Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
A carboxylate‐directed palladium‐catalyzed Mizoroki–Heck alkenylation of γ,δ‐unsaturated carboxylic acids with alkenyl bromides is reported. This carboxylate group is effective for chelation to a Pd ...center, enabling the distal alkenylation of electronically unbiased internal alkenes in the formation of conjugated 1,3‐dienes with high stereoselectivity. In addition, the conjugated 1,3‐diene products can be used for synthetic applications through reduction, epoxidation, methylation, amidation, and cycloaddition.
Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer ...(TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.
•Fucoidan from Laminaria japonica exerts antitumor effects.•Fucoidan suppresses proangiogenesis and micrometastasis in TNBC.•Fucoidan blocks MAPK and PI3K signaling in TNBC.
Background
Liver functional reserve is a major prognostic determinant in patients with hepatocellular carcinoma (HCC). The albumin–bilirubin (ALBI) score is an objective method to assess the severity ...of cirrhosis in this setting. However, calculation of the ALBI score is complex and difficult to access in clinical practice. Recently, the EZ (easy)‐ALBI score was proposed as an alternative biomarker of liver injury. We aimed to evaluate the prognostic role of the EZ‐ALBI score in HCC from early to advanced stages.
Methods
A total of 3794 newly diagnosed HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were determined by using the multivariate Cox proportional hazards model.
Results
The EZ‐ALBI score showed good correlation with the ALBI score (correlation coefficient, 0.965; p < 0.001). The correlation of the EZ‐ALBI score was highly preserved in different Child–Turcotte–Pugh (CTP) classifications, treatment methods, and Barcelona Clinic Liver Cancer (BCLC) stages (correlation coefficients, 0.90–0.97). In the Cox multivariate analysis, age >65 years, male sex, serum α‐fetoprotein >20 ng/ml, large or multiple tumors, total tumor volume >100 cm3, vascular invasion or distant metastasis, ascites, poor performance status, EZ‐ALBI grade 2 and 3, and noncurative treatments were independently associated with increased mortality (all p < 0.05). Moreover, EZ‐ALBI grade can stratify long‐term survival in patients with different CTP class, treatment strategy, and BCLC stage.
Conclusions
The EZ‐ALBI score is an easy and feasible method to evaluate liver functional reserve. As a new prognostic biomarker in HCC, the predictive power of the EZ‐ALBI grade is independent across different cancer stages and treatments.
The 2022 International Consensus Classification (ICC) recategorized myeloid neoplasms based on recent advances in the understanding of the biology of hematologic malignancies, in which ...myelodysplastic syndrome (MDS) with blasts of 10%–19% is classified as MDS/acute myeloid leukemia (AML), MDS with mutated SF3B1, irrespective of the number of ring sideroblasts, as MDS‐SF3B1, and those with multi‐hit TP53 mutations as MDS with mutated TP53. In the analysis of 716 patients with MDS diagnosed according to the 2016 WHO classification, we found that 75.3% of patients remained in the MDS group based on the ICC, while 24.7% of patients were reclassified to the MDS/AML group after the exclusion of 15 patients who were classified to the AML group. Patients with MDS/AML showed a distinct mutational landscape and had poorer outcomes, compared to those with MDS. In the MDS group, patients with MDS‐SF3B1 had higher frequencies of DNMT3A and TET2 mutations than those with MDS, not otherwise specified, with single lineage dysplasia or multilineage dysplasia. Patients with mutated TP53 were associated with dismal outcomes, irrespective of the blast percentage. In conclusion, this study showed that the ICC facilitates efficient segregation and risk‐stratification of MDS which can help guide the treatment choice of patients with the disease.
Case allocation of MDS patients defined by 2016 WHO classification and 2022 ICC.
We developed mesoporous silica nanoparticle (MSN) as a multifunctional vehicle for enzyme delivery. Enhanced transmembrane delivery of a superoxide dismutase (SOD) enzyme embedded in MSN was ...demonstrated. Conjugation of the cell-penetrating peptide derived from the human immunodeficiency virus 1 (HIV) transactivator protein (TAT) to mesoporous silica nanoparticle is shown to be an effective way to enhance transmembrane delivery of nanoparticles for intracellular and molecular therapy. Cu,Zn-superoxide dismutase (SOD) is a key antioxidant enzyme that detoxifies intracellular reactive oxygen species, ROS, thereby protecting cells from oxidative damage. In this study, we fused a human Cu,Zn-SOD gene with TAT in a bacterial expression vector to produce a genetic in-frame His-tagged TAT-SOD fusion protein. The His-tagged TAT-SOD fusion protein was expressed in E. coli using IPTG induction and purified using FMSN-Ni-NTA. The purified TAT-SOD was conjugated to FITC-MSN forming FMSN-TAT-SOD. The effectiveness of FMSN-TAT-SOD as an agent against ROS was investigated, which included the level of ROS and apoptosis after free radicals induction and functional recovery after ROS damage. Confocal microscopy on live unfixed cells and flow cytometry analysis showed characteristic nonendosomal distribution of FMSN-TAT-SOD. Results suggested that FMSN-TAT-SOD may provide a strategy for the therapeutic delivery of antioxidant enzymes that protect cells from ROS damage.
Nasopharyngeal carcinoma (NPC) is one of the most aggressive malignant tumors of the head and neck. Xanthohumol (Xn) is a compound extracted in a high concentration from the hard resin of hops ...(Humulus lupulus L.), the basic raw material of beer. This study investigated the apoptotic effect and anticancer properties of Xn in human NPC cell lines. Our study demonstrated that at the concentration 40 μM, Xn significantly reduced cell viability and promoted cell cycle arrest in the G2/M phase in two cell lines. The results indicated that Xn induced apoptosis in NPC cell lines through annexin V/propidium iodide staining, chromatin condensation, and apoptosis‐related pathways. Xn upregulated the expression of apoptosis‐related proteins, namely DR5, cleaved RIP, caspase‐3, caspase‐8, caspase‐9, PARP, Bim, and Bak, and it downregulated the expression of Bcl‐2. Xn upregulated the c‐Jun N‐terminal kinase (JNK) in the mitogen‐activated protein kinase (MAPK), and the inhibition of JNK clearly resulted in decreasing expression of Xn‐activated cleaved caspase‐3 and PARP. Our research provides sufficient evidence to confirm that Xn induces the MAPK JNK pathway to promote apoptosis of NPC and is expected to become a safe and acceptable treatment option for human NPC.
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