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Basal cell carcinoma (BCC) is a locally invasive epithelial cancer that is primarily driven by the Hedgehog (HH) pathway. Advanced BCCs are a critical subset of BCCs that frequently acquire resistance to Smoothened (SMO) inhibitors and identifying pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify a PI3K pathway expression signature in BCC. Pharmacological inhibition of PI3K activity in BCC cells significantly reduces cell proliferation and HH signaling. However, treatment of Ptch1fl/fl; Gli1-CreERT2 mouse BCCs with the PI3K inhibitor BKM120 results in a reduction of tumor cell growth with no significant effect on HH signaling. Downstream PI3K components aPKC and Akt1 showed a reduction in active protein, whereas their substrate, cyclin-dependent kinase inhibitor p21, showed a concomitant increase in protein stability. Our results suggest that PI3K promotes BCC tumor growth by kinase-induced p21 degradation without altering HH signaling.

Background: Expenditures for postacute care in total joint arthroplasty (TJA) have risen dramatically over recent decades. Therefore, efforts are underway to better identify cost savings in postacute rehabilitation centers, such as skilled nursing facilities (SNFs). The primary purpose of this study was to analyze gait training achievements in post-TJA patients in the interval between hospital discharge and the patients’ first 4 days at the SNF. Identification of potential losses in therapeutic progress may lead the way for improved patient care, outcomes, and cost savings. Our hypothesis is that patients discharged to an SNF will have a decline in gait achievements upon transfer from the hospital. Methods: A total of 68 patients who underwent TJA were included. The total distance ambulated during physical therapy (PT) was recorded for the last day of hospital therapy and the first 4 days at the SNF as well as the reported visual analog scale (VAS) pain scores. Results: There was a 73% decline in distance ambulated on SNF day 0 ( Hospital: 138.6 ft vs SNF: 37.9 ft; P < .001) and a 50% decline on SNF day 1 ( Hospital: 103.0 ft; SNF vs 51.1 ft; P < .001) compared to the last hospital session. There were no significant differences in distance walked on SNF days 3 and 4 relative to the last hospital session. The VAS pain scores did not significantly differ on SNF days 0 and 1 compared to the last hospital day but began to significantly decline on SNF day 3 ( Hospital: 4.9; SNF: 3.3; P = .02) and day 4 ( Hospital: 3.9; SNF: 2.3; P = .03). Conclusion: There was a significant decline in ambulatory proficiency in post-TJA patients on the day of and the day following hospital discharge to an SNF. These deficits cannot be attributed to heightened pain levels. Early and progressive ambulation is a recognized component of appropriate PT following TJA. This study therefore highlights the transition from hospital to SNF as a crucial and novel target for improvement in post-TJA care.