The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1–P4′ amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.
<b><i>Introduction:</i></b> There is a paucity of reports describing the clinical course and likely postnatal outcomes of prenatally identified simple cystic abdominopelvic lesions which are not associated with the ovary. <b><i>Objective:</i></b> The aim of this study was to describe the natural history and postnatal outcomes of prenatally discovered abdominopelvic cystic lesions seen at our center. <b><i>Methods:</i></b> This study is a retrospective review of all newborns with prenatally discovered non-ovarian simple cystic abdominal or pelvic lesions (September 2012–December 2018). Prenatal solid organ involvement, lesion size, and postnatal clinical outcomes are described. <b><i>Results:</i></b> Sixty-six patients with 68 cystic lesions were identified; 22 patients with 24 lesions met the defined study criteria and were included. Eleven (46%) resolved prenatally, while 5 (21%) resolved by 18 months of age. Of the 10 lesions associated with an organ, 4 (40%) resolved prenatally. Of the remaining 14 lesions not associated with a solid organ, 7 (50%) resolved prenatally. Seven lesions (29%) required postnatal surgical intervention. Larger maximum prenatal lesions tended toward postnatal surgical intervention (one-way ANOVA: <i>p</i> = 0.072). <b><i>Conclusions:</i></b> The majority of simple non-ovarian cystic abdominopelvic lesions at our center resolved in the perinatal period. Due to the low frequency of these lesions at fetal centers, a larger multicenter study based on a consistent monitoring protocol should be undertaken to better describe the resolution patterns of simple non-ovarian cystic lesions for improved prenatal counseling.
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