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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-6-21
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0893-3952
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
877-85
pubmed:dateRevised
2008-5-14
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
pubmed:year
2005
pubmed:articleTitle
Absence of caspase 3 activation in neoplastic cells of nasopharyngeal carcinoma biopsies predicts rapid fatal outcome.
pubmed:affiliation
Department of Pathology, VU Medical Center, Amsterdam, The Netherlands. jj.oudejans@azvu.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't