Soichiro Ando

Evidence for mRNA expression of vascular endothelial growth factor by X-ray irradiation in a lung squamous carcinoma cell line

Vascular endothelial growth factor (VEGF) is a multipotent cytokine which plays an important role in various angiogenic conditions as well as in some tumor behaviors. Here we examined the induction of VEGF mRNA by X-ray irradiation in a lung squamous cell carcinoma cell line (RERF-LC-AI). Irradiating the cells with 15 Gy X-rays significantly increased the mRNA expression up to 2.5-fold of control at a post-irradiation time of 16-24 h. The induction of VEGF mRNA by X-ray irradiation was completely blocked by treating cells with either genistein (Src tyrosine kinase inhibitor) or H7 (protein kinase C inhibitor). This suggests that the mechanism of induction might be concerned with the pathway which triggers Src tyrosine kinase of the cell surface and the protein kinase C pathway.

A prospective study of indications for mediastinoscopy in lung cancer with CT findings, tumor size, and tumor markers

BACKGROUND Biopsies by mediastinoscopy remain the most reliable preoperative staging method for N2 lung cancer. Because it is neither practical nor economical to recommend mediastinoscopy for all candidates for surgery, we developed indicational criteria for video-assisted mediastinoscopy (VAM) and carried out a prospective study to validate its usefulness. METHODS Patients with resectable primary lung cancer were chosen for VAM when at least one of three clinical indicators was present: (1) computed tomographic evidence of mediastinal adenopathy, (2) elevated levels of serologic tumor markers, and (3) diameters of primary cancers (> 2 to 3 cm). Patients without positive nodes (group 2) underwent thoracotomy, and patients with positive nodes (group 3) received induction therapy. When none of these criteria were met (group 1), thoracotomy with R2b lymph node dissection was performed without VAM. RESULTS One hundred twenty-one men and 82 women (total, 203) were eligible for the study. The mean age of the patients was 64.4 years (range, 39 to 75 years) with primary lung cancer. The patients were comprised of 135 adenocarcinomas, 46 squamous cell cancers, and 22 other carcinomas. There were 78 patients in group 1, 87 in group 2, and 38 in group 3. The stages of group 2 patients were more advanced (chi2 = 63.2668; p < 0.001) than those of group 1. As the incidence of positive indicators for VAM increased, the ratios of N2 patients increased from 2.5% (all negative) to 90.4% (triple positive: p < 0.001). The correlation of our criteria with the pathology findings revealed a diagnostic sensitivity of 95.8% and a negative predictive value of 97.4%. Using three indicators for N2 prediction, we selected 96% (46 of 48) pN2, N3 patients and avoided 37% (76 of 203) unnecessary VAMs. CONCLUSIONS We established and validated currently useful criteria for VAMs in the management of primary lung cancer.

Induction by carbon-ion irradiation of the expression of vascular endothelial growth factor in lung carcinoma cells

Purpose : To investigate the induction by carbon- ion irradiation of vascular endothelial growth factor (VEGF) mRNA and protein. Materials and methods : RERF-LC-AI lung squamous carcinoma cells were irradiated with carbon ions of either 13.3, 50 or 90keV/mum. Colony formation was used to determine cell survival. VEGF mRNA and protein of the irradiated cells were quantified by Northern blot analysis and ELISA assay, respectively. Genistein, Src tyrosine kinase inhibitor and H7, protein kinase C inhibitor, were used to inhibit VEGF mRNA expression. Results : The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and 90 keV/mum) was 1.10, 1.97 and 2.30, respectively, in terms of D10 values. Single doses of 15 Gy with either X-rays or carbon ions significantly induced VEGF mRNA expression at 16-24 h after irradiation with a maximum induction of 2.81-fold. A significant increase was also observed in VEGF protein levels, detected in culture supernatant 24 h after irradiation with 50 and 90keV/ μ m carbon ions. Neither mRNA nor protein induction showed a dependence on LET. The induction of VEGF mRNA by carbon-ion irradiation was completely inhibited by pretreating cells with genistein and H7, indicating that Src tyrosine kinase and protein kinase C on cell surface membranes is involved in the induction. Conclusion : Irradiation of lung carcinoma cells with carbon ions induced VEGF mRNA expression and increased protein levels. The induction was dose-dependent. Radiation-induced DNA damage and/or its repair may not be a prerequisite for the induction of VEGF mRNA.PURPOSE To investigate the induction by carbon- ion irradiation of vascular endothelial growth factor (VEGF) mRNA and protein. MATERIALS AND METHODS RERF-LC-AI lung squamous carcinoma cells were irradiated with carbon ions of either 13.3, 50 or 90keV/microm. Colony formation was used to determine cell survival. VEGF mRNA and protein of the irradiated cells were quantified by Northern blot analysis and ELISA assay, respectively. Genistein, Src tyrosine kinase inhibitor and H7, protein kinase C inhibitor, were used to inhibit VEGF mRNA expression. RESULTS The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and 90keV/microm) was 1.10, 1.97 and 2.30, respectively, in terms of D10 values. Single doses of 15 Gy with either X-rays or carbon ions significantly induced VEGF mRNA expression at 16-24h after irradiation with a maximum induction of 2.81-fold. A significant increase was also observed in VEGF protein levels, detected in culture supernatant 24h after irradiation with 50 and 90keV/microm carbon ions. Neither mRNA nor protein induction showed a dependence on LET. The induction of VEGF mRNA by carbon-ion irradiation was completely inhibited by pretreating cells with genistein and H7, indicating that Src tyrosine kinase and protein kinase C on cell surface membranes is involved in the induction. CONCLUSION Irradiation of lung carcinoma cells with carbon ions induced VEGF mRNA expression and increased protein levels. The induction was dose-dependent. Radiation-induced DNA damage and/or its repair may not be a prerequisite for the induction of VEGF mRNA.

Spontaneous regression of bone metastasis from renal cell carcinoma; A case report

BackgroundSpontaneous regression of metastatic renal cell carcinoma is rarely observed.Case presentationMetastatic renal cell carcinoma was identified in a 70-year-old male using computed tomography-guided percutaneous needle biopsy. Two months after the diagnosis, a partial resection of the sternal bone was performed. Pathological examination revealed granulated tissue with bleeding and necrosis but no carcinogenic cells.ConclusionWe report a pathologically identified case in which a sternal bone metastasis that was noticed two years after radical nephrectomy regressed completely and spontaneously.

The significance of tumour markers as an indication for mediastinoscopy in non‐small cell lung cancer

Objective:  The purpose of this study was to verify the significance of tumour markers as indicators for mediastinoscopy in non‐small cell lung cancer.