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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 181 records · Page 10Linked to original sources

Pathophysiological response of cytokines and vasoactive agents in patients undergoing total gastrectomy.

OBJECTIVE: To investigate the involvement of vasoactive agents, endothelin (ET)-1, and atrial natriuretic peptide (ANP), and the responses of cytokines in patients undergoing total gastrectomy. DESIGN: Prospective study. SETTING: University hospital, Japan. SUBJECTS: 20 patients with advanced gastric cancer who had undergone total gastrectomy with lymph node dissection. INTERVENTIONS: Serum or plasma samples collected on the day before the operation, at the time of skin closure, and on postoperative days 1, 3, 5, and 7. MAIN OUTCOME MEASURES: Concentrations of acute phase reactants, cytokines (interleukin (IL)-1, tumour necrosis factor (TNF) and interleukin (IL)-6), and vasoactive agents (ET-1 and ANP). RESULTS: There were significant increases in concentrations of IL-6 and acute phase reactants postoperatively. ET-1 and ANP concentrations did not change significantly. CONCLUSION: There was no correlation between concentrations of the vasoactive agents ET-1 and ANP, and those of acute phase reactants or cytokines in serum or plasma in patients undergoing total gastrectomy.

Acute-Phase Proteins↗

Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human 'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas.

The gene encoding human pancreatic ribonuclease 1 (hpRNasel) was fused with a gene encoding human epidermal growth factor (hEGF). The hybrid human protein was isolated from Escherichia coli inclusion bodies, refolded and purified to homogeneity. The fusion protein competed with 125I-hEGF for binding to hEGF receptors (EGFR) and had ribonucleolytic activities approaching those of hpRNase1. Several conformations having different enzymatic activities could be detected after reversed-phase high-performance liquid chromatographic analysis, the less hydrophobic molecules being the most active. The hybrid protein was specifically cytotoxic to A431, an EGFR overexpressing squamous carcinoma cell line, with an IC50 of approximately 10(-7) M. In contrast, recombinant hpRNase1 had an IC50 higher than 10(-4) M. A mixture of free hEGF and free hpRNasel was not more cytotoxic than hpRNasel alone and no cytotoxicity was detected in EGFR-deficient control cells. Taken together, these data suggest that this construct might be useful for targeted therapy of esophageal, lung and other squamous cell carcinomas and also breast cancers overexpressing EGFR, which correlate with a poor prognosis and cannot be cured by surgery alone. Engineering hybrid molecules with endogenous human proteins for targeted therapy may alleviate the dose-limiting immunogenicity and toxicity of conventional immunotoxins.

Binding, Competitive↗

An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer.

The purpose of this study was to evaluate the feasibility and efficacy of 3-hour infusional paclitaxel for the treatment of advanced gastric cancer with measurable metastatic diseases. Eligibility criteria included no more than one regimen of prior chemotherapy. Paclitaxel was administered as an intravenous infusion over 3 hours at a dose of 210 mg/m2 every 3 weeks. Premedication of dexamethazone, ranitidine, and diphenhydramine were given to all patients. Sixteen patients were registered in the study. One patient did not receive paclitaxel because of gastrointestinal bleeding before the initiation of drug's administration. Thirteen of the 15 patients had a prior history of chemotherapy. Although 10 patients (67%) developed grade 4 neutropenia, no serious infections occurred during the study. Nonhematologic toxicities were generally mild. Three (20%) patients who showed evidences of resistance to the previous intensive regimen achieved a partial response. In conclusion, a 3-hour infusion of paclitaxel is a safe and promising treatment for advanced gastric cancer. Paclitaxel appears to be non-cross resistant to other agents that are commonly used for gastric cancer. A large-scale phase II study is now underway.

Adult↗

Case report: Metachronous early gastric carcinoma in a reconstructed gastric tube after radical operation for oesophageal carcinoma.

The incidence of double cancer has increased as a result of the significant advances in both diagnostic procedures and anti-cancer therapy, and as the outcome of oesophageal squamous cell carcinoma (ESCC) has improved, the number of cases of double cancer of the oesophagus and stomach has also increased. Two patients with metachronous early gastric carcinoma in a reconstructed gastric tube were successfully treated after subtotal oesophagectomy for ESCC. These cases have shown that early diagnosis of second cancer is very important for curative therapy.

Adenocarcinoma↗

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats.

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.

Animals↗

[Laparoscopic surgery for early gastric cancer--its advantages and pitfalls].

We have successfully established two different laparoscopic procedures for early gastric cancer since March 1992, which are laparoscopic wedge resection of the stomach using a lesion-lifting method and laparoscopic intragastric mucosal resection. The indication is as follows; (A) mucosal cancer, (B) < 25 mm, if the lesion is elevated type, (C) < 15 mm and Ul (-), if the lesion is depressive type. The advantages of these methods are; 1) minimally invasiveness, 2) sufficient surgical margin, 3) feasibility of detailed histology, 4) feasivility of perigastric lymph node dissection. In contrast, there are several problems to be solved, which are; 1) preoperative diagnostic accuracy of the depth of cancer invasion, 2) possibility of reoperation because of sm invasion or lymphatic or venous invasion in final histology, 3) possibility of postoperative stenosis after laparoscopic intragastric mucosal resection for the lesion near the cardia, 4) incidence of metachronous multiple gastric cancer. In conclusion, if the indication is properly selected, these laparoscopic procedures are curative and minimally invasive treatment for early gastric cancer.

Gastric Mucosa↗

[Telomerase assay for diagnosis of esophageal cancer].

Esophageal squamous cell carcinoma is one of the aggressive diseases that has poor outcome. Therefore it is appeared that early diagnosis is very important for improving its outcome. Iodine staining method is useful for detecting the abnormal squamous epithelium and unstaining lesions by iodine contain the early esophageal cancers. Recently, telomerase activity that provides an immortal capacity for the cells has been measured in many tissues. We measured the telomerase activity in the samples of unstaining lesion by iodine using a polymerase chain reaction-based assay and described the relation between telomerase activity and histopathological findings.

Biomarkers, Tumor↗

[Recent progress of matrix metalloproteinase (MMP) research and its clinical application for cancer therapy].

The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound zinc-endopeptidases. These enzymes are capable of degrading the extracellular matrix, including collagens, laminin, proteoglycan and fibronectin. In some human cancers, a positive correlation has been demonstrated between MMP expression and the likelihood of developing metastasis. An imbalance between MMPs and the tissues inhibitor of metalloproteinases (TIMPs) may play a significant role in the invasive phenotype of cancers. Although TIMPs have been shown to inhibit tumor metastasis in some in vivo models, they are not suitable for pharmacologic applications due to their short half-life in vivo and large molecular size. In this paper, recent advances in MMP research and reports of clinical applications of synthetic MMP inhibitors for cancer patients are reviewed.

Humans↗

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↗

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↗