Neck control after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancers

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate neck control outcomes after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancer.</p> <p>Methods</p> <p>We retrospectively reviewed medical records of fifty patients with node-positive head and neck cancer who received definitive radiochemotherapy. Twelve patients subsequently underwent neck dissection for suspicious recurrent or persistent disease. A median dose of 70 Gy (range 60-70.6) was delivered to involved nodes. Response evaluation was performed at a median of 5 weeks after completion of radiotherapy.</p> <p>Results</p> <p>Neck failure was observed in 11 patients and the 3-year regional control (RC) rate was 77.1%. Neck dissection was performed in 10 of the 11 patients; seven of these cases were successfully salvaged, and the ultimate rate of neck control was 92%. The remaining two patients who received neck dissection had negative pathologic results. On univariate analysis, initial nodal size > 2 cm, a less-than-complete response at the primary site, post-radiotherapy nodal size > 1.5 cm, and post-radiotherapy nodal necrosis were associated with RC. On multivariate analysis, less-than-complete primary site response and post-radiotherapy nodal necrosis were identified as independent prognostic factors for RC.</p> <p>Conclusions</p> <p>The neck failure rate after definitive radiochemotherapy without planned neck dissection was 22%. Two-thirds of these were successfully salvaged with neck dissection and the ultimate neck control rate was 92%. Our results suggest that planned neck dissection might not be necessary in patients with complete response of primary site, no evidence of residual lesion > 1.5 cm, or no necrotic lymph nodes at the 1-2 months follow-up evaluation after radiotherapy.</p

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

BACKGROUND: Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured. Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination. RESULTS: The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively. CONCLUSIONS: The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model

The Role of Sphingosine Kinase 1/Sphingosine-1-Phosphate Pathway in the Myogenic Tone of Posterior Cerebral Arteries

AIMS: The goal of the current study was to determine whether the sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) pathway is involved in myogenic vasoconstriction under normal physiological conditions. In the present study, we assessed whether endogenous S1P generated by pressure participates in myogenic vasoconstriction and which signaling pathways are involved in SK1/S1P-induced myogenic response under normal physiological conditions. METHODS AND RESULTS: We measured pressure-induced myogenic response, Ca(2+) concentration, and 20 kDa myosin light chain phosphorylation (MLC(20)) in rabbit posterior cerebral arteries (PCAs). SK1 was expressed and activated by elevated transmural pressure in rabbit PCAs. Translocation of SK1 by pressure elevation was blocked in the absence of external Ca(2+) and in the presence of mechanosensitive ion channel and voltage-sensitive Ca(2+) channel blockers. Pressure-induced myogenic tone was inhibited in rabbit PCAs treated with sphingosine kinase inhibitor (SKI), but was augmented by treatment with NaF, which is an inhibitor of sphingosine-1-phosphate phosphohydrolase. Exogenous S1P further augmented pressure-induced myogenic responses. Pressure induced an increase in Ca(2+) concentration leading to the development of myogenic tone, which was inhibited by SKI. Exogenous S1P further increased the pressure-induced increased Ca(2+) concentration and myogenic tone, but SKI had no effect. Pressure- and exogenous S1P-induced myogenic tone was inhibited by pre-treatment with the Rho kinase inhibitor and NADPH oxidase inhibitors. Pressure- and exogenous S1P-induced myogenic tone were inhibited by pre-treatment with S1P receptor blockers, W146 (S1P1), JTE013 (S1P2), and CAY10444 (S1P3). MLC(20) phosphorylation was increased when the transmural pressure was raised from 40 to 80 mmHg and exogenous S1P further increased MLC(20) phosphorylation. The pressure-induced increase of MLC(20) phosphorylation was inhibited by pre-treatment of arteries with SKI. CONCLUSIONS: Our results suggest that the SK1/S1P pathway may play an important role in pressure-induced myogenic responses in rabbit PCAs under normal physiological conditions

Crystallization and preliminary X-ray crystallographic studies of the ice-binding protein from the Antarctic yeast Leucosporidium sp. AY30. Corrigendum

A correction to the article by Park et al. [(2011). Acta Cryst. F67, 800–802]

Experience of non-vascular complications following endovascular aneurysm repair for abdominal aortic aneurysm

Endovascular aneurysm repair (EVAR) for the treatment of abdominal aortic aneurysm (AAA) is a widely used method, and its decreased invasiveness compared to traditional surgical repair has brought about reduced rates of morbidity and mortality. Several vascular complications related to the procedure have been reported, but non-vascular complications have rarely occurred. We report herein the case of a 78-year-old man who underwent EVAR for AAA and presented with active duodenal ulcer bleeding and acute acalculous cholecystitis as complications after the procedure. We must consider that a wide spectrum of complications may occur following EVAR, and therefore it is important to evaluate the risks of complication and to take the necessary measures to minimize them

Development of a high yield purification process for the production of influenza virus vaccines

Production of influenza virus in animal cells has emerged as an alternative to conventional platforms such as egg-based production system. Animal cells, especially MDCK and VERO cell lines, are widely used as the primary production cell for influenza virus vaccine because of their high susceptibility to infection with various influenza viruses. Recently, a robust and reliable purification process was successfully developed for the production of quadri-valent HA proteins (from two strains of the type A virus and two strains of the type B virus) by using animal cell-based production system in Green Cross Corp., Korea. The UF/DF process, Benzonase treatment at high temperature as well as column chromatography strategy was optimized to maximize the final HA production yields. Benzonase treatment was conducted to reduce in hcDNA (host cell DNA) because hcDNA was main impurity for cell-based influenza virus vaccine. A simple and stable UF/DF process has been tested with membrane molecular weight cutoffs of 100 and 300 kDa as well as 0.2 and 0.45 um microfiltration membrane. Anion exchange chromatography (AEC) and size exclusion chromatography (SEC) were selected for acceptable reduction in hcDNA and HCP. AEC was used to separate hcDNA from virus at a salt concentration of 0.5 M sodium chloride. The HA yield through AEC & SEC combination process was sufficiently achieved under specific purification process condition. Overall, the amount of residual hcDNA was reduced to an acceptable level (10ng/dose) and the increased HA yield was maintained throughout the whole process. The performance, productivity and scalability of the purification process were successfully demonstrated in over 30 GMP batches using 4 different influenza virus strains