Image-guided interstitial high-dose-rate brachytherapy in the treatment of metastatic esophageal squamous cell carcinoma

Purpose: To evaluate the efficacy of computed tomography (CT)- and magnetic resonance imaging (MRI)-guided interstitial high-dose-rate brachytherapy (HDR IBT = IBT) in patients with metastatic esophageal squamous cell carcinoma. Material and methods: Eleven patients with 21 unresectable metastases of histologically proven esophageal squamous cell carcinoma were included in this retrospective study. Fourteen visceral and 7 lung metastases were treated with image-guided (CT or open MRI guidance) IBT using a 192 lridium source (single fraction irradiation). Clinical and imaging follow-up were performed every 3 months after treatment. Primary endpoint was local tumor control (LTC) and safety. Furthermore, we analyzed safety, progression-free survival (PFS), and overall survival (OS). Results: The median diameter of the target lesions was 2.2 cm (range: 0.7-6.8 cm), treated with a median D-100 of 20.1 Gy (range: 10-25 Gy). During a median follow-up of 6.3 months (range: 3-21.8 months), three patients displayed local recurrences, resulting in LTC of 85.7%. Median PFS was 3.4 months and median OS after IBT was 13.7 months. No severe adverse events (grade 3+) requiring hospitalization or invasive intervention were recorded. Conclusions: Image-guided IBT is a safe and effective treatment in patients with metastasized esophageal squamous cell carcinoma

Immunoproteasome subunit ß5i/LMP7-deficiency in atherosclerosis

Abstract Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR−/−LMP7−/− and LDLR−/− mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively. Lesion burden was similar between genotypes in both stages. Macrophage content and abundance of polyubiquitin conjugates in aortic root plaques were unaltered by β5i/LMP7-deficiency. In vitro experiments using bone marrow-derived macrophages (BMDM) showed that β5i/LMP7-deficiency did not influence macrophage polarization or accumulation of polyubiquitinated proteins and cell survival upon hydrogen peroxide and interferon-γ treatment. Analyses of proteasome core particle composition by Western blot revealed incorporation of standard proteasome subunits in β5i/LMP7-deficient BMDM and spleen. Chymotrypsin-, trypsin- and caspase-like activities assessed by using short fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes. Taken together, deficiency of IP subunit β5i/LMP7 does not disturb protein homeostasis and does not aggravate atherogenesis in LDLR−/− mice