Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Design, synthesis, and anti-inflammatory activity of indole-2-formamide benzimidazole[2,1-b]thiazole derivatives.

Molecular hybridization is a widely employed technique in medicinal chemistry for drug modification, aiming to enhance pharmacological activity and minimize side effects. The combination of an indole ring and imidazole[2,1-b]thiazole has shown promising potential as a group that exhibits potent anti-inflammatory effects. In this study, we designed and synthesized a series of derivatives comprising indole-2-formamide benzimidazole[2,1-b]thiazole to evaluate their impact on LPS-induced production of pro-inflammatory cytokines NO, IL-6, and TNF-α release, as well as iron death in RAW264.7 cells. The findings revealed that most compounds effectively inhibited LPS-induced production of pro-inflammatory cytokines NO, IL-6, and TNF-α release in RAW264.7 cells. Compound 13b exhibited the most potent anti-inflammatory activity among the tested compounds. The results of the cytotoxicity assay indicated that compound 13b was nontoxic. Additionally, compound 13b was found to elevate the levels of ROS, MDA, and Fe2+, while reducing GSH content, thereby facilitating the iron death process. Consequently, compound 13b showed promise for future development as an anti-inflammatory drug.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Anlotinib Combined With Toripalimab as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Prospective, Multicenter, Phase II Study.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (HCC), the first-line therapeutic options are still relatively limited, and treatment outcomes remain poor. We aimed to assess the efficacy and safety of anlotinib combined with toripalimab as first-line therapy for unresectable HCC. METHODS: In this single-arm, multicenter, phase II study (ALTER-H-003), patients with advanced HCC without previous systemic anticancer therapy were recruited. Eligible patients were given anlotinib (12 mg on days 1-14) combined with toripalimab (240 mg on day 1) in a 3-week cycle. The primary endpoint was the objective response rate (ORR) by immune-related Response Evaluation Criteria in Solid Tumours (irRECIST)/RECIST v1.1 and modified RECIST (mRECIST). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Between January 2020 and Jul 2021, 31 eligible patients were treated and included in the full analysis set. At data cutoff (January 10, 2023), the ORR was 29.0% (95% CI: 12.1%-46.0%) by irRECIST/RECIST v1.1, and 32.3% (95% CI: 14.8%-49.7%) by mRECIST criteria, respectively. Confirmed DCR and median DoR by irRECIST/RECIST v1.1 and mRECIST criteria were 77.4 % (95% CI: 61.8%-93.0%) and not reached (range: 3.0-22.5+ months), respectively. Median PFS was 11.0 months (95% CI: 3.4-18.5 months) and median OS was 18.2 months (95% CI: 15.8-20.5 months). Of the 31 patients assessed for adverse events (AEs), the most common grade ≥ 3 treatment-related AEs were hand-foot syndrome (9.7%, 3/31), hypertension (9.7%, 3/31), arthralgia (9.7%, 3/31), abnormal liver function (6.5%, 2/31), and decreased neutrophil counts (6.5%, 2/31). CONCLUSIONS: Anlotinib combined with toripalimab showed promising efficacy and manageable safety in Chinese patients with unresectable HCC in the first-line setting. This combination therapy may offer a potential new therapeutic approach for patients with unresectable HCC.

Comprehensive analysis in the nutritional composition, phenolic species and in vitro antioxidant activities of different pea cultivars.

In this study, ten pea (Pisum sativum L.) varieties were compared in their nutrient composition, phenolic compounds, antioxidant properties and their diversity were deciphered by multivariate analysis of correlation analysis and principal component analysis (PCA). The ten pea cultivars are rich in nutrients with different contents in lipid (0.57 to 3.52%), dietary fiber (11.34 to 16.13%), soluble sugar (17.53 to 23.99%), protein (19.75 to 26.48%) and starch (32.56 to 48.57%). Through the UPLC-QTOF-MS and HPLC-QQQ-MS/MS analysis, the ethanol extracts of ten peas mainly included 12 kinds of phenolic substances and showed good antioxidant activities on the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). The phenolic content and protocatechuic acid showed a positive correlation with antioxidant capacity. All results provide theoretical basis for the development and rational application of different varieties of peas and their related products.

Vincosamide Has a Function for Inhibiting Malignant Behaviors of Hepatocellular Carcinoma Cells.

Background: Vincosamide (Vinco) was first identified in the methanolic extract of the leaves of Psychotria leiocarpa, and Vinco has important anti-inflammatory effects and activity against cholinesterase, Vinco also has a trait to anti-tumor. However, whether Vinco can inhibit the malignant behaviors of hepatocellular carcinoma (HCC) cells is still unclear. In the present study, we explored the role of Vinco in suppressing the malignant behaviors of HCC cells. Methods: MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide), trypan blue exclusion assay, the Cell Counting Kit (CCK)-8 and flow cytometric analysis were applied to detect the proliferation and apoptosis of HCC cells; electron microscopy was performed to observe the change of cellular mitochondrial morphology; scratch repair and Transwell assays were used to analyze the migration and invasion of HCC cells; expression and localization of proteins were detected by laser confocal microscopy and Western blotting; the growth of the cancer cells in vivo was assessed in a mouse tumorous model. Results: At a dose of 10 - 80 µg/mL, Vinco inhibited the proliferation, migration, invasion and promoted apoptosis of HCC cells in a dose-dependent manner but had low cytotoxicity effect on normal liver cells. Additionally, 80 µg/mL of Vinco could significantly disrupt the morphology of mitochondria, suppress the migration and invasion of HCC cells. The growth of HCC cells in the animal tumorous model was significantly inhibited after treatment with Vinco (10 mg/kg/day) for 3 days. The results of the present study indicated that Vinco (10 - 80 µg/mL) played a role in activating caspase-3, promoting the expression of phosphate and tension homology deleted on chromosome 10 (PTEN), and inhibiting the phosphorylation of AKT (Ser473) and mTOR (Thr2448); Vinco also has a trait for suppressing the expression of CXCR4, Src, MMP9, EpCAM, Ras, Oct4 and cancer stem cell "stemness markers" CD133 and CD44 in HCC cells. Conclusions: Vinco has a role in inhibiting the malignant behaviors of HCC cells; the role molecular mechanism of Vinco may be involved in restraining expression of the growth-, metastasis-related factors, such as Src, Ras, MMP9, EpCAM, CXCR4; activating the activity of caspase-3 and blocking PI3K/AKT signaling pathway. Thus, Vinco should be considered as a new chemotherapy agent for HCC patients.

[Comparison of atmospheric particulate matter and aerosol optical depth in Beijing City].

The pollution of particulate matter was serious in Beijing City from the synchronous observation of particulate matter mass concentration and aerosol optical characteristics in 2009. The annual mean concentrations of PM2.5 and PM10 were (65 +/- 14) microg x m(-3) and (117 +/- 31) microg x m(-3), respectively, which exceeded the national ambient air quality annual standards to be implemented in 2016. There were 35% and 26% days of 2009 that the daily standards were exceeded. There was a significant correlation between fine particulate (PM2.5) and inhalable particle (PM10), with a correlation coefficient (R) of approximately 0.90 (P < 0.001). PM10 contained a large percentage of PM2.5, with an annual percentage of about 61%. The percentage became much higher from spring to winter, while the correlation between PM2.5 and PM10 became much stronger. The annual mean of AOD (500 nm) and Angstrom exponent were (0.55 +/- 0.1) and (1.12 +/- 0.08), respectively. There were significant correlations between PM2.5, PM10 and AOD in the four seasons and the whole year, and the correlation coefficients were greater than or equal to 0.50. Furthermore, the correlation functions and coefficients had seasonal variations. The correlations were more significant in summer and autumn than in spring and winter. The annual correlation could cover up the seasonal systematic differences. The correlations between AOD revised by Mixed Layer Height and PM2.5 PM10 revised by Relative Humidity became stronger, and the exponential correlations were superior to the linear correlations.