Background: Anlotinib, an antiangiogenic multi-target tyrosine kinase inhibitor, significantly improved clinical benefit in many solid tumours. TQB2450 is an engineered anti-programmed death-ligand 1 antibody. This study aimed to assess the safety and effect of TQB2450 plus anlotinib in patients with advanced solid tumour.Methods: This phase Ib study, which included a dose-escalating phase and an expansion phase, enrolled patients with advanced or metastatic solid tumour who had standard treatment failure or no standard treatment between June 2019 and January 2020. Eligible patients were firstly enrolled into sequential dose-escalating cohorts including 10mg and 12mg anlotinib plus TQB2450 following the conventional 3+3 design. If the starting dose of 10mg anlotinib led to !2 dose-limiting toxicities (DLTs), 8mg anlotinib would be administered. After the dose-escalating phase completed, eligible patients were enrolled into the expansion cohort. The primary outcomes were safety and objective response rate (ORR).

IntroductionRUNX2 is overexpressed in gastric cancer but the mechanism(s) through which it promotes tumor progression remain undefined. Here, we investigated the role of RUNX2 on gastric cancer pathogenesis at the molecular level.MethodsThe qRT-PCR and western bolt were utilized to examine the mRNA and protein levels. CCK-8, Transwell and wound healing assays were used to measure cell proliferation, invasion and migration. CHIP-PCR gel electrophoresis was used to verify RUNX2 as a transcription factor for MMP13 and MGAT5. The in vivo assay was utilized to assess tumor growth. In vivo assay was used to evaluate tumor growth, aberrant expression of RUNX2 and lung metastasis of gastric cancer.ResultsRUNX2 is overexpressed in MKN-45 and AGS cells. Genetic RUNX2 silencing reduced the proliferation, invasion and migration of MKN-45 and AGS cells. Analysis of the gastric cancer samples from the database revealed a significant positive correlation between MGAT5, MMP13, and RUNX2 expression. JASPAR analysis revealed that there was a potential binding site of RUNX2 in the promoter regions of MGAT5 and MMP13, and the experimental results confirmed that RUNX2 could regulate the expression of MGAT5 and MMP13 respectively. In vivo assays confirmed the aberrant expression of RUNX2 in mouse models of gastric cancer and reduced growth and lung metastasis in RUNX2 silenced xenograft tumors assessed.ConclusionCollectively, these data reveal that RUNX2 enhances MGAT5 and MMP13 expression in gastric cancer cells and represents a biomarker and potential therapeutic target for gastric cancer therapy.

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PurposeMetastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established.Materials and MethodsWe retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022.ResultsOverall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first‐line treatment was 18%. Three of the four patients with BRAF‐mutated CM responded to dabrafenib and trametinib treatment. The median progression‐free survival (PFS) and overall survival (OS) of first‐line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver‐directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites.ConclusionCM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases.