Cancer represents a large group of diseases accounting for nearly 10 million deaths each year. Various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, and immunotherapy, have been applied for cancer treatment. However, the outcomes remain largely unsatisfying. Melatonin, as an endogenous hormone, is associated with the circadian rhythm moderation. Many physiological functions of melatonin besides sleep–wake cycle control have been identified, such as antioxidant, immunomodulation, and anti-inflammation. In recent years, an increasing number of studies have described the anticancer effects of melatonin. This has drawn our attention to the potential usage of melatonin for cancer treatment in the clinical setting, although huge obstacles still exist before its wide clinical administration is accepted. The exact mechanisms behind its anticancer effects remain unclear, and the specific characters impede its in vivo investigation. In this review, we will summarize the latest advances in melatonin studies, including its chemical properties, the possible mechanisms for its anticancer effects, and the ongoing clinical trials. Importantly, challenges for the clinical application of melatonin will be discussed, accompanied with our perspectives on its future development. Finally, obstacles and perspectives of using melatonin for cancer treatment will be proposed. The present article will provide a comprehensive foundation for applying melatonin as a preventive and therapeutic agent for cancer treatment.

Background: Oral squamous cell carcinomas are one of the most common cancers worldwide with aggressive behavior and poor prognosis. Reactive oxygen species (ROS) are associated with cancer and cause various types of regulated cell death (RCD). Inducing the RCD pathway by modulating ROS levels is imperative to conquer cancers. The aim of this study is to investigate the synergistic anticancer effects of melatonin and erastin on ROS modulation and subsequent RCD induction. Methods: Human tongue squamous cell carcinoma cell lines (SCC-15 cells) were treated with melatonin, erastin, or their combination. Cell viability, ROS levels, autophagy, apoptosis, and ferroptosis levels were tested according to the results of the PCR array, which were verified with/without the induction and inhibition of ROS by H₂O₂ and N-acetyl-L-cysteine, respectively. In addition, a mouse-based subcutaneous oral cancer xenograft model was constructed to identify the effects of melatonin, erastin, and their combination on the autophagy, apoptosis, and ferroptosis levels in isolated tumor tissues. Results: ROS levels were increased by the administration of melatonin at high concentrations (mM), and the combination of melatonin with erastin enhanced the levels of malonic dialdehyde, ROS, and lipid ROS, and reduced the levels of glutamate and glutathione. SQSTM1/p62, LC3A/B, cleaved caspase-3, and PARP1 protein levels in SCC-15 cells were also increased by melatonin plus erastin treatment, which further increased as ROS accumulated, and decreased as ROS levels were suppressed. Combined treatment of melatonin and erastin markedly reduced the tumor size in vivo, demonstrated no obvious systemic side effects, and significantly enhanced the apoptosis and ferroptosis levels in the tumor tissues, in parallel with decreased autophagy levels. Conclusions: Melatonin combined with erastin exhibits synergistic anticancer effects without adverse reactions. Herein, this combination might become a promising alternative strategy for oral cancer treatment. Graphical

Computer assisted head and neck reconstruction has gained popularity over the past few years. In computer assisted surgery (CAS), surgical margins are predetermined in virtual surgery and resection guides are designed to be fitted intra-operatively. However, concerns have been raised regarding the oncological safety of predetermined surgical margins. Therefore, the aim of this study was to compare surgical margins, recurrence and survival outcomes in patients underwent CAS and non-CAS in head and neck reconstruction. We retrospectively reviewed the patients underwent oral and maxillofacial malignancies surgical excision and free flap reconstruction from October 2014 to December 2019 by the same chief surgeon. Patients were divided into two groups depending on whether CAS and predetermined surgical margins were adopted. The primary outcome was surgical resection margin and the secondary outcomes included recurrence and survival. A total of 66 subjects were recruited with 37 in the CAS group and 29 in the non-CAS group. The follow-up rate was 100%. The average follow-up time was 24.5 months. No significant difference in resection margin was identified between the groups (p = 0.387). Tumor staging, margin status, perineural invasion, lymphovascular invasion and extranodal extension were identified as significant factors influencing survival. Both before and after adjustment for these prognostic factors identified, CAS and non-CAS group showed no significant difference in survival outcome. Predetermined surgical margins do not compromise oncological safety in terms of resection margin, disease recurrence and patient survival.

Spatial deviations of the temporomandibular joint (TMJ) after oncological mandibular reconstruction are important to the aesthetic and functional rehabilitation. The aim of this study was to clarify whether and how three dimensionally (3D) printed patient-specific surgical plates, and the preservation of the condyle or ramus, affect spatial deviations of the TMJ. A total of 33 patients who underwent mandibular reconstruction via computer-assisted surgery were included. Regarding absolute deviations, patients in the 3D-printed plate group showed smaller TMJ deviations compared to those in the conventional plate group. There was no difference in absolute deviations of the TMJ regardless of whether the condyle or ramus was preserved. Regarding physiological deviations, the impact on the contralateral TMJ was smaller in the 3D-printed plate group. Patients with both the condyle and ramus removed had significantly higher deviations of the condyle and joint space. In summary, 3D-printed patient-specific surgical plates improved the spatial accuracy of the TMJ. Under physiological conditions, TMJ deviations on the operated side were mainly affected by the preservation of the condyle. Removal of both the condyle and ramus caused more severe spatial interference to the TMJ; this should be further confirmed.