RESUMEN
Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.
Asunto(s)
Neoplasias Asociadas a Colitis , Colitis , Panax notoginseng , Saponinas , Animales , Colitis/complicaciones , Colitis/tratamiento farmacológico , Neoplasias Asociadas a Colitis/tratamiento farmacológico , Humanos , Macrófagos , Ratones , Saponinas/farmacología , Saponinas/uso terapéutico , Microambiente TumoralRESUMEN
BACKGROUND AND PURPOSE: Previous studies have demonstrated that the erbium:YAG laser is two to three times more efficient for laser lithotripsy than the holmium:YAG laser. However, the lack of a suitable optical fiber delivery system remains a major obstacle to clinical application of Er:YAG laser lithotripsy. This paper describes the initial testing of a hybrid germanium oxide/silica optical fiber for potential endoscopic use with the Er:YAG laser. MATERIALS AND METHODS: Er:YAG laser radiation with a wavelength of 2.94 microm, a pulse energy of 10 to 600 mJ, a pulse length of 220 microsec, and pulse-repetition rates of 3 to 10 Hz was focused into either 350- or 425- microm-core hybrid germanium/silica fibers in contact with human uric acid or calcium oxalate monohydrate stones. RESULTS: Average Er:YAG pulse energies of 157 +/- 46 mJ (66 J/cm(2)) (N = 8) were delivered at 10 Hz through the 425-microm hybrid fibers in contact with urinary stones before fiber damage was observed. A maximum pulse energy of 233 mJ (98 J/cm(2)) was also measured through the hybrid fiber in contact with the stones. These values are significantly greater than the stone ablation thresholds of 15 to 23 mJ (6-10 J/cm(2)) and the fiber damage thresholds measured for germanium oxide, 18 +/- 1 mJ (13 J/cm(2)), and sapphire, 73 mJ (51 J/cm(2)), optical fibers during Er:YAG laser lithotripsy (P < 0.05). CONCLUSIONS: A prototype hybrid germanium/silica optical fiber demonstrated better performance than both germanium oxide and sapphire fibers for transmission of Er:YAG laser radiation during in vitro lithotripsy.
Asunto(s)
Litotripsia por Láser/instrumentación , Óxido de Aluminio , Erbio , Tecnología de Fibra Óptica , Germanio , Humanos , Técnicas In Vitro , Fibras Ópticas , Dióxido de Silicio , Cálculos Urinarios/terapiaRESUMEN
The erbium:YSGG and erbium:YAG lasers are used for tissue ablation in dermatology, dentistry and ophthalmology. The purpose of this study was to compare germanium oxide and sapphire optical fibres for transmission of sufficient Q-switched erbium laser pulse energies for potential use in both soft and hard tissue ablation applications. Fibre transmission studies were conducted with Q-switched (500 ns) Er:YSGG (lambda=2.79 microm) and Er:YAG (lambda=2.94 microm) laser pulses delivered at 3 Hz through 1-m-long, 450-mum germanium oxide and 425-mum sapphire optical fibres. Transmission of free-running (300 micros) Er:YSGG and Er:YAG laser pulses was also conducted for comparison. Each set of measurements was carried out on seven different sapphire or germanium fibres, and the data were then averaged. Fibre attenuation of Q-switched Er:YSGG laser energy measured 1.3+/-0.1 dB/m and 1.0+/-0.2 dB/m for the germanium and sapphire fibres, respectively. Attenuation of Q-switched Er:YAG laser energy measured 0.9+/-0.3 dB/m and 0.6+/-0.2 dB/m, respectively. A maximum Q-switched Er:YSGG pulse energy of 42 mJ (26-30 J/cm(2)) was transmitted through the fibres. However, fibre tip damage was observed at energies exceeding 25 mJ (n=2). Both germanium oxide and sapphire optical fibres transmitted sufficient Q-switched Er:YSGG and Er:YAG laser radiation for use in both soft and hard tissue ablation. This is the first report of germanium and sapphire fibre optic transmission of Q-switched erbium laser energies of 25-42 mJ per pulse.