RESUMO
The members of the cytokine interleukin 17 (IL-17) family, along with their receptors (IL-17R), are vital players in a range of inflammatory diseases and cancer. Although generally regarded as proinflammatory, the effects they exhibit on cancer progression are a double-edged sword, with both antitumor and protumor activities being discovered. There is growing evidence that the IL-17 signaling pathways have significant impacts on the tumor microenvironment (TME), immune response, and inflammation in various types of cancer, including pancreatic cancer. However, the detailed mechanistic functions of the IL-17/IL-17R families in pancreatic cancer were rarely systematically elucidated. This review considers the role of the IL-17/IL-17R families in inflammation and tumor immunity and elaborates on the mechanistic functions and correlations of these members with pathogenesis, progression, and chemoresistance in pancreatic cancer. By summarizing the advanced findings on the role of IL-17/IL17R family members and IL-17 signaling pathways at the molecular level, cellular level, and disease level in pancreatic cancer, this review provides an in-depth discussion on the potential of IL-17/IL-17R as prognostic markers and therapeutic targets in pancreatic cancer.
Assuntos
Interleucina-17 , Neoplasias Pancreáticas , Humanos , Citocinas , Inflamação , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
Photothermal therapy (PTT) exhibits an excellent therapeutic effect in cancer treatment, but some cancers are still facing rapid recurrence due to the presence of heat-resistant cells, which express heat shock proteins (HSP) to defend against hyperthermia. Inspired by optogenetics, we firstly designed a caged TNF-related apoptosis-inducing ligand (TRAIL) expressing plasmid under HSP70 protomer (HSP70-TRAIL) as the thermal-activated gene therapy agent to induce the apoptosis of heat resistant cells. Then, the caged HSP70-TRAIL was decorated on the surface of the photothermal agent (semiconducting nanoparticles, SPNs) through electrostatic adsorption to obtain SPN@HSP70-TRAIL-GFP (SPNHT). Under 1064 nm near-infrared second region (NIR-II) laser irradiation, the SPNHT acted as an emerging photothermal agent for PTT. Importantly, the caged HSP70-TRAIL could be further activated by PTT to express TRAIL on demand to concurrently kill survival cells for overcoming the problem of tumor recurrence after PTT. Both in vitro and in vivo studies demonstrated that the SPNHT nano-system with the ability of NIR-II photothermal-triggered TRAIL in situ expression possessed an admirable synergistic anti-cancer efficacy for HCC. This work offers new tactics for effective treatment of cancer, which showed a great significance for reducing the rate of cancer recurrence after PTT treatment.
Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica , Adsorção , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Imagem Óptica , Fármacos Fotossensibilizantes/químicaRESUMO
We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.