Müller Cell Regulated Microglial Activation and Migration in Rats With N-Methyl-N-Nitrosourea-Induced Retinal Degeneration

During the pathogenesis of retinitis pigmentosa (RP), the roles of retinal microglial cells after activation have not been fully elucidated. Herein, experimental RP was induced in Sprague Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg, and the effects of MNU on the retinas were evaluated, respectively, by retinal histology and electroretinography recordings at serial time points. Time-dependent and gradual loss of photoreceptor cells, disrupted arrangement of the outer nuclear layer (ONL), and significant reductions in both a-wave and b-wave amplitudes were observed. Morphology changes were observed in retinal microglial cells; meanwhile, with time, the number of Iba1-positive microglia and their infiltration into the ONL gradually increased. Furthermore, physical interaction of microglial-Müller cell processes following microglial activation was observed after MNU injection. In addition, Müller cells increased CX3CL1 secretion, enhanced microglial cell migration, and upregulated the CX3CR1 expression of the latter. Our observations implied that, during the pathogenesis of RP by MNU, microglial cells exhibit a prominent morphology change and Müller cells can induce activated microglia infiltration by increasing secretion of the chemotaxis factor, CX3CL1, and promoting the migration of retinal microglial cells. This novel finding highlights a potential therapeutic target aimed at regulating the microglial response

Combined all‐trans retinoic acid with low‐dose apatinib in treatment of recurrent/metastatic head and neck adenoid cystic carcinoma: A single‐center, secondary analysis of a phase II study

Abstract Background Treatment options are limited for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). We aimed to evaluate the preliminary results of the efficacy and safety of all‐trans retinoic acid (ATRA) combined with low‐dose apatinib in patients with R/M ACCHN according to a secondary analysis of a phase II study. Methods Patients from a phase II study (NCT02775370) who orally administered 500 milligram (mg) apatinib daily until treatment‐related adverse events (AEs) intolerance or progression occurred were eligible for inclusion. Patients were further treated with combination therapy of ATRA (25 mg/m2/day) and apatinib (250 mg/day) between March 2019 and October 2021 until progression of disease (PD). Results A total of 16 patients were included with nine (56.3%) males and aged 35–69 years old. All recruited patients previously received anti‐angiogenic therapy then withdrew due to toxicities or progression occurred. The objective response rate (ORR) and disease control rate (DCR) were 18.8% and 100%, respectively. During a median follow‐up of 23.9 months (range:17.8–31.7 months), 11 (68.8%) patients developed PD and one of them died in 20.9 months. The median of progression‐free survival (PFS) was 16.3 months (95% CI: 7.2–25.4 months), and the 6‐month, 12‐month, and 24‐month PFS rates were 100%, 81.3%, and 33.3%, respectively. The grade 3 adverse events were albuminuria (n = 2, 12.5%) and hand‐foot syndrome (n = 1, 6.25%). Conclusion All‐trans retinoic acid combined with low‐dose apatinib might be a potential efficacy therapeutic option for patients with R/M ACCHN. This finding will be further confirmed by our registered ongoing trial, the APLUS study (NCT 04433169)

Adjuvant PD-1 antibody in recurrent, previously irradiated oral cavity cancer treated with salvage surgery

Objectives: The role of re-irradiation after salvage surgery for recurrent oral cavity cancer (OCC) is controversial. We evaluated the efficacy and safety of adjuvant toripalimab (PD-1 antibody) in this patient setting. Materials and methods: In this phase II study, patients after salvage surgery with OCC occurring in an area of previously irradiated were enrolled. Patients received toripalimab 240 mg once every 3 weeks for 12 months, or combined with S-1 orally for 4–6 cycles. The primary endpoint was 1-year progression-free survival (PFS). Results: Between April 2019 and May 2021, 20 patients were enrolled. Sixty percent patients had ENE or positive margins, 80% were restaged as stage IV, and 80% were previously treated with chemotherapy. The 1-year PFS and overall survival (OS) were 58.2%, and 93.8%, respectively, for patients with CPS ≥ 1, which was significantly better than those of the real-world reference cohort (p = 0.001 and 0.019). No grade 4–5 toxicities were reported, and only one patient experienced grade 3 immune related adrenal insufficiency and discontinued treatment. The 1-year PFS and OS were significantly different for patients with CPS < 1, CPS 1–19 and CPS ≥ 20 (p = 0.011 and 0.017, respectively). The peripheral blood B cell proportion was also correlated with PD in 6 months (p = 0.044). Conclusion: Adjuvant toripalimab or combine with S-1 after salvage surgery showed improved PFS compared with a real-world reference cohort in recurrent, previously irradiated OCC, and favorable PFS were observed in patients with a higher CPS and peripheral B cell proportion. Further randomized trials are warranted

Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma

With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia–Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education