Effects of Cyclical Intermittent Hypoxia on Local (Primary Breast) and Distal (Metastases to the brain) tumors

2016 ABSM Junior Faculty Research Grant

Diane Lim, MD
University of Pennsylvania

Key Project Outcome

The AASM Foundation grant supported important work where we developed a triple transgenic mouse model of lung cancer using a Cre virus to turn on cancer. These mice were then exposed to cyclical intermittent hypoxia (CIH, the underlying problem of obstructive sleep apnea) and we demonstrated that this made the lung cancer progress more compared to mice not exposed to CIH.

We then improved this model by using more specific Cre viruses to turn on lung cancer within the type 2 alveolar cell or the Club cell. In addition, we were successful in developing 4 clone cancer cells, and we have almost completed the characterization of each clone cell in regards to primary cancer/survival curve and metastastic profiles.

Detecting micrometastases in organs outside the lung has proven to be technically very difficult, but we have worked on better immunohistochemistry techniques to improve sensitivity of detecting metastases and we are still working on more sensitive PCR techniques to provide quantitative load of metastases. Because this mouse model of lung cancer is immunocompetent we are able to assess the effects of checkpoint inhibitors on tumor progression both when exposed to CIH and compared to Sham (room air).

Journal Articles


S Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse