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Biomedical subjects

N Tanigawa

Publications and source records attributed to N Tanigawa.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Immunohistochemical study on the progression of colorectal cancer--with respect to apoptotic index, expression of apoptosis-related gene products, and labeling index of proliferating cell nuclear antigen (PCNA)].

To clarify the biological changes in the development and progression of colorectal cancer, immunohistochemical examination was performed with a particular focus on the activity of apoptosis, the expression of apoptosis-related gene products and cell proliferation activity, assessed by the labeling index of proliferating cell nuclear antigen (PCNA). Seventy-six resected specimens of colorectal cancer were used to investigate the expression of apoptosis-related gene products, Bcl-2 protein and PCNA labeling index, as well as the apoptotic index using the TUNEL method. Seventy-five percent of 60 advanced cancer specimens was negative for Bcl-2 protein, and the proportion was higher than that in early cancer specimens. The apoptotic index (AI) in the advanced cancers was significantly higher than in the early stage of cancers. Meanwhile, the percentage of PCNA-positive cells for the advanced cancers was significantly higher than for early cancer. This study demonstrated a decrease in Bcl-2 protein expression, an increase in tumor cell apoptosis, and opposite an increase of cellular proliferation activity in the progression of colon cancer from early to the advanced stage of the disease.

Apoptosis↗
PubMed1997

Association of vascular endothelial growth factor expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet-derived endothelial cell growth factor expression in human colorectal cancer.

To examine the association of vascular endothelial growth factor (VEGF) expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet-derived endothelial cell growth factor (dThdPase/PD-ECGF) expression in human colorectal cancer, immunohistochemical studies were performed on 136 cases of resected colorectal cancer specimens using antibodies for VEGF, KDR, CD34 and dThdPase/PD-ECGF. Fifty-nine cases (43%) were evaluated as positive for VEGF staining and 71 cases (52%) were evaluated as positive for dThdPase/PD-ECGF staining. The expression of VEGF correlated significantly with vessel counts and the expression of dThdPase/PD-ECGF (P = 0.01 and 0.01, respectively). Cox proportional hazards model analysis showed that vessel counts and VEGF expression were significant and independent prognostic factors, but that KDR expression was not.

Adult↗
PubMed1997

[A case report of perforated early gastric cancer].

An 83-year-old woman was seen at the First Department of Medicine Fukui Medical School because of upper abdominal pain. A simple chest film taken in the upright position revealed free air under the diaphragm. She was referred to the department and underwent a laparotomy with a diagnosis of acute panperitonitis due to a perforated gastric ulcer. At laparotomy, there was a perforation measuring 5 x 5 mm at the anterior gastric body of the lesser curvature, covered with abdominal wall. Billroth I gastrectomy was carried out with no lymph node dissection. The histological examination of the surgical specimen showed early gastric cancer of type IIc invading the submucosal layer around the ulcer in the gastric wall, composed of well differentiated adenocarcinoma. The perforated early gastric cancers often present difficulty in diagnosis pre or intra-operatively. So it is important to examine closely the resected specimen intra-operatively and perform frozen section diagnosis whenever possible. Forty-six cases of perforated early gastric cancer collected from the Japanese literature are also discussed.

Adenocarcinoma↗
PubMed1997

Tumor angiogenesis and mode of metastasis in patients with colorectal cancer.

Neovascularization promotes tumor growth by facilitating nutrient exchange and by the paracrine effect. To investigate the relationship between tumor angiogenesis and patient outcome in colorectal cancer, 133 primary tumors were immunostained for CD34 antigen. Blood vessels within five microscopic fields at x200 were counted, and the mean was assigned. Mean patient age was 62.9 years, mean follow-up was 56.4 months, and mean vessel count was 112 (range, 23-298). Cox proportional hazards model and multivariate logistic regression analyses showed that the vessel count was the most important prognostic factor and correlated significantly with hematogenous, but not peritoneal or lymph node, metastasis.

Adenocarcinoma↗
PubMed1997

Spontaneous apoptosis is inversely related to intratumoral microvessel density in gastric carcinoma.

Increasing evidence from experimental studies indicates that apoptosis may be related to angiogenesis in tumor progression. To explore how spontaneous apoptosis correlates with tumor angiogenesis, we measured the apoptotic index (AI) using the ApopTag kit (Oncor) and intratumoral microvessel density using an anti-CD34 monoclonal antibody in 101 cases of gastric carcinoma. Immunohistochemical staining for Ki-67 labeling index and the expression of p53 were conducted simultaneously. Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities (r = -0.4066, P < 0.0001) and failed to find significant correlations between AI and Ki-67 labeling index, as well as the expression of p53. The results of this study demonstrated for the first time that the incidence of apoptosis in gastric carcinoma is significantly influenced by the extent of neovascularization and suggests that tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.

Apoptosis↗
PubMed1997

Tumor vascularity correlates with the prognosis of patients with esophageal squamous cell carcinoma.

BACKGROUND: Angiogenesis is essential for the growth of solid tumors. Intratumoral microvessel count, which represents a measure of tumor angiogenesis, has been associated with the overall survival of patients with a variety of malignancies. However, little is known about the significance of neovascularization in esophageal squamous cell carcinoma. METHODS: In this study, the role of tumor angiogenesis as a prognostic indicator was examined in esophageal squamous cell carcinomas from 43 patients. Vascular endothelial cells were stained with anti-CD34 and anti-von Willebrand factor monoclonal antibodies before being quantitated by light microscopy (x 200). RESULTS: Significant correlation between vessel counts for two antibodies was observed, although counts for CD34 were approximately three times higher. Intratumoral vessel counts were significantly higher in tumors with deeper penetration. Multivariate analyses indicated that vessel counts determined by either CD34 or von Willebrand factor staining, as well as lymph node metastasis, were identified as significant and independent prognostic factors in patients with esophageal squamous cell carcinoma. CONCLUSIONS: These findings support the hypothesis that tumor angiogenesis is closely related to the overall survival of patients with esophageal squamous cell carcinoma. The extent of tumor vascularity may serve as a reliable prognostic marker with which patients at risk for recurrence can be identified.

Aged↗
PubMed1997

Effect of spinal cord preconditioning on paraplegia during cross-clamping of the thoracic aorta.

BACKGROUND: Paraplegia is a devastating complication of operations for thoracic or thoracoabdominal aneurysms. Preconditioning the brain with sublethal ischemia induces resistance to subsequent ordinarily lethal ischemia (ischemic tolerance). We investigated whether ischemic tolerance could be induced by preconditioning canine spinal cord. The role of heat-shock proteins (HSP) in this process was investigated. METHODS: In experiment 1, the preconditioning group (n = 6) had aortic cross-clamping for 20 minutes, whereas controls (n = 6) had no cross-clamping. After 48 hours the aorta was cross-clamped for 60 minutes in both groups. Neurologic examination was performed 24 hours later and the spinal cord was studied for immunohistochemically. In experiment 2, either 48 hours after 20 minutes of clamping or after sham operation (n = 4), HSP were investigated immunohistochemically. RESULTS: In experiment 1, 3 of 6 controls became paraplegic but none of the 6 preconditioning group dogs became paraplegic. The HSP appeared on sections from all 6 PC dogs and 3 control dogs that did not exhibit paraplegia. In experiment 2, HSP were present in clamped animals but could not be detected after sham operation. CONCLUSIONS: Ischemic tolerance was induced by preconditioning the canine spinal cord, in which HSP are believed to be involved.

Animals↗
PubMed1997

Enhancement of drug sensitivity and a bystander effect in PC-9 cells transfected with a platelet-derived endothelial cell growth factor thymidine phosphorylase cDNA.

5'-Deoxy-5-fluorouridine (5'-DFUR) and 1-(tetrahydro-2-furyl)-5-fluorouracil (tegafur), prodrugs of 5-fluorouracil (5-FU), are anticancer agents activated by thymidine phosphorylase (dThdPase). As it is well known that the levels of dThdPase are higher in tumours than in normal tissue, it should be advantageous to use such pyrimidine antimetabolites for the selective inhibition of tumour growth. However, tumours are not necessarily sensitive to 5'-DFUR and tegafur because their levels of dThdPase vary. In this study, we examined whether transfection of tumour cells with a human platelet-derived endothelial cell growth factor (PD-ECGF) complementary DNA (cDNA) expressing dThdPase would sensitize the cells to the cytotoxic effects of pyrimidine antimetabolites in vitro. A cDNA encoding PD-ECGF was transfected into PC-9 cells (human lung adenocarcinoma). The transfected cells, PC9-DPE2, had a more than 50 times higher activity of dThdPase than the parental PC-9 cells or control PC-9 cells transfected with the pcDNA3 vector alone (PC9-D1). They were more sensitive than parental PC-9 or PC9-D1 cells not only to 5'-DFUR and tegafur but also to 5-FU. In addition, we demonstrated that PC9-DPE2 cells are able to potentiate the cytotoxic effects of 5'-DFUR towards co-cultured parental PC-9 cells. This "bystander effect' did not require cell-cell contact. These results suggest that transfection of PD-ECGF (dThdPase) genes may be useful as a gene therapy strategy for cancer treatment.

Antineoplastic Agents↗
PubMed1997

Association of tumour vasculature with tumour progression and overall survival of patients with non-early gastric carcinomas.

In order to investigate the relationship between intratumoral vasculature and progression of gastric carcinomas and between vessel counts and survival of patients with non-early gastric carcinoma, we counted the intratumoral microvessels and compared their numbers with clinicopathological parameters, as well as with the patients' survival. Microvessels were stained with anti-CD34 monoclonal antibody before counting by microscopy (x200). In a group of 181 patients who had undergone tumour resection and were followed for more than 24 months the vessel counts for 83 patients with stage IV disease were significantly higher than those for patients with any other stage of disease. Among various clinicopathological variables, haematogenous metastasis, lymph node metastasis, peritoneal metastasis, stage IV disease and non-curative resection were more frequent in the patients with highly vascularized tumours (intratumoral vessel count > 155) than in those with less vascularized tumours. As a classification of stage IV disease such as haematogenous or peritoneal metastasis generally indicates non-curative resection, it can be considered that the development of stage IV disease is associated with the increase in tumour angiogenesis. Both univariate and multivariate analyses showed that the intratumoral vessel count was significantly predictive of overall survival, when tested as either a continuous or dichotomous variable. Cox hazards model analysis showed that the vessel count was one of the significant and independent prognostic variables. Patients with highly vascularized tumours were significantly more likely to die than those with less vascularized tumours. Assessment of tumour vasculature may therefore be important, not only for its prognostic value, but also as it may help to predict responses to angiogenesis-inhibiting agents.

Adult↗
PubMed1997

Quantitation of sinusoid-like vessels in hepatocellular carcinoma: its clinical and prognostic significance.

Angiogenesis is crucial for tumor growth and metastasis. Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between tumor vascularity and the outcome of patients with HCC has not been evaluated. To clarify whether tumor angiogenesis is related to the prognosis of patients, immunohistochemical staining, using anti-von Willebrand factor (vWF) and anti-CD34, was applied in resected specimens from 43 cases of HCC. In nonmalignant tissue, staining was confined to vessels in the portal tract and to a few periportal sinusoids with both of the endothelial markers applied. In tumor tissue, however, sinusoid-like vessels reacted intensively with anti-CD34 but not with anti-vWF. The intratumor microvessel density (MVD) highlighted by anti-CD34 was 297 +/- 88 (per 0.74 mm2), which was significantly higher than that highlighted by anti-vWF (4 +/- 7). When only the MVD highlighted by anti-CD34 was analyzed, tumor diameter larger than 2 cm, poor differentiation (Edmondson's II to IV), and portal invasion were significantly related to the subgroup with MVD > or = 290. Overall survival curves of patients with MVD < 290 were better, and these patients were more likely to remain tumor free. Cox hazards model revealed intratumor MVD and Edmondson's grade to be independent prognostic factors for the overall survival of patients. These results demonstrated for the first time that tumor angiogenesis assessed by anti-CD34 was correlated with the outcome of patients with HCC, suggesting a potential role for anti-CD34 in the diagnosis and treatment of HCC.

Adult↗
PubMed1997

Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma.

PURPOSE: The relationship between the expression of vascular endothelial growth factor (VEGF) and its receptor, KDR, in human gastric carcinoma tissues and tumor angiogenesis, as well as patient outcome, were investigated. MATERIALS AND METHODS: One hundred sixty-three primary tumor specimens were investigated by immunohistochemical studies with anti-VEGF, anti-KDR, and anti-CD34 antibodies and by monitoring patients for at least 2 years after surgery. RESULTS: For intensity of VEGF staining, 48 tumors were graded as 0, 36 as 1+, 63 as 2+, and 16 as 3+. Tumors with strong VEGF staining, assessed as 2+ and 3+, had significantly higher vascularity than those with weak VEGF. Eighty-eight tumors (54%) were positive for KDR. There was no association between KDR expression and tumor vascularity. No close correlation was found between VEGF and KDR expressions. The Cox proportional hazards model identified intratumoral vessel count as the most significant and independent prognostic factor among various clinicopathologic factors. In contrast, overall survival rates for 84 patients with weak VEGF staining tumors and 79 with strong VEGF staining tumors were not significantly different. Patients with tumors of either localized Borrmann types or well-differentiated histologies, which are found more frequently in tumors with strong VEGF staining, survived significantly longer than those with tumors of either infiltrative Borrmann types or poorly differentiated histologies. CONCLUSION: We suggest that expression of VEGF is more frequently found in tumors with well-differentiated histology and plays a role in the promotion of angiogenesis in human gastric carcinomas.

Aged↗
PubMed1997

[Detection of P-glycoprotein and its clinical significance].

There is considerable variation in the assays used to evaluate the expression of mdr1 in various human malignancies. Current methodology includes reverse transcriptase polymerase chain reaction (RT-PCR) for assay of mdr1 mRNA, and immunohistochemistry or flow cytometry for detection of the multidrug transporter, P-glycoprotein(P-gp). Normal tissues, such as gastrointestinal mucosa, biliary tract and kidney, express high levels of P-gp, which suggests physiologic functions for this transporter. The some evidence suggests that mdr1 expression is a prognostic factor for response to chemotherapy, as well as for subsequent survival in various kind of tumors. We have developed a novel method using flow cytometry for detection of P-gp in gastric carcinomas. A strong correlation was noted between the flow cytometric data and the degree of drug resistance assessed by thymidine incorporation assay (TIA). We believe that this technique may have a significant potential to be utilized in prediction of P-gp related drug resistance in clinical cancer chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Correlations between cell proliferating activity and apoptosis in the colorectal cancer and apoptosis in the mucosa adjacent to colorectal cancer].

To investigate the growth and progression of colorectal cancer, cell production versus cell loss in colorectal cancer was examined using the proliferating cell nuclear antigen (PCNA) positivity rate and apoptotic index (AI). Cell loss was then examined using AI in the mucosa adjacent to colorectal cancer. The higher the PCNA positivity rate, the higher the apoptotic index in colorectal cancer. These results suggested that changes in cell production and cell loss may be closely correlated and play a role in the growth and progression of colorectal cancer. In patients with advanced colorectal cancer, the mucous composition of the adjacent mucosa was classified as sialomucin-predominant. Apoptosis at the proliferating zone in the mucosa adjacent to colorectal cancer (one or two glandular ducts) was also examined using the TUNEL method. This suggests that the mucosa adjacent to cancer is involved in apoptosis.

Apoptosis↗
PubMed1997

[Three-dimensional transesophageal echocardiographic assessment for prosthetic valves].

We evaluated three-dimensional transesophageal echocardiographic assessment of the implanted mechanical valves by rotational scanning method. Patients were 7 mitral valve replacement and one aortic valve replacement, 2 mitral and aortic valve replacement. In 2 cases of 7 mitral valve replacement, the prosthetic valve regurgitation was evaluated using by color Doppler echocardiography. In this study, multiplane transesophageal probe was used. It rotated at 2-degree intervals from 0 to 180 degrees and the three-dimensional reconstruction was performed by echo scan workstation system (TOMTEC Inc, Munich, Germany). In mitral valve replacement cases, the valve motion of bileaflet valve (St. Jude Medical valve and ATS valve) were showed very clearly. The struts was easily recognized in the St. Jude Medical valve (SJM valve) cases. In one of SJM valve cases, the pannus formation was revealed, but it did not disturb valve motion. The prosthetic valve regurgitation can be seen accurately. However, aortic valve and ball valve cases cannot be reconstructed because of artifact from prosthetic valve and ultrasonic direction. The prosthetic valve regurgitation, pannus formation which was difficult to be showed in two-dimensional echocardiography and relationship between annulus and sewing cuff can be evaluated by this three-dimensional echocardiography. In this study, this system has some problems, for example real-time evaluation is impossible, aortic valve and ball valve cases cannot be reconstructed. However, we think that this new technology is suitable for evaluating valve thrombus, valve dysfunction and paravalvular leakage. In conclusion, the three-dimensional echo-cardiography demonstrated, reliable and accurate examination, and it can evaluate various complications of prosthetic valve.

Adult↗
PubMed1997

Assessment of plaque rupture by intravascular ultrasound.

To investigate the mechanism of plaque rupture, we carried out morphologic and quantitative assessments of ruptured plaque with a 30-MHz intravascular ultrasound catheter before coronary intervention. Plaque rupture, defined as an echolucent intraplaque area communicating with arterial lumen, was noted in all of 22 patients with coronary artery disease examined in the study. The plaque was eccentric in 16 patients (73%) and in 10 of these 16 patients there was a tear at the margin of the plaque (63%). Calcification was noted in only 6 patients (22%). Plaque area ranged from 8.7 to 44.1 mm2. The ruptured area ranged widely, from 1.0 to 14.0 mm2, and the percent ruptured area also ranged widely, from 3.9% to 50.9%. Fibrous cap was recognized in 20 patients. The thickness of the fibrous cap ranged from 0.1 to 0.6 mm (mean, 0.36 mm) and thinning of the fibrous cap was noted in 16 patients (80%). From these results, we conclude that intravascular ultrasound can provide detailed observations of plaque rupture consistent with pathologic studies. Accordingly, it is a suitable method for evaluation of plaque rupture in vivo. Plaque weakness, due to the presence of atheromatous core, thin fibrous cap, and no calcification, seems to be the major determinant of plaque rupture. In addition, the great variation in cap thickness and ruptured area suggests the role of other triggers, such as mechanical and hemodynamic stress, in plaque rupture.

Coronary Artery Disease↗
PubMed1997

Improvement of in vitro chemosensitivity assay for human solid tumors by application of a preculture using collagen matrix.

The use of [3H]thymidine incorporation assay (TIA) to evaluate the drug response of tumor cells has been recognized as a useful chemosensitivity assay for fresh human tumor specimens. However, its low evaluability has been a disadvantage for clinical application. To overcome this drawback, we have applied a preculture stage prior to the TIA. This preculture requires plating the tumor cell suspension onto a collagen matrix for 24 h. In 29 fresh human tumor specimens, a significant increase in both cell viability (P < 0.05) and [3H]thymidine incorporation (P < 0.001) of the cultured cells was observed with preculturing; the composition of cancer cells (epithelial membrane antigen positive) and stromal cells (vimentin positive) did not change. In comparisons between 66 specimens that were precultured and 705 specimens that were not, the evaluability rate increased significantly from 48.5% (342/705) to 75.8% (50/66; P < 0.0001) after preculturing. No significant change in in vitro chemosensitivities was observed. When the clinical responses for cancer chemotherapy were retrospectively compared with the in vitro sensitivities of the corresponding drugs on 16 patients who had measurable lesions, the correlation between the two was satisfactorily strong; the prediction accuracy for sensitivity was 83.3% (5/6), the prediction accuracy for resistance was 95.0% (19/20), and the overall correlation was 92.3% (24/26). These results indicate that TIA with preculturing yields increased rates of evaluability, preserving in vitro drug responses of cultured tumor cells, and has an improved potential to be used for determining clinical chemotherapy.

Antineoplastic Agents↗