As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.
What is known and objective Camrelizumab is a recently developed PD‐1 inhibitor in China applied in treating different cancers including lung cancer. This study is designed to evaluate the efficacy, safety and prognostic factors for camrelizumab plus carboplatin and pemetrexed (CP) chemotherapy in treating patients with advanced lung adenocarcinoma. Methods Of 51 advanced lung adenocarcinoma patients with negative driver genes who received camrelizumab plus CP chemotherapy were recruited. These patients received four cycles of camrelizumab plus CP chemotherapy in a 21‐day cycle. Then, camrelizumab, pemetrexed or camrelizumab plus pemetrexed was administered as maintenance therapy. Results and discussion The rates of complete response, partial response, stable disease and progressive disease were 2.0%, 56.8%, 19.6% and 5.9%, respectively; while treatment response of 15.7% of patients was missing or not evaluable. The objective response and disease control rates were 58.8% and 78.4%, respectively. With a median follow‐up period of 14.9 months (the follow‐up duration ranged from 3.9 months to 24.3 months), 41 (83.4%) cases of disease progression and 22 (43.1%) cases of death were recorded. The median progression‐free survival (PFS) was 10.5 months (95% confidence interval (CI): 8.4–12.6 months) with a 1‐year PFS rate of 36.3% and a 2‐year PFS rate of 7.5%. In addition, the median overall survival (OS) was 18.7 months (95% CI: 16.4–21.0 months) with a 1‐year OS rate of 79.1% and a 2‐year OS rate of 30.4%. In consideration of safety, the most frequent adverse events were peripheral neuropathy (37.3%), neutropenia (37.3%), alopecia (35.3%), etc. and most of them were grade 1–2 and could be controlled. What is new and Conclusion Camrelizumab plus CP chemotherapy achieves favourable efficacy and tolerable adverse events in advanced lung adenocarcinoma patients.
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