The anti-tumoral effects of the oxygen carrier YQ23 in a triple-negative breast cancer syngeneic model.

BACKGROUND: Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype, is associated with poor prognosis and high mortality rate. In the search for effective therapeutic options, preclinical studies have suggested using systemic oxygenation to inhibit tumor growth and metastasis in various cancer models, including TNBC, by weakening the hypoxia-A2A adenosine receptors (A2AR)-driven immunosuppression in the tumor microenvironment (TME). In our present study, a hemoglobin-based oxygen carrier (HBOC) "YQ23" was tested for its role in modulating the TME and tumor inhibition. METHODS: A syngeneic TNBC mouse model was established by inoculating 4T1 cells subcutaneously in BALB/c mice. Tumor (~100 mm3) bearing mice were treated either with saline or YQ23 (400 mg/kg) i.v. once weekly. To prove the immune-regulatory role of YQ23, CD4+ and CD8+ cells were depleted from a group of mice prior to treatment. Tumor growth was monitored for four weeks while xenografts were isolated at the end of the treatment for ex vivo immunohistological examination. RESULTS: YQ23 significantly inhibited the tumor growth, and this suppressive effect was abolished by depleting the host immune cells. Immunohistochemical staining of xenograft sections showed YQ23 reduced the level of hypoxia and adenosine producing ecto-enzyme CD73. Although there was no significant difference in the make up of the intra-tumoral immune populations, we observed a down-regulation of the immune checkpoint PD-1. In concordance with the weakened immunosuppression, the inflammatory cytokine interferon γ and cytolytic granzyme B were upregulated. CONCLUSIONS: YQ23 treatment may be a potential therapeutic strategy to modulate the TME in TNBC.

The effect of social fathers on the cognitive skills of out-of-wedlock children in the U.S.

There are two competing views regarding the presence of social fathers on childrens' cognitive ability: (1) either the social father provides more financial resources which benefit the children or (2) the mother with new partners may shift the focus away from the children. Previous research focused on older children or adolescents and ignored the self-selection problem. We use data from the Fragile Families and Child Wellbeing Study (FFCWS), and a sample of younger children. Using propensity score matching method (nonparametric methods), we find that children with social fathers scored around three points less in a cognitive ability test than children living only with biological mothers (assuming that self-selection is based on observables). The result remains robust when using a control-function analysis (parametric method).