THE ROLE OF TLR3 SIGNALING IN CHEMORESISTANCE OF HEAD AND NECK SQUAMOUS CELL CARCINOMA

Presentation: B047
Topic: Immunobiology / Immunotherapy of H&N Cancer
Type: Poster
Date:
Session:
Authors: Hui-Ching Chuang, MD, PhD
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Institution(s): Kaoshiung Chang Gung Memorial Hospital
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Squamous cell carcinoma of head and neck (HNSCC) is one of the important malignancies around the world. Among them, oral cancer ranks fourth in the incidence of malignancy of the male patients in Taiwan. Oral cancer grows rapidly, resulting in mortality in patients with distant and regional lymph node metastasis.Cisplatin is an effective antitumor agent and is one of the most widely used drugs either alone or in combination with other chemotherapeutic agents or with radiotherapy in the management of locally advanced or recurrent HNSCC . Chemoresistance to cisplatin significantly contributes to treatment failure in clinical management of HNSCC. In response to chemotherapeutic agents, damage-associated molecular patterns (DAMPs) inside the cell are released or secreted from damaged or dead/dying cells. DAMPs interact with pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), the NOD-like receptors and RIG-I-like receptors , and activate systemic inflammatory response in the absence of infection.In our limited data revealed cisplatin treatment could active not only TLR3 pathway, also RLRs signaling. TLR3 knockdown significantly decreased the expression of CCL5 and increased the expression of necroptotic factors after cisplatin treatment in vitro. In addition, cisplatin treatment increased more HMGB1 expression in TLR3 knockdown cells . These results suggested that tumor cells with reduced TLR3 are more susceptible to cisplatin-induced necroptosis as compared with control cells.Further, we created two different orthotopic nude mice models, submucosa tongue injection and subcutaneous flank injection in our present study. We compared the growth rate of TLR3 knockdown and control cells in nude mice. TLR3 knockdown cells has less tumorigenicity than control cells in both nude mice models. Our in vitro and in vivo experiments imply TLR3 signaling did affect the tumor growth and development of HNSCC. TLR3 signaling in tumor cells may significantly reduce therapeutic efficacy by promoting survival and protecting from apoptosis or necroptosis.

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