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January 26, 2015Proceedings of the National Academy of Sciences210 citationsOpen Access

Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery

MDMeenal DattaLVLaura E. ViaWKWalid S. Kamoun

Key Points

  • To investigate whether anti-VEGF treatment can normalize granuloma vasculature in tuberculosis and improve drug delivery.
  • Evaluated the effects of bevacizumab on granuloma vasculature
  • Assessed structural and functional changes in vasculature
  • Analyzed small molecule tracer delivery post-treatment.
  • Bevacizumab normalized granuloma vasculature, leading to improved structure and function
  • Enhanced delivery of low-molecular-weight tracers observed post-treatment
  • Indicates potential for better TB treatment outcomes with combined therapies.

Abstract

Significance Tuberculosis (TB) is the second most lethal pathogen worldwide. Pulmonary granulomas are a hallmark of this disease. By discovering similarities between granulomas and solid cancerous tumors, we identified a novel therapeutic target for TB, the abnormal granuloma-associated vasculature that contributes to the abnormal granuloma microenvironment. We then asked if we could “normalize” granuloma vasculature by blocking VEGF signaling, an approach originally shown to enhance cancer treatment. Our results demonstrate that bevacizumab, a widely prescribed anti-VEGF antibody for cancer and eye diseases, is able to create more structurally and functionally normal granuloma vasculature and improve the delivery of a low-molecular-weight tracer. This effect suggests that vascular normalization in combination with anti-TB drugs has the potential to enhance treatment in patients with TB.

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Cite This Study

Datta et al. (2015) studied this question.

synapsesocial.com/papers/69e0816f3dcc343e9cc11f7bhttps://doi.org/10.1073/pnas.1424563112
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