Incomplete radiofrequency ablation provokes colorectal cancer liver metastases through heat shock response by PKCα/Fra-1 pathway

Objective: Incomplete radiofrequency ablation(ICR) has been proposed as a major cause of recurrence in the treatment of hepatic metastatic tumors.We tried to determine the mechanisms of this progression in colorectal cancer(CRC) liver metastasis(CRLMs)Methods: We have established a mouse model of radiofrequency ablation(RFA) therapy to demonstrate increased risk of recurrence of CRLMs with ICR.Here we focused on heat shock-induced CRC malignancy.Sub-lethal heat shock(HS) in CRC cell lines provoked cell growth, invasion, and tumor initiation in vitro and in vivo.Results: We found that Fra-1, which lies downstream of PKCα-ERK1/2 signaling, was significantly increased by HS compared with the untreated CRC cells.Silencing Fra-1 reversed the tumor promoting effects of HS.Furthermore, proliferation and tumor initiation inducer c-Myc, together with tumor invasion inducer matrix-metalloprotase 1(MMP-1) expression were up-regulated by AP-1/Fra-1 induced genes transcription.Conclusions: Our study demonstrated that ICR generated HS induces CRC malignancy by targeting Fra-1, which could be a potential prognostic marker and a promising therapeutic strategy to prevent disease recurrence after radiofrequency ablation treatment.

Conversion therapy for advanced cholangiocarcinoma in the era of molecular targeted therapy and immune therapy

Cholangiocarcinoma(CCA)encompasses a range of neoplasms,namely intrahepatic CCA,perihilar CCA,and distal CCA,which are distinguished by their anatomical origin.In cases where radical resection of CCA is feasible and the patient’s physical condition permits surgical intervention,it is advisable to proceed with surgical treatment(1).However,the insidious onset of the disease restricts surgical candidacy to only 20-30%of patients(2,3).For those with unresectable CCAs,the recommended initial treatment is gemcitabine plus cisplatin(GemCis)chemotherapy(4).