Annexin A2 (ANXA2) is a well-known calcium-dependent phospholipid binding protein widely distributed in the nucleus, cytoplasm and extracellular surface of various eukaryotic cells. It has been recognized as a pleiotropic protein affecting a wide range of molecular and cellular processes. Dysregulation and abnormal expression of ANXA2 are linked to a large number of prevalent diseases, including autoimmune and neurodegenerative disease, antiphospholipid syndrome, inflammation, diabetes mellitus and a series of cancers. Accumulating data suggest that ANXA2 is aberrantly expressed in a wide spectrum of cancers, and exerts profound effects on tumor cell adhesion, proliferation, apoptosis, invasion and metastasis as well as tumor neovascularization via different modes of action. However, despite significant research, our knowledge of the mechanism by which ANXA2 participates in cancer development remains fragmented. The present review systematically summarizes the effects of ANXA2 on tumor progression, in an attempt to gain an improved understanding of the underlying mechanisms and to provide a potential effective target for cancer therapy.

CCR9+ T cells have an increased potential to be activated and therefore may mediate strong antitumor responses. Here, we found, however, that CCL25, the only chemokine for CCR9+ cells, is not expressed in human or murine triple-negative breast cancers (TNBCs), raising a hypothesis that intratumoral delivery of CCL25 may enhance antitumor immunotherapy in TNBCs. We first determined whether this approach can enhance CD47-targeted immunotherapy using a tumor acidity–responsive nanoparticle delivery system (NP-siCD47/CCL25) to sequentially release CCL25 protein and CD47 small interfering RNA in tumor. NP-siCD47/CCL25 significantly increased infiltration of CCR9+CD8+ T cells and down-regulated CD47 expression in tumor, resulting in inhibition of tumor growth and metastasis through a T cell–dependent immunity. Furthermore, the antitumor effect of NP-siCD47/CCL25 was synergistically enhanced when used in combination with programmed cell death protein–1/programmed death ligand-1 blockades. This study offers a strategy to enhance immunotherapy by promoting CCR9+CD8+ T cell tumor infiltration.

The use of arsenic trioxide (As2O3, ATO) combined with all-trans retinoic acid (ATRA) has recently been reported to induce remission in patients with acute promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly due to the small number of the available cases. In this study, therefore, we present a clinical study using a combination of ATO with low-dose ATRA (LD-ATRA) to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients). Therapeutic outcomes using the ATO/LD-ATRA approach were compared with those of APL patients treated either with ATO alone (65 patients) or ATRA alone (51 patients). The results showed that the ATO/LD-ATRA approach provided significantly better therapeutic outcomes as compared to either ATO or ATRA alone, as evidenced by lower mortality, a higher CR rate and a reduced period to CR. In addition, the toxic side-effects have been no worse with the combined ATO/LD-ATRA treatment than with either ATO or ATRO alone and in some cases have been reduced. These data suggest that the ATO/LD-ATRA regimen is superior to either regimen given alone to patients with APL.

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The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM.