Browsing by Subject "Disease free survival"

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Open Access
Adjuvant autologous melanoma vaccine for macroscopic stage III disease: survival, biomarkers, and improved response to CTLA-4 blockade
(Hindawi Limited, 2016) Lotem, M.; Merims, S.; Frank, S.; Hamburger, T.; Nissan, A.; Kadouri, L.; Cohen, J.; Straussman, R.; Eisenberg, G.; Frankenburg, S.; Carmon, E.; Alaiyan, B.; Shneibaum, S.; Ayyildiz, Z. O.; Isbilen, M.; Senses, K. M.; Ron, I.; Steinberg, H.; Smith, Y.; Shiloni, E.; Gure, A. O.; Peretz, T.
Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.
Open Access
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.
Open Access
Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal
(American Association for the Advancement of Science (A A A S), 2013) Gao J.; Aksoy, B. A.; Dogrusoz, U.; Dresdner, G.; Gross, B.; Sumer, S. O.; Sun, Y.; Jacobsen, A.; Sinha, R.; Larsson, E.; Cerami, E.; Sander, C.; Schultz, N.
The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics. © 2013 American Association for the Advancement of Science.
Open Access
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.
Open Access
Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer
(Springer Netherlands, 2017-09) Taskoparan, B.; Seza, E. G.; Demirkol, S.; Tuncer, S.; Stefek, M.; Gure, A. O.; Banerjee, S.
Purpose: Aldo-keto reductases (including AKR1B1 and AKR1B10) constitute a family of oxidoreductases that have been implicated in the pathophysiology of diabetes and cancer, including colorectal cancer (CRC). Available data indicate that, despite their similarities in structure and enzymatic functions, their roles in CRC may be divergent. Here, we aimed to determine the expression and functional implications of AKR1B1 and AKR1B10 in CRC. Methods: AKR1B1 and AKR1B10 gene expression levels were analyzed using publicly available microarray data and ex vivo CRC-derived cDNA samples. Gene Set Enrichment Analysis (GSEA), The Cancer Genome Atlas (TCGA) RNA-seq data and The Cancer Proteome Atlas (TCPA) proteome data were analyzed to determine the effect of high and low AKR1B1 and AKR1B10 expression levels in CRC patients. Proliferation, cell cycle progression, cellular motility, adhesion and inflammation were determined in CRC-derived cell lines in which these genes were either exogenously overexpressed or silenced. Results: We found that the expression of AKR1B1 was unaltered, whereas that of AKR1B10 was decreased in primary CRCs. GSEA revealed that, while high AKR1B1 expression was associated with increased cell cycle progression, cellular motility and inflammation, high AKR1B10 expression was associated with a weak inflammatory phenotype. Functional studies carried out in CRC-derived cell lines confirmed these data. Microarray data analysis indicated that high expression levels of AKR1B1 and AKR1B10 were significantly associated with shorter and longer disease-free survival rates, respectively. A combined gene expression signature of AKR1B10 (low) and AKR1B1 (high) showed a better prognostic stratification of CRC patients independent of confounding factors. Conclusions: Despite their similarities, the expression levels and functions of AKR1B1 and AKR1B10 are highly divergent in CRC, and they may have prognostic implications.
Open Access
Outcomes following total laryngectomy for squamous cell carcinoma: one centre experience
(Elsevier Masson, 2012) Leong, S. C.; Kartha, S. -S.; Kathan, C.; Sharp, J.; Mortimore, S.
Objectives: To evaluate the clinical outcomes of total laryngectomy (TL), complications and factors affecting survival. Design: Retrospective review of hospital electronic database for head and neck squamous cell carcinoma (SCCa). Setting: Large district general hospital in England, United Kingdom. Participants: Patients who had TL between January 1994 and January 2008. Main outcome measures: 5-year disease specific survival (DSS) and disease-free survival (DFS). Results and conclusions: Seventy-one patients were reviewed, of whom 38 (54%) had laryngeal SCCa and 33 (46%) hypopharyngeal SCCa. The overall mean survival period following TL was 42.4 months. The 5-year DSS and DFS was better for laryngeal SCCa compared to hypopharyngeal SCCa, although not statistically significant (P = 0.090, P = 0.54 respectively). Patients treated for laryngeal SCCa had a mean survival period of 47.5 months compared to 36.5 months for hypopharyngeal disease. Those who had laryngeal recurrence after primary radiotherapy (RT) demonstrated statistically better survival probability than those who had hypopharyngeal recurrence (P = 0.011). Patients without cervical lymphadenopathy had statistically better survival (P = 0.049). The most common early complication was related to the cardiorespiratory system. One fatal complication of erosion of the brachiocephalic artery due to the laryngectomy tube was noted. The most common late complication was neopharyngeal stenosis. The commonest cause of death was due to locoregional recurrence, followed by medical co-morbidities. Patients referred to specialised head and neck clinic had a better survival probability than those referred to a general ENT clinic (P = 0.37). While there is increasing tendency towards laryngeal conservation, total laryngectomy remains a robust treatment option in selected patients. © 2012 Elsevier Masson SAS.