The present study was undertaken to investigate the expression of prostate-specific membrane antigen (PSMA) in normal breast tissues, in cancerous breast tissues and in distant metastases from patients with breast cancer. Immunohistochemical analysis was performed to determine PSMA expression and angiogenic activity using anti-PSMA mAb and anti-CD31 mAb respectively. Immunofluorescence staining was applied to confirm the exact co-localization of PSMA and CD31. We observed different patterns of PSMA expression between normal and cancerous tissues. Normal breast tissues showed PSMA expression only in normal glandular cells. However, primary breast tumors and distant metastases showed PSMA expression in tumor cells and in tumor-associated neovasculature. PSMA score group status in primary breast tumors was significantly associated with histologic type and tumor grade (p = 0.026 and p = 0.004 respectively). Distant metastases showed higher PSMA expression in tumor-associated neovasculature comparing with primary tumors. Moreover, brain tumor-associated neovasculture had significantly higher expression of PSMA comparing with bone tumor-associated neovasculture. The localized binding of PSMA mAb to the neovasculature endothelium was confirmed with the double Immunofluorescence staining. Ga-PSAM imaging of a patient with metastatic breast cancer showed strong tracer uptake in all known skeletal metastases. To the best of our knowledge, this study is the second one that has assessed PSMA expression in a large number of breast cancer patients. Our findings showed that PSMA is particularly expressed in tumor-associated neovasculature of breast tumors and its distant metastases, thus enhancing the evidence on the potential usefulness of PSMA as a therapeutic vascular target.

Crayfish can be used as model organisms in phylogeographic and divergence time studies if reliable calibrations are available. This study presents a comprehensive investigation into the phylogeography of the European stone crayfish ( Austropotamobius torrentium ) and includes samples from previously unstudied sites. Two mitochondrial markers were used to reveal evolutionary relationships among haplogroups throughout the species’ distributional range and to estimate the divergence time by employing both substitution rates and geological calibration methods. Our haplotype network reconstruction and phylogenetic analyses revealed the existence of a previously unknown haplogroup distributed in Romania's Apuseni Mountains. This haplogroup is closely related to others that are endemic in the Dinarides, despite their vast geographical separation (~600 km). The separation is best explained by the well‐dated tectonic displacement of the Tisza–Dacia microplate, which started in the Miocene (~16 Ma) and possibly carried part of the A. torrentium population to the current location of the Apuseni Mountains. This population may thus have been isolated from the Dinarides for a period of ca. 11 m.y. by marine and lacustrine phases of the Pannonian Basin. The inclusion of this geological event as a calibration point in divergence time analyses challenges currently accepted crayfish evolutionary time frames for the region, constraining the evolution of this area's crayfish to a much earlier date. We discuss why molecular clock calibrations previously employed to date European crayfish species divergences should therefore be reconsidered.

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Using the fixed point method, we establish a generalized Ulam -Hyers stability result for the monomial functional equation in the setting of complete random p-normed spaces. As a particular case, we obtain a new stability theorem for monomial functional equations in β-normed spaces.