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2.  Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity 
British Journal of Cancer  2009;100(9):1393-1399.
Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis, and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and eIF4E-binding proteins (4E-BPs). Our hypothesis was that the combined analyses of these pathway components would allow insights into eIF4E activity and its influence on cancer. We have determined expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 within 424 breast tumours, and have carried out analyses to combine these and relate the product to patient survival, in order to estimate eIF4E activity. We show that this analysis gives greater prognostic insights than that of eIF4E alone. We show that eIF4E and 4E-BP expression are positively associated, and that 4E-BP2 has a stronger influence on cancer behaviour than 4E-BP1. Finally, we examine eIF4E, estimated eIF4E activity, and phosphorylated 4E-BP1 as potential predictive biomarkers for eIF4E-targeted therapies, and show that each determines selection of different patient groups. We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E.
doi:10.1038/sj.bjc.6605044
PMCID: PMC2694424  PMID: 19367274
translation factors; predictive biomarkers; Cox regression; pathway biomarker
4.  The Electrospray Ionization - Mass Spectra of Erythromycin A Obtained from a Marine Streptomyces sp. Mutant 
In our ongoing search for production improvements of bioactive secondary metabolites from marine Streptomyces through the induction of mutations using UV light, out of 145 isolates, mutant 10/14 was able to produce potent antibacterial metabolites other than the parent strain as established by chromatographic analysis. Up-scaling fermentation of mutant 10/14, followed by working up and isolation delivered five metabolites, phenazine, 1-acetyl-β -carboline, perlolyrin and erythromycin A, along with an oily substance. The latter two compounds were responsible for the antibacterial activity of the strain. In this article, we discuss with the mutation of the marine Streptomyces sp. AH2, bioactivity evaluation, fermentation and isolation of the microbial metabolites. Moreover, we study to first time in detail the 1D and 2D NMR and ESI MS data including ESI MS2 and MS3 patterns combined with HRESI MS of erythromycin A.
doi:10.4103/0250-474X.42979
PMCID: PMC2792501  PMID: 20046738
Marine Streptomyces mutation; bioactivity evaluation; ESI-MS/MS; erythromycin A
5.  Post traumatic laryngeal incompetence 
Self-inflicted laryngeal injuries are rare. This is a case of attempted suicide with a knife. The patient was brought into A&E and initial attempts at repair of the laryngo-skeletal structures were performed Later it became evident that the patient had an insensate hypofunctioning larynx. We present a technique aimed at rehabilitating the poorly functioning, incompetent larynx without the necessity for a permanent tracheostomy or laryngectomy. A single surgical procedure combining a cricopharyngeal myotomy, an anterior hyoid suspension and vocal fold angmentations was performed in an attempt to avoid a laryngectomy in non-malignant pathology. The long-term results of this surgery would need to be subjected to further evaluation.
doi:10.1007/BF03008029
PMCID: PMC3451333  PMID: 23120187
Laryngeal injury; Aspiration; Amerior hyoid suspension; Cricopharyngeal myotomy
6.  Wild-type oestrogen receptor beta (ERβ1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers 
British Journal of Cancer  2004;91(9):1694-1702.
doi:10.1038/sj.bjc.6602183
PMCID: PMC2409946  PMID: 15477865
breast cancer; ER gene expression; tamoxifen; oestrogen receptor beta; tumour progression
7.  Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27 
British Journal of Cancer  2004;90(1):182-188.
doi:10.1038/sj.bjc.6601449
PMCID: PMC2395338  PMID: 14710227
breast cancer; neoplastic progression; heat shock protein 27
8.  HLA-DR and tuberculin tests in rheumatoid arthritis and tuberculosis. 
Responses to four new tuberculins were found to be significantly reduced in 46 patients with rheumatoid arthritis in comparison with a control group of 79. Except for tuberculin itself, the same was found in 111 patients with tuberculosis. In common with patients with tuberculosis and leprosy, those with rheumatoid arthritis did not respond to common mycobacterial (group i) antigen. Three DR haplotypes were found to have significant effects on skin test responsiveness of the rheumatoid patients but had little or no effect on that of the patients with tuberculosis and none on that of the healthy control group. Rheumatoid patients with the HLA-DR4 haplotype had significantly greater responses to all four reagents than did non-DR4 patients, but their responses to leprosin A and scrofulin remained significantly lower than those of the control group. Possession of HLA-DR3 haplotype was associated with skin test positivity approaching normal, but the sizes of responses were reduced. Possession of DR7 was associated with an unexpected reduction in skin test positivity, especially in the case of tuberculin. These results support the hypothesis that mycobacteria, or autoantigens cross reactive with mycobacteria, may be involved in the aetiology of rheumatoid arthritis. The results also show that the regulation and specificity of responsiveness to mycobacterial antigens are different in patients with rheumatoid arthritis with different HLA-DR haplotypes.
PMCID: PMC1003677  PMID: 2784308

Results 1-8 (8)