The Immunogenic Connection of Thermal and Nonthermal Molecular Effects in Modulated Electro-Hyperthermia

Hyperthermia in oncology is an emerging complementary therapy. The clinical results depend on multiple conditional factors, like the type of cancer, the stage, the applied treatment device, and the complementary conventional therapy. The molecular effect could also be different depending on the temperature, heating dose, kind of energy transfer, and timing sequences compared to the concomitant treatment. This article examines the molecular impacts of a specific technique used in oncological hyperthermia called modulated electro-hyperthermia (mEHT). What sets mEHT apart is its emphasis on harnessing the combined effects of thermal and nonthermal factors. Nonthermal energy absorption occurs through the excitation of molecules, while the thermal component ensures the ideal conditions for this process. The applied radiofrequency current selects the malignant cells, and the modulation drives the nonthermal effects to immunogenic cell death, helping to develop tumor-specific antitumoral immune reactions. The synergy of the thermal and nonthermal components excites the lipid-assembled clusters of transmembrane proteins (membrane rafts) as the channels of transient receptor potentials (TRPs), the heat-shock proteins (HSPs), the voltage-gated channels, and the voltage-sensitive phosphatases (VSPs). All these transmembrane compartments channeling various ionic species (like calcium and proton) interact with the cytoskeleton and are involved in the apoptotic signal pathways.

Blood and Histopathological Biomarkers of Immune-related Adverse Effects of Treatment with Immune Checkpoint Inhibitors

Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune checkpoint inhibitors have renewed the hope of many patients for a more effective treatment.However,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced toxicities.Hence,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.

Sintilimab-induced autoimmune diabetes:A case report and review of the literature

BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ICIs and can be troublesome and life threatening.CASE SUMMARY We report a 78-year-old woman with no history of diabetes who presented with hyperglycemia up to 23.4 mmol/L(random blood glucose level)after 14 courses of sintilimab.Hemoglobin A1c was 8.2%,fasting insulin was 0.29 mIU/mL,and fasting C-peptide was decreased to a level with negative autoantibodies.Combing her medical history and laboratory examination,she was diagnosed with programmed cell death(PD)-1-inhibitor-induced,new-onset autoimmune DM.After controlling her blood glucose,she was treated with daily insulin by subcutaneous injection.She was allowed to continue anti-PD-1 therapy and she still obtained some therapeutic efficacy.We also reviewed some published cases(n=36)of PD-1/PD-ligand 1(PD-L1)inhibitor-induced DM.We also discuss potential pathogenic mechanisms,clinical features,prognostic markers(βcell antibodies,human leukocyte antigen type,PD-L1 Level)of this rare adverse effect.CONCLUSION It is important for all clinicians to be aware of DM as an irAEs of ICIs.

Immune response induced by hematoporphyrin derivatives mediated photodynamic therapy:Immunogenic cell death and elevated costimulatory molecules

Photodynamic therapy(PDT)not only destroys tumor cells directly but also induced anti-tumor immune response through damage-associated molecular patterns(DAMPs).It is reported that anti-tumor response was associated with light dose and photosensitizer used in PDT.In this study,4T1 tumor cells were implanted on both the right and left flanks of mice.Only the right tumor was treated by HpD-PDT,while the left tumor was not irradiated.The anti-tumor immune response induced by HpD-PDT was investigated.The expression of DAMPs and costimulatory molecules induced by HpD-PDT were tested by immuno fluorescence and flow cytometry in vivo.Different light doses of PDT were designed to treat 4T1 cells.The killing effect was assessed by CCK-8 kit and apoptosis kit.The expression of DAMPs on 4T1 cells after HpDPDT were evaluated by flow cytometry,western blot and ATP kit.This study showed that CD4^(+)T,CD8^(+)T and the production of IFN-γwere increased significantly on day 10 in righttumor after PDT treatment compared with control group.HpD-PDT enhanced the expression of calreticulin(CRT)on tumor tissue.Importantly,co-stimulatory molecular OX-40 and 4-1BB were elevated on CD8^(+)T cells.In vitro,immunogenic death of 4T1 cells was induced after PDT.Besides,the expression of DAMPs increased with the increasing of energy density.This study indicates that anti-tumor immune effect was induced by HpD-PDT.The knowledge of the involvement of CRT,ATP and co-stimulatory molecules uncovers important mechanistic insight into the anti-tumor immunogenicity.It was the first time that co-stimulatory molecules were investigated and found to elevate after PDT.

Study of the effects of bisphenol A using human fetal lung fibroblasts

Bisphenol A(BPA,2,2-bis(4-hydroxyphenyl)propane;CAS#80-05-7)is a highly produced industrial chemical,with an estimated four billion kilograms produced worldwide each year(reviewed in Vandenberg et al.,2010).BPA serves as a monomer in the manufacture of polycarbonate,a hard,clear plastic.Polycarbonate plastics are used in many consumer products,such as reusable water bottles.BPA is also widely used to make epoxy resins,which are used as coating on the inside of

Photosynthetic microorganisms coupled photodynamic therapy for enhanced antitumor immune effect

The ideal photodynamic therapy(PDT)should effectively remove the primary tumor,and produce a stronger immune memory effect to inhibit the tumor recurrence and tumor metastasis.However,limited by the hypoxic and immunosuppressive microenvironment,the PDT efficiency is apparently low.Here,Chlorella(Chl.)is exploited to enhance local effect by producing oxygen to reverse hypoxia,and release adjuvants to reverse immunosuppressive microenvironment to enhance abscopal effect afterwards.Results from different animal models indicated that Chl.could enhance local effect and PDT related immune response.Ultimately,Chl.coupled PDT elicited anti-tumor effects toward established primary tumors(inhibition rate:90%)and abscopal tumors(75%),controlled the challenged tumors(100%)and alleviated metastatic tumors(90%).This Chl.coupled PDT strategy can also produce a stronger anti-tumor immune memory effect.Overall,this Chl.coupled PDT strategy generates enhanced local tumor killing,boosts PDT-induced immune responses and promotes anti-tumor immune memory effect,which may be a great progress for realizing systemic effect of PDT.

Developing and studying the dynamical behavior of a nonlinear mathematical model for cancers with tumor by considering immune system role

We are constrained by widespread cancerous diseases to improve treatment methods which save patients and provide better living conditions during and after the treatment period.Because of the complexity of the treatment process,mathematical models need to be used in order to have a better understanding of the process.However,deriving an adequate complex model that can capture the disease pattern which could be confirmed by simulations and experiments has its own barriers.In this paper,a new mathematical model is developed concerning immune system effect on cancer.The model is introduced using nonlinear ordinary differential equations.Also,the qualitative behavior of the proposed system is studied in order to examine the extent of the model with respect to the nature of tumor evolution.Thus,number and status of equilibria points in line with the existence of limit cycles are obtained for sub-systems and the whole system.Meanwhile,possible bifurcations are mentioned,and the consequent evolutions are described.It is shown that the model conforms well to natural possibilities,cancer growth or remission.Thus,the model would be fit for further studies for prediction and contemplating treatment method,especially for immune stimulating drugs and immunotherapy.

Hygroscopicity measurement of sodium carbonate,β-alanine and internally mixed β-alanine/Na2CO3 particles by ATR-FTIR

Water-uptakes of pure sodium carbonate(Na2CO3),pureβ-alanine and internally mixedβ-alanine/Na2CO3 aerosol particles with different mole ratios are first monitored using attenuated total reflectance Fourier transform infrared spectroscopy(ATR-FTIR)technique.For pure Na2CO3 aerosol particles,combining the absorptions at 877 and 1422 cm-1 with abrupt water loss shows the efflorescence relative humidity(ERH)of 62.9%–51.9%.Upon humidifying,solid Na2CO3 firstly absorbs water to from Na2CO3·H2O crystal at 72.0%RH and then deliquesces at 84.5%RH(DRH).As for pureβ-alanine particles,the crystallization takes place in the range of 42.4%–33.2%RH and becomes droplets at^88.2%RH.Whenβ-alanine is mixed with Na2CO3 at various mole ratios,it shows no efflorescence of Na2CO3 whenβ-alanine to Na2CO3 mole ratio(OIR)is 2:1.For 1:1 and 1:2β-alanine/Na2CO3 aerosols,the ERHs of Na2CO3 are 51.8%–42.3%and 57.1%–42.3%,respectively.Whileβ-alanine crystal appears from 62.7%RH for 2:1 and 59.4%RH for both 1:1 and 1:2 particles and lasts to driest state.On hydration,the DRH is 44.7%–75.2%for Na2CO3 with the OIR of 1:1 and 44.7%–69.0%for 1:2 mixture,and those of β-alanine are 74.8% for 2:1 mixture and 68.9%for two others.After the first dehumidification–humidification,all the water contents decrease despite of constituent fraction.And at^92%RH,the remaining water contents are 92%,89%and 82%at^92%RH,corresponding to OIR of 2:1,1:1 and 1:2 mixed system,respectively.