Cellular senescence is one of the key strategies to suppress expansion of cells with mutations. Senescence is induced in response to genotoxic and oxidative stress. Here we show that the transcription factor Bach1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1), which inhibits oxidative stress-inducible genes, is a crucial negative regulator of oxidative stress-induced cellular senescence. Bach1-deficient murine embryonic fibroblasts showed a propensity to undergo more rapid and profound p53-dependent premature senescence than control wild-type cells in response to oxidative stress. Bach1 formed a complex that contained p53, histone deacetylase 1 and nuclear co-repressor N-coR. Bach1 was recruited to a subset of p53 target genes and contributed to impeding p53 action by promoting histone deacetylation. Because Bach1 is regulated by oxidative stress and heme, our data show that Bach1 connects oxygen metabolism and cellular senescence as a negative regulator of p53.

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Fish bones are one of the most frequently observed ingested foreign bodies in the pharynx-esophagus. Fish bones have a tendency to stick and penetrate the mucosa, which can occasionally lead to severe or lethal complications. The extraluminal migration of fish bones in the upper digestive tract is a rare event, and it is even more unlikely that the foreign body will remain in the neck for a prolonged period. We report the unique case of a 69-year-old woman who remained asymptomatic, while a fish bone was lodged in her neck for 9 months. Finally, after her anterior neck had become swollen, she underwent neck exploration, which revealed that the fish bone was embedded in the scar tissue running from within the thyroid gland to outside of the thyroid. Treatment proceeded without complications, and the foreign body was removed successfully. The length of the fish bone was 34 mm. Intraoperative ultrasonography was able to identify the fish bone in situ using real-time imaging; therefore, we recommend this technique for locating migrated foreign bodies in the neck. Ingested fish bones are one of the most frequently observed foreign bodies in the pharynx-esophagus (Remsen et al. 1983;Loh et al. 2000;Athanassiadi et al. 2002); particularly in East Asia, a whole fish is often served without removing its bones. Owing to their fine, linear, and sharp structure, fish bones have a tendency to stick and penetrate the mucosa, which can occasionally lead to severe or lethal complications. The extraluminal migration of fish bones in the upper digestive tract has been reported only rarely, and it is even more unlikely that the foreign body will remain in the neck for a prolonged period. In addition, although neck exploration for migrated foreign bodies is a difficult procedure, there are a few studies used intraoperative ultrasonography in the head and neck region (Ng et al. 2003;Masuda et al. 2006). We report the rare case of a migratory fish bone that remained asymptomatic in the neck for 9 months before its removal, and include a review of the related literature. Clinical ReportA 69-year old woman was referred to our institution with an enlarged anterior neck. Local neck symptoms had worsened compared with those a few days before presentation. A computed tomography (CT) scan revealed a softtissue shadow of increased density, and a fine linear radiopaque object was found located in the right neck region. The patient remembered that a fish rib bone had stuck in her throat while she was eating a grilled fish (a horse mackerel) 9 months ago, although she had been asymptomatic until the present time.Physical examination revealed skin flare and swelling on the anterior neck across a region that was approximately 60 mm in diameter, and the center part of the involved area had an eroded surface with easy bleeding. No fever was present and the patient did not report tenderness in the affected region. No abnormal findings were found in any other region of the head and neck. A blood examination revealed slightly increased levels of white...

Reactive oxygen species (ROS), by-products of aerobic respiration, promote genetic instability and contribute to the malignant transformation of cells. Among the genes related to ROS metabolism, Bach1 is a repressor of the oxidative stress response, and a negative regulator of ROS-induced cellular senescence directed by p53 in higher eukaryotes. While ROS are intimately involved in carcinogenesis, it is not clear whether Bach1 is involved in this process. We found that senescent Bach1-deficient mouse embryonic fibroblasts (MEFs) underwent spontaneous immortalization the same as did the wild-type cells. When transduced with constitutively active Ras (H-Ras(V12)), the proliferation and colony formation of these cells in vitro were markedly reduced. When transplanted into athymic nude mice, the growth and vascularization of tumors derived from Bach1-deficient cells were also decreased. Gene expression profiling of the MEFs revealed a new H-Ras(V12) signature, which was distinct from the previously reported signatures in epithelial tumors, and was partly dependent on Bach1. The Bach1-deficient cells showed diminished phosphorylation of MEK and ERK1/2 in response to H-Ras(V12), which was consistent with the alterations in the gene expression profile, including phosphatase genes. Finally, Bach1-deficient mice were less susceptible to 4-nitroquinoline-1-oxidide (4-NQO)-induced tongue carcinoma than wild-type mice. Our data provide evidence for a critical role of Bach1 in cell transformation and tumor growth induced by activated H-Ras(V12).

Background: Adenoid cystic carcinoma is a rare malignant tumor arising from exocrine glands such as the major and minor salivary glands of the paranasal sinuses or the external auditory canal. Although multiple retrospective clinical studies of ACC have been reported to date, clinical questions, such as 1) long-term prognosis beyond 20 years, 2) usefulness and suitability for treatment of therapeutic interventions, 3) therapeutic goal to aim for, and 4) prognosis by recurrence sites, are still unclear. Methods: To improve understanding and management of adenoid cystic carcinoma of the head and neck (ACC), a retrospective study with 58 new ACC cases between 1991 and 2016 was performed. The median observation period was 66.8 months (range 3-316 months). The overall clinical stages were as follows: I, 6.9%; II, 25.9%; III, 19.0%; and IV, 48.2%. Histology was cribriform/tubular type (C-T type) in 62.0% and solid type in 27.5%. The main treatment strategy was definitive surgery, which was performed in 75.2% of cases.