PubMed Health⌕ Search

Biomedical subjects

Ichiro Fukai

Publications and source records attributed to Ichiro Fukai.

At least 19 recordsLinked to original sources
PubMed2006

ACTH-secreting thymic carcinoid associated with multiple endocrine neoplasia type 1.

Thymic carcinoids are classified into three categories: (1) nonsecretory tumors, (2) hormonal secretory tumors, and (3) tumors associated with multiple endocrine neoplasia type 1. We report a rare case with adrenocorticotropic hormone secreting thymic carcinoid with multiple endocrine neoplasia type 1. Radiologic examination showed an anterior mediastinal mass and a parathyroid tumor. Blood analysis revealed high levels of parathyroid hormone and adrenocorticotropic hormone. Urine cortisol and 17-hydroxycorticoids levels were also elevated. Extended thymectomy was performed. Subsequently adjuvant radiation therapy and parathyroid tumor resection were performed. A germline mutation of exon 7 in the multiple endocrine neoplasia type 1 gene was detected and a somatic mutation of exon 9 was demonstrated in the thymic tumor.

ACTH Syndrome, Ectopic↗
PubMed2005

Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay.

Epidermal growth factor receptor (EGFR) gene mutations have been found in a subset of non-small cell lung cancer (NSCLC) with good clinical response to gefitinib therapy. A quick and sensitive method with large throughput is required to utilize the information to determine whether the molecular targeted therapy should be applied for the particular NSCLC patients. Using probes for the 13 different mutations including 11 that have already been reported, we have genotyped the EGFR mutation status in 94 NSCLC patients using the TaqMan PCR assay. We have also genotyped the EGFR mutations status in additional 182 NSCLC patients, as well as 63 gastric, 95 esophagus and 70 colon carcinoma patients. In 94 NSCLC samples, the result of the TaqMan PCR assay perfectly matched with that of the sequencing excluding one patient. In one sample in which no EGFR mutation was detected by direct sequencing, the TaqMan PCR assay detected a mutation. This patient was a gefitinib responder. In a serial dilution study, the assay could detect a mutant sample diluted in 1/10 with a wild-type sample. Of 182 NSCLC samples, 46 mutations were detected. EGFR mutation was significantly correlated with gender, smoking status, pathological subtypes, and differentiation of lung cancers. There was no mutation detected by the TaqMan PCR assay in gastric, esophagus and colon carcinomas. TaqMan PCR assay is a rapid and sensitive method of detection of EGFR mutations with high throughput, and may be useful to determine whether gefitinib should be offered for the treatment of NSCLC patients. The TaqMan PCR assay can offer us a complementary and confirmative test.

Adolescent↗
PubMed2005

EGFR Mutation status in Japanese lung cancer patients: genotyping analysis using LightCycler.

PURPOSE: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in approximately 25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. EXPERIMENTAL DESIGN: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. RESULTS: In exon 21, EGFR mutations (CTG --> CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P < 0.0001), Brinkman index (600 < or = versus 600, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. CONCLUSIONS: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.

Adenocarcinoma↗
PubMed2005

Endoscopic thoracic sympathectomy for palmar hyperhidrosis: efficacy of T2 and T3 ganglion resection.

BACKGROUND: Endoscopic thoracic sympathectomy has been considered an effective treatment for palmar hyperhidrosis. However, the extent of resection has not been determined in terms of efficacy and complications. We compared the efficacy and complications of 2-ganglion and single-ganglion resection in patients with palmar hyperhidrosis. METHODS: From 1995 to 2000, 75 patients underwent resection of thoracic ganglion T2 and T3. From 2000 to 2003, 67 patients underwent resection of only the T2 ganglion. Eighty of the 142 patients (56%) answered a detailed questionnaire, the results of which were analyzed. RESULTS: Gender, age, family history, and distribution of sweating were similar in both groups. Recurrence rates 1 and 2 years after endoscopic thoracic ganglionectomy were between 0% and 3% in T2 and T3 resection, and between 15% and 19% in T2 resection only. In the combined T2 and T3 resection group, 100% of patients noticed compensatory sweating; in T2 resection, 90% of patients noticed compensatory sweating. As for rates of satisfaction, T2 and T3 resection was superior to T2 resection. CONCLUSIONS: High recurrence rates of palmar hyperhidrosis after single-ganglion resection are reported in the present study. Two-ganglion resection is a superior surgical method to prevent recurrence of palmar hyperhidrosis.

Adolescent↗
PubMed2004

Elevated serum epidermal growth factor receptor level in stage IV thymoma.

Using the enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as a predictor of the development and extension of thymoma. Serum samples were collected from 31 patients with thymoma and 16 patients with nonmalignant thoracic disease before clinical treatment. There was no difference between the serum EGFR levels of the patients with thymoma and the nonmalignant controls, being 49.1 +/- 136.3 and 22.6 +/- 7.3 fm/ml, respectively ( P = 0.11). However, patients with stage IV thymoma had significantly higher EGFR levels than those with stage I or stage II thymoma, the respective values being 127.8 +/- 243.9, 10.9 +/- 9.2 ( P = 0.02), and 19.7 +/- 10.6 ( P = 0.0433) fm/ml. The serum EGFR levels were similar in the pathological subtypes. These findings suggest that serum EGFR levels may serve as a marker that could be used as a diagnostic indicator of the invasion of thymoma.

Biomarkers, Tumor↗
PubMed2004

Arg and DAP3 expression was correlated with human thymoma stage.

Thymoma is one of the most common solid tumors in the mediastinum. As 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. The recent reports showed that the gain of chromosome 1q regions was frequent in thymoma. We investigated the use of oligonucleotide arrays to monitor in vivo gene expression levels at chromosome 1q regions in the early- (stage I or II) and late-stage (stage IVa) 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 36 thymoma patients. Using both the methods, candidate genes were come up. These are Arg tyrosine kinase and death-associated protein 3 (DAP3), which are known as ionizing radiation resistance conferring proteins. The Arg/GAPDH mRNA level in stage IV thymoma (90.716 +/- 177.851) was significantly higher than in stage I thymoma (10.335 +/- 25.744, P = 0.0465). The DAP3/GAPDH mRNA level in stage IV thymoma (17.424 +/- 20.649) was significantly higher than in stage I thymoma (5.184 +/- 3.878, P = 0.0305). DAP3 expression was also correlated with the WHO classification. The combined use of oligonucleotide microarray and real-time RT-PCR analyses provided a candidate molecular marker surrounding the development and progression of thymoma correlated with chromosome 1q.

Apoptosis Regulatory Proteins↗
PubMed2004

Histone deacetylase 1 mRNA expression in lung cancer.

Histone deacetylases (HDACs) play a crucial role in tumorigenesis, however, the expression status of HDACs in lung cancer tissues has not been reported. We have investigated that HIDAC 1 mRNA levels and other clinico-pathological data, including MTA 1 mRNA expression in lung cancer. The study included 102 lung cancer cases. The HDAC1 mRNA levels were quantified by real time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler (Roche Molecular Biochemicals, Mannheim, Germany). The HDAC1/GAPDH mRNA levels were not significantly different in tumor tissues from lung cancer (30.654 +/- 33.047) and adjacent non-malignant lung tissues (18.953 +/- 56.176 , P = 0.1827). No significant difference in HDAC1/GAPDH mRNA levels was found among age, gender, and lymph node metastasis. The HDAC1/GAPDH mRNA levels were significantly higher in stage III or IV lung cancer (50.929 +/- 120.433) than in stage I lung cancer (11.430 +/- 25.611, P = 0.0472). HDAC1/GAPDH mRNA levels were significantly higher in T3 or T4 lung carcinoma (54.326 +/- 127.018) than in T1 or T2 lung cancers (14.790 +/- 48.670, P = 0.1601). HDAC1/GAPDH mRNA levels were correlated with MTA1/GAPDH mRNA levels (y = 0.0106x + 2.5827 , P = 0.0352 ). HDAC1/GAPDH mRNA levels were also correlated with HDAC1 protein (P = 0.0484) expression by immunohistochemistry. Using the LightCycler RT-PCR assay, the HDAC1 gene expression might correlate with progression of lung cancers. However, further studies are needed to confirm the impact of HDAC1 for the molecular target of the lung cancer.

Adult↗
PubMed2004

Endostatin gene transfection using a cationic lipid: advantages of transfection before tumor cell inoculation and repeated transfection.

Intravenous endostatin gene transfection results in tumor suppression in a murine pulmonary metastasis model. We transfected the endostatin gene at different times, in order to achieve an optimal protective effect. pST2-Endo encoding murine endostatin was injected in a complex with cationic lipid. Pulmonary metastases were caused by intravenous injection of murine fibrosarcoma cells. Mice were observed for 14 days following fibrosarcoma cell inoculation (FSI). In the study groups, the animals were transfected with pST2-Endo at three different times: 2 days before and 3 and 7 days after FSI. In the group transfected with pST2-Endo 2 days before FSI, the weights of the lungs and tumor-occupied area ratio were significantly less than in the other groups. Significant inhibition of tumor neovascularization was documented by means of CD31 immunohistochemistry. The effect of repeated endostatin transfection on survival after FSI was determined. Animals repeatedly transfected with the endostatin gene survived significantly longer than the groups treated with a single endostatin gene transfection. A stable endostatin-expressing fibrosarcoma transfectant was created and tested for migration and invasion. Compared with controls, endostatin expression reduced migration and invasion by 15%. It is concluded that endostation gene transfection before FSI and repeated transfection thereafter results in significant tumor suppression.

Animals↗
PubMed2004

Decreased Hrad6B expression in lung cancer.

Human homologues of yeast Rad 6 (Hrad6B) encode ubiquitin-conjugating enzymes and complement the DNA repair and UV mutagenesis defects of Saccharomyces cerevisiae rad6 mutant. There is a larger subgroup with reduced DNA repair capacity that is likely to be at increased cancer risk. The authors investigated Hrad6B expression in lung cancer. An attempt was made to determine the influence of Hrad6B expression on clinicopathological features for patients with lung cancer who had undergone surgery. Expression of Hrad6B messenger RNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 110 lung carcinomas and adjacent histological non-malignant lung samples from patients for whom follow-up data were available using LightCycler. The Hrad6B/glyceraldehydes-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the lung cancer tissue (4.078+/-5.674) as compared with the non-malignant lung tissue (10.495+/-12.976, p<0.001). There was no relationship between Hrad6B/GAPDH expression and age, clinical stages, T-status, N-status, and pathological subtypes in lung cancer tissues. Hrad6B/GAPDH mRNA levels in males (3.521+/-4.280) and in females (6.420+/-8.167) were significantly different (p=0.0443) in lung cancer tissues, but not in non-malignant lung tissues. Heavy smokers had a slight non-significant tendency (p=0.0857) towards lower Hrad6B/GAPDH mRNA levels (3.453+/-4.743) in their lung cancer tissues as compared with light or non-smokers. Thus decreased Hrad6B mRNA expression might be a biomarker for decreased DNA repair capacity and the dysfunction of Hrad6B might play a role in the tobacco-related oncogenesis of lung cancer.

Aged↗
PubMed2004

Expression of Smac/DIABLO is a novel prognostic marker in lung cancer.

Recently Smac/DIABLO (second mitochondria-derived activator of caspase) has been identified as a proapoptotic protein that inhibits IAPs (inhibitors of apoptosis proteins). Smac is expressed ubiquitously in many organs, including the lung. Here we evaluated the expression of Smac mRNA with real-time reverse-transcription PCR in 88 primary lung cancers and matched normal tissues. Smac mRNA expression in tumor tissues was significantly lower than that in normal tissues (p<0.0001). In squamous cell carcinomas, Smac mRNA expression was significantly lower than that in adenocarcinomas (p=0.0072). Smac mRNA expression in T2-T4 tumors was significantly lower than that in T1 tumors (p=0.0006). The expression of Smac in the tumors of smokers was lower than that in the tumors of non-smokers (p=0.0011). The prognosis of patients with a tumor exhibiting a low expression of Smac mRNA was worse than that in those with a tumor exhibiting high Smac mRNA expression (log-rank test, p=0.047). These results indicate that Smac expression may play a role in the carcinogenesis, progression, and prognosis of primary lung cancer.

Apoptosis Regulatory Proteins↗
PubMed2003

Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in thymoma.

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.

Adult↗
PubMed2003

Multicystic mesothelial cyst of the mediastinum: report of a case.

We report the rare case of a multicystic mesothelial cyst of the mediastinum. A 43-year-old man was referred to our department after a routine chest X-ray showed an anterior mediastinum mass. The lesion was resected by thoracoscopy, which revealed multicystic, thin-walled tense masses arising in the anterior mediastinum. The cysts were not adherent to the pericardium or to the thymus of the right lobe. Immunohistochemistry revealed that the cyst was lined with a layer of mesothelial cells and there were no malignant foci. The lining cells were positive for keratin and negative for the lymphocyte marker. These findings were consistent with a diagnosis of multicystic mesothelial cyst.

Adult↗
PubMed2003

Elevated serum epidermal growth factor receptor level is correlated with lymph node metastasis in lung cancer.

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) and the group with elevated 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.

Aged↗
PubMed2003

Hrad17 expression in thymoma.

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.

Cell Cycle Proteins↗
PubMed2003

Expression of matrix metalloproteinases 2 and 7 in tumor cells correlates with the World Health Organization classification subtype and clinical stage of thymic epithelial tumors.

To investigate the roles of matrix metalloproteinases (MMPs) in thymic epithelial tumors, we examined the expression of MMP-2, -7, and -9; membrane-type 1 (MT1)-MMP; and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 57 tumors by immunohistochemistry and in selected 15 cases by in situ hybridization. The tumors consisted of 5 type A, 12 type AB, 11 type B1, 11 type B2, 9 type B3, and 9 type C thymomas according to the World Health Organization histologic classification system and of 22 stage I, 13 stage II, 8 stage III, and 14 stage IV thymomas according to the Masaoka staging system. In the positive cases, MMPs and TIMP-2 were expressed in both tumor cells and stromal cells. The cellular localization of MMPs detected by immunohistochemistry was almost identical with that of the mRNA signals detected by in situ hybridization. MMP-2 and MMP-7 were predominantly expressed in type B3 thymoma and type C thymoma, respectively. Expression of MT1-MMP and TIMP-2 correlated with that of MMP-2, indicating a proteolytic activation of the latter. MMP-9 was prominent in type B2 thymoma. Expression in tumor cells of MMP-2 or MMP-7 was also correlated with clinical stage. 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 MMP-2 and MMP-7 may contribute to the tumor aggressiveness and malignant potential.

Adult↗
PubMed2003

Saber-sheath malacic trachea remodeled and fixed into a normal shape by long-term placement and then removal of gianturco wire stent.

We report the case of a 59-year-old man who presented with major dyspnea due to saber-sheath malacic trachea associated with chronic pulmonary obstructive disease. The placement of a temporary tracheal stent alleviated his dyspnea very well; hence the stent was replaced with a Gianturco wire stent (Cook Cardiology, Bloomington, IN). However, this required removal due to wire-stent-related complications 2 years after the replacement. Surprisingly the trachea had been remodeled to a normal shape resulting in comfortable, functional respiratory status. A review of the literature reveals our case to be the first report of curing saber-sheath malacic trachea without leaving any prostheses or other foreign materials.

Bronchoscopy↗
PubMed2003

Gelatinolytic activity of matrix metalloproteinase in lung cancer studied using film in situ zymography stamp method.

In this study, we investigated activity of matrix metalloproteinase (MMP) of lung cancer by newly developed film in situ zymography (FIZ) stamp method, which allows visual localization of gelatinolytic activity within the cut surface of a tumor. We performed FIZ stamp method and conventional gelatin zymography in 39 resected specimen of lung cancer. The degree of gelatinolytic activity was scored (FIZ score) and correlated with the clinicopathological factors of the tumor. FIZ score of normal lung was very low. Lung cancer tissue had consistently higher FIZ score than the matched normal lung tissue. There were statistically significant differences in the FIZ score according to the pathological stage (P = 0.0015), nodal status (P = 0.0007) and lymphatic invasion (P = 0.0004). Direct correlation was observed between the FIZ score and MMP-2 activity (rho = 0.568, P = 0.0030) as quantitated using conventional gelatin zymography. MMP-2 may play an important role in the lymphatic invasion of lung cancer. FIZ stamp method may be a simple and useful diagnostic aid for the presence of cancer cells in the resected specimen.

Adenocarcinoma↗