Abstract:
:The hypothesis tested was that mutant tumor DNA shed into plasma would show predictive value for monitoring response to therapy in non-small cell lung carcinoma patients. Pretreatment plasma specimens from 25 patients on a phase I trial were evaluated, 12 with paired posttreatment specimens, and 138 patients on the Southwest Oncology Group S0003 trial, 38 with paired posttreatment specimens, for the presence of K-RAS mutations. Thirteen tumor specimens from the phase I trial patients and seven tumor specimens from S0003 patients were also available for comparative analysis of K-RAS mutations in tumor tissue and plasma. All patients were treated similarly with paclitaxel, and carboplatin chemotherapy. DNA was extracted and mutational analyses performed using an RFLP-PCR assay. K-RAS mutations were found in plasma DNA in 5/25 of the phase I patients (20%). Median survival was 10 months in all patients, 11.4 months in the wild-type K-RAS group, and 3.3 months in the mutant K-RAS group (P = 0.056). Point mutations in plasma DNA were identical to mutations found in the tumors, confirming the tumor as the source. In two patients with K-RAS mutations pretreatment, posttreatment plasmas were evaluated: a patient with clinical progressive disease retained the mutant DNA, while in a patient with a complete response (CR), the K-RAS mutation was no longer detectable. In an ongoing analysis of S0003 patients, to date, K-RAS mutations have been found in the plasma of 14 patients (10.1%). In 42 matched pre- and posttreatment specimens from both phase I and S0003 trials, four patients had K-RAS mutations pretreatment that were not detectable posttreatment. Of these, two had a clinical CR or partial response, and the other two had stable disease. It was concluded that detection of tumor DNA in plasma is feasible using molecular techniques and that this approach shows promise for monitoring patient response to therapy.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Kimura T,Holland WS,Kawaguchi T,Williamson SK,Chansky K,Crowley JJ,Doroshow JH,Lenz HJ,Gandara DR,Gumerlock PHdoi
10.1196/annals.1318.010subject
Has Abstractpub_date
2004-06-01 00:00:00pages
55-60eissn
0077-8923issn
1749-6632pii
1022/1/55journal_volume
1022pub_type
杂志文章abstract::Fifty-eight contributors from 12 European and 2 American sarcoidosis centers have collaborated in a survey to define many questions concerning the use of 67Ga lung scan in sarcoidosis. The new quantitative scoring methods based on digital evaluation seem better in detecting lung activity. In 20.1% of untreated patient...
journal_title:Annals of the New York Academy of Sciences
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abstract::Despite new technological advances in the rehabilitation of audition in profoundly deaf children, auditory training remains a fundamental part of their education. Consequently, it is necessary to learn what kind of stimuli, what kind of auditory tasks, and what kind of learning procedures generate faster and more long...
journal_title:Annals of the New York Academy of Sciences
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abstract::We have earlier shown that monkeys reared with daily alternating monocular occlusion for the first few months of life develop large horizontal strabismus, A/V patterns, dissociated vertical deviation (DVD), and dissociated horizontal deviation (DHD). Here, we present results from neurophysiological experiments that sh...
journal_title:Annals of the New York Academy of Sciences
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abstract::Although stress is tightly connected with elevated levels of catecholamines, stress effects on target structures of catecholamine action--adrenoceptors (ARs)--has not been deeply studied yet. Similarly, very little is known about changes of muscarinic receptors (MRs) during stress. We determined changes in these recep...
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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更新日期:2009-04-01 00:00:00
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journal_title:Annals of the New York Academy of Sciences
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更新日期:1995-01-17 00:00:00
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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abstract::The investigations with the NZB X SWR model show that the development of systemic autoimmune disease is a multistep, multigene process. Severe lupus nephritis in the NZB X SWR hybrids results from the interaction of genes inherited from both the autoimmune NZB and the normal SWR parents. A similar genetic interaction ...
journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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abstract::Regardless of how creative, innovative, and elegant our computational methods, the ultimate proof of an algorithm's worth is the experimentally validated quality of its predictions. Unfortunately, this truism is hard to reduce to practice. Usually, modelers produce hundreds to hundreds of thousands of predictions, mos...
journal_title:Annals of the New York Academy of Sciences
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abstract::Immune stimulation increases the activity of the HPA axis, a phenomenon directly or indirectly mediated through cytokines. We have used two models, the peripheral administration of endotoxin (LPS) or turpentine-induced tissue injury to show that corticotropin-releasing factor (CRF) and vasopressin (VP), hypothalamic p...
journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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abstract::Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotox...
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abstract::In this chapter, we examine the possibility that negative emotions contribute to the relationship between socioeconomic status (SES) and health. A model of the associations among SES, emotion, and health is presented first. We then review the evidence for this model, showing associations of SES with depression, hopele...
journal_title:Annals of the New York Academy of Sciences
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abstract::Fifteen patients with coccidioidal meningitis were treated with high doses of ketoconazole for up to 4 years. Five patients were treated with ketoconazole alone. One clinically failed, one developed hepatotoxicity, and three achieved remission of meningitis. One patient received intrathecal AMB in addition to ketocona...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
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更新日期:1988-01-01 00:00:00
abstract::Over the last years, El Sistema--the Venezuelan project started in 1975 and now acknowledged worldwide as the most significant example of collective music education--has inspired a profusion of remarkable initiatives on all continents. From the original impulse by founder José Antonio Abreu, strong social principles o...
journal_title:Annals of the New York Academy of Sciences
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abstract::It has been hypothesized that a central even in the early pathogenesis of sporadic Alzheimer disease (SAD) is the dysfunction of the neuronal insulin receptor signal transduction. To prove this, this receptor was inhibited by a triplicate icv application of STZ. Insulin binding sites were upregulated as in SAD. With r...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
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更新日期:2000-01-01 00:00:00