Cisplatin is one of the most widely used anticancer drugs. Its side effects, however, have motivated researchers to search for equally effective analogs that are better tolerated. Selectively targeting cancer tissue is one promising strategy. For this purpose, a platinum(IV) complex was conjugated to the cancer-targeting peptide chlorotoxin (CTX, TM601) in order to deliver cisplatin selectively to cancer cells. The 1:1 Pt-CTX conjugate was characterized by mass spectrometry and gel electrophoresis. Like most platinum(IV) derivatives, the cytotoxicity of the conjugate was lower in cell culture than that of cisplatin, but greater than those of its Pt(IV) precursor and CTX in several cancer cell lines.

Development of multicellular organs requires the coordination of cell differentiation and patterning. Critical for sound detection, the mammalian organ of Corti contains functional units arranged tonotopically along the cochlear turns. Each unit consists of sensory hair cells intercalated by nonsensory supporting cells, both specified and radially patterned with exquisite precision during embryonic development. However, how cell identity and radial patterning are jointly controlled is poorly understood. Here we show that β-catenin is required for specification of hair cell and supporting cell subtypes and radial patterning of the cochlea in vivo. In 2 mouse models of conditional β-catenin deletion, early specification of Myosin7-expressing hair cells and Prox1-positive supporting cells was preserved. While β-catenin-deficient cochleae expressed FGF8 and FGFR3, both of which are essential for pillar cell specification, the radial patterning of organ of Corti was disrupted, revealed by aberrant expression of cadherins and the pillar cell markers P75 and Lgr6. Moreover, β-catenin ablation caused duplication of FGF8-positive inner hair cells and reduction of outer hair cells without affecting the overall hair cell density. In contrast, in another transgenic model with suppressed transcriptional activity of β-catenin but preserved cell adhesion function, both specification and radial patterning of the organ of Corti were intact. Our study reveals specific functions of β-catenin in governing cell identity and patterning mediated through cell adhesion in the developing cochlea.

No abstract

BackgroundThe impact of close surgical margins on oncologic outcomes in HPV‐related oropharyngeal squamous cell carcinoma (HPV + OPSCC) is unclear.MethodsRetrospective case series including patients undergoing single modality transoral robotic surgery (TORS) for HPV + OPSCC at three academic medical centers from 2010 to 2019. Outcomes were compared between patients with close surgical margins (<1 mm or requiring re‐resection) and clear margins using the Kaplan–Meier method.ResultsNinety‐nine patients were included (median follow‐up 21 months, range 6–121). Final margins were close in 22 (22.2%) patients, clear in 75 (75.8%), and positive in two (2.0%). Eight patients (8.1%) recurred, including two local recurrences (2.0%). Four patients died during the study period (4.0%). Local control (p = 0.470), disease‐free survival (p = 0.513), and overall survival (p = 0.064) did not differ between patients with close and clear margins.ConclusionsPatients with close surgical margins after TORS for HPV + OPSCC without concurrent indications for adjuvant therapy may be considered for observation alone.

ACC is a rare malignant tumor of the salivary glands. In this contemporary review, we explore advances in identification of targetable alterations and clinical trials testing these druggable targets. A search of relevant articles and abstracts from national meetings and three databases, including PubMed, Medline, and Web of Science, was performed. Following keyword search analysis and double peer review of abstracts to ensure appropriate fit, a total of 55 manuscripts were included in this review detailing advances in molecular targets for ACC. The most researched pathway associated with ACC is the MYB–NFIB translocation, found to lead to dysregulation of critical cellular pathways and thought to be a fundamental driver in a subset of ACC disease pathogenesis. Other notable molecular targets that have been studied include the cKIT receptor, the EGFR pathway, and NOTCH1, all with limited efficacy in clinical trials. The ongoing investigation of molecular abnormalities underpinning ACC that may be responsible for carcinogenesis is critical to identifying and developing novel targeted therapies.