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排序方式: 共有288条查询结果,搜索用时 15 毫秒
1.
Dimitroff CJ Klohs W Sharma A Pera P Driscoll D Veith J Steinkampf R Schroeder M Klutchko S Sumlin A Henderson B Dougherty TJ Bernacki RJ 《Investigational new drugs》1999,17(2):121-135
Angiogenesis, the formation of new blood vessels from an existing vasculature, is requisite for tumor growth. It entails intercellular coordination of endothelial and tumor cells through angiogenic growth factor signaling. Interruption of these events has implications in the suppression of tumor growth. PD166285, a broad-spectrum receptor tyrosine kinase (RTK) inhibitor, and PD173074, a selective FGFR1TK inhibitor, were evaluated for their anti-angiogenic activity and anti-tumor efficacy in combination with photodynamic therapy (PDT). To evaluate the anti-angiogenic and anti-tumor activities of these compounds, RTK assays, in vitro tumor cell growth and microcapillary formation assays, in vivo murine angiogenesis and anti-tumor efficacy studies utilizing RTK inhibitors in combination with photodynamic therapy were performed. PD166285 inhibited PDGFR--, EGFR-, and FGFR1TKs and c-src TK by 50% (IC50) at concentrations between 7–85nM. PD173074 displayed selective inhibitory activity towards FGFR1TK at 26nM. PD173074 demonstrated (>100 fold) selective growth inhibitory action towards human umbilical vein endothelial cells compared with a panel of tumor cell lines. Both PD166285 and PD173074 (at 10nM) inhibited the formation of microcapillaries on Matrigel-coated plastic. In vivo anti-angiogenesis studies in mice revealed that oral administration (p.o.) of either PD166285 (1–25 mg/kg) or PD173074 (25–100 mg/kg) generated dose dependent inhibition of angiogenesis. Against a murine mammary 16c tumor, significantly prolonged tumor regressions were achieved with daily p.o. doses of PD166285 (5–10 mg/kg) or PD173074 (30–60 mg/kg) following PDT compared with PDT alone (p<0.001). Many long-term survivors were also noted in combination treatment groups. PD166285 and PD173074 displayed potent anti-angiogenic and anti-tumor activity and prolonged the duration of anti-tumor response to PDT. Interference in membrane signal transduction by inhibitors of specific RTKs (e.g. FGFR1TK) should result in new chemotherapeutic agents having the ability to limit tumor angiogenesis and regrowth following cytoreductive treatments such as PDT. 相似文献
2.
D J Johnson V Amarnath K Amarnath H Valentine W M Valentine 《Toxicological sciences》2003,76(1):65-74
Differences in the toxicities observed for dithiocarbamates have been proposed to result from the influence of nitrogen substitution, oxidation state, and route of exposure. To better characterize the fate of dithiocarbmates in vivoas a function of structure and route of exposure, rats were administered equimolar doses of carbon disulfide (CS2), N-methyldithiocarbamate, pyrrolidine dithiocarbamate, N,N-diethyldithiocarbamate, or disulfiram daily for five days, either po or ip, and sequential blood samples obtained. Protein dithiocarbamates formed by the in vivo release of CS2, parent dithiocarbamate, and protein-bound mixed disulfides were assessed in plasma and hemolysate by measuring toluene trithiocarbonate generated upon treatment with toluene-3, 4-dithiol (TdT). To aid in determining the bioavailability of CS2 from the administered dithiocarbamates, the urinary CS2 metabolites, 2-thiothiazolidine-4-carboxylic acid (TTCA) and 2-thiothiazolidin-4-ylcarbonylglycine (TTCG), were also determined. The levels of TdT-reactive moieties detected depended upon both the compound administered and the route of exposure. Parent dithiocarbamates, with the exception of disulfiram, were eliminated from blood within 24 h; but protein associated TdT-reactive moieties persisted and accumulated with repeated exposure, regardless of the route of exposure. N-Methyldithiocarbamate demonstrated the greatest potential to produce intracellular globin modifications, presumably through its unique ability to generate a methylisothiocyanate metabolite. Urinary excretion of TTCA and TTCG was more sensitive than TdT analysis for detecting dithiocarbamate exposure, but TdT analysis appeared to be a better indicator of in vivo release of CS2 by dithiocarbamates than were urinary CS2 metabolites. These data suggest that CS2 is a more important metabolite, following oral exposure, than are other routes of exposure, e.g., inhalation or dermal. In addition, data also suggest that acid stability, nitrogen substitution, and route of exposure are important factors governing the toxicity observed for a particular dithiocarbamate. 相似文献
3.
Tripathi Siddhi Amarnath Gowdagere Shamanna Muddugangadhar Byrasandra Channapa Sharma Ashish Choudhary Suchismita 《Journal of Indian Prosthodontic Society》2014,14(1):110-114
The functional surfaces of the porcelain fused to metal fixed partial dentures are often abraded to adjust occlusion, such restorations are often found to fail in service. This study was therefore conducted to study the effect of surface abrasion on flexural strength of glazed porcelain fused to metal samples. It was also the aim of this study to find the effect of re-glazing on flexural strength of abraded samples. A total of ninety glazed porcelain fused to metal bar samples of the dimension 15 mm × 2 mm × 1.5 mm were fabricated. These samples were then divided into three groups (30 samples each) according to the surface treatments: group A-glazed (control); group B-abraded and group C-abraded and then re-glazed (self-glazed). Flexural strength was measured by using three point bend test on universal testing machine (texture analyser) with a cross-head speed of 0.6 mm/min. Peak force at the time of failure for all the samples was recorded. Statistical analysis found that mean flexural strength was highest for group A-80.65 ± 12.81 MPa; as compared to group B-74.18 ± 10.74 MPa and group C-77.85 ± 9.39 MPa. Student’s t test indicated that the difference in the flexural strength between groups A and B was significant while it was non-significant between groups B and C and also between groups A and C. The ‘f’ test indicated that the difference between the groups was non-significant. This study therefore showed that there is a marked decrease in the flexural strength of the porcelain fused to metal restorations after occlusal abrasion. The study also found that reglazing of these restorations may not restore their flexural strength significantly. 相似文献
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5.
Amarnath R. Allu Sathravada Balaji Kavya Illath Chaithanya Hareendran T. G. Ajithkumar Kaushik Biswas K. Annapurna 《RSC advances》2018,8(26):14422
Understanding the conductivity variations induced by compositional changes in sodium super ionic conducting (NASICON) glass materials is highly relevant for applications such as solid electrolytes for sodium (Na) ion batteries. In the research reported in this paper, NASICON-based NCAP glass (Na2.8Ca0.1Al2P3O12) was selected as the parent glass. The present study demonstrates the changes in the Na+ ion conductivity of NCAP bulk glass with the substitution of boron (NCABP: Na2.8Ca0.1Al2B0.5P2.7O12) and gallium (NCAGP: Na2.8Ca0.1Al2Ga0.5P2.7O12) for phosphorus and the resulting structural variations found in the glass network. For a detailed structural analysis of NCAP, NCABP and NCAGP glasses, micro-Raman and magic angle spinning-nuclear magnetic resonance (MAS-NMR) spectroscopic techniques (for 31P, 27Al, 23Na, 11B and 71Ga nuclei) were used. The Raman spectrum revealed that the NCAP glass structure is more analogous to the AlPO4 mesoporous glass structure. The 31P MAS-NMR spectrum illustrated that the NCAP glass structure consists of a high concentration of Q0 (3Al) units, followed by Q0 (2Al) units. The 27Al MAS-NMR spectrum indicates that alumina exists at five different sites, which include AlO4 units surrounded by AlO6 units, Al(OP)4, Al(OP)5, Al(OAl)6 and Al(OP)6, in the NCAP glass structure. The 31P, 27Al and 11B MAS-NMR spectra of the NCABP glass revealed the absence of B–O–Al linkages and the presence of B3–O–B4–O–P4 linkages which further leads to the formation of borate and borophosphate domains. The 71Ga MAS-NMR spectrum suggests that gallium cations in the NCAGP glass compete with the alumina cations and occupy four (GaO4), five (GaO5) and six (GaO6) coordinated sites. The Raman spectrum of NCAGP glass indicates that sodium cations have also been substituted by gallium cations in the NCAP glass structure. From impedance analysis, the dc conductivity of the NCAP glass (∼3.13 × 10−8 S cm−1) is slightly decreased with the substitution of gallium (∼2.27 × 10−8 S cm−1) but considerably decreased with the substitution of boron (∼1.46 × 10−8 S cm−1). The variation in the conductivity values are described based on the structural changes of NCAP glass with the substitution of gallium and boron.Understanding the conductivity variations induced by compositional changes in sodium super ionic conducting (NASICON) glass materials is highly relevant for applications such as solid electrolytes for sodium (Na) ion batteries. 相似文献
6.
Singh Ayesha Coulter Amanda R. Trainor Patrick J. Singam Narayana Sarma V. Aladili Bahjat N. Amraotkar Alok R. Owolabi Ugochukwu S. DeFilippis Andrew P. 《Journal of thrombosis and thrombolysis》2021,51(1):120-128
Journal of Thrombosis and Thrombolysis - Platelet activation and subsequent aggregation is a vital component of atherothrombosis resulting in acute myocardial infarction. Therefore, quantifying... 相似文献
7.
Alain P. Gobert Olivier Boutaud Mohammad Asim Irene A. Zagol-Ikapitte Alberto G. Delgado Yvonne L. Latour Jordan L. Finley Kshipra Singh Thomas G. Verriere Margaret M. Allaman Daniel P. Barry Kara M. McNamara Johanna C. Sierra Venkataraman Amarnath Mohammed N. Tantawy Diane Bimczok M. Blanca Piazuelo M. Kay Washington Keith T. Wilson 《Gastroenterology》2021,160(4):1256-1268.e9
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8.
Shoba Amarnath 《European journal of immunology》2013,43(9):2255-2258
9.