Biomedical subjects

N Kaibara

Publications and source records attributed to N Kaibara.

At least 73 records · Page 4Linked to original sources

PubMed1999

Neoangiogenesis and relationship to nuclear p53 accumulation and vascular endothelial growth factor expression in advanced gastric carcinoma.

Recent studies have shown that tumor suppressor genes, particularly p53, may play a crucial regulatory role in the control of angiogenesis. Accordingly, we analyzed the correlation between p53 accumulation and the expression of vascular endothelial growth factor (VEGF) and microvessel counts in a series of human gastric adenocarcinomas by immunohistochemical staining. p53 expression was absent in 35 cases (29.7%), weak in 34 cases (28.8%), moderate in 35 cases (29.7%), and strong in 14 cases (11.8%). The prognosis of patients with both absent and weak expression of p53 was significantly better than that of patients with both moderate and strong expression of p53. VEGF expression was significantly associated with increased p53 expression. Moreover, increasing expression of p53 significantly correlated with an increase in microvessel counts. Nuclear p53 accumulation may correlate with tumor angiogenesis through VEGF upregulation in gastric carcinomas.

Adenocarcinoma↗

PubMed1999

Expression of MAGE genes and survival in patients with hepatocellular carcinoma.

The human melanoma antigen (MAGE) gene family encode tumor-specific antigens recognized by autologous cytotoxic T lymphocytes. Some of these antigens may be potentially useful for cancer-specific immunotherapy. The expression of MAGE genes has been reported not only in melanoma but also in various other malignant tumors. However, little is known about the expression of these genes in human hepatocellular carcinoma (HCC). We therefore analyzed, by means of a reverse transcription-polymerase chain reaction (RT-PCR), the expression of MAGE-1, MAGE-2, and MAGE-3 genes in 60 tissue samples resected from HCCs. The MAGE-1, MAGE-2, and MAGE-3 genes were expressed in 18 (30.0%), 9 (15.0%), and 15 (25.0%), respectively, of the 60 tumor-tissue samples. Nineteen (31.7%) samples expressed at least one of the three MAGE genes, and 8 (13.3%) expressed all three genes. In contrast, none of the MAGE genes was expressed in any of the 60 adjacent non-tumorous liver samples. The age of patients was significantly older in at least one MAGE-positive group (MAGE-positive groups) than in the MAGE-negative ones (p<0.05). The tumor size was significantly larger in MAGE-positive groups than in the negative ones (p<0.05). The serum alpha-fetoprotein level was significantly lower in MAGE-positive groups than in negative ones (p<0.05). Patients with tumors expressing at least one MAGE gene showed a better recurrence-free survival rate than those with tumors showing no MAGE gene expression (p<0.05). These results indicated that the MAGE genes were exclusively expressed in cancerous tissues of a considerable proportion of patients affected by HCC, and that some of these patients might be potential candidates for tumor-specific immunotherapy using the MAGE encoded antigens.

Adult↗

PubMed1999

Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis.

BACKGROUND: Less invasive treatment is the current trend in many surgical fields. Most patients with early gastric cancer do not have lymph node metastasis. Thus extensive resection of the stomach and extended lymph node dissection do not appear to be necessary. METHODS: In a retrospective study, 890 consecutive patients with early gastric cancer who had undergone standard gastrectomy were assessed for depth of invasion, gross appearance, and maximum diameter of the tumor to examine the possibility of limiting the extent of lymph node dissection. A variety of limited gastrectomies have been developed and now include endoscopic mucosal resection, wedge resection, segmental gastrectomy, limited proximal gastrectomy, and distal hemigastrectomy. RESULTS: A retrospective study revealed that extensive lymph node dissection did not improve the survival of patients with early gastric cancer. Endoscopic mucosal resection was suitable for cancers of the depressed type of less than 1 cm in diameter and the elevated type of less than 2 cm in diameter. Wedge, segmental, or limited proximal gastrectomy was suitable for the elevated type of 2 to 3 cm in diameter. The elevated type of more than 3 cm in diameter and the depressed type of 1 to 3 cm in diameter sometimes involved metastasis to group 1 nodes. The depressed type of more than 3 cm in diameter sometimes involved metastasis to group 2 nodes. Thus such cases should be treated by gastrectomy with dissection of potentially metastatic lymph nodes. CONCLUSIONS: Limitation of the extent of gastrectomy and lymph node dissection may be possible, depending on the gross appearance and size of the tumor.

Adult↗

PubMed1999

Expression of vascular endothelial growth factor correlates with hematogenous recurrence in gastric carcinoma.

BACKGROUND: It has recently been reported that the microvessel density in a tumor correlates with hematogenous metastasis in gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of vascular endothelial growth factor (VEGF), which was thought to be a potent angiogenesis-promoting factor, and hematogenous recurrence in advanced gastric carcinoma. METHODS: The expression of VEGF and the density of the microvessels were examined by immunohistochemistry in patients with advanced gastric carcinoma with serosal invasion who had undergone curative resection. RESULTS: The prognosis of patients with a VEGF-negative tumor was significantly better than that of patients with a VEGF-positive tumor. Multivariate analysis by Cox proportional hazards model showed that the expression of VEGF was an independent prognostic indicator. The expression of VEGF provided a significant estimate of relative risk for the development of hematogenous recurrence by multivariate logistic regression analysis. The microvessel count in VEGF-positive tumors was significantly higher than that in VEGF-negative tumors. CONCLUSIONS: VEGF is associated with hematogenous recurrence. Assessment of the expression of VEGF may therefore prove valuable in identifying patients with gastric carcinoma at high risk for recurrence who would benefit from adjuvant therapy.

Adult↗

PubMed1999

A prospective pilot study of extended (D3) and superextended para-aortic lymphadenectomy (D4) in patients with T3 or T4 gastric cancer managed by total gastrectomy.

BACKGROUND: Japanese surgeons have been actively performing extended lymphadenectomy (D2, removal of perigastric nodes and nodes along the left gastric, common hepatic, celiac and splenic arteries; or D3, D2 plus removal of nodes in the hepatoduodenal ligament, in the retropancreatic space and along the vessels of the transverse mesocolon). In recent years interest has expanded to superextended lymphadenectomy (D4) of nodes around abdominal aorta (para-aortic lymph nodes from aortic hiatus to aortic bifurcation). Because the therapeutic value of this D4 procedure remains controversial, we initiated a prospective study to compare D3 and D4 lymphadenectomy. METHODS: Seventy patients with T3 or T4 gastric cancer and without macroscopic metastasis to the para-aortic nodes treated by potentially curative total gastrectomy were randomized to D4 (group A, n = 35) and D3 (group B, n = 35) lymphadenectomies. RESULTS: Metastases to para-aortic nodes were found in 4 patients. Postoperative survival after D4 resection was not statistically significant between the groups. Postoperative morbidity for group A was greater. In group A 4 patients had postoperative retention of intra-abdominal fluid (lymphorrhea) and 4 others had prolonged diarrhea. One patient in each group died of postoperative complications. CONCLUSIONS: Surgical treatment of microscopic disease in grossly normal para-aortic lymph nodes may generate occasional long-term survivors. Selecting appropriate candidates who might benefit from D4 resections needs to be refined. On the basis of this study, a nationwide study should be considered.

Aged↗

PubMed1999

[Studies on recurrent breast cancer--clinicopathological factors and p53, p21Cip1/Waf1 and cyclin D1 protein expression].

Of patients radically operated on for breast cancer in our department, 46 patients who had recurrent breast cancer were clinicopathologically evaluated to clarify the prognostic factors of recurrent breast cancer. Furthermore, p53, p21 and cyclin D1 protein expression were studied immunohistochemically and their prognostic value was evaluated. The relapse-free interval was highly related to the survival rate after the recurrence. p53 overexpression was correlated with the progression of clinical stage and lymph node metastasis and negatively correlated with the expression of estrogen receptor. The p21 positive and p53 negative cases had a significantly better prognosis than the p21 negative and p53 positive cases. The combination of p53 and p21 protein expression seemed to have prognostic value in recurrent breast cancer.

Breast Neoplasms↗

PubMed1998

Serum concentration of CD44 variant 6 and its relation to prognosis in patients with gastric carcinoma.

BACKGROUND: The expression of variant isoforms of CD44 is correlated with the ability of tumor cells to metastasize in some clinical carcinomas. In this study, the serum concentration of soluble splice isoforms of CD44 that shared exon variant 6 (sCD44v6) were measured and the histologic expression of CD44v6 in tumors from patients with gastric carcinoma examined. METHODS: Serum samples were obtained from 102 patients with primary gastric carcinoma before surgery and serum levels of sCD44v6 were determined with an enzyme-linked immunoadsorbent assay. The expression of CD44v6 in tumors was examined by immunohistochemical staining. RESULTS: Both the serum concentration of sCD44v6 and its expression in tumors were associated significantly with the depth of invasion of the tumor, lymph node metastasis, and clinical stage in patients with diffuse type gastric carcinoma. Among patients with gastric carcinoma, the serum level of sCD44v6 was higher in those with CD44v6 positive tumor cells than in those with CD44v6 negative tumor cells. The serum level of sCD44v6 was a prognostic indicator in patients with diffuse type gastric carcinoma, as was the histologic expression of CD44v6. However, neither CD44v6 nor sCD44v6 was a predictor of survival time in patients with intestinal type gastric carcinoma. CONCLUSIONS: It appears that CD44v6 and sCD44v6 are related to the progression of diffuse type gastric carcinoma. An elevated serum level of sCD44v6 may be useful as a prognostic indicator in patients with diffuse type gastric carcinoma.

Adult↗

PubMed1998

Computerized nuclear morphometry of hepatocellular carcinoma and its relation to proliferative activity.

BACKGROUND AND OBJECTIVES: Nuclear profiles have been reported as useful prognostic predictor in various cancers. Data from computerized morphometries are objective and can be quickly derived using conventional microscopic analysis. However, it remains to be shown what types of pathological and biological factors influence the nuclear features. The aim of this study was to evaluate the correlation between the morphological nuclear features and clinicopathological parameters in patients with hepatocellular carcinoma (HCC). METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 76 patients with hepatocellular carcinoma who underwent hepatectomy at our hospital. In each case, 300 cancer nuclei were analyzed randomly on routine hematoxylin&eosin-stained slides through the use of a computer-assisted image analysis system that allowed us to trace the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patient survival, clinicopathologic status, and the proliferative activity of cancer cells. RESULTS: The mean nuclear area of poorly differentiated carcinoma was significantly larger than that of moderately and well differentiated carcinoma (P = 0.0003). Significant correlation was detected between the nuclear area of cancer cells and proliferative activity associated with proliferating cell nuclear antigen labeling index (PCNA LI) of cancer cells (r = 0.372, P = 0.0008). Moreover, blood vessel invasion of cancer cells or intrahepatic metastasis were more frequently detected in patients with large nuclear areas. Even though the nuclear area was not an independent prognostic factor in the multivariate analysis, the 5-year survival rate of the 35 patients who had tumors with large nuclear areas (>50 microm2, 25.9%) was significantly lower than that of the 36 patients who had tumors with small nuclear areas (< or =50 microm2, 63.3%, P = 0.001). CONCLUSIONS: The nuclear area of HCC correlates with cell differentiation and cell proliferative activity. Moreover, HCC with a large nuclear area has high potential for blood vessel invasion and intrahepatic metastasis. Thus, nuclear morphometry can be used as an useful morphological predictor for malignant potential in patients with HCC.

Adolescent↗

PubMed1998

Expression of E-cadherin, alpha-catenin, beta-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: an immunohistochemical study.

Immunolocalization of E-cadherin (E-cad), alpha-catenin, beta-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, alpha-catenin, beta-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, alpha-catenin and beta-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, alpha-catenin, and beta-catenin was the same or reduced when compared with non-cancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, alpha-catenin, and beta-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for beta-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, alpha-catenin, and beta-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that beta-catenin down-regulation is associated with c-erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5.

Adult↗

PubMed1998

Levels of serum-soluble receptor for interleukin-2 in patients with colorectal cancer.

The preoperative levels of serum-soluble receptor for interleukin-2 (IL-2R) were determined by an enzyme-linked immunosorbent assay in 38 patients undergoing surgery for colorectal cancer and 98 healthy controls. The levels of serum-soluble IL-2R in the patients with colorectal cancer were significantly higher than those in the normal controls (P < 0.05). Markedly elevated levels of serum-soluble IL-2R were recognized in patients with stage IV cancer, those with Dukes' stage D cancer, and those with liver metastasis. Moreover, the prognosis of patients with low levels of IL-2R (<531 U/ml) was significantly better than that of those with high levels (P < 0.05). These findings demonstrate that an elevated concentration of soluble IL-2R might be a useful indicator of liver metastasis and poor prognosis in patients with colorectal carcinoma.

Adenocarcinoma↗

PubMed1998

Effective TAE therapy using Lipiodol with epirubicin for liver metastases of nonfunctioning islet cell carcinoma of the pancreas.

We report the response of two patients with advanced nonfunctioning islet cell carcinoma of the pancreas with liver metastases treated with a combination of surgi-cal resection and transarterial embolization (TAE), using Lipiodol with epirubicin. After pretreatment evaluation, the two patients were diagnosed with nonfunctioning islet cell carcinoma of the pancreas with liver metastases. Preoperatively, in both patients, TAE was performed through the hepatic arteries, using Lipiodol and sponzel plus epirubicin. Surgical resection of the primary tumor (radical distal pancreatectomy and pancreaticoduodenectomy) was performed. After surgical resection and evaluation of the malignant histopathological features of the neoplasms, chemotherapy, which included oral 5-fluorouracil (FU), and transarterial infusion therapy, using Lipiodol with epirubicin, was administered to the patients. Follow-up evaluation of the two patients by computerized tomography (CT) scan showed a reduction in the size of the metastatic hepatic masses after several chemoembolizations through the hepatic arteries. This combined treatment modality may be an effective therapeutic strategy for improved management of patients with advanced nonfunctioning islet cell carcinoma of the pancreas with liver metastases.

Adult↗

PubMed1998

Apoptosis as a prognostic factor in colorectal carcinoma.

We investigated the occurrence of apoptotic cell death in 104 colorectal carcinomas by terminal-deoxynucleotidyl-transferase-mediated dUTP-diotin nick end-labeling (TUNEL) to determine whether apoptosis could be a useful prognostic factor. The apoptotic index (AI) was calculated as the percentage of positive cancer cells per 1,000 cancer cells, the median AI being 4.1, with a range of 1.9-4.7. Apoptosis was less frequently observed in tumors with higher malignant potential, such as those at advanced stages Dukes B, C and D, than those at Dukes stage A (P < 0.05); in tumors showing evidence of moderate differentiation than in well-differentiated tumors (P < 0.05); and in tumors with venous invasion or lymph node metastasis than in those without these features (P < 0.05). Moreover, the subgroup of patients with a low AI of < 4.1 had a significantly poorer survival rate than the subgroup with a high AI in tumors at Dukes stage C, the 5-year survival rates being 33% vs 68% (P < 0.05; Cox-Mantel). Our findings suggest that less apoptosis might result in a greater progression of colorectal carcinoma, and that the rate of apoptosis might be an indicator of the degree of malignancy. Thus it would appear that the frequency of apoptosis in tumor cells could be a useful prognostic factor in colorectal carcinoma.

Adenocarcinoma↗

PubMed1998

Expression of p53 and p21 are independent prognostic factors in patients with serosal invasion by gastric carcinoma.

To evaluate whether the expression of p53 and that of p21 are independent prognostic factors in patients with advanced gastric cancer, we investigated clinicopathological factors and the expression of p53 and p21 in 158 patients with gastric cancer that had invaded the serosa and who had undergone curative gastrectomy. In multivariate survival analysis of 156 surviving patients, we evaluated the size of the tumor, lymph node metastasis, venous invasion, lymph node dissection, expression of p53, and expression of p21 as independent prognostic factors. Moreover, we divided patients into four groups according to the expression of p53 and p21 in their tumors [group A, p53-/p21-, N = 40 (one died within 30 days of surgery); group B, p53-/p21+, N = 23; group C, p53+/p21-, N = 58; and group D, p53+/p21+, N = 37 (one died within 30 days of surgery)]. The 5- and 10-year survival rates of 39 patients in group A were 71.7% and 64.3%, those of 23 patients in group B were 81.4% and 81.4%, those of 58 patients in group C were 35.6% and 30.2%, and those of 36 patients in group D were 67.9% and 60.7%. The prognosis of patients in group C was poorer than that of patients in the other three groups. This result indicates that the evaluation of the expression of both p53 and p21 expression might provide prognostic information that is more accurate than that provided by evaluation of the expression of p53 alone.

Adult↗

PubMed1998

Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue.

It has been reported that decreased numbers of dendritic cells (DCs) are correlated with poor prognosis in some types of malignancy, such as gastric cancer. However, factors that determine the density of DCs have not been characterized. It was recently reported that vascular endothelial growth factor (VEGF) inhibits the functional maturation of DCs from CD34+ precursors. In this study, we analysed the relationship between the expression of VEGF and the density of DCs in gastric carcinoma tissues by immunohistochemical staining. The extent of infiltration by DCs was graded from marked to slight on the basis of the mean densities of DCs. The prognosis of patients with marked infiltration was significantly better than that of patients with slight infiltration among patients who had undergone curative resection. Multivariate analysis showed that infiltration by DCs was an independent prognostic indicator. Furthermore, there was an inverse correlation between the density of DCs and the expression of VEGF Our results suggest that expression of VEGF might be associated with tumour progression and poor prognosis not only because VEGF stimulates angiogenesis, but also because it allows tumours to escape from attack by the immune system in patients with gastric carcinoma.

Adenocarcinoma↗

PubMed1998

Pretreatment with restriction enzyme or bovine serum albumin for effective PCR amplification of Epstein-Barr virus DNA in DNA extracted from paraffin-embedded gastric carcinoma tissue.

An association between Epstein-Barr virus (EBV) and gastric carcinoma has been studied through the EBV genome present in the carcinoma cells. Recently, we found that EBV DNA in paraffin-embedded gastric carcinoma tissue was detected effectively by PCR after pretreatment of the extracted DNA with a restriction enzyme, BamHI or EcoRI. Here, we show that the PCR amplification was also enhanced by pretreatment of the DNA with other restriction enzymes or with bovine serum albumin and several other proteins. Treatment with these proteins may remove a PCR inhibitor(s) in the DNA samples extracted from the paraffin blocks.

Animals↗

PubMed1998

A progressive postoperative increase in the serum level of soluble receptors for interleukin-2 is an indicator of a poor prognosis in patients with gastric cancer.

Activated T lymphocytes release a soluble form of IL-2R (SoIL-2R) into the bloodstream, which can be detected by CD25 monoclonal antibody. Perioperative changes of serum levels of SoIL-2R and the number of CD25-positive cells were monitored simultaneously to clarify the clinical implications of SoIL-2R in patients with gastric cancer (n=91). Preoperative levels of SoIL-2R were significantly higher than in normal controls and levels were a useful indicator of possible lymph node involvement. Postoperative levels of SoIL-2R increased independently of the number of CD25-positive cells. Patients with progressive postoperative increases in levels of SoIL-2R had both a significantly high frequency of postoperative relapse and a poor prognosis. Increased SoIL-2R may reduce the availability of IL-2 by binding to it. Postoperative progressive increases in SoIL-2R appear to be a good indicator for a poor prognosis in patients with gastric cancer.

Adult↗

PubMed1998

Aberrant p16INK4 expression related to clinical stage and prognosis in patients with pancreatic cancer.

The p16 tumor suppressor gene is thought to play an important role in cell cycle regulation by encoding for protein products that can inhibit the progression from G1 to S phase in the cell cycle. Recently, the p16 gene has been found to be mutated or deleted in a variety of different types of primary human malignant tumors and human-derived malignant tumor cell lines. In this study, primary ductal pancreatic adenocarcinomas from 32 human patients were analyzed immunohistochemically for expression of p16 protein, with emphasis on the role of abberant p16 protein expression as a prognostic indicator. In addition, the same tumors were also assessed for p53 protein expression, AgNOR counts, and DNA ploidy. Nineteen out of the 32 cases (59%) showed positive immunoreactivity for p16 protein in their tumors and a significant association was found between lack of p16 protein expression, and both advancing clinical stage classification of disease, and poorer survival (p<0.05). The rate of positive immunoreactivity for p53 protein expression was 59%, however, no clear association was found between p53 protein expression, and either clinical stage of disease, or survival. These findings suggest that alteration of the p53 gene may be a relatively early event in pancreatic tumorigenesis, whereas alteration of the p16 gene is more likely to be correlated with tumor progression in pancreatic malignancies. Further survival analysis revealed that all five of the 32 cases that survived for three years or longer had positive immunostaining for p16 protein, and a relatively low level of AgNOR counts. In four out of five of these patients, the tumors also exhibited negative immunostaining for p53 protein and DNA diploidy. These findings suggest that molecular analysis of patient tumor sections may yield potentially useful prognostic indicators for patients undergoing surgical resection for pancreatic cancer.

Aged↗

PubMed1998

Telomerase activity and microsatellite instability in colorectal cancer and adenoma.

In order to examine their roles in carcinogenesis or in progression of colorectal carcinoma, we investigated telomerase activity and microsatellite instability in 67 non-familial colorectal cancers and in 18 adenomas. The incidence of detectable telomerase activity increased from 22% of normal colorectal mucosas adjacent to carcinoma, and 33% of adenomas, to 75% of carcinomas. On the other hand, the incidence of detectable microsatellite instability in carcinomas (30%) was almost the same as in adenomas (22%). No significant correlation was detected in the incidence of telomerase activity and microsatellite instability in carcinomas or in adenomas. Moreover, the incidence of telomerase activity and microsatellite instability did not increase during the progression of carcinomas. These results indicate that telomerase activity and microsatellite instability are independent events in colorectal carcinogenesis, and that telomerase activity and microsatellite instability are not correlated with the progression of colorectal carcinoma. However, in 13 multiple cancers, the incidence of telomerase activity (92%) and the incidence of microsatellite instability (54%) was higher than that of telomerase activity (70%) and that of microsatellite instability (24%) in 54 sporadic cancers. Moreover, the incidence of telomerase activity and that of microsatellite instability in adenomas with carcinomas (45% and 36% respectively) was higher than that of telomerase activity and microsatellite instability in adenomas without carcinomas (14% and 0% respectively). These results indicate that telomerase activity and microsatellite instability may play an important role in multicentric carcinogenesis in colorectal carcinoma.

Adenoma↗