Paul M. Harari

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BACKGROUND We hypothesized that chronic inhibition of epidermal growth factor receptor (EGFR) by cetuximab, a monoclonal anti-EGFR antibody, induces up-regulation of its ligands resulting in resistance and that microRNAs (miRs) play an important role in the ligand regulation in head and neck squamous cell carcinoma (HNSCC). METHODOLOGY/PRINCIPAL FINDINGS(More)
Signaling through the insulin-like growth factor-I receptor (IGF-IR) is implicated in cellular proliferation, apoptosis, carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. Targeted disruption of IGF-IR signaling combined with cytotoxic therapy may therefore yield improved anti-cancer efficacy over conventional treatments alone. In(More)
BACKGROUND Vascular endothelial growth factor (VEGF) plays a critical role in tumor angiogenesis. Bevacizumab is a humanized monoclonal antibody that neutralizes VEGF. We examined the impact on radiation response by blocking VEGF signaling with bevacizumab. METHODS Human umbilical vein endothelial cell (HUVEC) growth inhibition and apoptosis were examined(More)
The sensitivity of only a few tumors to anti-epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) can be explained by the presence of EGFR tyrosine kinase (TK) domain mutations. In addition, such mutations were rarely found in tumor types other than lung, such as pancreatic and head and neck cancer. In this study we sought to elucidate(More)
The use of intensity-modulated radiation therapy (IMRT) is rapidly advancing in the field of radiation oncology. Intensity-modulated radiation therapy allows for improved dose conformality, thereby affording the potential to decrease the spectrum of normal tissue toxicities associated with IMRT. Preliminary results with IMRT are quite promising; however,(More)
This study investigated the dosimetric differences in treatment plans from flattened and flattening filter-free (FFF) beams from the TrueBeam System. A total of 104 treatment plans with static (sliding window) intensity-modulated radiotherapy beams and volumetric-modulated arc therapy (VMAT) beams were generated for 15 patients involving three cancer sites.(More)
The epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and several other human cancers. Monoclonal antibodies, such as cetuximab that block EGFR signaling, have emerged as valuable molecular targeting agents in clinical cancer therapy. Prolonged exposure to cetuximab can result in cells(More)
BACKGROUND Duligotuzumab, a novel dual-action humanized IgG1 antibody that blocks ligand binding to epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody-dependent cell-mediated cytotoxicity. High tumor-expression of neuregulin 1 (NRG1), a(More)
We have identified a cooperative interaction between radiation and intratumoral injection of anti-GD2 immu-nocytokine (hu14.18-IL2) in murine tumor models. In a moderate size (~200 mm 3), single tumor, B78 melanoma model this combination results in complete tumor regression in 71% of animals and a memory T cell response. We hypothesized that intratumoral(More)
PURPOSE To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. METHODS AND MATERIALS Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were(More)