Affiliation: Ottawa Health Research Institute
- Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomasJim Dimitroulakos
Department of Cellular and Molecular Biology, The University Health Network, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
Neoplasia 4:337-46. 2002..Our data suggest that the depletion of nonsterol mevalonate metabolites, particularly GGPP, can be potential mediators of lovastatin-induced apoptosis of HNSCC and CC cells...
- Activation of the integrated stress response regulates lovastatin-induced apoptosisNima Niknejad
Centre for Cancer Therapeutics, Ottawa Health Research Institute, Ontario K1H 8L6, Canada
J Biol Chem 282:29748-56. 2007..Therefore, lovastatin, by targeting mevalonate synthesis, is a potent inducer of the ISR through a novel and as yet unrecognized mechanism...
- Activating Transcription Factor 3 regulates in part the enhanced tumour cell cytotoxicity of the histone deacetylase inhibitor M344 and cisplatin in combinationCarly St Germain
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, K1H 8L6, Canada
Cancer Cell Int 10:32. 2010..In this study, we evaluated the role of ATF3 in regulating the co-operative cytotoxicity of cisplatin in combination with an HDAC inhibitor...
- Strategies to enhance epidermal growth factor inhibition: targeting the mevalonate pathwayJim Dimitroulakos
Centre for Cancer Therapeutics, Ottawa Hospital Regional Cancer Centre and Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Clin Cancer Res 12:4426s-4431s. 2006..The combination of erlotinib and rosuvastatin has been proposed for a phase I/II study in advanced non-small cell lung carcinoma...
- Lovastatin-induced apoptosis is mediated by activating transcription factor 3 and enhanced in combination with salubrinalNima Niknejad
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada Faculty of Medicine and the Department of Biochemistry, University of Ottawa, Ottawa, ON, Canada
Int J Cancer 134:268-79. 2014..Importantly, combining lovastatin with salubrinal enhanced ATF3 expression and induced synergistic cytotoxicity in SCC cells. ..
- Lovastatin induces multiple stress pathways including LKB1/AMPK activation that regulate its cytotoxic effects in squamous cell carcinoma cellsLaurie Ma
Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ontario, Canada
PLoS ONE 7:e46055. 2012..In recent studies, we demonstrated the ability of lovastatin, an inhibitor of mevalonate synthesis, to induce the Integrated Stress Response as well as inhibiting epidermal growth factor receptor (EGFR) activation...
- Targeting the mevalonate pathway inhibits the function of the epidermal growth factor receptorAngela J Mantha
Centre for Cancer Therapeutics and Medical Oncology, Ottawa Regional Cancer Centre, Ottawa Health Research Institute, 503 Smyth Road, Ottawa, Ontario, Canada K1H 1C4
Clin Cancer Res 11:2398-407. 2005..Mevalonate metabolites play significant roles in the function of the EGFR; therefore, mevalonate pathway inhibitors may potentiate EGFR-targeted therapies...
- Lovastatin enhances gefitinib activity in glioblastoma cells irrespective of EGFRvIII and PTEN statusCatia Cemeus
Centre for Cancer Therapeutics, The Ottawa Health Research Institute and Ottawa Regional Cancer Centre, 503 Smyth Road, Third Floor, Ottawa, ON, Canada, K1H 1C4
J Neurooncol 90:9-17. 2008..These studies demonstrate the potential of lovastatin to augment the cytotoxic effects of gefitinib and provide a rationale for combined statin/EGFR targeted therapies in glioblastoma patients...
- Enhancement of cisplatin cytotoxicity by disulfiram involves activating transcription factor 3Anna O'Brien
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, 501 Smyth Road, Box 926, Ottawa, ON, K1H 8L6, Canada
Anticancer Res 32:2679-88. 2012..Activating transcription factor 3 (ATF3), a stress-inducible gene, is a regulator of cisplatin-induced cytotoxicity, and enhancement of the ATF3 expression potentiates this cytotoxicity...
- Epidermal growth factor receptor-targeted therapy potentiates lovastatin-induced apoptosis in head and neck squamous cell carcinoma cellsAngela J Mantha
Centre for Cancer Therapeutics, Ottawa Regional Cancer Centre, 503 Smyth Road, Third Floor, Ottawa, Ontario, K1H 1C4, Canada
J Cancer Res Clin Oncol 129:631-41. 2003..In this study, we evaluated the potential of a number of chemotherapeutics that demonstrate activity in HNSCC, including an inhibitor of epidermal growth factor receptor (EGFR) to potentiate the cytotoxic effects of lovastatin...
- Cisplatin induces cytotoxicity through the mitogen-activated protein kinase pathways and activating transcription factor 3Carly St Germain
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
Neoplasia 12:527-38. 2010..This study identifies cisplatin as a MAPK pathway-dependent inducer of ATF3, whose expression influences cisplatin's cytotoxic effects...
- Lovastatin inhibits VEGFR and AKT activation: synergistic cytotoxicity in combination with VEGFR inhibitorsTong T Zhao
Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
PLoS ONE 5:e12563. 2010..The vascular endothelial growth factor receptor (VEGFR) and EGFR share similar activation, internalization and downstream signaling characteristics...
- Lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma and neuroblastoma cells: enhanced differentiation and apoptosis in combination with dbcAMPDanielle E Arnold
Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa Regional Cancer Centre, 503 Smyth Road, Third Floor, Ottawa, ON, K1H 1C4, Canada
Mol Cell Biochem 345:1-11. 2010..This study suggests the potential of combining these therapeutic approaches in EC and NB patients...
- Monensin inhibits epidermal growth factor receptor trafficking and activation: synergistic cytotoxicity in combination with EGFR inhibitorsKhalil Dayekh
Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, The University of Ottawa, Ottawa, Ontario, Canada Faculty of Medicine and the Department of Biochemistry, The University of Ottawa, Ottawa, Ontario, Canada
Mol Cancer Ther 13:2559-71. 2014..These results suggest the potential clinical utility of combining monensin with erlotinib in patients with HNSCC...
- miR Profiling Identifies Cyclin-Dependent Kinase 6 Downregulation as a Potential Mechanism of Acquired Cisplatin Resistance in Non-Small-Cell Lung CarcinomaJair Bar
Division of Medical Oncology, University of Ottawa Faculty of Medicine and The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
Clin Lung Cancer . 2015..Platinum-based chemotherapeutic drugs are the most active agents in treating advanced disease. Resistance to these drugs is common and multifactorial; insight into the molecular mechanisms involved will likely enhance efficacy...
- Sensitivity of cervical carcinoma cells to vesicular stomatitis virus-induced oncolysis: potential role of human papilloma virus infectionFabrice Le Boeuf
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
Int J Cancer 131:E204-15. 2012..Taken together, these results demonstrate that HPV-infected cells are susceptible to oncolytic virus therapy and that this approach may represent a novel therapeutic approach in HPV positive CC and HNSCC patients...
- The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancerJohanne Weberpals
Division of Gynaecologic Oncology, The Ottawa Hospital, Ottawa, Ontario, Canada
Int J Cancer 124:806-15. 2009..In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro...
- Stage-dependent differential expression of microRNAs in colorectal cancer: potential role as markers of metastatic diseaseMichael M Vickers
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Clin Exp Metastasis 29:123-32. 2012..We have further found that an analysis of these five miRs expression levels in primary tumors significantly correlates with the presence of metastatic disease, making this a potential clinically useful prognostic tool...
- miR-105 inhibits prostate tumour growth by suppressing CDK6 levelsD Rice Honeywell
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
PLoS ONE 8:e70515. 2013..Our results suggest that miR-105 inhibits tumour cell proliferation and hence may represent a novel therapeutically relevant cellular target to inhibit tumour growth or a marker of aggressive tumours in prostate cancer patients. ..
- The effect of the histone deacetylase inhibitor M344 on BRCA1 expression in breast and ovarian cancer cellsJohanne I Weberpals
Division of Gynaecologic Oncology, The Ottawa Hospital, 501 Smyth Road, Ottawa, K1H 8L6, Canada
Cancer Cell Int 11:29. 2011..abstract:..
- A Phase I trial of prolonged administration of lovastatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or of the cervixJennifer J Knox
Departments of Medical Oncology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, 5 218, 610 University Avenue, Toronto, Ont, Canada M5G 2M9
Eur J Cancer 41:523-30. 2005..We conclude that the administration of lovastatin at 7.5 mg/kg/day for 21 consecutive days on a 28-day schedule is well tolerated in patients with good renal function and warrants further clinical evaluation...