Personalized Treatment of Recurrent, Metastatic Head and Neck Cancer Guided by Patient-Derived Xenograft Models.

Recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) is associated with a poor prognosis and short survival duration. There is an urgent need to identify personalized predictors of drug response to guide the selection of the most effective therapy for each individual recurrence. We tested the feasibility of patient-derived xenografts (PDX) for guiding their RMHNSCC salvage treatment. Fresh tumor samples from eligible, consented patients were implanted into mice. Established tumors were expanded in mouse PDX cohorts to identify responses to candidate salvage drug treatments in parallel testing. Patients alive and suitable for chemotherapy were treated based on responses determined by PDX testing. Nine patient tumors were successfully engrafted in mice with an average time of 89.2±41.7 days. Four patients' PDX models underwent parallel drug testing. Two patients received PDX-guided therapy. In one of these patients, single agents of cetuximab and paclitaxel demonstrated the best responses in the PDX model, and this patient exhibited sequential partial responses to each drug, including a 17-month clinical response to cetuximab. The main limitation of PDX testing for RMHNSCC was the time delay in obtaining testing results. Despite this, parallel PDX testing may be feasible for a subset of patients and appears to correlate with clinical benefit.

An Electronic Information Kiosk for Enhancing Patient Accrual for Cancer Clinical Trials: A Pilot and Feasibility Study.

Introduction Low accrual to clinical trials for solid tumors at our institution led to a review of possible modifiable factors within our control. This led to a pilot project to determine whether improved patient awareness could alter accrual rates to active trials. Methods An information kiosk was located at the patient library on the ground floor of the London Regional Cancer Program. Adult cancer patients were invited to learn more about clinical trials from our research navigator, including specific trials open in our center, and to participate in the study, which involved a brief satisfaction and demographics survey. Results Three hundred and eighty-six (386) patients interacted with the clinical trial information kiosk over the eight weeks it was open. Of these, 32 patients consented and filled out surveys, which indicated an overall positive interaction with the kiosk. Unfortunately, in the time period examined, clinical trial accrual rates appeared to decrease when the pre- and post-kiosk activation periods were compared (44 versus 37 patients accrued to various trials). Conclusion Our pilot study found that the implementation of a clinical trial information kiosk was easy to understand and useful for patients to learn more about clinical trials. Barriers to this patient satisfaction translating into increased accrual rates in our center included suboptimal kiosk location and lack of guidance to the kiosk from clerical staff. High patient satisfaction scores support the potential value of permanent clinical trial information kiosks in our cancer center, but this requires increased attention to visibility, location, and staff education.

Tn5 transposition in Escherichia coli is repressed by Hfq and activated by over-expression of the small non-coding RNA SgrS.

BACKGROUND: Hfq functions in post-transcriptional gene regulation in a wide range of bacteria, usually by promoting base pairing of mRNAs with trans-encoded sRNAs. It was previously shown that Hfq down-regulates Tn10 transposition by inhibiting IS10 transposase expression at the post-transcriptional level. This provided the first example of Hfq playing a role in DNA transposition and led us to ask if a related transposon, Tn5, is similarly regulated. RESULTS: We show that Hfq strongly suppresses Tn5 transposition in Escherichia coli by inhibiting IS50 transposase expression. However, in contrast to the situation for Tn10, Hfq primarily inhibits IS50 transposase transcription. As Hfq does not typically function directly in transcription, we searched for a transcription factor that also down-regulated IS50 transposase transcription and is itself under Hfq control. We show that Crp (cyclic AMP receptor protein) fits these criteria as: (1) disruption of the crp gene led to an increase in IS50 transposase expression and the magnitude of this increase was comparable to that observed for an hfq disruption; and (2) Crp expression decreased in hfq (-) . We also demonstrate that IS50 transposase expression and Tn5 transposition are induced by over-expression of the sRNA SgrS and link this response to glucose limitation. CONCLUSIONS: Tn5 transposition is negatively regulated by Hfq primarily through inhibition of IS50 transposase transcription. Preliminary results support the possibility that this regulation is mediated through Crp. We also provide evidence that glucose limitation activates IS50 transposase transcription and transposition.