PARP inhibitor olaparib sensitizes esophageal carcinoma cells to fractionated proton irradiation.

Proton beam therapy (PBT) combined with chemotherapy, such as cis-diamminedichloroplatinum (II) (CDDP) and 5-fluorouracil (5-FU), has been employed as an alternative approach to improve clinical outcomes. PBT has been reported to be effective against esophageal cancer. However, apart from 5-FU and CDDP, almost no other drug has been tested in combined chemotherapy with PBT. Therefore, we investigated the effects of a poly (ADP-ribose) polymerase inhibitor on enhancing proton beam effects using esophageal cancer cell lines that exhibit resistance to radiation and CDDP. Esophageal squamous cell carcinoma cell lines OE-21 and KYSE-450 were exposed to the drugs for 1 h prior to irradiation. The cell survival curve was obtained using a clonogenic assay and the sensitizing effect ratio (SER) was calculated. The clonogenic assay was used to compare the effect of multi-fractioned irradiation between 8 Gy/1 fraction (fr) and 8 Gy/4 fr. γH2AX, Rad51, BRCA1, BRCA2 and 53BP1 foci were detected via immunofluorescence. Olaparib exhibited an SER of 1.5-1.7 on PBT. The same sensitizing effect was exhibited in multi-fractioned irradiation, and the combined use increased the expression of double-strand breaks and homologous recombination-related genes in an additive manner. Such additive effects were not observed on non-homologous end joining-related genes. We demonstrated that olaparib has a high sensitizing effect on PBT in platinum- and radiation-resistant esophageal cancer cells. Our results suggest a potential clinical application of olaparib-proton irradiation (PT) against platinum- and radiation-resistant esophageal cancer.

Changes of portal pressure before and after interventional embolization with α-cyanoacrylate alkyl for portal hypertension and their clinical significance / 中华消化杂志

Objective To study the changes of portal vein pressure before and after interventional embolization with α-cyanoacrylate alkyl and their clinical significance. Methods Thirty five patients with esophageal-gastric variceal bleeding were included. Esophageal-gastric fundal varices were embolized with e-cyanoacrylate alkyl in 35 patients, and 10 of them were treated with combination of partial splenic emblization. Portal pressure was measured directly before and after interventional embolization. The patients were followed up for 3-18 months. The changes of the liver functions and complications after the embolization were observed. Results All bleeding were controlled successfully. The main portal pressure in those who received variceal embolization only increased significantly from (32.54±5.23) cm H2O (1 cm H2O=0. 098 kPa) to (37.45±5. 11) cm H2O; superior mesenteric vein pressure increased from (31.46±4.35) cmH2O to (34.33±4.68)cm H2O; and the level of serum albumin raised from (30.45±5.78) g/L to (34.57±6.84) g/L 3 weeks after embolization. Whereas the main portal pressure in those who received both variceal and partial splenic embolizations, decreased significantly from (32. 68±4. 89) cm H2O to (28. 70±4. 58) cm H2O; superior mesenteric vein pressure decreased from (31.46±4.35) cm H2O to (28.03±4.12) cm H2O; and splenic vein pressure decreased from (32.89±4.79) cm H2O to (28.81±5. 12) cm H2O.Conclusions Esophageal-gastric variceal embolization is effective for varieeal bleeding. The increase of main portal pressure after embolization may be benefit for liver function, while the rise of superior mesenteric vein pressure may increase the risk of portal hypertensive gastrointestinal re-bleeding.Esophageal-gastric variceal embolization combined with partial splenic embolization may reduce the incidence of portal hypertension and gastrointestinal re-bleeding, but will increase the risk of ascites.