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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 847 records · Page 47Linked to original sources

Usefulness of Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) as a marker of distant metastasis from hepatocellular carcinoma.

The objective of this study was to clarify the relationship between the serum level of the Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) and the clinical features including sex, age, Child's classification, virus markers, tumour size, tumour stage, distant metastasis, histopathologic findings, portal thrombus and outcome of hepatocellular carcinoma (HCC). We measured the AFP-L3 levels in 170 HCC cases at the time of diagnosis using lectin-affinity electrophoresis followed by antibody-affinity blotting. The patients were divided into two groups, those who were AFP-L3 positive (n=56; AFP-L3 >/=15% relative to the total alpha-fetoprotein (AFP) concentration) and those who were AFP-L3 negative (n=114; AFP-L3 <15%). Then we examined the association between the serum AFP-L3 level and the clinical features of HCC. No significant differences were found in age, sex, and virus markers between the AFP-L3-positive and -negative groups. However, patients in the positive group had worse liver function and larger tumours compared to the negative group. They also had more advanced cancer with poor tumour histology compared to the negative group. Distant metastasis was diagnosed significantly more often in the positive group than that in the negative group. There was no significant correlation between the AFP-L3 level and portal thrombus. Although the follow-up period was brief the prognosis for the positive group clearly was poor. These results suggest that AFP-L3 is a useful indicator of distant metastasis and a poor prognosis for HCC.

Adult↗

Perioperative quantitative analysis of cytokeratin 20 mRNA in peripheral venous blood of patients with colorectal adenocarcinoma.

Hematogenous dissemination is a significant short-coming of colorectal carcinoma treatment. To screen patients with high risk for such blood-borne metastasis, we previously developed a highly sensitive system for the detection of cytokeratin 20 (CK-20) mRNA in blood. For a more practical application, we improved this system by making it quantitative and capable of analyzing peripheral venous blood for the detection of perioperative changes in CK-20 mRNA. CK-20 mRNA was not always detected in the preoperative blood, even in patients in an advanced stage, but it was identified without fail in intra- and post-operative blood. In addition, more copies of CK-20 mRNA were observed in the intra-operative blood than in pre- and post-operative blood. This study suggests that analysis of perioperative changes may provide important information for the precise evaluation of hematogenous dissemination and of the effect of surgical maneuvers on recurrence.

Adenocarcinoma↗

Polymorphic variation of the ARP gene on 3p21 in Japanese esophageal cancer patients.

Allelic loss of the short arm of chromosome 3 is common in esophageal squamous cell carcinoma (ESC) and its premalignant lesions. The ARP gene (Arginine Rich Protein) was mapped to 3p21, and frequent variations of the triplet, AGG, repeat around codon 50 of the ARP gene were reported in a variety of human cancers. To examine the involvement of the ARP gene in esophageal cancer, we screened mutations around codon 50 in 35 ESC tumours and matched normal tissues. Sequence variants were observed in four ESC tumours; two (AGG)2 insertions, one ATG50-to-AGG substitution and one AGG deletion. However, they were also found in its corresponding normal tissues, suggesting that variation of the ARP gene found in ESC is polymorphic. We next analyzed sequence changes in 48 unrelated Japanese healthy individuals. They consist of 33 wild-type homozygotes, nine (AGG)2 insertion/wild-type heterozygotes, two (AGG)2 insertion homozygotes, one AGG deletion/wild-type heterozygote and three ATG50-to-AGG substitution/wild-type heterozygotes. Allele frequencies for wild-type, (AGG)2 insertion, ATG50-to-AGG substitution and AGG deletion are 0.82, 0.14, 0.03 and 0.01, respectively. Observed genotype frequencies fit well with the Hardy-Weinberg's law. Significant difference was not observed between allele distributions in normal and cancer patient populations.

Asian People↗

Concurrent chemoradiotherapy combined with intraoperative radiotherapy for locally advanced pancreatic cancer: a feasibility study.

Initial clinical results of concurrent chemoradiotherapy combined with high-dose intraoperative radiotherapy (IOR) for locally advanced pancreatic cancer were analyzed. Between June 1996 and May 1999, 6 patients with locally advanced pancreatic cancer without distant metastasis were treated with preoperative concurrent chemoradiotherapy followed by IOR. Preoperative radiation therapy was given by the dynamic arc conformal technique with a daily fraction of 1.8 Gy to a total dose of 45 Gy in 5 weeks. Cisplatin (5 mg/day for 4 weeks) and 5-fluorouracil (250 mg/day for 5 weeks) were administered continuously during preoperative radiation therapy. IOR as a single dose of 28 or 30 Gy was given to the gross tumor volume using electron beams of 15- to 22-MeV. Concurrent chemoradiotherapy was well tolerated, although all of the patients complained of nausea and fatigue. Two patients developed grade III leukopenia. No other serious acute toxicity was noted. The median survival time of the 6 patients was 17.5 months, which was significantly longer than that of our historical control treated with external radiation therapy with IOR (8 months), although the difference in survival was borderline significant (p=0.068). Concurrent chemoradiotherapy followed by high-dose IOR was well tolerated in patients with locally advanced pancreatic cancer, and the initial clinical results appeared promising.

Adult↗

Membrane fluidity correlates with liver cancer cell proliferation and infiltration potential.

We developed a method to measure membrane fluidity of living cancer cells in two- and three-dimensional cultures, and found that there was a close relationship between the membrane fluidity of cancer cells and their proliferative and infiltrative ability. Membrane fluidity is thus a promising indicator of the probability of cancer recurrence.

Bromodeoxyuridine↗

Carbohydrate antigens as a risk factor for hematogenous recurrence of esophageal squamous cell carcinoma patients.

The patients with hematogenous recurrence have a poor prognosis in esophageal squamous cell carcinoma (SCC). Recent developments have suggested the important role of sialyl Lewis A and X in the step of hematogenous metastasis. To evaluate the role of two carbohydrate antigens on hematogenous recurrence in esophageal SCC, we examined clinicopathological features and the expression of sialyl Lewis A and X in 125 patients retrospectively. Thirty-three out of 125 patients had hematogenous recurrence after curative esophagectomy. sLeA and sLex expression correlated with hematogenous recurrence (p=0.026, p=0.043 respectively), and sLeA expression was correlated with pM (lymph). Cox proportional hazards model and logistic regression analysis revealed that pN and pM lymph were significant prognostic factors and predictive factors of hematogenous recurrence in esophageal SCC. Although, neither sLeA nor sLeX were significant factors affecting survival in esophageal SCC, logistic regression analysis demonstrated that increased tumoral expression of sLeA and sLeX were risk factors of hematogenous recurrence in esophageal SCC. In conclusion, patients with lymph node metastasis, in particular those with distant lymph node metastasis, the expression of sLeA and sLeX may suggest a higher incidence of hematogenous recurrence in esophageal SCC. New strategies for specific inhibition of cancer cell attachment to vascular endothelial cells should be considered for the patients with the increased tumoral expression of either sLeA or sLeX.

Antigens, Tumor-Associated, Carbohydrate↗

c-erbB-2, p53 protein expression and steroid hormone receptors in breast carcinomas: an immunohistochemical study.

p53, c-erbB-2 protein, steroid hormone receptors, and their correlation with clinicopathologic features were investigated in 70 primary breast carcinomas. All markers were measured immunohistochemically on paraffin sections. Altered p53 expression was found in 27.1% of cases and was associated with negative estrogen receptor status. p53 immunostaining was correlated weakly with histologically lymphatic vessel invasion of carcinoma. c-erbB-2 protein overexpression was seen in 48.6% of cases. A trend was observed in the correlation between c-erbB-2 immunostaining and regional lymph node metastases. Estrogen receptor status was not associated with any histologic or clinical parameters, whereas progesterone receptor status was associated with lymph node metastasis and histologically lymphatic vessel invasion of cancer. PgR status, p53 and c-erbB-2 immunostaining may prove to be an additional criterion in histologic diagnosis of breast cancer.

Adult↗

Percutaneous injection of a low-concentration alkaline solution targeting hepatocellular carcinoma.

We developed a percutaneous low-concentration alkali injection therapy (PLAIT) targeting hepatocellular carcinoma (HCC), and compared the necrotic areas in the livers of rats that had received PLAIT [an alkaline solution of sodium hydroxide (NaOH)] with those that had received percutaneous ethanol injection therapy (PEIT) and percutaneous acetic acid injection therapy (PAIT). The necrotic area increased with increasing concentrations of NaOH solution. The survival rate of rats was 100% up to a concentration of 4 N; however, the rate dropped below 80% with concentrations over 5 N. Also, at a concentration of 2 N, the necrotic area increased with increasing quantities from 0.01 ml to 0.1 ml. PLAIT using 0.05 ml of 2 N NaOH was 1.56 times more effective than PEIT using 0.05 ml of 99.5% ethanol, and 63.33% less effective than PAIT using 0.05 ml of 50% acetic acid. However, the survival rate after PAIT was 50%, while that after PLAIT was 100%. Histopathological observation of normal rat livers after injection of 2 N NaOH at a volume of 0.05 ml showed that the tissue necrosis spread radially from the site immediately after injection by PLAIT, but necroses were not found in other organs. We conclude that PLAIT has promise as a new form of local therapy for HCC.

Animals↗

Progression of esophageal carcinoma by loss of EGF-STAT1 pathway.

PURPOSE: In only a very limited number of cultured cell lines, epidermal growth factor (EGF), a potent mitogen for many kinds of cells, was shown to activate STAT1 (signal transducer and activator of transcription 1) protein, which can transmit signals that cause cell growth arrest and apoptosis. The purpose of this work is to elucidate the physiologic and/or pathological significance of this EGF-STAT1 pathway. MATERIALS AND METHODS: A series of cultured cell lines that had been established from surgical specimens of esophageal squamous cell carcinoma was studied for the existence of the EGF-STAT1 pathway. Normal esophageal squamous epithelial cells either explanted from non-neoplastic portions of surgically removed human esophageal tissue or in bovine esophageal epithelium in situ were examined as well. RESULTS: EGF treatment leads to a strong growth arrest in three of the 30 esophageal squamous cell carcinoma cell lines. STAT1 was found to be activated by EGF in the three cell lines but not in the others. EGF can also activate STAT1 in cultured normal esophageal squamous epithelial cells. STAT1 is at the activated state in the basal cell layer of the bovine esophageal epithelium. Notably, patients who had harbored the cancer cells with the EGF-STAT1 pathway had a dramatically better prognosis. DISCUSSION: The EGF-STAT1 pathway may be intrinsic to esophageal epithelial lineage of cells and is lost in a considerable fraction of the carcinomas. This loss appears to cause a significantly more malignant clinical course. These findings may point out a critical step in the progression of esophageal cancer and could lead to the development of useful clinical applications.

Blotting, Northern↗

Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells.

We have examined the relationship between the expression and activation of the IL-6 receptor and the possible involvement of IL-6 in the resistance of radiation-induced apoptosis in pancreatic cancer cells. Levels of IL-6 in the incubation media measured with ELISA were 1900 pg/ml in CFPAC-1, 54 pg/ml in HPAC and less than 0.2 pg/ml in MIAPaCa-2 and AsPC-1. Western blot demonstrated gp80 protein (IL-6 receptor a subunit) in all pancreatic cancer cell lines except in AsPC-1. When immunoprecipitation was performed, the bands indicating phosphorylated gp130 (IL-6Rbeta) were observed in CFPAC-1 and HPAC, however, no band was found in MIAPaCa-2 or in AsPC-1 cells. RT-PCR and Western blot demonstrated that mRNA and protein expression for Bcl-2 and Bcl-XL was substantially increased by the IL-6 treatment in CEPAC-1 cells, but not in AsPC-1 cells. Neither exogenous IL-6 nor neutralizing anti-IL-6 mAb affected the proliferation of CFPAC-1 and AsPC-1 cells. However, the IL-6 treatment significantly attenuated the susceptibility to radiation in CFPAC-1 cells but not in AsPC-1 cells, and the neutralizing anti-IL-6 mAb significantly increased the radiosensitivity of CFPAC-1 cells. The results indicated that IL-6 might be produced in a paracrine and/or autocrine fashion in pancreatic cancer cells. In-6 inhibits radiation-induced apoptosis and enhances the survival of the cells through a functional receptor system, which is associated with the up-regulation of anti-apoptotic Bcl-2 family proteins, especially Bcl-XL.

Apoptosis↗

Some properties of avian adenoviruses isolated from chickens with inclusion body hepatitis in Japan.

Outbreaks of inclusion body hepatitis were observed in broiler chickens on a poultry farm during 3 years. Avian adenovirus-like agents were isolated during these years from livers of diseased chickens. Round-cell-type cytopathogenic effect and intranuclear inclusion bodies were produced in chicken kidney cell cultures inoculated with these agents. Properties of the agents were as follows: resistant to ether, chloroform, socium deoxycholate, trypsin, heating at 50 C, and pH 3.0; sensitive to 5-iodo-deoxyuridine; and pathogenic to chicken embryos. From these properties and ultrastructural findings of the agents, these were identified as avian adenovirus. Day-old commercial chicks were insusceptible to these viruses. Maternal antibody levels in commercial chicks were considerable. Surveys for neutralizing index to the virus were performed on chickens in the field, and all sera tested were positive. Electron-microscope examination showed that these viruses contained avian-adenovirus-associated virus.

Adenoviridae↗

Postoperative radiation therapy for esophageal cancer.

The value of postoperative radiation therapy (RT) was investigated in 77 patients with esophageal cancer resected between 1977 and 1986. Surgical resection was palliative in 13 of these patients. Although seven of them underwent postoperative irradiation to the residual tumor, all of the patients died within one year. Following potentially curative resection performed in 64 patients, 31 patients received 50 Gy of postoperative RT to the lower neck and the mediastinum (group Ia), seven were unable to receive full-dose postoperative RT (group Ib), and 26 were not treated with postoperative RT (group II). The 5-year survival rate estimated by the Kaplan-Meier method was 54% for group Ia, 29% for group Ib, and 33% for group II, with the difference between groups Ia and II being significant (p less than 0.025). The local recurrence rate in the mediastinum was lower in group Ia than in group II. Prophylactic postoperative RT for esophageal cancer is a safe and effective regimen for patients with resected disease.

Adult↗

Metabolism of cholecystokinin-33 in vivo: effect of L-364,718, a CCK receptor antagonist.

Metabolism of cholecystokinin (CCK) and the effect of L-364,718, a specific CCK-A receptor antagonist, on the metabolism of CCK were examined in dogs. In conscious dogs, 45 min intravenous infusion of synthetic human CCK-33 (100 pmol/Kg/hr) caused an integrated CCK response over 90 min of 675 +/- 51 pmol-90 min/L, and the plasma CCK levels declined promptly with a t1/2 of 2.2 +/- 0.3 min after cessation. Organ extraction of CCK-33 by the kidney, mesenteric organs, and liver was examined in anesthetized dogs. From the gradients of the plasma levels between afferent and efferent vessels for each organ after bolus injection of CCK-33 (50 pmol/Kg), renal extraction ratio was 0.30 +/- 0.04, and mesenteric extraction ratio was 0.19 +/- 0.04. Hepatic extraction was not detected. T1/2 and extraction ratios were not affected by the preinjection of L-364,718 (20 nmol/Kg). The results indicate in dogs that exogenously administered CCK-33 is degraded by the mesenteric organs as well as the kidney but not by the liver, and that receptor-mediated mechanisms are not involved in these degradation pathways of CCK.

Anesthesia↗

Growth suppression of esophageal cancer cells by p16INK4 and p15INK4B in vitro.

PURPOSE: We investigate whether p16INK4 and p15INK4B inhibit cellular proliferation and exert a growth suppressive effect on esophageal cancer cells. MATERIALS AND METHODS: The growth suppressive effects of p16INK4 and p15INK4B were evaluated by transfecting vectors containing the p16INK4 cDNA or the p15INK4B cDNA, or both, constitutively driven by a cytomegalovirus promoter, into two human esophageal cancer cell lines containing or lacking endogenous p16INK4 and/or p15INK4B. RESULTS: These experiments demonstrated that in both cells lines tested, the numbers of cells surviving dramatically decreased in p16INK4-transfected and p15INK4B-transfected cells compared with control vector-transfected cells. There was no significant difference in the degree of growth inhibition between p16INK4-transfected and pI5INK4B-transfected cell lines. CONCLUSIONS: These results suggest that p16INK4 and p15INK4B play important roles in the initiation or promotion of esophageal cancer. The inactivation of p16INK4 and p15INK4B may contribute to uncontrolled growth in human cancer.

Carcinoma, Squamous Cell↗

Mechanism of apoptosis induced by cisplatin and VP-16 in PANC-1 cells.

Cisplatin and VP-16 were used to study the induction of apoptosis in Panc-1 cells. Cisplatin and VP-16 inhibited the growth of Panc-1 cells. After 2 hours exposure to cisplatin or VP-16, attached and detached cells were subjected to TUNEL staining to calculate the ratio of apoptosis. In detached cells TUNEL positive ratios increased in a time- and dose-dependent manner. In Western blotting, Bax expression was obviously up-regulated, but Bcl-2 remained almost constant. The results suggested that in Panc-1 cells cisplatin and VP-16 induced apoptotic cell death which was mediated through the interaction of Bax expression in the presence of mutated p53.

Antineoplastic Agents↗

Results of pancreatectomy with radiation therapy for pancreatic cancer.

BACKGROUND/AIMS: Surgical resection provides the only chance for long-term survival for adenocarcinoma of the pancreas. However, a major problem of surgery appears to be post-resection recurrence. The purpose of the current study was to evaluate the efficacy of intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) in combination with resective surgery. METHODOLOGY: 86 patients received radiotherapy combined with resection surgery and 64 patients received surgery alone. Of 86 patients, 37 received postoperative EBRT, 14 received IORT, and 31 received both. The primary outcome variable analyzed was survival. RESULTS: The survival curve in patients who received radiotherapy combined with resective surgery was significantly better than that in patients who only received surgery (MST: 12.8 vs. 7.9 months). The number of patients in both groups was equally populated on the basis of potentially prognostic factors such as gender and age of patients, type of resection, vascular resection, location of the tumor, and pTNM classification. Among the subgroups of the patients, adjuvant radiotherapy showed significant survival benefit in the patient group with pT3 tumor, pN positive and R0 surgery. CONCLUSIONS: Adjuvant radiotherapy including TORT with resection surgery for adenocarcinoma of the pancreas is accomplished with acceptable risk and provides significant survival benefit.

Adenocarcinoma↗

[Interpretation of the quantitative data of the computerized baropodometry in normal subjects].

The present work intended to test the validity of the quantitative datas provided by computerized baropodometry based in three comparisons: between static vertical force on the three regions of the foot and weight, between vertical force on the three regions of the foot during gait and weight, and between peak plantar pressure on the three regions of the foot and weight. It was used body weight because the calibration of the equipment is done in relation to the body weight of the patient. It was selected ten volunteers without foot pain complaints, age between 27-54 years old, 6 women and 4 men. The equipment used was the FSCAN version 1.821 (Teckscan, Boston MA), with new insoles. At the static assessment, the correlation between vertical force and weight was statistically significant only to the midfoot. At the assessment during gait the correlation between vertical force and weight was statistically significant for all regions of the foot and the correlation between peak plantar pressure and weight was statistically significant only to the midfoot. The clinical interpretation of the quantitative data provided by this exam must be done with caution due to uncount variables that are involved.

Adult↗