Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results

Purpose:To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization(PETACE)for patients with unresectable hepatocellular carcinoma(HCC).Materials and methods:We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1,2015 and August 30,2016.The complication rate,tumor response rate,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Adverse events were generally mild and included abdominal pain and fever,although a major complication was reported in 1 patient(1.8%).During a median follow-up of 10.0 months(range,3.0-24.0 months),14 patients(25.5%)achieved a complete tumor response,25(45.5%)had a partial response,9(16.4%)showed stable disease,and 7(12.7%)had disease progression.The 1-month overall response rate was 70.9%,and the local tumor response rate was 89.0%.The 1-month tumor response rate was 100%for Barcelona Clinic Liver Cancer(BCLC)stage A or B disease and 62.8%for BCLC stage C disease.The median PFS was 6.1 months(95%confidence interval[95%CI],3.4-8.8 months;range,1.0-24.0 months).The median OS was 11.0 months(95%CI,7.1-14.9 months;range,2.0-24.0 months).Kaplan-Meier analysis(log-rank test)found significant differences in OS between patients grouped by tumor number(P=0.006),tumor size(P=0.035),and Eastern Cooperative Oncology Group(ECOG)score(P=0.005).The tumor number(1 vs.>2)was the only factor independently associated with OS(hazard ratio[HR],2.867;95%CI,1.330-6.181;P=0.007).Conclusions:PE-TACE for unresectable HCC may be safe,with favorable tumor response rates and survival time,especially in patients with a single large tumor.Longer follow-up using a larger series is necessary to confirm these preliminary results.

Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis

Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However,the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum(ER)-associated degradation(ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its Cterminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1-or TER94-deficient progenitors. Further removal of reactive oxygen species(ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance(ER protein quality control) in tissue homeostasis and tumor development.