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Compounds Leads (compound + lead)
Selected AbstractsChemotherapy with 5-fluorouracil and a platinum compound improves outcomes in metastatic small bowel adenocarcinoma,CANCER, Issue 8 2008Michael J. Overman MD Abstract BACKGROUND. Metastatic small bowel adenocarcinoma (SBA) has a poor prognosis. Because of the rarity of SBA, only a few studies have evaluated the role of chemotherapy in the treatment of metastatic SBA; thus, the benefit, if any, of adding a platinum compound to fluorouracil (5-FU) is unknown. The objective of this retrospective study was to determine whether the addition of a platinum compound to 5-FU provided any benefit in the treatment of patients with metastatic SBA. METHODS. The authors identified 80 patients with metastatic SBA who were treated with chemotherapy at the University of Texas M. D. Anderson Cancer Center between 1978 and 2005. Response rates, progression-free survival (PFS), and overall survival (OS) were compared between patients who received 5-FU and a platinum compound and patients who received other chemotherapy combinations. RESULTS. The median patient age was 53 years. The primary tumor site was the jejunum in 35 patients (43%), duodenum in 30 patients (38%), ileum in 6 patients (8%), and nonspecified small bowel in 9 patients (11%). Of all 80 patients, 29 patients (36%) received 5-FU and a platinum compound, 41 patients (51%) received 5-FU without a platinum compound, and 10 patients (13%) received non-5-FU,based treatment. Compared with other chemotherapy regimens, treatment with 5-FU and a platinum agent resulted in a higher response rate (46% vs 16% with other regimens; P = .01) and longer median PFS (8.7 months vs 3.9 months; P , .01) but not better OS (14.8 months vs 12 months; P = .1). In multivariate analysis, treatment with 5-FU and a platinum compound was a significant predictor of response (odds ratio, 4.5; 95% confidence interval [CI], 1.3-15.8; P = .02) and PFS (hazard ratio. 0.49; 95% CI, 0.29-0.84; P = .01) but only reached borderline significance for OS (hazard ratio, 0.63; 95% CI, 0.37-1.07; P = .08). CONCLUSIONS. To the authors' knowledge, the current analysis represents the largest number of patients with metastatic SBA treated with chemotherapy in the literature, and the results suggested that the combination of 5-FU and a platinum compound leads to a higher response rate and PFS compared with other chemotherapy regimes. The authors concluded that prospective investigation of platinum analogues in the treatment of SBA is warranted. Cancer 2008. © 2008 American Cancer Society. [source] Microbiological investigation of methane- and hydrocarbon-discharging mud volcanoes in the Carpathian Mountains, RomaniaENVIRONMENTAL MICROBIOLOGY, Issue 4 2006Karine Alain Summary Paclele Mici is a terrestrial mud volcano field located in the Carpathian Mountains (Romania), where thermal alteration of sedimentary organic compounds leads to methane, higher hydrocarbons and other petroleum compounds that are continuously released into the environment. The hydrocarbons represent potential substrates for microorganisms. We studied lipid biomarkers, stable isotope ratios, the effect of substrate (methane, other organic compounds) addition and 16S rRNA genes to gain insights into the hitherto unknown microbial community at this site. Quantitative real-time polymerase chain reaction analysis demonstrated that bacteria were much more abundant than archaea. Phylogenetic analyses of 16S rDNA clone sequences indicated the presence of bacterial and archaeal lineages generally associated with the methane cycle (methanogens, aerobic and anaerobic methanotrophs), the sulfur cycle (sulfate reducers), and groups linked to the anaerobic degradation of alkanes or aromatic hydrocarbons. The presence of sulfate reducers, methanogens and methanotrophs in this habitat was also confirmed by concurrent surveys of lipid biomarkers and their isotopic signatures. Incubation experiments with several common and complex substrates revealed the potential of the indigenous microbial community for sulfate reduction, methanogenesis and aerobic methanotrophy. Additionally, consistently to the detection of methane-oxidizing archaea (ANME) and 13C-depleted archaeal lipids, a weak but significant activity of anaerobic methane oxidation was measured by radiotracer techniques and in vitro. This survey is the first to report the presence and activity of ANME in a terrestrial environment. [source] 31P CP/MAS NMR of polycrystalline and immobilized phosphines and catalysts with fast sample spinningMAGNETIC RESONANCE IN CHEMISTRY, Issue 6 2003S. Reinhard Abstract Cross-polarization (CP) at fast magic angle spinning (MAS) frequencies leads to a splitting of the Hartmann,Hahn (HH) matching profile into a centerband and additional bands of higher orders. The matching profiles differ with the substance categories. Therefore, signal intensity is usually lost, when e.g. the routine standard NH4H2PO4 is used for optimizing the 1H,31P HH match prior to measuring phosphines and their metal complexes in polycrystalline or immobilized form. Here, a variety of model compounds, such as Ph2PCH2CH2PPh2 and (CO)2Ni(PPh3)2, which can be used as 31P CP standards for analogous substances or materials are presented. Investigating the influences of MAS frequency, contact time, 1H pulse power and sample volume on the matching profiles of the model compounds leads to general trends. Thereby, a new strategy for measuring difficult samples with CP at high MAS rates has been developed: their optimum CP parameters are derived from the most intense maxima in the HH matching profiles of the corresponding model compounds. This new strategy is compared with variations of a conventional ramp sequence. Although the latter generally provide smaller signal half-widths, the new strategy leads to higher signal intensities. The new method was successfully applied to polycrystalline and immobilized phosphines and catalysts. Copyright © 2003 John Wiley & Sons, Ltd. [source] Ab initio Study of Mechanism of Forming a Germanic Hetero-Polycyclic Compound between Germylidene (H2C=Ge:) and AcetoneCHINESE JOURNAL OF CHEMISTRY, Issue 8 2010Xiuhui Lu Abstract The mechanism of the cycloaddition reaction of forming a germanic hetero-polycyclic compound between singlet germylidene (R1) and acetone (R2) has been investigated with CCSD(T)//MP2/6-31G* method. From the surface energy profile, it can be predicted that the dominant reaction pathway for this reaction consists of three steps: (1) the two reactants (R1, R2) firstly form a twisted four-membered ring intermediate (INT2); (2) the intermediate (INT2) reacts further with acetone (R2) to give another intermediate (INT4); (3) intermediate (INT4) isomerizes to a hetero-polycyclic germanic compound (P4) via a transition state TS4. The presented rule of this reaction: the [2+2] cycloaddition effect between the , orbital of germylidene and the , orbital of ,-bonded compounds leads to the formation of four-membered ring intermediate (INT2). The 4p unoccupied orbital and the lone-pair sp electrons of Ge in the four-membered ring intermediate (INT2) react with the , orbital and the antibonding ,* orbital of ,-bonded compounds, respectively, forming the ,,p and sp, ,* cyclic donor-acceptor bonds, resulting in the generation of a stable germanic hetero-polycyclic compound (P4). [source] | ||||||||||