Showing papers by "Yoshitaka Fujii published in 2003"
TL;DR: The results indicate that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following DNA double-strand breaks, as well as that induced by TNF-alpha and UV irradiation.
317 citations
TL;DR: The data suggest that reduced Syk expression in breast cancers is associated with distant metastasis and poor prognosis; therefore, Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human breast cancer.
95 citations
TL;DR: It is indicated that overexpression of a dominant-negative variant of Stat5 suppresses ER transcriptional activity and induces apoptosis in estrogen-responsive breast cancer tissue culture cells.
Abstract: Signal transducer and activator of transcription (Stat) 5 regulates growth, differentiation, and survival of mammary and hematopoietic cells. The role of Stat5 in breast cancer has not been established, although Stat5 is critical for some hematopoietic malignancies. We detected for the first time that Stat5b is constitutively activated in human breast cancer cell lines, and analysed the role of Stat5 in estrogen receptor(ER)-positive breast cancer cell lines using dominant-negative variants of Stat5. Two distinct carboxyl-truncated Stat5a derivatives were generated. Stat5aDelta740 corresponded to a naturally occurring alternative splice variant, and Stat5aDelta713 was analogous to an 80 kDa Stat5a product of a nuclear protease. Stat5aDelta740 and Stat5aDelta713 displayed comparable dominant-negative properties and suppressed transcriptional activity of wild-type Stat5a and Stat5b equally well. Cotransfection experiments revealed that Stat5aDelta740 completely blocked transcriptional activity of endogenous estrogen receptor in T47D and MCF7 cells, and of both ER alpha and ER beta in COS-7 cells. Stat5aDelta740 was selected for adenoviral delivery, and high-efficiency expression of tyrosine phosphorylated Stat5aDelta740 was achieved in infected cells. Adenoviral-mediated Stat5aDelta740 induced apoptosis in T47D cells but not in caspase-3-negative MCF7 cells. The present study indicates that overexpression of a dominant-negative variant of Stat5 suppresses ER transcriptional activity and induces apoptosis in estrogen-responsive breast cancer tissue culture cells.
87 citations
TL;DR: Cten/GAPDH mRNA expression has been correlated with evidence of tumor progression in terms of T and overall stage of lung cancer, suggesting that cell motility or migration might play a role in progression of lung cancers.
53 citations
TL;DR: Serum EGFR levels may serve as a marker that can be used as an indicator of lymph node metastasis in lung cancer, however, there was no difference between levels in patients with lung cancer and those in nonmalignant-disease controls, indicating that the measurement of serum EG FR levels was of limited value in the detection of lung cancer.
Abstract: Background: Using an enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as predictors of the development and extent of lung cancer.
Methods: The study included 106 lung cancer patients and 16 patients with nonmalignant thoracic disease. Serum samples were collected before clinical treatment.
Results: There was no difference between serum EGFR levels in patients with lung cancer (21.275 ± 22.035 fm/ml) in comparison with those in nonmalignant-disease controls (22.630 ± 7.330 fm/ml; P = 0.8083). However, lung cancer patients with lymph node metastasis (23.515 ± 20.065 fm/ml) had significantly higher EGFR levels compared with those in patients without lymph node metastasis (16.390 ± 10.970 fm/ml; P = 0.0228). The serum EGFR levels were similar in samples from lung cancer patients with various pathological subtypes. There was no difference in the prognosis between the lung cancer group with normal EGFR levels ( 850 ng/ml).
Conclusion: Serum EGFR levels may serve as a marker that can be used as an indicator of lymph node metastasis in lung cancer. However, there was no difference between levels in patients with lung cancer and those in nonmalignant-disease controls, indicating that the measurement of serum EGFR levels was of limited value in the detection of lung cancer.
35 citations
TL;DR: The findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.
Abstract: Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. In this study, we investigated whether intravenous administration of endostatin gene complexed with a cationic vector (GL67/DOPE or PEI22K) could inhibit the development of lung tumors in mice injected i.v. with NFSa Y83 fibrosarcoma cells (5×105) which frequently form lung metastasis. mRNA and protein of the transfected gene were produced in the lung and other organs of the transfected mice as assessed by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. Single intravenous injection of the endostatin gene (60 μg) complexed with either GL67/DOPE or PEI22K on day 3 or day 7 after fibrosarcoma cell inoculation significantly inhibited tumor formation in the lung as evidenced by the reduced number of lung tumors and lung weight, and prolonged survival of the endostatin gene-transfected mice compared with control mice. These findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.
27 citations
TL;DR: It is demonstrated that p33(ING1b) acts like a coactivator for ERalpha and stimulates estrogen-induced ERalpha transcriptional activity consistent with a function for p 33(ING 1b) in chromatin remodeling.
21 citations
TL;DR: The present study suggests that certain MMPs may play an important role in the tumor progression of different subtypes of thymic epithelial tumors and that M MP-2 and MMP-7 may contribute to the tumor aggressiveness and malignant potential.
19 citations
TL;DR: The correlation of SAGE and HAGE expression with clinicopathological features in patients with lung cancer who had undergone surgery was reported, and detection for SAGE mRNA expression is possible in lung cancer samples, suggesting the usefulness of detection for HAGE RNA expression is limited for lung cancer.
Abstract: Aims: SAGE and HAGE are recently isolated genes, which were thought to be expressed tumour-specifically, and are potentially coding for tumour-specific antigens recognized by T lymphocytes The expression of these genes may serve as a useful diagnostic marker in detecting malignant disease We report the correlation of SAGE and HAGE expression with clinicopathological features in patients with lung cancer who had undergone surgery Methods: Expression of SAGE and HAGE messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 102 lung carcinomas and adjacent histological normal lung samples using LightCycler Results: SAGE/GAPDH mRNA expression was not significantly different between the tumour of lung cancer tissue (3777±10802) and normal lung tissue (3028±3356, p =07283) There was no relationship between SAGE gene expression and age, gender or N-status SAGE/GAPDH expression was significantly higher in stage III–IV lung cancer (6180±16475) than in stage I lung cancer (1534±2591, p =00393) SAGE/GAPDH expression was also significantly higher in T4 lung cancer (9183±23117) than in T2 lung cancer (2676±5943, p =00362) and T1 lung cancer (2373±3433, p =00371) Conclusions: Detection for SAGE mRNA expression is possible in lung cancer samples There was no relationship between HAGE gene expression and clinicopathological factor, such that the usefulness of detection for HAGE mRNA expression is limited for lung cancer
17 citations
TL;DR: The combined use of measurements of TS and DPD mRNA levels using real-time RT-PCR analyses may provide an indication of the selective cytoxicity of 5-FU on thymoma.
Abstract: Purpose: Thymoma is one of the most common solid tumors in the mediastinum. However, there is no definitive consensus regarding the optimal adjuvant chemotherapy for advanced thymoma.
Methods: To predict tumor sensitivity to 5-fluorouracil (5-FU) in thymoma, we investigated the mRNA levels of thymidylate synthase (TS), the key enzyme that catalyzes the methylation of deoxyuridine monophosphate, and correlates with the resistance of 5-FU and dihydropyrimidine dehydrogenase (DPD), which degrades 5-FU in thymoma. We used real-time quantitative reverse transcription–polymerase chain reaction (RT-PCR) using the LightCycler to monitor the TS and DPD gene expression levels in thymoma tissue specimens from patients, coamplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard.
Results: In the resected tumor specimens, TS and DPD mRNA levels were 3.876 and 14.651, respectively. Both the TS and DPD mRNA levels were significantly higher in the tumor tissue specimens than in the normal adjacent thymus tissue specimens. No significant correlations were observed between the TS or DPD levels and other clinicopathological factors.
Conclusions: The combined use of measurements of TS and DPD mRNA levels using real-time RT-PCR analyses may provide an indication of the selective cytoxicity of 5-FU on thymoma. In general, 5-FU itself is not considered to be a useful treatment for thymoma. The usufulness of DPD-inhibiting fluoropyrimidine (DIF) drugs for thymoma should therefore be further considered.
16 citations
TL;DR: Energy metabolism in SMVO during ischemia was reduced more slowly than in SMAO, but recovery after reperfusion was poorer inSMVO, and Hist, mucosal and subserosal hemorrhage was more severe in SM VO.
Abstract: Background Although it is less frequently encountered, mesenteric vein occlusion poses as important a problem as mesenteric artery occlusion The energy metabolism of intestinal tissue during venous occlusion and reperfusion was studied Methods Male Wistar rats were studied in four groups of 17 animals each Intestinal ischemia was induced by clamping the superior mesenteric artery ([SMA] occlusion [O]) or vein (SMVO) for 30 or 60 min, followed by reperfusion Magnetic resonance spectroscopy was employed to continuously monitor the energy metabolism Additionally, intestinal motility was monitored and histological examination was performed on resected specimens Results Energy metabolism in SMVO during ischemia was reduced more slowly than in SMAO, but recovery after reperfusion was poorer in SMVO During ischemia, the contractive response of the intestine lasted longer in SMVO than in SMAO Histologically, mucosal and subserosal hemorrhage was more severe in SMVO Conclusions In contrast to SMAO, SMVO caused less severe reduction of energy metabolism, at the expense of hemorrhage and tissue damage
TL;DR: The data suggest that Id2's role in the oncogenesis or progression of neuroblastoma is minimal, and his expression in resected clinical samples of Neuroblastoma needs to be studied.
Abstract: Aims: Inhibitors of DNA binding 2 (Id2) has been reported to be overexpressed in neuroblastoma cell lines carrying extra copies of the N-myc gene. It has been suggested that Id2 may be involved in the disturbed regulation of cell cycle by interfering with retinoblastoma protein. Methods: In this report we assessed Id2 gene expression in 20 neuroblastoma samples and eight normal ganglion tissues using quantitative reverse transcription-PCR (RT-PCR). Id2 expression in resected clinical samples of neuroblastoma needs to be studied. Results: Id2 messenger RNA (mRNA) was expressed in all the neuroblastoma samples. The level of Id2 mRNA expression was not influenced by the patient's age, gender, tumor's clinical stage, DNA ploidy pattern, histological pattern, the level of N-myc mRNA expression and whether the patient was found by mass screening or by symptom. Id2 was also expressed in comparable levels in normal differentiated sympathetic ganglion in adult. Conclusion: Our data suggest that Id2's role in the oncogenesis or progression of neuroblastoma is minimal.
TL;DR: The combined use of oligonucleotide microarray, real‐time RT‐PCR, and ELISA analyses provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of thymoma.
Abstract: Thymoma is one of the most common solid tumors in the mediastinum. Because there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular-genetic analysis of patients' tissues. Recent reports showed that genetic aberrations in thymoma were most frequently seen in chromosome 6q regions. We investigated the use of oligonucleotide arrays to monitor in vivo expression levels of genes in chromosome 6 regions in early- (stage I or II) and late- (stage IVa) stage thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 48 thymoma patients and sandwich ELISA for 33 thymoma patients. Using both methods, a candidate gene was identified which was overexpressed in stage IV thymoma. This was a known glycosylphosphatidyl inositol (GPI)-anchored protein (GPI-80), which is highly homologous with Vanin-1, a mouse thymus homing protein. Serum level of GPI-80 was confirmed to be elevated in stage IV thymoma compared with in stage I thymoma by using sandwich ELISA. The combined use of oligonucleotide microarray, real-time RT-PCR, and ELISA analyses provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of thymoma.
TL;DR: FIZ stamp method may be a simple and useful diagnostic aid for the presence of cancer cells in the resected specimen and MMP-2 may play an important role in the lymphatic invasion of lung cancer.
TL;DR: Findings suggest that TIMPs and MMPs play an important role in the invasion of thymoma.
TL;DR: The decreased expression of angioarrestin mRNA was the early phase phenomena for tumor progression from lung cancer, Alternatively, loss of antianiogenesis might play a role in oncogenesis for lung cancer.
Abstract: Aims: Angioarrestin is a recently isolated gene, which has a novel function as an angiogenesis inhibitor. Angiogenesis plays an important role in tumorigenesis. It has been reported that the angioarrestin expression was decreased in lung cancer. We attempted to determine the influence of angioarrestin expression on clinicopathological features in patients with lung cancer who had undergone surgery.
Methods: Expression of angioarrestin messenger RNA was evaluated by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 93 lung carcinomas and adjacent histological normal lung samples using LightCycler.
Results: Angioarrestin/GAPDH mRNA expression was significantly decreased in the tumor of lung cancer tissue (86.676±123.505) than in the normal lung tissue (1154.218±2003.508, p<0.0001), although only four lung cancer tissues had more than one tumor/normal ratio of angioarrestin/GAPDH mRNA expression. There was no relationship between angioarrestin gene expression and age, gender or T-status. However, decreased angioarrestin/GAPDH expression was especially seen at stage I lung cancer (54.156±62.783) when compared to stage II–IV lung cancer (110.315±151.359, p=0.0316). Decreased angioarrestin/GAPDH expression was especially seen at N0 lung cancer (56.396±69.941) when compared to N2 lung cancer (137.522±180.489, p=0.0362).
Conclusions: The decreased expression of angioarrestin mRNA was the early phase phenomena for tumor progression from lung cancer. Alternatively, loss of antianiogenesis might play a role in oncogenesis for lung cancer.
TL;DR: Biweekly pac litaxel may be suitable for patients receiving paclitaxel for palliative therapy, as tolerance was similar to that with the weekly schedule, but with the advantage of increased convenience.
Abstract: This study was conducted to evaluate the efficacy and the toxicity of paclitaxel administered as a biweekly 1-h infusion (120 mg/m2). Twenty patients with metastatic breast cancer were enrolled in this study. Paclitaxel was administered at a dose of 120 mg/m2 by an intravenous 1-h infusion every 2 weeks. The primary objectives of the study were the response rate and toxicity. Pharmacokinetic analysis was conducted in 7 of the 20 patients treated with paclitaxel. Four of the 20 patients had grade 3 or 4 neutropenia. Arthralgia or myalgia was observed in 8 of the 20 patients. Grade 2 or 3 neurotoxicity was observed in 6 of the 20 patients. In the 20 assessable patients, there was one complete response and eight partial responses. The overall response rate was 45%. The mean time to progression was 5.4 months. Biweekly paclitaxel may be suitable for patients receiving paclitaxel for palliative therapy, as tolerance was similar to that with the weekly schedule, but with the advantage of increased convenience.
TL;DR: PPAR-gamma may have played a role in the reduction of VMA and possibly in the regression of early-onset neuroblastoma.
TL;DR: This case is believed to be the first report of curing saber-sheath malacic trachea without leaving any prostheses or other foreign materials.
TL;DR: Investigations showed that Hrad17 protein was highly expressed in invasive thymoma tumor tissue but not within the normal thymus tissue, and no relationship was seen between Hrad 17 gene expression and age, gender, or pathologicalThymoma subtypes.
Abstract: Objectives: We used palindromic polymerase chain reaction-driven complementary deoxyribonucleic acid differential display to identify and isolate a gene, the human homolog of the Schizosaccharomyces pombe checkpoint gene rad17 (Hrad17), from colon cancer tissue. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes—events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in thymoma, especially in invasive thymoma. We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with thymoma who had undergone surgery. Methods: Expression of Hrad17 messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction using a LightCycler in 38 thymomas and 10 adjacent histologically normal thymus samples from patients for whom follow-up data was available. Results: Hrad17 transcripts were detected in all 38 tumor samples (8.789±7.337) at levels significantly higher than those in normal thymus samples (1.908±2.267, p<0.0001). No relationship was seen between Hrad17 gene expression and age, gender, or pathological thymoma subtypes. Hrad17 mRNA expression in invasive thymomas (stage II–IV, 10.067±5.293) was significantly higher than that in stage I thymomas (5.193±4.485, p=0.0168). Immunohistochemistry showed that Hrad17 protein was highly expressed in invasive thymoma tumor tissue but not within the normal thymus tissue. Conclusions: Hrad17 was highly expressed in invasive thymoma.
TL;DR: It is confirmed that stewart分類IIIb型の右側大動脈弓と診断した is real.
Abstract: 右側大動脈弓に合併した早期食道癌の1手術例を経験した. 症例は58歳の男性. 健診時の上部消化管内視鏡検査にて異常を指摘され, 当院を紹介された. 術前の諸検査から右側大動脈弓を伴う食道表在癌と診断し, 食道亜全摘術・胸骨後胃管再腱術を施行した. 食道への到達経路には左開胸を用いた. 術中所見では, 下行大動脈に憩室がみられ, 左鎖骨下動脈が同部より分岐していたことから, stewart分類IIIb型の右側大動脈弓と診断した. また, 食道癌の占居部位はこの大動脈憩室と左動脈管索が食道を圧排する部位に一致していた. 右大動脈弓に合併した食道癌の報告はまれで, 本邦では自験例を含め7例のみであった.
TL;DR: Investigation of FHIT mRNA levels in a series of thymomas found decreased FHit expression might be seen in early stage thymoma, suggesting that loss ofFHIT expression may associate with tumorigenesis ofThymoma.
Abstract: Aims: The FHIT gene is located at 3p14.2 a region frequently lost in multiple tumour types. Loss of FHIT expression has been found to occur frequently in multiple tumour types. We wished to investigate that FHIT mRNA levels in a series of thymomas. Methods: Expression of FHIT messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) using a LightCycler in 49 thymomas and 11 adjacent histologically normal thymus samples from patients. Results: FHIT transcripts in tumour samples (28.6±35.8) at levels significantly lower than those in normal thymus samples (573.9±1028.0, p =0.001). No relationship was seen between FHIT gene expression and age, gender, or pathological thymoma subtypes. FHIT mRNA expression in invasive thymomas (stage II–IV, 34.5±39.2) was significantly higher than that in stage I thymomas (20.7±29.7, p =0.01). Immunohistochemistry showed that p21 protein positive thymoma had a tendency towards higher FHIT gene expression than in p21 negative thymoma. Conclusions: Decreased FHIT expression might be seen in early stage thymoma, suggesting that loss of FHIT expression may associate with tumorigenesis of thymoma.