rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-6-21
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pubmed:abstractText |
Poor prognosis in nasopharyngeal carcinoma patients may result from resistance to the apoptosis-inducing effect of radio- and/or chemotherapy. Apoptosis depends on proper activation of caspase 3, resulting in cleavage of key proteins like PARP-1. To investigate whether disruption of the apoptosis pathway results in therapy-resistant tumour cells, we investigated whether absence of caspase 3 activation in tumour biopsies of nasopharyngeal carcinoma patients is related to poor clinical outcome. Moreover, we investigated whether absence of caspase 3 activation is related to loss of procaspase 3 expression or expression of the apoptosis regulators p53, bcl-2 and XIAP. We studied 36 Indonesian nasopharyngeal carcinoma patients without evidence of distant metastases who were treated with curative intent by radiotherapy only. Activation of caspase 3 and expression of the different markers were determined using specific antibodies. Levels of caspase 3 activation were determined by quantifying positively staining tumour cells. Nasopharyngeal carcinoma-derived C15 and C17 tumour cells were used as control. Absence of caspase 3 activation was strongly related to a poor clinical response to radiotherapy and to a higher T and N stage, resulting in a particularly poor clinical outcome with regard to progression-free (P<0.0001) and overall survival time (P<0.0001). Absence of caspase 3 activation was significantly correlated to loss of expression of procaspase 3 (P=0.04). In nasopharyngeal carcinoma patients treated with curative intent, absence of active caspase 3-positive neoplastic cells predicts rapid fatal outcome, and is associated with poor response to radiotherapy and high T and N stage at time of presentation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0893-3952
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
877-85
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pubmed:dateRevised |
2008-5-14
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pubmed:meshHeading |
pubmed-meshheading:15803189-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:15803189-Apoptosis,
pubmed-meshheading:15803189-Biopsy,
pubmed-meshheading:15803189-Caspase 3,
pubmed-meshheading:15803189-Caspases,
pubmed-meshheading:15803189-Cell Line, Tumor,
pubmed-meshheading:15803189-Enzyme Activation,
pubmed-meshheading:15803189-Etoposide,
pubmed-meshheading:15803189-Female,
pubmed-meshheading:15803189-Humans,
pubmed-meshheading:15803189-Immunohistochemistry,
pubmed-meshheading:15803189-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:15803189-Male,
pubmed-meshheading:15803189-Middle Aged,
pubmed-meshheading:15803189-Multivariate Analysis,
pubmed-meshheading:15803189-Nasopharyngeal Neoplasms,
pubmed-meshheading:15803189-Nasopharynx,
pubmed-meshheading:15803189-Proteins,
pubmed-meshheading:15803189-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15803189-Survival Analysis,
pubmed-meshheading:15803189-Survival Rate,
pubmed-meshheading:15803189-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:15803189-X-Linked Inhibitor of Apoptosis Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Absence of caspase 3 activation in neoplastic cells of nasopharyngeal carcinoma biopsies predicts rapid fatal outcome.
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pubmed:affiliation |
Department of Pathology, VU Medical Center, Amsterdam, The Netherlands. jj.oudejans@azvu.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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