Functional morphology of the pharyngeal teeth of the ocean sunfish, Mola mola.

Many fish use a set of pharyngeal jaws in their throat to aid in prey capture and processing, particularly of large or complex prey. In this study-combining dissection, CT scanning, histology, and performance testing-we demonstrate a novel use of pharyngeal teeth in the ocean sunfish (Mola mola), a species for which pharyngeal jaw anatomy had not been described. We show that sunfish possesses only dorsal pharyngeal jaws where, in contrast to their beaklike oral teeth, teeth are recurved spikes, arranged in three loosely connected rows. Fang-like pharyngeal teeth were tightly socketed in the skeletal tissue, with shorter, incompletely-formed teeth erupting between, suggesting tooth replacement. Trichrome staining revealed teeth anchored into their sockets via a combination of collagen bundles originating from the jaw connective tissue and mineralized trabeculae extending from the teeth bases. In resting position, teeth are nearly covered by soft tissue; however, manipulation of a straplike muscle, running transversely on the dorsal jaw face, everted teeth like a cat's claws. Adult sunfish suction feed almost exclusively on gelatinous prey (e.g., jellyfish) and have been observed to jet water during feeding and other activities; flume experiments simulating jetting behavior demonstrated adult teeth caught simulated gelatinous prey with 70%-100% success, with the teeth immobile in their sockets, even at 50x the jetting force, demonstrating high safety factor. We propose that sunfish pharyngeal teeth function as an efficient retention cage for mechanically challenging prey, a curious evolutionary convergence with the throat spikes of divergent taxa that employ spitting and jetting.

A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer.

Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor responses in subcutaneous and orthotopic cancer models and results in complete regression of carcinogen-induced premalignant lesions. In a phase 1/2, open-label, single-arm trial (NCT03502148), primary endpoints of efficacy (≥30% tumor volume reduction) and safety (incidence of DLTs) of neoadjuvant PRV111 were reached, with 69% tumor reduction in ~7 days and over 87% response rate. Secondary endpoints (cisplatin biodistribution, loco-regional control, and technical success) were achieved. No DLTs or drug-related serious adverse events were reported. No locoregional recurrences were evident in 6 months. Integration of PRV111 with current standard of care may improve health outcomes and survival of patients with OCSCC.