Design, Synthesis, and Biological Evaluation of Androgen Receptor (AR) Antagonist-Heat Shock Protein 90 (Hsp90) Inhibitor Conjugates for Targeted Therapy of Castration-Resistant Prostate Cancer.

Androgen deprivation in cases of castration-resistant prostate cancer (CRPC) leads to adverse effects, including loss of muscle and bone mass and gain of subcutaneous fat. The tumor-specific suppression of androgen receptor (AR) signaling, while not global, may reduce side effects. We present a class of small-molecular conjugates consisting of an AR antagonist linked to a heat shock protein 90 (Hsp90) inhibitor. We demonstrate that the high accumulation of Hsp90 on the surface of CRPC cells allows uptake of conjugates and increases the enrichment of drugs in the tumor cells. After penetrating prostate cancer cells, the conjugates not only inhibit AR function by the antagonist component but also bind to Hsp90 and suppress the AR protein level. Compared to AR antagonists, these conjugates showed improved tumor-targeting ability and enhanced potency against Enzalutamide-resistant 22Rv1 cells.

[Evaluation of the prevalence of the maxillary molars with two palatal roots by cone-beam CT].

OBJECTIVE: To investigate the characteristic of the maxillary molars with two palatal roots and its prevalence by cone-beam computered tomography. METHODS: Cone-beam CT (CBCT) images of dentitions were collected retrospectively from 528 patients comprising 1957 maxillary molars. The characteristic and prevalence of maxillary molars with two palatal roots was analyzed. The tooth position, sex and unilateral and bilateral occurrence were recorded. RESULTS: The prevalence of two palatal roots was 0.72%(14/1957). Maxillary second molar with two palatal roots was detected in 1.12%(11/979), which showed a statistically higher prevalence than maxillary first molar 0.31%(3/978). This prevalence did not differ with sex or the side(P > 0.05). The mean distance of interorifice from the mesiolpalatal canal to the distopalatal canal was (2.84 ± 0.50) mm, and the angle between two palatal roots was on average (34.6 ± 16.1) °,which were significantly greater than the mean distance of interorifice from the two buccal roots (2.15 ± 0.82) mm and the angle between the two roots was (21.3 ± 12.2) °. CONCLUSIONS: The prevalence of maxillary second molars with two palatal roots was higher than that of the first malars. The angle between the two palatal roots brings difficulty to root canal therapy, so the consciousness of double palatal roots of maxillary molars was helpful for clinical operation.