Semaphorin 3C as a Therapeutic Target in Prostate and Other Cancers.

The semaphorins represent a large family of signaling molecules with crucial roles in neuronal and cardiac development. While normal semaphorin function pertains largely to development, their involvement in malignancy is becoming increasingly evident. One member, Semaphorin 3C (SEMA3C), has been shown to drive a number of oncogenic programs, correlate inversely with cancer prognosis, and promote the progression of multiple different cancer types. This report surveys the body of knowledge surrounding SEMA3C as a therapeutic target in cancer. In particular, we summarize SEMA3C's role as an autocrine andromedin in prostate cancer growth and survival and provide an overview of other cancer types that SEMA3C has been implicated in including pancreas, brain, breast, and stomach. We also propose molecular strategies that could potentially be deployed against SEMA3C as anticancer agents such as biologics, small molecules, monoclonal antibodies and antisense oligonucleotides. Finally, we discuss important considerations for the inhibition of SEMA3C as a cancer therapeutic agent.

Gender of Department Chair and Paid Parental Leave Benefits in Academic Radiology Residency Programs.

RATIONALE AND OBJECTIVES: Residency training often overlaps with prime childbearing years, yet variability in availability and duration of parental leave in residency can complicate the decision to become parents. Gender disparities in attitudes towards parenthood in residency is well recognized, with females generally reporting more concerns surrounding prolonged training, hindrance of future career plans, and negative perception from peers. However, gender of the department chair has not yet been examined as a factor influencing parental leave policies for residents in Radiology. MATERIALS AND METHODS: The gender of the department chair and parental leave policies for residents in 209 ACGME accredited diagnostic radiology programs across the United States were procured from their websites. These programs were stratified into 6 geographical regions to identify regional differences. Chi-squared analyses were used to compare availability of paid parental benefits with the gender of department chairs. RESULTS: Seventy-seven percent of diagnostic radiology program department chairs were male. 34 of 49 programs (69%) with female department chairs advertised paid parental benefits, compared to 61 of 160 programs (38%) chaired by males (P < 0.001). When stratified by region, this gender difference remained statistically significant in the mid-Atlantic and New England. CONCLUSION: Female gender of the department chair was associated with the increased availability of paid parental leave benefits for residents, yet females hold fewer academic leadership positions than males. Future discussions regarding parental leave policies for residents will have to consider the unique challenges in residency such as length of training and burden on coresidents.

Semaphorin 3 C drives epithelial-to-mesenchymal transition, invasiveness, and stem-like characteristics in prostate cells.

Prostate cancer (PCa) is among the most commonly-occurring cancers worldwide and a leader in cancer-related deaths. Local non-invasive PCa is highly treatable but limited treatment options exist for those with locally-advanced and metastatic forms of the disease underscoring the need to identify mechanisms mediating PCa progression. The semaphorins are a large grouping of membrane-associated or secreted signalling proteins whose normal roles reside in embryogenesis and neuronal development. In this context, semaphorins help establish chemotactic gradients and direct cell movement. Various semaphorin family members have been found to be up- and down-regulated in a number of cancers. One family member, Semaphorin 3 C (SEMA3C), has been implicated in prostate, breast, ovarian, gastric, lung, and pancreatic cancer as well as glioblastoma. Given SEMA3C's roles in development and its augmented expression in PCa, we hypothesized that SEMA3C promotes epithelial-to-mesenchymal transition (EMT) and stem-like phenotypes in prostate cells. In the present study we show that ectopic expression of SEMA3C in RWPE-1 promotes the upregulation of EMT and stem markers, heightened sphere-formation, and cell plasticity. In addition, we show that SEMA3C promotes migration and invasion in vitro and cell dissemination in vivo.