Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2022)

In cancer, autophagy has been shown to promote resistance to chemotherapy by inducing pro-survival mechanisms. This observation has led to basic and clinical studies combining chloroquine, an autophagy inhibitor, with standard chemotherapies. However, the range of particular chemotherapies likely to benefit from this combination remains unclear. Here we apply DrugCell, a deep learning model of the molecular pathways that govern cancer therapeutic response, to systematically prioritize drugs that promote cell survival through the activation of autophagy. Using this approach, we analyze the response of tumor cell lines to 684 drugs, identifying 21 for which resistance or sensitivity is modulated by genetic mutations in autophagy pathways. We systematically screen these prioritized drugs against a fluorescent readout of autophagic flux, confirming that 14 stimulate this pathway and 1 leads to pathway suppression, for a hit rate of 15/22 or 71%. In contrast, only 1 in 6 of a control set of drugs is found to affect autophagy activity. Finally, we test eight of the autophagy activators for synergy with chloroquine treatment, finding that four are highly synergistic, producing a BLISS score greater than 10. These results suggest that, for these drugs (JQ1, tosedostat, leptomycin B, vorinostat), chloroquine inhibition of autophagic flux interferes with autophagy as a survival response.

  • 2 supplemental PDFs
  • 4 supplemental ZIPs
Cover page: A Neural Network Model of Cancer Identifies Chemotherapies Synergistic with Autophagy Inhibition
  • Article
  • Peer Reviewed
UC San Diego Previously Published Works (2020)

Background

An engorged venous plexus may mimic nerve compression from a herniated disk on the magnetic resonance (MR) studies as they both have similar signal intensities. During a laminectomy, if an engorged venous plexus is encountered instead of a disk herniation, there may be marked unanticipated bleeding.

Case description

A 58-year-old female who had a prior anterior lumbar interbody fusion later returned with recurrent radiculopathy. Adjacent segment disease from a spinal disk herniation was suspected based on the surgical history, physical examination, and imaging (MRI) findings. Rather than a disk, an engorged venous plexuses (EVP) was encountered intraoperatively.

Conclusion

Here, we discussed our findings regarding a lumbar EVP rather than a herniated disk and reviewed the current literature. Although rare, a higher index of suspicion for these vascular malformations based on combined historical information and MRI studies should allow one to better detect and/or anticipate an EVP rather than a routine disk.
    Cover page: Engorged venous plexus mimicking adjacent segment disease: Case report and review of the literature
    Top