Clinical Efficacy of Antianlotinib Combined with Immune Checkpoint Inhibitors in the Treatment of Advanced Non-Small-Cell Lung Cancer and Its Effect on Serum VEGF, CEA, and SCC-Ag.

Purpose: This study is aimed at investigating the clinical safety and effectiveness of anlotinib combined with immune checkpoint inhibitors (ICIs) in the treatment of non-small-cell lung cancer (NSCLC). Methods: We selected 68 NSCLC patients treated at the Tumor Hospital Affiliated to Nantong University from October 2019 to January 2022. Patients receiving ICI monotherapy were included in the control group (n = 36), whereas patients receiving anlotinib combined with ICIs were enrolled in the study group (n = 32). The survival, adverse reactions (AEs), and short-term clinical effectiveness of the two groups were observed. The tumor markers (vascular endothelial growth factor (VEGF), carcino-embryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-AG)) and T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+) were determined before and after treatment. Results: Compared with the control group, the disease-control rate (DCR) and objective response rate (ORR) in the study group were substantially higher than that of the control group (62.50 vs. 36.11, 81.25 vs. 55.56; P < 0.05). The serum levels of VEGF, CEA, and SCC-AG in the two groups were considerably lower after two cycles of treatment (P < 0.05), and the serum levels of VEGF, CEA, and SCC-AG in the study group were significantly lower than those in the control group (P < 0.05). Following therapy, CD8+ in both groups decreased dramatically (P < 0.05), whereas CD3+, CD4+, and CD4+/CD8+ were significantly increased, but there was no statistical difference between the two groups (P > 0.05). The incidence of gastrointestinal, respiratory, cardiovascular, and immune-related adverse events did not significantly differ between the two groups (P > 0.05). The median progression-free survival (PFS) in the control and study groups for the first-line treatment patients was 7.2 and 9.8 months, respectively, whereas for the second-line treatment patients, it was 4.2 and 6.4 months, respectively. The mean PFS of study group was substantially longer than that of the control group regardless of the first- or second-line treatment. According to Cox analysis, the number of drug lines and TNM stage was independent risk variables impacting the prognosis of patients in this study. Conclusion: The combination of anlotinib with ICIs was more effective than either agent alone in the first- and second-line treatment of patients with advanced NSCLC. This treatment regimen did not interfere with immunological recovery or increase side effects.

Relieving immunosuppression by Endo@PLT targeting anti-angiogenesis to improve the efficacy of immunotherapies.

Low levels of immune infiltrates in the tumor milieu hinder the effectiveness of immunotherapy against immune-cold tumors. In the current work, a tumor-targeting drug delivery system composed of Endo-loaded platelets (Endo@PLT) was developed to relieve immunosuppression by achieving tumor vascular normalization. Endo@PLT reprogrammed the immunostimulatory phenotype, achieving excellent PD-1 immunotherapy in vivo.

Characterization of Phenotypic and Genotypic Traits of Klebsiella pneumoniae from Lung Cancer Patients with Respiratory Infection.

BACKGROUND: Klebsiella pneumoniae has been a leading healthcare-acquired infection (HAI) agent worldwide for decades. However, the epidemiological characteristics of K. pneumoniae in lung cancer patients with respiratory infection are unclear. Here, we characterized the frequency of K. pneumoniae in lung cancer patients with respiratory infection in a cancer hospital in China and determined the antibiotic resistance profile, virulence phenotype and clonal relationships among these K. pneumoniae strains. METHODS: The clinical data of lung cancer patients with respiratory infection from September 2017 to October 2018 were retrospectively evaluated. Microbiological methods, antimicrobial susceptibility tests, pulsed-field gel electrophoresis (PFGE), polymerase chain reaction (PCR) assays, Sanger sequencing and Galleria mellonella larvae infection model were used in this study. RESULTS: During the study period, a total of 47 lung cancer patients with respiratory infection caused by bacteria were identified, among 27 patients were identified as positive for K. pneumoniae and the positive rate was 57.45%. Among 37 nonduplicate K. pneumoniae strains from these 27 patients, 19 isolates (51.4%) were classified as multidrug resistant (MDR) with high-level resistance to, at least one agent in three or more antibiotic categories, including polymyxin B and tigecycline. Sixteen of the 37 strains (43.2%) were hypermucoviscous isolates. Extended spectrum ß-lactamases-producing K. pneumoniae strains consisted of two dominant PFGE types. Furthermore, the assessment of virulence potential using a G. mellonella larvae infection model showed that K. pneumoniae isolated from these patients exhibited a high virulence level. CONCLUSION: Our data showed that K. pneumoniae is the most critical cause of lung infection in patients with lung cancer in this hospital. The various drug resistance and virulence backgrounds of K. pneumoniae may make this clinical center a breeding ground for superbugs. It is paramount to enhance surveillance of K. pneumoniae strains and take control measures.

Long noncoding RNA LINC00337 accelerates the non-small-cell lung cancer progression through inhibiting TIMP2 by recruiting DNMT1.

Accumulating evidence reveals the essential roles of long noncoding RNAs (lncRNAs) in the non-small-cell lung cancer (NSCLC) tumorigenesis. Here, our research investigated the biological roles of novel lncRNA LINC00337 in the NSCLC tumorigenesis and discover the potential mechanism. In the NSCLC tissue and cell lines, LINC00337 was found to be remarkedly up-regulated, and the ectopic LINC00337 overexpression indicated the poor survival of NSCLC patients. In vitro, gain and loss of functional assays showed that LINC00337 promoted the progression of NSCLC cells, including proliferation and invasion. In vivo, LINC00337 knockdown inhibited the tumor growth of NSCLC cells. Mechanically, LINC00337 could recruit the epigenetic repressor DNMT1 to the promoter region of TIMP2 to silence its expression. In conclusion, our study found the critical regulation of lncRNA LINC00337 for the NSCLC through epigenetic regulation, which may serve as a predictive biomarker and potential therapeutic target.

Upregulation of circ_001569 predicts poor prognosis and promotes cell proliferation in non-small cell lung cancer by regulating the Wnt/ß-catenin pathway.

Circular RNAs (circRNAs) are a large class of RNAs that have previously been identified to be involved in certain diseases, including the development of cancer. However, the role of circ_001569 in non-small cell lung cancer (NSCLC) remains unknown. In the present study, it was demonstrated that expression levels of circ_001569 were significantly increased in NSCLC tissues compared with in adjacent normal tissues. Increased circ_001569 expression was closely associated with tumor differentiation, lymph node metastasis and Tumor-Node-Metastasis classification in NSCLC. Patients that exhibited higher circ_001569 expression demonstrated a poorer survival outcome compared with patients with lower circ_001569 expression. Functional assay results indicated that the knockdown of circ_001569 inhibited the cell proliferation ability of NSCLC in vitro. In addition, it was identified that circ_001569 knockdown reduced the mRNA and protein expression levels of Wnt/ß-catenin pathway-associated genes proto-oncogene protein Wnt1, transcription factor 4 and ß-catenin in NSCLC cells. Therefore, the results indicated that circ_001569 promoted cell proliferation by regulating the Wnt/ß-catenin pathway in NSCLC, and circ_001569 may be a potential target of NSCLC treatment.