Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection

UVB-induced cutaneous photodamage/photoaging is characterized by qualitative and quantitative deterioration in dermal extracellular matrix (ECM) components such as collagen and elastic fibers. Disappearance of microfibrillar-associated protein 4 (MFAP-4), a possible limiting factor for cutaneous elasticity, was documented in photoaged dermis, but its function is poorly understood. To characterize its possible contribution to photoprotection, MFAP-4 expression was either augmented or inhibited in a human skin xenograft photodamage murine model and human fibroblasts. Xenografted skin with enhanced MFAP-4 expression was protected from UVB-induced photodamage/photoaging accompanied by the prevention of ECM degradation and aggravated elasticity. Additionally, remarkably increased or decreased fibrillin-1-based microfibril development was observed when fibroblasts were treated with recombinant MFAP-4 or with MFAP-4-specific siRNA, respectively. Immunoprecipitation analysis confirmed direct interaction between MFAP-4 and fibrillin-1. Taken together, our findings reveal the essential role of MFAP-4 in photoprotection and offer new therapeutic opportunities to prevent skin-associated pathologies

The biological features and prognosis of breast cancer diagnosed during pregnancy: A case-control study.

Background. Breast cancer during pregnancy (BCP) is relatively rare and is associated with controversies about its biology and prognosis. Hence, we designed a case-control study to examine tumor features and outcome in a series of BCP patients diagnosed and treated in a single institution. Material and methods. We identified 65 patients diagnosed with BCP and for each; we selected two non-pregnant breast cancer patients, who were matched for age, year of surgery, stage, and neoadjuvant chemotherapy. We then compared the differences in pathology, immunohistochemical features (ER, PR, HER2 and ki-67), disease-free (DFS) and overall survival (OS). Results. We did not find any significant differences in tumor characteristics between the two groups. However, at a median follow-up of four years, BCP patients had an inferior DFS (HR 2.3; 95% CI 1.3-4.2), after adjustment for possible confounding covariates. No difference in OS was observed. However, upon restricting the analysis to patients who did not receive neoadjuvant chemotherapy, patients with BCP had inferior OS as well (HR 2.6; 95% CI 1.0-6.5). No association between induction of abortion and prognosis was observed. Conclusions. While we did not observe any differences in tumor features, BCP patients have poorer prognosis compared to age and stage-matched control. Further studies should try to elucidate reasons for such poor outcome.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe