Pemigatinib in previously treated Chinese patients with locally advanced or metastatic cholangiocarcinoma carrying FGFR2 fusions or rearrangements: A phase II study.

OBJECTIVE: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. BACKGROUND: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries. METHODS: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3-week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee. RESULTS: As of January 29, 2021, 31 patients were enrolled. The median follow-up was 5.1 months (range, 1.5-9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3-68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4-100). The median time to response was 1.4 months (95% CI, 1.3-1.4), the median duration of response was not reached, and the median progression-free survival was 6.3 months (95% CI, 4.9-not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment-emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostly

[The effects of transferring DPC4-adenovirus on pancreatic adenocarcinoma cells].

OBJECTIVE: To observe the effect of transferring DPC4-adenovirus on pancreatic cells. METHODS: The recombined wild DPC4 gene and replication-deficiency adenovirus was transfected into cultured pancreatic adenocarcinoma cells and exograft pancreatic adenocarcinoma at the axillary flank of nude mice. The expression of objective gene was evaluated by flow cytometry and immunohistological chemistry assay. The cell cycle was also measured by flow cytometry. The related data were collected and analyzed with statistical methods. RESULTS: in viro, the suppression rate of transferring DPC4-adenovirus on cultured pancreatic adenocarcinoma cells was 30% on the fourth day. The fluorescence intensity of PD cells, P cells, HD cells, PA (Pc-3-Adenovirus) cells was higher than that of HS766T cells and HA cells (P<0.05). After transfection, PD cells proliferated most slowly, while H and HA proliferated most quickly (P<0.05). Significant difference was seen between the volume of exograft tumor of the controlled group and that of the treatment group (P<0.05). After transfection, the proliferation of cultured pancreatic adenocarcinoma cells was suppressed, the cells of G1 phase increased obviously (P<0.05) while the cells of S phase decreased (P<0.05), although no obvious increase of apoptosic cell number was observed. CONCLUSION: The DPC4-adenovirus can be transfected into pancreatic adenocarcinoma cells effectively. It could suppress the proliferation of pancreatic adenocarcinoma cells in vivo and in vitro.

Modified techniques of heterotopic total small intestinal transplantation in rats.

AIM: To establish a successful model of heterotopic total small intestinal transplantation (SIT) in rats in order to reduce the complications and increase the survival rate. METHODS: A total of 196 Wistar rats underwent heterotopic SIT with microsurgical technique. Technical modifications included shortening fasting time and supplying energy before surgery, administering optimal volume of crystalloid fluid to the donor and recipient during surgical procedures, reducing mechanical and ischemic injuries to donor intestine, revascularizing small intestinal graft with a combination of conventional aorta to aorta anastomosis and a cuffed portal vein to left renal vein anastomosis which resulted in an acceptably short warm ischemic time, and also an adequate blood supply and drainage of the graft. RESULTS: The average time for the donor surgery was 86 min +/- 20 min, the mean operative time for the recipient was 115 min +/-20 min and warm ischemia time was shortened to 40 min +/- 5 min. There was a shorter revascularizing time of the graft, the abdominal aorta (AA) to AA anastomosis being 21 min +/- 10 min, and the cuffed portal vein (PV) to the renal vein anastomosis being 5 min +/- 5 min. The one-week survival rate of 98 rats with SIT was 88.78% (87/98), without thrombosis and stenosis of anastomosis. The longest survival time of recipient rats was more than 389 days after SIT, the rats were maintaining normal weight, with perfect intestinal function and intact intestinal histology. CONCLUSION: These modified techniques for SIT would remarkably reduce the complications and improve survival rate in rats, which provided a potentially more consistent and practical model for experimental and clinical studies.