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71.
Francis DL Visvikis D Costa DC Arulampalam TH Townsend C Luthra SK Taylor I Ell PJ 《European journal of nuclear medicine and molecular imaging》2003,30(7):988-994
Ohne Zusammenfassung 相似文献
72.
3'-deoxy-3'-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography 总被引:10,自引:0,他引:10
Barthel H Cleij MC Collingridge DR Hutchinson OC Osman S He Q Luthra SK Brady F Price PM Aboagye EO 《Cancer research》2003,63(13):3791-3798
3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) has been proposed as a new marker for imaging tumor proliferation by positron emission tomography (PET). The uptake of [(18)F]FLT is regulated by cytosolic S-phase-specific thymidine kinase 1 (TK1). In this article, we have investigated the use of [(18)F]FLT to monitor the response of tumors to antiproliferative treatment in vivo. C3H/Hej mice bearing the radiation-induced fibrosarcoma 1 tumor were treated with 5-fluorouracil (5-FU; 165 mg/kg i.p.). Changes in tumor volume and biodistribution of [(18)F]FLT and 2-[(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) were measured in three groups of mice (n = 8-12/group): (a) untreated controls; (b) 24 h after 5-FU; and (c) 48 h after 5-FU. In addition, dynamic [(18)F]FLT-PET imaging was performed on a small animal scanner for 60 min. The metabolism of [(18)F]FLT in tumor, plasma, liver, and urine was determined chromatographically. Proliferation was determined by staining histological sections for proliferating cell nuclear antigen (PCNA). Tumor levels of TK1 protein and cofactor (ATP) were determined by Western blotting and bioluminescence, respectively. Tumor [(18)F]FLT uptake decreased after 5-FU treatment (47.8 +/- 7.0 and 27.1 +/- 3.7% for groups b and c, respectively, compared with group a; P < 0.001). The drug-induced reduction in tumor [(18)F]FLT uptake was significantly more pronounced than that of [(18)F]FDG. The PET image data confirmed lower tumor [(18)F]FLT retention in group c compared with group a, despite a trend toward higher radiotracer delivery for group c. Other than phosphorylation in tumors, [(18)F]FLT was found to be metabolically stable in vivo. The decrease in tumor [(18)F]FLT uptake correlated with the PCNA-labeling index (r = 0.71, P = 0.031) and tumor volume changes after 5-FU treatment (r = 0.58, P = 0.001). In this model system, the decrease in [(18)F]FLT uptake could be explained by changes in catalytic activity but not translation of TK1 protein. Compared with group a, TK1 levels were lower in group b (78.2 +/- 5.2%) but higher in group c (141.3 +/- 9.1%, P < 0.001). In contrast, a stepwise decrease in ATP levels was observed from group a to b to c (P < 0.001). In conclusion, we have demonstrated the ability to measure tumor response to antiproliferative treatment with [(18)F]FLT and PET. In our model system, the radiotracer uptake was correlated with PCNA-labeling index. The decrease in [(18)F]FLT uptake after 5-FU was more pronounced than that of [(18)F]FDG. [(18)F]FLT is, therefore, a promising marker for monitoring antiproliferative drug activity in oncology that warrants additional testing. 相似文献
73.
Osman S Rowlinson-Busza G Luthra SK Aboagye EO Brown GD Brady F Myers R Gamage SA Denny WA Baguley BC Price PM 《Cancer research》2001,61(7):2935-2944
The tricyclic carboxamide N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is a DNA-intercalating agent capable of inhibiting both topoisomerases I and II and is currently in Phase II clinical trial. Many related analogues have been developed, but despite their potent in vitro cytotoxicities, they exhibit poor extravascular distribution. As part of an ongoing drug development program to obtain related "minimal intercalators" with lower DNA association constants, we have compared the biodistribution and metabolite profiles of the prototype compound, DACA, with three analogues to aid rational drug selection. All of these compounds share a common structural feature, N-dimethyl side chain, which was radiolabeled with the positron-emitting radioisotope, carbon-11. This strategy was selected because it allows promising candidates emerging from preclinical studies in animals to be evaluated rapidly in humans using positron emission tomography (PET). The acridine DACA, the phenazine SN 23490, the pyridoquinoline SN 23719, and the dibenzodioxin SN 23935 were found to be cytotoxic in in vitro assays with an IC50 of 1.4-1.8 microM, 0.4-0.6 microM, 1.3-1.6 microM, and 24-36 microM, respectively, in HT29, U87MG, and A375M cell lines. Ex vivo biodistribution studies with carbon-11 radiolabeled compounds in mice bearing human tumor xenografts showed rapid clearance of 11C-radioactivity (parent drug and metabolites) from blood and the major organs. Rapid hepatobiliary clearance and renal excretion were also observed. There was low [<5% of injected dose/gram (%ID/g)] and variable uptake of 11C-radioactivity in three tumor types for all of the compounds. Tumor (U87MG) to blood 11C-radioactivity for [11C]DACA, [11C](9-methoxyphenazine-1-carboxamide (SN 23490), [11C]2-(4-pyridyl)quinoline-8-carboxamide (SN 23719), and [11C]dibenzo[1,4]dioxin-1-carboxamide (SN 23935) at 30 min were 2.9 +/- 1.1, 2.3 +/- 0.6, 2.6 +/- 0.6, and 0.7 +/- 0.2, respectively. For SN 23719, the distribution of 11C-radioactivity in normal tissues and tumors determined ex vivo was in broad agreement with that determined in vivo by whole body PET scanning. [11C]DACA was rapidly and extensively metabolized to several plasma metabolites and a major tumor metabolite. In contrast, [11C]SN 23935, [11C]SN 23490, and [11C]SN 23719 showed less extensive metabolism. In the tumor samples, the parent [11C]DACA and [11C]SN 23935 represented between 0.3 and 1.5%ID/g, whereas [11C]SN 23490 and [11C]SN 23719 represented between 1.5 and 2.8%ID/g. In conclusion, by using a strategy with 11C-labeling, we have determined the tissue distribution and metabolic stability of novel tricyclic carboxamides with the view of selecting analogues with potentially better in vivo activity against solid tumors. SN 23490 and SN 23719 had more favorable distribution and metabolic stability compared with DACA and SN 23935 and may warrant further development. The radiolabeling strategy used allows ex vivo and in vivo evaluation of promising anticancer agents in animals and offers the potential of rapid translation to studies in humans using PET. 相似文献
74.
75.
蛇胆汁中牛磺胆酸含量测定方法的比较研究 总被引:2,自引:0,他引:2
目的:比较分析了3种测定蛇胆汁中主要成分牛磺胆酸含量的方法,制定科学合理统一的质量标准。方法:用薄层层析-磷钼酸比色法、薄层扫描法及高效液相色谱法对蛇胆汁中主要成分牛磺胆酸进行测定,并将结果进行比较分析。结果:薄层层析-磷钼酸比色法、薄层扫描法及高效液相色谱法的含量测定结果有一定差异,平均回收率分别为97.48%,98.51%和100.34%,RSD分别为4.6%,4.3%和1.5%。结论:高效液 相似文献
76.
R Luthra A H Sarris S Hai A V Paladugu J E Romaguera F F Cabanillas L J Medeiros 《American journal of clinical pathology》1999,112(4):524-530
We describe the usefulness of a real-time polymerase chain reaction (PCR) assay for detection of the t(11;14)(q13;q32), most commonly present in mantle cell lymphoma (MCL). This assay is based on the 5'-->3' exonuclease activity of Taq polymerase, which cleaves an internal probe labeled with a reporter dye at its 5' end and a quencher dye at its 3' end during PCR. The real-time t(11;14) PCR assay was established using DNA from a case of MCL with the t(11;14), amplifiable using conventional PCR and primers specific for the major translocation cluster (MTC) region of the bcl-1 locus and the immunoglobulin heavy chain joining region gene (JH). The specificity was determined by analyzing DNA from 82 cases: 50 MCL, 27 other types of non-Hodgkin lymphoma (NHL), and 5 reactive lymphoid proliferations. The real-time t(11;14) PCR results were correlated with data obtained by a conventional PCR assay. By using the real-time assay, bcl-1 MTC/JH DNA fusion sequences were detected in 25 of 50 MCLs but not in other NHLs or reactive lymphoid proliferations. Concordance between real-time and conventional PCR methods for MCL was 96% and for all samples was 98%. The results demonstrate that this real-time PCR method to detect bcl-1 MTC/JH DNA fusion sequences is specific and reliable. In addition, the results are available immediately following amplification, without standard post-PCR manipulations. 相似文献
77.
78.
Lymphangiomas in children: MR imaging 总被引:9,自引:0,他引:9
Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence. 相似文献
79.
Padam Singh J. Paul Kanotra Dinesh Luthra Gajan Singh Sunil Kotwal 《Indian journal of otolaryngology and head and neck surgery》2000,52(2):189-190
Surcomatoid Carcinoma are rare lesions reported in many organs including the larynx. This report describes such a mixed tumour occuring in the larynx. The clinico pathological features and treatment are described. 相似文献
80.
S. W. Woo PhD S. Bang HS M. W. Chung PhD S. K. Jin PhD Y. S. Kim† MD PhD S. H. Lee‡ MD PhD 《Journal of clinical pharmacy and therapeutics》2009,34(5):561-567
Background & Objective: Angiotensin converting enzyme (ACE) inhibitors are used widely in therapy for hypertension, congestive heart failure and myocardial infarction. However, coughing, one of their major adverse effects limits their use. It is documented that Asians are more liable to coughing than Europeans. The aim of this study was to investigate genetic polymorphism involved in ACE inhibitor-induced coughing.
Methods: We monitored hypertensive subjects ( n = 110) treated with ACE inhibitors, and tested for any associations between ACE inhibitor-induced coughing and polymorphisms in the genes for ACE and the bradykinin B2 receptor, which are suspected to be related to coughing.
Results & Discussion: We found no significant differences between the groups with coughing and without coughing in the frequency of ACE I/D (Insertion/Deletion) polymorphisms. One single nucleotide polymorphism was discovered in the promoter (−58T/C) and, one in intron-exon junction upsteam of exon 2 (−59C/A), of the bradykinin B2 receptor gene. However, no significant correlation was found between those genotypes or allele distributions and ACE inhibitor-induced coughing.
Conclusion: We found no significant links between polymorphisms of the ACE gene or bradykinin B2 receptor gene with ACE inhibitor-induced coughing in hypertensive Koreans. But, the topic remains controversial and requires more study. 相似文献
Methods: We monitored hypertensive subjects ( n = 110) treated with ACE inhibitors, and tested for any associations between ACE inhibitor-induced coughing and polymorphisms in the genes for ACE and the bradykinin B2 receptor, which are suspected to be related to coughing.
Results & Discussion: We found no significant differences between the groups with coughing and without coughing in the frequency of ACE I/D (Insertion/Deletion) polymorphisms. One single nucleotide polymorphism was discovered in the promoter (−58T/C) and, one in intron-exon junction upsteam of exon 2 (−59C/A), of the bradykinin B2 receptor gene. However, no significant correlation was found between those genotypes or allele distributions and ACE inhibitor-induced coughing.
Conclusion: We found no significant links between polymorphisms of the ACE gene or bradykinin B2 receptor gene with ACE inhibitor-induced coughing in hypertensive Koreans. But, the topic remains controversial and requires more study. 相似文献