Apatinib combined with camrelizumab in the treatment of recurrent/metastatic nasopharyngeal carcinoma: a prospective multicenter phase II study.

Background: Preclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). Methods: Patients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190. Results: This study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths. Conclusion: In patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities.

Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation.

During mesenchymal development, the sources of mechanical forces transduced by cells transition over time from predominantly cell-cell interactions to predominantly cell-extracellular matrix (ECM) interactions. Transduction of the associated mechanical signals is critical for development, but how these signals converge to regulate human mesenchymal stem cells (hMSCs) mechanosensing is not fully understood, in part because time-evolving mechanical signals cannot readily be presented in vitro. Here, we established a DNA-driven cell culture platform that could be programmed to present the RGD peptide from fibronectin, mimicking cell-ECM interactions, and the HAVDI peptide from N-cadherin, mimicking cell-cell interactions, through DNA hybridization and toehold-mediated strand displacement reactions. The platform could be programmed to mimic the evolving cell-ECM and cell-cell interactions during mesenchymal development. We applied this platform to reveal that RGD/integrin ligation promoted cofilin phosphorylation, while HAVDI/N-cadherin ligation inhibited cofilin phosphorylation. Cofilin phosphorylation upregulated perinuclear apical actin fibers, which deformed the nucleus and thereby induced YAP nuclear localization in hMSCs, resulting in subsequent osteogenic differentiation. Our programmable culture platform is broadly applicable to the study of dynamic, integrated mechanobiological signals in development, healing, and tissue engineering.

Environmentally Compatible Wearable Electronics Based on Ionically Conductive Organohydrogels for Health Monitoring with Thermal Compatibility, Anti-Dehydration, and Underwater Adhesion.

Hydrogel-based electronics have found widespread applications in soft sensing and health monitoring because of their remarkable biocompatibility and mechanical features similar to human skin. However, they are subjected to potential challenges like structural failure, functional degradation, and device delamination in practical applications, especially facing extreme environmental conditions (e.g., abnormal temperature and humidity). To address these, ionically conductive organohydrogel-based soft electronics are developed, which can perform at subzero and elevated temperatures (thermal compatibility) as well as at dehydrated and hydrated environments (hydration compatibility) for extended applications. More specifically, gelatin/poly(acrylic acid-N-hydrosuccinimide ester) (PAA-NHS ester)-based ionic-conductive organohydrogel is synthesized. By introducing a glycerol-water binary solvent system, the gel can maintain mechanical softness in a wide temperature range (from -80 to 60 °C). Besides, excellent conductivity is achieved under various conditions by soaking the gel into lithium chloride anhydrous (LiCl) solution. Strong adhesion with skin, even under water, can be realized by covalent bonds between NHS ester from gel and amino groups from human skin. The excellent performances of LiCl-loaded PAA-based organohydrogel (L-PAA-OH)-based electronics are further demonstrated under freezing and high temperatures as well as underwater conditions, unveiling their promising prospects in wearable health monitoring in various conditions.

Efficacy and safety of intensity-modulated radiotherapy alone versus intensity-modulated radiotherapy plus chemotherapy for treatment of intermediate-risk nasopharyngeal carcinoma.

BACKGROUND: This study directs to evaluate the efficacy and safety of intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy in intermediate-risk NPC (stage II and T3N0M0). METHODS: A total of 124 patients with stage II and T3N0M0 NPC were pair-matched (1:1 ratio) to form two groups: an IMRT-alone group and an IMRT/chemotherapy group. Survival outcomes (overall survival [OS], disease-free survival [DFS], locoregional relapse-free survival [LRRFS], distant metastasis-free survival [DMFS]) and treatment-related grade 3-4 acute toxicity events were compared between the groups. RESULTS: Survival outcomes for patients with stage II and T3N0M0 NPC were quiet comparable between patients treated with IMRT alone versus patients treated with IMRT/chemotherapy: 5-year OS was 91.9% vs. 90.3%, respectively (P = 0.727); DFS was 87.1% vs. 88.7%, respectively (P = 0.821); LRFFS was 96.8% vs. 95.2%, respectively (P = 0.646), and DMFS was 91.9% vs. 91.5%, respectively (P = 0.955). Grade 3 acute toxicities were significantly higher with IMRT/chemotherapy than with IMRT alone: mucositis, 15% vs. 5% (P = 0.004); leukopenia/neutropenia, 8% vs. 1% (P <  0.015); and nausea/vomiting, 22% vs. 3% (P <  0.001). CONCLUSION: For intermediate-risk (stage II and T3N0M0) NPC patients, the addition of chemotherapy to IMRT does not appear to provide any survival benefit. Moreover, grade 3 acute toxicities are also more common in patients receiving IMRT plus chemotherapy.

LncRNA DGCR5 regulates the non-small cell lung cancer cell growth, migration, and invasion through regulating miR-211-5p/EPHB6 axis.

Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancers worldwide. In recent years, importance of noncoding RNAs including long noncoding RNA and microRNA in regulating tumor progression has been appreciated. Abnormally expression of DiGeorge syndrome critical region gene 5 (DGCR5) was found in multiple human cancers but its function in NSCLC is largely unknown. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to explore DGCR5 expression level in NSCLC. Bioinformatic analyses were conducted to explore the targets of DGCR5. Cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were performed to analyze functions of DGCR5. RT-qPCR revealed that DGCR5 expression in NSCLC cells was significantly lower than in normal cell. DGCR5 overexpression suppresses NSCLC cell growth, migration, and invasion. Online algorithms found EPH receptor B6 (EPHB6) and DGCR5 contains same miR-211-5p binding region. The predicted connections were further validated by luciferase activity reporter assay. Recue experiments showed DGCR5 regulates NSCLC cell behaviors via targeting miR-211-5p/EPHB6. These findings collectively identified DGCR5/miR-211-5p/EPHB6 triple axis in NSCLC, which may novel understanding regarding the tumorigenesis of NSCLC.

[Weekly irinotecan plus capecitabine as a second-line chemotherapy for advanced gastric cancer: an analysis of 21 cases].

OBJECTIVE: To evaluate the efficacy and adverse effects of weekly irinotecan combined with capecitabine as a second-line chemotherapy for treatment of advanced gastric cancer. METHODS: Twenty-one patients with advanced gastric cancer who had failed first-line therapy received irinotecan on days 1 and 8 plus capecitabine on days 1-14 for a 21-day cycle. Each patient was treated for at least two cycles and evaluated 4 weeks later for the responses. RESULTS: Of the 21 patients, none showed complete remission (CR), 5 (23.8%) showed partial remission (PR), 6 (28.6%) showed stable disease (SD) and 10 (47.6%) showed progressive disease (PD). The overall response rate was 23.8%, and 11 patients (52.4%) benefited (CR+PR+SD) from the clinical therapy, with a mean time to tumor progression of 3.61±0.97 months. The main adverse effects of this regimen included myelosuppression, nausea, vomiting and diarrhea. CONCLUSION: The regimen of weekly irinotecan plus capecitabine has a definite effect for treatment of advanced gastric cancer with tolerable toxicity.