The expression and biological role of IL33 in colon cancer is poorly understood. In this study, we show that IL33 is expressed by vascular endothelial cells and tumor cells in the human colon cancer microenvironment. Administration of human IL33 and overexpression of murine IL33 enhanced human and murine colon cancer cell growth in vivo, respectively. IL33 stimulated cell sphere formation and prevented chemotherapy-induced tumor apoptosis. Mechanistically, IL33 activated core stem cell genes NANOG, NOTCH3, and OCT3/4 via the ST2 signaling pathway, and induced phosphorylation of c-Jun N terminal kinase (JNK) activation and enhanced binding of c-Jun to the promoters of the core stem cell genes. Moreover, IL33 recruited macrophages into the cancer microenvironment and stimulated them to produce prostaglandin E2, which supported colon cancer stemness and tumor growth. Clinically, tumor IL33 expression associated with poor survival in patients with metastatic colon cancer. Thus, IL33 dually targets tumor cells and macrophages and endows stem-like qualities to colon cancer cells to promote carcinogenesis. Collectively, our work reveals an immune-associated mechanism that extrinsically confers cancer cell stemness properties. Targeting the IL33 signaling pathway may offer an opportunity to treat patients with metastatic cancer.
To achieve superior therapeutic efficacy, the combination chemotherapy using two or more anticancer drugs in clinical practice has been generally accepted as a feasible strategy. On account of the concept of combination chemotherapy, co-delivery of anticancer drugs with nanotechnology gradually becomes a desired strategy and one of the research frontiers on modern drug delivery. In recent years, nano drug co-delivery system (NDCDS), which loads at least two anticancer drugs with different physicochemical and pharmacological properties into a combination delivery system, has achieved rapid development. NDCDS synergistically inhibited the growth of the tumor compared with the free drugs. In this review, we highlighted the current state of co-delivery nanoparticles and the most commonly used nanomaterial, discussed challenges and strategies, and prospect future development. ARTICLE HISTORY
Summary The emerging Porcine circovirus type 3 (PCV3) is associated with porcine dermatitis and nephropathy syndrome, reproductive failure and cardiac and multisystemic inflammation. To trace the prevalence and evolution of PCV3 in pigs with respiratory diseases or digestive diseases in China, 616 samples were collected from 21 provinces or municipalities of China from 2015 to 2017. All samples were analysed with PCR and a cap‐gene‐based phylogeny. The results indicated that the positive rate of PCV3 was 12.2% (75/616) at the sample level; 24.1% (42/174) at the farm level; 10.4% (50/480) in the digestive‐disease‐affected samples; 26.6% (25/94) in the respiratory‐disease‐affected samples; all 42 healthy samples were negative for PCV3. A statistical analysis showed that PCV3 infection was closely associated with both digestive diseases (p < 0.05) and respiratory diseases (p < 0.01). A sequence analysis revealed that the cap genes of the 51 PCV3 strains identified in our study shared nucleotide homologies of 97.2%–100% and amino acid homologies of 96.3%–100%. A total of 17 amino acid mutations were observed among the Cap proteins of the 51 PCV3 strains, of which R10/K, A24/V, R27/K, T77/S, F104/Y, I150/L are mutations among worldwide strains. A phylogenetic analysis demonstrated that the 51 PCV3 strains formed three clades, including PCV3a (15/51, 29.4%), PCV3b (21/51, 41.2%) and PCV3c (15/51, 29.4%). These data provide evidence that PCV3 exhibits high prevalence and genetic diversity and is associated with digestive diseases and respiratory diseases in pig.
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