excised, leaving only the ischemic lobes. In both groups, IL-1alpha was undetectable in blood, but increased in liver tissue. TNF increased in both blood and liver tissue as reperfusion time increased. Histological evidence of tissue injury was minimal in the IL-1ra-treated group. Furthermore, in the IL-1ra-treated group, the production of TNF decreased in both blood and liver tissue compared with the nontreated group. Survival rates in the IL-1ra-treated and nontreated group were 80% and 30%, respectively. The data demonstrated that the production of IL-1 and TNF increases in hepatic I-R injury and that pretreatment with IL-1ra protects the liver from ischemic insult, indicating an important role for IL-1 in I-R injury.
Animals↗
Antitumor activity of paclitaxel against human breast carcinoma xenografts serially transplanted into nude mice.
BACKGROUND: Paclitaxel (BMS-181339: Taxol) is a promising agent against previously treated breast cancer. The antitumor activity of paclitaxel was evaluated using five human breast carcinoma xenografts in nude mice. METHODS: Paclitaxel at 20 mg/kg dissolved in 0.2 ml ethanol/cremophor EL solution was administered intraperitoneally daily for 5 days. RESULTS: Paclitaxel showed significant antitumor activity against MCF-7 and MX-1, but only limited activity against the other three xenografts (R-27, Br-10, and T-61), suggesting its substantially different antitumor spectrum from conventional antibreast cancer drugs. The different sensitivity of xenografts to paclitaxel was successfully reproduced in vitro using the MTT assay, when the cutoff concentration of paclitaxel was 20 microg/ml. CONCLUSION: Since no significant differences were observed in the pharmacokinetics of paclitaxel in sensitive and resistant tumor cell lines, the efficacy of this agent seemed to depend on the sensitivity of tumor cells rather than the intratumoral concentration of agent.
Animals↗
The role of stromal cells in the expression of interstitial collagenase (matrix metalloproteinase-1) in the invasion of gastric cancer.
BACKGROUND AND OBJECTIVES: In one of the steps of tumor invasion and metastasis, tumor cells must invade surrounding tissues and degrade the components of the basement membranes. Interstitial collagenase (matrix metalloproteinase-1: MMP-1) has been also investigated in relation to cancer invasion and metastasis. METHODS: We investigated the formation and mechanism of MMP-1 expression using gastric cancer cell lines and gastric fibroblasts derived from normal gastric mucosa by ELISA and immunohistochemistry. RESULTS: Production of MMP-1 protein in gastric fibroblasts was stimulated significantly by adding the conditioned medium of MKN-74. Localization of MMP-1 protein in the xenografted gastric cancer cell lines was heterogeneous according to different cell lines. CONCLUSIONS: These results suggested that the production of MMP-1 protein in tumor invasion was regulated by interaction between stromal cells, particularly fibroblasts, and tumor cells.
Animals↗
CA19-9 as a predictor of recurrence in patients with colorectal cancer.
BACKGROUND AND OBJECTIVES: CA19-9 is a cancer-associated carbohydrate antigen that plays a role in the process of tumor progression as an adhesion molecule. METHODS: We evaluated the prognostic value of CA19-9 tumor expression and CA19-9 preoperative and postoperative serum levels in colorectal cancer patients treated by complete resection. The most powerful discrimination was achieved using the three CA19-9 markers in combination. RESULTS: CA19-9 tumor expression was identified by immunostaining in 71.0% (86/121) of primary carcinomas. Positive CA19-9 serum levels (> or = 37 U/ml) were restricted to cases with positive tumor expression, and CA19-9 was detected more frequently in preoperative serum (20.6%, 25/121) than in 1-month postoperative serum (6.6%, 8/121). Positive tumor expression, positive preoperative serum level, and positive postoperative serum level were all predictive of increased cancer mortality. Patients with three negative parameters had no recurrences and 97.1% 5-year survival, whereas patients with three positive parameters had 62.5% recurrence and 42.8% 5-year survival. CONCLUSIONS: CA19-9 detection in tumor tissue and serum identified patients at high risk of cancer recurrence and death and may be useful in selecting patients for adjuvant therapy.
Adult↗
Frozen-section-guided breast-conserving surgery: implications of diagnosis by frozen section as a guide to determining the extent of resection.
This study was conducted to analyze retrospectively the results of performing sector resection on 56 breasts in 54 patients with breast cancer. The glands were resected with a 2-cm tumor-free margin on both lateral sides and the distal side, and with more than a 3-cm tumor-free margin on the nipple side. The frequency of positive resection margins for the cancer cells was 7/56 (12.5%) on the nipple side and 12/46 (26.1%) on the lateral sides, with an overall frequency of 15/56 (26.8%). There were positive resected margins for cancer cells on both the nipple and lateral sides in 4/46 patients (9%). Assuming the equivocal margins were positive for cancer cells, an accurate diagnosis by frozen section examination was made in 51 of the 56 operations (91.1%). Additional resection of the margins was performed in all 20 cases of a positive resected margin for cancer cells according to the diagnosis by frozen section. Thereafter, the resected margins became negative in 13 cases (65%), but remained positive in 7 cases (35%). These results show that performing diagnosis by frozen section of the surgical margins is an effective guide to resecting tumors adequately.
Adult↗
Per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer: the ultimate sphincter-preserving operation.
PURPOSE: The most important goal of sphincter-preserving operations for rectal cancer is to secure a distal surgical margin of safety and the anal sphincter. However, it is not always easy to transect the rectum and to secure a distal surgical margin of safety through the abdominal approach for tumors situated extremely low in the rectum. The aim of this study was to describe and to evaluate a new technique of per anum intersphincteric rectal dissection and coloanal anastomosis. METHODS: The rectum, including the entire width of the internal anal sphincter, is transected circumferentially via the anal route to secure the surgical margin of safety under direct vision and is mobilized proximally as far as possible through the intersphincteric plane. Per anum coloanal anastomosis is performed following transabdominal resection of the rectum. RESULTS: This technique has been used in 12 patients. There have been no instances of short-term or long-term anastomotic complications. CONCLUSIONS: This technique is safe when anastomosis must be performed at the dentate line. It is the best sphincter-preserving operation for lower rectal cancer and does not result in serious postoperative anal dysfunction.
Anal Canal↗