Genetic variation modulates susceptibility to aberrant DNA hypomethylation and imprint deregulation in naïve pluripotent stem cells.

Naïve pluripotent stem cells (nPSC) frequently undergo pathological and not readily reversible loss of DNA methylation marks at imprinted gene loci. This abnormality poses a hurdle for using pluripotent cell lines in biomedical applications and underscores the need to identify the causes of imprint instability in these cells. We show that nPSCs from inbred mouse strains exhibit pronounced strain-specific susceptibility to locus-specific deregulation of imprinting marks during reprogramming to pluripotency and upon culture with MAP kinase inhibitors, a common approach to maintain naïve pluripotency. Analysis of genetically highly diverse nPSCs from the Diversity Outbred (DO) stock confirms that genetic variation is a major determinant of epigenome stability in pluripotent cells. We leverage the variable DNA hypomethylation in DO lines to identify several trans-acting quantitative trait loci (QTLs) that determine epigenome stability at either specific target loci or genome-wide. Candidate factors encoded by two multi-target QTLs on chromosomes 4 and 17 suggest specific transcriptional regulators that contribute to DNA methylation maintenance in nPSCs. We propose that genetic variants represent candidate biomarkers to identify pluripotent cell lines with desirable properties and might serve as entry points for the targeted engineering of nPSCs with stable epigenomes. Highlights: Naïve pluripotent stem cells from distinct inbred mouse strains exhibit variable DNA methylation levels at imprinted gene loci.The vulnerability of pluripotent stem cells to loss of genomic imprinting caused by MAP kinase inhibition strongly differs between inbred mouse strains.Genetically diverse pluripotent stem cell lines from Diversity Outbred mouse stock allow the identification of quantitative trait loci controlling DNA methylation stability.Genetic variants may serve as biomarkers to identify naïve pluripotent stem cell lines that are epigenetically stable in specific culture conditions.

Downward Terrestrial Gamma-Ray Flash Observed in a Winter Thunderstorm.

During a winter thunderstorm on 24 November 2017, a strong burst of gamma rays with energies up to ∼10 MeV was detected coincident with a lightning discharge, by scintillation detectors installed at the Kashiwazaki-Kariwa Nuclear Power Station at sea level in Japan. The burst had a subsecond duration, which is suggestive of photoneutron production. The leading part of the burst was resolved into four intense gamma-ray bunches, each coincident with a low-frequency radio pulse. These bunches were separated by 0.7-1.5 ms, with a duration of ≪1 ms each. Thus, the present burst may be considered as a "downward" terrestrial gamma-ray flash (TGF), which is analogous to upgoing TGFs observed from space. Although the scintillation detectors were heavily saturated by these bunches, the total dose associated with them was successfully measured by ionization chambers, employed by nine monitoring posts surrounding the power plant. From this information and Monte Carlo simulations, the present downward TGF is suggested to have taken place at an altitude of 2500±500 m, involving 8_{-4}^{+8}×10^{18} avalanche electrons with energies above 1 MeV. This number is comparable to those in upgoing TGFs.

The relationship between anagliptin concentration showing over 80% inhibition of plasma dipeptidyl peptidase-4 activity and its protective effect against glucagon-like peptide-1 degradation.

In dipeptidyl peptidase-4 (DPP-4) inhibitors, the inhibition of plasma DPP-4 activity by 80% is considered sufficient to have an effect on glycemic control improvement through the elevation of intact glucagon-like peptide-1 (GLP-1). To clarify whether or not the 80% inhibition is sufficient to protect against GLP-1 degradation, we investigated rats with a continuous infusion of exogenous GLP-1. When GLP-1 was infused into the femoral or portal vein, the steady state active GLP-1 levels in plasma significantly increased (P<0.05) at the 80% inhibitory concentration (IC80) of anagliptin (a highly selective DPP-4 inhibitor) against plasma DPP-4 activity, compared with control. In addition, the peptide levels increased in a concentration-dependent manner at drug concentrations from IC80 to 10-fold IC80, and the levels at the 10-fold IC80 were significantly higher (P<0.05) than those at IC80. The concentration dependency on GLP-1 increment was also confirmed based on the experiment in which the endogenous active GLP-1 levels were measured after an oral carbohydrate load. These findings suggest that an almost complete inhibition (80%) of plasma DPP-4 activity was insufficient to protect GLP-1 degradation, and much higher drug concentrations such as 10-fold IC80 are necessary to potently protect GLP-1 from degradation by DPP-4 commonly present in blood and tissues.

Chronic administration of DSP-7238, a novel, potent, specific and substrate-selective DPP IV inhibitor, improves glycaemic control and beta-cell damage in diabetic mice.

AIMS: The purpose of this study is to assess the in vitro enzyme inhibition profile of DSP-7238, a novel non-cyanopyrrolidine dipeptidyl peptidase (DPP) IV inhibitor and to evaluate the acute and chronic effects of this compound on glucose metabolism in two different mouse models of type 2 diabetes. METHODS: The in vitro enzyme inhibition profile of DSP-7238 was assessed using plasma and recombinant enzymes including DPP IV, DPP II, DPP8, DPP9 and fibroblast activation protein alpha (FAPalpha) with fluorogenic substrates. The inhibition type was evaluated based on the Lineweaver-Burk plot. Substrate selectivity of DSP-7238 and comparator DPP IV inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin) was evaluated by mass spectrometry based on the changes in molecular weight of peptide substrates caused by release of N-terminal dipeptides. In the in vivo experiments, high-fat diet-induced obese (DIO) mice were subjected to oral glucose tolerance test (OGTT) following a single oral administration of DSP-7238. To assess the chronic effects of DSP-7238 on glycaemic control and pancreatic beta-cell damage, DSP-7238 was administered for 11 weeks to mice made diabetic by a combination of high-fat diet (HFD) and a low-dose of streptozotocin (STZ). After the dosing period, HbA1c was measured and pancreatic damage was evaluated by biological and histological analyses. RESULTS: DSP-7238 and sitagliptin both competitively inhibited recombinant human DPP IV (rhDPP IV) with K(i) values of 0.60 and 2.1 nM respectively. Neither vildagliptin nor saxagliptin exhibited competitive inhibition of rhDPP IV. DSP-7238 did not inhibit DPP IV-related enzymes including DPP8, DPP9, DPP II and FAPalpha, whereas vildagliptin and saxagliptin showed inhibition of DPP8 and DPP9. Inhibition of glucagon-like peptide-1 (GLP-1) degradation by DSP-7238 was apparently more potent than its inhibition of chemokine (C-X-C motif) ligand 10 (IP-10) or chemokine (C-X-C motif) ligand 12 (SDF-1alpha) degradation. In contrast, vildagliptin and saxagliptin showed similar degree of inhibition of degradation for all the substrates tested. Compared to treatment with the vehicle, single oral administration of DSP-7238 dose-dependently decreased plasma DPP IV activity and improved glucose tolerance in DIO mice. In addition, DSP-7238 significantly decreased HbA1c and ameliorated pancreatic damage following 11 weeks of chronic treatment in HFD/STZ mice. CONCLUSIONS: We have shown in this study that DSP-7238 is a potent DPP IV inhibitor that has high specificity for DPP IV and substrate selectivity against GLP-1. We have also found that chronic treatment with DSP-7238 improves glycaemic control and ameliorates beta-cell damage in a mouse model with impaired insulin sensitivity and secretion. These findings indicate that DSP-7238 may be a new therapeutic agent for the treatment of type 2 diabetes.

Development of micromachining technology in ion microbeam system at TIARA, JAEA.

An ion-beam-lithography technique has been progressed in the microbeam systems at Japan Atomic Energy Agency (JAEA) Takasaki. In order to obtain a high-precision measure for microbeam size estimation with a high precision, we applied this technique combined with the electroplating process to make a Ni relief pattern as a resolution standard used in secondary electron imaging. As a result, the smallest beam size could be recorded. The scattering of ions in the materials influenced the spatial resolution and this is also discussed.

Increased mitochondrial DNA induces acquired docetaxel resistance in head and neck cancer cells.

Docetaxel is one of the most effective chemotherapeutic agents against cancer; nevertheless, some patients develop resistance. Unfortunately, their causes and mechanisms remain unknown. We created docetaxel-resistant DRHEp2 from human laryngeal cancer HEp2 and investigated the roles of mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) on docetaxel resistance. DRHEp2 had greatly increased mtDNA content. Reduction of mtDNA content in DRHEp2 by ethidium bromide treatment reduced the resistance. These results indicate the possible roles of mtDNA-coded enzymes in mitochondrial respiratory chain (MRC) in resistant mechanisms. Oligomycin A, an Fo-ATPase inhibitor, eliminated docetaxel resistance in DRHEp2; in contrast, inhibitors of other MRC did not. RNA interference targeted to Fo-ATPase d-subunit restored docetaxel-induced cytotoxicity to DRHEp2. These results indicate the roles of Fo-ATPase for resistant mechanisms. Docetaxel induced ROS generation in HEp2 but not in DRHEp2 and antioxidant pyrrolidine dithiocarbamate eliminated docetaxel-induced cytotoxicity, suggesting roles of ROS in docetaxel-induced cell death. Furthermore, inhibition of Fo-ATPase by Oligomycin A induced docetaxel-mediated ROS generation in DRHEp2. Taken together, DRHEp2 acquired docetaxel resistance through increasing Fo-ATPase, which led to diminish docetaxel-induced ROS generation and subsequently inhibited cell death. In conclusion, mtDNA plays an important role in developing docetaxel resistance through the reduction of ROS generation by regulating Fo-ATPase.

Hippocalcin protects hippocampal neurons against excitotoxin damage by enhancing calcium extrusion.

Hippocalcin, which is a member of the neuronal calcium-sensor protein family, is highly expressed in hippocampal pyramidal cells. Recently, it was demonstrated that hippocalcin deficit caused an increase in neuronal cell death in the field CA3 of Ammon's horn (CA3) region of the hippocampus following the systemic injection of kainic acid. Treatment with kainic acid results in seizure-induced cell death in CA3. In the present study, we injected quinolinic acid, which is an N-methyl-d-aspartate receptor agonist, into the hippocampal field CA1 of Ammon's horn (CA1) region in hippocalcin-knockout (-/-) mice, a procedure which mimics transient ischemia. Although significant pyknotic changes were observed at the injected site in wild-type (+/+) mice 24 h after injection, the area of pyknotic cells extended throughout the hippocampus in -/- mice. The quantification of cell numbers in Nissl-stained sections indicated that the cell damage in -/- mice was more severe than that in +/+ mice. The density of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling-positive cells roughly paralleled that of Nissl-stained pyknotic cells. Primary cultures of hippocampal neurons showed that the number of surviving neurons from -/- mice after 7 days in culture was smaller than the number from +/+ mice. The measurement of intracellular calcium concentrations in single cells revealed that the calcium extrusion from -/- neurons was slower than that from +/+ neurons. The involvement of hippocalcin in the upkeep of calcium extrusion was confirmed using hippocalcin-expressing COS7 cells. These results suggest that hippocalcin plays an important role in calcium extrusion from neurons and, in turn, helps to protect them against calcium-dependent excitotoxin damage in the hippocampus.

[Liposarcoma originating in the neck and the mediastinum after removal of mediastinal lipoma].

A 47-year-old man, who had undergone removal of an upper mediastinal lipoma 9 years previously, was referred to our hospital for swelling of the right neck and wheezing. The chest X-ray showed enlargement of the upper mediastinum. Contrast-enhanced chest computed tomography and magnetic resonance imaging demonstrated a tumor with fatty density extended from the upper mediastinim to the right side of the neck. Two-stage tumor resection was carried out. On gross pathological examination the tumor was soft and fatty. Microscopic examination revealed well differentiated liposarcoma. Postoperative radiation therapy (50 Gy) was carried out. The patient remains free of disease 3 years after radiation therapy.

Search for low-mass exoplanets by gravitational microlensing at high magnification.

Observations of the gravitational microlensing event MOA 2003-BLG-32/OGLE 2003-BLG-219 are presented, for which the peak magnification was over 500, the highest yet reported. Continuous observations around the peak enabled a sensitive search for planets orbiting the lens star. No planets were detected. Planets 1.3 times heavier than Earth were excluded from more than 50% of the projected annular region from approximately 2.3 to 3.6 astronomical units surrounding the lens star, Uranus-mass planets were excluded from 0.9 to 8.7 astronomical units, and planets 1.3 times heavier than Saturn were excluded from 0.2 to 60 astronomical units. These are the largest regions of sensitivity yet achieved in searches for extrasolar planets orbiting any star.

Immunoregulatory defects of V alpha 24V+ beta 11+ NKT cells in development of Wegener's granulomatosis and relapsing polychondritis.

The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V beta 11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener's granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4(+) V alpha 24(+)V beta 11(+) NKT cells as well as CD1d-alpha-GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to alpha-GalCer. The dysfunction of NKT cells to recognize ligands such as alpha-GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.

Linkage and mapping analysis of a non-susceptibility gene to densovirus (nsd-2) in the silkworm, Bombyx mori.

Nonsusceptibility to Bombyx mori densovirus type 2 (BmDNV-2) is controlled by a recessive non-susceptibility gene, nsd-2 (non-susceptibility to DNV-2) in B. mori. Taking advantage of a lack of crossing over in females, reciprocal backcrossed F1 (BF1) progeny were used for linkage analysis and mapping of nsd-2 using silkworm strains C124 and 902, which are classified as being highly susceptible and non-susceptible to DNV-2, respectively. BF1 larvae were inoculated twice with DNV-2 virus at the first and second instar stages. DNA was extracted from each of the surviving fifth instar larvae and analysed by RFLP inheritance patterns using probes specific to each of the 28 linkage groups of B. mori. Our results indicated that the non-susceptibility gene was linked to linkage group 17, since all surviving larvae showed the homozygous profile of strain 902 in their genotype. The other linkage groups showed mixtures of heterozygous and homozygous genotypes, indicating an independent assortment. A linkage map of 30.6 cM was constructed for linkage group 17 with nsd-2 mapped at 24.5 cM and three closely linked cDNA markers were identified.

In vitro and in vivo activities of anti-influenza virus compound T-705.

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC(50)s) of 0.013 to 0.48 microg/ml, while it showed no cytotoxicity at concentrations up to 1,000 microg/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitor-resistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC(50)s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 x 10(2) PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.

A rare case of carcinosarcoma of the maxillary sinus with osteosarcomatous differentiation.

A unique case of carcinosarcoma in the maxillary sinus is reported. A 47-year-old man visited our hospital with complaints of right nasal obstruction and bloody rhinorrhea. Examination revealed a hemorrhagic mass with necrosis in the maxillary sinus that infiltrated the right nasal cavity. Histologically, the tumor was composed of both carcinomatous and sarcomatous elements. Nests of squamous cell carcinoma and adenocarcinoma were scattered in the sarcomatous element with osteosarcomatous differentiation. No distinct demarcation between the two elements was observed and some spindle-shaped cells in the sarcomatous component were immunoreactive to epithelial markers by immunohistochemical staining. Although the histogenesis of carcinosarcoma remains unclear, the histologic pattern of the present case indicates the possibility that a multipotential cell, capable of both epithelial and mesenchymal differentiation, was the origin of the rare tumor.

Herpes simplex virus type 1 reactivation and antiviral therapy in patients with acute peripheral facial palsy.

OBJECTIVE: Recent studies provide compelling data for the hypothesis that herpes simplex virus type I (HSV-1) is implicated in the pathogenesis of idiopathic peripheral facial palsy (Bell's palsy). The present study analyzed the severity of facial palsy in patients with HSV-1 reactivation and sought to determine the efficacy of acyclovir-prednisone therapy for these patients. MATERIALS AND METHODS: In total, 176 patients, clinically diagnosed with Bell's palsy. were divided into three groups by polymerase chain reaction (PCR) and serological tests--31 patients with HSV-1 reactivation, 45 patients with VZV reactivation (zoster sine herpete) and 100 patients without HSV-1 or VZV reactivation (Bell's palsy). RESULTS: The difference in the worst grade of facial palsy between patients with zoster sine herpete and Bell's palsy was significant (P = 0.01 10, Mann-Whitney U-test). In contrast, no difference in the severity of palsy was observed between patients with HSV-1 reactivation and Bell's palsy. Twelve patients received acyclovir-prednisone treatment within 7 days of onset based on positive PCR results and ten of the 12 (83%) recovered completely. In contrast, 14 patients with HSV-1 reactivation received prednisone treatment because their PCR tests were performed at a later date; ten of these 14 (71%) recovered completely. The difference in the cure rate between the two treatment groups was not significant (P > 0.05, Fisher exact test). CONCLUSIONS: The results indicate that the severity of palsy in patients with HSV-1 reactivation is similar to that in patients with Bell's palsy and suggest that early diagnosis of HSV-1 reactivation by PCR and subsequent acyclovir-prednisone therapy do not improve recovery from facial palsy.

Herpes virus reactivation and serum tumor necrosis factor-alpha levels in patients with acute peripheral facial palsy.

Recent studies have shown that tumor necrosis factor-alpha (TNF-alpha) plays an important regulatory role in several inflammatory and infectious diseases. In the present study, we evaluated serum TNF-alpha levels of patients with acute peripheral facial palsy using an ELISA method. We examined sera from each group (n = 25 per group) of patients with herpes simplex virus type 1 reactivation (HSV-1). varicella-zoster virus (VZV) reactivation, and with no HSV or VZV reactivation. We also tested the sera of 25 normal controls. No significant difference was found between the serum TNF-alpha levels in facial palsy and controls. No correlation was found between serum TNF-alpha levels in cases with HSV-1 or VZV reactivation and with no HSV-1 or VZV reactivation. These results indicate that serum TNF-alpha levels are not affected by HSV-1 or VZV reactivation in patients with facial palsy.

A clinical study on the cervical lymph node metastasis of maxillary sinus carcinoma.

OBJECTIVE: To improve the management of maxillary sinus carcinoma, we retrospectively investigated the significance of cervical lymph node metastasis in our treated cases and discussed how to deal with the cervical lymph node metastasis as a prognostic factor. METHODS: Medical records of 118 patients with maxillary sinus carcinoma diagnosed and treated in our institute from 1982 to 1997 were retrospectively reviewed. Tumors were staged according to UICC classification 1987. The cumulative survival was analyzed by the Kaplan-Meier method. Generally, the patients had undergone preoperative radiotherapy and surgery. We examined the cervical lymph node metastasis detected at the first examination and the subsequent cervical lymph node metastasis in relation to the prognoses. RESULTS: The incidence of cervical lymph node metastasis at the initial diagnosis was 7.9% (n = 9), and that of secondary cervical lymph node metastasis without recurrence at the primary site after the first treatment was 8.3% (n = 9). In most cases, we observed metastasis to the lymph nodes in the submandibular region and in the jugular chain. The result of treatment of cervical lymph node metastasis was grave. Among the patients with cervical lymph node metastasis detected at the first examination, four patients developed local recurrence and three patients developed distant metastasis. On the other hand, among those with secondary cervical metastasis, three patients developed neck recurrence and three patients developed distant metastasis, but no local recurrence. CONCLUSIONS: In the cervical metastasis of maxillary sinus carcinoma, it is important to treat the primary lesion completely. In addition to it. we should control cervical metastasis and careful neck dissection is required. For the patients with cervical lymph node metastasis, it is necessary to consider the further treatment of distant metastasis.

Correlation of clinicopathological parameters and biological markers related to apoptosis and proliferative activity with a clinical outcome in squamous cell carcinoma of the larynx treated with concurrent chemoradiotherapy.

OBJECTIVE: This study was designed to determine whether biological markers related to apoptosis or proliferative activity are associated with the clinical outcome in patients with squamous cell carcinoma (SCC) of the larynx treated with concurrent chemoradiotherapy. METHODS: Immunostaining with antibodies specific to p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 59 patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation dose of 40-65 Gy over 4-6.5 weeks). RESULTS: Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS: P = 0.001). Patients with bcl-2 positive tumors had better OS than those with bcl-2 negative tumors in both univariate (P = 0.002) and multivariate analyses (P < 0.001 ). In the univariate analysis, a considerable difference in OS was observed among the expressions of bax (P = 0.077), MIB-1 proteins (P = 0.071). and OS. but the difference was not statistically significant. CONCLUSION: This study indicates that nodal status is the major prognostic tactor in patients with SCC of the larynx treated with concurrent chemoradiotherapy. These results provide useful information for predicting prognosis. Further analysis of biological factors is needed to evaluate the value as predictive markers.

Concurrent chemotherapy and radiotherapy as initial treatment for stage II supraglottic squamous cell carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of concurrent carboplatin (CBDCA) and radiotherapy for laryngeal carcinoma. we investigated survival rates and laryngeal preservation rates in patients with this treatment modality and those with radiation therapy only. METHODS: We underwent chemotherapy with CBDCA and conventional radiotherapy concurrently to 17 patients with untreated stage II (T2NOM0) supraglottic squamous cell carcinoma since November 1990. CBDCA (100 mg/m2) was administered intravenously once a week concurrently with radiotherapy (2.5 Gy/fr, 4 times a week). At the dose of 40 Gy, the results were evaluated, and some of the patients underwent planned surgery and others continued the radiotherapy up to 65 Gy. RESULTS: Overall 5-year survival rate by Kaplan-Meier method was 81.1%. Actual laryngeal preservation rate was 76.0%. Toxicity over grade III was noticed in two patients. Compared with 14 cases of historical controls, which were treated by radiation therapy alone between 1988 and 1990, the cases with concurrent radiotherapy and chemotherapy had statistically significant advantage in overall successful laryngeal preservation rate (P < 0.05), whereas the two groups were not significantly different in the overall 5-year survival rate.

Clinical study of adenoid cystic carcinoma of the head and neck.

OBJECTIVE: We examined prognostic factors and outcome of the primary treatment in patients with adenoid cystic carcinoma (ACC) of the head and neck. METHODS: Twenty patients with ACC of the head and neck who had been treated in our institution from 1985 to 1998 were enrolled in this study. Disease-specific survival rate was analyzed by the Kaplan-Mejer method, and the log-rank test was applied to compare the survival rates. RESULTS: The overall 5- and 10-year survival rates determined by Kaplan-Meier analysis were 81 and 57%, respectively. Patients with major salivary gland ACC obtained the best 10-year survival rate (83%), while those with paranasal sinus ACC had the worst survival rate (33%). Predominance of the solid component on pathological examination might indicate a worse prognosis. Our study revealed that postoperative radiotherapy could yield better control of the lesion focus. Chemotherapy failed in some patients and was not dramatically effective by itself. CONCLUSIONS: The long-term prognosis of ACC was poor. Long-term follow-up is necessary for better prognosis of patients treated with radical treatment regimens.