Clinical outcomes of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and anti-PD-1 immunotherapy for unresectable intrahepatic cholangiocarcinoma.

OBJECTIVE: To compare the treatment efficacy and safety of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death 1 (PD-1) immunotherapy combined with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). METHODS: Patients with unresectable ICC received TKIs and anti-PD-1 immunotherapy combined with HAIC (HTP group) or TACE (TTP group) were included. The clinicopathological characteristics, treatment efficacy, and adverse events (AEs) were compared between the two groups. The factors associated with response rate to the treatments were evaluated. RESULTS: A total of 58 patients were enrolled, with 39 in the HTP group and 19 in the TTP group. Patients in the HTP group exhibited a better objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] 48.7% vs 15.8%, P = 0.02; modified RECIST [mRECIST] 61.5% vs 21.1%, P = 0.004) and disease control rate (DCR; 82.1% vs 36.8%, P = 0.001) compared to the TTP group. The median progression-free survival (PFS) rate was not reached and the 1-year PFS rate was 61.9% in the HTP group, whereas the median PFS was 11.0 months and the 1-year PFS rate was 31.6% in the TTP group. The type of treatment and tumor size were significant factors for the response rate. More patients in the HTP group presented rash, abdominal pain and hand-foot syndrome, but all AEs were relieved after symptomatic treatment, and no treatment-related death occurred. CONCLUSIONS: For unresectable ICC, treatment with a combination of HAIC with TKIs and anti-PD-1 immunotherapy was effective and safe. Tumor size might serve as a significant factor for the response rate following treatment for unresectable ICC.

A general strategy to prepare different types of polysaccharide-graft-poly(aspartic acid) as degradable gene carriers.

Owing to their unique properties such as low cytotoxicity and excellent biocompatibility, poly(aspartic acid) (PAsp) and polysaccharides are good candidates for the development of new biomaterials. In order to construct better gene delivery systems by combining polysaccharides with PAsp, in this work, a general strategy is described for preparing series of polysaccharide-graft-PAsp (including cyclodextrin (CD), dextran (Dex) and chitosan (CS)) gene vectors. Such different polysaccharide-based vectors are compared systematically through a series of experiments including degradability, pDNA condensation capability, cytotoxicity and gene transfection ability. They possess good degradability, which would benefit the release of pDNA from the complexes. They exhibit significantly lower cytotoxicity than the control 'gold-standard' polyethylenimine (PEI, ∼25kDa). More importantly, the gene transfection efficiency of Dex- and CS-based vectors is 12-14-fold higher than CD-based ones. This present study indicates that properly grafting degradable PAsp from polysaccharide backbones is an effective means of producing a new class of degradable biomaterials.

Acetonitrile-triaqua-[3-eth-oxy-1,8-(3,6,9-trioxaundecane-1,11-diyldi-oxy)-9H-xanthen-9-one]terbium(III) tris-(perchlorate).

In the title compound, [Tb(CH(3)CN)(C(23)H(26)O(8))(H(2)O)(3)](ClO(4))(3), the Tb(3+) atom is eight-coordinated by one N atom of an acetonitrile molecule, three water O atoms and four ligand O atoms. The Tb(3+) atom is located on one side of the macrocycle and the carbonyl oxygen coordinated to the terbium [Tb1-O1= 2.210 (3) Å] is bent out of the xanthone plane by 0.514 (3) Å. The geometry around terbium is a distorted two-capped trigonal prism.