Browsing by Subject "Neoplasm Recurrence, Local"

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    Early outcomes after transoral CO2 laser resection of laryngeal and hypopharyngeal squamous cell carcinoma: One centre's experience
    (Cambridge University Press, 2010) Leong, S. C.; Kathan, C.; Mortimore, S.
    Objectives: To review early oncological outcomes following transoral CO2 laser resection of laryngeal and hypopharyngeal squamous cell carcinoma. Design: Retrospective review of hospital electronic database. Setting: Large district general hospital in England, UK.Main outcome measures: Patients' three-year disease-specific survival and disease-free survival were evaluated, including post-operative complications, voice quality and swallowing status. Results: Seventy-seven patients (16 women and 61 men) were identified. Transoral laser excision of squamous cell carcinoma of the larynx was undergone by 65 patients, and the same procedure in the hypopharynx by 12. Patients with laryngeal cancer had statistically better disease-specific survival than those with hypopharyngeal cancer (p=0.021), although the cumulative disease-free survival probability was 0.71 for both larynx and hypopharynx groups. Patients who underwent laryngectomy following failed laser treatment or as a salvage procedure had poorer outcomes.Conclusions: The overall results of this study were comparable with those of other, larger studies. At three-year follow up, cumulative disease-specific survival probabilities were 0.92 and 0.71 for laryngeal and hypopharyngeal squamous cell carcinoma, respectively. Copyright © JLO (1984) Limited 2009.
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    The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelialmesenchymal transition in breast cancer
    (Impact Journals LLC, 2016) Raza, U.; Saatci, O.; Uhlmann, S.; Ansari, S. A.; Eyüpoglu, E.; Yurdusev, E.; Mutlu, M.; Ersan, P. G.; Altundağ, M. K.; Zhang, J. D.; Dogan, H. T.; Güler, G.; Şahin, Ö.
    Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPRCas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant-p53 which acts as a 'molecular switch' between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53- mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis.