Biomedical subjects

I Fukai

Publications and source records attributed to I Fukai.

At least 19 recordsLinked to original sources

PubMed2003

Clinical significance of tissue inhibitor of metalloproteinase and matrix metalloproteinase mRNA expression in thymoma.

BACKGROUND: Matrix metalloproteinases (MMPs) are proteolytic enzymes which degrade extracellular matrix and basement membrane. There is much evidence that their increased expression is correlated with tumor aggressiveness in various carcinomas. Tissue inhibitor of metalloproteinases (TIMPs) are the specific inhibitors of MMPs. MMPs and TIMPs are considered to play an important role in carcinoma invasion and metastasis. We hypothesized that MMPs and TIMPs also play an important role in thymoma. MATERIALS AND METHODS: This study included 34 thymoma cases. The mRNA levels of MMP-1, -7, and -9, TIMP-1 and -2, and GAPDH were quantified by real-time polymerase chain reaction using LightCycler. We also performed immunohistochemistry for TIMP-1. RESULTS: The TIMP-1/GAPDH mRNA expression level was significantly higher in invasive (stage II-IV) thymomas (means +/- SE, 81.4 +/- 28.1) than in noninvasive (stage I) thymomas (30.9 +/- 8.3, P = 0.026). The MMP-1/GAPDH mRNA expression level was also higher in invasive thymomas (19.7 +/- 7.5) than in non invasive thymomas (2.26 +/- 1.72, P = 0.020). Immunopositivity of TIMP-1 was localized in stromal cells adjacent to the advancing margin of the tumor. CONCLUSIONS: These findings suggest that TIMPs and MMPs play an important role in the invasion of thymoma.

Gene Expression↗

PubMed2003

Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery.

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 x 10(5)) 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 microg) 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.

Animals↗

PubMed2002

[Surgery for multiple primary lung cancers].

Thirty-eight patients (3.4%) of multiple primary lung cancers were treated among 1,106 patients of lung cancer at Nagoya City University Hospital. Twenty-eight patients had multiple lung lesions at the same time. Ten had the second primary lung cancer from 5 to 12 years after the first operation. Thirty-six patients had the second operation, and two had adjuvant therapy for lung cancer. Their 5 year survival rate was 36%. Especially of the patients with stage I lung cancer, 5 year survival rate was 65%. Radical but less invasive operation like VATS should be chosen for their treatment.

Adenocarcinoma↗

PubMed2002

[Therapeutic options which potentially cure patients with thymoma].

This study reports clinicopathologic features, treatment, and outcome of 107 thymomas, especially focusing on a combined modality program using hemithorax irradiation (HI) and restaging surgery using corticosteroid for advanced thymoma showing disseminative lesions. The use of HI after presumably total resection of the dissemination under posterolateral thoracotomy had no effect on reducing the incidence of relapsing. On the other hand, our own experience revealed that corticosteroid caused degenerative changes in the epithelial cells and lymphocytes of thymomas. The fact led us administer corticosteroid not only in preoperative setting but during postoperative HI. A better prognosis may be anticipated, although the follow up period is short and the number of patients involved is small.

Adrenal Cortex Hormones↗

PubMed2001

Expression of the MTA1 mRNA in thymoma patients.

The MTA1 gene is a recently identified metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in thymoma. Expression of MTA1 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 30 thymoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage IV thymoma (6.431+/-3.404) was significantly higher than the level in stage I thymoma (2.592+/-1.902, P=0.0081). There was a tendency towards higher MTA1/GAPDH mRNA level in stage IV thymoma when compared to stage II thymoma (3.746+/-3.292, P=0.072). Thus our results show that the expression of the MTA1 gene is closely related to invasiveness in thymoma. The gene MTA1 could potentially provide information on the mechanism of tumor invasion and metastasis.

Adult↗

PubMed2001

Expression of the cdc25B gene as a prognosis marker in non-small cell lung cancer.

There is an evidence to suggest that cdc25B phosphatase is an oncogenic. We hypothesized that cdc25B gene may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of cdc25B messenger RNA was evaluated by reverse transcription polymerase chain reaction in 55 non-small cell lung carcinomas and adjacent histological normal lung samples using LightCycler. The data was analyzed in reference to clinicopathological data and survival data. There was no difference of cdc25B expression level between the NSCLC tissue and normal lung tissue. There was no relationship between cdc25B gene expression and age, gender, N or T-status and clinical stage. However, the NSCLC patients with high cdc25B expression had significantly poor survival than the patients with low cdc25B expression (P=0.0173). Thus we suggest that cdc25B may predict poor survival.

Adenocarcinoma↗

PubMed2001

Expression of the sensitive to apoptosis gene, SAG, as a prognostic marker in nonsmall cell lung cancer.

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel sensitive to apoptosis gene, SAG, may be expressed in tumors of patients with nonsmall cell lung cancer (NSCLC) and may affect their clinical outcome. Expression of SAG messenger RNA was evaluated by reverse transcription polymerase chain reaction in 80 nonsmall cell lung carcinomas and 65 adjacent histologic nonmalignant lung samples using a LightCycler. The data were analyzed in reference to clinicopathologic data and survival. The SAG/GAPDH mRNA level in 80 NSCLC was 2.337 +/- 1.972. Of 65 paired NSCLC and nonmalignant lung samples, SAG/GAPDH mRNA levels were 2.313 +/- 2.064 and 1.696 +/- 1.910, respectively. The SAG mRNA level was significantly higher in NSCLC compared with nonmalignant lung tissue (p = 0.0169). There was no relationship between SAG gene expression and age, gender, T- or N-status or clinical stages. The NSCLC patients with high SAG/GAPDH expression (>1.8) had significantly poorer survival than the patients with low SAG/GAPDH expression (<1.8, p = 0.0227). Thus we suggest that SAG gene expression in NSCLC may be a useful prognostic marker.

Adenocarcinoma↗

PubMed2001

Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients.

Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. We investigated the serum periostin level in thymoma patients, and attempted to determine the correlation between serum periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January 1994 and July 1996. Serum periostin levels were not significantly different between the thymoma patients (1264.4+/-122.9 ng/ml) and the normal control (962.0+/-118.6 ng/ml) (P=0.0877). There was no relationship between serum periostin level and age, gender or pathological subtype. However the serum periostin level of stage IV patients (1497.0+/-285.8 ng/ml) was significantly higher than normal control (P=0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma.

Age Factors↗

PubMed2001

Serum level of the periostin, a homologue of an insect cell adhesion molecule, as a prognostic marker in nonsmall cell lung carcinomas.

BACKGROUND: Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end, which suggests that it is a secreted protein. Recently, the authors developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. METHODS: The authors investigated the serum periostin level in lung carcinoma patients and attempted to determine the influence of serum periostin level on clinical outcome for patients with nonsmall cell lung carcinoma (NSCLC) who had undergone surgery between January 1994 and July 1996. Expression of periostin messenger RNA was also examined by in situ RNA hybridization for lung carcinomas. RESULTS: The periostin gene was shown to be highly expressed at the tumor periphery of lung carcinoma tissue but not within the tumor by in situ RNA hybridization. Serum periostin levels were not significantly different between the NSCLC patients (1142.1 +/- 89.2 ng/mL) and the normal control (962.0 +/- 118.6 ng/mL) (P = 0.2985). There was no relation between serum periostin level and gender, stage, bone metastasis, N status, or T status. However, the serum periostin levels of NSCLC patients had decreased significantly by 4 weeks after the resection of the tumor. The NSCLC patients with high periostin level (> 962 ng/mL) had significantly poorer survival than the patients with normal periostin level (P = 0.0406). Using the Cox proportional hazards regression model, the authors found that stage (P < 0.0001) and serum periostin level (P = 0.0226) were independent prognostic factors. CONCLUSIONS: The in situ RNA hybridization data from the current study suggested that expression of periostin may be involved in tumor invasionand that the serum periostin level may serve as a prognostic marker for NSCLC.

Adult↗

PubMed2001

Expression of the prothymosin alpha mRNA correlated with that of N-myc in neuroblastoma.

Neuroblastoma is the most common malignant solid cancers in early childhood. Overexpression of the proto-oncogene, N-myc, has been reported to be correlated with more malignant course of the disease. Prothymosin alpha, a cellular proliferation-associated gene, is reported to be a target of myc and elevated in several malignant cells and tissues. Expression of prothymosin alpha and N-myc messenger RNAs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) assay in 18 tumor samples from neuroblastoma using LightCycler. The data was analyzed in reference to clinicopathological factors. There was a tendency that higher prothymosin alpha transcripts levels in the tumor samples from younger patients (<1year.) when compared to the older group (>1 year.) (P=0.0845). There was no relationship between prothymosin alpha gene expression and gender (P=0.3029), mass screening case or not (P=0.3007), or stage. The prothymosin alpha mRNA expression levels were correlated with N-myc mRNA levels (P=0.006). Thus we suggest that prothymosin alpha plays an active role as a target of N-myc in neuroblastoma.

Age Factors↗

PubMed2001

Clinical significance of matrix metalloproteinase-7 and Ets-1 gene expression in patients with lung cancer.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is a member of the MMP family and has a wide variety of substrate spectra. Ets domain transcription factors are reported to play an important role in carcinoma invasion and metastasis. The regulatory role of Ets-1 has been shown in several MMPs. We have hypothesized that MMP-7 and Ets-1 mRNA levels could be predictors of the development and invasion of lung cancer. METHODS: The study included 73 lung cancer cases. The mRNA levels were quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR) using a LightCycler. RESULTS: No significant difference in MMP-7 and Ets-1 mRNA levels was found among gender, age, and pathological subtype. The MMP-7 mRNA levels were elevated in tumor tissues from stage II-IV lung cancer (1.629 +/- 2.267) compared to those from stage I lung cancer (0.762 +/- 1.463) (P = 0.0290). There was a tendency toward higher MMP-7 mRNA expression levels in tumors with lymph node metastasis (1.728 +/- 2.432) compared to those without lymph node metastasis (1.141 +/- 1.838) (P = 0.1076). Thus, MMP-7 mRNA levels may serve as a marker of higher stages in lung cancer. No significant difference in Ets-1 mRNA levels was found among clinical stages and T-status. The Ets-1 mRNA levels were elevated in tumors from N2 patients (7.512 +/- 13.306) compared to those from N0 patients (2.525 +/- 4.719) (P = 0.0209). Ets-1 mRNA levels showed a positive correlation with MMP-7 expression (P = 0.0042). CONCLUSIONS: Using the LightCycler RT-PCR assay, the determination of MMP-7 and Ets-1 mRNA levels might provide a potential marker for advanced lung cancer. However, further studies and a longer follow-up are needed to confirm the impact of MMP-7 in the biological behavior of the tumor.

Adult↗

PubMed2001

Histopathologic changes of thymoma preoperatively treated with corticosteroids.

Preoperative treatment of thymoma in advanced stages with corticosteroids may reduce the size of the tumor, but no precise histologic evaluation has been performed. We examined the histopathologic features of pretreatment biopsy and posttreatment surgical specimens of eleven cases of thymoma with such treatment to see the changes of the histologic subtypes based on Muller-Hermelink classification. All specimens were also assessed immunohistochemically for MIB-1 labeling and apoptotic cells to verify the effectiveness of this pretreatment. Seven tumors clinically diminished in size after the treatment with corticosteroids. Fungal infection occurred in three cases postoperatively. The histology of mixed thymomas (two cases) was converted to that of medullary thymoma. Predominantly cortical thymomas (four cases) and cortical thymomas (three cases) changed to show similar histologic features; both became epithelial-rich thymoma with large polygonal tumor cells having indistinct cell borders. In contrast, two well-differentiated thymic carcinomas showed at surgery more prominent squamoid appearance with distinct cell borders. The apoptotic indices of epithelial cells were increased (P = 0.001), and the MIB-1 indices tended to be decreased with corticosteroid treatment. These results suggest that there may be a histogenetic relationship between medullary and mixed thymomas and also between predominantly cortical and cortical thymomas. Corticosteroids may cause degenerative changes in the epithelial cells and lymphocytes and, in thymomas in advanced stages, corticosteroid pretreatment may be warranted, although attention should be paid to infection after surgery.

Adrenal Cortex Hormones↗

PubMed2001

Autoantibody to gravin is expressed more strongly in younger and nonthymomatous patients with myasthenia gravis.

Gravin is expressed in several cell and tissue types as either 300 kDa doublet or 250 kDa proteolytic products. It is a cytoplasmic antigen that reacts with the serum of patients with myasthenia gravis (MG). Autoantibodies to gravin residues 1477-1781 are highly specific for MG. In the present study, we examined residues 1477-1781 in detail and found that residues 1542-1547 of gravin protein, which had sequence homology with the binding sequences of two protein A-kinase anchoring proteins, were highly reactive to MG serum. Antigravin antibody activities were stronger in younger and nonthymomatous patients. These findings suggest that antigravin antibody activities could be a useful prognostic factor and that the gravin antibody of MG may have a function which prevents the protein A-kinase binding pathway.

A Kinase Anchor Proteins↗

PubMed2001

Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1,080 +/- 1,185pg/ml) compared with those in the healthy volunteers (407 +/- 589 microg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2740 +/- 631 pg/ml) compared with those in the healthy volunteers (1728 +/- 1,192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors.

Adult↗

PubMed2001

Expression of the prothymosin-a gene as a prognostic factor in lung cancer.

Prothymosin-alpha (PTalpha) is known to play a role in cell proliferation, and the PTalpha mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTalpha mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTalpha and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTalpha and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTalpha mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTalpha and c-myc. PTalpha mRNA overexpression in lung cancer was correlated with a poor prognosis.

Aged↗

PubMed2001

Expression of the antiapoptosis gene, AAC-11, as a prognosis marker in non-small cell lung cancer.

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel apoptosis inhibitor gene, antiapoptosis clone 11 (AAC-11), may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of AAC-11 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 94 non-small cell lung carcinomas and adjacent histologically normal lung samples. The data was analyzed in reference to clinicopathological and survival data. AAC-11 transcripts were detected in 12 (12.7%) of the tumor samples, although five of paired normal lung samples showed very weak expression. There was no relationship between AAC-11 gene expression and age, gender, N or T-status. AAC-11 was preferentially expressed in squamous cell carcinoma (26.9% of squamous cell carcinoma vs. 7% of adenocarcinoma). The NSCLC patients with AAC-11 expression had significantly poor survival than the patients without AAC-11 expression (P=0.0360). Although the AAC-11 gene was not expressed in a majority of NSCLC tumors, we suggest that AAC-11 may predict poor survival.

Adenocarcinoma↗

PubMed2001

Overexpression of Hrad17 gene in non-small cell lung cancers correlated with lymph node metastasis.

We used palindromic PCR-driven cDNA differential display technique to identify and isolate a gene, human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, from colon cancer tissues. 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 non-small cell lung cancer (NSCLC). We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with NSCLC who had undergone surgery. Expression of Hrad17 messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 102 non-small cell lung carcinomas and adjacent histologically normal lung samples from patients for whom follow up data were available. Hrad17 transcripts were detected in 26 (25.5%) of the tumor samples, although some of the paired normal lung samples showed weak expression. There was no relationship between Hrad17 gene expression and age, gender or T-status. About 13 of 31 (41.9%) NSCLC patients with Hrad17 overexpressions were node positive, on the other hand, 13 of 76 (18.3%) cases without Hrad17 overexpressions were node positive. Thus the expression of Hrad17 mRNA correlated with lymph node metastasis (P=0.0231) from NSCLC. Hrad17 protein was highly expressed at the advancing margin of the tumor of lung cancer tissue but not within the normal lung tissue by immunohistochemistry. Thus the expression of Hrad17 might correlate with more advanced NSCLC.

Adult↗

PubMed2001

Expression of the cdc25B mRNA correlated with that of N-myc in neuroblastoma.

BACKGROUND: Neuroblastoma is one of the most common solid tumors in early childhood. Overexpression of the proto-oncogene N-myc has been reported to be correlated with more malignant course of the disease. cdc25B is reported to be a target of myc and elevated in several malignant cells and tissues. METHODS: Expression of cdc25B and N-myc messenger RNAs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) assay in 20 tumor samples from neuroblastoma using LightCycler. The data were analyzed with reference to clinicopathological factors. Immunohistochemistry for cdc25B was also performed. RESULTS: There was no significant difference in the cdc25B expression between patient groups according to age, gender and clinical stage. The cdc25B mRNA expression levels were significantly correlated with N-myc mRNA levels (y = -0.445 + 20.577x, p < 0.0001). CONCLUSION: We could not establish the clinical significance to determine the cdc25B mRNA level from neuroblastoma. However, we suggest that cdc25B may play an active role as a target of N-myc in neuroblastoma, although the biological function of cdc25B in neuroblastoma remains to be clarified.

Cell Cycle Proteins↗