Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non-small cell lung cancer cells.

In the present study, we found that Ginsenoside Rg3 attenuated the stemness of non-small cell lung cancer (NSCLC) cells, evident by decreasing spheroid formation ability, ALDH1 activity and stemness marker expression. Furthermore, osimertinib-resistant NSCLC cells displayed a stronger stemness than the parental cells. Ginsenoside Rg3 reduced the stemness and osimertinib resistance of osimertinib-resistant cells. RNA-sequencing revealed that Hippo signaling was shown on the top of the most upregulated pathways regulated by Ginsenoside Rg3 in NSCLC cells, and YAP/TAZ expression was suppressed by Ginsenoside Rg3. Notably, the inhibitor of Hippo signaling attenuated the effects of Ginsenoside Rg3 on the stemness of NSCLC cells. Therefore, Ginsenoside Rg3 attenuates the osimertinib resistance of NSCLC cells via suppressing the stemness, which is dependent on Hippo pathway.

Clinical Therapy: HAIC Combined with Tyrosine Kinase Inhibitors and Programmed Cell Death Protein-1 Inhibitors versus HAIC Alone for Unresectable Hepatocellular Carcinoma.

Purpose: The majority of new diagnoses of hepatocellular carcinoma (HCC) still pertain to unresectable cases. Currently, the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors has become the mainstream treatment. According to multiple clinical guidelines, it is strongly advised to consider local therapy as the primary treatment choice for uHCC. This research was conducted to examine the safety and effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with TKIs and PD-1 inhibitors for the treatment of uHCC. Methods: Between 2015 and 2020, 208 HCC patients received HAIC alone or HAIC in combination with TKIs and PD-1 inhibitors. The overall survival(OS), and progression-free survival(PFS) and the best treatment response were compared between the two treatment groups. Propensity score matching (PSM)was used to minimize confounding bias. Results: Among the enrolled patients, 116 patients (55.8%) received combination therapy, while 92 patients (44.2%) received HAIC alone. The baseline characteristics were similar between the two groups. After PSM, 82 pairs of well-matched liver cancer patients were selected; the overall response rate in the combination group trended better than that in the HAIC alone group. The hazard ratios (HRs) for OS and PFS of the combination approach compared to the HAIC-alone approach were 0.47 (95% CI, 0.322-0.687; p<0.001) and 0.58 (95% CI, 0.397-0.848; p=0.005), respectively. Conclusion: For uHCC patients, combination therapy can provide better OS and PFS compared to HAIC alone.

Efficacy of PD-1/PD-L1 Inhibitors versus Chemotherapy in Lung Cancer with Brain Metastases: A Systematic Review and Meta-Analysis.

Immune checkpoint inhibitors (ICIs) are widely used to treat local or metastatic lung cancer. However, the efficacy of ICI in patients with brain metastases (BM) from lung cancer is unknown. This study aimed to evaluate the efficacy of PD-1/PD-L1 ICIs compared with chemotherapy for patients with lung cancer with BM. Electronic databases (PubMed, Embase, The Cochrane Library, and Web of Science) were searched. The meta-analysis assessed overall survival (OS) and progression-free survival (PFS) of the PD-1/PD-L1 inhibitors axis and its relationship with pathological type, drug modality, and the treatment line number in patients with BM from lung cancer. We included 694 patients with BM from lung cancer from 11 randomized controlled trials. Statistical analysis showed that compared with chemotherapy, PD-1/PD-L1 inhibitors could significantly prolong OS (hazard ratio (HR) = 0.75, 95%confidence interval (95%CI) = 0.51-0.99) and PFS (HR = 0.65, 95%CI = 0.51-0.80). In the subgroup analysis, ICIs plus chemotherapy improved PFS (HR = 0.60, 95%CI = 0.40-0.80), but not OS (HR = 0.75, 95%CI = 0.30-1.19). The efficacy of ICI monotherapy in patients with BM was significantly different between OS and PFS: OS pooled HR = 0.81 (95%CI = 0.57-1.05) and PFS = 0.78 (95%CI = 0.62-0.94). Among different pathological types, the OS pooled HR was 0.67 (95%CI = 0.39-0.95) for non-small cell lung cancer (NSCLC) and 0.94 (95%CI = 0.56-1.33) for small cell lung cancer (SCLC); the PFS pooled HR was 0.58 (95%CI = 0.39-0.76) for NSCLC and 0.79 (95%CI = 0.65-0.93) for SCLC. Subgroups analysis of treatment line showed that no advantage for OS with ICIs as first-line or subsequent-line therapy, whereas ICIs as first-line (HR = 0.63, 95%CI = 0.53-0.74) and second-line (HR = 0.62, 95%CI = 0.62-0.96) benefitted PFS. This meta-analysis implied that compared with chemotherapy, PD-1/PD-L1 inhibitors significantly improved efficacy treatment of patients with BM from lung cancer. Further studies are needed to confirm the role of ICIs in different pathological types and drug treatment modalities.

Antibiotic use is a negative predictor of the efficacy and toxicity of epidermal growth factor receptor-targeted therapy in advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is closely associated with inflammation and chronic infection. Antibiotics are frequently prescribed for NSCLC patients in combination with epidermal growth factor receptor (EGFR)-targeted treatment in the presence of infection. The association between antibiotic use and the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has not previously been thoroughly investigated. Therefore, the present study investigated whether antibiotics could affect the efficacy and toxicity of EGFR-TKI treatment, with the aim of restricting the use of antibiotics in combination with targeted therapy in patients with advanced NSCLC in the near future. All patients received treatment with EGFR-TKIs until disease progression, unacceptable toxicity or other factors, including death, pregnancy or unwillingness to further receive targeted therapy, were observed. Patients were retrospectively divided into two groups: Group A, which was treated with EGFR-TKIs and antibiotics; and Group B, which was treated with EGFR-TKIs alone. Patients having used antibiotics 6 months prior to EGFR-TKI therapy were also included in the study. Antibiotic use negatively affected the median progression-free survival (PFS) following EGFR-TKI treatment in NSCLC compared with that in patients not treated with antibiotics; median PFS in Group A was 6.6 months, whereas median PFS in Group B was 10.1 months. Antibiotics also increased the toxicity of targeted therapy for advanced NSCLC. There were significant statistical differences between the two groups in the occurrence of the adverse events of diarrhea and dyspnea. In conclusion, antibiotics decreased the efficacy of first-line targeted therapy in advanced NSCLC and increased incidences of diarrhea and dyspnea. Large randomized studies are needed to identify the impact of antibiotic use on EGFR-TKI treatment for NSCLC.

Identification of the BRAF V600E mutation in a patient with sclerosing pneumocytoma: A case report.

OBJECTIVES: Sclerosing pneumocytoma (sclerosing hemangioma, SP) is a rare benign tumor of the lung with a low risk of recurrence. The genomic profile of SP is not well-known. Here we report gene mutation findings in a 17-year-old girl with SP. MATERIALS AND METHODS: Immunohistochemistry (IHC), next-generation sequencing (NGS), and sanger sequencing were performed on the tumor tissue of this patient for pathological diagnosis and gene mutation analysis. RESULTS AND CONCLUSION: Two mutations were identified in the tumor tissue by NGS and sanger sequencing: AKT1 E17K and BRAF (B-Raf proto-oncogene, serine/threonine kinase) V600E. This is the first case report of a BRAF V600E mutation in a patient with SP. This discovery extends our understanding of the pathogenesis of SP, and suggests the need for future testing of BRAF V600E in this rare tumor type.

Bacterial lactase genes diversity in intestinal mucosa of mice with dysbacterial diarrhea induced by antibiotics.

The current study aimed at exploring the diversity of bacterial lactase genes in the intestinal mucosa of mice with dysbacterial diarrhea induced by antibiotics and to provide experimental basis for antibiotics-induced diarrhea. Mice model of dysbacterial diarrhea was established by gastric perfusion with mixture of cephradine capsules and gentamicin sulfate (23.33 mL kg-1 d-1), twice a day and continuously for 5 days. Intestinal mucosa from jejunum to ileum was collected, and bacterial metagenomic DNA was extracted for Miseq metagenome sequencing to carry out diversity analysis. The results showed that specific operational taxonomic units (OTUs) were 45 in the control group and 159 in the model group. The Chao1, ACE, Shannon and Simpson indices in model group were significantly higher (P < 0.01 or P < 0.05) than control group. Principal component analysis (PCA) and box chart of the control group were relatively intensive, while in the model group, they were widely dispersed. Furthermore, the inter-group box area was higher than that in the intra-group. Compared with the model group, the abundance of bacterial lactase genes in Proteobacteria from the intestinal mucosa of the control group was higher, but lower in Actinobacteria and unclassified bacteria. At the genus level, the relative abundance of bacterial species and taxon units in model group was obviously increased (P < 0.05). Our results indicate that antibiotics increased the diversity and abundance of bacterial lactase genes in the intestinal mucosa, as the abundance of Betaproteobacteria, Cupriavidus, Ewingella, Methyloversatilis, Rhodocyclaceae and Rhodocyclales. In addition, antibiotics become an additional source for lactase genes of Ewingella, Methyloversatilis, Mycobacterium, Microbacterium, Beutenberqia and Actinomyces.

MICB microsatellite polymorphism is associated with ulcerative colitis in Chinese population.

The MHC class I-related molecules A and B (MICA and MICB) are stress-inducible cell surface antigens that are recognized by immunocytes bearing the receptor NKG2D, including intestinal epithelial Vdelta1 gammadelta T cells, which may play a role in immunological reaction in intestinal mucosa. The present study was aimed to investigate the association of the microsatellite polymorphisms in the intron 1 of MICB and the MICA-MICB haplotype with the susceptibility to ulcerative colitis (UC) in Chinese population. The microsatellite polymorphisms of MICB were genotyped in unrelated 127 Chinese patients with UC and 193 ethnically matched healthy controls by a semiautomatic fluorescently labeled PCR method. All the subjects were the Chinese with Han nationality. The frequency of MICB-CA18 was significantly higher in UC patients compared with the healthy controls (14.0% vs. 5.8%, P = 0.0016, Pc = 0.024, OR = 2.637, 95%CI: 1.443-4.820) and was increased in the female patients compared with the female healthy controls (18.3% vs. 4.1%, P = 0.0006, Pc = 0.0080, OR = 5.224, 95%CI: 1.940-14.069). Thus, MICB-CA18 is positively associated with UC and female UC patients in Chinese population.