Metformin reverses PARP inhibitors-induced epithelial-mesenchymal transition and PD-L1 upregulation in triple-negative breast cancer.

Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as promising targeted therapies for BRCA-mutated cancers by blocking repair of DNA double-strand breaks. However, resistance to PARP inhibitors (PARPi) has been described in some patients lowering the overall response rates. To investigate the underlying mechanisms of PARPi resistance, we developed the adaptive resistant clones in triple-negative breast cancer cell lines.

Synergism of PARP inhibitor fluzoparib (HS10160) and MET inhibitor HS10241 in breast and ovarian cancer cells.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are promising targeted therapeutics for breast and ovarian cancers bearing a germline mutation ( ), and several have already received regulatory approval in the United States. In patients with a cancer, PARPi can increase the burden of unrepaired DNA double-strand breaks by blocking PARP activity and trapping PARP1 onto damaged DNA. Resistance to PARP inhibitors can block the formation of DNA double-strand breaks through BRCA-related DNA repair pathway.

Preparation of polyphosphazene hydrogels for enzyme immobilization.

We report on the synthesis and application of a new hydrogel based on a methacrylate substituted polyphosphazene. Through ring-opening polymerization and nucleophilic substitution, poly[bis(methacrylate)phosphazene] (PBMAP) was successfully synthesized from hexachlorocyclotriphosphazene. By adding PBMAP to methacrylic acid solution and then treating with UV light, we could obtain a cross-linked polyphosphazene network, which showed an ultra-high absorbency for distilled water.

Induction of biliary cholangiocarcinoma cell apoptosis by 103Pd cholangial radioactive stent gamma-rays.

Background: In recent years, interventional tumor therapy, involving implantation of intra-cholangial metal stents through percutaneous trans-hepatic punctures, has provided a new method for treating cholangiocarcinoma. (103)Pd cholangial radioactive stents can concentrate high radioactive dosages into the malignant tumors and kill tumor cells effectively, in order to prevent re-stenosis of the lumen caused by a relapsed tumor. The aim of the present study was to investigate the efficacy of gamma-rays released by the (103)Pd biliary duct radioactive stent in treating cholangiocarcinoma via induction of biliary cholangiocarcinoma cell apoptosis.

103Pd-induced apoptosis of proliferative smooth muscle cells in bile ducts of dogs: significance and effects on related genes.

Background: With the objective of developing a locally-produced radioactive stent, the present study used in vivo animal experiments to explore apoptosis of proliferative smooth muscle cells resulting from facilitation of the expression of genes caused by gamma-radiation in order to prevent bile duct restenosis. We therefore explored the effects and significance of gamma-radiation on the activity of caspase-3, Fas and Bcl-2 genes in apoptosis of proliferative smooth muscle cells in the bile duct walls of dogs.

Methods: Twelve dogs were randomly divided into 2 groups (6 in each group).

103Pd radioactive stent inhibits biliary duct restenosis and reduces smooth muscle actin expression during duct healing in dogs.

Background: This study was designed to assess the expression of smooth muscle actin (SMA) in the healing process after implanting a (103)Pd radioactive stent in the biliary duct, and to discuss the function and significance of this stent in preventing biliary stricture formation.

Methods: A model of biliary injury in dogs was made and then a (103)Pd radioactive stent was positioned in the biliary duct. The expression and distribution of SMA were assessed in the anastomotic tissue 30 days after implantation of the stent.

[Effect of 103palladium radioactive stent on expression of smooth muscle actin in bile duct during healing process and its significance].

Objective: To observe the effect of radiation on the expression of smooth muscle actin (SMA) in the bile duct during the healing process and the inhibitory function of (103)palladium (Pd) radioactive stent on the stricture of bile duct after injury.

Methods: Twelve mongrel dogs were made models of bile duct injury: duodenotomy was performed, a balloon catheter was inserted into the general bile duct and saline with high pressure was perfused thereinto to cause laceration of the mucosa, and then the balloon catheter was withdrawn and ordinary alloy stent or (103)Pd radioactive stent was inserted into the general bile duct. Thirty days after the dogs were killed.

[Expression and significance of caspase-3 gene in apoptotic muscle cells 103Pd radioactive stent bile duct in dogs].

Objective: To discuss the expression and significance of caspase-3 gene in the apoptotic muscle cells in gamma-radiation-induced muscle cell lines.

Methods: The caspase-3 mRNA in the control and gamma-radiation induced apoptotic muscle cells was analysed by RT-PCR.

Results: The expression of caspase-3 gene transcript was higher in 103Pd radioactive stent dog bile duct than in general stent dog bile duct, and apoptotic muscle cells were higher in 103Pd radioactive stent dog bile duct than in general stent dog bile duct.

Intrabiliary radiation inhibits smooth muscle formation and biliary duct remodelling after balloon overstretching injury in dogs.

Background: Internal metallic stents have been widely used in clinical practice, but a high postoperative restenosis rate limits its application. The purpose of this study was to determine the effect of intrabiliary radiation on muscle formation and biliary duct remodeling after biliary duct balloon injury in dogs.

Methods: Twenty male dogs (15 - 20 kg) were randomly divided into treatment group (n = 10) and control group (n = 10).