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

Establishment of Monitoring System to Detect Single Copy DNA Included in One Genome but not in Another Using Representational Difference Analysis

Polyrnerase chain reaction (PCR) -coupled subtractive procedure, representa-tional difference analysis (RDA) , is an efficient method to find the differences between two complex genomes. RDA has been applied to detect genetic lesions in cancer, the identification of unknown pathogens from the genomes, and the isolation of polymorphic markers. However, characterization of various clones obtained by RDA is time consuming and laborious work, and it is of great impor-tance to monitor whether RDA really works. To establish a monitoring system to detect single copy target DNA, we studied whether RDA could detect four fragments of non-human DNA which were added in one genome but not in another. We were able to successfully detect the target DNAs which were mixed at the ratio of single and ten copies per haploid genome using RDA with some modification of the original protocol. We confirmed that RDA was sensi-tive and effective enough to detect such genetic lesions as occurred in cancer cells. The target DNA used in this model could be utilized as a positive control in other applications of RDA

Intensification therapy with anti-parathyroid hormone-related protein antibody plus zoledronic acid for bone metastases of small cell lung cancer cells in severe combined immunodeficient mice

金沢大学附属病院がん高度先進治療センターBone metastases occur in more than one-third of patients with advanced lung cancer and are difficult to treat. We showed previously the therapeutic effect of a third-generation bisphosphonate, minodronate, and antiparathyroid hormone-related protein (PTHrP) neutralizing antibody on bone metastases induced by the human small cell lung cancer cell line, SBC-5, in natural killer cell-depleted severe combined immunodeficient mice. The purpose of our current study was to examine the effect of the combination of PTHrP antibody and zoledronic acid, which has been approved to treat bone metastases, against bone metastases produced by SBC-5 cells expressing PTHrP. Treatment with PTHrP antibody and/or zoledronic acid did not affect the proliferation of SBC-5 cells in vitro. Repeated treatments with either PTHrP antibody or zoledronic acid inhibited the formation of osteolytic bone metastases of SBC-5 cells but had no effect on metastases to visceral organs. Importantly, combined treatment with PTHrP antibody and zoledronic acid further inhibited the formation of bone metastases. Histologic assays showed that, compared with either PTHrP antibody or zoledronic acid alone, their combination decreased the number of tumor-associated osteoclasts and increased the number of apoptotic tumor cells. These findings suggest that this novel dual-targeting therapy may be useful for controlling bone metastases in a subpopulation of small cell lung cancer patients. Copyright © 2009 American Association for Cancer Research.全文公開20100

Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab

Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy

The Rise And Development Of The Fruit Industry On The Okayama Plain.

PhDGeographyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/182060/2/5803682.pd