Successful treatment of persistent bronchorrhea by gefitinib in a case with Recurrent Bronchioloalveolar Carcinoma: a case report

BACKGROUND: Bronchorrhea is one of late complaints in patients with bronchioloalveolar carcinoma (BAC) and hampers their quality of life. Although an effective treatment for bronchorrhea in these patients has not been established, recently we have treated effectively one case of persistent bronchorrhea associated with clinical recurrent BAC with gefitinib (ZD1839, 'Iressa™'; AstraZeneca Japan; Osaka, Japan). CASE PRESENTATION: A 63-year-old Japanese female had undergone left pneumonectomy with radical lymph node dissection (ND2a) for diffuse type bronchioloalveolar carcinoma originated in left lower lobe. Multiple pulmonary metastases in right lung were found one year after operation. Pulmonary metastatic lesion has grown and she complained of progressive symptoms of massive watery sputum and dyspnea, four years after operation. Although her symptom was getting worse in spite of routine treatment, it completely disappeared within 2 weeks of starting oral gefitinib. Thereafter, she has been symptom-free and shows good partial response on repeat scan after 9 months of oral gefitinib. CONCLUSIONS: The dramatic remission of persistent bronchorrhea by gefitinib in the presented case suggests that gefitinib might be a promising option for bronchioloalveolar carcinoma, particularly in cases with severe bronchorrhea. Although it is not possible to comment on whether the improvement came from tumor cell death itself or suppressive effect of mucin synthesis by the epidermal growth factor receptor-tyrosine kinase inhibitory action

Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts

AbstractObjectiveAccumulation of smooth muscle cells and extracellular matrix in the intima of artery bypass grafts induces neointimal hyperplasia, resulting in graft failure. We investigated the inhibitory effect of locally applied cilostazol, an inhibitor of cyclic adenosine monophosphate phosphodiesterase III, on neointimal hyperplasia and the role of tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts.Methods and resultsWe established a distal anastomotic stricture model of free artery graft stenosis using rat abdominal aorta. In this model, neointimal hyperplasia was observed not only in the distal anastomotic site but also in the graft body at postoperative day 14 and was markedly progressed at day 28. Strong expression of tenascin-C was found in the media and neointima of the graft body. When cilostazol was locally administered around the graft using Pluronic gel, neointimal hyperplasia of the graft was significantly suppressed in comparison with gel-treated control graft. The mean neointima/media area ratio was reduced by 86.6% for the graft body and by 75.8% for the distal anastomotic site versus the control. Cilostazol treatment decreased cell proliferation and tenascin-C expression in the neointima. In an in vitro experiment using cultured smooth muscle cells isolated from rat aorta, cilostazol completely suppressed the tenascin-C mRNA expression induced by platelet-derived growth factor-BB.ConclusionA single topical administration of cilostazol may suppress neointimal hyperplasia by inhibiting cell proliferation and tenascin-C synthesis in free artery grafts, presenting the potential for clinical use in vascular surgery

Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats

AbstractObjectivesp38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats.MethodsRats were divided into 4 groups: (1) the control group (daily 0.9% saline), (2) the FR group (daily FR167653, 2 mg · kg−1 · d−1), (3) the MCT group (daily 0.9% saline the day after a single monocrotaline dose, 60 mg/kg), and (4) the MCT+FR group (daily FR167653, 2 mg · kg−1 · d−1, the day after a single MCT dose). Body weight, pulmonary artery pressure, and morphometric changes of the pulmonary artery with the histopathologic method were observed weekly for 4 weeks. Also, p38 mitogen-activated protein kinase activity and inflammatory cytokine expression in the lung were measured.ResultsFour weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT+FR group was lower than in the MCT group (MCT+FR vs MCT: 24.7 ± 1.9 vs 36.5 ± 2.1 mm Hg; P < .05). In morphometric analysis the percentage of medial wall thickness and the percentage of muscularization in the MCT+FR group were reduced compared with those in the MCT group after 4 weeks (P < .05); however, the number of macrophages was not significantly different. p38 mitogen-activated protein kinase activity was significantly attenuated in the MCT+FR group compared with in the MCT group (7.2 ± 0.52 vs 2.1 ± 0.23 fold-increase, P < .05, at 1 week). Although mRNA levels of tumor necrosis factor α and interleukin 1β were reduced in the MCT+FR group compared with in the MCT group (tumor necrosis factor α: 1.18 ± 0.36 vs 3.05 ± 1.12 fold-increase, P < .05, at 2 weeks; interleukin 1β: 2.2 ± 0.34 vs 4.4 ± 1.09 fold-increase, P < .05, at 1 week), FR167653 did not suppress increased monocyte chemotactic protein 1 mRNA expression induced by monocrotaline (3.2 ± 0.62 vs 3.1 ± 0.42 fold-increase, at 1 week).ConclusionFR167653 significantly attenuates the expression of inflammatory cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38 mitogen-activated protein kinase might play a central role in the molecular events that underlie the development and progression of pulmonary hypertension

Surface Oxygen Vacancy Formation Energy Calculations in 34 Orientations of beta-Ga2O3 and theta-Al2O3

Computational exploration of previously unknown reactive sites is a powerful strategy for the emergence of new catalytic reactions. Exotic surfaces can be theoretically investigated, but there are very few, if any, computational models of high-index orientations that consider the reconstruction of the surface. A workflow to efficiently obtain a set of accessible terminations by removing those that are metastable against macroscopic facet formation and by comparing cleaved surfaces and surfaces suggested by a genetic algorithm (GA) for promising orientations is proposed and demonstrated using 34 orientations of beta-Ga2O3 and theta-Al2O3. Seven and six terminations considered to be experimentally accessible are found for beta-Ga2O3 and theta-Al2O3, respectively, where the highest surface energy was roughly twice that of the lowest. The lowest surface 0 vacancy formation - energies (E-Ovac) among accessible surfaces are 3.04 and 5.46 eV in the (101) and (20 (1) over bar) terminations for beta-Ga2O3 and theta-Al2O3, respectively, where the decreases in E-Ovac, from the most stable surface are 1.32 and 1.11 eV, respectively. The E-Ovac in accessible surfaces showed a good correlation with the descriptors of the local coordination environment, suggesting that exploiting surface O in an unfavorable environment in an accessible termination would enhance O-vacancy-related catalyst performance even in materials that do not show reactivity on the most stable surface

Frontier Molecular Orbital Based Analysis of Solid-Adsorbate Interactions over Group 13 Metal Oxide Surfaces

Adsorption is an essential process that takes place in heterogeneous catalysis. In the current study, solid-adsorbate interactions occurring between a variety of small molecules and surfaces of group beta metal oxides, including beta-Ga2O3(100), beta-Ga2O3(001), theta-Al2O3 (100), theta-Al2O3 (001), theta-Al2O3 (010), In2O3(110), and In2O3(111), were investigated using density functional theory calculations and a machine learning (ML)-based statistical method. The adsorbates utilized for this purpose include CO, CO2, ND NH3, H2O, acetonitrile, acetone, acetamide, acetic acid, alkanes, alkenes, aromatic compounds, alcohols, and amines. The results show that the adsorption energies (E-ads) of each metal oxide surface correlate linearly with the highest occupied molecular orbital (HOMO) energies of the adsorbates and not with energies of the lowest unoccupied molecular orbital (LUMO) of the small molecules. Moreover, in these systems, contributions to molecular adsorption are dominated by interactions between the HOMOs of the adsorbates and the surface conduction band of the metal oxides. Furthermore, the surface energy was found to be an important parameter influencing E-ads values of different metal oxides. Finally, the results of statistical analysis using a ML approach confirmed that adsorbate HOMOs and surface energy of metal oxides are the most influential factors governing molecular adsorption, and also demonstrated that dipole moments of adsorbates contribute to controlling to adsorption

Clinical significance of radiofrequency ablation and metastasectomy in elderly patients with lung metastases from musculoskeletal sarcomas

Background: The incidence of sarcoma diagnosed in the elderly population may be rising due to the increasing life expectancy. The purpose of our study was to evaluate the efficacy of lung metastasectomy and radiofrequency (RF) ablation in elderly sarcoma patients (65 years or older) with lung metastases, compared with adult sarcoma patients younger than 65 years (20-64 years). Materials and Methods: We retrospectively evaluated the clinical efficacy of metastasectomy and lung RF ablation in sarcoma patients with lung metastases. Results: Between 2001 and 2010, lung metastases were detected in 66 adult patients with musculoskeletal sarcomas. Twenty-five patients with lung metastasis were elderly. Twelve of the 25 patients were treated with lung metastasectomy and/or RF ablation. In contrast, 41 patients were adult patients younger than 65 years. Twenty of these 41 patients were treated with lung metastasectomy and/or RF ablation. The 1 and 3-year survival rates after initial treatment for lung metastases were 81.8% and 38.4% in 12 elderly patients, respectively. Compared with the control group, the survival rate in the elderly patients was not significantly different. Conclusion: We conclude that elderly sarcoma patients with lung metastases should always be considered for either metastasectomy or RF ablation