A5029833435- Renal and related cancers
- PI3K/AKT/mTOR signaling in cancer
- Renal cell carcinoma treatment
- Ovarian cancer diagnosis and treatment
- Thyroid Cancer Diagnosis and Treatment
- Genetic and Kidney Cyst Diseases
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Hedgehog Signaling Pathway Studies
- Lung Cancer Treatments and Mutations
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Oral microbiology and periodontitis research
- Cancer Genomics and Diagnostics
- Tumors and Oncological Cases
- Characterization and Applications of Magnetic Nanoparticles
- Magnetic Bearings and Levitation Dynamics
- BRCA gene mutations in cancer
- Ferroptosis and cancer prognosis
- Cell death mechanisms and regulation
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Proteoglycans and glycosaminoglycans research
- Ear and Head Tumors
Memorial Sloan Kettering Cancer Center
2009-2022
Cleveland Clinic
2021
Wuhan University
2021
New York Proton Center
2014
Dalhousie University
2009
Mutations in isocitrate dehydrogenase (IDH) genes occur multiple cancer types, lead to global changes the epigenome, and drive tumorigenesis. Yet, effective strategies targeting solid tumors harboring IDH mutations remain elusive. Here, we demonstrate that IDH-mutant gliomas cholangiocarcinomas display elevated DNA damage. Using vitro preclinical animal models of glioma cholangiocarcinoma, developed treatment use a synthetic lethality approach reduced damage repair conferred by mutant using...
Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head neck squamous cell carcinoma. Targeted agents such as cetuximab erlotinib are currently used patients with carcinoma, but, this disease, genomic alterations that cause activation determine response pharmacologic inhibition remain ill-defined. Here, we present a detailed dissection EGFR/PI3K pathway, composed sequencing core components,...
Streptococcus mutans in dental biofilms is regularly exposed to cycles of acidic pH during the ingestion fermentable dietary carbohydrates. The ability S. tolerate low crucial for its virulence and pathogenesis caries. To better understand acid tolerance mechanisms, we performed genome-wide transcriptional analysis response an signal. preliminary results showed that adaptation 5.5 induced differential expression nearly 14 % genes genome, including 169 upregulated 108 downregulated genes,...
Hürthle cell carcinomas (HCCs) display two exceptional genotypes: near-homoplasmic mutation of mitochondrial DNA (mtDNA) and genome-wide loss heterozygosity (gLOH). To understand the phenotypic consequences these genetic alterations, we analyzed genomic, metabolomic, immunophenotypic data HCC other thyroid cancers. Both mtDNA mutations profound depletion citrate pools are common in malignancies, suggesting that cancers broadly equipped to survive tricarboxylic acid cycle impairment, whereas...
Mutation of the PARK2 gene can promote both Parkinson's Disease and cancer, yet underlying mechanisms how controls cellular physiology is incompletely understood. Here, we show that tumor suppressor apoptotic regulator BCL-XL modulates programmed cell death. Analysis approximately 10,000 genomes uncovers a striking pattern mutual exclusivity between genetic loss amplification BCL2L1, implicating these genes in common pathway. directly binds to ubiquitinates BCL-XL. Inactivation leads...
Hurthle cell carcinomas (HCCs) are refractory to radioactive iodine and unresponsive chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic cancer. Our previous study on genomic landscape HCCs identified high incidence disruptions mTOR pathway effectors. Here, we report detailed analysis signaling in line patient-derived xenograft mouse models HCCs. We show upregulated targeting using inhibitors suppresses tumor growth primary...
<p>Pan-AKT inhibitor treatment of XTC.UC1 cells does not result in large decreases proliferation. A, Comparison MK2206 NTHY-ori (top) and (bottom) cells. B, Immunoblot analysis mTOR signaling treated with for 0, 1, 2, 3 days.</p>
<p>Quantitative RT-PCR primer sequences</p>
<p>Quantitative RT-PCR primer sequences</p>
<div>Abstract<p>Hurthle cell carcinomas (HCCs) are refractory to radioactive iodine and unresponsive chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic cancer. Our previous study on genomic landscape HCCs identified high incidence disruptions mTOR pathway effectors. Here, we report detailed analysis signaling in line patient-derived xenograft mouse models HCCs. We show upregulated targeting using inhibitors...
<p>mTOR inhibitor treatment suppresses XTC.UC1 cell proliferation in vitro. Comparison of dose response three mTOR inhibitors rapamycin, AZD8055 and AZD2014 cells with 16-day-treatment.</p>
<p>Somatic genomic mutations in XTC.UC1 and HCC. Significantly mutated genes, as determined by the MutSig algorithm are shown. Left: overall count for each gene. Right: gene list.</p>
<p>Combination treatment with rapamycin and lenvatinib in PDX model TC1m1. A, Combination resulted enhanced decrease CD31 staining endothelial vessels compared to alone or alone. B, The average IMVD values of tumors from mice treated different drugs were decreased 44.5% (rapamycin), 60.6% (lenvatinib), 16.9% (combination lenvatinib), respectively, that vehicle control group.</p>
<p>Combination treatment with rapamycin and lenvatinib in PDX model TC1m1. A, Combination resulted enhanced decrease CD31 staining endothelial vessels compared to alone or alone. B, The average IMVD values of tumors from mice treated different drugs were decreased 44.5% (rapamycin), 60.6% (lenvatinib), 16.9% (combination lenvatinib), respectively, that vehicle control group.</p>
<p>A, Combination treatment of XTC.UC1 with rapamycin and the pan-AKT inhibitor MK2206 MEK PD325902. B, Cell proliferation assay cells treated or AZD8055 alone in combination C, Immunoblot analysis mTOR signaling at 5 hours after AZD 8055 Rapamycin combined did not further reduce cell proliferation, despite inhibition p-AKT(S473). PD325901 result reduction proliferation.</p>
<div>Abstract<p>Hurthle cell carcinomas (HCCs) are refractory to radioactive iodine and unresponsive chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic cancer. Our previous study on genomic landscape HCCs identified high incidence disruptions mTOR pathway effectors. Here, we report detailed analysis signaling in line patient-derived xenograft mouse models HCCs. We show upregulated targeting using inhibitors...
<p>Pan-AKT inhibitor treatment of XTC.UC1 cells does not result in large decreases proliferation. A, Comparison MK2206 NTHY-ori (top) and (bottom) cells. B, Immunoblot analysis mTOR signaling treated with for 0, 1, 2, 3 days.</p>
<p>Somatic genomic mutations in XTC.UC1 and HCC. Significantly mutated genes, as determined by the MutSig algorithm are shown. Left: overall count for each gene. Right: gene list.</p>
<p>A, Combination treatment of XTC.UC1 with rapamycin and the pan-AKT inhibitor MK2206 MEK PD325902. B, Cell proliferation assay cells treated or AZD8055 alone in combination C, Immunoblot analysis mTOR signaling at 5 hours after AZD 8055 Rapamycin combined did not further reduce cell proliferation, despite inhibition p-AKT(S473). PD325901 result reduction proliferation.</p>