25 research outputs found
Multidisciplinary Management of Locally Advanced and Metastatic Cutaneous Squamous Cell Carcinoma
Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cSCC) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cSCC face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist. Patients with advanced cSCC are often deemed ineligible for either or both of curative surgery and radiation therapy (RT) and, until recently, were limited to off-label systemic cisplatinâfluorouracil or cetuximab therapy, which offers modest clinical benefits and potentially severe toxicity. A new systemic therapy, cemiplimab, has been approved for the treatment of locally advanced and metastatic cSCC. In the present review, we provide recommendations for patient classification and staging based on current guidelines, direction for determining patient eligibility for surgery and RT, and an overview of the available systemic treatment options for advanced cSCC and of the benefits of a multidisciplinary approach to patient management
Quality-of-life analysis with intermittent vismodegib regimens in patients with multiple basal cell carcinomas: patient-reported outcomes from the MIKIE study
International audienc
Qualityâofâlife analysis with intermittent vismodegib regimens in patients with multiple basal cell carcinomas: patientâreported outcomes from the MIKIE study
International audienc
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Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis.
A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and nonâfollicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell selfârenewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering