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Y Kakeji

Publications and source records attributed to Y Kakeji.

At least 19 recordsLinked to original sources
PubMed2006

Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study.

BACKGROUND AND STUDY AIMS: The Confocal Endomicroscopy System (Optiscan Pty Ltd. and Pentax Corp.) is a newly developed imaging tool that uses laser light and optical technology to visualize living tissue at the cellular level. Digital images of cells magnified 1000-fold appear in real time on a computer screen, which enables immediate detection of changes in cellular structure without the need for a biopsy. The aim of this study was to assess the features of the cellular architecture of cancerous tissue that can be used in the differential diagnosis of cancerous tissue and normal mucosa using this system's image-processing software. PATIENTS AND METHODS: A total of 27 gastric cancers were examined ex vivo using confocal endomicroscopy. A fluorescent contrast agent, acriflavine, was applied topically to normal and to cancerous mucosa. In vivo imaging of the gastric mucosa after intravenous injection of fluorescein sodium was also performed in nine patients with gastritis or gastric cancer. RESULTS: The nuclear area in the ex vivo specimens was calculated using Scion Image software. The mean nuclear area of cancer cells was found to be significantly larger than that of normal cells in 18/27 gastric cancers (67 %). The mean nuclear area of the cancers tended to be larger than that of normal mucosa, especially in cases of differentiated adenocarcinoma. In more than half the cases, it was possible to diagnose malignancy automatically using confocal endomicroscopy and image-processing software without the need for biopsy and pathological examination. In vivo imaging of cancerous lesions showed irregularity in cellularity and vascularity. CONCLUSION: The ability of this imaging device to differentiate between normal tissue and cancerous tissues gives it potential value as a new screening tool for early detection of malignancy.

Adenocarcinoma↗
PubMed2005

Two-field lymph-node dissection may be enough to treat patients with submucosal squamous cell carcinoma of the thoracic esophagus.

Significance of extended radical surgical treatment including three-field lymph node dissection for squamous cell carcinoma (SCC) of the esophagus remains debatable. The aim of the current study was to reconsider the merits and demerits obtained by three-field lymph node dissection for esophageal carcinoma and also to attempt to elucidate an appropriate surgical strategy for submucosal SCC of the thoracic esophagus. Thirty-one patients with SCC of the thoracic esophagus who had been treated with esophagectomy and two-field (thoracic and abdominal) lymph node dissection without preoperative therapies were enrolled. Five-year survival rate was 75.0% and the incidence proportion of postoperative complication was 9.7%. These data regarding postoperative outcome of patients were by no means inferior to those in the previous reports referring the prognosis of patients with esophageal carcinoma who had been treated with three-field lymph node dissection. Authors would like to mention that two-field lymph node dissection associated with reduced incidence of postoperative complications might be enough to treat the submucosal SCC of the thoracic esophagus.

Adult↗
PubMed2004

Correlation of ABO blood group with clinicopathologic characteristics of patients with esophageal squamous cell carcinoma.

The aim of the current study was to determine the nvolvement of ABO blood group in clinicopathologic features in squamous cell carcinoma (SCC) of the esophagus, that has not previously been studied fully. Two hundred and eighty four consecutive patients with esophageal SCC were enrolled for the study. The relationship between patients' ABO blood group and the clinicopathologic features was analyzed. The proportion of poorly differentiated SCC among patients with blood group O was significantly lower than in those patients with other blood types (P = 0.001). The mean size of the tumors in patients with blood group AB was significantly larger than those in patients with other blood groups. The proportion of tumors associated with venous invasion was significantly higher in patients with blood type A than those of tumors in other blood types (P = 0.007). The TNM stages of tumors in blood group AB were found to be significantly more advanced (P = 0.036) than other groups. The functional significance of ABO blood group distribution might be associated with biological behavior of SCCs. However, it was found not to be a clinical predictor for the prognosis of the patients with esophageal SCC.

ABO Blood-Group System↗
PubMed2002

Clinical significance of vascular endothelial growth factor expression in gastric cancer.

Vascular endothelial growth factor (VEGF) is an angiogenic factor in human cancer tissue. To clarify the clinical significance of this factor, we investigated the VEGF expression in early and advanced gastric cancer. This study included analysis of data on 243 patients with gastric cancer, including 118 in the early stage and 125 in the advanced stage. VEGF was immunohistochemically stained. Of 243 tumors, 102 (42%) were VEGF-positive. The VEGF-positive gastric cancers were larger, more invasive, and classified in the more advanced stage than VEGF negative ones. Patients with VEGF-positive cancers had significantly lower survival rates than did those with negative ones, both in early and advanced stages (P < 0.05, P < 0.01, respectively). The VEGF-positive isolates had more hematogenous metastases than VEGF-negative ones. Multivariate analysis revealed VEGF to be an independent prognostic factor and independent risk factor for liver metastasis. The VEGF expression in cancer cells can serve as a pertinent prognostic indicator both in early and advanced gastric cancer.

Adenocarcinoma↗
PubMed2001

Growth pattern and expressions of cell cycle regulator proteins p53 and p21WAF1/CIP1 in early gastric carcinoma.

BACKGROUND: The growth pattern of early gastric carcinoma, as based on a volumetric analysis, reflects the biologic characteristics of a tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with the case of a superficially spreading (Super) type. The wild-type of the p53 protein plays an important role in cell growth regulation and apoptosis. The p21 protein, which is encoded by the WAF1/CIP1 gene, is a downstream target effector of wild-type p53 protein, and these proteins act as tumor suppressors in a negative cell-cycle regulation. METHODS: In 133 Japanese patients with early gastric carcinoma with submucosal invasion, expressions of p53 and p21 proteins were studied immunohistochemically, and the relation between growth pattern and expressions was analyzed. RESULTS: Early gastric carcinomas were grouped into the superficially spreading (Super) type 40 (30.1%) cases, expansively penetrating growth (Pen-A) type 28 (21.1%), infiltratively penetrating growth (Pen-B) type 20 (15.0%), small mucosal type 35 (26.3%), and mixed type 10 (7.5%). The Pen-A type tumors were characterized by the highest incidence of p53 expression and loss of p21 expression, and the rate of p53-positive and/or p21-negative cases was 71.4%. There were significant differences in the incidence of the p53 expression (50.0% vs.25.0%), the loss of p21 expression (53.6% vs. 27.5%), and the 5-year survival rate (83.2 %vs. 97.2%) between the Pen-A type and the Super type. CONCLUSIONS: Thus, deregulation of the cell cycle by p53 and p21 in this study was shown to play an important role in progression of Pen-A type early gastric carcinoma.

Aged↗
PubMed2001

Prognostic significance of natural killer cell activity in patients with gastric carcinoma: a multivariate analysis.

OBJECTIVE: Natural cytotoxicity, mediated by natural killer (NK) cells, has been believed to play an important role in inhibiting experimental tumor metastasis, and diminished NK cell activities leads to a high incidence of tumor occurrence. Despite convincing evidence from experimental studies, the role of NK cells in the immunological surveillance against cancer in human is poorly defined. METHODS: The present study was based on a retrospective analysis of data on 156 patients with gastric cancer, who were surgically treated in the Department of Surgery II, Kyushu University Hospital from 1993 to 1996. All patients were examined for NK cell activity based on a peripheral blood sampling done preoperatively. RESULTS: Significant association between NK cell activity and clinicopathological parameters including tumor size, lymphatic involvement, vascular involvement, and lymph node metastases was evident. When comparing the two groups according to NK cell activity, tumors with low NK cell activity tend to have lymphatic involvement. The 5-yr survival rates were 94.6% and 72.3% for those with NK cell activity > 25% lysis and < or = 25% lysis, respectively, the value being statistically significant (p < 0.05). The independent risk factors for prognosis examined by logistic regression analysis were lymphatic involvement. NK cell activity, depth of tumor invasion, and lymph node dissection. CONCLUSIONS: These current data showed that NK cell activity may be related to tumor volume and dissemination. Measurement of preoperative NK cell activity may be pertinent for the prognosis of patients with gastric cancer and for follow-up clinical management.

Cytotoxicity, Immunologic↗
PubMed2001

Overexpression of vascular endothelial growth factor C is related to lymphogenous metastasis in early gastric carcinoma.

Vascular endothelial growth factor C (VEGF-C) is considered to be potentially lymphangiogenic and can selectively induce hyperplasia of the lymphatic vasculature. In this study, we clarified the clinicopathological features of early gastric carcinoma (EGC) that has metastasized to the lymph nodes, as well as the correlation between lymphogenous metastases in EGC and the expression of VEGF-C and VEGF. We selected 35 cases of lymph node metastasis-positive [n(+)] EGC and 70 cases of lymph node metastasis-negative [n(-)] EGC for the present study. The expression of VEGF and VEGF-C was investigated with immunohistochemical staining using monoclonal antibodies against VEGF and VEGF-C. Clinicopathologically, there were significant differences in median size (4.1 +/- 2.4 vs. 2.4 +/- 1.7 cm), lymphatic invasion (54 vs. 4%) and venous invasion (23 vs. 3%) between n(+) EGC and n(-) EGC. Immunohistochemically, the incidence of positive expression of VEGF-C in lymphatic invasion-positive EGC (36%) was significantly higher than that in lymphatic invasion-negative EGC (14%). The incidence of positive expression of VEGF-C in n(+) or venous invasion-positive EGC tended to be higher than that in n(-) or venous invasion-negative EGC. In conclusion, lymphatic invasion was significantly increased in VEGF-C-positive EGC.

Aged↗
PubMed2001

Tumor growth patterns and biological characteristics of early gastric carcinoma.

Gastric cancer is a major malignant disease. The development of new diagnostic techniques and mass screening have led to increased detection rates of patients with early-stage gastric cancer in Japan. However, after curative resection of early gastric cancer, there are various types of recurrences, and residual occult disease and distant micrometastasis precede death. The growth and metastatic potential of cancer cells are closely related to the postoperative outcome, and patients at risk for cancer-related death after surgery have to be closely monitored to prevent tumor recurrence. The biological behavior of cancer cells should be determined in patients with early gastric cancer and with a less favorable prognosis to detect potential early recurrences in the liver. Two types of growth patterns have been found in early gastric cancer: the superficially spreading (Super) type and the penetrating (Pen) type, and the clinicopathological and biological characteristics of each type have been extensively determined. A subtype of the Pen-type gastric cancer, which is progressing expansively with complete destruction of the muscularis mucosae (Pen A type) has a less favorable prognosis due to early recurrences in the liver. These clinical cancer types are closely related to chromosomal instability in DNA aneuploidy and p53 overexpression, and vascular endothelial growth factor activation induced tumor angiogenesis, vascular invasion and hematogenous metastasis. Thus, patients with Pen-A-type cancer showing expansive tumor growth had a poorer postoperative outcome and a hematogenous-related recurrence of the cancer. Antiangiogenic approaches in a postoperative setting may prove to be effective in preventing tumor recurrence and improving the prognosis for these patients.

Adenocarcinoma↗
PubMed2001

[Angiogenesis and macrophage infiltration in Borrmann type IV gastric cancer].

The clinical significance of angiogenesis was investigated in Borrmann type IV gastric cancer. Tumors with high microvessel density (MVD) often metastasized to the liver and lymph nodes. A significant correlation was recognized between macrophage infiltration and MVD. However, MVD was not a prognostic factor. Peritoneal dissemination was a prognostic factor in Borrmann type IV gastric cancer. Thus, angiogenesis plays an important role in the metastasis, but not prognosis in Borrmann type IV gastric cancer.

Aged↗
PubMed2000

Diminished expression of ING1 mRNA and the correlation with p53 expression in breast cancers.

p33(ING1) is a novel candidate tumor suppressor and its overexpression induces growth arrest or apoptosis in different cell lines. These functions of p33(ING1) depend largely on the activity of p53, and p53-dependent activation of the transcription from the p21/WAF1 promoter also requires p33(ING1). We examined the expression of ING1 mRNA in breast cancer cell lines and clinical breast cancer tissues, using quantitative RT-PCR and real time TaqMan technology. In breast cancer cell lines, ING1 mRNA was expressed at almost the same level. However, in a comparison between the cancer and matched normal tissues, a significant decrease in ING1 mRNA expression was found in 17 of 24 (70.8%) breast cancer tissues. We also examined the correlation between ING1 mRNA expression and p53 expression. There was a significant decrease of ING1 mRNA in nine of 15 tumors negative for p53 immunostaining, most of which were considered to have wild type p53. In these tumors, p53 may not function in case of a decreased expression of p33(ING1), and the lack of cell cycle regulation may correlate with the carcinogenesis and tumor progression.

Breast Neoplasms↗
PubMed2000

Postoperative outcome and sites of recurrence in patients following curative resection of gastric cancer.

BACKGROUND: Recurrence occurs in a variety of forms and in different organs after 'curative resection' of gastric cancer. This study investigated the postoperative prognosis for each type of recurrence. METHODS: From 1969 to 1988, 939 patients with gastric cancer underwent curative resection; data on 130 of 207 patients who died with recurrence were analysed. Attention was focused on the site of recurrence and the postoperative outcome. RESULTS: Haematogenous recurrence was evident in 54 per cent (70 of 130 patients), peritoneal recurrence in 43 per cent (56 of 130), lymph node recurrence in 12 per cent (16 of 130) and local recurrence in 22 per cent (29 of 130). Thirty-three patients (25 per cent) had recurrences at multiple sites. Peritoneal and local recurrences were related to infiltrative growth, in contrast to haematogenous and lymphatic recurrences. There were no statistical differences in survival time among each type of recurrence and survival was not related to the number of sites of recurrence. Survival did not depend on factors of sex, age, tumour location, tumour size, depth of invasion, tissue differentiation, histological growth pattern, lymphatic and vascular involvement, lymph node metastasis and extent of lymph node dissection. CONCLUSION: The clinicopathological characteristics of gastric cancer determine the type of recurrence, although the clinical outcome is the same for each type of tumour and is not related to the number of sites of recurrence.

Humans↗
PubMed2000

Time trends of surgical treatment and the prognosis for Japanese patients with gastric cancer.

The incidence of gastric cancer is much higher in Japan than in other countries even though diagnostics and treatments of such patients have improved. The objective of this study was to present an overview of the past, present and future of surgical treatment for our patients with gastric cancer. We analysed data on 2152 Japanese men and women with gastric cancer who underwent surgical resection from 1965 to 1995 at Kyushu University in Fukuoka, Japan, based on a univariate and the multivariate analysis. We focused on time trends of surgical treatment and the postoperative outcome. Over the years, there have been favourable changes in the numbers of patients with early gastric cancer. In all cases of gastric cancer, the rate of 18% in the first six year period (group 1) was 57% in the last 5 year period (group 6). Size of the tumour was smaller, well-differentiated tumour tissue was more common, and lymphatic involvement was less frequent. Lymph node metastasis, liver metastasis and peritoneal dissemination all decreased. Extensive lymph node dissection was more frequently done and the rate of curative resection (curability A and B) increased. With increases in identifying the early stage of cancer and better perioperative care, mortality rates 30 days after the surgery greatly decreased. Multivariate analysis revealed that the 10 factors of depth of invasion, lymph node metastasis, lymph node dissection, tumour size, liver metastasis, peritoneal dissemination, lymphatic invasion, vascular invasion, lesion in the whole stomach and lesion in the middle stomach were independent factors for determining the prognosis. Detection of the tumour in an early stage, standardized surgical treatment, including routine lymph node dissection, close follow-up schedules and better perioperative management are expected to increase survival time for patients with this malignancy.

Female↗
PubMed2000

Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma.

BACKGROUND: Hematogenous metastasis occurs when cancer cells released from the primary site enter blood vessels and are transported to distant organs, where they attach and proliferate. Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells. METHODS: We analyzed data on 1184 Japanese adult men and women with gastric cancer with respect to the relation between vascular invasion and the potential for tumor angiogenesis and metastasis. All these patients were treated from 1976 to 1995 in the Department of Surgery II, Kyushu University. In 300 patients, the expression of vascular endothelial growth factor (VEGF) and p53 protein in tumor tissues was examined by using an immunohistochemical staining method or Northern blotting or both. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody. RESULTS: Vascular invasion was evident in 254 patients (21.5%), and in these patients lymphatic invasion was more frequent and the rate of lymph node metastasis was higher in relation to the extent of vascular invasion. The positive findings were directly related to the depth of invasion and the presence of lymph node and liver metastasis. Tumor invasive and metastatic rates increased in relation to the extent of vascular invasion. Expressions of VEGF and p53 protein were higher and microvessel density was more prominent in tumor tissues in relation to the extent of vascular invasion. A close relation between VEGF and p53 protein expressions was also noted in tumors that showed vascular invasion. The expression of VEGF is one of the independent risk factors for vascular invasion. The postoperative outcome was poorer in patients with vascular invasion in relation to the extent of vascular invasion. CONCLUSIONS: Our findings show that gastric cancers with characteristics of vascular invasion have greater intratumoral angiogenesis and that VEGF and p53 overexpression is associated with intratumoral angiogenesis and metastases to distant organs.

Adult↗
PubMed2000

Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer.

The cell synthesis of heat shock proteins is increased by a variety of environmental and pathophysiological stressful conditions. The 70-kD heat shock protein family (HSP70 family) which constitutively expresses hsc70 and heat-inducible hsp70 is thought to be involved in protein-protein interactions, including oncogene products. We investigated the HSP70 family expression and biological behavior of gastric cancer, and its relation to p53 overexpression. Expressions of HSP70 and p53 in 164 primary gastric tumors were determined immunohistochemically. Exploratory data were analyzed on a set of 164 primary gastric cancers, and we constructed in prognostic significance of the HSP70 expression level and the relation to p53 overexpression. Expression of HSP70 (hsc70 and hsp70) were detected in nuclei and/or cytoplasm of cancer cells. Western blotting analysis showed that hsc70 and hsp70 were both expressed in five gastric cancer cell lines. Immunohistochemically stained positive cells of HSP70 varied from 0 (very weak) to 100%, in each case. The median level of positive cell rate was 19.0%. A HSP70 expression of over 19.0% was related to the differentiated tissue type of gastric cancer, but not to other clinicopathological factors. There was no difference in survival rates in subjects with higher and lower groups of HSP70 expression. HSP70 expression was also not related to p53 overexpression in the nuclei and p53 overexpression-related poorer prognosis. Our findings show that the expression of HSP70 is not associated with tumor advance-related characteristics or with the prognosis of gastric cancer. Measurements of HSP70 expression do not appear to be a useful prognostic marker.

Adenocarcinoma↗
PubMed2000

Clinicopathological features and overexpression of matrix metalloproteinases in intramucosal gastric carcinoma with lymph node metastasis.

Endoscopic mucosal resection, which has been widely accepted for the treatment of intramucosal gastric carcinoma (IMGC) because of the minimal invasiveness of the procedure and the sustained quality of life it provides, can only be used on the premise that the carcinoma has no lymph node metastasis. We evaluated the clinicopathological and biological features of IMGC with lymph node metastases in relation to matrix metalloproteinase (MMP) expression. Fifteen cases of lymph node metastasis-positive [n(+)] IMGC and 59 cases of lymph node metastatic-negative [n(-)] IMGC were obtained. The expression of MMP-2 and MMP-9 was investigated with immunohistochemical methods. Clinicopathologically, n(+)-IMGCs were more likely to be of a larger size, to be of poorly differentiated adenocarcinoma, to have had lymphatic permeation [ly(+)], and to have ulcerations within the lesion compared to n(-)-IMGCs. The incidence of the positive expression of MMP-9 in n(+)-IMGCs (67%) or ly(+)-IMGCs (86%) was significantly higher than that in n(-)-IMGCs (32%) or ly(-)-IMGCs (34%). Even in IMGCs, carcinoma cells may produce MMPs that can degrade the basement membrane, allowing them to permeate the lymph capillary. Ulcerations within the lesion may also facilitate the interchange of lymphatic flow between the mucosa and the submucosa, promoting the development of lymph node metastases.

Carcinoma↗
PubMed2000

Application of quantitative RT-PCR using "TaqMan" technology to evaluate the expression of CK 18 mRNA in various cell lines.

Reverse transcriptase polymerase chain reaction (RT-PCR) is often used for sensitive detection of micrometastasis in peripheral blood, lymph nodes and bone marrow. While the utility of this method has been documented, it also has limitations in the detection of micrometastasis. The mRNA of target genes can be detected in healthy donors or in samples used for negative control, therefore the non-quantitativeness of conventional RT-PCR has been called into question. We analyzed the expression level of cytokeratin (CK) 18 mRNA in established esophageal and gastrointestinal carcinoma cell lines and non-epithelial cells, using quantitative RT-PCR, based on real time 'TaqMan TM' technology. CK 18 mRNA is more highly expressed in carcinoma cells than in non-epithelial cells. However, the expression level in non-epithelial cells was easily detected using conventional RT-PCR and agarose gel electrophoresis. In an analysis of CK 18 mRNA expression in peripheral venous blood in 13 healthy volunteers, we found that CK 18 mRNA was much less expressed than in cancer cell lines. However, the expression in all samples was at a level which was also detected using conventional RT-PCR. It would thus seem that not only qualitative, but also quantitative analysis, of the target mRNA is important to detect micrometastasis. Quantitative RT-PCR methods will make comparisons of the possible differences in expression levels of the target gene. For clinical applications, much further study is needed.

Adult↗
PubMed1999

Reduced expression of p33(ING1) and the relationship with p53 expression in human gastric cancer.

p33(ING1) is a novel growth inhibitor candidate for a tumor suppressor gene. p33(ING1) cooperates with p53 and negatively regulates cell growth by activating transcription from the p21/WAF1 promoter even though it has no significant sequence similarity to p53. We first compared p33(ING1) expression in human gastric cancers and matched normal tissues using quantitative RT-PCR and real time 'Taqman TM' technology. A significant decrease in p33(ING1) expression was evident in 15 of 20 gastric cancers. In immunohistochemical analysis, p53 protein expression was detected in 4 of 20 (20%) tumors, and 12 of 15 (80%) tumors with decreasing p33(ING1) expression in RT-PCR had the wild type p53. When we examined the sequence of p33(ING1) in 12 gastrointestinal carcinoma cell lines, we found mutation in only one cell line, HCT116. Our findings are interpreted to mean that p33(ING1) may function as a tumor suppressor in gastric carcinogenesis, even though the gene is preserved in the majority of gastrointestinal carcinomas. It should be noted that expression of p33 decreased in many cancer patients, and the biological effects of p33(ING1) and p53 are interrelated and require the activity of both genes.

Adenocarcinoma↗