Autologous adipose tissue or adipose tissue with additive adipose-derived mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast cancer patients who undergo mastectomy. ADSCs play an important role in the angiogenesis and adipogenesis, which make it much better than other materials. However, ADSCs may promote residual tumor cells to proliferate or metastasize, and the mechanism is still not fully understood. In this study, we demonstrated that human ADSCs (hADSCs) could facilitate tumor cells growth after co-injection with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but hADSCs showed limited effect on the growth of MDA-MB-231 BCCs. Intriguingly, compared with ZR-75-30 tumor cells, MCF7 tumor cells were more potentially promoted by hADSCs in the aspects of angiogenesis and proliferation. Consistent with this, cytokine and angiogenesis array analyses showed that after co-injection with hADSCs, the CXCL1 and CXCL8 concentration were significantly increased in MCF7 tumor, but only moderately increased in ZR-75-30 tumor and did not increase in MDA-MB-231 tumor. Furthermore, we found that CXCL1/8 were mainly derived from hADSCs and could increase the migration and tube formation of human umbilical vein endothelial cells (HUVECs) by signaling via their receptors CXCR1 and CXCR2. A CXCR1/2-specific antagonist (SCH527123) attenuated the angiogenesis and tumor growth in vivo. Our findings suggest that CXCL1/8 secreted by hADSCs could promote breast cancer angiogenesis and therefore provide better understanding of safety concerns regarding the clinical application of hADSCs and suggestion in further novel therapeutic options. Stem Cells 2017;35:2060-2070.
In this paper, we first show a projectivization formula for the derived category, where E is a coherent sheaf on a regular scheme which locally admits two-step resolutions. Second, we show that "flop-flop=twist" results hold for flops obtained by two different Springer-type resolutions of a determinantal hypersurface. As a consequence this gives higher dimensional examples of flops presenting perverse schobers proposed by 16]. Applications to symmetric powers of curves, Abel-Jacobi maps and Θ-flops following Toda [72] are also discussed.
Paclitaxel (PTX) has shown pleiotropic immunologic effects on the tumor microenvironment, and nanomicelle has emerged as a promising strategy for PTX delivery. However, the detailed mechanisms remain to be fully elucidated. Meanwhile, immunogenic cell death (ICD) is an effective approach to activate the immune system. This study investigated the ICD effect of PTX and how nanomicelle affected the immune-activation ability of PTX. Methods: The ICD effects of PTX were identified via the expression of ICD markers and cell vaccine experiment. Tumor size and overall survival in multiple animal models with treatment were monitored to evaluate the antitumor effects. The mechanisms of PTX-induced ICD and antitumor immunity were determined by detecting gene expression related to ER stress and analyzing immune cell profile in tumor after treatment. Results: We revealed the immune-regulation mechanism of PTX nanomicelle by inducing ICD, which can promote antigen presentation by dendritic cells (DCs) and activate antitumor immunity. Notably, nanomicelle encapsulation protected the ICD effects and immune activation, which were hampered by immune system impairment caused by chemotherapy. Compared with traditional formulations, a low dose of nanomicelle-encapsulated PTX (nano-PTX) treatment induced immune-dependent tumor control, which increased the infiltration and function of both T cells and DCs within tumors. However, this antitumor immunity was hampered by highly expressed PD-1 on tumor-infiltrating CD8 + T cells and upregulated PD-L1 on both immune cells and tumor cells after nano-PTX treatment. Combination therapy with a low dose of nano-PTX and PD-1 antibodies elicited CD8 + T cell-dependent antitumor immunity and remarkably improved the therapeutic efficacy. Conclusions: Our results provide systemic insights into the immune-regulation ability of PTX to induce ICD, which acts as an inducer of endogenous vaccines through ICD effects, and also provides an experimental basis for clinical combination therapy with nano-PTX and PD-1 antibodies.
miR-15 (microRNA 15) and miR-16 are frequently deleted or down-regulated in many cancer cell lines and various tumour tissues, suggesting that miR-15a/16-1 plays important roles in tumour progression and might be a method for cancer treatment. We have developed a vector-based plasmid to explore the anti-tumour efficacy of miR-15a/16-1 in colon cancer in vivo. It is proposed that miR-15a and miR-16-1 target cyclin B1 (CCNB1), which associates with several tumorigenic features such as survival and proliferation. The levels of miR-15a and miR-16-1 in colon cancer cells were inversely correlated with CCNB1 expression, and there was consensus between miR-15a/16-1 and CCNB1 mRNA sequences by analysing homology. Vector-based miR-15a/16-1 expression plasmid was constructed and transfected into HCT 116 and SW620 colon cancer cells in vitro. The effects produced on cell viability and angiogenesis were analysed using flow cytometric analysis, colony formation analysis and tube formation analysis. CCNB1 expression down-regulation was checked by Western blotting. Systemic delivery of miR-15a/16-1 plasmids encapsulated in cationic liposome led to a significant inhibition of subcutaneous tumour growth and angiogenesis in tumour tissues, whereas no effects were observed with liposome carrying the non-specific plasmid. In summary, miR-15a/16-1 has been applied in colon cancer treatment in vivo, and resulted in effective colon tumour xenografts growth arrest and angiogenesis decrease. These findings suggest that systemic delivery of vector-based miR-15a/16-1 expression plasmid can be an approach to colon cancer therapy.
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