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991.
992.
Taliani S Pugliesi I Barresi E Simorini F Salerno S La Motta C Marini AM Cosimelli B Cosconati S Di Maro S Marinelli L Daniele S Trincavelli ML Greco G Novellino E Martini C Da Settimo F 《Journal of medicinal chemistry》2012,55(4):1490-1499
In an effort to identify novel ligands possessing high affinity and selectivity for the A(2B) AR subtype, we further investigated the class of 3-aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones V, previously disclosed by us as selective A(1) AR antagonists. Preliminary assays on a number of triazinobenzimidazoles derived from our "in-house" collection revealed that all the derivatives selected showed significant affinity at A(2B) AR, no affinity at A(3) AR, and various degrees of selectivity toward A(1) and A(2A) ARs. Investigation of a new series featuring modified substituents at the 10-position (4'-chlorophenyl or phenylethyl groups), and a chlorine atom at the 7-position (X) of the triazinobenzimidazole nucleus, yielded highly potent and selective A(2B) AR antagonists. The presence of a pendant 3-phenyl ring appears to hamper the interaction with A(2A) AR, conferring high A(2B)/A(2A) AR selectivity. Derivative 13 (X = Cl, R = C(6)H(5)) is the most potent and selective compound, with an IC(50) of 3.10 nM at A(2B) AR and no affinity at A(1), A(2A), and A(3) ARs. 相似文献
993.
N Margiotta C Marzano V Gandin D Osella M Ravera E Gabano JA Platts E Petruzzella JD Hoeschele G Natile 《Journal of medicinal chemistry》2012,55(16):7182-7192
Although the encouraging antitumor activity of [PtCl(2)(cis-1,4-DACH)] (1; DACH = diaminocyclohexane) was shown in early studies almost 20 years ago, the compound has remained nearly neglected. In contrast, oxaliplatin, containing the isomeric 1(R),2(R)-DACH carrier ligand, enjoys worldwide clinic application as a most important therapeutic agent in the treatment of colorectal cancer. By extending the investigation to human chemotherapy-resistant cancer cells, we have demonstrated the real effectiveness of 1 in circumventing cisplatin and oxaliplatin resistance in LoVo colon cancer cells. The uptake of compound 1 by the latter cells was similar to that of sensitive LoVo cells. This is not the case for all other compounds considered in this investigation. Interaction with double-stranded DNA, investigated by a biosensor assay and by quantum mechanical/molecular mechanical geometry optimization of the 1,2-GG intrastrand cross-link, does not show significant differences between 1 and oxaliplatin. However, the DNA adducts of 1 are removed from repair systems with lower efficiency and are more effective in inhibiting DNA and RNA polymerase. 相似文献
994.
995.
Rita Cortesi Laura Ravani Enea Menegatti Elisabetta Esposito F. Ronconi 《Indian journal of pharmaceutical sciences》2012,74(5):415-421
This study compares the behaviour of budesonide-containing microparticles made of Eudragit®RS or Eudragit®RS/Eudragit®RL 70:30 (w/w) prepared either by solvent evaporation or spray-drying technique. The loading efficiency of budesonide within microparticles was about 72% for microparticles prepared by solvent evaporation and around 78% for spray-dried microparticles. Thermal analyses were assessed to collect information about the structural stability of budesonide within the polymeric microspheres. The in vitro release was performed using simulating gastric (fasted state simulated gastric fluid) and intestinal (fasted state simulated intestinal fluid) fluids as the receiving solutions. After 3 h the drug release from Eudragit®RS/Eudragit®RL microparticles was about 6-fold higher than that obtained in the case of monopolymer microparticles. Using fasted state simulated intestinal fluid the drug was released between 4 and 30% in both types of preparations. Eudragit®RS microparticles showed a better protection of the drug from gastric acidity than those of Eudragit®RS/Eudragit®RL allowing us to propose Eudragit®RS microparticles as a hypothetical system of colon specific controlled delivery. 相似文献
996.
Canetta E Mazilu M De Luca AC Carruthers AE Dholakia K Neilson S Sargeant H Briscoe T Herrington CS Riches AC 《Journal of biomedical optics》2011,16(3):037002
Standard Raman spectroscopy (SRS) is a noninvasive technique that is used in the biomedical field to discriminate between normal and cancer cells. However, the presence of a strong fluorescence background detracts from the use of SRS in real-time clinical applications. Recently, we have reported a novel modulated Raman spectroscopy (MRS) technique to extract the Raman spectra from the background. In this paper, we present the first application of MRS to the identification of human urothelial cells (SV-HUC-1) and bladder cancer cells (MGH) in urine samples. These results are compared to those obtained by SRS. Classification using the principal component analysis clearly shows that MRS allows discrimination between Raman spectra of SV-HUC-1 and MGH cells with high sensitivity (98%) and specificity (95%). MRS is also used to distinguish between SV-HUC-1 and MGH cells after exposure to urine for up to 6 h. We observe a marked change in the MRS of SV-HUC-1 and MGH cells with time in urine, indicating that the conditions of sample collection will be important for the application of this methodology to clinical urine samples. 相似文献
997.
Curigliano G Locatelli M Fumagalli L Brollo J Munzone E Nolé F Criscitiello C Goldhirsch A 《Expert opinion on investigational drugs》2012,21(2):191-204
INTRODUCTION: The choice of adjuvant treatments for women with breast cancer is based on several features that take into account the heterogeneity of the disease. Questions raised during the decision process include the following: i) What leads to the use of endocrine therapy? ii) What leads to the use of anti-HER2 therapy? iii) What justifies the use of chemotherapy? AREAS COVERED: Choices of adjuvant treatment are based on parameters defined by molecular characterization of breast cancer subtypes or by approximations to this classification using traditional clinical-pathological features. Clinicians should consider cases within the various distinct subpopulation in order to properly select the most 'personalized' adjuvant therapeutic approach. Sensitivity to chemotherapy and/or targeted agents in subtypes of breast cancers are predictable based on gene pathway alterations and associated gene products. This review covers several clinical data on several investigational agents for early-stage breast cancer molecular subtypes. We selected from literature data prospective Phase I, II and III clinical trials of chemotherapy (weekly or daily schedules), including indicators of activity and toxicity and data on survival/mortality. EXPERT OPINION: The future of many investigational therapeutics in breast cancer is linked to our ability to identify the most druggable target in each subtype. 相似文献
998.
Antonucci R Zaffanello M Puxeddu E Porcella A Cuzzolin L Pilloni MD Fanos V 《Current drug metabolism》2012,13(4):474-490
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in pregnancy to treat fever, pain and inflammation. Indications for chronic use of these agents during pregnancy are inflammatory bowel or chronic rheumatic diseases. Since the seventies, NSAIDs have been used as effective tocolytic agents: indomethacin has been the reference drug, delaying delivery for at least 48 hours and up to 7-10 days. Additionally, self-medication with NSAIDs is practiced by pregnant women. NSAIDs given to pregnant women cross the placenta and may cause embryo-fetal and neonatal adverse effects, depending on the type of agent, the dose and duration of therapy, the period of gestation, and the time elapsed between maternal NSAID administration and delivery. These effects derive from the action mechanisms of NSAIDs (mainly inhibition of prostanoid activity) and from the physiological changes in drug pharmacokinetics occurring during pregnancy. Increased risks of miscarriage and malformations are associated with NSAID use in early pregnancy. Conversely, exposure to NSAIDs after 30 weeks' gestation is associated with an increased risk of premature closure of the fetal ductus arteriosus and oligohydramnios. Fetal and neonatal adverse effects affecting the brain, kidney, lung, skeleton, gastrointestinal tract and cardiovascular system have also been reported after prenatal exposure to NSAIDs. NSAIDs should be given in pregnancy only if the maternal benefits outweigh the potential fetal risks, at the lowest effective dose and for the shortest duration possible. This article discusses in detail the placental transfer and metabolism of NSAIDs, and the adverse impact of prenatal NSAID exposure on the offspring. 相似文献
999.
1000.
Ruggeri G Bandiera E Zanotti L Belloli S Ravaggi A Romani C Bignotti E Tassi RA Tognon G Galli C Caimi L Pecorelli S 《Clinica chimica acta; international journal of clinical chemistry》2011,412(15-16):1447-1453
BackgroundTwo commercial immunoassays for HE4 have been compared and the diagnostic accuracy of HE4, CA 125 and the combinatory ROMA algorithm for epithelial ovarian cancer (EOC) has been evaluated.MethodsHE4 and CA125 were measured on sera obtained from 259 women (73 healthy, 90 with benign ovarian or adnexal diseases, 96 with EOC). The ARCHITECT CMIA HE4 assay was compared with the Fujirebio EIA HE4, and the risk for EOC by the combinatory ROMA algorithm (HE4 + CA 125) was assessed with both HE4 assays.ResultsThe CMIA HE4 assay showed a good linearity (r > 0.9998) and precision (interassay and total CVs < 4%). The correlation with EIA HE4 was linear (r = 0.994), with an average bias of 0.4%. By ROC curve analysis, the sensitivity for EOC at a fixed specificity of 90%, 95% and 99% was 89.6%, 84.4% and 79.2% by CMIA HE4, 84.4%, 83.3% and 79.2% by EIA HE4, 86.5%, 76.0% and 59.4% by CMIA CA125. The accuracy of the ROMA algorithm determined by CMIA or EIA HE4 was very similar (AUC 87.1% vs. 87.6%; p = n.s.) and greater in menopause.ConclusionsThe two HE4 assays showed a good correlation and similar clinical value, with a greater precision for CMIA. HE4 was more specific and accurate than CA125, supporting its use in addition to clinical and imaging criteria for the discrimination of benign from malignant ovarian lesions. The ROMA algorithm showed a good accuracy for discriminating women at high risk for EOC. 相似文献