Masanobu Kiriyama

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

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.

Expression of the MTA1 mRNA in advanced lung cancer

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 non-small cell lung cancer (NSCLC). Expression of MTA1 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 74 non-small cell lung carcinoma 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 II-IV NSCLC (3.465+/-3.675) was significantly higher than the level in stage I NSCLC (1.614+/-2.434, P=0.0153). MTA1/GAPDH mRNA levels in T4 NSCLC (4.377+/-4.169) was significantly higher than the level in T1 NSCLC (1.966+/-2.148, P=0.0351) and in T2 NSCLC (2.048+/-1.899, P=0.0269), respectively. MTA1/GAPDH mRNA level in NSCLC with lymph node metastasis (4.242+/-3.758) was significantly higher in NSCLC without lymph node metastasis (P=0.0169). Our results show that the expression of the MTA1 gene is closely related to invasiveness and metastasis in NSCLC. The gene MTA1 could thus potentially provide information on the mechanism of cancer invasion and metastasis.

Decreased perioxisome proliferator-activated receptor gamma gene expression was correlated with poor prognosis in patients with lung cancer

Activation of the nuclear hormone receptor perioxisome proliferator-activated receptor gamma (PPARgamma) inhibits cell growth and induces apoptosis in several human cancers. We have hypothesized that PPARgamma mRNA levels could be predictors of the differentiation and survival of lung cancer. The study included 77 lung cancer cases. The mRNA levels were quantified by real time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler. The PPARgamma mRNA levels were decreased in tumor tissues from lung cancer (0.579 +/- 1.255) compared to the normal adjacent lung tissues (4.191 +/- 2.868) (P = 0.0001). No significant difference in PPARgamma mRNA levels was found among gender, age, and pathological subtype. The PPARgamma mRNA levels were higher in tumor tissues from higher differentiated lung cancer. The NSCLC patients with low PPARgamma mRNA expression (< 0.5) had significantly worse survival than the patients without low PPARgamma mRNA levels (P = 0.0438, Breslow-Gehan-Wilcoxon test; P = 0.0168, Coxs proportional-Hazards regression model). Thus, PPARgamma mRNA levels may serve as a prognostic marker in lung cancer. Using the LightCycler RT-PCR assay, the determination of PPARgamma mRNA levels might provide a potential marker for treatment of lung cancer by PPARgamma agonist. However, further studies and a longer follow up are needed to confirm the impact of PPARgamma in the biological behavior of the tumor.

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.

Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury

OBJECTIVES In lung ischemia-reperfusion injury, neutrophil migration from the vasculature to the interstitial spaces plays a major role in tissue injury. Degradation of the basement membrane, which is composed of extracellular matrix (ECM) molecules, is necessary for neutrophil migration. Matrix metalloproteinases (MMPs) might play a role in ECM degradation in lung ischemia-reperfusion injury. We evaluated the changes in the activity of MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expressions using rat lung transplantation models. METHODS We divided animals into 4 groups. Groups I and II served as control groups with intact lungs (Group I) and 24-hour cold-preserved lungs (Group II). Groups III and IV received lung grafts after 24-hour cold preservation. The recipient animals were sacrificed 1 hour (Group III) or 24 hours (Group IV) after transplantation. We evaluated lung injury histologically. We assessed MMP activity using zymography. We assessed MMP-2, MMP-9, and TIMP-1 gene expression using biplex reverse transcriptase-polymerase chain reaction method. RESULTS In Groups III and IV, we noted severe ischemia-reperfusion injury. We noted no significant difference in enzyme activity and gene expression of MMP-2 between Groups I and IV. The MMP-9 activity and gene expression were low during ischemia and increased on reperfusion. TIMP-1 gene expression was low during ischemia and at the early phase of reperfusion, and showed a dramatic increase at the late phase of reperfusion. CONCLUSIONS Matrix metalloproteinase 9, but not MMP-2, may play an important role in ischemia-reperfusion injury. TIMP-1 increases at the late phase of reperfusion and may compensate for the activity of MMP-9.

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.

Sclerosing hemangioma with metastases to multiple nodal stations.

We present a case of a large pulmonary sclerosing hemangioma with metastases to multiple lymph nodal stations and suspected contralateral pulmonary metastasis. Four cases (including the present) have been reported to have lymph node metastasis, and all had large tumors exceeding 3.5 cm in diameter. Accordingly, resection of sclerosing hemangioma is advisable while the tumor is small. Even in cases with a large sclerosing hemangioma, lymph node metastasis may be uncommon. However lymph node dissection may be necessary to detect lymph node metastasis in selected cases.

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

Abstract 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 ± 1 185 pg/ml) compared with those in the healthy volunteers (407 ± 589 pg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2 740 ± 631 pg/ml) compared with those in the healthy volunteers (1 728 ± 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.

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.

Expression of the Prothymosin-α Gene as a Prognostic Factor in Lung Cancer

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