ThermomiR-377-3p-induced Suppression of Cirbp Expression Is Required for Effective Elimination of Cancer Cells and Cancer Stem-like Cells by Hyperthermia

In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold-inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Our results firstly revealed that hyperthermia significantly attenuated the stemness property of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)-like population. Moreover, hyperthermia substantially improved the sensitivity of radiation-resistant NPC cells and CSC-like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti-tumor-killing activity of hyperthermia against NPC cells and CSC-like cells, whereas ectopic expression of Cirbp compromised tumor-killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377–3p improved the sensitivity of NPC cells and cancer stem-like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp nearly completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377–3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Technology development of hyperthermic pressurized intraperitoneal aerosol chemotherapy (hPIPAC)

Background Optimized drug delivery systems are needed for intraperitoneal chemotherapy. The aim of this study was to develop a technology for applying pressurized intraperitoneal aerosol chemotherapy (PIPAC) under hyperthermic conditions (hPIPAC). Methods This is an ex-vivo study in an inverted bovine urinary bladder (IBUB). Hyperthermia was established using a modified industry-standard device (Humigard). Two entry and one exit ports were placed. Warm-humid CO2 was insufflated in the IBUB placed in a normothermic bath to simulate body thermal inertia. The temperature of the aerosol, tissue, and water bath was measured in real-time. Results Therapeutic hyperthermia (target tissue temperature 41–43 °C) could be established and maintained over 30 min. In the first phase (insufflation phase), tissue hyperthermia was created by insufflating continuously warm-humid CO2. In the second phase (aerosolization phase), chemotherapeutic drugs were heated up and aerosolized into the IBUB. In a third phase (application phase), hyperthermia was maintained within the therapeutic range using an endoscopic infrared heating device. In a fourth phase, the toxic aerosol was discarded using a closed aerosol waste system (CAWS). Discussion We introduce a simple and effective technology for hPIPAC. hPIPAC is feasible in an ex-vivo model by using a combination of industry-standard medical devices after modification. Potential pharmacological and biological advantages of hPIPAC over PIPAC should now be evaluated.

Magnetic Field Effect on Sisko Fluid Flow Containing Gold Nanoparticles through a Porous Curved Surface in the Presence of Radiation and Partial Slip

The radiation and magnetic field effects of nanofluids play a significant role in biomedical engineering and medical treatment. This study investigated the performance of gold particles in blood flow (Sisko fluid flow) over a porous, slippery, curved surface. The partial slip effect was considered to examine the characteristics of nanofluid flow in depth. The foremost partial differential equations of the Sisko model were reduced to ordinary differential equations by using suitable variables, and the boundary value problem of the fourth-order (bvp4c) procedure was applied to plot the results. In addition, the effects of the parameters involved on temperature and velocity were presented in light of the parametric investigation. A comparison with published results showed excellent agreement. The velocity distribution was enhanced due to the magnetic field, while the temperature increased due to the effects of a magnetic field and radiation, which are effective in therapeutic hyperthermia. In addition, the nanoparticle suspension showed increased temperature and decelerated velocity.

Preparation and Characterization of PMMA-Based Cements Containing Magnetic Nanoparticles for the Magnetic Hyperthermia

Three types of polymethylmethacrylate(PMMA)-based cements containing magnetic (Fe3O4) particles were developed and their properties were evaluated. The commercial available PMMA cement (PMMAc) was used as a control material. The setting time of the cement extended while the compressive strength of the samples decreased with increasing Fe3O4 content. There was no obvious difference in peak temperature between the cements during the setting reaction. The cement with 10 wt% Fe3O4 in an alternating magnetic field (AMF) of 125 Gs and cement with 20 wt% Fe3O4 in an AMF of 100 Gs could generate enough heat for the therapeutic hyperthermia of bone metastasis.