Electronic structures of B-2p and C-2p of boron-doped diamond film by soft X-ray absorption and emission spectroscopy

X-ray absorption (XAS) and emission (XES) spectroscopy near B-K and C-K edges have been performed on metallic (~1at%B, B-diamond) and semiconducting (~0.1at%B and N, BN-diamond) doped-diamond films. Both B-K XAS and XES spectra shows metallic partial density of state (PDOS) with the Fermi energy of 185.3 eV, and there is no apparent boron-concentration dependence in contrast to the different electric property. In C-K XAS spectrum of B-diamond, the impurity state ascribed to boron is clearly observed near the Fermi level. The Fermi energy is found to be almost same with the top of the valence band of non-doped diamond, E_V, 283.9 eV. C-K XAS of BN-diamond shows both the B-induced shallow level and N-induced deep-and-broad levels as the in-gap states, in which the shallow level is in good agreement with the activation energy (E_a=0.37 eV) estimated from the temperature dependence of the conductivity, namely the change in C-2p PDOS of impurity-induced metallization is directly observed. The electric property of this diamond is mainly ascribed to the electronic structure of C-2p near the Fermi level. The observed XES spectra are compared with the DVX-alpha cluster calculation. The DVX-alpha result supports the strong hybridization between B-2p and C-2p observed in XAS and XES spectra, and suggests that the small amount of borons (<1at%) in diamond occupy the substitutional site rather than interstitial site.Comment: submitted to Phys. Rev. B, 5 pages and 5 figure

Afatinib Prolongs Survival Compared with Gefitinib in an Epidermal Growth Factor Receptor-Driven Lung Cancer Model

An irreversible ErbB family blocker is expected to inhibit tumors with activating epidermal growth factor receptor (EGFR) mutations more strongly than reversible EGFR tyrosine kinase inhibitors and to overcome acquired resistance to the T790M secondary mutation. Eleven-week-old transgenic mice with Egfr exon 19 deletion mutation were treated with afatinib, gefitinib, or vehicle for 4 weeks. All mice were sacrificed at 15 weeks of age, and the number of superficial left lung tumors with a long axis exceeding 1 mm was counted. The afatinib-treated group had significantly fewer tumors than the vehicle group (P < 0.01) and tended to have fewer tumors than the gefitinib-treated group (P = 0.06). Pathologically, gefitinib-treated mice had clearer, more nodular tumors than afatinib-treated mice. Immunoblotting showed that afatinib suppressed not only pEGFR but also pHER2, and induced apoptosis for longer periods than gefitinib. Subsequently, when each drug was administered 5 days per week until death, afatinib significantly enhanced mouse survival compared with gefitinib (median survival time: 456 days vs. 376.5 days; log-rank test, P < 0.01). Finally, the combination of afatinib with bevacizumab was found to be superior to either drug alone in exon 19 deletion/T790M and L858R/T790M xenograft tumors. Overall, afatinib was more potent than gefitinib in tumors harboring an exon 19 deletion mutation, and the combination of afatinib with bevacizumab efficiently suppressed tumors harboring the T790M secondary mutation

Protective Effects of Bisoprolol against Acute Exacerbation in Moderate-to-Severe Chronic Obstructive Pulmonary Disease

Although recent retrospective studies suggested that the use of β-blockers appears to help improve the mortality rate and decrease the rate of exacerbation in chronic obstructive pulmonary disease (COPD) patients with heart failure, the effects of β-blockers on COPD patients without heart failure have not been established. Based on previous reports, we have launched a multicenter, prospective, single-arm phase II study to evaluate the preventive effect of the cardioselective β-blocker bisoprolol in COPD exacerbation, in Japanese individuals with moderate-to-severe COPD who do not have heart failure but do have hypertension requiring the use of medication. The primary endpoint is the rate of mild-to-severe COPD exacerbation. The results of this study will clarify whether bisoprolol can prevent exacerbation in COPD patients without heart failure

Randomized Phase II Study Comparing Mannitol with Furosemide for the Prevention of Renal Toxicity Induced by Cisplatin-based Chemotherapy with Short-term Low-volume Hydration in Advanced Non-small Cell Lung Cancer: The OLCSG1406 Study Protocol

Although cisplatin-based chemotherapy shows a survival advantage compared to carboplatin for treating advanced non-small cell lung cancer, high-volume hydration and a long infusion time are necessary to avoid nephrotoxicity, and cisplatin-based chemotherapy has been difficult to administer in outpatient settings. A low-volume hydration method using mannitol or furosemide as forced diuresis was recently introduced, but there are no clear conclusions regarding which agent should be used. We describe our ongoing randomized phase II trial (the OLCSG1406 Study) evaluating the efficacy of forced diuresis. This study will clarify whether mannitol or furosemide is more suitable in cisplatin-based chemotherapy with low-volume hydration

Treatment for a non-compliant patient with cancer and epilepsy

　A 58-year-old man with cervical esophageal cancer and a history of epilepsy was treated with chemoradiotherapy from May of 2013. When tube feeding was initiated due to aspiration pneumonitis, the patient showed a degree of irritability that affected routine staff work and treatment compliance. We attempted to perform supportive care for maladjustment by the notice, the fast, and the tube feeding, but there was no improvement. After we added carbamazepine, primidone, and propericiazine (which had been canceled at the initiation of the tube feeding) to the patient's intravenous phenytoin, the symptoms and treatment compliance improved significantly. We concluded that the causes of the patient's irritability were maladjustment and his epilepsy

Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency

The effectiveness of vandetanib, an agent that targets RET, VEGFR and EGFR signaling, against EGFR-mutant lung cancer cells with PTEN loss was investigated. Two EGFR mutant non-small cell lung cancer (NSCLC) cell lines, PC-9 (PTEN wild type) and NCI-H1650 (PTEN null), were used. We transfected an intact FTEN gene into H1650 cells and knocked down PTEN expression in PC-9 cells using shRNA. The effectiveness of gefitinib and vandetanib was assessed using a xenograft model. While PC-9 cells were more resistant to vandetanib than gefitinib, H1650 cells were more sensitive to vandetanib than gefitinib. Both gefitinib and vandetanib suppressed the activation of EGFR and MAPK in H1650 cells, although phosphorylated AKT levels were not affected. In an H1650 cell xenograft model, vandetanib was also more effective than gefitinib. Although PTEN-transfected H1650 cells did not show restoration of sensitivity to gefitinib in vitro, the xenograft tumors responded to gefitinib and vandetanib. Knockdown of PTEN in PC-9 cells caused resistance to gefitinib. In conclusion, vandetanib might be effective in NSCLC with EGFR mutations that lack FTEN expression. The contribution of PTEN absence to vandetanib activity in NSCLC cells harboring EGFR mutations should be further examined