Development of nickel-metal hydride cell

National Space Development Agency of Japan (NASDA) has conducted the research and development (R&D) of battery cells for space use. A new R&D program about a Nickel-Metal Hydride (Ni-MH) cell for space use from this year, based on good results in evaluations of commercial Ni-MH cells in Tsukuba Space Center (TKSC), was started. The results of those commercial Ni-MH cell's evaluations and recent status about the development of Ni-MH cells for space use are described

A case of early-stage lung cancer detected by autofluorescence bronchoscopy

A 71-year-old man was referred to our hospital for further examination of abnormal sputum cytology. No abnormal nodular shadows were detected in chest X-ray and chest CT. The location of the tumor was clearly identified as a defect of autofluorescence by autofluorescence bronchoscopy at the bifurcation between the left B1+2 and B3 bronchi, whereas it was quite difficult by conventional bronchoscopy. Trans bronchial biopsy revealed squamous cell carcinoma. Further examinations yielded the diagnosis of early-stage lung cancer. Photodynamic therapy was performed and complete response was confirmed. This case indicates the efficacy of auto fluorescence bronchoscopy for detecting early-stage lung cancer

Levels of soluble vascular endothelial growth factor receptor 1 are elevated in the exudative pleural effusions

Purpose : Vascular endothelial growth factor (VEGF) plays a critical role in the production of malignant pleural effusions. In the present study, we examined the levels of soluble VEGF receptor-1 (sVEGFR-1) and angiopoietin-2 (Ang-2), as possible regulators of VEGF activity, in transudative and exudative pleural effusions. Methods : Forty-two patients were included in this study : 4 with transudative pleural effusions due to heart failure (HF), 38 with exudative pleural effusions (lung cancer [LC], 22 ; other malignant diseases [MD], 10 ; tuberculosis [TB], 6) . The levels of VEGF, Ang-2, and sVEGFR-1 in the pleural effusions were measured by an enzyme-linked immunosorbent assay. Results : The levels of VEGF, Ang-2, and sVEGFR-1 in exudative effusions were higher than those in transudative effusions. Interestingly, the levels of VEGF and Ang-2 in bloody effusions were significantly higher than those in non-bloody effusions (p < 0.05), but the level of sVEGFR-1 in bloody effusions was lower than that in non-bloody effusions. The levels of VEGF and Ang-2 were significantly higher in the malignant effusions, compared with effusion from HF and TB (p < 0.05). In addition, sVEGFR-1 was significantly higher in the effusion from LC, MD, and TB compared with effusion from HF (p < 0.05). In the malignant effusions, direct correlations were observed among VEGF, sVEGFR-1, and Ang-2. Conclusions : The sVEGFR-1 levels were elevated in exudative pleural effusions, and were lower in bloody effusions than in non-bloody effusions, thus suggesting the regulatory role of sVEGFR-1 in the exudative pleural effusions

Effect of clarythromycin on the distant metastases of human lung cancer cells in SCID mice

Recently, the use of macrolides is suggested to be therapeutically effective in prolonging the survival of patients with inoperable non-small cell lung cancer. The purpose of this study was to examine therapeutic effects of a macrolide, clarythromycin (CAM) on the metastastic developments of two different human non-small cell lung cancers (squamous cell lung carcinoma RERF-LC-AI, and adenocarcinoma PC-14) in severe combined immunodeficient (SCID) mice depleted or undepleted of natural killer (NK) cells, respectively. CAM, injected subcutaneously at doses of 5 and 10 mg/kg body weight/day from day 7 to 41 after i.v. inoculation of human lung cancer cells, was not effective in inhibiting their distant organ metastases in SCID mice. CAM at concentrations of less than 10 μg/ml did not have a direct influence on the proliferation of these tumor cells in vitro. Although CAM alone was not effective in augmenting NK activity, it augmented the IL-2-induced killer (LAK) activity against Daudi cells in vitro. These results suggest that CAM alone may not be enough to control the spread of non-small cell lung cancer in the patient with T cell dysfunction

ヒト ハイガン サイボウ ニヨル ガンセイ キョウスイ ケイセイ ニオケル VEGF Vascular Endothelial Growth Factor ノ イギ

The purpose of this study was to determine the molecular mechanisms that regulate the pathogenesis of malignant pleural effusion (PE) associated with advanced stage human non-small cell lung cancer. Intravenous injection of human PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells into nude mice yielded numerous lung lesions. PC14 PE6 lung lesions invaded the pleura and produced PE containing a high level of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), resulting in vascular hyperpermeability in the thoracic cavity. Lung lesions produced by H226 cells were confined to the lung parenchyma and did not induce PE. The expression of VEGF/VPF mRNA and protein by the cell lines directly correlated with PE formation. Transfection of H226 cells with either sense-VEGF 165 or sense-VEGF 121 genes did not increase cell invasion into the pleura nor induce formation of PE. However, the injection of the VEGF/ VPF-transfected H226 cells into the pleural space resulted in induction of vascular hyperpermeability and PE, indicating that the production of malignant PE requires tumor cells to invade the pleura and express high levels of VEGF/VPF. Therefore, targeting these steps may control malignant PE in lung cancer patients. PTK787, an inhibitor of VEGF/VPF receptor tyrosine kinase phosphorylation, does not affect the in vitro proliferation of PC14PE6 cells. Oral feeding with PTK787 significantly reduced the formation of PE, but not the number of lung lesions of PC14PE6 cells. Furthermore, treatment with PTK787 significantly suppressed vascular hyperpermeability of PE-bearing mice, suggesting that PTK787 reduced PE formation mainly by inhibition of vascular permeability. Therefore, the VEGF/VPF receptor tyrosine kinase inhibitor PTK787 could be useful clinically for the control of malignant PE in lung cancer patients

Autofluorescence bronchoscopy, a novel modality for the early detection of bronchial premalignant and malignant lesions

Lung cancer is the leading cause of cancer deaths in developed countries. Recently, autofluorescence bronchoscopy has been reported to improve the early detection of lung cancer in high-risk individuals. In the present study, we evaluated the efficacy of autofluorescence bronchoscopy for the early detection of bronchial premalignant and malignant lesions. From November 2000 through March 2004, 123 high-risk individuals (114 men and 9 women with a mean age of 68 years) were enrolled. Among 282 biopsy specimens, 93 (33.0%) were premalignant or malignant lesions. The sensitivity and negative predictive value for the detection of bronchial premalignant and malignant lesions were significantly higher with the addition of autofluorescence bronchoscopy than white light bronchoscopy alone. Moreover, the sensitivity for the detection of bronchial premalignant lesions was extremely higher with the addition of autofluorescence bronchoscopy than white light bronchoscopy alone, whereas there was no significant difference between autofluorescence bronchoscopy and white light bronchoscopy alone for the detection of non-malignant and malignant lesions. Autofluorescence bronchoscopy is a novel modality for the early detection of bronchial abnormality, especially for bronchial premalignant lesions

The role of cyclosporin A on antibody-dependent monocytemediated cytotoxicity against human multidrug-resistant cancer cells

A P-glycoprotein (P-gp) inhibitor, cyclosporin A (CsA) was found to enhance the susceptibility of multidrug resistant (MDR) cancer cells to anti-P-gp antibody-dependent cellular cytolysis (ADCC) by monocytes, but the exact mechanism is unknown. In this study, we examined whether CsA enhanced the susceptibility of MDR cells through its inhibitory effect of P-gp function by using anti-ganglioside GM2 (GM2) monoclonal antibody (Ab), KM966, instead of anti-P-gp Ab, MRK16. Monocyte-ADCC induced by both KM966 and MRK16 against P-gp positive human MDR ovarian cancer cells was significantly augmented by addition of CsA. KM966, but not MRK16, induced monocyte-ADCC against P-gp negative human ovarian cancer cells and CsA enhanced this ADCC activity, indicating that suppressive effect of P-gp function by CsA was not essential to the enhancement of ADCC. Moreover, pretreatment of tumor cells with CsA augmented their susceptibility to monocyte-ADCC irrespective of P-gp expression. Interestingly, KM966 or MRK16 induced monocyte-ADCC against various human lung cancer cells expressing either GM2 or P-gp, but CsA did not affect these ADCC. These findings suggest that CsA may enhance the susceptibility to the monocyte-ADCC of ovarian cancer cells, but not of lung cancer cells, irrespective of its suppressive effect of P-gp function

Hepatocyte growth factor reduces susceptibility to an irreversible epidermal growth factor receptor inhibitor in EGFR-T790M mutant lung cancer

金沢大学附属病院がん高度先進治療センターPurpose: The secondary T790M mutation in epidermal growth factor receptor (EGFR) is the most frequent cause of acquired resistance to the reversible EGFR tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib, in lung cancer. Irreversible EGFR-TKIs are expected to overcome the reversible EGFR-TKI resistance of lung cancer harboring T790M mutation in EGFR. However, it is clear that resistance may also develop to this class of inhibitors. We showed previously that hepatocyte growth factor (HGF) induced gefitinib resistance of lung cancer harboring EGFR-activating mutations. Here, we investigated whether HGF induced resistance to the irreversible EGFR-TKI, CL-387,785, in lung cancer cells (H1975) harboring both L858R activating mutation and T790M secondary mutation in EGFR. Experimental Design: CL-387,785 sensitivity and signal transduction in H1975 cells were examined in the presence or absence of HGF or HGF-producing fibroblasts with or without HGF-MET inhibitors. Results: HGF reduced susceptibility to CL-387,785 in H1975 cells. Western blotting and small interfering RNA analyses indicated that HGF-induced hyposensitivity was mediated by the MET/phosphoinositide 3-kinase/Akt signaling pathway independent of EGFR, ErbB2, ErbB3, and ErbB4. Hyposensitivity of H1975 cells to CL-387,785 was also induced by coculture with high-level HGF-producing lung fibroblasts. The hyposensitivity was abrogated by treatment with anti-HGF neutralizing antibody, HGF antagonist NK4, or MET-TKI. Conclusions: We showed HGF-mediated hyposensitivity as a novel mechanism of resistance to irreversible EGFR-TKIs. It will be clinically valuable to investigate the involvement of HGF-MET-mediated signaling in de novo and acquired resistance to irreversible EGFR-TKIs in lung cancer harboring T790M mutation in EGFR. ©2010 AACR