Not Only Hypoxia- but Radiation-Induced Epithelial-Mesenchymal Transition Is Modulated by Hypoxia-Inducible Factor 1 in A549 Lung Cancer Cells.

Hypoxia leads to post-treatment metastasis and recurrences of cancer via the epithelial-mesenchymal transition (EMT). Radiotherapy itself may also contribute to the acquisition of EMT phenotypes. Despite extensive studies on the EMT driven by either hypoxia or radiation stimuli, the molecular mechanisms characterizing these EMT events remain unclear. Thus, we aimed to evaluate the differences in the molecular pathways between hypoxia-induced EMT (Hypo-EMT) and radiation-induced EMT (R-EMT). Further, we investigated the therapeutic effects of HIF-1α inhibitor (LW6) on Hypo-EMT and R-EMT cells. A549 cells, lung adenocarcinoma cell line, acquired enhanced wound-healing activity under both hypoxia and irradiation. Localization of E-cadherin was altered from the cell membrane to the cytoplasm in both hypoxia and irradiated conditions. Of note, the expression levels of vimentin, one of the major EMT markers, was enhanced in irradiated cells, while it decreased under hypoxia condition. Importantly, LW6 significantly blocked EMT-related malignant phenotypes in both Hypo-EMT cells and R-EMT cells with concomitant re-location of E-cadherin onto the cell membrane. Moreover, LW6 deflected stress responsive signalling, JNK, activated sustainably under hypoxic condition, and the blockage of JNK impaired EMT phenotypes. Together, this work demonstrated the molecular events underlying Hypo-EMT and R-EMT, and highlighted HIF-1α as a therapeutic target not only in Hypo- EMT, but also in R-EMT.

Efficiency of leukocyte depletion filters and micro-aggregate filters following intra-operative cell salvage during cesarean delivery.

BACKGROUND: Intra-operative cell salvage is not routinely used during cesarean delivery because it is not cost-effective for patients at low risk of hemorrhage and there are theoretical concerns about amniotic fluid embolism. Some guidelines recommend using leukocyte depletion filters to decrease the risk of amniotic fluid embolism before re-infusing salvaged blood, but these filters are not available in Japan. We compared the efficacy and safety of leukocyte depletion and micro-aggregate filters in combination with intra-operative cell salvage during cesarean delivery. METHODS: Blood was collected in a Cell Saver 5 reservoir during cesarean delivery. Four samples were collected: pre-wash, post-wash, post-filtration with a leukocyte depletion filter and post-filtration with a micro-aggregate filter. Each sample was analyzed for amniotic fluid markers of zinc coproporphyrin-1 and sialyl-Tn, for fetal hemoglobin, and the sample underwent pathological examination for white blood cells and squamous cells. Post-filtration samples were compared using paired t-tests with P <0.05 indicating statistical significance. RESULTS: Zinc coproporphyrin-1 and sialyl-Tn were negative at almost all sample points. Squamous cells decreased by 59.1% post-wash and 91.2% post-filtration using a leukocyte depletion filter. Leukocyte depletion filters removed 99.7% of white blood cells and were more effective in removing white blood cells than micro-aggregate filters (P=0.02). CONCLUSION: Leucocyte depletion filters are more effective in removing white blood cells and squamous cells than micro-aggregate filters, and their introduction for intra-operative cell salvage during cesarean delivery should be considered in Japanese clinical practice.

Clinical results of accelerated hypofractionated radiotherapy for central-type small lung tumours.

PURPOSE: We evaluated the efficacy and toxicity of accelerated hypofractionated radiotherapy (ahypof-rt) for central-type small lung tumours. METHODS: Between November 2006 and January 2015, 40 patients with central-type small lung tumours underwent ahypof-rt delivered using 10 MV X-rays and a coplanar 3-field technique. The number of fractions ranged from 24 to 28, with a fraction size of 2.5-3 Gy. A total dose of 69-75 Gy to the isocentre of the planning target volume was administered to each patient. Cumulative survival and local control rates were calculated using the Kaplan-Meier method. RESULTS: The 27 men and 13 women enrolled in the study had a median age of 79 years (range: 60-87 years). The tumour stage was T1a in 9 patients, T1b in 17 patients, and T2a in 14 patients, with a median size of 26.5 cm (range: 11-49 cm). The median follow-up period was 23 months. A complete response was achieved in 3 patients (7.5%), and a partial response, in 17 patients (42.5%). The overall 2-year and 3-year local control rates were 87.3% and 81.8% respectively; the 2-year and 3-year overall survival rates were 78.9% and 66.7% respectively. Grade 3 pneumonitis occurred in 3 patients; no other severe adverse events (≥grade 3) were observed in any patient. CONCLUSIONS: Accelerated hypofractionated radiotherapy using a fraction size of 2.5-3 Gy was highly safe and can be a more effective treatment option than conventional radiotherapy for patients with central-type small lung tumours.

Glial fibrillary acidic protein (GFAP) and anti-GFAP autoantibody in canine necrotising meningoencephalitis.

To establish clinical markers for canine necrotising meningoencephalitis (NME) and to elucidate its pathogenesis, glial fibrillary acidic protein (GFAP) and anti-GFAP autoantibodies were measured in the cerebrospinal fluid (CSF) of 32 dogs with NME, 23 dogs with other inflammatory central nervous system (CNS) diseases, 27 dogs with miscellaneous CNS diseases and 25 healthy dogs, including five pugs. The dogs with NME had the highest levels of anti-GFAP autoantibodies. The diagnostic sensitivity and specificity of anti-GFAP autoantibodies for NME were 91 per cent and 73 per cent, respectively. Some of the dogs with NME and the healthy pugs, had high CSF concentrations of GFAP, suggesting a breed-specific fragility of astrocytes. The leakage of GFAP and the development of autoimmunity may be key to understanding the pathogenesis of NME.

Central fibrosarcoma of bone. Report of a case.

A case of a 46-year-old Japanese male having fibrosarcoma of bone is reported. The tumor developed in the proximal metaphysis of the left femur. During the three years following onset of the disease with symptoms of local pain and mass, the patient was operated on three times (curettage and bone graft, curettage and bone graft with Jwett's nail fixation and disarticulation). The tumor was found to be an intraosseous translucent lesion on x-ray examiation. Histologically, the tumor consisted of compact or loose, atypical spindle cells, producing abundant collagen-fibers without any osteoid, bony or cartilage formation. From the clinical and pathological findings, this case is thought to be a typical central fibrosarcoma of bone.