BackgroundCyclooxygenase-2 (COX-2) is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Correlations between the expression of COX-2 with tumor growth and distant metastasis have become an issue; thus, attention has been paid to COX-2 as a prognostic factor. Various studies examined the relationship between COX-2 immunohistochemistry (IHC) overexpression with the clinical outcome in patients with colorectal cancer, but yielded conflicting results. The prognostic significance of COX-2 overexpression in colorectal cancer remains controversial.MethodsElectronic databases updated to October 2012 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between COX-2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed.ResultsWe performed a meta-analysis of 23 studies (n  =  4567 patients) that evaluated the correlation between COX-2 overexpression detected by IHC and survival in patients with colorectal cancer. Combined hazard ratios suggested that COX-2 overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio]  =  1.193, 95% CI [confidence interval]: 1.02 ∼ 1.37), but not disease free survival (DFS) (HR  =  1.25, 95% CI: 0.99 ∼ 1.50) in patients with colorectal cancer.ConclusionsCox-2 overexpression in colorectal cancer detected by IHC appears to have slightly worse overall survival. However, the prognostic value of COX-2 on survival in colorectal cancer still needs further large-scale prospective trials to be clarified.

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BackgroundCholangiocarcinoma, or bile duct cancer, is a gastrointestinal cancer with limited therapeutic options and a poor outcome. Studies have revealed that some major driver genes are associated with cholangiocarcinoma, but no targeted therapies have been approved. Immune checkpoint inhibitors, which are represented by inhibitors of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), have emerged as a potential therapy for multiple types of solid cancers.Case presentationA 53-year-old female presented with postoperative recurrence of PD-L1-positive intrahepatic cholangiocarcinoma with a high tumour mutational burden. This patient exhibited a marked response to the combination of anti-PD-1 immunotherapy and chemotherapy.ConclusionsAs far as we know, this is the first case report on the success of the combination of immunotherapy and chemotherapy for advanced cholangiocarcinoma with PD-L1 positivity and a high tumour mutational burden.

Objective: The specific purpose of this study is to investigate the impact exosomes from adipose-derived mesenchymal stem cell (AMSC) has on non-small cell lung carcinoma (NSCLC) and the relative applications. Methods: circ_100395, miR-141-3p, and LATS2 were expressed and detected in NSCLC and paracancerous tissues as well as NSCLC cell lines. Pearson correlation analysis, Dual-Luciferase Reporter Assay and RNA pull-down assay were used to validate their expression and interaction, respectively. After isolation and culture of AMSCs, exosomes were extracted and identified. EdU, epithelial-mesenchymal transition (EMT), and cell colony formation assay were used to distinguish the biological activity of the cells. Expression Hippo/YAP signalling pathway-related proteins were measured by western blotting. Subsequently, tumour volume and weight were confirmed based on xenograft nude mice models, Ki-67 and LATS2 expression was observed by immunohistochemistry. Results: circ_100395 was lowly expressed in NSCLC tissues or cells. The negative correlations and interactions were confirmed between circ_100395 and miR-141-3p, miR-141-3p, and LATS2. AMSC-derived exosomes with overexpression of circ_100395 (exo-circ_100395) significantly inhibited the biological activity as well as EMT of H1650 cells and Hippo/YAP signalling pathway activity. In addition, exo-circ_100395 markedly reduced tumour volume and weight as well as Ki-67 and LASP1 expression in vivo. However, overexpressed miR-141-3p or knocked down LATS2 alleviated the above effects. Conclusion: Exo-circ_100395 can increase LATS2 expression by sponging miR-141-3p to regulate Hippo/YAP signalling pathway, thereby inhibiting NSCLC malignant transformation.

Abstract:Objective: To explore the effects of transforming growth factor β1 (TGF-β1) on dendritic cells (DC). Methods: Murine bone marrow cells were cultured with GM-CSF and TGF-β1 to develop TGF-β1-treated DC (TGFβ-DC). Then they were stimulated by lipopolysaccharide (LPS). Their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was measured by mixed lymphocyte reaction (MLR) using BrdU ELISA method and IL-12p70 protein was detected by ELISA. The expression of Toll-like receptor 4 (TLR4) was analyzed by semi quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and FCM. Results: Compared to immature DC (imDC) cultured by GM-CSF alone, the TGFβ-DC express lower CD80, CD86, I-A b and CD40. The TGFβ-DC were resistant to maturation with LPS. Maturation resistance was evident from a failure to up-regulate co-stimulatory molecules (CMs), to stimulate larger T cells proliferation and to enhance secretion of IL-12p70. We also found that TGF-β1 could down-regulate TLR4 expression on TGFβ-DC. Conclusion: TGFβ-DC are resistant to maturation stimulus (LPS) and might have some correlation with the down-modulation of TLR4 expression.

Background While there have been encouraging preliminary clinical results for immune checkpoint inhibitors (ICIs) in BTCs, it remains a challenge to identify the subset of patients who may benefit. In this study, we evaluated the efficacy of ICI treatment in patients with advanced BTCs, and explored potential biomarkers that are predictive of response. Methods The study enrolled 26 patients with advanced microsatellite stable BTCs (15 with gallbladder cancers [GCs] and 11 with intrahepatic cholangiocarcinoma [ICCs]) who received ICI treatment. Targeted next‐generation sequencing (NGS) was performed on tumor tissue samples collected from 17 patients. Clinical and genomic characteristics were assessed for the correlation with clinical outcome. Results Analysis of the baseline clinical characteristics showed that performance score (PS) of 0 was associated with a better prognosis than PS of 1 (HR = 1.08 × 109; 95% CI, 0∼Inf; P = .002). No significant correlations were found between clinical outcome and inflammation‐related indicators. NGS profiling of the available tumor tissues, revealed largely non‐overlapping somatic alterations between GCs and ICCs. Mutations in LRP1B (HR = 0.26; 95% CI, 0.06‐1.21; P = .067), ERBB2 (HR = 0.15; 95% CI, 0.02‐1.19; P = .04), or PKHD1 (HR < 0.01; 95% CI, 0‐Inf; P = .04) showed strong association with increased progression‐free survival (PFS) benefit. Subsequent analysis showed that alterations in the RTK‐RAS pathway were associated with improved outcomes (HR = 0.12; 95% CI, 0.02‐0.63; P = .003). Tumor mutation burden (TMB) was higher in patients with GC than those with ICC, and was associated with LRP1B mutations (P = .032). We found that patients with 19q amplification (19q Amp) and 9p deletion (9p Del) had poor PFS outcome (19q Amp, HR = 15.4; 95% CI, 2.7‐88.5; P < .001; 9p Del; HR = 4.88 × 109; 95% CI, 0‐Inf; P < .001), while those with chromosomal instability derived PFS benefit (HR = 0.24; 95% CI, 0.05‐1.17; P = .057). Conclusion Our study identified several potential clinical and genomic features that may serve as biomarkers of clinical response to ICIs in advanced BTCs patients. A larger sample size is required for further verification.

Prolonged gemcitabine infusion combined with carboplatin is manageable and tolerated, and its efficacy is similar to that of other chemotherapeutic schemes used for NSCLC treatment.

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