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Biomedical subjects

I Fukai

Publications and source records attributed to I Fukai.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Expression of the protein gene product 9.5, PGP9.5, is correlated with T-status in non-small cell lung cancer.

BACKGROUND: In a tumor, increased deubiquitination of cyclins by a protein gene product gene, PGP9.5, could contribute to the uncontrolled growth of somatic cells that is a hallmark of cancer. We hypothesized that PGP9.5 may be expressed in tumors of patients with non-small cell lung cancer (NSCLC). METHODS: Expression of PGP9.5 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 95 non-small cell lung carcinomas and adjacent histological normal lung samples. The data were analyzed with reference to clinicopathological factors. RESULTS: PGP9.5 transcripts were detected in 18 (12.8%) of the tumor samples, although some of paired normal lung samples showed very weak expression. There was no relationship between PGP9.5 gene expression and age, gender, N-status or pathological subtype. PGP9.5 gene was preferentially expressed in T3/T4 NSCLC (12/41, 29.3%) compared with T1/T2 NSCLC (6/54, 11.1%) (p = 0.0482). CONCLUSIONS: Although the PGP9.5 gene was not expressed in a majority of NSCLC tumors, we suggest that PGP9.5 may correlate with tumor invasion or progression of NSCLC.

Adult↗

Expression of Periostin, homologous with an insect cell adhesion molecule, as a prognostic marker in non-small cell lung cancers.

We used our palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique to identify and isolate a gene, designated periostin, from cancer tissues and found it to be overexpressed in several human tumors. We attempted to determine the influence of periostin expression on clinical outcome in patients with non-small cell lung cancer (NSCLC) by reverse transcriptase (RT)-PCR analysis. Periostin gene was highly expressed at the tumor periphery of lung cancer tissue but not within the tumor by in situ RNA hybridization, suggesting that expression of periostin may be involved in the process of tumor invasion. Periostin transcripts were detected in 50 (49.0%) of the tumor samples, although some paired normal lung samples showed weak expression. There was no relationship between periostin gene expression and gender, N- or T-status. The NSCLC patients with periostin expression had significantly poorer survival than the patients without periostin expression (P = 0.0338).

Adenocarcinoma↗

A critical role for p59(fyn) in CD2-based signal transduction.

TCR- but not CD2-triggered IL-2 production is p56(lck) dependent. To test the hypothesis that p59(fyn), a second src-family protein tyrosine kinase (PTK) expressed in T lymphocytes, might be an essential upstream component of the CD2 signaling pathway, we generated human (h) CD2 transgenic (tg) fyn(+/+) and fyn(-/-) mice. Clustering of hCD2 molecules on resting peripheral T lymphocytes results in Ca(2+) mobilization, activation of MAPK and cellular proliferation. In contrast, in the absence of p59(fyn), these CD2-initiated activities are markedly reduced, while TCR-triggered proliferation is unaffected. Several CD2 pathway components regulated by p59(fyn) have been identified including phospholipase C-gamma1 (PLC-gamma1), Vav, protein kinase C-theta isoform (PKC-theta), docking protein (Dok), focal adhesion kinase (FAK) and Pyk2. Decreased inducible PKC-theta catalytic activity and Vav phosphorylation likely account for diminished p38 and JNK activation in hCD2tg fyn(-/-) mice. Moreover, deficiency in fyn-dependent PLC-gamma1 catalytic activity may contribute to reduced PKC-alpha-dependent ERK activation. Of note, CD2-dependent Dok but not linker from activated T cells (LAT) tyrosine phosphorylation requires p59(fyn). Furthermore, that FAK and Pyk2 are target substrates implies that p59(fyn) may be an important regulator of T cell adhesion as well. Collectively, these data identify p59(fyn) as a key PTK in CD2-mediated activation of mature T lymphocytes.

Animals↗

Evaluation of new TNM lung cancer classification.

OBJECTIVE: A new staging system for lung cancer was proposed by the Union Internationale Contre le Cancer in 1997, with Stages I and II subdivided and T3N0M0 assigned as stage IIB. We studied the usefulness of this new classification. METHODS: Subjects were 753 patients with non-small-cell lung cancer undergoing pulmonary resection and follow-up data were retrospectively reviewed. RESULTS: A significant difference was seen between stage IA and IB survival--70.4% vs 52%. No significant difference was seen between survival for T3N0M0, T1N1M0 and T2N1M0--35.3%, 42.3%, and 43.8%--at 5 years. We found, however, that the prognosis for T3N2M0 tumors--6.5% 5-year survival--is too poor to be grouped with other N2 diseases having a better prognosis--23.9% 5-year survival. Significant differences were also seen in the survival of T3N0 or T3N1 patients by organ and diseases involving the rib, diaphragm, or mediastinum may be classified as T4. CONCLUSION: The new staging system predicts patient outcome fairly well and the modification is well grounded. It appears, however, to be appropriate to subdivide T3 tumors by invaded organs and T3N2M0 disease may be better classified as stage IIIB. The classification of pulmonary metastasis appears to require further improvement.

Adult↗

Left diaphragmatic hernia complicated by perforation of an intrathoracic gastric ulcer into the aorta: report of a case.

We describe herein a rare but fatal complication of diaphragmatic hernia that occurred in a 51-year-old man 3 years after his diaphragm had been repaired by a polytetrafluoroethylene sheet following resection during pleuropneumonectomy for a left pleural mesothelioma. He was admitted to our hospital in shock status, and was found to have massive bleeding from the nasogastric tube. An emergency operation revealed that an ulcer of the stomach, which had been displaced into the left thorax, had perforated directly into the descending aorta.

Aorta, Thoracic↗

Thymic neuroendocrine tumor (thymic carcinoid): a clinicopathologic study in 15 patients.

BACKGROUND: Thymic neuroendocrine tumor (carcinoid tumor) is rare, and prognosis for patients with this tumor has been difficult to predict. METHODS: The medical records of 15 patients were reviewed, and the patients were classified according to tentative TNM classification and histologic grade. RESULTS: Ten (66.7%) of 15 patients were male. Lymph node metastases were identified in 9 (60%) of 15 patients at the time of resection. There were one grade 1, nine grade 2, and five grade 3 tumors. Total resection was possible in 13 patients. Distant metastases developed in 10 (76.9%) of these 13 patients, although no local recurrence developed. Of these 10 patients, 6 died of distant metastases 5 to 25 months after the recurrence. Three patients are still alive, with metastases to the bone, spleen, and pleura 1 to 24 months after the diagnosis of recurrence. Two patients are presently tumor free (T1N0, grade 3 and T3N2, grade 2), but only 1 has survived beyond 5 years. CONCLUSIONS: Thymic neuroendocrine tumor must be regarded as a malignant neoplasm that is prone to metastasize to mediastinal lymph nodes and to distant sites, even after total excision. Neither T and N classification nor histologic grade has been successful in predicting the outcome of a patient with this tumor. More aggressive management, including adjuvant therapies and reexcision of subsequent tumors, may result in increased survival.

Adult↗

[Surgical treatment for lung cancer invading thoracic aorta].

We experienced three surgical cases of lung cancer invading thoracic aorta, and discussed some problems in order to improve the surgical outcome. In the first case, the patient had a ruptured descending aortic aneurysm into a tumor of left lung. Following urgent graft replacement of descending aorta, left pneumonectomy was carried out, but the patient died of bone marrow dissemination which was probably caused by aspiration of the tumor cells on cardiopulmonary bypass. In the second case, the patient underwent resection of the left upper lobectomy combined with resections of the left subclavian artery and distal aortic arch, but died of perforation of aortic arch due to vascular injury by cross clamp. In the third case, an operation was successfully performed for lung cancer invading the aortic arch. Left upper lobectomy with associated resection of aortic arch, left subclavian and common carotid arteries was performed. Both arteries were replaced with a Gelseal Graft.

Adenocarcinoma↗

[Treatment of non-thymic malignant tumors of the mediastinum].

Nonthymic malignant tumors of the mediastinum are quite rare. Primary mediastinal malignant lymphomas, malignant mediastinal neurogenic tumors, and primary malignant mediastinal mesenchymal tumors are reviewed and discussed in terms of the problems in their treatment.

Adolescent↗

Chondrosarcoma originating from the trachea.

We report a tracheal chondrosarcoma in a 54-year-old man, treated with neodymium:yttrium-aluminum garnet laser vaporization via fiberoptic bronchoscopy followed by surgical resection. Chondrosarcomas of the trachea are extremely rare tumors. To our knowledge, there are 9 cases of chondrosarcoma of the trachea reported in the English-language literature, to which we add the tenth.

Biopsy↗

Elevated plasma thymosin-alpha1 levels in lung cancer patients.

OBJECTIVE: Prothymosin-alpha, the precursor of thymosin-alpha1, may play a role in cell proliferation, and the plasma level of thymosin-alpha1 may reflect the degree of proliferation of the tumor cells. METHODS: Recently, a new sandwich immunoradiometric assay for thymosin-alpha1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-alpha1 in 131 lung cancer patients. RESULTS: We found that the mean plasma thymosin-alpha1 levels in lung cancer patients were higher than in normal individuals (P < 0.001). However, half of the patients showed normal levels. Thymosin-alpha1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-alpha1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P = 0.03). Survival of patients with normal levels of plasma thymosin-alpha1 was significantly better than that with higher levels (P = 0.04). CONCLUSIONS: The plasma level of thymosin-alpha1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.

Adenocarcinoma↗

[Intrapulmonary laceration revealed by computed tomography in a patient with pneumomediastinum].

An 18-year-old man had bronchial asthma and a pneumomediastinum. A computed tomographic scan of the chest revealed the pneumomediastinum, intrapulmonary laceration of the S1b, and a small amount of air in the perivascular space from V1a to V1. Increased pressure in intrapulmonary airways may have resulted in ruptured S1b alveoli and air leakage into the interstitium between the surrounding secondary lobules. The air may have moved along the perivascular space (pulmonary vein) toward the hilum, and eventually into the mediastinum. We know of no previous report of pneumomediastinum in which images of intrapulmonary lesions are presented. In this case computed tomography revealed the mechanism by which the pneumomediastinum probably developed.

Adolescent↗

Extended thymectomy for myasthenia gravis patients: a 20-year review.

BACKGROUND: Since 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated. METHODS: Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point. RESULTS: Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome. CONCLUSIONS: Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

Adult↗

Esophageal tracheobronchoplasty for diseases of the central airway.

Three infants with congenital tracheal stenosis and three adults with various diseases of the central airway underwent esophageal tracheobronchoplasty to repair long-segment stenoses and defects. The primary operative goal was enlargement of the stenosis (n = 4), repair of the defect (n = 1), or both (n = 1). Cardiopulmonary support was required in two cases. All three infants were operated on for generalized congenital tracheal stenoses. There was one postoperative death on the fifth day. Another infant died of pneumonia 3 months after operation. Tracheal patency was excellent in two infants. One infant is well without symptoms 6 years after the operation, although balloon dilation was required three times during the first postoperative year. In the three adult patients, the primary diseases were congenital tracheal stenosis, iatrogenic injury associated with relapsing polychondritis, and malignant mediastinal tumor involving the trachea. All lesions involved both the trachea and main stem bronchi. Postoperative airway patency was excellent in all three adults, although expandable metallic stents had to be inserted in one patient. Postoperative pulmonary function was improved, particularly forced expiratory volume in 1 second and peak expiratory flow rate. Although the postoperative mortality rate was still high, especially among the infants, and prolonged postoperative ventilatory support was required for five of the six patients, long-term patency and postoperative pulmonary functional improvement are encouraging.

Adult↗