A5084956725- Autophagy in Disease and Therapy
- Histone Deacetylase Inhibitors Research
- PARP inhibition in cancer therapy
- PI3K/AKT/mTOR signaling in cancer
- Calcium signaling and nucleotide metabolism
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- MicroRNA in disease regulation
- Genomics, phytochemicals, and oxidative stress
- HER2/EGFR in Cancer Research
- Ferroptosis and cancer prognosis
- Ubiquitin and proteasome pathways
- Medical Imaging Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Renal and related cancers
- Renal cell carcinoma treatment
- Mitochondrial Function and Pathology
- Angiogenesis and VEGF in Cancer
- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Cancer Research and Treatments
BC Cancer Agency
2011-2016
University of British Columbia
2014
Simon Fraser University
2014
Occupational Cancer Research Centre
2010
Maastricht University
2002-2009
Maastro Clinic
2006-2009
Radiotherapie Groep
2009
Triple-negative breast cancers (TNBC) are defined by a lack of expression estrogen receptor (ER), progesterone (PR), and human epidermal growth factor 2 (ERBB2/HER2). Although initially responsive to chemotherapy, most recurrent TNBCs develop resistance, resulting in disease progression. Autophagy is lysosome-mediated degradation recycling process that can function as an adaptive survival response during chemotherapy contribute chemoresistance. Our goal was determine whether autophagy...
Gefitinib (Iressa(®), ZD1839) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. We report on an early cellular response to gefitinib that involves induction functional autophagic flux in phenotypically diverse breast cancer cells were sensitive (BT474 and SKBR3) or insensitive (MCF7-GFPLC3 JIMT-1) gefitinib. Our data show elevation autophagy gefitinib-treated correlated with downregulation AKT ERK1/2 signaling course treatment. Inhibition...
The PI3K/AKT/mTOR pathway is commonly over activated in glioblastoma (GBM), and Rictor was shown to be an important regulator downstream of this pathway. EGFR overexpression also frequently found GBM tumors, both are associated with increased proliferation, invasion, metastasis poor prognosis. This research evaluated vitro vivo whether the combined silencing would result therapeutic benefits. potential targeting these proteins combination conventional agents proven activity patients...
HER2-positive breast cancers exhibit high rates of innate and acquired resistance to trastuzumab (TZ), a HER2-directed antibody used as first line treatment for this disease. TZ may in part be mediated by frequent co-expression EGFR sustained activation the mammalian target rapamycin (mTOR) pathway. Here, we assessed feasibility combining inhibitor gefitinib mTOR everolimus (RAD001) treating HER2 overexpressing with different sensitivity TZ. The RAD001 combination was broadly evaluated...
Abstract Background: Resistance against HER2 targeted agents ultimately limits the therapeutic success in patients with HER2-positive breast cancer. It was shown that PIK3CA mutations contribute to lapatinib resistance and achieving control of a downstream PI3K/mTOR signaling is necessary for optimal effectiveness blockade. We others have catalytic mTORC1/2 inhibitors reverse inhibit growth HER2-overexpressing cancer models vitro vivo. However, activity these hindered by compensatory...
Abstract Lapatinib, a dual epidermal growth factor receptor 1 (EGFR) and human 2 (HER2) tyrosine kinase inhibitor, has emerged as second line therapy for breast cancer patients who relapse following trastuzumab is being tested in clinical trials single agent or combination settings. However, like trastuzumab, development of resistance to lapatinib presents problem the clinic. A number mechanisms have been proposed explain both intrinsic acquired HER2 targeted therapies, one which involves...
Abstract Introduction: Triple-negative breast cancer (TNBC), defined by a lack of expression the estrogen, progesterone and HER-2 receptors, remains major clinical challenge due to higher recurrence rates poorer prognosis compared other subtypes cancer. Tumors that initially respond chemotherapy - core treatment option for patients with an advanced disease eventually develop resistance. New therapeutic options are urgently required TNBC. Autophagy, lysosome-mediated degradation recycling...
<p>Supplementary Figure legends</p>
<p>EPI treatment (100-400 nM) results in altered transcript levels of autophagy genes surviving cells.</p>
<p>Establishment of saturation levels BAF for MDA-MB-231, R8, SUM159PT and R75.</p>
<p>Pharmacologic inhibition of autophagy sensitizes EPI-sensitive BT549 and EPI-resistant R75 TNBC cells.</p>
<p>Detailed description of Alamar blue assay, QRT-PCR, transfections, siRNA, western blot analyses, autophagic flux IHC, and associated references.</p>
<p>Supplementary Figure legends</p>
<p>Detailed description of Alamar blue assay, QRT-PCR, transfections, siRNA, western blot analyses, autophagic flux IHC, and associated references.</p>
<p>Establishment of saturation levels BAF for MDA-MB-231, R8, SUM159PT and R75.</p>
<p>Pharmacologic inhibition of autophagy sensitizes EPI-sensitive BT549 and EPI-resistant R75 TNBC cells.</p>