The role of the cytoskeleton in migration and proliferation of a cultured human gastric cancer cell line using a new metastasis model.

Using an in vitro model for investigating the mechanism of migration and proliferation of a cultured human gastric cancer cell line which we established recently, we studied the suppressive effect of inhibitors of the cytoskeleton proteins, actin and myosin, on the migration and proliferation of cancer cells. These inhibitors suppressed the capacity of cancer cells to migrate and proliferate dose-dependently. Thus the integrity of the cytoskeletal system may play an important role in the mechanism of metastasis of gastric cancer cells.

Effects of rebamipide on bile acid-induced inhibition of gastric epithelial repair in a rabbit cell culture model.

BACKGROUND: Anti-ulcer agents exert various functional effects on gastric epithelial cells. AIM: The effects of a novel gastro-cytoprotective agent (rebamipide) on epithelial restoration following bile acid damage were assessed using primary cultured rabbit gastric epithelial cells. METHODS: Rebamipide was added to complete confluent cell sheets with deoxycholic acid just after creating a cell-free wound (2 mm2). The restoration was monitored and analysed by phase contrast microscopy and an image analyser for 48 h. The migration speed was measured during the initial 3 h after wounding. Cell proliferation was detected by staining for bromodeoxyuridine (BrdU) at 12-h intervals. The labelling index was calculated per unit area. The major cytoskeletal protein actin was detected by immunohistochemical staining. RESULTS: In the controls, restoration was completed 48 h following wounding. Deoxycholic acid retarded this process. The addition of rebamipide to deoxycholic acid abolished the bile acid-induced retardation. The migration speed was 26 microns/h in the controls. 15 microns/h in the deoxycholic acid group and 27 microns/h in the deoxycholic acid plus rebamipide group. In the controls, BrdU-positive cells, which were rarely detected in the initial 24 h, were maximal at 36 h (labelling index 1.7%). In the deoxycholic acid group, proliferation was inhibited (peak labeling index; 0.5% at 48 h). Actin-containing stress fibres were detected throughout the cells and the periphery of the lamellipodia in the controls, and were disrupted in the deoxycholic acid-treated group. Rebamipide prevented these effects. CONCLUSIONS: Deoxycholic acid significantly retarded restoration by the inhibition of both cell migration and proliferation, potentially through an effect on the cytoskeleton. Rebamipide protected the mucosal cells from bile acid mediated injury.

The incidence of reflux oesophagitis after cure of Helicobacter pylori in a Japanese population.

AIM: To investigate the incidence of reflux oesophagitis after antibacterial therapy for Helicobacter pylori infection in our patient population. METHODS: Subjects were 451 H. pylori-infected patients (primary symptom: peptic ulcer disease in 347, nonulcer dyspepsia in 100, and reflux oesophagitis in four): 11 of these patients had reflux oesophagitis on study entry. H. pylori infection was treated by a proton pump inhibitor/amoxycillin-clarithromycin regimen for either 7 or 14 days. Each patient was examined by endoscopy before treatment and more than 6 months after treatment to compare oesophageal findings. In addition, 227 patients were interviewed regarding reflux symptoms, using symptom questionnaires, before and more than 6 months after treatment. RESULTS: Among 440 patients who did not have reflux oesophagitis prior to antibacterial treatment (340 peptic ulcer patients and 100 nonulcer dyspepsia patients), 23 patients whose infection was eradicated developed reflux oesophagitis (5.4%). The 11 patients who had reflux oesophagitis prior to treatment were all successfully cured of infection. Six of these patients showed no change in their oesophagitis, while the condition improved in three and worsened in two. Symptom scores improved in 34 of the 36 patients who reported reflux symptoms. Among 19 patients who showed persistent infection, only one developed reflux oesophagitis (5.2%), while none complained of newly developed symptoms following treatment. CONCLUSIONS: Development of reflux oesophagitis after treatment of H. pylori infection was observed in a Japanese population. However, the incidence of this condition was comparable between those with persistent H. pylori infection and those in whom the infection was eradicated.

Effects of epidermal growth factor and insulin on migration and proliferation of primary cultured rabbit gastric epithelial cells.

We assessed the influence of epidermal growth factor (EGF) and insulin on gastric epithelial restoration in vitro. Rabbit gastric epithelial cells were cultured and formed a complete monolayer cell sheet in 2 days. We created a wound (1.8 +/- 0.05 mm2) by denuding an area of cells, and EGF (0.1-30 ng/ml) and/or insulin (1 nM-1 microM) was added. The restoration process, which included cell migration and proliferation, was monitored by measuring the cell-free area every 12 h for 2 days. Proliferating cells were detected by sequential staining with bromodeoxyuridine (BrdU). Control cells showed complete repair in 36-48 h and restoration was accelerated dose-dependently by EGF or insulin. EGF plus insulin further accelerated restoration, which was then completed in 12-24 h. EGF and/or insulin increased the number of BrdU- positive cells. The results indicated that EGF and insulin additively accelerated gastric epithelial wound repair by stimulating both the migration and the proliferation of gastric epithelial cells (particularly the former).

Epithelial-mesenchymal interaction in gastric mucosal restoration.

In this review article we discuss the role of growth factors in gastric ulcer healing using an in vitro wound repair model with gastric epithelial and mesenchymal cells. Several growth factors accelerate gastric epithelial and mesenchymal wound healing in vitro with acceleration of cell migration and proliferation. Epidermal growth factor, transforming growth factor-alpha (TGFalpha), hepatocyte growth factor, and insulin accelerate predominantly gastric epithelial wound healing; and TGFbeta and basic fibroblast growth factor predominantly accelerate gastric mesenchymal wound healing. Platelet-derived growth factor-betabeta and insulin-like growth factor-1 (IGF-1) accelerate both significantly. Among these growth factors, IGF-1 produced from fibroblasts plays a key role in the gastric epithelial-mesenchymal interaction during the process of gastric wound healing.

[UFTPM (UFT + CDDP + MMC) therapy for progressive stomach cancer. Research Association of Progressive Stomach Cancer].

We organized a cooperative research group consisting of 10 institutions and UFTPM therapy was given patients with unresectable and postoperatively relapsed stomach cancer. As the result, 20 cases were registered and the ratio of PR according to the criteria of stomach cancer chemotherapy was 4 out of 17 complete cases (23.5%), excluding 3 incomplete cases. The efficacy for the cases treated with more than 2 courses was 36.4% (4/11) and that for cases with 3 courses was 75% (3/4). One case with 3 courses was resectable and the cancer cells disappeared. Adverse effects of grade 3 or more according to the WHO criteria were observed in 20% of the cases.

[A case of advanced gastric cancer remarkably responding to preoperative UFT-E therapy].

We here reported a case of advanced gastric cancer remarkably responding to preoperative short-term UFT-E chemotherapy. UFT-E was orally administered preoperatively for about a month to the patient with type 2 advanced gastric cancer. After the chemotherapy the cancer was found to be remarkably decreased in size and denatured. The amount of residual cancer cells was limited by histopathological examination following the operation and diagnosed as Grade 3 based on the criteria of histological evaluation of chemotherapy for cancer. We continued to administer UFT-E postoperatively and the patient is still alive without symptoms.

Heating properties of re-entrant resonant cavity applicator for brain tumor with simple head model.

We have already confirmed the effectiveness of the re-entrant resonant cavity applicator system with non-invasive experiments of heating cylindrical agar phantoms and computer simulations. This paper discusses the heating properties of the developed heating system with a human head model made of agar for brain tumor hyperthermia treatment. First, we present the results of heating a uniform agar head model with the developed heating system. In the experiments, the temperature rise at the center of the agar was about 8 degrees C, it was found that the center of the agar is heated to maximum temperature non-invasively. Second, we present the results of heating a non-uniform agar head model having an oral cavity and a nasal cavity. We found that the center of the agar can be heated to maximum temperature as well as uniform agar head model. From these results, it is confirmed that the possibility of effective hyperthermia for various types of deep-seated brain tumors.

Finite element analysis of the re-entrant type resonant cavity applicator for brain tumor hyperthermia.

In this paper, we have proposed a new heating method in which high frequency electric fields in a re-entrant type resonant cavity are used for the heating of deeply seated tumors. In this method, a human head is placed between the gap of the inner re-entrant cylinders, and is heated with electromagnetic fields stimulated in the cavity without contact between the surface of the human head and the applicator. Here, we proposed a new method to control the heating area. In this method, the resonant frequency inside the cavity was changed, then we use the TM010-like mode and the TM012-like mode from various types of the resonant frequency. First, the computer simulation results of electric and magnetic field patterns are presented. Second, a comparison of the heating properties of TM010-like mode and TM012-like mode are discussed. The heating area of the center of agar phantom is more concentrated by using TM012-like mode than that of using TM010-like mode. From these results, it is confirmed that the proposed method can be controlled to heat the various sizes of deep tumors.

Heating properties of re-entrant resonant applicator for brain tumor by electromagnetic heating modes.

This paper discusses a new method to control the heating area of a re-entrant resonant cavity applicator for brain tumor hyperthermia treatment non-invasively. We have already discussed about the effectiveness of a developed system with experiments of heating an agar phantom and computer simulations. Here, in order to heat a deep brain tumor, we propose the heating method of using several electromagnetic heating modes which are transverse magnetic (TM) modes. In this method, TM010-like and TM012-like modes obtained by selecting resonant frequencies can be used to heat the deep brain tumors. To control the heating area of the modes the agar phantom is used in the heating experiments by the developed system. From these results, we found that the heating area of the agar phantom by using TM012-like mode is about 50% of the heating area of TM010-like mode. It is found that the proposed heating system can be applicable to the hyperthermia treatment of brain tumors corresponding to the size and the position where it occurred.

Role of extracellular matrix on colonic cancer cell migration and proliferation.

A simplified method to quantitatively analyze the migration and proliferation capacity of a colonic cancer cell line (SW837) in vitro was developed. The objective of this study was to evaluate the role of the extracellular matrix in colon cancer metastasis. We used this model to investigate the effects of the extracellular matrix components collagen type I and type IV, laminin, and fibronectin on the migration and the proliferation of cancer cells. Migration was fastest on laminin and slowest on collagen type I. Further, proliferation was highest on laminin of all extracellular matrices groups studied. Therefore, it is concluded that laminin had pronounced effects on migration and proliferation of SW837 cells. These findings suggest that the composition of the extracellular matrix plays an important role in the mechanism of metastasis of colon cancer cells.

Radiological retrospective study of gastric cancer in humans: two patterns of development in elevated type gastric cancer.

A better understanding of the process of gastric cancer development would undoubtedly be helpful in diagnosis and treatment. However, there is little literature available concerning the natural history of elevated type gastric cancer in humans and this disease had not been systematically investigated. In this study the natural history of elevated type human gastric cancer was retrospectively investigated in 12 radiologically followed-up patients. The cases were divided into two groups according the whether obvious abnormal findings were absent (group A, n = 5) or present (group B, n = 7) at initial examination. Clinico-pathological features, including outcomes and DNA content of the tumours in both groups, were investigated and compared. Although the mean period between the initial and final examinations was significantly shorter in group A (19.6 +/- 11.7 months) than in group B (43.4 +/- 17.3 months), tumour size was significantly larger in group A (5.5 +/- 2.5 cm) than in group B (2.4 +/- 2.5 cm). Furthermore, group A showed deeper neoplastic cell invasion and worse outcomes. The DNA content of two cases in group A and four cases in group B was examined. One case in group A showed and aneuploid pattern, while all of those in group B showed a diploid pattern. These results indicate that the tumours in group A grew much faster than those in group B, which suggests the presence of two different patterns of development in elevated type gastric cancer.

How useful is the detection kit for antibody to Helicobacter pylori in urine (URINELISA) in clinical practice?

OBJECTIVE: Increased knowledge of the significance of Helicobacter pylori (H. pylori) infection in gastric disorders has accelerated the trend of screening patients with dyspepsia for its infection. Serological examination of antibody for H. pylori has been widely performed. Recently, a urine-based enzyme-linked immunosorbent assay (URINELISA) kit for detection of antibody for H. pylori has been developed. Accordingly, we evaluated its diagnostic accuracy in clinical practice. METHODS: Subjects of this study were 132 patients who presented at our university hospital because of dyspeptic symptoms (81 men, 51 women; age, 41.5+/-1.4 yr). 13C urea breath test, blood drawing for serological antibody for H. pylori infection by four different kits, and urine collection for the URINELISA test for detection of the antibody were performed. Diagnostic accuracy of the commercially available antibodies in serum and in urine were investigated using the results of the 13C urea breath test as the gold standard. RESULTS: Sensitivity, specificity, and accuracy of URINELISA were 86.3% (95% confidence intervals [CI], 76-93%), 91.5% (95% CI, 81-97%), and 88.6% (95% CI, 82-93%), respectively, which were comparable to those of imported serological kits. CONCLUSIONS: The URINELISA kit for detecting anti-H. pylori antibody in urine provides diagnostic accuracy comparable to that of imported kits for detecting antibodies in serum and is considered to be clinically useful for the diagnosis of H. pylori infection.

Polyarteritis nodosa associated with gastric carcinoma and hepatitis B virus infection.

Several cases of polyarteritis nodosa associated with malignant disorders have been reported, most with bone marrow-related tumors. We report polyarteritis nodosa presenting with a fever of unknown origin and muscle weakness that was complicated by advanced gastric carcinoma and hepatitis B virus-positive cirrhosis. Vasculitis was diagnosed after gastrectomy from histologic findings of arterial vasculitis on the resected gastric carcinoma. Our case is so far the second such report of polyarteritis nodosa associated with gastric cancer.