943 resultados para Photius I, Saint, Patriarch of Constantinople, ca. 820-ca. 891.


Relevância:

100.00% 100.00%

Publicador:

Resumo:

PURPOSE: We conducted a phase I/II clinical trial to determine the safety and feasibility of combining vorinostat with 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer (mCRC) and elevated intratumoral thymidylate synthase (TS).

METHODS: Patients with mCRC who had failed all standard therapeutic options were eligible. Intratumoral TS mRNA expression and peripheral blood mononuclear cell (PBMC) histone acetylation were measured before and after 6 consecutive days of vorinostat treatment at 400 mg PO daily. 5-FU/LV were given on days 6 and 7 and repeated every 2 weeks, along with continuous daily vorinostat. Dose escalation occurred in cohorts of three to six patients.

RESULTS: Ten patients were enrolled. Three dose levels were explored in the phase I portion of the study. Two dose-limiting toxicities (DLTs) were observed at the starting dose level, which resulted in dose de-escalation to levels -1 and -2. Given the occurrence of two DLTs at each of the dose levels, we were unable to establish a maximum tolerated dose (MTD). Two patients achieved significant disease stabilization for 4 and 6 months. Grade 3 and 4 toxicities included fatigue, thrombocytopenia and mucositis. Intratumoral TS downregulation > or = 50% was observed in one patient only. Acetylation of histone 3 was observed in PBMCs following vorinostat treatment.

CONCLUSIONS: The study failed to establish a MTD and was terminated. The presence of PBMC histone acetylation indicates biological activity of vorinostat, however, consistent reductions in intratumoral TS mRNA were not observed. Alternate vorinostat dose-scheduling may alleviate the toxicity and achieve optimal TS downregulation.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Electron-impact excitation data for He-like ions are of significant importance for diagnostic applications to both laboratory and astrophysical plasmas. Here we report on the first fully relativistic R -matrix calculations with radiation damping for the He-like ions Fe 24+ and Kr 34+ . Effective collision strengths for these two ions have been determined with and without damping over a wide temperature range for all transitions between the 49 levels through n = 5. We find that damping has a pronounced effect on the effective collision strengths for excitation to some of the low-lying levels, but its effect on excitation to the vast majority of levels is small. At the energy of a resonance peak, we also investigate the effect of radiation damping on the angular distribution of scattered electrons. Finally, we compare our results for Fe 24+ with an earlier intermediate coupling frame transformation R -matrix calculation with radiation damping by Whiteford et al ( J. Phys. B: At. Mol. Opt. Phys. 34 3179) and find good agreement, especially for excitation to the lower levels.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

A cabinet card portrait of an unidentified woman by I. H. Lewis, a photographer

Relevância:

100.00% 100.00%

Publicador:

Resumo:

James Monroe (1758-1831) was appointed Secretary of State by President James Madison in 1811. He remained in this position until March, 1817, with the exception of the period from October 1, 1814, to February 28, 1815, when he was ad interim Secretary of State. Monroe encouraged President James Madison and Congress to declare war on Great Britain, feeling it would be the most effective way to change offensive British policies. The United States declared war on June 17, 1812, after which he served as Secretary of War. Monroe later became President of the United States from 1817 until 1824.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

A letter of marque addressed to Captain James Rogers, commander of the boat Retaliation, and signed by James Monroe, secretary of state. Letters of marquee provided legal authority for an armed vessel to capture enemy ships and commit acts which would otherwise constitute piracy. The letter has no date, but was likely created during the War of 1812, and authorizes the Captain to attack and capture enemy vessels.