Biomedical subjects

Naoki Okumura

Publications and source records attributed to Naoki Okumura.

9 recordsLinked to original sources

PubMed2007

Serum cytokine levels in response to hepatic cryoablation.

BACKGROUND AND OBJECTIVES: Cryogenic treatment sometimes stimulates the immune system by releasing intracellular antigens. We evaluated anti-tumor immune response by analyzing alterations in serum cytokine levels. METHODS: Percutaneous cryosurgery was performed in 13 patients with unresectable tumors. Serum levels of interleukin (IL) -4, -6, and -10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma were measured by enzyme-linked immunosorbent assay (ELISA). The Th1/Th2 ratio was estimated from the IFN-gamma/IL-4 ratio. RESULTS: Levels of serum factors in the immune reaction (IR) group, in which tumor necrosis was identified not only in the treated area but also away from the treated area, were compared with those in the local effect (LE) group. Serum amyloid A (SAA), C-reactive protein (CRP), and IL-6 levels were increased in both groups after three treatments. The serum IL-10 level tended to increase with the number of treatments. Pretreatment IL-10 levels in the LE group were significantly greater than those in the IR group, and the maximum value in the LE group (59.5 +/- 13.2 pg/ml) was greater than that in the IR group (47.0 +/- 15.0 pg/ml). The TNF-alpha level was increased in the IR group. Pretreatment TNF-alpha levels and maximum levels in response to treatment were significantly greater in the IR group than in the LE group (P = 0.0313). The Th1/Th2 ratio was increased in the IR group, and the maximum ratio was significantly greater in the IR group than in the LE group. CONCLUSION: It might be possible to evaluate the appearance of immune responses to cryosurgery by monitoring serum cytokine levels.

Aged↗

PubMed2006

Pharmacokinetic analysis of platelet-activating factor in the tears of guinea pigs with allergic conjunctivitis.

PURPOSE: The aim of this study was to examine the levels of platelet-activating factor (PAF) and lyso-PAF in tears from experimental animals developing allergic conjunctivitis (AC). METHODS: AC was induced in guinea pigs by application of ovalbumin in eye drops. Tear samples were collected from 5 actively sensitized animals and from 5 unsensitized control animals before the challenge, and 1, 2, 4, and 6 h postchallenge. C18:0-PAF, C18:0-lyso-PAF, C16:0-PAF, and C16:0-lyso-PAF levels in the tear samples were determined using liquid chromatography-tandem mass spectrometry. RESULTS: The concentrations of C16:0-PAF, C16:0-lyso-PAF, and C18:0-lyso-PAF were measurable in both unsensitized and sensitized groups, whereas C18:0-PAF was undetectable in tear samples from either group. The levels of C16:0-PAF, C16:0-lyso-PAF, and C18:0-lyso-PAF in sensitized animals increased throughout the time course of the experiment, whereas there was no corresponding increase in the levels of these molecules in the unsensitized group. There were strong correlations between the concentrations of C16:0-PAF and C16:0-lyso-PAF, both in the sensitized and in the unsensitized group, and the concentrations of C16:0-lyso-PAF and C18:0-lyso-PAF within each group. CONCLUSIONS: The data from this study demonstrated that the levels of PAF and lyso-PAF increase in tears in a guinea pig model of AC development and implicate a role for PAF for the development of AC.

Animals↗

PubMed2006

Vascular endothelial growth factor protects hepatoma cells against oxidative stress-induced cell death.

BACKGROUND: The aim of the present study was to examine coordination of the vascular endothelial growth factor (VEGF) and VEGF receptor (Flk-1) system and to study control of VEGF expression by oxidative stress, which is considered a model for chronic liver disease. METHODS: Cell viability was determined by test method with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-dephenyl tetrazolium bromide (MTT). Expressions of cellular proteins were evaluated by western blot analysis. RESULTS: The c-Met tyrosine phosphorylation in PLC/PRF/5 hepatoma cells was increased by treatment with 20 ng/mL hepatocyte growth factor (HGF), and extracellular signal-regulated kinase (ERK) was also activated. Although Flk-1 was phosphorylated in response to VEGF (>50 ng/mL), phosphorylated ERK was not detected at these concentrations. A total of 5.0 and 10 micromol/L hydrogen peroxide (H(2)O(2)) caused cell death in a dose-dependent manner after 24 h. On western blot analysis at 1 h with H(2)O(2), rapid phosphorylation of both ERK1/2 and c-Jun NH(2)-terminal kinase (JNK) was observed. In the first 6 h, H(2)O(2) induced cell death for 58.4 +/- 6.8%, whereas the presence of 100 ng/mL VEGF improved the survival rate to 77.2 +/- 4.2%. The VEGF significantly decreased H(2)O(2)-induced cell death after 12 h, whereas HGF (20 ng/mL) did not have a similar effect. When cells were incubated with 5 micromol/L H(2)O(2), expression of VEGF protein was detected. Furthermore, H(2)O(2)-induced phosphorylation of ERK and JNK was also reduced by VEGF (100 ng/mL). In contrast, HGF did not induce phosphorylation of ERK and JNK. CONCLUSION: Hepatoma cells might be able to survive under continuous oxidative stress through expression of VEGF.

Carcinoma, Hepatocellular↗

PubMed2005

Platelet-activating factor in human normal tears.

PURPOSE: To measure the concentrations of platelet-activating factor (PAF) and lyso-PAF in tears of human eyes. METHODS: Unilateral tear samples were collected from the conjunctival cul-de-sac of 12 healthy volunteers without any past histories of ocular surface diseases and 10 patients with allergic conjunctivitis (AC) by graduated disposable microcapillaries. C18:0-PAF, C18:0-lyso-PAF, C16:0-PAF, and C16:0-lyso-PAF levels were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). RESULTS: The concentrations of C18:0-PAF, C18:0-lyso-PAF, C16:0-PAF, and C16:0-lyso-PAF in tears from healthy volunteers were 0.44 +/- 0.39, 51.7 +/- 63.4, 61.9 +/- 75.9, and 10.7 +/- 14.7 ng/ml, respectively. Higher, but not significantly different, concentrations of all the four kinds of PAF molecules were detected in tears from AC patients. Significant correlations were demonstrated between the concentrations of C18:0-PAF and C18:0-lyso-PAF (r = 0.906; p < 0.01 in normal healthy volunteers and r = 0.939; p < 0.01 in AC patients), and between those of C16:0-PAF and C16:0-lyso-PAF (r = 0.944; p < 0.01 in normal healthy volunteers and r = 0.806; p = 0.015 in AC patients). Moreover, C18:0-PAF concentrations correlated significantly with those of C16:0-PAF (r = 0.885; p < 0.01 in normal healthy volunteers and r = 0.927; p < 0.01 in AC patients), while C18:0-lyso-PAF concentrations correlated significantly with those of C16:0-lyso-PAF (r = 0.972; p < 0.01 in normal healthy volunteers and r = 0.891; p < 0.01 in AC patients). CONCLUSIONS: To our knowledge, this is the first report of the concentrations of different species of PAF (C18:0-PAF, C18:0-lyso-PAF, C16:0-PAF, and C16:0-lyso-PAF) in human tears.

Adult↗

PubMed2004

[Evaluation of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer].

We evaluated the effect of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer. We performed an intra-arterial infusion chemotherapy (5-FU was injected continuously: 250 mg/day/body x 28 days, CDDP was injected weekly: 5 mg/day x 5 days) associated with radiotherapy (2-3 Gy/day x 20-30 days) for local recurrence of rectal cancer with the aim of pain-relief. Both patients markedly tended to feel less pain after the radiotherapy. Radiotherapy has been useful for pain-relief of the localized bone metastasis. The present intra-arterial infusion chemotherapy associated with radiotherapy was a possible local therapy for local recurrence of rectal cancer in the pelvis. Although the survival benefit depends on the presence of other site of recurrence, this procedure is useful for the improvement of QOL by relieving the pain of the patients.

Aged↗

PubMed2002

Estradiol stabilizes p53 protein in breast cancer cell line, MCF-7.

Overexpression of the oncoprotein MDM2, an important regulator of the p53 tumor suppressor protein, is often observed in breast cancer tissues and cell lines, particularly in those which express estrogen receptor alpha (ERalpha). In MCF-7 breast cancer cell line possessing wild-type p53, ERalpha, and overexpressing MDM2, p53 accumulation was stimulated by 17beta-estradiol (E2) in a concentration-dependent manner. On the other hand, E2 caused no change of the expression of p53 mRNA, indicating that E2 affects p53 at the post-transcriptional level. To analyze the mechanism of p53 accumulation by E2, the stability of p53, ERalpha and MDM2 proteins was analyzed in the presence of cycloheximide under an E2-supplemented or -depleted condition. E2 significantly extended the half-life of p53 protein, but shortened that of ERalpha in MCF-7 cells. E2 significantly decreased the stability of p90(MDM2) and p60(MDM2) in MCF-7. Interestingly, E2 increased the ratio p60(MDM2)/p90(MDM2) inversely proportionally to the degradation of p53. These results suggest that the ratio of the two MDM2 proteins, p90(MDM2) and p60(MDM2), may affect the accumulation of wild-type p53 protein in response to E2.

Blotting, Northern↗

PubMed2002

[Evaluation of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer].

We evaluated the effect of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer. Of 405 patients undergoing colectomy in our department from July 1993 to February 2002, 38 had liver metastasis. We performed catheterization intra-operatively or postoperatively, and intra-arterial infusion chemotherapy was given for liver metastasis from colorectal cancer. Thirty-eight patients were treated with four different arterial infusion courses that mainly consisted of 5-FU. The 5-year survival rate was 8%. Maximal survival period was 68 months, and mean survival was 22 months. The effective rate was 20% Intra-arterial infusion chemotherapy was a useful treatment for liver metastasis from colorectal cancer. Resection of the liver metastasis was the first choice for operative liver metastases from colorectal cancer, and we performed intra-arterial infusion chemotherapy for patients postoperatively or patients with non-operative liver metastasis.

Adult↗

PubMedDate not supplied

Distinct promoter usage of mdm2 gene in human breast cancer.

Human breast cancers, especially estrogen receptor alpha (ER(alpha))-positive ones, often overexpress the oncoprotein MDM2 without mdm2 gene amplification. The mdm2 gene is transcribed into two different mRNAs, namely L-mdm2 and S-mdm2, which are generated from promoters P1 (constitutive) and P2 (regulated by tumor suppressor p53), respectively. To cast light on the mechanisms of MDM2 overexpression, we measured the expression levels of these mdm2 mRNAs using RT-PCR analysis in three human breast cancer cell lines and 15 breast cancer samples obtained from surgery. ER(alpha)-positive MCF-7 cells, which possess wild-type p53, displayed dominant expression of S-mdm2. In contrast, two other cell lines with mutant p53, T47-D (ER(alpha)-positive) and MDA-MB-231 (ER(alpha)-negative), showed almost equivalent expression of L-mdm2 and S-mdm2. Treatment of 17beta-estradiol (E2) significantly enhanced the expression of S-mdm2 but not that of L-mdm2 in MCF-7. Among 6 breast cancer samples regarded as ER(alpha)-positive with wild-type p53, 5 samples showed increased expression of S-mdm2. Expression of S-mdm2 was stimulated in 2 ER(alpha)-positive samples with mutant p53. In contrast, 4 of 5 samples which express mutant p53 without ER(alpha) showed poor expression of S-mdm2. There is a tendency that ER(alpha)-positive breast cancers with wild-type p53 preferably use P2 promoter for the expression of mdm2, possibly through E2-induced accumulation of p53. However, wild-type p53 and ER(alpha) are not necessarily enough for the utilization of S-mdm2. Tumors with mutant p53 also showed expression of S-mdm2 in some cases. These results strongly suggest that other factor(s) is also implicated in the promoter usage of mdm2 gene in human breast cancer tissues.

Adult↗

PubMedDate not supplied

A modified reconstruction method to prevent critical complications after pancreatoduodenectomy.

BACKGROUND/AIMS: A new method of reconstructing the pancreatic stump after pancreatoduodenectomy (PD) is necessary to improve the postoperative mortality rate. Thus, we modified the pancreatoenteric procedure to reduce anastomotic leakage from the pancreatic stump after PD, and we conducted a study to evaluate the usefulness of the new procedure on the basis of patients' postoperative condition. METHODOLOGY: We compared the postoperative condition of 21 patients who underwent PD with the new separated loop (SL) reconstruction (6 men, 11 women; mean age, 67.7+/-7.2 years) to that of 31 patients (12 men, 19 women; mean age, 66.8+/-10.3 years) who underwent PD with pancreatogastrostomy (PG). In the SL reconstruction procedure, the proximal jejunum is brought up behind the colon, and an end-to-side choledochojejunostomy is made with a single layer of interrupted sutures. Approximately 20cm of the jejunum is fitted with a fixed stomach tube for postoperative enteral feeding, and the cut proximal jejunum is positioned next to the pancreatic stump. A pancreatic tube is inserted into the lumen of the pancreatic duct and fixed without closing the pancreatic duct. Pancreatojejunostomy is achieved as an end-to-end anastomosis with the pancreatic stump telescoping into the proximal jejunum. Approximately 20cm of the jejunum is anastomosed side-to-end to the stomach, and end-to-side jejunojejunostomy is made to complete a Y-type reconstruction. Each patient's postoperative condition was also assessed on the basis of serum albumin (ALB), cholinesterase and total cholesterol (T-CHO) levels on postoperative days (PODs) 14 and 28. RESULTS: A high level of amylase in drainage fluid was noted in two (6.5%) and delayed gastric emptying in four (12.9%) of the patients in the PG group. There were no complications in the SL group. Postoperative levels of ALB on POD 14 and T-CHO on POD 28 were significantly higher than in the PG group. CONCLUSIONS: The SL method is safe and does not induce complications after PD. Our results indicate that this method may provide a favored outcome.

Aged↗