Chemoradiotherapy after curative surgery for locally advanced pancreatic cancer: A 20-year single center experience.

INTRODUCTION: Pancreatic adenocarcinoma (PAC) is a highly malignant tumor with relevant morbidity and mortality. The role of adjuvant chemoradiotherapy (CRT) for primarily resected tumors remains controversial. We aimed to assess the outcome of patients treated at our institution with postoperative CRT for PAC. METHODS: We present a retrospective case series of patients with pancreatic adenocarcinoma at a single center in Switzerland. These patients were treated by primary surgery followed by adjuvant CRT between 1995 and 2015. The results were compared with published data. RESULTS: Median follow-up for the 60 patients was 33 months (range 19.9-193.9); median overall survival (OS) for patients undergoing a resection followed by combined CRT was 25.5 months. Overall, disease-free survival (DFS) was 15.2 months. A local recurrence occurred in 14 patients (23.3%) after a median time of 8.8 months, and in 43 patients (71.7%) distant metastasis was demonstrated with a median time to metastasis of 10.6 months. CONCLUSION: This retrospective study represents one of the sole reviews of outcome data after adjuvant CRT in resected PAC in Europe within the past years. OS was comparable to that of other institutional outcome data published previously but inferior when compared to most recent published results with an intense chemotherapy. However, not all patients are suitable to undergo such an intense chemotherapy with modified FOLFIRINOX after the extensive surgery for the PAC - these patients could benefit from adding adjuvant CRT to a less intensive chemotherapy with gemcitabine to enhance the benefit regarding locoregional recurrence-free survival.

Targeting of an abundant cytosolic form of the protein import receptor at Toc159 to the outer chloroplast membrane.

Chloroplast biogenesis requires the large-scale import of cytosolically synthesized precursor proteins. A trimeric translocon (Toc complex) containing two homologous GTP-binding proteins (atToc33 and atToc159) and a channel protein (atToc75) facilitates protein translocation across the outer envelope membrane. The mechanisms governing function and assembly of the Toc complex are not yet understood. This study demonstrates that atToc159 and its pea orthologue exist in an abundant, previously unrecognized soluble form, and partition between cytosol-containing soluble fractions and the chloroplast outer membrane. We show that soluble atToc159 binds directly to the cytosolic domain of atToc33 in a homotypic interaction, contributing to the integration of atToc159 into the chloroplast outer membrane. The data suggest that the function of the Toc complex involves switching of atToc159 between a soluble and an integral membrane form.