Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined.</p> <p>Methods</p> <p>Cells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins.</p> <p>Results</p> <p>When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.</p> <p>Conclusion</p> <p>These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.</p

Imprint cytological feature of large cell neuroendocrine carcinoma of the gallbladder : A case report

Large cell neuroendocrine carcinoma (LCNEC) is a rare poorly differentiated carcinoma with neuroendocrine differentiation showing aggressive clinical behavior. We herein report a case of gallbladder LCNEC, which was difficult to differentiate from poorly differentiated adenocarcinoma. An imprint cytology was very useful for the final diagnosis in this case. A 56-year-old male with left exophthalmos was admitted to the hospital. Radiological examinations revealed the presence of a left gallbladder tumor with orbital metastasis. The histological diagnosis was poorly differentiated adenocarcinoma, and intensive chemoradiotherapy was administered. Unfortunately, the patient died of extensive metastases 36 months after the initial onset of symptoms. An autopsy revealed a tumor mass in the gallbladder associated with multiple liver and peritoneal metastases. Imprint cytology of the main tumor revealed cytological features of LCNEC, and additional histological examinations confirmed this diagnosis. Although performing a histological examination is important for making a final diagnosis, imprint cytology is powerful tool for differential diagnosis of LCNEC, especially in patients with carcinoma with poor differentiation

Risk factors of first bite syndrome

Objective : First bite syndrome is a complication of surgical resection of parapharyngeal space tumors and the development of cramping pain in the parotid region with the first bite of a meal. The present study aimed to identify the potential risk factors for the development of first bite syndrome. Methods : We retrospectively reviewed 30 consecutive patients with parapharyngeal space tumors who had been surgically treated between August 2003 and December 2015 at our department. Results : The tumor site (prestyloid or retrostyloid) and surgical approach (transcervical-parotid, transparotid, or transcervical) were not correlated with the development of first bite syndrome. Ligation and mobilization of the external carotid artery was significantly correlated with the development of first bite syndrome. Moreover, patients with complete resection of the parotid gland did not experience first bite syndrome. Discussion : The present findings suggest that concomitant surgical settings of 1) sympathetic denervation of the parotid gland with ligation of the external carotid artery or injury of the sympathetic nerve plexus around the external carotid artery during its mobilization, and 2) residual parotid gland tissue are risk factors for the development of first bite syndrome after surgical resection of parapharyngeal space tumors

Sideward Peak of Intermediate Mass Fragments in High Energy Proton Induced Reactions

Intermediate mass fragment (IMF) formation in the 12 GeV proton induced reaction on Au target is analyzed by using a combined framework of a transport model (JAM/MF) and a newly developed non-equilibrium percolation (NEP) model. In this model, we can well reproduce the mass distribution of fragments. In addition, the sideward peaked angular distribution would emerge under the condition that the fragment formation time is very short, around 20 fm/c. Within this short time period, the un-heated part of the residual nucleus is kept to have doughnut shape, then the Coulomb repulsion from this shape strengthens the sideward peak of IMF.Comment: 22 pages, Latex, 6 embedded PS figure

Essential role of Notch signaling in effector memory CD8+ T cell–mediated airway hyperresponsiveness and inflammation

Adoptive transfer of in vivo–primed CD8+ T cells or in vitro–generated effector memory CD8+ T (TEFF) cells restores airway hyperresponsiveness (AHR) and airway inflammation in CD8-deficient (CD8−/−) mice. Examining transcription levels, there was a strong induction of Notch1 in TEFF cells compared with central memory CD8+ T cells. Treatment of TEFF cells with a γ-secretase inhibitor (GSI) strongly inhibited Notch signaling in these cells, and after adoptive transfer, GSI-treated TEFF cells failed to restore AHR and airway inflammation in sensitized and challenged recipient CD8−/− mice, or to enhance these responses in recipient wild-type (WT) mice. These effects of GSI were also associated with increased expression of the Notch ligand Delta1 in TEFF cells. Treatment of sensitized and challenged WT mice with Delta1-Fc resulted in decreased AHR and airway inflammation accompanied by higher levels of interferon γ in bronchoalveolar lavage fluid. These results demonstrate a role for Notch in skewing the T cell response from a T helper (Th)2 to a Th1 phenotype as a consequence of the inhibition of Notch receptor activation and the up-regulation of the Notch ligand Delta1. These data are the first to show a functional role for Notch in the challenge phase of CD8+ T cell–mediated development of AHR and airway inflammation, and identify Delta1 as an important regulator of allergic airway inflammation

Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages

The first extensively drug resistant (XDR) Neisseria gonorrhoeae strain with high resistance to the extended-spectrum cephalosporin ceftriaxone was identified in 2009 in Japan, but no other strain with this antimicrobial-resistance profile has been reported since. However, surveillance to date has been based on phenotypic methods and sequence typing, not genome sequencing. Therefore, little is known about the local population structure at the genomic level, and how resistance determinants and lineages are distributed and evolve. We analysed the whole-genome sequence data and the antimicrobial-susceptibility testing results of 204 strains sampled in a region where the first XDR ceftriaxone-resistant N. gonorrhoeae was isolated, complemented with 67 additional genomes from other time frames and locations within Japan. Strains resistant to ceftriaxone were not found, but we discovered a sequence type (ST)7363 sub-lineage susceptible to ceftriaxone and cefixime in which the mosaic penA allele responsible for reduced susceptibility had reverted to a susceptible allele by recombination. Approximately 85 % of isolates showed resistance to fluoroquinolones (ciprofloxacin) explained by linked amino acid substitutions at positions 91 and 95 of GyrA with 99 % sensitivity and 100 % specificity. Approximately 10 % showed resistance to macrolides (azithromycin), for which genetic determinants are less clear. Furthermore, we revealed different evolutionary paths of the two major lineages: single acquisition of penA X in the ST7363-associated lineage, followed by multiple independent acquisitions of the penA X and XXXIV in the ST1901-associated lineage. Our study provides a detailed picture of the distribution of resistance determinants and disentangles the evolution of the two major lineages spreading worldwide

Quantum Molecular Dynamics Approach to the Nuclear Matter Below the Saturation Density

Quantum molecular dynamics is applied to study the ground state properties of nuclear matter at subsaturation densities. Clustering effects are observed as to soften the equation of state at these densities. The structure of nuclear matter at subsaturation density shows some exotic shapes with variation of the density.Comment: 21 pages of Latex (revtex), 9 Postscript figure

Minute ampullary carcinoid tumor with lymph node metastases: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Carcinoid tumors are usually considered to have a low degree of malignancy and show slow progression. One of the factors indicating the malignancy of these tumors is their size, and small ampullary carcinoid tumors have been sometimes treated by endoscopic resection.</p> <p>Case presentation</p> <p>We report a case of a 63-year-old woman with a minute ampullary carcinoid tumor that was 7 mm in diameter, but was associated with 2 peripancreatic lymph node metastases. Mild elevation of liver enzymes was found at her regular medical check-up. Computed tomography (CT) revealed a markedly dilated common bile duct (CBD) and two enlarged peripancreatic lymph nodes. Endoscopy showed that the ampulla was slightly enlarged by a submucosal tumor. The biopsy specimen revealed tumor cells that showed monotonous proliferation suggestive of a carcinoid tumor. She underwent a pylorus-preserving whipple resection with lymph node dissection. The resected lesion was a small submucosal tumor (7 mm in diameter) at the ampulla, with metastasis to 2 peripancreatic lymph nodes, and it was diagnosed as a malignant carcinoid tumor.</p> <p>Conclusion</p> <p>Recently there have been some reports of endoscopic ampullectomy for small carcinoid tumors. However, this case suggests that attention should be paid to the possibility of lymph node metastases as well as that of regional infiltration of the tumor even for minute ampullary carcinoid tumors to provide the best chance for cure.</p

A Planetary Microlensing Event with an Unusually Red Source Star: MOA-2011-BLG-291

We present the analysis of planetary microlensing event MOA-2011-BLG-291, which has a mass ratio of $q=(3.8\pm0.7)\times10^{-4}$ and a source star that is redder (or brighter) than the bulge main sequence. This event is located at a low Galactic latitude in the survey area that is currently planned for NASA's WFIRST exoplanet microlensing survey. This unusual color for a microlensed source star implies that we cannot assume that the source star is in the Galactic bulge. The favored interpretation is that the source star is a lower main sequence star at a distance of $D_S=4.9\pm1.3\,$kpc in the Galactic disk. However, the source could also be a turn-off star on the far side of the bulge or a sub-giant in the far side of the Galactic disk if it experiences significantly more reddening than the bulge red clump stars. However, these possibilities have only a small effect on our mass estimates for the host star and planet. We find host star and planet masses of $M_{\rm host} =0.15^{+0.27}_{-0.10}M_\odot$ and $m_p=18^{+34}_{-12}M_\oplus$ from a Bayesian analysis with a standard Galactic model under the assumption that the planet hosting probability does not depend on the host mass or distance. However, if we attempt to measure the host and planet masses with host star brightness measurements from high angular resolution follow-up imaging, the implied masses will be sensitive to the host star distance. The WFIRST exoplanet microlensing survey is expected to use this method to determine the masses for many of the planetary systems that it discovers, so this issue has important design implications for the WFIRST exoplanet microlensing survey