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71.
Work in progress: [18F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain 总被引:3,自引:0,他引:3
72.
Mark L. Sundermeyer MD Stuart R. Lessin MD Neal J. Meropol MD 《Current colorectal cancer reports》2006,2(3):125-133
The promise of targeted therapeutics is tumor selectivity. The gold standard for this approach is monoclonal antibodies with
exquisite target specificity. In the case of colorectal cancer, this promise has been partially fulfilled. The epidermal growth
factor and vascular endothelial growth factor pathways were identified as putative therapeutic targets and inhibitory antibodies
were developed with clinical activity. However, although these reagents are not associated with toxicities characteristic
of traditional cytotoxics, they are not devoid of side effects. In fact, these side effects can generally be explained on
the basis of expected biologic effects of the reagents, highlighting the notion that targets with true tumor specificity remain
elusive. In this review, we will profile the unique toxicities associated with monoclonal antibody inhibitors of the epidermal
growth factor receptor and vascular endothelial growth factor, and offer suggestions for management. 相似文献
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Richard Pazdur M.D. Neal J. Meropol Ephraim S. Casper C. Fuchs Harold O. Douglass Jr. Mark Vincent James L. Abbruzzese 《Investigational new drugs》1995,13(4):355-358
SummaryBackground Currently available therapies for advanced pancreatic cancer offer only palliative benefits, and patients with this disease have a poor prognosis. We undertook a phase II trial of ZD1694 (TomudexTM), a quinazoline folate analogue that is a potent and selective thymidylate synthase inhibitor, to determine this analogue's efficacy and safety in patients with advanced pancreatic adenocarcinoma.Patients and methods ZD1694, 3.0 mg/m2, was administered to 42 adult patients with pancreatic adenocarcinoma as a 15-minute intravenous infusion every 3 weeks for up to 6 doses. Objective tumor response was assessed every 6 weeks; clinical examinations, adverse event assessments, and clinical laboratory tests were performed every 3 weeks.Results ZD1694 produced an overall response rate of 5% (95% confidence limits [CI], 1% to 16%) in the study group. Of 42 patients, 2 (5%) had a partial response, 12 (29%) had stable disease, 21 (50%) had disease progression, and 5 (11%) could not be evaluated for response. Grade 3 vomiting, grades 3 and 4 fever, grade 3 leukopenia, grade 4 thrombocytopenia, and grades 3 and 4 liver function elevations were reported. Toxic effects with ZD1694 were reversible and manageable.Conclusions ZD1694 has an acceptable safety profile but limited activity in patients with advanced pancreatic cancer.Tomudex is a tradename, the property of Zeneca Limited. Supported by a grant from Zeneca Limited. 相似文献
75.
Quantitative coronary arteriography: design and validation 总被引:1,自引:0,他引:1
The authors assessed the performance of an automatic and rapid coronary quantification method by evaluating its accuracy in a stenosis phantom. Measurements were obtained with a lucite phantom with 2-, 3-, and 4-mm vessel diameters and concentric stenoses of 33%, 50%, 67%, and 75%. Direct digital angiographic images as well as 10 X 10 spot films and 35-mm cine angiography films were acquired with and without structural noise and mask subtraction. The films were digitized with magnification factors of one and two. An interactive analysis program was used to automatically determine the vessel edges with a Gaussian fit to the cross-sectional density profiles perpendicular to the center line of the vessel. Relative changes of the densitometric cross-sectional area along the vessel were used to assess the percentage of stenosis. Densitometric measurements were comparable in both digital and cine angiograms (r = .99 and r = .98, respectively); however, diameter measurements showed a higher variability and were dependent on the amount of magnification applied to the images. 相似文献
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78.
Clairton F de Souza MD PhD Monica L Acosta BSc MSc PhD Philip J Polkinghorne MD FRANZCO Charles NJ McGhee MB BSc PhD FRANZCO Michael Kalloniatis MSc PhD 《Clinical & experimental optometry》2013,96(5):504-507
We localised amino acids in the mid‐peripheral aged human retina and a retina that had undergone radiation treatment 10 years earlier. The distribution pattern of glutamate, γ‐amino butyric acid (GABA), glycine, glutamine and taurine, reflected patterns established in the primate retina. The retina that had undergone radiation exposure displayed both anatomical and neurochemical remodelling. The proximal retina comprised around 40 to 45 per cent of the total retina and neuronal kinesis and aberrant neuronal projections were also present. Amino acid neurochemistry was strikingly different with Müller cells displaying GABA loading, glycinergic neurons displaced and displaying a very high level of glycine labelling. We conclude that radiation exposure triggered these changes in the human retina and likely reflects general remodelling of structure and function following ischaemic damage to endothelial cells. 相似文献
79.
KM Mair E Robinson KA Kane S Pyne RR Brett NJ Pyne S Kennedy 《British journal of pharmacology》2010,161(1):176-192
Background and purpose:
This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats.Experimental approach:
Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg−1 of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg−1 oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI.Results:
A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT0/(1 +MED). LT0 is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL−1.Conclusions:
The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics. 相似文献80.