ABSTRACT
Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.
ABSTRACT
Objective To explore the CT features of gastrointestinal tract diospyrobezoar and its complications,to improve the recognition. Methods The plain CT scan of 36 patients with gastrointestinal tract diospyrobezoar confirmed by gastroscope and surgery were analyzed retrospectively.Results The number and location of diospyrobezoar showed by CT were consistent with the results of gastroscope and surgery.There were 1 1 cases of stomach diospyrobezoar,1 9 cases of small intestine diospyrobezoar,and 6 cases of stomach and small intestine diospyrobezoar.32 cases were solitary lesion,and 4 cases were multiple lesions.A total of 41 diospyrobezoars were removed, most of which were wel-l defined ovoid mass.3 1 lesions presented mottled internal gas bubbles with high-density encapsulating wall.6 lesions showed mottled gas pattern without encapsulating wall.4 lesions showed uneven high density.Over time,1 lesion moved in the digestive tract and the boundary and density were changed.Complications:gastric and duodenal diospyrobezoar accompanied by gastric retention,which manifested as a significant expansion of the gastric cavity effusion.Small intestine diospyrobezoar was accompanied by small bowel obstruction,which showed that the proximal intestinal tube of the diospyrobezoar was obviously dilated,and the distal intestine was suddenly collapsed.There was a focal transition zone between them.Conclusion Gastrointestinal tract diospyrobezoar has a variety of CT manifestations,of which oval shape,clear boundary,uneven mass composed of gas and soft tissue are common.