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ABSTRACT: Radiotherapy is the principal modality used to treat early stage laryngeal cancer. Unfortunately treatment failures occur in 10-25% of patients. Subsequent salvage surgery is technically more difficult, with increased complication and failure rates. The ability to predict or prevent radioresistance would improve the poor survival associated with this disease. Cox-2 is an inducible enzyme involved with prostaglandin synthesis. We investigated a potential role for Cox-2 in predicting radioresistance in laryngeal cancer.
Using immunohistochemical techniques we examined the expression of Cox-2 protein in 122 pre-treatment laryngeal biopsies. All tumours were treated with single modality radiotherapy (curative intent). The group comprised of 61 radioresistant and 61 radiosensitive tumours matched for T stage, laryngeal subsite, gender and smoking history.
Cox-2 expression was detected in 41 of 61 (67%) biopsy samples from patients with radioresistant tumours and 25 of 61 (41%) radiosensitive tumours. Overexpression was significantly associated with radioresistant tumours (P = 0.004). Cox-2 has a 67% accuracy in predicting radiotherapy failure.
Cox-2 may have prognostic value in predicting response to radiotherapy. Cox-2 inhibitors such as NS-398 have been shown to enhance the effects of radiotherapy. We suggest that their use may be beneficial in patients who are destined to fail radiotherapy.
Annals of Oncology 06/2004; 15(5):797-801. · 6.43 Impact Factor
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ABSTRACT: Small cell lung cancer (SCLC) is a major cause of cancer related morbidity and mortality. Karyotypic studies have revealed numerous chromosomal aberrations in most SCLC however, classical G-banding analysis is unable to fully characterise complex marker chromosomes. Recent developments in molecular cytogenetics now allow accurate identification of the chromosomal components of complicated rearrangements. We have applied the technique of multicolour fluorescence in situ hybridization (M-FISH) in combination with comparative genomic hybridization (CGH) to the analysis of 5 SCLC cell lines and 1 primary tumour specimen to characterise the chromosomal abnormalities. CGH analysis identified many similarities between specimens, with frequent DNA copy number decreases on chromosomes 3p, 5q, 10, 16q, 17p and frequent gains on 3q, 1p, 1q and 14q. In contrast, M-FISH analysis revealed a large number of structural abnormalities, with each specimen demonstrating an individual pattern of chromosomal translocations. Forty different translocations were identified with the vast majority (39) being unbalanced. Chromosome 5 was the most frequently rearranged chromosome (9 translocations) followed by chromosomes 2, 10 and 16 (6 translocations each). Further investigation of these frequently involved chromosomes is warranted to establish whether consistent break points are involved in these translocations, causing dysregulation of specific genes that are crucial for tumour progression and secondly to identify the affected genes.
International Journal of Cancer 12/2002; 102(3):230-6. · 5.44 Impact Factor
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ABSTRACT: The breast cancer cell line MCF-7 is a widely used model in breast cancer research however a number of conflicting reports have been published regarding its biological properties. We hypothesised that there will be significant in vitro mutation and genotypic evolution over time in this cell line. To assess the genetic divergence of MCF-7 at the chromosomal level, we analysed MCF-7 cell lines grown independently at three different laboratories using M-FISH and CGH. In addition, MCF-7 cells from our own laboratory were also analysed at two time points 18 months apart. Several common chromosomal translocations were identified in all variants of the cell lines. In addition, a significant number of unique abnormalities were identified, characterising each of the variants studied. Genotypic differences between cell lines grown independently in different laboratories would significantly alter the phenotypic characteristics of each cell line rendering biological properties inconsistent between laboratories.
International Journal of Oncology 04/2002; 20(3):489-94. · 2.40 Impact Factor
