Summary Squamous cell carcinomas (SCCs) are heterogeneous tumors that are sustained by tumor propagating cancer cells (TPCs). SCCs frequently resist chemotherapy through mechanisms that are still unknown. Here, we combine H2BGFP based pulse-chasing with cell surface markers to distinguish quiescent from proliferative TPCs within SCCs. We find that quiescent TPCs resist DNA damage and exhibit increased tumorigenic potential in response to chemotherapy, whereas proliferative TPCs undergo apoptosis. Quiescence is regulated by TGFβ/SMAD signaling, which directly regulates cell cycle gene transcription to control a reversible G1 cell cycle arrest, independent of p21CIP function. Indeed, genetic or pharmacological TGFβ inhibition increases the susceptibility of TPCs to chemotherapy as it prevents entry into a quiescent state. These findings provide direct evidence that TPCs can reversibly enter a quiescent, chemoresistant state which underscores the need for combinatorial approaches to improve treatment of chemotherapy-resistant SCCs.

Although the principles that balance stem cell self-renewal and differentiation in normal tissue homeostasis are beginning to emerge, it is still unclear whether cancer cells with tumor initiating potential are similarly governed, or whether they have acquired distinct mechanisms to sustain self-renewal and long-term tumor growth. Here we show that the transcription factor Sox2, which is not expressed in normal skin epithelium and is dispensable for epidermal homeostasis, marks tumor initiating cells (TICs) in cutaneous squamous cell carcinomas (SCC). We demonstrate that Sox2 is required for SCC growth in mouse and human, where it enhances Nrp1/Vegf signaling to promote the expansion of TICs along the tumor-stroma interface. Our findings suggest that distinct transcriptional programs govern self-renewal and long-term growth of TICs and normal skin epithelial stem and progenitor cells. These programs present promising diagnostic markers and targets for cancer specific therapies.

Objective: Our aim is to emphasize the varied presentation of acute disseminated encephalomyelitis (ADEM) to help health care professionals improve recognition of the disease in a timely manner, thereby allowing for the selection of an appropriate treatment regimen. Therefore, this may avoid neurocognitive consequences and the ultimate fatality of the patient.Patients and Methods: This is a retrospective case series involving 7 cases of children presenting to the Pediatric Emergency Department of Hackensack University Medical Center who were ultimately diagnosed with ADEM.Results: In many of the cases, a preceding viral-like illness with nonspecific symptomatology made it difficult to accurately establish an initial diagnosis. Ultimately, the neurologic symptoms spontaneously resolved or improved with administration of high-dose steroids. Conclusions:Children presenting to the emergency department with nonspecific symptoms associated with any neurological deficits should undergo further investigation using magnetic resonance imaging and lumbar puncture to rule out rare yet possibly fatal diseases such as ADEM.