Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hyp...Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hypermetabolic response,including high fever,tachycardia,and elevated end-tidal carbon dioxide(ETCO_(2)).The successful treatment lies in the timely recognition and early use of dantrolene.[1]As an inhibitor of Ca2+release through ryanodine receptor(RYR)channels,the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca2+signaling and a lifesaving treatment for MH.[2]Dominant mutations in the skeletal muscle RYR1 gene are well-recognized causes of both malignant hyperthermia susceptibility(MHS)and central core disease(CCD).展开更多
The preparation of γ-Fe<sub>2</sub>O<sub>3</sub>/Gd<sub>2</sub>O<sub>3</sub> nanocomposite for possible use in magnetic hyperthermia application was done by ball millin...The preparation of γ-Fe<sub>2</sub>O<sub>3</sub>/Gd<sub>2</sub>O<sub>3</sub> nanocomposite for possible use in magnetic hyperthermia application was done by ball milling technique. The nanocomposite was characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The heating efficiency and the effect of milling time (5 h and 30 h) on the structural and magnetic properties of the nanocomposite were reported. XRD analysis confirms the formation of the nanocomposite, while magnetization measurements show that the milled sample present hysteresis with low coercivity and remanence. The specific absorption rate (SAR) under an alternating magnetic field is investigated as a function of the milling time. A mean heating efficiency of 68 W/g and 28.7 W/g are obtained for 5 h and 30 h milling times respectively at 332 kHz and 170 Oe. The results showed that the obtained nanocomposite for 5 h milling time is a promising candidate for magnetic hyperthermia due to his properties which show an interesting magnetic behavior and high specific absorption rate.展开更多
Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency mo...Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.展开更多
Magnetic particle imaging(MPI)technology can generate a real-time magnetic nanoparticle(MNP)distribution image for biological tissues,and its use can overcome the limitations imposed in magnetic hyperthermia treatment...Magnetic particle imaging(MPI)technology can generate a real-time magnetic nanoparticle(MNP)distribution image for biological tissues,and its use can overcome the limitations imposed in magnetic hyperthermia treatments by the unpredictable MNP distribution after the intratumoral injection of nanofluid.However,the MNP concentration distribution is generally difficult to be extracted from MPI images.This study proposes an approach to extract the corresponding concentration value of each pixel from an MPI image by a least squares method(LSM),which is then translated as MNP concentration distribution by an interpolation function.The resulting MPI-based concentration distribution is used to evaluate the treatment effect and the results are compared with the ones of two baseline cases under the same dose:uniform distribution and MPI-based distribution considering diffusion.Additionally,the treatment effect for all these cases is affected by the blood perfusion rate,which is also investigated deeply in this study.The results demonstrate that the proposed method can be used to effectively reconstruct the concentration distribution from MPI images,and that the weighted LSM considering a quartic polynomial for interpolation provides the best results with respect to other cases considered.Furthermore,the results show that the uniformity of MNP distribution has a positive correlation with both therapeutic temperature distribution and thermal damage degree for the same dose and a critical power dissipation value in the MNPs.The MNPs uniformity inside biological tissue can be improved by the diffusion behavior after the nanofluid injection,which can ultimately reflect as an improvement of treatment effect.In addition,the blood perfusion rate considering local temperature can have a positive effect on the treatment compared to the case which considers a constant value during magnetic hyperthermia.展开更多
Hyperthermia treatment using appropriate magnetic materials in an alternating magnetic field to generate heat has been proposed as a low-invasive cancer treatment method. Magnetite iron oxide nanoparticles (Fe<sub&...Hyperthermia treatment using appropriate magnetic materials in an alternating magnetic field to generate heat has been proposed as a low-invasive cancer treatment method. Magnetite iron oxide nanoparticles (Fe<sub>3</sub>O<sub>4</sub>) are expected to be an appropriate type of magnetic material for this purpose due to its biocompatibility. Several polymers are used to Fe<sub>3</sub>O<sub>4</sub> MNPs to avoid or decrease agglomeration, and in most cases increase dispersion stability. In this review, we will give briefly how these coated magnetite nanoparticles (PMNPs) are synthesized in the first part. The main characterization techniques usually used to study the properties of these MNPs are prseneted in the second part. Finally, most recent results on the heating ability of polymeric coated magnetite nanoparticles (PMNPs) are given in the last part of this review.展开更多
BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mE...BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.展开更多
BACKGROUND Malignant hyperthermia(MH)is a hypermetabolic disorder of skeletal muscles triggered by exposure to volatile anesthetics and depolarizing muscular relaxants.It manifests with clinical presentations such as ...BACKGROUND Malignant hyperthermia(MH)is a hypermetabolic disorder of skeletal muscles triggered by exposure to volatile anesthetics and depolarizing muscular relaxants.It manifests with clinical presentations such as tachycardia,muscle rigidity,hyperpyrexia,and rhabdomyolysis in genetically predisposed individuals with ryanodine receptor or calcium voltage-gated channel subunit alpha1 S mutations.Local anesthetics,such as lidocaine,are generally considered safe;however,complications can arise,albeit rarely.Lidocaine administration has been reported to induce hypermetabolic reactions resembling MH in susceptible individuals.The exact mechanism by which lidocaine might trigger MH is not fully understood.Although some mechanisms are postulated,further research is needed for a better understanding of this.CASE SUMMARY We present the case of MH in a 43-year-old male patient with an unknown genetic predisposition following a lidocaine injection during a dental procedure.This case serves as a reminder that while the occurrence of lidocaine-induced MH is rare,lidocaine can still trigger this life-threatening condition.Therefore,caution should be exercised when administering lidocaine to individuals who may be susceptible to MH.It is important to note that prompt intervention played a crucial role in managing the patient’s symptoms.Upon recognizing the early signs of MH,aggressive measures were initiated,including vigorous intravenous normal saline administration and lorazepam.Due to the effectiveness of these interventions,the administration of dantrolene sodium,a specific antidote for MH,was deferred.CONCLUSION This case highlighted the significance of vigilant monitoring and swift action in mitigating the detrimental effects of lidocaine-induced MH.Caution should be exercised when administering lidocaine to individuals who may be predisposed to MH.It is very important to be aware and vigilant of the signs and symptoms of MH as early recognition and treatment intervention are important to prevent serious complications to decrease mortality.展开更多
Objective: To investigate the electromagnetic field and specific absorptionrate (SAR) distribution of different structure applicators with different depths for treating bonetumors using microwave hyperthermia. Methods...Objective: To investigate the electromagnetic field and specific absorptionrate (SAR) distribution of different structure applicators with different depths for treating bonetumors using microwave hyperthermia. Methods: The finite element method (FEM) was used to calculate,electromagnetic field and SAR distribution. Two different structure applicators were simulated. Theone is simple coaxial antenna, which has been successfully used in clinic treating bone tumors inTangdu hospital of the Forth Military Medical University several years. It was formed by a coaxialcable peeled off the out copper at end. The other applicator was coaxial- slot antenna, which waswidely used in microwave hyperthermia. The applicator inserted into the cylindrical bone withdifferent depths, and worked at the frequency of 2 450 MHz. Results: The electric field and SARgenerated by the simple coaxial applicator were mainly concentrated out the tissues, and were notuniform in the tissues, while the coaxial- slot applicator well transmits the electric field and SARinto the tissues, and can easily treat different position by adjusting the slat position.Conclusion: The results calculated by EFM, were well accordant with the experimental and clinicalresulls, and will be important for improving the clinical effects of microwave hyperthermia.展开更多
Research progress and frontiers of magnetic-mediated hyperthermia （MMH） are presented, along with clinical trials in Germany, the US, Japan, and China. Special attention is focused on MMH mediated by magnetic nanopa...Research progress and frontiers of magnetic-mediated hyperthermia （MMH） are presented, along with clinical trials in Germany, the US, Japan, and China. Special attention is focused on MMH mediated by magnetic nanoparticles, and multifunctional magnetic devices for cancer multimodality treatment are also introduced.展开更多
One of the most frequently applied bioelectromagnetic effects is the deep heating of the living species with EMF energy. Despite its long history, hyperthermia is a rarely applied oncotherapy. The reason is its contro...One of the most frequently applied bioelectromagnetic effects is the deep heating of the living species with EMF energy. Despite its long history, hyperthermia is a rarely applied oncotherapy. The reason is its controversial results and complicated control. One of the solutions is concentrating the electromagnetic energy nanoscopically on the parts of the malignant cells instead of heating up the complete tumor-mass. This approach is a kind of non-uniform energy absorption, providing energy liberation only in the selected regions. The energy-absorption of the malignant cells targets the membranes and creates a situation far from thermal equilibrium. The selection of the malignant cells is based on their decided differences from their healthy counterparts. The distinguishing parameters are the electromagnetic properties of the components of the malignant tissue which are the physiologic differences between the malignant cells and their healthy counterparts. The targets realize nano-range heating, using natural nanoclusters on the cell-membrane without artificially implementing them. This energy absorption generates consequent reactions, like programmed cell-death (apoptosis) continued by immunogenic cell-death involving extended immune reactions.? The applied radiofrequency current is amplitude modulated by time-fractal modulation pattern. The accurately matched impedance realizes the self-selective mechanisms which are promoted by stochastic resonances. This complex method is a new kind of hyperthermia, named mEHT. Our objective is to analyze the problems of the selective, non-equilibrium energy absorption, and present a solution by the electromagnetic mechanisms for an effective and controllable hyperthermia in oncology.展开更多
AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carc...AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carcinoma(HCC).METHODS:Patients with advanced primary HCC were included in this study.CIK cells were perfused intraperitoneal twice a week,using 3.2 × 10 9 to 3.6 × 10 9 cells each session.Local RF hyperthermia was performed 2 h after intraperitoneal perfusion.Following an interval of one month,the next course of treatment was administered.Patients received treatment until disease progression.Tumor size,immune indices(CD3 +,CD4 +,CD3 + CD8 +,CD3 + CD56 +),alpha-fetoprotein(AFP) level,abdominal circumference and adverse events were recorded.Time to progression and overall survival(OS) were calculated.RESULTS:From June 2010 to July 2011,31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study.Patients received an average of 4.2 ± 0.6 treatment courses(range,1-8 courses).Patients were followed up for 8.3 ± 0.7 mo(range,2-12 mo).Following combination treatment,CD4 +,CD3 + CD8 + and CD3 + CD56 + cells increased from 35.78% ± 3.51%,24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48%(P = 0.016),39.67% ± 3.38%(P = 0.008) and 10.72% ± 0.67%(P = 0.001),respectively.AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL(P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm(P = 0.002).The disease control rate was 67.7%.The most common adverse events were low fever and slight abdominal erubescence,which resolved without treatment.The median time to progression was 6.1 mo.The 3-,6-and 9-mo and 1-year survival rates were 93.5%,77.4%,41.9% and 17.4%,respectively.The median OS was 8.5 mo.CONCLUSION:Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe,can efficiently improve immunological status,and may prolong survival in HCC patients.展开更多
Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with nefe...Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with neferine（Nef） in adriamycin（ADM） resistant human SGC7901/ADM gastric cancer cells.The MDR cells were heated at 42℃ and 45℃ for 30 min alone or combined with 10 μg/mL Nef.The cytotoxic effect of ADM was evaluated by MTT assay.Cellular plasma membrane lipid fluidity was detected by fluorescence polarization technique.Intracellular accumulation of ADM was monitored with high performance liquid chromatography.Mdr-1 mRNA,P-glycoprotein（P-gp）,γH2AX expression and γH2AX foci formation were determined by real-time PCR,Western blot and immunocytochemical staining respectively.It was found that different heating methods induced different cytotoxic effects.Water submerged hyperthermia had the strongest cytotoxicity of ADM and Nef combined with hyperthermia had a synergistic cytotoxicity of ADM in the MDR cells.The water submerged hyperthermia increased the cell membrane fluidity.Both water submerged hyperthermia and Nef increased the intracellular accumulation of ADM.The water submerged hyperthermia and Nef down-regulated the expression of mdr-1 mRNA and P-gp.The water submerged hyperthermia could damage DNA and increase the γH2AX expression of SGC7901/ADM cells.The higher temperature was,the worse effect was.Our results show that combined treatment of hyperthermia with Nef can synergistically reverse MDR in human SGC7901/ADM gastric cancer cells.展开更多
AIM:To study the methods of preparing the magnetic nano-microspheres of Fe2O3 and As2O3/Fe2O3 complexes and their therapeutic effects with magnetic fluid hyperthermia(MFH). METHODS:Nanospheres were prepared by chemica...AIM:To study the methods of preparing the magnetic nano-microspheres of Fe2O3 and As2O3/Fe2O3 complexes and their therapeutic effects with magnetic fluid hyperthermia(MFH). METHODS:Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed.Hemolysis,micronucleus,cell viability,and LD50 along with other in vivo tests were performed to evaluate the Fe2O3 microsphere biocompatibility.The inhibition ratio of tumors after Fe2O3 and As2O3/Fe2O3 injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. RESULTS:Fe2O3 and As2O3/Fe2O3 particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope.Upon exposure to an alternating magnetic field(AMF),the temperature of the suspension of magnetic particles increased to 41-51℃,depending on different particle concentrations,and remained stable thereafter.Nanosized Fe2O3 microspheres are a new kind of biomaterial without cytotoxic effects.The LD50 of both Fe2O3 and As2O3/Fe2O3 in mice was higher than 5 g/kg.One to four weeks after Fe2O3 and As2O3/Fe2O3 complex injections into healthy pig livers,no significant differences were found in serum AST,ALT,BUN and Cr levels among thepigs of all groups(P>0.05),and no obvious pathological alterations were observed.After exposure to alternating magnetic fields,the inhibition ratio of the tumors was significantly different from controls in the Fe2O3 and As2O3/Fe2O3 groups(68.74% and 82.79%,respectively; P<0.01).Tumors of mice in treatment groups showed obvious necrosis,while normal tissues adjoining the tumor and internal organs did not. CONCLUSION:Fe2O3 and As2O3/Fe2O3 complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore,nanospheres are ideal carriers for tumortargeted therapy.展开更多
AIM:To investigate the change in expression of p53 ,Bcl-2 ,and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy and t...AIM:To investigate the change in expression of p53 ,Bcl-2 ,and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy and thermochemoradiotherapy. METHODS:Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43℃,60 min),the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches:hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy,and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane,cytoplasm and nuclei of tumor cells of p53,Bcl-2,and Bax after treatment,were observed by immunohistochemistry staining. RESULTS:All of the six treatment modalities down-regulated the expression of p53,Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia,with chemotherapy,and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 ± 0.009 vs 0.155 ± 0.0115,P < 0.01) and Bcl-2 (0.086 ± 0.010 vs 0.026 ± 0.0170,P < 0.01) and up-regulating Bax expression (0.091 ± 0.0013 vs 0.207 ± 0.027,P < 0.01) compared with any single therapy.CONCLUSION:Hyperthermia enhances the effect of radio-and chemotherapy on tumors by changing the expression of apoptosis genes,such as p53,Bcl-2 and Bax.展开更多
AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2...AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2(colon cancer cell line) and T3M4(pancreatic cancer cell line) were treated by cisplatin and different temperature setting(37 ℃ to 45 ℃) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7 ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 ℃ to 41 ℃ in neither cancer cell line. However, a temperature of 43 ℃ enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3 M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3 M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 ℃ by 30%, 20%, and 18% in AGS, Caco-2, and T3 M4 cells, respectively.CONCLUSION In addition to cisplatin, hyperthermia up to 43 ℃ does not affect the viability of cancer cells in a synergistic manner.展开更多
Thirty pathologically diagnosed patients with grade Ⅲ-Ⅳ primary or recurrent malignant glioma （tumor diameter 3-7 cm） were randomly divided into two groups. The control group underwent conventional radiotherapy an...Thirty pathologically diagnosed patients with grade Ⅲ-Ⅳ primary or recurrent malignant glioma （tumor diameter 3-7 cm） were randomly divided into two groups. The control group underwent conventional radiotherapy and chemotherapy. In the hyperthermia group, primary cases received hyperthermia treatment, and patients with recurrent tumors were treated with hyperthermia in com- bination with radiotherapy and chemotherapy. Hyperthermia treatment was administered using a 13.56-MHz radio frequency hyperthermia device. Electrodes were inserted into the tumor with the aid of a CT-guided stereotactic apparatus and heat was applied for 1 hour. Dudng 3 months a^er hyperthermia, patients were evaluated with head CT or MRI every month. Gliomas in the hyper- thermia group exhibited growth retardation or growth termination. Necrosis was evident in 80% of the heated tumor tissue and there was a decrease in tumor diameter. Our findings indicate that ra- dio frequency hyperthermia has a beneficial effect in the treatment of malignant glioma.展开更多
Objective： To assess the safety and clinical antiangiogenic effect of recombinant adenovirus-p53 （rAd-p53） combined with hyperthermia plus or not plus radiotherapy in advanced cancer. Methods： Expression of Vascul...Objective： To assess the safety and clinical antiangiogenic effect of recombinant adenovirus-p53 （rAd-p53） combined with hyperthermia plus or not plus radiotherapy in advanced cancer. Methods： Expression of Vascular epithelial growth factor （VEGF） after intratumoral injection of rAd-p53 was assayed by immunohistochemistry （IHC） imaging. Forty-four patients with advanced cancer were enrolled into this clinical study. The patients were intratumorally injected with rAd-p53 （Gendicine） at a dose of 1×1012 vp once a week, with a total of 4-54 （mean 7.7） times. Total of 4-29 （mean 8.5） times of hyperthermia was given to the patients. Among the 44 patients, 30 patients were concurrently added with radiotherapy of a total dose 30-76 Gy/15-38 f/3-8 w （mean 58 Gy）. Results： Before and after intratumoral injection of rAd-p53, the VEGF IHC positive cell scores were 2.80 and 1.50, respectively （P=0.031）. The treatment of rAd-p53 combined with hyperthermia plus or not plus radiotherapy in advanced cancer achieved CR rate of 13.60% （6/44）, and PR rate of 29.6% （13/44）, and thus the effective rate was 43.2%. In addition to 6 patients with CR, 19 patients （19/38, 50.0%） had low density area （LDA） of more than 50% area on CT image within tumor indicating tumor tissue necrosis. Conclusions： Our data indicate that rAd-p53 inhibits VEGF expression and angiogenesis, and promotes tumor necrosis and shrinkage induced by hyperthermia plus or not plus radiotherapy in advanced cancer.展开更多
Magnetite (Fe3O4) nanoparticles with different magnetic properties were prepared by coprecipitation of Fe3+ and Fe2+ with aqueous NaOH solution. The inductive heat properties of Fe3O4 nanoparticles in an alternating c...Magnetite (Fe3O4) nanoparticles with different magnetic properties were prepared by coprecipitation of Fe3+ and Fe2+ with aqueous NaOH solution. The inductive heat properties of Fe3O4 nanoparticles in an alternating current (AC) magnetic field were investigated for local hyperthermia. The maximum saturation magnetization Ms of Fe3O4 nanoparticles is 65.53 emu·g-1 under the optimum conditions of Fe3+: Fe2+ molar ratio at 1.8:1. The Ms of Fe3O4 nanoparticles decreased as the Fe3+/Fe2+ molar ratio increased. But the coercivity Hc increases with the increasing of Fe3+/Fe2+ molar ratio. Exposed in the AC magnetic field for 29 min, the temperatures of physiological saline suspension containing Fe3O4 nanoparticles were 42-97.5 ℃. The inductive heat property of Fe3O4 nanoparticles in AC magnetic field decreases as Hc increases, but increases with the increasing of Ms. The Fe3O4 nanoparticles would be useful as good thermoseeds for localized hyperthermia treatment of cancers.展开更多
AIM:To investigate the effect of hyperthermia on hy-poxia-induced epithelial-mesenchymal transition (EMT) in HepG2 hepatocellular carcinoma (HCC) cells, and its mechanism. METHODS:Cells were treated with hyperthermia ...AIM:To investigate the effect of hyperthermia on hy-poxia-induced epithelial-mesenchymal transition (EMT) in HepG2 hepatocellular carcinoma (HCC) cells, and its mechanism. METHODS:Cells were treated with hyperthermia at 43 ℃ for 0.5 h, followed by incubation under hypoxic or normoxic conditions for 72 h. Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by immunofluorescence assay or Western blot. The protein and mRNA expressions of Snail were also determined by Western blot and reverse transcrip-tion-polymerase chain reaction. Cell migratory capacity was evaluated. RESULTS:Hypoxia induced EMT in HepG2 cells, which was evidenced by morphological, molecular and func-tional changes, including the formation of a spindle shape and the loss of cell contact. The expression of E-cadherin was decreased but the expression of vimentin was increased; also, the migratory capability was increased by 2.2 ± 0.20-fold as compared with normoxia. However, those effects were inhibited by hyperthermia pretreatment. Furthermore, protein synthesis and mRNA expression of Snail in the cells were enhanced by hy-poxia as compared with normoxia, and also significantly inhibited by hyperthermia pretreatment. CONCLUSION:Hyperthermia may inhibit hypoxia-induced EMT in HepG2 HCC cells, and the mechanism may involve inhibition of induced expression of Snail.展开更多
Aim To prepare and characterize ferromagnetic fluids for hyperthermia of tumor. Methods Ferromagnetic fluids （FFs） of magnetite （Fe3O4） was prepared in the presence of polyethylene glycol （PEG-6000） by chemical ...Aim To prepare and characterize ferromagnetic fluids for hyperthermia of tumor. Methods Ferromagnetic fluids （FFs） of magnetite （Fe3O4） was prepared in the presence of polyethylene glycol （PEG-6000） by chemical precipitation method. The iron content of the FFs was determined by spectrophotometric method using o-phenanthroline. The FFs/PEG-6000 was characterized by transmission electron microscopy （TEM）, X-ray diffraction （XRD）, infrared spectrometry （IR）, and vibrating sample magnetometer （VSM）. Heating effects of the FFs was measured in an alternating magnetic field in vitro. The hyperthermia of FFs in a rabbit was performed. Results The FFs/PEG-6000 was proved to be composed of Fe3O4 by XRD and IR. TEM showed that the ferromagnetic particles appeared to be almost spherical and dispersed well The average particle size was 13.3 ± 3.8 nm by XRD. The saturation magnetization and residual magnetization of the FFs were 23.39 A/m （1.556 emu/g） and 0.56 A/m （0.02604 emu/g）, respectively. The coercive force was 12 Oe. The specific absorption rate （SAR） of FFs was 69 ± 10W/g [Fe]. After direct injection of FFs to hepatic VX2 carcinoma of a rabbit, the temperature in the core of the tumor was between 41 - 46 ℃ in an alternating magnetic field. Conclusion FFs/PEG-6000 was expected to be useful in hyperthermia of tumor.展开更多
文摘Malignant hyperthermia(MH)is a genetic disorder of skeletal muscle cells that affects muscle cytoplasmic calcium homeostasis,with high mortality and low morbidity.Generally,it presents with non-specific signs of a hypermetabolic response,including high fever,tachycardia,and elevated end-tidal carbon dioxide(ETCO_(2)).The successful treatment lies in the timely recognition and early use of dantrolene.[1]As an inhibitor of Ca2+release through ryanodine receptor(RYR)channels,the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca2+signaling and a lifesaving treatment for MH.[2]Dominant mutations in the skeletal muscle RYR1 gene are well-recognized causes of both malignant hyperthermia susceptibility(MHS)and central core disease(CCD).
文摘The preparation of γ-Fe<sub>2</sub>O<sub>3</sub>/Gd<sub>2</sub>O<sub>3</sub> nanocomposite for possible use in magnetic hyperthermia application was done by ball milling technique. The nanocomposite was characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The heating efficiency and the effect of milling time (5 h and 30 h) on the structural and magnetic properties of the nanocomposite were reported. XRD analysis confirms the formation of the nanocomposite, while magnetization measurements show that the milled sample present hysteresis with low coercivity and remanence. The specific absorption rate (SAR) under an alternating magnetic field is investigated as a function of the milling time. A mean heating efficiency of 68 W/g and 28.7 W/g are obtained for 5 h and 30 h milling times respectively at 332 kHz and 170 Oe. The results showed that the obtained nanocomposite for 5 h milling time is a promising candidate for magnetic hyperthermia due to his properties which show an interesting magnetic behavior and high specific absorption rate.
文摘Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.
文摘Magnetic particle imaging(MPI)technology can generate a real-time magnetic nanoparticle(MNP)distribution image for biological tissues,and its use can overcome the limitations imposed in magnetic hyperthermia treatments by the unpredictable MNP distribution after the intratumoral injection of nanofluid.However,the MNP concentration distribution is generally difficult to be extracted from MPI images.This study proposes an approach to extract the corresponding concentration value of each pixel from an MPI image by a least squares method(LSM),which is then translated as MNP concentration distribution by an interpolation function.The resulting MPI-based concentration distribution is used to evaluate the treatment effect and the results are compared with the ones of two baseline cases under the same dose:uniform distribution and MPI-based distribution considering diffusion.Additionally,the treatment effect for all these cases is affected by the blood perfusion rate,which is also investigated deeply in this study.The results demonstrate that the proposed method can be used to effectively reconstruct the concentration distribution from MPI images,and that the weighted LSM considering a quartic polynomial for interpolation provides the best results with respect to other cases considered.Furthermore,the results show that the uniformity of MNP distribution has a positive correlation with both therapeutic temperature distribution and thermal damage degree for the same dose and a critical power dissipation value in the MNPs.The MNPs uniformity inside biological tissue can be improved by the diffusion behavior after the nanofluid injection,which can ultimately reflect as an improvement of treatment effect.In addition,the blood perfusion rate considering local temperature can have a positive effect on the treatment compared to the case which considers a constant value during magnetic hyperthermia.
文摘Hyperthermia treatment using appropriate magnetic materials in an alternating magnetic field to generate heat has been proposed as a low-invasive cancer treatment method. Magnetite iron oxide nanoparticles (Fe<sub>3</sub>O<sub>4</sub>) are expected to be an appropriate type of magnetic material for this purpose due to its biocompatibility. Several polymers are used to Fe<sub>3</sub>O<sub>4</sub> MNPs to avoid or decrease agglomeration, and in most cases increase dispersion stability. In this review, we will give briefly how these coated magnetite nanoparticles (PMNPs) are synthesized in the first part. The main characterization techniques usually used to study the properties of these MNPs are prseneted in the second part. Finally, most recent results on the heating ability of polymeric coated magnetite nanoparticles (PMNPs) are given in the last part of this review.
文摘BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.
文摘BACKGROUND Malignant hyperthermia(MH)is a hypermetabolic disorder of skeletal muscles triggered by exposure to volatile anesthetics and depolarizing muscular relaxants.It manifests with clinical presentations such as tachycardia,muscle rigidity,hyperpyrexia,and rhabdomyolysis in genetically predisposed individuals with ryanodine receptor or calcium voltage-gated channel subunit alpha1 S mutations.Local anesthetics,such as lidocaine,are generally considered safe;however,complications can arise,albeit rarely.Lidocaine administration has been reported to induce hypermetabolic reactions resembling MH in susceptible individuals.The exact mechanism by which lidocaine might trigger MH is not fully understood.Although some mechanisms are postulated,further research is needed for a better understanding of this.CASE SUMMARY We present the case of MH in a 43-year-old male patient with an unknown genetic predisposition following a lidocaine injection during a dental procedure.This case serves as a reminder that while the occurrence of lidocaine-induced MH is rare,lidocaine can still trigger this life-threatening condition.Therefore,caution should be exercised when administering lidocaine to individuals who may be susceptible to MH.It is important to note that prompt intervention played a crucial role in managing the patient’s symptoms.Upon recognizing the early signs of MH,aggressive measures were initiated,including vigorous intravenous normal saline administration and lorazepam.Due to the effectiveness of these interventions,the administration of dantrolene sodium,a specific antidote for MH,was deferred.CONCLUSION This case highlighted the significance of vigilant monitoring and swift action in mitigating the detrimental effects of lidocaine-induced MH.Caution should be exercised when administering lidocaine to individuals who may be predisposed to MH.It is very important to be aware and vigilant of the signs and symptoms of MH as early recognition and treatment intervention are important to prevent serious complications to decrease mortality.
文摘Objective: To investigate the electromagnetic field and specific absorptionrate (SAR) distribution of different structure applicators with different depths for treating bonetumors using microwave hyperthermia. Methods: The finite element method (FEM) was used to calculate,electromagnetic field and SAR distribution. Two different structure applicators were simulated. Theone is simple coaxial antenna, which has been successfully used in clinic treating bone tumors inTangdu hospital of the Forth Military Medical University several years. It was formed by a coaxialcable peeled off the out copper at end. The other applicator was coaxial- slot antenna, which waswidely used in microwave hyperthermia. The applicator inserted into the cylindrical bone withdifferent depths, and worked at the frequency of 2 450 MHz. Results: The electric field and SARgenerated by the simple coaxial applicator were mainly concentrated out the tissues, and were notuniform in the tissues, while the coaxial- slot applicator well transmits the electric field and SARinto the tissues, and can easily treat different position by adjusting the slat position.Conclusion: The results calculated by EFM, were well accordant with the experimental and clinicalresulls, and will be important for improving the clinical effects of microwave hyperthermia.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.81172182,81172120,and 81041040)the 7th Singapore–China Cooperative Research Project Call between Agency of Science,Technology and Research(A*STAR)+1 种基金Singapore and the Ministry of Science and Technology(MOST),China(Grant No.20113010006)the National Key Technology Support Program(Grant No.2012857818)
文摘Research progress and frontiers of magnetic-mediated hyperthermia （MMH） are presented, along with clinical trials in Germany, the US, Japan, and China. Special attention is focused on MMH mediated by magnetic nanoparticles, and multifunctional magnetic devices for cancer multimodality treatment are also introduced.
文摘One of the most frequently applied bioelectromagnetic effects is the deep heating of the living species with EMF energy. Despite its long history, hyperthermia is a rarely applied oncotherapy. The reason is its controversial results and complicated control. One of the solutions is concentrating the electromagnetic energy nanoscopically on the parts of the malignant cells instead of heating up the complete tumor-mass. This approach is a kind of non-uniform energy absorption, providing energy liberation only in the selected regions. The energy-absorption of the malignant cells targets the membranes and creates a situation far from thermal equilibrium. The selection of the malignant cells is based on their decided differences from their healthy counterparts. The distinguishing parameters are the electromagnetic properties of the components of the malignant tissue which are the physiologic differences between the malignant cells and their healthy counterparts. The targets realize nano-range heating, using natural nanoclusters on the cell-membrane without artificially implementing them. This energy absorption generates consequent reactions, like programmed cell-death (apoptosis) continued by immunogenic cell-death involving extended immune reactions.? The applied radiofrequency current is amplitude modulated by time-fractal modulation pattern. The accurately matched impedance realizes the self-selective mechanisms which are promoted by stochastic resonances. This complex method is a new kind of hyperthermia, named mEHT. Our objective is to analyze the problems of the selective, non-equilibrium energy absorption, and present a solution by the electromagnetic mechanisms for an effective and controllable hyperthermia in oncology.
基金Supported by The National Natural Science Foundation of China,No.81273814
文摘AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carcinoma(HCC).METHODS:Patients with advanced primary HCC were included in this study.CIK cells were perfused intraperitoneal twice a week,using 3.2 × 10 9 to 3.6 × 10 9 cells each session.Local RF hyperthermia was performed 2 h after intraperitoneal perfusion.Following an interval of one month,the next course of treatment was administered.Patients received treatment until disease progression.Tumor size,immune indices(CD3 +,CD4 +,CD3 + CD8 +,CD3 + CD56 +),alpha-fetoprotein(AFP) level,abdominal circumference and adverse events were recorded.Time to progression and overall survival(OS) were calculated.RESULTS:From June 2010 to July 2011,31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study.Patients received an average of 4.2 ± 0.6 treatment courses(range,1-8 courses).Patients were followed up for 8.3 ± 0.7 mo(range,2-12 mo).Following combination treatment,CD4 +,CD3 + CD8 + and CD3 + CD56 + cells increased from 35.78% ± 3.51%,24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48%(P = 0.016),39.67% ± 3.38%(P = 0.008) and 10.72% ± 0.67%(P = 0.001),respectively.AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL(P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm(P = 0.002).The disease control rate was 67.7%.The most common adverse events were low fever and slight abdominal erubescence,which resolved without treatment.The median time to progression was 6.1 mo.The 3-,6-and 9-mo and 1-year survival rates were 93.5%,77.4%,41.9% and 17.4%,respectively.The median OS was 8.5 mo.CONCLUSION:Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe,can efficiently improve immunological status,and may prolong survival in HCC patients.
基金supported by grants from Natural Science Foundation of Hunan Province(No.07JJ4009)Project of the Department of Science and Technology of Hunan Province(No. 2010FJ6029)+2 种基金Research and Innovation Conditions Project of Hunan Province(No.2010TT2034)125 Talent Project of the Third Xiangya Hospital of Central South Universitythe Freedom Explore Program of Central South University(No. 2011QNZT193),China
文摘Multidrug resistance（MDR） plays a major obstacle to successful gastric cancer chemotherapy.The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with neferine（Nef） in adriamycin（ADM） resistant human SGC7901/ADM gastric cancer cells.The MDR cells were heated at 42℃ and 45℃ for 30 min alone or combined with 10 μg/mL Nef.The cytotoxic effect of ADM was evaluated by MTT assay.Cellular plasma membrane lipid fluidity was detected by fluorescence polarization technique.Intracellular accumulation of ADM was monitored with high performance liquid chromatography.Mdr-1 mRNA,P-glycoprotein（P-gp）,γH2AX expression and γH2AX foci formation were determined by real-time PCR,Western blot and immunocytochemical staining respectively.It was found that different heating methods induced different cytotoxic effects.Water submerged hyperthermia had the strongest cytotoxicity of ADM and Nef combined with hyperthermia had a synergistic cytotoxicity of ADM in the MDR cells.The water submerged hyperthermia increased the cell membrane fluidity.Both water submerged hyperthermia and Nef increased the intracellular accumulation of ADM.The water submerged hyperthermia and Nef down-regulated the expression of mdr-1 mRNA and P-gp.The water submerged hyperthermia could damage DNA and increase the γH2AX expression of SGC7901/ADM cells.The higher temperature was,the worse effect was.Our results show that combined treatment of hyperthermia with Nef can synergistically reverse MDR in human SGC7901/ADM gastric cancer cells.
基金Supported by The National Natural Science Foundation of China,30770584the State 863 Plan,2002AA302207,2007AA03Z356
文摘AIM:To study the methods of preparing the magnetic nano-microspheres of Fe2O3 and As2O3/Fe2O3 complexes and their therapeutic effects with magnetic fluid hyperthermia(MFH). METHODS:Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed.Hemolysis,micronucleus,cell viability,and LD50 along with other in vivo tests were performed to evaluate the Fe2O3 microsphere biocompatibility.The inhibition ratio of tumors after Fe2O3 and As2O3/Fe2O3 injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. RESULTS:Fe2O3 and As2O3/Fe2O3 particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope.Upon exposure to an alternating magnetic field(AMF),the temperature of the suspension of magnetic particles increased to 41-51℃,depending on different particle concentrations,and remained stable thereafter.Nanosized Fe2O3 microspheres are a new kind of biomaterial without cytotoxic effects.The LD50 of both Fe2O3 and As2O3/Fe2O3 in mice was higher than 5 g/kg.One to four weeks after Fe2O3 and As2O3/Fe2O3 complex injections into healthy pig livers,no significant differences were found in serum AST,ALT,BUN and Cr levels among thepigs of all groups(P>0.05),and no obvious pathological alterations were observed.After exposure to alternating magnetic fields,the inhibition ratio of the tumors was significantly different from controls in the Fe2O3 and As2O3/Fe2O3 groups(68.74% and 82.79%,respectively; P<0.01).Tumors of mice in treatment groups showed obvious necrosis,while normal tissues adjoining the tumor and internal organs did not. CONCLUSION:Fe2O3 and As2O3/Fe2O3 complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore,nanospheres are ideal carriers for tumortargeted therapy.
基金Supported by the Clinical Research Foundation of Tianjin Medical University, No. 2002KY18
文摘AIM:To investigate the change in expression of p53 ,Bcl-2 ,and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy and thermochemoradiotherapy. METHODS:Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43℃,60 min),the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches:hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy,and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane,cytoplasm and nuclei of tumor cells of p53,Bcl-2,and Bax after treatment,were observed by immunohistochemistry staining. RESULTS:All of the six treatment modalities down-regulated the expression of p53,Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia,with chemotherapy,and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 ± 0.009 vs 0.155 ± 0.0115,P < 0.01) and Bcl-2 (0.086 ± 0.010 vs 0.026 ± 0.0170,P < 0.01) and up-regulating Bax expression (0.091 ± 0.0013 vs 0.207 ± 0.027,P < 0.01) compared with any single therapy.CONCLUSION:Hyperthermia enhances the effect of radio-and chemotherapy on tumors by changing the expression of apoptosis genes,such as p53,Bcl-2 and Bax.
基金Supported by the Research Council of Lithuania,No.SEN-01/2015
文摘AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2(colon cancer cell line) and T3M4(pancreatic cancer cell line) were treated by cisplatin and different temperature setting(37 ℃ to 45 ℃) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7 ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 ℃ to 41 ℃ in neither cancer cell line. However, a temperature of 43 ℃ enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3 M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3 M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 ℃ by 30%, 20%, and 18% in AGS, Caco-2, and T3 M4 cells, respectively.CONCLUSION In addition to cisplatin, hyperthermia up to 43 ℃ does not affect the viability of cancer cells in a synergistic manner.
基金financially sponsored by the Overseas Returnees of Heilongjiang Province in China,No.IC03C182003-2005
文摘Thirty pathologically diagnosed patients with grade Ⅲ-Ⅳ primary or recurrent malignant glioma （tumor diameter 3-7 cm） were randomly divided into two groups. The control group underwent conventional radiotherapy and chemotherapy. In the hyperthermia group, primary cases received hyperthermia treatment, and patients with recurrent tumors were treated with hyperthermia in com- bination with radiotherapy and chemotherapy. Hyperthermia treatment was administered using a 13.56-MHz radio frequency hyperthermia device. Electrodes were inserted into the tumor with the aid of a CT-guided stereotactic apparatus and heat was applied for 1 hour. Dudng 3 months a^er hyperthermia, patients were evaluated with head CT or MRI every month. Gliomas in the hyper- thermia group exhibited growth retardation or growth termination. Necrosis was evident in 80% of the heated tumor tissue and there was a decrease in tumor diameter. Our findings indicate that ra- dio frequency hyperthermia has a beneficial effect in the treatment of malignant glioma.
文摘Objective： To assess the safety and clinical antiangiogenic effect of recombinant adenovirus-p53 （rAd-p53） combined with hyperthermia plus or not plus radiotherapy in advanced cancer. Methods： Expression of Vascular epithelial growth factor （VEGF） after intratumoral injection of rAd-p53 was assayed by immunohistochemistry （IHC） imaging. Forty-four patients with advanced cancer were enrolled into this clinical study. The patients were intratumorally injected with rAd-p53 （Gendicine） at a dose of 1×1012 vp once a week, with a total of 4-54 （mean 7.7） times. Total of 4-29 （mean 8.5） times of hyperthermia was given to the patients. Among the 44 patients, 30 patients were concurrently added with radiotherapy of a total dose 30-76 Gy/15-38 f/3-8 w （mean 58 Gy）. Results： Before and after intratumoral injection of rAd-p53, the VEGF IHC positive cell scores were 2.80 and 1.50, respectively （P=0.031）. The treatment of rAd-p53 combined with hyperthermia plus or not plus radiotherapy in advanced cancer achieved CR rate of 13.60% （6/44）, and PR rate of 29.6% （13/44）, and thus the effective rate was 43.2%. In addition to 6 patients with CR, 19 patients （19/38, 50.0%） had low density area （LDA） of more than 50% area on CT image within tumor indicating tumor tissue necrosis. Conclusions： Our data indicate that rAd-p53 inhibits VEGF expression and angiogenesis, and promotes tumor necrosis and shrinkage induced by hyperthermia plus or not plus radiotherapy in advanced cancer.
文摘Magnetite (Fe3O4) nanoparticles with different magnetic properties were prepared by coprecipitation of Fe3+ and Fe2+ with aqueous NaOH solution. The inductive heat properties of Fe3O4 nanoparticles in an alternating current (AC) magnetic field were investigated for local hyperthermia. The maximum saturation magnetization Ms of Fe3O4 nanoparticles is 65.53 emu·g-1 under the optimum conditions of Fe3+: Fe2+ molar ratio at 1.8:1. The Ms of Fe3O4 nanoparticles decreased as the Fe3+/Fe2+ molar ratio increased. But the coercivity Hc increases with the increasing of Fe3+/Fe2+ molar ratio. Exposed in the AC magnetic field for 29 min, the temperatures of physiological saline suspension containing Fe3O4 nanoparticles were 42-97.5 ℃. The inductive heat property of Fe3O4 nanoparticles in AC magnetic field decreases as Hc increases, but increases with the increasing of Ms. The Fe3O4 nanoparticles would be useful as good thermoseeds for localized hyperthermia treatment of cancers.
基金Supported by Medical Science and Technology Innovation Foundation of Nanjing Military Command of Chinese People’s Liberation Army, No. 11MA036Natural Science Foundation of China, No. 81000998
文摘AIM:To investigate the effect of hyperthermia on hy-poxia-induced epithelial-mesenchymal transition (EMT) in HepG2 hepatocellular carcinoma (HCC) cells, and its mechanism. METHODS:Cells were treated with hyperthermia at 43 ℃ for 0.5 h, followed by incubation under hypoxic or normoxic conditions for 72 h. Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by immunofluorescence assay or Western blot. The protein and mRNA expressions of Snail were also determined by Western blot and reverse transcrip-tion-polymerase chain reaction. Cell migratory capacity was evaluated. RESULTS:Hypoxia induced EMT in HepG2 cells, which was evidenced by morphological, molecular and func-tional changes, including the formation of a spindle shape and the loss of cell contact. The expression of E-cadherin was decreased but the expression of vimentin was increased; also, the migratory capability was increased by 2.2 ± 0.20-fold as compared with normoxia. However, those effects were inhibited by hyperthermia pretreatment. Furthermore, protein synthesis and mRNA expression of Snail in the cells were enhanced by hy-poxia as compared with normoxia, and also significantly inhibited by hyperthermia pretreatment. CONCLUSION:Hyperthermia may inhibit hypoxia-induced EMT in HepG2 HCC cells, and the mechanism may involve inhibition of induced expression of Snail.
文摘Aim To prepare and characterize ferromagnetic fluids for hyperthermia of tumor. Methods Ferromagnetic fluids （FFs） of magnetite （Fe3O4） was prepared in the presence of polyethylene glycol （PEG-6000） by chemical precipitation method. The iron content of the FFs was determined by spectrophotometric method using o-phenanthroline. The FFs/PEG-6000 was characterized by transmission electron microscopy （TEM）, X-ray diffraction （XRD）, infrared spectrometry （IR）, and vibrating sample magnetometer （VSM）. Heating effects of the FFs was measured in an alternating magnetic field in vitro. The hyperthermia of FFs in a rabbit was performed. Results The FFs/PEG-6000 was proved to be composed of Fe3O4 by XRD and IR. TEM showed that the ferromagnetic particles appeared to be almost spherical and dispersed well The average particle size was 13.3 ± 3.8 nm by XRD. The saturation magnetization and residual magnetization of the FFs were 23.39 A/m （1.556 emu/g） and 0.56 A/m （0.02604 emu/g）, respectively. The coercive force was 12 Oe. The specific absorption rate （SAR） of FFs was 69 ± 10W/g [Fe]. After direct injection of FFs to hepatic VX2 carcinoma of a rabbit, the temperature in the core of the tumor was between 41 - 46 ℃ in an alternating magnetic field. Conclusion FFs/PEG-6000 was expected to be useful in hyperthermia of tumor.
