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H Nagawa

Publications and source records attributed to H Nagawa.

At least 37 records · Page 2Linked to original sources
PubMed2005

High hRFI expression correlates with resistance to fluoropyrimidines in human colon cancer cell lines and in xenografts.

We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-alpha induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoropyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue microarray consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy.

Carrier Proteins↗
PubMed2005

Impaired ambulatory venous function in lymphedema assessed by near-infrared spectroscopy.

AIM: The aim of this study was to investigate venous function in patients with leg lymphedema during exercise using near-infrared spectroscopy (NIRS), compared with that of patients with chronic venous insufficiency (CVI). METHODS: Forty-three legs of 33 patients (5 males, 28 females; mean age: 53 years) with leg lymphedema without varicose veins or deep vein thrombosis underwent a treadmill walking test with simultaneous NIRS. For comparison, 136 legs of 91 patients (35 males, 56 females; mean age: 56 years) with varicose veins as a CVI group and 45 legs of 38 healthy volunteers (23 males, 15 females; mean age: 50 years) were also evaluated in the same method. Deoxygenated hemoglobin (HHb) was continuously measured during exercise, and the ambulatory venous retention index (AVRI) of each leg was obtained from the serial changes in HHb. RESULTS: The mean AVRI of the lymphedema group was significantly higher than that of healthy legs and significantly lower than of legs with moderate or severe CVI. Furthermore, it was similar to that in the mild CVI group. CONCLUSIONS: Venous function is impaired in exercising legs with lymphedema, and corresponds to that in legs with mild venous insufficiency. The treatment of lymphedema should take CVI into consideration.

Adult↗
PubMed2005

Long-term results of combined iliac endovascular intervention and infrainguinal surgical revascularization for treatment of multilevel arterial occlusive disease.

AIM: The purpose of this study was to investigate the long-term results of combined iliac endovascular intervention and infrainguinal surgical revascularization. METHODS: A retrospective review of 39 infrainguinal bypasses combined with iliac endovascular intervention in 35 patients over a 16-year period was performed (Combined group). These results were compared to those of 43 infrainguinal bypasses performed with suprainguinal bypass operation in 39 patients (Surgical group), who had iliac lesions not amenable to angioplasty/stenting. There was no significant difference in the preoperative limb ischemic symptoms between them. RESULTS: Although the proportion of patients with coronary artery disease in the Combined group was significantly higher than that in the Surgical group, there was a trend toward lower morbidity/mortality in the Combined group compared with the Surgical group (8.6% vs 15.4%; P=0.3706). No significant differences in the rates of clinical and hemodynamic improvement and limb salvage rate were observed between the two groups. The primary patency rate of infrainguinal bypass at 1, 3, and 5 years was 83.2%, 80%, and 71.2% in the Combined group, and 97.1%, 89.9%, and 80.5% in the Surgical group, respectively. The secondary patency rate at 1, 3, and 5 years was 91.9%, 91.9%, and 76.3% in the Combined group, and 97.1%, 89.9%, and 84.6% in the Surgical group, respectively. Importantly, there was no significant difference in the primary/secondary patency rates between the two groups (Kaplan-Meier, log-rank test, primary patency, P=0.116; secondary patency, P=0.4407). CONCLUSIONS: Infrainguinal surgical reconstruction combined with iliac endovascular procedure may reduce operative risk, and further, long-term patency is comparable to that in the Surgical group.

Aged↗
PubMed2005

Persistent sciatic artery in a patient with extracranial internal carotid artery aneurysm and infrarenal abdominal aortic aneurysm. A case report.

A rare case of a persistent sciatic artery (PSA) in a patient with aneurysms of the internal carotid artery and abdominal aorta is presented. A 70-year-old man was referred with intermittent claudication of the right lower extremity. Angiography and computed tomography demonstrated that this symptom was due to occlusion of the PSA. On preoperative examinations, aneurysms of the extracranial internal carotid artery and abdominal aorta were incidentally discovered, and then surgically treated prior to the management of PSA. Systemic examinations must be performed in patients with PSA in order to scrutinize associated anomalies or vascular disease.

Aged↗
PubMed2004

Hyperlipidaemia is positively correlated with lymph node metastasis in men with early gastric cancer.

BACKGROUND: Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of serum lipid levels on tumour metastasis is not clearly understood. METHODS: The association between lymph node metastasis and preoperative serum levels of total cholesterol (TC) and triglyceride (TG) as well as various pathological findings for tumours was examined in 353 patients with early gastric cancer who underwent gastrectomy with classical lymphadenectomy. RESULTS: The rate of lymph node metastasis was significantly higher in patients with early gastric cancer who had hypercholesterolaemia (TC 220 mg/dl or greater) or hypertriglyceridaemia (TG 150 mg/dl or greater). The tendency was more prominent in men, and multivariate analysis showed that hypertriglyceridaemia was an independent risk factor for nodal metastasis in men, in addition to pathological invasion to the submucosal layer or to lymphatic vessels. In contrast, neither hypercholesterolaemia nor hypertriglyceridaemia showed a significant association with nodal status in women with early gastric cancer. CONCLUSION: Raised serum lipid levels might favour the development of lymph node metastasis in men with early-stage gastric cancer. In patients with early gastric cancer serum lipid levels should be checked before operation, and the use of minimal local treatments must be considered carefully in male patients with hyperlipidaemia.

Adult↗
PubMed2004

Genetic characterization of colorectal cancers in young patients based on chromosomal loss and microsatellite instability.

BACKGROUND: In recent studies a high frequency of microsatellite instability among colorectal cancers in young patients has been reported, but the frequency of microsatellite instability (MSI) and chromosomal instability among colorectal cancers in young patients has not yet been fully elucidated. Only one report showed an increased loss of heterozygosity (LOH) ratio at 9p locus, which harbors tumor suppressor genes p16. The LOH and MSI status among colorectal cancers in young patients was examined. METHODS: Twenty-five patients under 40 years of age diagnosed with colorectal cancer were examined for MSI and LOH using 17 microsatellite markers, and also p16 expression patterns were evaluated by immunohistochemistry and methylation status of the p16 gene was assessed by methylation-specific PCR. RESULTS: MSI was observed in only one case (4%). LOH at 2p, 5q, 9p, 11q, 17p, and 18q was observed in 41%, 59%, 42%, 35%, 46%, and 56% of cases, respectively. Eighty-three percent of patients showed p16-positive expression patterns. Fifty percent of colorectal cancers in young patients exhibited p16 methylation (3/6). CONCLUSIONS: Our study demonstrated that colorectal cancers in young patients without MSI showed a high frequency of LOH at the 9p locus. However, LOH status at 9p and p16 expression pattern did not show a significant correlation. Other tumor suppressor genes on the 9p, with the exception of p16, may play an important role in the carcinogenesis of colorectal cancers in young patients.

Adenocarcinoma↗
PubMed2004

Effects of expression of hRFI on adenoma formation and tumor progression in colorectal adenoma-carcinoma sequence.

For colorectal carcinomas as well as colonic polyps we investigated the expression of a newly discovered gene, hRFI, which is isolated by the yeast two-hybrid screening using hTid as a bait and expressed highly in esophageal carcinomas. Immunohistochemical staining was performed on 48 colorectal carcinomas and 77 colorectal polyps consisting of 70 adenomas and 7 hyperplastic polyps using the antibody of hRFI. We analyzed the expression of hRFI and the correlation between the percentage of staining of each and their clinico-pathological characteristics. Protein coding by hRFI was specifically and diffusely expressed in most of the cancerous regions of the colorectum. Also, in the early stage of colorectal adenomas, staining of hRFI was focal, and the percentage area of diffuse staining increased as the degree of dysplasia progressed. Although all normal colorectal glands and most hyperplastic polyps (71.4%) showed no staining of hRFI, most colorectal adenomas and carcinomas (93.2%) showed a focal or diffuse staining (P<0.001). Furthermore, the percentage of diffuse staining in carcinomas (81.3%) was significantly higher than in adenomas (5.7%) (P<0.001). hRFI is highly expressed in colorectal carcinomas. In the adenoma-carcinoma sequence, hRFI is involved at the initial tumor formation and its diffuse expression is associated with colorectal carcinogenesis. This evidence suggests that hRFI may act as an oncogenic molecule affecting the apoptotic pathway.

Adenoma↗
PubMed2004

Hemodynamic influence of peripheral vascular occlusive disease on abdominal aortic aneurysms.

AIM: Clinical evidence indicates that hemodynamic conditions such as peripheral vascular occlusive disease (PVOD) influence abdominal aortic aneurysm (AAA) disease. METHODS: We retrospectively analyzed 406 operated cases of AAA at our institute over the last 15 years, and compared 39 patients with PVOD to those without, to examine hemodynamic effects and risk factors. Aneurysm size at operation, rupture, shape, expansion rate and several preoperative risk factors were compared. RESULTS: Mean aortic diameter in the AAA with PVOD patients (56.8+/-17.8 mm) showed no significant difference to that in the AAA without PVOD group (60.4+/-14.8 mm). However, the subgroup of AAA with PVOD in whom the aneurysm was found prior to PVOD diagnosis (67.8+/-18.1 mm) (n=19) showed a larger mean AAA diameter compared to the AAA (not followed up until operative indication/prior to operation) without PVOD group (60.4+/-14.8 mm), (n=340), (p=0.04). Smoking was the only preoperative risk factor to show a difference between AAA patients with and without PVOD. The aneurysm expansion rate was determined retrospectively in 13 patients with PVOD who had been followed for at least 1 year by CT scan and 17 patients without PVOD. The rate in the PVOD group was 8.1 mm/year, which was significantly faster than that in PVOD-free patients (4.6 mm/year), (p=0.03). CONCLUSIONS: The findings of a large diameter and fast expansion rate in AAA patients with concomitant PVOD suggest that the hemodynamic effects of PVOD have a great influence on AAA development.

Adult↗
PubMed2004

Contralateral stenosis as a risk factor for carotid endarterectomy measured by near infrared spectroscopy.

AIM: It is still controversial whether the existence of a contralateral stenosis is a risk factor during carotid endarterectomy (CEA). We used a near infrared spectroscopy (NIRS) monitoring system during CEA to evaluate the hemodynamic effect of contralateral stenosis during cross clamping of the carotid arteries. METHODS: We monitored 34 consecutive cases of CEA, using NIRS. Tissue oxygen index (TOI), as a parameter of oxygenation, and total hemoglobin index (THI), as a parameter of blood volume, were measured during cross-clamping the carotid arteries. We evaluated the relationship between these results and the pre- and intraoperative characteristics including the existence of a contralateral stenosis and the results of single-photon emission computed tomography (SPECT). RESULTS: Bilateral TOI and THI correlated well with the severity of the stenosis of the contralateral internal carotid artery, and ipsilateral THI correlated with the cerebrovascular reserve measured by SPECT. CONCLUSIONS: A contralateral stenosis is a risk factor for CEA from the hemodynamical point of view, and extreme care should be taken when performing CEA in patients with bilateral stenoses.

Aged↗
PubMed2003

Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: results of a 23-year surveillance programme in the Japanese population.

Patients with long-standing ulcerative colitis (UC) are known to have an increased risk for the development of colorectal cancer (CRC). The aim of this study was to clarify the cumulative risk for the development of dysplasia or invasive cancer and the effectiveness of surveillance colonoscopy in the Japanese population. A total of 217 patients received a total of 1027 surveillance colonoscopies between January 1979 and December 2001 at the University of Tokyo hospital. Patients with invasive cancer found in the surveillance group were compared to those referred to our hospital from the other hospitals without surveillance colonoscopy. Surveillance colonoscopy confirmed 15 patients with definite dysplasia. Of these, five were proved to have invasive cancer in the resected specimens. The cumulative risk for the development of invasive cancer at 10, 20, and 30 years was 0.5, 4.1, and 6.1%, respectively, while that for the development of definite dysplasia at 10, 20, and 30 years was 3.1, 10.0, and 15.6%, respectively. All the patients with invasive cancer in the surveillance group remained alive, while three out of four patients in the nonsurveillance group died. Our surveillance programme is useful for detecting UC-associated CRC, and survival may be improved by surveillance colonoscopy.

Adolescent↗
PubMed2003

Patients with extraintestinal manifestations have a higher risk of developing pouchitis in ulcerative colitis: multivariate analysis.

BACKGROUND: Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) have been the surgical treatments of choice for ulcerative colitis (UC). However, the IPAA is sometimes complicated with pouchitis. Furthermore, the cumulative risk and risk factors for developing pouchitis in patients with UC undergoing IPAA have not been reported in any Asian population. The aim of our study is to clarify the cumulative risk and risk factors for developing pouchitis in Japanese patients with UC undergoing IPAA. METHODS: Fifty-eight patients with UC undergoing IPAA were retrospectively evaluated for the presence of pouchitis, gender, age of onset, history of smoking, presence of extraintestinal manifestations (EIMs) and type of operation. The diagnosis of pouchitis was based on the pouchitis disease activity index. The cumulative risk and risk factors for developing pouchitis were assessed. RESULTS: The cumulative risks for developing pouchitis at 1 and 5 years were 9.0% and 14.4%, respectively. The estimated risks of pouchitis at 5 years was 48.1% in patients with EIMs and 4.6% in those without. Both univariate and multivariate analyses revealed that the presence of EIMs is a significant risk factor (hazard ratio 16.85, 95% confidence interval 3.12-91.00; P=0.001). CONCLUSIONS: The presence of EIMs is a significant risk factor for the development of pouchitis in Japanese patients with UC undergoing IPAA.

Colitis, Ulcerative↗
PubMed2003

Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku70 expression.

The identification of predictive indicators of radiosensitivity is extremely useful in selecting patients suited for preoperative radiotherapy and avoiding unnecessary preoperative treatment. In this study, we evaluated the possible role of the immunohistochemical expression pattern of p53 and Ku70 protein in determining tumor radiosensitivity in rectal cancer before preoperative irradiation. We examined pretreatment biopsy materials from 111 patients by immunohistochemistry. The expression pattern of p53 and Ku70 was evaluated for association with tumor radiosensitivity, which was defined according to the criteria of the Japanese Research Society for Cancer of the Colon and Rectum. There was a significant correlation between the expression pattern of p53 and tumor radiosensitivity (P = 0.045); Ku70 and tumor radiosensitivity (P < 0.001); and the combination of p53 and Ku70, and tumor radiosensitivity (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in both p53 and Ku70-positive cases for radioresistance were all superior to those of the group positive for p53 alone. In conclusion the examination of the combination of p53 and Ku70 may predict the radiosensitivity of rectal cancer before preoperative irradiation.

Adult↗
PubMed2003

Beta-chemokine, macrophage inflammatory protein-1beta (MIP-1beta), is highly expressed in diffuse type human gastric cancers.

Chemokines have been shown to be expressed in some malignant or precancerous tissues. However, the role of these chemokines on tumor development or progression is not clear. The expression patterns of chemokines in gastric cancer tissues were examined in 86 surgically resected samples using immunohistochemistry. Macrophage inflammatory protein-1beta (MIP-1beta) was clearly detected in many gastric carcinoma cells. In most of the differentiated carcinomas, intracellular localization of MIP-1beta was detected in more than 5% of cancer cells, although the percentages of MIP-1beta-positive cells differed among each sample. Undifferentiated carcinomas showed contrasted staining pattern between solid type and non-solid (diffuse) type. MIP-1beta was totally absent in all the poorly differentiated carcinomas with solid type growth pattern (por1). In contrast, MIP-1beta was highly expressed in all of the non-solid type of poorly differentiated carcinoma (por2) and signet-ring cell carcinoma samples. In particular, MIP-1beta was strongly stained in carcinoma cells at the front of invasive lesions. In 43 diffuse type undifferentiated cancers, tumors with high expression of MIP-1beta exhibited significantly more lymph node metastasis. Our results suggest a possibility that MIP-1beta may be related to the scattering and invasion step of gastric carcinoma cells with undifferentiated phenotype.

Chemokine CCL4↗
PubMed2002

Bcl-2, Bcl-xL and c-FLIP(L) potentially regulate the susceptibility of human peripheral blood monocyte-derived dendritic cells to cell death at different developmental stages.

We examined the susceptibility of human monocyte-derived dendritic cells (DCs) to spontaneous and CD95-mediated cell death at different developmental stages. Time course experiments revealed that the susceptibility of mature dendritic cells (mDCs) to spontaneous cell death was significantly lower than that of immature dendritic cells (iDCs) in a long-term culture under cytokine-free conditions, and the treatment with GM-CSF rescued these cells from spontaneous cell death at the late culture period. iDCs and mDCs expressed similar levels of CD95 whereas both cell types were relatively resistant to CD95-mediated cell death. Antigen (Ag)-specific and nonspecific cognate interaction with T cells failed to cause cell death of iDCs and mDCs. iDCs constitutively expressed transcripts and intracellular products of Bcl-2 and Bcl-xL, but not cellular FLICE-inhibitory protein(long (c-FLIP(L)), while the increased expressions of Bcl-2, Bcl-xL and c-FLIP(L) were observed in mDCs. These results suggest that the selective expressions of Bcl-2, Bcl-xL and c-FLIP(L) may be involved in the difference in the susceptibility to cell death between iDCs and mDCs.

CASP8 and FADD-Like Apoptosis Regulating Protein↗