Triple-negative breast cancer (TNBC) is a group of heterogeneous and refractory breast cancers with the absence of estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor ...receptor 2 (HER2). Over the past decade, antibody drug conjugates (ADCs) have ushered in a new era of targeting therapy. Since the epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) are over expressed on triple-negative breast cancer, we developed novel ADCs by conjugating benzylguanine (BG)-modified monomethyl auristatin E (MMAE) to EpCAM- and EGFR-specific SNAP-tagged single chain antibody fragments (scFvs). Rapid and efficient conjugation was achieved by SNAP-tag technology. The binding and internalization properties of scFv-SNAP fusion proteins were confirmed by flow cytometry and fluorescence microscopy. The dose-dependent cytotoxicity was evaluated in cell lines expressing different levels of EGFR and EpCAM. Both ADCs showed specific cytotoxicity to EGFR or EpCAM positive cell lines via inducing apoptosis at a nanomolar concentration. Our study demonstrated that EGFR specific scFv-425-SNAP-BG-MMAE and EpCAM-specific scFv-EpCAM-SNAP-BG-MMAE could be promising ADCs for the treatment of TNBC.
This study was undertaken to investigate fetal anatomy with the use of standard views and a scoring system, to investigate interobserver variability, and to compare ultrasound modes simultaneously ...with the measurement of nuchal translucency (11-14 weeks' gestation).
Twelve fetal anatomic regions were defined as standard views (n
=
60) and assessed with the use of a scoring system (1
=
not seen, 2
=
seen uncertainly, 3
=
seen acceptably, 4
=
well seen, and 5
=
very well seen). The variation of scores and interobserver variability were analyzed (n
=
40), the B-mode was compared with tissue harmonic and compound imaging (n
=
60).
The overall average score (11
+
0 to 13
+
6 weeks) with tissue harmonic and compound imaging was 3.56 (well seen) and increased with gestation. The highest score was for the neck and the lowest for the cerebellum. The proportion of identical scores for each given region showed a range of 58% to 83%. Tissue harmonic and compound imaging was significantly better than the plain B-mode,
P < .001 (sign test).
Transabdominal fetal anatomy scanning with standard fetal anatomy views at 11 to 14 weeks of gestation is possible with good reproducibility and demonstrability when harmonic and compound imaging are used.
