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Abstract: Alpha-melanocyte stimulating hormone (α-MSH) plays a crucial role in the regulation of immune and inflammatory reactions. Here we report that SVα-MSH, a novel α-MSH analog, could ameliorate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in a preventive and therapeutic manner. SVα-MSH treatment induced the production of regulatory T (Treg) cells and reduced the Th17 cells in the CNS of EAE mice. SVα-MSH-treated PLP peptide 139–151-specific T cells showed a down-regulation of T cell activation markers CD69 and CD134. SVα-MSH did not induce apoptosis but blocked the G1/S phase transition, reduced the expression of cyclin E, Cdk2 and the activity of NFAT and AP-1 transcription factors. Thus, SVα-MSH acts as a novel immunotherapeutic approach in the treatment of autoimmune attack on the CNS. [Copyright &y& Elsevier]

Background: Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer. There is currently a lack of data on the dynamic expression of genes related to bone remodeling during the development of mandibular ORN. This study aimed to establish an animal model of ORN in Sprague Dawley (SD) rats, detect the expression of genes related to bone metabolism, observe morphological changes, and clarify the mechanism of ORN., Methods: A total of 24 male SD rats in group 1 were randomly divided into four groups (n=6/group): group a, normal control; group b, simple tooth extraction; group c, simple radiation; and group d, radiation extraction group. The right mandible of rats in groups c and d was irradiated with a single dose of 35 Gy. The right mandibles were taken from each group for morphological observation 90 days after irradiation. SD rats in group 2 (n=144) were randomly divided into four groups (in similar fashion to group 1 but with groups a', b', c', and d'). Samples were collected at six time points after irradiation. Histopathological changes were observed, and Western blotting (WB) was used to analyze protein expression., Results: The formation of dead bone and pathological fracture was visible under micro-computed tomography (micro-CT), and tissue biopsy showed late fibrosis repair. In group d', osteogenesis and osteoclasis coexisted in the early irradiation stage. Vascular endothelial growth factor (VEGF) receptor expression was lower in groups c' and d' than in group a'. On day 45, runt-related transcription factor 2 (RUNX2) expression in group d' was lower than that in the other groups. The ratio of receptor activator of nuclear factor-κβ ligand to osteoprotegerin (RANKL:OPG) differed significantly among groups b', c', and d' on the 45th day (d' > c' > b')., Conclusions: Radiation and vascular function damage resulted in the lower expression of VEGF. The first 15 days after radiation was mainly characterized by new bone formation. After 15 days, bone resorption increased. Tooth extraction trauma can aggravate the bone metabolism imbalance and promote ORN occurrence. These findings shed light on the mechanism of ORN., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-47/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Paclitaxel (PTX) is capable of aggravating radiation-induced pulmonary fibrosis (RIPF), but the mechanism is unknown. Spry2 is a negative regulator of receptor tyrosine kinase-related Ras/Raf/extracellular signal regulated kinase (ERK) pathway. This experiment was aimed at exploring whether the aggravation of RIPF by PTX is related to Spry2. The RIPF model was established with C57BL/6 mice by thoracic irradiation, and PTX was administered concurrently. Western blot was used to detect the expression level of ERK signaling molecules and the distribution of Spry2 in the plasma membrane/cytoplasm. Co-immunoprecipitation (co-IP) and immunofluorescence were used to observe the colocalization of Spry2 with the plasma membrane and tubulin. The results showed that PTX-concurrent radiotherapy could aggravate fibrotic lesions in RIPF, downregulate the content of membrane Spry2, and upregulate the levels of p-c-Raf and p-ERK in lung tissue. It was found that knockdown of Spry2 in fibroblast abolished the upregulation of p-c-Raf and p-ERK by PTX. Both co-IP results and immunofluorescence staining showed that PTX increased the binding of Spry2 to tubulin, and microtubule depolymerizing agents could abolish PTX's inhibition of Spry2 membrane distribution and inhibit PTX's upregulation of Raf/ERK signaling. Both nintedanib and ERK inhibitor were effective in relieving PTX-exacerbated RIPF. Taken together, the mechanism of PTX's aggravating RIPF was related to its ability to enhance Spry2's binding to tubulin, thus attenuating Spry2's negative regulation on Raf/ERK pathway. SIGNIFICANCE STATEMENT: This study revealed that paclitaxel (PTX) concurrent radiation therapy exacerbates radiation-induced pulmonary fibrosis during the treatment of thoracic tumors, which is associated with PTX restraining Spry2 and upregulating the Raf/extracellular signal regulated kinase signaling pathway, and provided drug targets for mitigating this complication., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC)., Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologically confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1., Findings: Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade ≥3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported., Conclusion: In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167., Funding: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015)., Competing Interests: Junyou Ge, Yan Qing and Dekang Zong are employees of Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd (Chengdu, China). All other authors declare no potential conflicts of interest., (© 2022 The Author(s).)

Objective: To explore the effectof tumor volume on pulmonary dose-volume parameters by intensity-modulated radiation therapy (IMRT) in non-small cell lung cancer (NSCLC), and to provide a basis for pulmonary dose parameters in IMRT treatment.
 Methods: A total of 204 patients with NSCLC received IMRT were retrospectively analyzed from June, 2009 to October, 2013. The prescribed dose of planning target volume (PTV) for primary tumor was 60-66Gy (2.00-2.25 Gy, 27-33 times in all). The fractional volume percent of the lung received a dose >5 or 20 Gy (V5, V20), and absolute volume of lung received a dose <5 Gy (AVS5).The mean lung dose (MLD) in normal tissues were analyzed. Regression model curve was used to analyze them along with the change of primary tumor volume.
 Results: With the increase in lung tumor volume, the V5, V20 and MLD presented quadratic equation curve, and AVS5 presented logarithmic equation. When the tumor volume, less than a certain value (294.6, 283.2, 304.9 cm3, respectively), the V5, V20 and MLD increased with tumor size and presented an increased quadratic curve; when the tumor volume was higher than a certain value (294.6, 283.2, 304.9 cm3 respectively), the V5, V20 and MLD was declined. The AVS5 was declined in a logarithmic curve along with the increase of tumor volume.
 Conclusion: With the increase in lung tumor volume, the change in rule of V5, V20, MLD and AVS5 is not completely equivalent. When the tumor volume exceeds a certain boundary value (about 300 cubic centimeter), the corresponding tumor diameter is about 7-8 cm. In addition to the focus on pulmonary V5, V20 and MLD, we should also pay more attention to AVS5 restrictions in establishment of IMRT in NSCLC.

Objective: To investigate the relationship between nutritional status and acute radiotoxicity of patients with head and neck cancer., Methods: Nutritional status and acute radiotoxicities of 130 head and neck cancer patients were prospectively surveyed during the 4th week of radiotherapy. Relationships between nutritional status and acute radiotoxicities were analyzed by canonical correlation., Results: The first canonical correlation coefficient was 0.653, statistically significant, which showed that some negative relationships were found between nutritional status (such as serum prealbumin, transferring, lymphocytes, lymphocyte percentage) and acute radiotoxicities (such as dry mouth, throat/sore throat, fatigue, radiation dermatitis) of head and neck cancer patients., Conclusion: When the detection value of serum prealbumin, transferrin, lymphocytes, lymphocyte percentage was below the normal, the appropriate nutritional support would be given to improve immunity and to relieve the acute radiotoxicitoes.