SCIENCE@home

Human glioblastoma cells exposed to long-term hypoxia and nutrient starvation stimulated induction of secondary T-cell leukemia in mice

T. Osawa,R. Tsuchida,M. Muramatsu,Y. Yuasa,M. Shibuya

Published 2011 in Blood Cancer Journal

ABSTRACT

Secondary leukemia occurs long after remission of the primary tumor with a history of chemo and radiation therapy; however, the mechanism of secondary leukemogenesis is not fully understood.1 In this study, we demonstrate cases of secondary T-cell leukemia in mice after complete regression of xenograft primary glioblastoma independent of chemo and radiotherapy. Recently, antiangiogenic therapy, often in combination with conventional chemotherapy, has been clinically validated for solid tumors.2 Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are major regulators of angiogenesis;3 indeed, a monoclonal anti-VEGF antibody (bevacizumab) and small molecular weight inhibitors of VEGFRs (sorafenib and sunitinib) have improved the therapeutic indexes of advanced malignancies, including the increase in disease-free survival in breast cancer, colorectal cancer, non-small cell lung carcinoma, renal cell carcinoma, hepatocellular carcinoma and glioblastoma. However, antitumor effect of anti-VEGF antibody and VEGF receptor inhibitors concomitant with increased invasiveness, and distant metastasis have been reported using preclinical cancer models.4 In addition, high-grade glioma patients following treatments with anti-VEGF antibody in combination with irinotecan demonstrated an effective response by the primary tumor, but also a high rate of distant tumor progression including tumor infiltration and vascular co-option.5 We previously reported that long-term hypoxia and nutrient starvation double-deprivation cycles increased cellular migration, invasion and distant metastasis in a murine cancer model, suggesting that this extreme tumor microenvironment could be a mechanism of the tumor aggressiveness following antiangiogenic therapy.6

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-10 of 10 references · Page 1 of 1

CITED BY

Showing 1-8 of 8 citing papers · Page 1 of 1