Abstract 6: A triple-helix forming oligonucleotide targeting a genomic locus is capable of sequence specific mutagenesis in human lymphoblastoid TK6 cells

Reshat, Reshat; Priestley, Catherine; Gooderham, Nigel J.

doi:10.1158/1538-7445.am10-6

Cited by 6 publications

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“…Annexin A1, a major substrate for epidermal growth factor receptor kinase, plays an important role in cancer development and progression [44,45]. Although expression of Annexin A1 was reported to be associated with a number of cancers including pancreatic cancer [46], the molecular mechanism underlying is unknown.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells

Wang

Zhang

et al. 2013

Exp Hematol Oncol

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Oxythiamine (OT), an analogue of anti-metabolite, can suppress the nonoxidative synthesis of ribose and induce cell apoptosis by causing a G1 phase arrest in vitro and in vivo. However, the molecular mechanism remains unclear yet. In the present study, a quantitative proteomic analysis using the modified SILAC method (mSILAC) was performed to determine the effect of metabolic inhibition on dynamic changes of protein expression in MIA PaCa-2 cancer cells treated with OT at various doses (0 μM, 5 μM, 50 μM and 500 μM) and time points (0 h, 12 h and 48 h). A total of 52 differential proteins in MIA PaCa-2 cells treated with OT were identified, including 14 phosphorylated proteins. Based on the dynamic expression pattern, these proteins were categorized in three clusters, straight down-regulation (cluster 1, 37% of total proteins), upright “V” shape expression pattern (cluster 2, 47.8% total), and downright “V” shape pattern (cluster 3, 15.2% total). Among them, Annexin A1 expression was significantly down-regulated by OT treatment in time-dependent manner, while no change of this protein was observed in OT dose-dependent fashion. Pathway analysis suggested that inhibition of transketolase resulted in changes of multiple cellular signaling pathways associated with cell apoptosis. The temporal expression patterns of proteins revealed that OT altered dynamics of protein expression in time-dependent fashion by suppressing phosphor kinase expression, resulting in cancer cell apoptosis. Results from this study suggest that interference of single metabolic enzyme activity altered multiple cellular signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells

Wang

Zhang

et al. 2013

Exp Hematol Oncol

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Time-Dependent Prognostic Impact of Circulating Tumor Cells Detection in Non-Metastatic Breast Cancer: 70-Month Analysis of the REMAGUS02 Study

Bidard

Belin

Delaloge

et al. 2013

International Journal of Breast Cancer

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Introduction. In non-metastatic breast cancer patients, the REMAGUS02 neoadjuvant study was the first to report a significant impact of circulating tumor cells (CTCs) detection by the CellSearch system on the distant metastasis-free survival (DMFS) and overall survival (OS) endpoints. However, these results were only reported after a short follow-up. Here, we present the updated data, with a longer follow-up. Material and Methods. CTC count was performed before and after neoadjuvant chemotherapy in 118 patients and correlated to survival. Results. CTC count results were available before and/or after neoadjuvant chemotherapy in 115 patients. After a median follow-up of 70 months, detection of ≥1 CTC/7.5 mL before chemotherapy (N = 95) was significantly associated with DMFS (P = 0.04) and OS (P = 0.03), whereas postchemotherapy CTC detection (N = 85) had no significant impact. In multivariable analysis, prechemotherapy CTC and triple negative phenotype were the two independent prognostic factors for survival. We observed that the CTC impact is most significant during the first three years of follow-up. Discussion. We confirm that the detection of CTC is independently associated with a significantly worse outcome, but mainly during the first 3-4 years of follow-up. No prognostic impact is seen in patients who are still relapse-free at this moment.

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First-Line Bevacizumab-Containing Therapy for Triple-Negative Breast Cancer: Analysis of 585 Patients Treated in the ATHENA Study

et al. 2012

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Background: The prognosis for patients with triple-negative breast cancer (TNBC) is poor and treatment options are limited. Bevacizumab improves the efficacy of standard first-line therapy in locally recurrent/metastatic breast cancer (LR/mBC). The benefit of bevacizumab seen in patients with TNBC appears similar to that observed in the overall population. We conducted an exploratory analysis of patients with TNBC treated in the single-arm routine oncology practice ATHENA study. Methods: Patients with previously untreated LR/mBC received standard first-line chemotherapy combined with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks, until progression, unacceptable toxicity, or patient/physician decision). Results: Of 2,264 patients treated in ATHENA, 585 (26%) had TNBC. Most patients received single-agent taxane with bevacizumab. In the TNBC subgroup, the overall response rate was 49%, including complete responses in 10%; only 16% had primary resistant disease. Median time to progression was 7.2 months (95% CI 6.6–7.8) and median overall survival was 18.3 months (95% CI 16.4–19.7). The 1-year overall survival rate was 60%. The safety profile in TNBC was consistent with results in the overall population. Conclusion: This exploratory subgroup analysis suggests that first-line chemotherapy in combination with bevacizumab is an active regimen in patients with metastatic TNBC.

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Abstract 6: A triple-helix forming oligonucleotide targeting a genomic locus is capable of sequence specific mutagenesis in human lymphoblastoid TK6 cells

Cited by 6 publications

References 0 publications

Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells

Inhibition of transketolase by oxythiamine altered dynamics of protein signals in pancreatic cancer cells

Time-Dependent Prognostic Impact of Circulating Tumor Cells Detection in Non-Metastatic Breast Cancer: 70-Month Analysis of the REMAGUS02 Study

First-Line Bevacizumab-Containing Therapy for Triple-Negative Breast Cancer: Analysis of 585 Patients Treated in the ATHENA Study

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