Small-Molecule Ferroptotic Agents with Potential to Selectively Target Cancer Stem Cells.

Effective management of advanced cancer requires systemic treatment including small molecules that target unique features of aggressive tumor cells. At the same time, tumors are heterogeneous and current evidence suggests that a subpopulation of tumor cells, called tumor initiating or cancer stem cells, are responsible for metastatic dissemination, tumor relapse and possibly drug resistance. Classical apoptotic drugs are less effective against this critical subpopulation. In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species to induce ferroptosis. Interestingly, we find that drug sensitivity is highest in tumor cells with a mesenchymal phenotype. Furthermore, these compounds showed enhanced toxicity towards mesenchymal breast cancer populations with cancer stem cell properties in vitro. In summary, we have identified a new class of small molecule ferroptotic agents that warrant further investigation.

Small-molecule anticancer agents kill cancer cells by harnessing reactive oxygen species in an iron-dependent manner.

In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species in an iron-dependent manner. Results of the preliminary studies are consistent with the recently described cell death mechanism ferroptosis. Studies are in progress to confirm ferroptosis as the cell death mechanism and to identify the specific molecular targets of these small molecule anticancer agents.

Organizing pneumonia related to electronic cigarette use: A case report and review of literature.

BACKGROUND AND OBJECTIVE: Electronic cigarettes (e cigarettes) are battery operated devices that produce aerosol by heating a solution typically made up of nicotine, propylene glycol, glycerin and flavouring agents. The use of e cigarettes has risen dramatically in recent years especially among adolescents and young adults. These devices have been marketed as safer alternatives to tobacco smoking by their manufactures despite lack of adequate safety data. METHODS: We present a case of 40-year-old female patient who developed significant pulmonary toxicity secondary to e cigarette use and searched existing literature relevant to the case. RESULTS: To our knowledge this is the second reported case of organizing pneumonia and tenth reported case of pulmonary toxicity related to e cigarette use. Our patient presented with symptoms of worsening dyspnoea and intermittent chest pain for past 1 month. She reported increased use of e cigarettes during this time period to help her quit smoking. Patient developed acute hypoxemic respiratory failure requiring intubation and mechanical ventilation. She was diagnosed with organizing pneumonia on open lung biopsy and was successfully treated with steroids along with abstinence from e cigarette use. CONCLUSIONS: As the current data on health effects of e cigarettes is limited, case reports can serve important piece of information in this regard. The use of e cigarettes has increased exponentially in recent years and continue to rise; therefore, physicians should be aware of adverse effects and toxicity related to its use.