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  • prognosis  (2)
  • Antisense phosphodiester oligonucleotide  (1)
  • 1
    ISSN: 1619-7089
    Keywords: Transforming growth factor α ; Antisense phosphodiester oligonucleotide ; Radioiodine labelling ; Biodistribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Watson-Crick base pairing rule provides the underlying principle for the antisense (AS) approach to inhibiting gene expression. Transforming growth factor α (TGFα) was the first growth factor to be associated with tumorigenesis, thus making the TGFα (mRNA) a potential target for AS therapy and offering the potential for monitoring of the progression of malignancy by non-invasive imaging with radiolabelled AS phosphodiester. Probe labelling and biodistribution were studied in the present report. A 23-mer oligonucleotide sequence was synthesized and grafted in 5′ with a tyramine group which was further radioiodinated. The radiolabelled AS was injected intratumorally in mammary tumour-bearing BALB/c mice (3 weeks after inoculation of 7·106 NS2T2A mammary cells). Biodistribution was monitored by sequential scintigraphy and organ radioactivity after autopsy. The 5′ tyramine group allowed specific and stable radiolabelling of the AS with125I. The125I AS oligonucleotide was rapidly cleared from the tumour by intestine and kidneys. Four hours after intratumoral injection, 6.5%±1.5% of the dose was retained in the tumour as non-degraded125I AS. It is concluded that 5′ tyraminylated AS provides information on the biodistribution of AS oligonucleotide following intratumoral injection. These data will contribute to the pharmacology of AS oligonucleotides which can be used for therapy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: epidermal growth factor ; EGF receptor ; immunoenzymatic assays ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a retrospective study of 319 primary breast cancers, we show that an immunoenzymatic assay of a solubilized fraction of EGF receptors indicates a prognostic value for EGFR which is in contradiction with some (but not all) other studies. It appears that different methodological approaches of measuring EGFR are not equivalent in terms of prognostic power. We emphasize the need for rigorous multicentric standardization and quality control of assays, followed by multistep validation of parameters oriented towards clinical use.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 14 (1989), S. 77-90 
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; estrogen receptor ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prognostic significance of EGFR (epidermal growth factor receptor) was studied in a cohort of 68 node-positive patients with breast cancer, who entered a controlled protocol of adjuvant therapy between February 1980 and June 1984. EGFR radioligand binding assay was carried out on frozen stored samples. Twenty five (37%) of 68 primary sites and 9 (41%) of 19 lymph node metastases assayed were EGFR-positive with a cut off value of 5 fmol/mg membrane protein; there is no statistical difference between the two distributions. EGFR was significantly correlated to ER and histological grade. EGFR-positive tumors and high levels of EGFR were mainly found in the ER-negative group of tumors (p = 0.008) and in histological grade III (p = 0.007). Fifty five patients could be followed for 40 to 92 months. EGFR was an independent prognostic factor for survival after 40 months (p = 0.05). EGFR+/ER− patients had the lowest survival probability, but statistical significance was not reached (p = 0.06). The EGFR phenotype appeared as a prognostic parameter in node-positive patients, individualizing subgroups of patients with different early outcome, with potential therapeutic implication especially in the group of ER-negative patients. These results emphasize the need for a standardized assay methodology and for further clinical studies, particularly in protocols where adjuvant hormonal therapy is prescribed on the basis of steroid hormone receptor status, in order to assess the respective prognostic worth of EGFR and ER (or PR).
    Type of Medium: Electronic Resource
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