Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat.

PubMed

Mete, Fatih; Kilic, Ertugrul; Somay, Adnan; Yilmaz, Bayram

2012-01-01

Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39 °C (Group I) and 41 °C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Serum corticosterone levels (3.22 ± 1.3) were significantly reduced in the 39 °C (1.3 ± 0.9) and 41 °C (1.09 ± 0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41 °C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39 °C compared to the control group (P<0.01). These parameters were more pronounced in the 41 °C hyperthermia group. Our results show that heat exposure-induced stress may cause delayed reduction in serum corticosterone levels which may be associated with behavioural deficits in pre-pubertal male rats.

A magnetic induction heating system with multi-cascaded coils and adjustable magnetic circuit for hyperthermia.

PubMed

Huang, Chi-Fang; Chao, Hsuan-Yi; Chang, Hsun-Hao; Lin, Xi-Zhang

2016-01-01

Based on the characteristics of cancer cells that cannot survive in an environment with temperature over 42 °C, a magnetic induction heating system for cancer treatment is developed in this work. First, the methods and analyses for designing the multi-cascaded coils magnetic induction hyperthermia system are proposed, such as internal impedance measurement of power generator, impedance matching of coils, and analysis of the system. Besides, characteristics of the system are simulated by a full-wave package for engineering optimization. Furthermore, by considering the safety factor of patients, a two-sectional needle is designed for hyperthermia. Finally, this system is employed to test the liver of swine in ex-vivo experiments, and through Hematoxylin and Eosin (H&E) stain and NADPH oxidase activity assay, the feasibility of this system is verified.

The changing face of malignant hyperthermia: less fulminant, more insidious..

PubMed

Heytens, L; Forget, P; Scholtès, J L; Veyckemans, F

2015-07-01

Modern anaesthetic techniques have resulted in the clinical presentation of malignant hyperthermia to be more often indolent and/or insidious than truly fulminant, as previously known in the anaesthetic community. We present four recently referred cases to illustrate this point: one late-onset case, two patients with slowly progressive hypercapnia as the sole sign and a fourth patient with postoperative myalgias and elevated creatine kinase. We also discuss the reasons for the shift in typical clinical presentation. The more insidious character of malignant hyperthermia is most likely due to the lower triggering potency of modern volatile anaesthetics, the mitigating effects of several intravenous drugs (neuromuscular blocking agents, alpha 2 adrenergic receptor agonists, beta adrenergic blockade) or techniques (neuraxial anaesthesia) and the routine use of end-tidal CO2 monitoring leading to the early withdrawal of triggering drugs. Awareness among anaesthetists of this change in presentation is important since the clinical diagnosis is often more doubtful and, if corroborative evidence is not sought, the diagnosis may be delayed or missed altogether.

Whole-body fluid distribution in humans during dehydration and recovery, before and after humid-heat acclimation induced using controlled hyperthermia.

PubMed

Patterson, M J; Stocks, J M; Taylor, N A S

2014-04-01

This experiment was designed to test the hypothesis that the plasma volume is not selectively defended during exercise- and heat-induced dehydration following humid-heat acclimation. Eight physically active males were heat acclimated (39.8 °C, relative humidity 59.2%) using 17 days of controlled hyperthermia (core temperature: 38.5 °C). Inter-compartmental fluid losses and movements were tracked (radioisotopes and Evans blue dye) during progressive dehydration (cycling) in these same conditions and also during a resting recovery without fluid replacement (28 °C), before (day 1), during (day 8) and after heat acclimation (day 22). On days 8 and 22, there were significant increases in total body water, interstitial fluid and plasma volume (P < 0.05), but the intracellular compartments did not change (P > 0.05). The baseline plasma volume remained expanded throughout: 43.4 [±2.6 (day 1)], 49.1 [±2.4 (day 8); P < 0.05] and 48.9 mL kg(-1) [±3.0 (day 22); P < 0.05]. During progressive dehydration, plasma reductions of 9.0% (±0.9: day 1), 12.4% (±1.6: day 8) and 13.6% (±1.2: day 22) were observed, with day 8 and 22 losses significantly exceeding day 1 (P < 0.05). During recovery, plasma volume restoration commenced, with the intracellular fluid contribution becoming more pronounced as acclimation progressed. It is concluded that the plasma volume was not defended more vigorously following humid-heat acclimation. Indeed, a greater fluid loss may well underlie the mechanisms for enhancing plasma volume recovery when heat acclimation is induced using the controlled-hyperthermia technique. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paudel, N; Shvydka, D; Karpov, V

Purpose: Hyperthermia, an established method of cancer treatment used in adjuvant to radiation and chemotherapy, can utilize metallic nanoparticles (NPs) for tumor heating with a microwave electromagnetic field. The high surface-area-to-volume ratio of nanoparticles makes them effective catalysts for free radical generation, thus amplifying the cell-killing effect of hyperthermia. We explore the effect of gold and platinum NPs in generating free radicals in aqueous media under a microwave field. Methods: Spin trap 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was mixed separately with 3.2 nm Mesogold and Mesoplatinum colloidal nanoparticle suspensions in deionized water to trap radicals. The mixtures were injected into a number ofmore » glass capillaries and exposed to the 9.68GHz microwave field of an electron paramagnetic resonance (EPR) spectrometer. The microwave radiation from the spectrometer served to both generate and detect the trapped radicals. Each sample was scanned at 12mW microwave power to obtain the initial signal of hydroxyl radicals (OH.), then at 39.8mW followed by 79.8 or 125mW, and finally re-scanned at 12mW. Radical signal intensities obtained by double integration of EPR spectra from the initial and the final scans were then compared. Results: Nanoparticle samples had no intentionally-added free radicals before the initial measurement. While samples with DMPO-water solution showed no OH. signal, all those with AuNPs or PtNPs developed an OH. signal during their first exposure to the microwave field. Depending upon the applied microwave power and time interval between the initial and the final EPR scans, an OH. intensity increase of ∼10-60% was found. This contradicts the typical trend of exponential decay of the OH. signal with time. Conclusion: The consistent increase in OH. intensity establishes that gold and platinum nanoparticles facilitate free radical generation under microwave irradiation. Our results suggest that NP-aided hyperthermia is accompanied by the generation of free radicals, which enhance the cell-killing effects of hyperthermia.« less

Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat

PubMed Central

Mete, Fatih; Kilic, Ertugrul; Somay, Adnan; Yilmaz, Bayram

2012-01-01

Background & objectives: Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Methods: Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39°C (Group I) and 41°C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Results: Serum corticosterone levels (3.22±1.3) were significantly reduced in the 39°C (1.3±0.9) and 41°C (1.09±0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41°C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39°C compared to the control group (P<0.01). These parameters were more pronounced in the 41°C hyperthermia group. Interpretation & conclusions: Our results show that heat exposure-induced stress may cause delayed reduction in serum corticosterone levels which may be associated with behavioural deficits in pre-pubertal male rats. PMID:22446867

Localised heating of tumours utilising injectable magnetic nanoparticles for hyperthermia cancer therapy.

PubMed

Tseng, H-Y; Lee, G-B; Lee, C-Y; Shih, Y-H; Lin, X-Z

2009-06-01

This study reports an investigation of hyperthermia cancer therapy utilising an alternating magnetic field to induce a localised temperature increase on tumours by using injectable magnetic nanoparticles. In-vitro and in-vivo experiments represent the feasibility of hyperthermia cancer therapy. A feedback temperature control system was first developed to keep the nanoparticles at a constant temperature to prevent overheating in the tumours such that a safer and more precise cancer therapy becomes feasible. By using the feedback temperature control system, magnetic nanoparticles can be heated up to the specific constant temperatures, 37, 40, 42, 45, 46 and 47 degrees C, respectively, with a variation less than 0.2 degrees C. With this approach, the in-vitro survival rate of tumour cells at different temperatures can be systematically explored. It was experimentally found that the survival rate of cancer cells can be greatly reduced while CT-26 cancer cells were heated above 45 degrees C. Besides, localised temperatures increase as high as 59.5 degrees C can be successfully generated in rat livers by using the proposed method. Finally, complete regression of tumour was achieved. The developed method used injectable magnetic nanoparticles and may provide a promising approach for hyperthermia cancer therapy.

Thermal Dose Fractionation Affects Tumor Physiologic Response

PubMed Central

Thrall, Donald E; Maccarini, Paolo; Stauffer, Paul; MacFall, James; Hauck, Marlene; Snyder, Stacey; Case, Beth; Linder, Keith; Lan, Lan; McCall, Linda; Dewhirst, Mark W.

2013-01-01

Purpose It is unknown whether a thermal dose should be administered using a few large fractions with higher temperatures or a larger number of fractions with lower temperatures. To evaluate this, we assessed the effect of administering the same total thermal dose, approximately 30 CEM43T90, in 1 versus 3–4 fractions per week, over 5 weeks. Materials and Methods Canine sarcomas were randomized to receive one of the hyperthermia fractionation schemes along with fractionated radiotherapy. Tumor response was based on changes in tumor volume, oxygenation, water diffusion quantified using MRI, and a panel of histologic and immunohistochemical endpoints. Results There was a greater reduction in tumor volume and water diffusion at the end of therapy In tumors receiving 1 hyperthermia fraction per week. There was a weak but significant association between improved tumor oxygenation 24 hours after the first hyperthermia treatment and extent of volume reduction at the end of therapy. Finally, the direction of change of HIF 1α and CA IX immunoreactivity after the first hyperthermia fraction was similar and there was an inverse relationship between temperature and the direction of change of CA IX. There were no significant changes in interstitial fluid pressure, VEGF, wVf, apoptosis or necrosis as a function of treatment group or temperature. Conclusions We did not identify an advantage to a 3–4/week hyperthermia prescription and response data pointed to a 1/week prescription being superior. PMID:22804741

Gold nanorod-based poly(lactic-co-glycolic acid) with manganese dioxide core-shell structured multifunctional nanoplatform for cancer theranostic applications.

PubMed

Wang, Lei; Li, Dong; Hao, Yongwei; Niu, Mengya; Hu, Yujie; Zhao, Hongjuan; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

2017-01-01

Recently, photothermal therapy has become a promising strategy in tumor treatment. However, the therapeutic effect was seriously hampered by the low tissue penetration of laser. Therefore, in this study, radiofrequency (RF) with better tissue penetration was used for tumor hyperthermia. First, one type of gold nanorods (AuNRs) suitable for RF hyperthermia was selected. Then, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with AuNRs and docetaxel (DTX) (PLGA/AuNR/DTX) NPs were constructed. Finally, manganese dioxide (MnO 2 ) ultrathin nanofilms were coated on the surfaces of PLGA/AuNR/DTX NPs by the reduction of KMnO 4 to construct the PLGA/AuNR/DTX@MnO 2 drug delivery system. This drug delivery system can not only be used for the combined therapy of chemotherapy and RF hyperthermia but can also produce Mn 2+ to enable magnetic resonance imaging. Furthermore, the RF hyperthermia and the degradation of MnO 2 can significantly promote the controlled drug release in a tumor region. The in vitro and in vivo results suggested that the PLGA/AuNR/DTX@MnO 2 multifunctional drug delivery system is a promising nanoplatform for effective cancer theranostic applications.

Gold nanorod–based poly(lactic-co-glycolic acid) with manganese dioxide core–shell structured multifunctional nanoplatform for cancer theranostic applications

PubMed Central

Wang, Lei; Li, Dong; Hao, Yongwei; Niu, Mengya; Hu, Yujie; Zhao, Hongjuan; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

2017-01-01

Recently, photothermal therapy has become a promising strategy in tumor treatment. However, the therapeutic effect was seriously hampered by the low tissue penetration of laser. Therefore, in this study, radiofrequency (RF) with better tissue penetration was used for tumor hyperthermia. First, one type of gold nanorods (AuNRs) suitable for RF hyperthermia was selected. Then, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with AuNRs and docetaxel (DTX) (PLGA/AuNR/DTX) NPs were constructed. Finally, manganese dioxide (MnO2) ultrathin nanofilms were coated on the surfaces of PLGA/AuNR/DTX NPs by the reduction of KMnO4 to construct the PLGA/AuNR/DTX@MnO2 drug delivery system. This drug delivery system can not only be used for the combined therapy of chemotherapy and RF hyperthermia but can also produce Mn2+ to enable magnetic resonance imaging. Furthermore, the RF hyperthermia and the degradation of MnO2 can significantly promote the controlled drug release in a tumor region. The in vitro and in vivo results suggested that the PLGA/AuNR/DTX@MnO2 multifunctional drug delivery system is a promising nanoplatform for effective cancer theranostic applications. PMID:28450782

Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

NASA Astrophysics Data System (ADS)

de Paula, Leonardo B.; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.; Tedesco, Antonio C.

2015-04-01

The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×1013 or 1.50×1013 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×1013 or 1.50×1013 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments.

Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

PubMed Central

Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

2013-01-01

Abstract Background and Purpose: The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. Materials and Methods: A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. Results: The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Conclusions: Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia. PMID:24112045

Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study

PubMed Central

GADALETA-CALDAROLA, GENNARO; INFUSINO, STEFANIA; GALISE, IDA; RANIERI, GIROLAMO; VINCIARELLI, GIANLUCA; FAZIO, VITO; DIVELLA, ROSA; DANIELE, ANTONELLA; FILIPPELLI, GIANFRANCO; GADALETA, COSMO DAMIANO

2014-01-01

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC. PMID:25202410

Role of CTGF in sensitivity to hyperthermia in ovarian and uterine cancers

DOE PAGES

Hatakeyama, Hiroto; Wu, Sherry Y.; Lyons, Yasmin A.; ...

2016-11-01

Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. Lastly, CTGF silencingmore » aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.« less

The induction of hyperthermia in rabbit liver by means of duplex stainless steel thermoseeds.

PubMed

Park, Byeong Ho; Koo, Bong Sig; Kim, Young Kon; Kim, Moon Kon

2002-01-01

To determine the heating characteristics of needle-shaped duplex stainless steel thermoseeds, and to evaluate their effectiveness in the induction of hyperthermia in rabbit liver. Thermoseeds of the two different shapes, L-shaped for single doses of hyperthermia and I-shaped for in-vitro study and repeated hyperthermic induction, were prepared. For the in-vitro study, an I-shaped thermoseed 0.23 mm in diameter and 25 mm long was placed inside a plastic tube filled with water. Heat was applied for 30 minutes within an induction magnetic field, and during this time changes in temperature were recorded using three thermocouples. For the in-vivo study, fifteen New Zealand white rabbits were divided into five equal groups. An I-shaped or L-shaped thermoseed was inserted in each rabbit's liver, and then placed within the center of the magnetic induction coil during a 30-minute period of hyperthermia. The rabbits in the first group were sacrificed immediately after hyperthermia was induced once, while those in the other groups were sacrificed at 1, 3, and 7 days, respectively, also after one induction. The remaining three rabbits were sacrificed 4 days after three consecutive daily treatment sessions. The resected segments of liver were subsequently evaluated histopathologically for the extent of coagulation necrosis caused by heating of the thermoseed. The in-vitro study demonstrated that the temperature in the thermoseed, which was 25.9 degrees C before heating and 54.8 degrees C after heating, rose rapidly at first but progressively less rapidly as time elapsed. Light microscopic examination of the rabbits' livers revealed coagulation necrosis and infiltration by inflammatory cells around the insertion site of the thermoseed. The maximum diameter of coagulation necrosis was 2.81+/-1.68 mm, and this occurred in the rabbits that were sacrificed 7 days after heat induction. Needle-shaped duplex stainless steel thermoseeds show temperature-dependent-type heating characteristics, and in rabbit liver, induced coagulation necrosis of surrounding tissues after heat is applied for 30 minutes. These thermoseeds may thus be useful for the induction of interstitial hyperthermia.

The Induction of Hyperthermia in Rabbit Liver by means of Duplex Stainless Steel Thermoseeds

PubMed Central

Koo, Bong Sig; Kim, Young Kon; Kim, Moon Kon

2002-01-01

Objective To determine the heating characteristics of needle-shaped duplex stainless steel thermoseeds, and to evaluate their effectiveness in the induction of hyperthermia in rabbit liver. Materials and Methods Thermoseeds of the two different shapes, L-shaped for single doses of hyperthermia and I-shaped for in-vitro study and repeated hyperthermic induction, were prepared. For the in-vitro study, an I-shaped thermoseed 0.23 mm in diameter and 25 mm long was placed inside a plastic tube filled with water. Heat was applied for 30 minutes within an induction magnetic field, and during this time changes in temperature were recorded using three thermocouples. For the in-vivo study, fifteen New Zealand white rabbits were divided into five equal groups. An I-shaped or L-shaped thermoseed was inserted in each rabbit's liver, and then placed within the center of the magnetic induction coil during a 30-minute period of hyperthermia. The rabbits in the first group were sacrificed immediately after hyperthermia was induced once, while those in the other groups were sacrificed at 1, 3, and 7 days, respectively, also after one induction. The remaining three rabbits were sacrificed 4 days after three consecutive daily treatment sessions. The resected segments of liver were subsequently evaluated histopathologically for the extent of coagulation necrosis caused by heating of the thermoseed. Results The in-vitro study demonstrated that the temperature in the thermoseed, which was 25.9℃ before heating and 54.8℃ after heating, rose rapidly at first but progressively less rapidly as time elapsed. Light microscopic examination of the rabbits' livers revealed coagulation necrosis and infiltration by inflammatory cells around the insertion site of the thermoseed. The maximum diameter of coagulation necrosis was 2.81 ± 1.68 mm, and this occurred in the rabbits that were sacrificed 7 days after heat induction. Conclusion Needle-shaped duplex stainless steel thermoseeds show temperature-dependent-type heating characteristics, and in rabbit liver, induced coagulation necrosis of surrounding tissues after heat is applied for 30 minutes. These thermoseeds may thus be useful for the induction of interstitial hyperthermia. PMID:12087199

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatakeyama, Hiroto; Wu, Sherry Y.; Lyons, Yasmin A.

Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. Lastly, CTGF silencingmore » aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.« less

Localized Hyperthermia for Enhanced Targeted Delivery of Polymer Therapeutics

NASA Astrophysics Data System (ADS)

Frazier, Nicholas

It is estimated that in 2016, more than 848,000 new cases of cancer will be diagnosed in men with more than a quarter being prostate cancer and more than 26,000 deaths attributed to this disease. Prostate cancer poses a limited risk when detected at an early stage and treatment of stages II-III has a 5-year survival rate of almost 100%. However, these early-stage cancers can eventually progress and develop into stage IV, dramatically dropping the 5-year survival rate to 28%. Thus, development of a new therapy is needed to fully eliminate these tumors. Combination of heat and chemotherapy improves therapeutic efficacy while allowing for reduced dosing of drugs and limiting side effects. Localized hyperthermia has been used to enhance the delivery of polymer therapeutics to prostate tumors through increased blood flow, vascular permeability, and incorporation of heat shock targeting. This strategy has been shown to increase the delivery and retention of polymer-drug conjugates leading to enhanced efficacy. Although much work has been done using this strategy, the effects of different thermal dosing on polymer accumulation are unknown. The first aim of this research is to examine how altering heating parameters influences polymer tumor accumulation. The hypothesis for this aim is that there is an optimal thermal treatment that leads to the maximal amount of polymer accumulation in the tumors. Additionally, the previously used heating method of plasmonic photothermal therapy (PPTT) can result in long-term accumulation of gold nanoparticles in healthy organs, potentially limiting clinical applicability. The second aim of this proposal will be focused on investigating the alternative method of high intensity focused ultrasound (HIFU) for selective heating of tumors and enhancing macromolecular delivery. HIFU has shown the capability for precise, noninvasive heating of specific regions within the prostate through magnetic resonance imaging (MRI) guidance. The hypothesis to be tested in this aim is that mild hyperthermia produced with HIFU will have the same effect as that produced by PPTT in improving the delivery of macromolecular systems to solid tumors. Finally, in the third aim, the enhanced delivery of targeted polymer therapeutics to prostate tumors in mice models will be investigated using mild hyperthermia produced with HIFU. In the long term, it is anticipated that HIFU can be used in conjunction with delivery of polymer-drug conjugates for enhanced efficacy and reduced toxicity of chemotherapy to produce a clinically relevant treatment of advanced prostate cancer.

Synthesis and characterization of Fe-based metal and oxide based nanoparticles: discoveries and research highlights of potential applications in biology and medicine.

PubMed

Long, Nguyen Viet; Thi, Cao Minh; Yong, Yang; Cao, Yanqin; Wu, Haibo; Nogami, Masayuki

2014-01-01

In this review, we have presented the controlled synthesis of Fe-based metal and oxide nanoparticles with large size by chemical methods. The issues of the size, shape and morphology of Fe nanoparticles are discussed in the certain ranges of practical applications in biology and medicine. The homogeneous nanosystems of Fe-based metal and oxide nanoparticles with various sizes and shapes from the nano-to-micro ranges can be used in order to meet the demands of the treatments of dangerous tumors and cancers through magnetic hyperthermia and magnetic resonance imaging (MRI). In this context, the polyhedral Fe-based metal and oxide nanoparticles having large size in the ranges from 1000 nm to 5000 nm can be potentially used in magnetic hyperthermia and MRI in the innovative drug delivery, diagnosis, treatment, and therapy of tumor and cancer diseases because of their very high bio-adaptability. We have suggested that high stability and durability of Fe-based metal and oxide nanoparticles are very crucial to recent magnetic hyperthermia and MRI technology. The roles of various Fe-based nanostructures are focused in biomedical applications of tumors and cancers diagnostics, targeted drug delivery, and magnetic hyperthermia. Finally, Fe-based, α-, β- and γ-Fe2O3, and Fe3O4-based nanoparticles are shortly discussed in various potential applications in catalysis, biology, and medicine.

Individualized Prediction of Heat Stress in Firefighters: A Data-Driven Approach Using Classification and Regression Trees.

PubMed

Mani, Ashutosh; Rao, Marepalli; James, Kelley; Bhattacharya, Amit

2015-01-01

The purpose of this study was to explore data-driven models, based on decision trees, to develop practical and easy to use predictive models for early identification of firefighters who are likely to cross the threshold of hyperthermia during live-fire training. Predictive models were created for three consecutive live-fire training scenarios. The final predicted outcome was a categorical variable: will a firefighter cross the upper threshold of hyperthermia - Yes/No. Two tiers of models were built, one with and one without taking into account the outcome (whether a firefighter crossed hyperthermia or not) from the previous training scenario. First tier of models included age, baseline heart rate and core body temperature, body mass index, and duration of training scenario as predictors. The second tier of models included the outcome of the previous scenario in the prediction space, in addition to all the predictors from the first tier of models. Classification and regression trees were used independently for prediction. The response variable for the regression tree was the quantitative variable: core body temperature at the end of each scenario. The predicted quantitative variable from regression trees was compared to the upper threshold of hyperthermia (38°C) to predict whether a firefighter would enter hyperthermia. The performance of classification and regression tree models was satisfactory for the second (success rate = 79%) and third (success rate = 89%) training scenarios but not for the first (success rate = 43%). Data-driven models based on decision trees can be a useful tool for predicting physiological response without modeling the underlying physiological systems. Early prediction of heat stress coupled with proactive interventions, such as pre-cooling, can help reduce heat stress in firefighters.

[Acquiring skills in malignant hyperthermia crisis management: comparison of high-fidelity simulation versus computer-based case study].

PubMed

Mejía, Vilma; Gonzalez, Carlos; Delfino, Alejandro E; Altermatt, Fernando R; Corvetto, Marcia A

The primary purpose of this study was to compare the effect of high fidelity simulation versus a computer-based case solving self-study, in skills acquisition about malignant hyperthermia on first year anesthesiology residents. After institutional ethical committee approval, 31 first year anesthesiology residents were enrolled in this prospective randomized single-blinded study. Participants were randomized to either a High Fidelity Simulation Scenario or a computer-based Case Study about malignant hyperthermia. After the intervention, all subjects' performance in was assessed through a high fidelity simulation scenario using a previously validated assessment rubric. Additionally, knowledge tests and a satisfaction survey were applied. Finally, a semi-structured interview was done to assess self-perception of reasoning process and decision-making. 28 first year residents finished successfully the study. Resident's management skill scores were globally higher in High Fidelity Simulation versus Case Study, however they were significant in 4 of the 8 performance rubric elements: recognize signs and symptoms (p = 0.025), prioritization of initial actions of management (p = 0.003), recognize complications (p = 0.025) and communication (p = 0.025). Average scores from pre- and post-test knowledge questionnaires improved from 74% to 85% in the High Fidelity Simulation group, and decreased from 78% to 75% in the Case Study group (p = 0.032). Regarding the qualitative analysis, there was no difference in factors influencing the student's process of reasoning and decision-making with both teaching strategies. Simulation-based training with a malignant hyperthermia high-fidelity scenario was superior to computer-based case study, improving knowledge and skills in malignant hyperthermia crisis management, with a very good satisfaction level in anesthesia residents. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Synthesis and application of magnetite dextran-spermine nanoparticles in breast cancer hyperthermia.

PubMed

Avazzadeh, Reza; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Amanpour, Saeid; Sadeghi, Mohsen

2017-09-01

Cancer treatment has been very challenging in recent decades. One of the most promising cancer treatment methods is hyperthermia, which increases the tumor temperature (41-45 °C). Magnetic nanoparticles have been widely used for selective targeting of cancer cells. In the present study, magnetic dextran-spermine nanoparticles, conjugated with Anti-HER2 antibody to target breast cancer cells were developed. The magnetic dextran-spermine nanoparticles (DMNPs) were prepared by ionic gelation, followed by conjugation of antibody to them using EDC-NHS method. Then the Prussian blue method was used to estimate the targeting ability and cellular uptake. Cytotoxicity assay by MTT showed that antibody-conjugated MNPs (ADMNPs) have no toxic effect on SKBR3 and human fibroblast cells. Finally, the hyperthermia was applied to show that synthesized ADMNPs, could increase the cancer cells temperature up to 45 °C and kill most of them without affecting normal cells. These observations proved that Anti-HER2 conjugated magnetic dextran-spermine nanoparticles can target and destroy cancer cells and are potentially suitable for cancer treatment.

Progressive exercise preconditioning protects against circulatory shock during experimental heatstroke.

PubMed

Hung, Ching-Hsia; Chang, Nen-Chung; Cheng, Bor-Chih; Lin, Mao-Tsun

2005-05-01

Heat shock protein (HSP) 72 expression protects against arterial hypotension in rat heatstroke. HSP72 can also be induced in multiple organs, including hearts from rats with endurance exercise. We validated the hypothesis that progressive exercise preconditioning may confer cardiovascular protection during heatstroke by inducing the overexpression of HSP72 in multiple organs. To deal with the matter, we assessed the effects of heatstroke on mean arterial pressure, heart rate, cardiac output, stroke volume, total peripheral vascular resistance, colonic temperature, blood gases, and serum or tissue levels of tumor necrosis factor-alpha (TNF-alpha) in urethane-anesthetized rats pretreated without or with progressive exercise training for 1, 2, or 3 weeks. In addition, HSP72 expression in multiple organs was determined in different groups of animals. Heatstroke was induced by exposing the rats to a high blanket temperature (43 degrees C); the moment at which mean arterial pressure decreased from the peak value was taken as the time of heatstroke onset. Previous exercise training for 3 weeks, but not 1 or 2 weeks, conferred significant protection against hyperthermia, arterial hypotension, decreased cardiac output, decreased stroke volume, decreased peripheral vascular resistance, and increased levels of serum or tissue TNF-alpha during heatstroke and correlated with overexpression of HSP72 in multiple organs, including heart, liver, and adrenal gland. However, 10 days after 3 weeks of progressive exercise training, when HSP72 expression in multiple organs returned to basal values, the beneficial effects exerted by 3 weeks of exercise training were no longer observed. These results strongly suggest that HSP72 preconditioning with progressive exercise training protects against hyperthermia, circulatory shock, and TNF-alpha overproduction during heatstroke.

Malignant hyperthermia

MedlinePlus

... about MH: Malignant Hyperthermia Association of the United States -- www.mhaus.org National Organization for Rare Disorders -- rarediseases.org/rare-diseases/malignant-hyperthermia NIH Genetics Home Reference -- ghr.nlm.nih.gov/condition/malignant-hyperthermia

Tailored Magnetic Nanoparticles for Optimizing Magnetic Fluid Hyperthermia

PubMed Central

Khandhar, Amit; Ferguson, R. Matthew; Simon, Julian A.; Krishnan, Kannan M.

2011-01-01

Magnetic Fluid Hyperthermia (MFH) is a promising approach towards adjuvant cancer therapy that is based on the localized heating of tumors using the relaxation losses of iron oxide magnetic nanoparticles (MNPs) in alternating magnetic fields (AMF). In this study, we demonstrate optimization of MFH by tailoring MNP size to an applied AMF frequency. Unlike conventional aqueous synthesis routes, we use organic synthesis routes that offer precise control over MNP size (diameter ~ 10–25 nm), size distribution and phase purity. Furthermore, the particles are successfully transferred to the aqueous phase using a biocompatible amphiphilic polymer, and demonstrate long-term shelf life. A rigorous characterization protocol ensures that the water-stable MNPs meet all the critical requirements: (1) uniform shape and monodispersity, (2) phase purity, (3) stable magnetic properties approaching that of the bulk, (4) colloidal stability, (5) substantial shelf life and (6) pose no significant in vitro toxicity. Using a dedicated hyperthermia system, we then identified that 16 nm monodisperse MNPs (σ ~ 0.175) respond optimally to our chosen AMF conditions (f = 373 kHz, Ho = 14 kA/m); however, with a broader size distribution (σ ~ 0.284) the Specific Loss Power (SLP) decreases by 30%. Finally, we show that these tailored MNPs demonstrate maximum hyperthermia efficiency by reducing viability of Jurkat cells in vitro, suggesting our optimization translates truthfully to cell populations. In summary, we present a way to intrinsically optimize MFH by tailoring the MNPs to any applied AMF, a required precursor to optimize dose and time of treatment. PMID:22213652

Targeted thermal therapy with genetically engineered magnetite magnetosomes@RGD: Photothermia is far more efficient than magnetic hyperthermia.

PubMed

Plan Sangnier, Anouchka; Preveral, Sandra; Curcio, Alberto; K A Silva, Amanda; Lefèvre, Chistopher T; Pignol, David; Lalatonne, Yoann; Wilhelm, Claire

2018-06-10

Providing appropriate means for heat generation by low intratumoral nanoparticle concentrations is a major challenge for cancer nanotherapy. Here we propose RGD-tagged magnetosomes (magnetosomes@RGD) as a biogenic, genetically engineered, inorganic platform for multivalent thermal cancer treatment. Magnetosomes@RGD are biomagnetite nanoparticles synthesized by genetically modified magnetotactic bacteria thanks to a translational fusion of the RGD peptide with the magnetosomal protein MamC. Magnetosomes@RGD thus combine the high crystallinity of their magnetite core with efficient surface functionalization. The specific affinity of RGD was first quantified by single-cell magnetophoresis with a variety of cell types, including immune, muscle, endothelial, stem and cancer cells. The highest affinity and cellular uptake was observed with PC3 prostatic and HeLa uterine cancer cells. The efficiency of photothermia and magnetic hyperthermia was then compared on PC3 cells. Unexpectedly, photothermia was far more efficient than magnetic hyperthermia, which was almost totally inhibited by the cellular environment. RGD targeting was then assessed in vivo at tumor site, in mice bearing PC3 tumors. As a result, we demonstrate that targeted magnetic nanoparticles could generate heat on a therapeutic level after systemic administration, but only under laser excitation, and successfully inhibit tumor progression. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeting HSP70-induced thermotolerance for design of thermal sensitizers.

PubMed

Calderwood, S K; Asea, A

2002-01-01

Thermal therapy has been shown to be an extremely powerful anti-cancer agent and a potent radiation sensitizer. However, the full potential of thermal therapy is hindered by a number of considerations including highly conserved heat resistance pathways in tumour cells and inhomogeneous heating of deep-seated tumours due to energy deposition and perfusion issues. This report reviews recent progress in the development of hyperthermia sensitizing drugs designed to specifically amplify the effects of hyperthermia. Such agents might be particularly useful in situations where heating is not adequate for the full biological effect or is not homogeneously delivered to tumours. The particular pathway concentrated on is thermotolerance, a complex, inducible cellular response that leads to heat resistance. This paper will concentrate on the molecular pathways of thermotolerance induction for designing inhibitors of heat resistance/thermal sensitizers, which may allow the full potential of thermal therapy to be utilized.

The role of temperature increase rate in combinational hyperthermia chemotherapy treatment

NASA Astrophysics Data System (ADS)

Tang, Yuan; McGoron, Anthony J.

2010-02-01

Hyperthermia in combination with chemotherapy has been widely used in cancer treatment. Our previous study has shown that rapid rate hyperthermia in combination with chemotherapy can synergistically kill cancer cells whereas a sub-additive effect was found when a slow rate hyperthermia was applied. In this study, we explored the basis of this difference. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. P-glycoprotein (P-gp) expression, Caspase 3 activity, and heat shock protein 70 (HSP 70) expression following the two different modes of heating were measured. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. Slow rate hyperthermia was provided by a cell culture incubator. Two sets of thermal doses were delivered by either slow rate or rapid rate hyperthermia. HSP70 expression was highly elevated under low dose slow rate incubator hyperthermia while maintained at the baseline level under the other three treatments. Caspase3 level slightly increased after low dose slow rate incubator hyperthermia while necrotic cell death was found in the other three types of heat treatment. In conclusion, when given at the same thermal dose, slow rate hyperthermia is more likely to induce thermotolerance. Meanwhile, hyperthermia showed a dose dependent capability in reversing P-gp mediated MDR; when MDR is reversed, the combinational treatment induced extensive necrotic cell death. During this process, the rate of heating also played a very important role; necrosis was more dramatic in rapid rate hyperthermia than in slow rate hyperthermia even though they were given at the same dose.

The Kadota Fund International Forum 2004-Clinical group consensus*

PubMed Central

van der Zee, J.; Vujaskovic, Z.; Kondo, M.; Sugahara, T.

2009-01-01

The results from experimental studies indicate that hyperthermia is both an effective complementary treatment to, and a strong sensitiser of, radiotherapy and many cytotoxic drugs. Since the first international hyperthermia conference in 1975, Washington DC, techniques to increase tumour temperature have been developed and tested clinically. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, perfusion hyperthermia of organs, limbs, or body cavities, and whole body hyperthermia. The clinical value of hyperthermia in combination with other treatment modalities has been shown by randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, for melanoma and sarcoma. The addition of hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects, and/or better overall survival rates. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. In spite of these good clinical results, hyperthermia has received little attention. Problems with acceptance concern the limited availability of equipment, the lack of awareness concerning clinical results, and the lack of financial resources. In this paper the most relevant literature describing the clinical effects of hyperthermia is reviewed and discussed, and means to overcome the lack of awareness and use of this modality is described. PMID:18283588

Heat stress decreases testicular germ cell proliferation and increases apoptosis in short term: an immunohistochemical and ultrastructural study.

PubMed

Kanter, Mehmet; Aktas, Cevat; Erboga, Mustafa

2013-03-01

Scrotal hyperthermia has been known as a cause of male infertility but the exact mechanism leading to impaired spermatogenesis is unknown. This work was aimed to investigate the role of scrotal hyperthermia on cell proliferation and apoptosis in testes. The rats were randomly allotted into one of the four experimental groups: A (control), B (1 day after scrotal hyperthermia), C (14 days after scrotal hyperthermia), and D (35 days after scrotal hyperthermia); each group comprised 7 animals. Scrotal hyperthermia was carried out in a thermostatically controlled water bath at 43°C for 30 min once daily for 6 consecutive days. Control rats were treated in the same way, except the testes were immersed in a water bath maintained at 22°C. Hyperthermia-exposed rats were killed under 50 mg/kg ketamine anaesthesia and tissue samples were obtained for biochemical and histopathological investigations. Hyperthermia treatment significantly decreased the testicular antioxidant system, including decreases in the glutathione level, superoxide dismutase, and glutathione peroxidase activities. Moreover, exposure to hyperthermia resulted in lipid peroxidation increase in testes. Our data indicate a significant reduction in the expression of proliferating cell nuclear antigen and an enhancement in the activity of terminal deoxynucleotidyl transferase dUTP nick end labelling after scrotal hyperthermia. In scrotal hyperthermia, the mitochondrial degeneration, dilatation of smooth endoplasmic reticulum, and enlarged intercellular spaces were observed in both Sertoli and spermatid cells. Scrotal hyperthermia is one of the major factors that impair spermatogenesis in testis. This heat stress is shown to be closely associated with oxidative stress, followed by apoptosis of germ cells.

Cyclooxygenase inhibitors are potent sensitizers of prostate tumours to hyperthermia and radiation.

PubMed

Asea, A; Mallick, R; Lechpammer, S; Ara, G; Teicher, B A; Fiorentino, S; Stevenson, M A; Calderwood, S K

2001-01-01

It has previously been demonstrated that hyperthermia can activate prostaglandin synthesis and that prostaglandins are protective against hyperthermia. This study examined the use of inhibitors of prostaglandin synthesis on the response of prostate tumours to hyperthermia. The non-steroidal anti-inflammatory drugs (NSAID) ibuprofen and sulindac, known cyclooxygenase inhibitors that inhibit prostaglandin production, were effective hyperthermia sensitizers and augmented growth delay of DU-145 and PC-3 prostate tumours to combined radiation and hyperthermia treatment protocols. Pre-treatment of mice with ibuprofen and sulindac at hyperthermia sensitizing doses resulted in significant (p < 0.01) inhibition of hyperthemia-induced serum prostaglandin E2. These findings indicate that NSAID may have both sensitizing effects on prostate tumour growth and may function by inhibiting prostaglandin synthesis.

Magnetic nanoparticle-conjugated polymeric micelles for combined hyperthermia and chemotherapy

NASA Astrophysics Data System (ADS)

Kim, Hyun-Chul; Kim, Eunjoo; Jeong, Sang Won; Ha, Tae-Lin; Park, Sang-Im; Lee, Se Guen; Lee, Sung Jun; Lee, Seung Woo

2015-10-01

Magnetic nanoparticle-conjugated polymeric micelles (MNP-PMs) consisting of poly(ethylene glycol)-poly(lactide) (PEG-PLA) and iron oxide nanoparticles were prepared and used as nanocarriers for combined hyperthermia and chemotherapy. Doxorubicin (DOX) was encapsulated in MNP-PMs, and an alternating magnetic field (AMF) resulted in an increase to temperature within a suitable range for inducing hyperthermia and a higher rate of drug release than observed without AMF. In vitro cytotoxicity and hyperthermia experiments were carried out using human lung adenocarcinoma A549 cells. When MNP-PMs encapsulated with an anticancer drug were used to treat A549 cells in combination with hyperthermia under AMF, 78% of the cells were killed by the double effects of heat and the drug, and the combination was more effective than either chemotherapy or hyperthermia treatment alone. Therefore, MNP-PMs encapsulated with an anticancer drug show potential for combined chemotherapy and hyperthermia.Magnetic nanoparticle-conjugated polymeric micelles (MNP-PMs) consisting of poly(ethylene glycol)-poly(lactide) (PEG-PLA) and iron oxide nanoparticles were prepared and used as nanocarriers for combined hyperthermia and chemotherapy. Doxorubicin (DOX) was encapsulated in MNP-PMs, and an alternating magnetic field (AMF) resulted in an increase to temperature within a suitable range for inducing hyperthermia and a higher rate of drug release than observed without AMF. In vitro cytotoxicity and hyperthermia experiments were carried out using human lung adenocarcinoma A549 cells. When MNP-PMs encapsulated with an anticancer drug were used to treat A549 cells in combination with hyperthermia under AMF, 78% of the cells were killed by the double effects of heat and the drug, and the combination was more effective than either chemotherapy or hyperthermia treatment alone. Therefore, MNP-PMs encapsulated with an anticancer drug show potential for combined chemotherapy and hyperthermia. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04130a

Tailored magnetic nanoparticles for optimizing magnetic fluid hyperthermia.

PubMed

Khandhar, Amit P; Ferguson, R Matthew; Simon, Julian A; Krishnan, Kannan M

2012-03-01

Magnetic Fluid Hyperthermia (MFH) is a promising approach towards adjuvant cancer therapy that is based on the localized heating of tumors using the relaxation losses of iron oxide magnetic nanoparticles (MNPs) in alternating magnetic fields (AMF). In this study, we demonstrate optimization of MFH by tailoring MNP size to an applied AMF frequency. Unlike conventional aqueous synthesis routes, we use organic synthesis routes that offer precise control over MNP size (diameter ∼10 to 25 nm), size distribution, and phase purity. Furthermore, the particles are successfully transferred to the aqueous phase using a biocompatible amphiphilic polymer, and demonstrate long-term shelf life. A rigorous characterization protocol ensures that the water-stable MNPs meet all the critical requirements: (1) uniform shape and monodispersity, (2) phase purity, (3) stable magnetic properties approaching that of the bulk, (4) colloidal stability, (5) substantial shelf life, and (6) pose no significant in vitro toxicity. Using a dedicated hyperthermia system, we then identified that 16 nm monodisperse MNPs (σ-0.175) respond optimally to our chosen AMF conditions (f = 373 kHz, H₀ = 14 kA/m); however, with a broader size distribution (σ-0.284) the Specific Loss Power (SLP) decreases by 30%. Finally, we show that these tailored MNPs demonstrate maximum hyperthermia efficiency by reducing viability of Jurkat cells in vitro, suggesting our optimization translates truthfully to cell populations. In summary, we present a way to intrinsically optimize MFH by tailoring the MNPs to any applied AMF, a required precursor to optimize dose and time of treatment. Copyright © 2011 Wiley Periodicals, Inc.

Meth math: modeling temperature responses to methamphetamine.

PubMed

Molkov, Yaroslav I; Zaretskaia, Maria V; Zaretsky, Dmitry V

2014-04-15

Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants.

Meth math: modeling temperature responses to methamphetamine

PubMed Central

Molkov, Yaroslav I.; Zaretskaia, Maria V.

2014-01-01

Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants. PMID:24500434

Magnetic Nanomaterials for Hyperthermia-based Therapy and Controlled Drug Delivery

PubMed Central

Kumar, Challa S. S. R.; Mohammad, Faruq

2011-01-01

Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term “Hyperthermia” in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term “hyperthermia” by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled Drug delivery through Bond Breaking (DBB) and Hyperthermia-based controlled Drug delivery through Enhanced Permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities in the combination of hyperthermia-based therapy and controlled drug release paradigms for successful application in personalized medicine. PMID:21447363

Prostacyclin-induced hyperthermia - Implication of a protein mediator

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williams, B. A.

1982-01-01

The mechanism of the prostacyclin-linked hyperthermia is studied in rabbits. Results show that intracerebroventricular administration of prostacyclin (PGI2) induces dose-related hyperthermia at room temperature (21 C), as well as at low (4 C) and high (30 C) ambient temperatures. It is found that this PGI2-induced hyperthermia is not mediated by its stable metabolite 6-keto prostaglandin F-1(alpha). Only one of the three anion transport systems, the liver transport system, appears to be important to the central inactivation of pyrogen, prostaglandin E2, and PGI2. Phenoxybenzamine and pimozide have no thermolytic effect on PGI2-induced hyperthermia, while PGI2 still induces hyperthermia after norepinephrine (NE) and dopamine levels are depleted by 6-hydroxydopamine. Indomethacin and SC-19220 (a PG antagonist) do not antagonize PGI2 induced hyperthermia, while theophylline does not accentuate the PGI2-induced hyperthermia. However, the hyperthermic response to PGI2 is attenuated by central administration of the protein synthesis inhibitor, anisomycin. It is concluded that PGI2-induced hyperthermia is not induced by NE, dopamine, or cyclic AMP, but rather that a protein mediator is implicated in the induction of fever by PG12.

Effects of acute hyperthermia on the carotid baroreflex control of heart rate in humans

NASA Astrophysics Data System (ADS)

Yamazaki, F.; Sagawa, S.; Torii, R.; Endo, Y.; Shiraki, K.

The purpose of this study was to examine the effect of hyperthermia on the carotid baroreceptor-cardiac reflexes in humans. Nine healthy males underwent acute hyperthermia (esophageal temperature 38.0° C) produced by hot water-perfused suits. Beat-to-beat heart rate (HR) responses were determined during positive and negative R-wave-triggered neck pressure steps from +40 to -65 mm Hg during normothermia and hyperthermia. The carotid baroreceptor-cardiac reflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure. Buffering capacity of the HR response to carotid distending pressure was evaluated in % from a reference point calculated as (HR at 0 mm Hg neck pressure-minimum HR)/HR range ×100. An upward shift of the curve was evident in hyperthermia because HR increased from 57.7+/-2.4 beats/min in normothermia to 88.7+/-4.1 beats/min in hyperthermia (P<0.05) without changes in mean arterial pressure. The maximum slope of the curve in hyperthermia was similar to that in normothermia. The reference point was increased (P<0.05) during hyperthermia. These results suggest that the sensitivity of the carotid baroreflex of HR remains unchanged in hyperthermia. However, the capacity for tachycardia response to rapid onset of hypotension is reduced and the capacity for bradycardia response to sudden hypertension is increased during acute hyperthermia.

Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin-mediated degradation of cellular FLIP(long) in human colon cancer cells

PubMed Central

Song, X; Kim, S-Y; Zhou, Z; Lagasse, E; Kwon, Y T; Lee, Y J

2013-01-01

Colorectal cancer is the third leading cause of cancer-related mortality in the world; the main cause of death of colorectal cancer is hepatic metastases, which can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c-FLIPL), a major regulator of the death receptor (DR) pathway of apoptosis, thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated mitochondria-independent apoptosis. We observed that overexpression of c-FLIPL in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia altered c-FLIPL protein stability without concomitant reductions in FLIP mRNA. Ubiquitination of c-FLIPL was increased by hyperthermia, and proteasome inhibitor MG132 prevented heat-induced downregulation of c-FLIPL. These results suggest the involvement of the ubiquitin-proteasome system in this process. We also found lysine residue 195 (K195) to be essential for c-FLIPL ubiquitination and proteolysis, as mutant c-FLIPL lysine 195 arginine (arginine replacing lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia-triggered degradation, and thus partially blocked the synergistic effect of Mapa and hyperthermia. Our observations reveal that hyperthermia transiently reduced c-FLIPL by proteolysis linked to K195 ubiquitination, which contributed to the synergistic effect between Mapa and hyperthermia. This study supports the application of hyperthermia combined with other regimens to treat colorectal hepatic metastases. PMID:23559011

Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin-mediated degradation of cellular FLIP(long) in human colon cancer cells.

PubMed

Song, X; Kim, S-Y; Zhou, Z; Lagasse, E; Kwon, Y T; Lee, Y J

2013-04-04

Colorectal cancer is the third leading cause of cancer-related mortality in the world; the main cause of death of colorectal cancer is hepatic metastases, which can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c-FLIP(L)), a major regulator of the death receptor (DR) pathway of apoptosis, thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated mitochondria-independent apoptosis. We observed that overexpression of c-FLIP(L) in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia altered c-FLIP(L) protein stability without concomitant reductions in FLIP mRNA. Ubiquitination of c-FLIP(L) was increased by hyperthermia, and proteasome inhibitor MG132 prevented heat-induced downregulation of c-FLIP(L). These results suggest the involvement of the ubiquitin-proteasome system in this process. We also found lysine residue 195 (K195) to be essential for c-FLIP(L) ubiquitination and proteolysis, as mutant c-FLIP(L) lysine 195 arginine (arginine replacing lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia-triggered degradation, and thus partially blocked the synergistic effect of Mapa and hyperthermia. Our observations reveal that hyperthermia transiently reduced c-FLIP(L) by proteolysis linked to K195 ubiquitination, which contributed to the synergistic effect between Mapa and hyperthermia. This study supports the application of hyperthermia combined with other regimens to treat colorectal hepatic metastases.

Microwave and radiofrequency techniques for clinical hyperthermia.

PubMed Central

Cheung, A. Y.

1982-01-01

Biological and practical constraints on the use of clinical hyperthermia for the management of cancer are discussed. Commonly used electromagnetic techniques for producing clinical hyperthermia are reviewed and compared. Innovative engineering designs leading to the realization of an integrated, safe and reliable clinical hyperthermia system are also presented. PMID:6950753

[Regional electro-hyperthermia--technical principles, clinical results and health insurance aspects].

PubMed

Heyll, Uwe

2012-06-01

The method of electro-hyperthermia is based on the production of alternating currents from capacitive coupled electrodes. Because of the associated heating of body tissues, the electro-hyperthermia is promoted as an alternative to the more sophisticated methods of scientific hyperthermia, which find use in oncologic diseases. The analysis of technical data, however, reveals that the electro-hyperthermia is not qualified for a focused, effective and therapeutically useful heating of circumscribed target areas. Data from clinical studies demonstrating efficacy for defined indications are not available. The application of electro-hyperthermia is excluded form the German system of public health insurance. As proof of medical necessity cannot be provided, there is also no claim for reimbursement from private health insurance. According to legal regulations in Germany, an invoice as hyperthermia treatment is usually not possible. Rather, an item from the electrotherapy section of the official provision of medical fees (GOA) has to be chosen.

Investigation properties of superparamagnetic nanoparticles and magnetic field-dependent hyperthermia therapy

NASA Astrophysics Data System (ADS)

Hedayatnasab, Z.; Abnisa, F.; Daud, W. M. A. Wan

2018-03-01

The application of superparamagnetic nanoparticles as heating agents in hyperthermia therapy has made a therapeutic breakthrough in cancer treatment. The high efficiency of this magnetic hyperthermia therapy has derived from a great capability of superparamagnetic nanoparticles to generate focused heat in inaccessible tumors being effectively inactivated. The main challenges of this therapy are the improvement of the induction heating power of superparamagnetic nanoparticles and the control of the hyperthermia temperature in a secure range of 42 °C to 47 °C, at targeted area. The variation of these hyperthermia properties is principally dependent on the magnetic nanoparticles as well as the magnetic field leading to enhance the efficiency of magnetic hyperthermia therapy at targeted area and also avoid undue heating to healthy cells. The present study evaluates the magnetic hyperthermia therapy through the determination of superparamagnetic nanoparticles properties and magnetic field’ parameters.

In Hyperthermia Increased ERK and WNT Signaling Suppress Colorectal Cancer Cell Growth

PubMed Central

Bordonaro, Michael; Shirasawa, Senji; Lazarova, Darina L.

2016-01-01

Although neoplastic cells exhibit relatively higher sensitivity to hyperthermia than normal cells, hyperthermia has had variable success as an anti-cancer therapy. This variable outcome might be due to the fact that cancer cells themselves have differential degrees of sensitivity to high temperature. We hypothesized that the varying sensitivity of colorectal cancer (CRC) cells to hyperthermia depends upon the differential induction of survival pathways. Screening of such pathways revealed that Extracellular Signal-Regulated Kinase (ERK) signaling is augmented by hyperthermia, and the extent of this modulation correlates with the mutation status of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Through clonal growth assays, apoptotic analyses and transcription reporter assays of CRC cells that differ only in KRAS mutation status we established that mutant KRAS cells are more sensitive to hyperthermia, as they exhibit sustained ERK signaling hyperactivation and increased Wingless/Integrated (WNT)/beta-catenin signaling. We propose that whereas increased levels of WNT and ERK signaling and a positive feedback between the two pathways is a major obstacle in anti-cancer therapy today, under hyperthermia the hyperinduction of the pathways and their positive crosstalk contribute to CRC cell death. Ascertaining the causative association between types of mutations and hyperthermia sensitivity may allow for a mutation profile-guided application of hyperthermia as an anti-cancer therapy. Since KRAS and WNT signaling mutations are prevalent in CRC, our results suggest that hyperthermia-based therapy might benefit a significant number, but not all, CRC patients. PMID:27187477

Recent advances in nanosized Mn-Zn ferrite magnetic fluid hyperthermia for cancer treatment.

PubMed

Lin, Mei; Huang, Junxing; Sha, Min

2014-01-01

This paper reviews the recent research and development of nanosized manganese zinc (Mn-Zn) ferrite magnetic fluid hyperthermia (MFH) for cancer treatment. Mn-Zn ferrite MFH, which has a targeted positioning function that only the temperature of tumor tissue with magnetic nanoparticles can rise, while normal tissue without magnetic nanoparticles is not subject to thermal damage, is a promising therapy for cancer. We introduce briefly the composition and properties of magnetic fluid, the concept of MFH, and features of Mn-Zn ferrite magnetic nanoparticles for MFH such as thermal bystander effect, universality, high specific absorption rate, the targeting effect of small size, uniformity of hyperthermia temperature, and automatic temperature control and constant temperature effect. Next, preparation methods of Mn-Zn ferrite magnetic fluid are discussed, and biocompatibility and biosecurity of Mn-Zn ferrite magnetic fluid are analyzed. Then the applications of nanosized Mn-Zn ferrite MFH in cancer are highlighted, including nanosized Mn-Zn ferrite MFH alone, nanosized Mn-Zn ferrite MFH combined with As2O3 chemotherapy, and nanosized Mn-Zn ferrite MFH combined with radiotherapy. Finally, the combination application of nanosized Mn-Zn ferrite MFH and gene-therapy is conceived, and the challenges and perspectives for the future of nanosized Mn-Zn ferrite MFH for oncotherapy are discussed.

Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle cell association/uptake and flux in blood-brain barrier models.

PubMed

Dan, Mo; Bae, Younsoo; Pittman, Thomas A; Yokel, Robert A

2015-05-01

Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux. Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell(®) models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure. AMF-induced hyperthermia for 0.5 h did not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell association/uptake. It also enhanced the flux of CNA-IONPs across the two in vitro BBB models compared to conventional hyperthermia and normothermia, in the absence of cell death. Citrate-IONP flux was not observed under these conditions. AMF-induced hyperthermia also significantly enhanced paracellular pathway flux. The mechanism appears to involve more than the increased temperature surrounding the CNA-IONPs. Hyperthermia induced by AMF activation of CNA-IONPs has potential to increase the BBB permeability of therapeutics for the diagnosis and therapy of various brain diseases.

Induced apoptosis by mild hyperthermia occurs via telomerase inhibition on the three human myeloid leukemia cell lines: TF-1, K562, and HL-60.

PubMed

Deezagi, Abdolkhaleg; Manteghi, Sanaz; Khosravani, Pardis; Vaseli-Hagh, Neda; Soheili, Zahra-Soheila

2009-09-01

The purpose of this research was to understand the effect of hyperthermia on the telomerase activity in human leukemic cell lines (HL-60, K562, and TF-1). The cells were treated by hyperthermia at the range of 41-44 degrees C for 120 min and incubated for 96 h. Then telomerase activity, cell proliferation, and apoptosis were assessed. The results indicated that hyperthermia significantly induced apoptosis on the cells. The cells exhibited pre-apoptotic pattern at 41 and 42 degrees C at 60-120 min and apoptotic pattern at 43 and 44 degrees C over 30 min after hyperthermia. Telomerase activity (that was assayed immediately after hyperthermia) was stable at 41-42 degrees C for 60 min but decreased to 35-40% at 120 min. However, at severe hyperthermia (43-44 degrees C) telomerase activity was decreased in a time- and dose-dependent manner. Following hyperthermia (41-44 degrees C up to 120 min), the cells were incubated for 96 h. In these conditions, the telomerase activity was decreased by about 60-80% in comparison with that untreated control cells.

Erythrocyte Osmotic Fragility Testing and the Prediction of Canine Malignant Hyperthermia Susceptibility

PubMed Central

Cribb, Peter H.; Olfert, Ernest A.; Reynolds, F. Barry

1986-01-01

A Doberman-German Shepherd cross-bred male dog, previously diagnosed as malignant hyperthermia susceptible, was mated to an unrelated nonsusceptible German Shepherd cross-bred female. The resultant litter was subjected to hematological, biochemical and erythrocyte osmotic fragility testing in an endeavor to predict the susceptibility of individuals to malignant hyperthermia. Laboratory evaluations were repeated at one year of age and the litter subjected to the halothane challenge test. No significant difference in erythrocyte osmotic fragility was found between malignant hyperthermia susceptible and nonsusceptible siblings at six weeks or at one year of age. Erythrocyte osmotic fragility, in both malignant hyperthermia susceptible and nonsusceptible animals, increased between six weeks and one year of age. Dantrolene sodium was an effective treatment for malignant hyperthermia in the dog when administered early in an episode and in adequate dosage. The initial sign of a malignant hyperthermia episode was a very rapid increase in end tidal partial pressure of carbon dioxide. This finding reinforces the value of capnographic monitoring in anesthesia. PMID:17422730

Effects of hyperthermia and hyperglycemia on the metastases formation and on survival of rat bearing W256 carcinosarcoma.

PubMed

Shah, S A; Jain, R K; Finney, P L

1982-01-01

Hyperthermia (temperatures less than 42 degrees C) is widely used in the treatment of cancer. Current thrust in this field is directed towards using agents which can potentiate the effects of hyperthermia. Combined local hyperthermia (43 degrees C/2 hours) and hyperglycemia (6g glucose/kg body weight; mean blood glucose levels of 500 mg%) was investigated for treating a metastasizing form of a rat W256 carcinosarcoma. Glucose loading of the tumor-bearing rats rendered the foot tumors physically more easy to heat (due to inhibition of tumor blood flow), but combined hyperthermia and hyperglycemia lead to a decrease in survival rate (13% compared to 41% with heat alone), most animals died with widespread metastases in lymph nodes, lungs and kidneys. The data does not support the postulate that hyperglycemia leads to sensitization of tumor destruction by hyperthermia. We suggest that Corynebacterium parvum, a non-specific immunostimulant, should be thoroughly investigated as a potentiator of hyperthermia.

Effects of the flavonoid drug quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo.

PubMed

Asea, A; Ara, G; Teicher, B A; Stevenson, M A; Calderwood, S K

2001-01-01

Tumour hyperthermia, although potentially a powerful therapeutic agent and radiation sensitizer, is hindered by a number of considerations including inhomogeneous heating of deep seated tumours due to energy deposition and perfusion issues. One solution is to design hyperthermia sensitizers to amplify the effects of hyperthermia, particularly at cold spots within the tumour undergoing treatment. This study examined the use of Quercetin, a flavonoid drug shown previously to antagonize the expression of HSP72 and induce apoptosis as a sensitizer of prostate cancer growth in vivo. Quercetin dose-dependently suppressed PC-3 tumour growth in vitro and in vivo. When combined in a treatment protocol with hyperthermia, quercetin drastically inhibited tumour growth and potently amplified the effects of hyperthermia on two prostate tumour types, PC-3 and DU-145 in vivo. These experiments, thus, suggest the use of Quercetin as a hyperthermia sensitizer in the treatment of prostate carcinoma.

Hyperthermia Using Nanoparticles – Promises and Pitfalls

PubMed Central

Kaur, Punit; Aliru, Maureen L.; Chadha, Awalpreet S.; Asea, Alexzander; Krishnan, Sunil

2016-01-01

An ever-increasing body of literature affirms the physical and biological basis for sensitization of tumors to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fueled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalizes on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia. PMID:26757879

Hyperthermia using nanoparticles--Promises and pitfalls.

PubMed

Kaur, Punit; Aliru, Maureen L; Chadha, Awalpreet S; Asea, Alexzander; Krishnan, Sunil

2016-01-01

An ever-increasing body of literature affirms the physical and biological basis for sensitisation of tumours to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fuelled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalises on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia.

The behavioral regulation of thirst, water collection and water storage in honey bee colonies.

PubMed

Ostwald, Madeleine M; Smith, Michael L; Seeley, Thomas D

2016-07-15

This study investigated how a honey bee colony develops and quenches its collective thirst when it experiences hyperthermia of its broodnest. We found that a colony must strongly boost its water intake because evaporative cooling is critical to relieving broodnest hyperthermia, and that it must rapidly boost its water intake because a colony maintains only a small water reserve. We also clarified how a colony's water collectors know when to spring into action - by sensing either more frequent requests for fluid or greater personal thirst, or both. Finally, we found that the behavioral flexibility of a colony's water collectors enables them not only to satisfy their colony's current water needs but also to buffer their colony against future extreme water stresses by storing water in their crops and in their combs. © 2016. Published by The Company of Biologists Ltd.

Depletion of serotonin synthesis with p-CPA pretreatment alters EEG in urethane anesthetized rats under whole body hyperthermia.

PubMed

Sinha, Rakesh Kumar; Aggarwal, Yogender

2007-01-01

Serotonin is believed as an important factor in brain function. The role of serotonin in cerebral psycho-patho-physiology has already been well established. However, the function of serotonin antagonist in anesthetized subjects under hyperthermia has not been studied properly. Experiments were performed in three groups of urethane-anesthetized rats, such as: (i) control group, (ii) whole body hyperthermia group and (iii) p-CPA (para-Chlorophenylalanine) pretreated hyperthermia group. Hyperthermia was produced by subjecting the rats to high ambient temperature of 38 +/- 1 degrees C (relative humidity 45-50%). Each group was divided for EEG (electroencephalogram) study and for determination of edematous swelling in the brain. Urethane anesthetized rats under hyperthermia show highly significant reduction in their survival time. The body temperature recorded during the hyperthermia was observed with significant and linear rise with marked increase in brain water content, which was analyzed just after the death of the subjects. The results of the electroencephalographic study in urethane-anesthetized rats recorded before death indicate that brain function varies in systematic manner during hyperthermia as sequential changes in EEG patterns were observed. However, a serotonin antagonist, p-CPA pretreatment increases the survival time with significant reduction in edematous swelling in brain but it does not affect the relationship between the core body temperature and the brain cortical potentials as observed in urethane anesthetized subjects exposed to whole body hyperthermia. The core body temperature in p-CPA pretreated rats show non-linear relationship with respect to the exposure time as it was observed in drug untreated subjects. The findings of the present study indicate that although pretreatment of p-CPA in rats has a marked correlation between the extravasations of the blood-brain barrier under hyperthermia but shows minimum effect on the EEG in a model of hyperthermia under irreversible anesthesia.

Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.

PubMed Central

O'Brien, P J

1986-01-01

This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367

Deep hyperthermia with the HYPERcollar system combined with irradiation for advanced head and neck carcinoma - a feasibility study.

PubMed

Verduijn, G M; de Wee, E M; Rijnen, Z; Togni, P; Hardillo, J A U; Ten Hove, I; Franckena, M; van Rhoon, G C; Paulides, M M

2018-05-11

Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patient's comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC. 119 hyperthermia treatments given to 27 patients were analyzed. Hyperthermia was applied once a week by the HYPERcollar aimed at achieving 39-43 °C in the target area, up to patients' tolerance. Pre-treatment planning was used to optimize treatment settings. When possible, invasive thermometry catheters were placed. Mean power applied during the 119 hyperthermia treatments ranged from 120 to 1007 W (median 543 W). 15 (13%) hyperthermia treatments were not fully completed due to: pain allocated to hyperthermia (6/15), dyspnea from sticky saliva associated with irradiation (2/15) and unknown reasons (7/15). No severe complications or enhanced thermal or mucosal toxicities were observed. Excluding post-operative treatment, response rates after 3 months were 46% (complete) and 7% (partial). Hyperthermia with the HYPERcollar proved to be safe and feasible with good compliance and promising outcome.

Intra-operative post-induction hyperthermia, possibly malignant hyperthermia: Anesthetic implications, challenges and management

PubMed Central

Gulabani, Michell; Gurha, Pavan; Ahmad, Sabih; Dass, Prashant

2014-01-01

Malignant Hyperthermia is a pharmacogenetic disorder. Classical manifestations comprise of tachycardia, increase in expired carbon dioxide levels, muscle rigidity, hyperthermia (>38.8°C) and unexpected acidosis. Here we report a case of 16-year-old female patient, ASA-I with chronic rhino-sinusitis and slight strabismus of the left eye posted for functional endoscopic sinus surgery, developing a rise in ETCO2 and temperature immediately following anesthesia induction. She was aggressively managed to an uneventful recovery. We present a case of intra-operative post-induction hyperthermia possibly MH, its anesthetic implications, challenges encountered and its management. PMID:25425784

Central effects of some peptide and non-peptide opioids and naloxone on thermoregulation in the rabbit

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williams, B. A.

1983-01-01

The effects of several peptide and non-peptide opiods and naloxone on induced hyperthermia is studied in rabbits. The effect of tyical mu, kappa, and sigma receptor antagonists (morphine, ketocyclazcine and SKF 10,0 10, 047) and some opioid peptides (Beta-endorphin /BE/, methionine-enkaphalin /ME/, and D-Ala2-methionine-enkaphalin-amide /DAME/ are determined. The role of prostaglandins (PG), cAMP, and norepinephrine (NE) in morphine, BE, and DAME induced hyperthermia is investigated. In addition, the effect of naloxone on pyrogen, arachidonic acid, PGE2, prostacyclin, dibutyryl cAMP, and NE induced hyperthermia is determined. Among other results, it is found that the three receptor antagonists induced hyperthermia in rabbits. BE, ME, and DAME were also found to cause hyperthermia, and it is suggested that they act on the same type of receptor. It is also determined that neither NE nor cAMP is involved in the hyperthermia due to morphine, BE, and DAME. It is suggested that an action of endogenous peptides on naloxone sensitive receptors plays little role in normal thermoregulation or in hyperthermia.

Ischemic Brain Injury Leads to Brain Edema via Hyperthermia-Induced TRPV4 Activation.

PubMed

Hoshi, Yutaka; Okabe, Kohki; Shibasaki, Koji; Funatsu, Takashi; Matsuki, Norio; Ikegaya, Yuji; Koyama, Ryuta

2018-06-20

Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain largely unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which male mouse brain slices were treated with oxygen-glucose deprivation (OGD) to mimic ischemia. We continuously measured the cross-sectional area of the brain slice for 150 min under macroscopic microscopy, finding that OGD induces swelling of brain slices. OGD-induced swelling was prevented by pharmacologically blocking or genetically knocking out the transient receptor potential vanilloid 4 (TRPV4), a member of the thermosensitive TRP channel family. Because TRPV4 is activated at around body temperature and its activation is enhanced by heating, we next elevated the temperature of the perfusate in the recording chamber, finding that hyperthermia induces swelling via TRPV4 activation. Furthermore, using the temperature-dependent fluorescence lifetime of a fluorescent-thermosensitive probe, we confirmed that OGD treatment increases the temperature of brain slices through the activation of glutamate receptors. Finally, we found that brain edema following traumatic brain injury was suppressed in TRPV4-deficient male mice in vivo Thus, our study proposes a novel mechanism: hyperthermia activates TRPV4 and induces brain edema after ischemia. SIGNIFICANCE STATEMENT Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which mouse brain slices were treated with oxygen-glucose deprivation. Using this system, we showed that the increase in brain temperature and the following activation of the thermosensitive cation channel TRPV4 (transient receptor potential vanilloid 4) are involved in the pathology of edema. Finally, we confirmed that TRPV4 is involved in brain edema in vivo using TRPV4-deficient mice, concluding that hyperthermia activates TRPV4 and induces brain edema after ischemia. Copyright © 2018 the authors 0270-6474/18/385700-10$15.00/0.

Peptide and non-peptide opioid-induced hyperthermia in rabbits

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williams, B. A.

1983-01-01

The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl-normetazocine was found to induce hyperthermia in rabbits. The similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME), and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) was also found to cause hyperthermia. Results indicate that only the liver-like transport system is important to the ventricular inactivation of BE and DAME. Prostaglandins and norepinephrine were determined not to be involved in peptide and nonpeptide opioid-induced hyperthermia. In addition, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and nonpeptide opioids. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine, BE, ME, and DAME since naloxone attenuated them. However, the hyperthermic response to ketocyclazocine and N-allyl-normetazocine was not antagonized by naloxone.

σ Receptor antagonist attenuation of methamphetamine-induced neurotoxicity is correlated to body temperature modulation.

PubMed

Robson, Matthew J; Seminerio, Michael J; McCurdy, Christopher R; Coop, Andrew; Matsumoto, Rae R

2013-01-01

Methamphetamine (METH) causes hyperthermia and dopaminergic neurotoxicity in the rodent striatum. METH interacts with σ receptors and σ receptor antagonists normally mitigate METH-induced hyperthermia and dopaminergic neurotoxicity. The present study was undertaken because in two experiments, pretreatment with σ receptor antagonists failed to attenuate METH-induced hyperthermia in mice. This allowed us to determine whether the ability of σ receptor antagonists (AZ66 and AC927) to mitigate METH-induced neurotoxicity depends upon their ability to modulate METH-induced hyperthermia. Mice were treated using a repeated dosing paradigm and body temperatures recorded. Striatal dopamine was measured one week post-treatment. The data indicate that the ability of σ receptor antagonists to attenuate METH-induced dopaminergic neurotoxicity is linked to their ability to block METH-induced hyperthermia. The ability of σ receptor antagonists to mitigate METH-induced hyperthermia may contribute to its neuroprotective actions.

Hyperthermia in the treatment of cancer: A review of the radiobiological basis

NASA Technical Reports Server (NTRS)

Baker, D. G.

1978-01-01

Temperatures in the range 41.5 C to 43.5 C tend to be more damaging to malignant than nonmalignant cells. Where local hyperthermia (41.5 C to 43.5 C) is combined with ionizing radiation, a significant therapeutic ratio may be realized. Total body hyperthermia, alone or combined with other therapeutic modalities, can provide palliation for some systemic malignancies but may not be as effective as local hyperthermia for treating local disease. The influence of hyperthermia on immune mechanisms and the risk of metastatic spread of potential tumor growth stimulation need further investigation. Among other questions needing elucidation before hyperthermia can be considered a standard treatment modality are the time-dose (for heating) relationships to produce an optimal therapeutic ratio and whether the late sequela of combined heat and ionizing radiation may result in an unacceptable risk of patient morbidity.

Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families.

PubMed

Sambuughin, N; Nelson, T E; Jankovic, J; Xin, C; Meissner, G; Mullakandov, M; Ji, J; Rosenberg, H; Sivakumar, K; Goldfarb, L G

2001-09-01

Malignant hyperthermia is a pharmacogenetic disorder associated with mutations in Ca(2+) regulatory proteins. It manifests as a hypermetabolic crisis triggered by commonly used anesthetics. Malignant hyperthermia susceptibility is a dominantly inherited predisposition to malignant hyperthermia that can be diagnosed by using caffeine/halothane contracture tests. In a multigenerational North American family with a severe form of malignant hyperthermia that has caused four deaths, a novel RYR1 A2350T missense mutation was identified in all individuals testing positive for malignant hyperthermia susceptibility. The same A2350T mutation was identified in an Argentinean family with two known fatal MH reactions. Functional analysis in HEK-293 cells revealed an altered Ca(2+) dependence and increased caffeine sensitivity of the expressed mutant protein thus confirming the pathogenic potential of the RYR1 A2350T mutation.

The influence of hyperthermia on intracranial pressure, cerebral oximetry and cerebral metabolism in traumatic brain injury

PubMed Central

Nyholm, Lena; Howells, Tim; Lewén, Anders; Hillered, Lars; Enblad, Per

2017-01-01

Background Hyperthermia is a common secondary insult in traumatic brain injury (TBI). The aim was to evaluate the relationship between hyperthermia and intracranial pressure (ICP), and if intracranial compliance and cerebral blood flow (CBF) pressure autoregulation affected that relationship. The relationships between hyperthermia and cerebral oximetry (BtipO2) and cerebral metabolism were also studied. Methods A computerized multimodality monitoring system was used for data collection at the neurointensive care unit. Demographic and monitoring data (temperature, ICP, blood pressure, microdialysis, BtipO2) were analyzed from 87 consecutive TBI patients. ICP amplitude was used as measure of compliance, and CBF pressure autoregulation status was calculated using collected blood pressure and ICP values. Mixed models and comparison between groups were used. Results The influence of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and BtipO2) was small, but individual differences were seen. Linear mixed models showed that hyperthermia raises ICP slightly more when temperature increases in the groups with low compliance and impaired CBF pressure autoregulation. There was also a tendency (not statistically significant) for increased BtipO2, and for increased pyruvate and lactate, with higher temperature, while the lactate/pyruvate ratio and glucose were stable. Conclusions The major finding was that the effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and BtipO2) were not extensive in general, but there were exceptional cases. Hyperthermia treatment has many side effects, so it is desirable to identify cases in which hyperthermia is dangerous. Information from multimodality monitoring may be used to guide treatment in individual patients. PMID:28463046

Effects of hyperthermia on ventilation and metabolism during hypoxia in conscious mice.

PubMed

Iwase, Michiko; Izumizaki, Masahiko; Kanamaru, Mitsuko; Homma, Ikuo

2004-02-01

Hyperthermia and hypoxia influence ventilation and metabolism; however, their synergistic effects remain unanswered. We hypothesized that an enhancement of ventilation induced by hyperthermia is competitive with hypoxic hypometabolism. We then examined the relationship of body temperature, hypoxia, and respiration in conscious mice, measuring minute ventilation (VE), aerobic metabolism, and arterial blood gases. All parameters were measured at two different body temperatures (BTs), approximately 37 degrees C (normothermia) and 39 degrees C (hyperthermia), under both normoxia (room air inhalation) and hypoxia (7% O2 inhalation). Under normoxia, VE and O2 consumption (VO2) were lower at hyperthermia than at normothermia, and the VE-VO2 ratio remained constant. PaCO2 values were normal at both BTs under normoxia. Hypoxic gas inhalation increased VE, which reached a peak in 2 min, then decreased at both BTs. VE remained at a higher level during hyperthermia than during normothermia throughout the 10 min experiment. VO2 decreased during hypoxia at both BTs. Hypoxia increased the VE-VO2 ratio because of relatively high VE with respect to the decreased VO2, which means hyperventilation. At hypoxia under hyperthermia, serious hyperventilation occurred with a further increase in VE. The augmented ventilation may be due to the thermal stimulus and a lowered thermoregulatory set point for hypoxia. Thus hyperthermia reduces ventilation and metabolism to maintain normocapnia; as a result, thermogenesis is reduced under normoxia. Hyperthermia augments hyperventilation induced by hypoxia, leading to severe hypoxic hypocapnia. Thermal stimuli may impair the adjustment of ventilation and metabolism when O2 is limited.

Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles.

PubMed

Wang, Lufang; Dong, Jian; Ouyang, Weiwei; Wang, Xiaowen; Tang, Jintian

2012-03-01

We investigated the effect and feasibility of hyperthermia treatment on subcutaneous pancreatic cancer in female Kunming mice, using a murine pancreatic cancer cell line (MPC-83) established by us and found in this study to originate from epithelial pancreatic acinus. Magnetic fluid (MF) with ferromagnetic particles of about 20 nm in size was used as a heating mediator. MF was injected into the subcutaneous nodules with subaxillary regions of mice 10 days after tumor transplantation; homogeneous distribution of magnetic nanoparticles in nodules was easily detected by X-ray 24 h later. Mice were allocated to four groups as follows: no treatment (control); MF injection alone; alternating magnetic field (AMF) irradiation alone; and MF injection and hyperthermia generated by applying AMF (300 kHz, 110 Gs). The two hyperthermia-treated subgroup tumors reached central temperatures of 47 and 51˚C, respectively, for 30 min; while rectal temperature in both subgroups remained below 36˚C. Tumor growth was inhibited and survival significantly prolonged in the hyperthermia group compared with other groups (P<0.05). Tumor cells near the MF in the hyperthermia group apoptosed or necrosed immediately after hyperthermia. By day 14, there were no subcutaneous nodules; and residual magnetic nanoparticles were ingested by phagocytes. Nuclear proliferating cell nuclear antigen (PCNA) decreased in hyperthermia group tumor cells compared to the other groups; cytoplasmic heat shock protein 70 (HSP 70) was conspicuously higher immediately after hyperthermia (P<0.05). This technique had therapeutic potential and provided a new idea in the treatment of pancreatic cancer.

Radiation enhanced efficiency of combined electromagnetic hyperthermia and chemotherapy of lung carcinoma using cisplatin functionalized magnetic nanoparticles.

PubMed

Babincová, M; Kontrisova, K; Durdík, S; Bergemann, C; Sourivong, P

2014-02-01

The effect of trimodality treatment consisting of hyperthermia, cisplatin and radiation was investigated in two non-small lung carcinoma cell lines with different sensitivities to cisplatin. Hyperthermia treatment was performed using heat released via Neél and Brown relaxation of magnetic nanoparticles in an alternating magnetic field. Radiation with dose 1.5 Gy was performed after 15 min electromagnetic hyperthermia and cisplatin treatment. Electromagnetic hyperthermia enhanced cisplatin-induced radiosensitization in both the cisplatin-sensitive H460 (viability 11.2 +/- 1.8 %) and cisplatin-resistant A549 (viability 14.5 +/- 2.3 %) lung carcinoma cell line. Proposed nanotechnology based trimodality cancer treatment may have therefore important clinical applications.

Combined magnetic nanoparticle-based microRNA and hyperthermia therapy to enhance apoptosis in brain cancer cells.

PubMed

Yin, Perry T; Shah, Birju P; Lee, Ki-Bum

2014-10-29

A novel therapy is demonstrated utilizing magnetic nanoparticles for the dual purpose of delivering microRNA and inducing magnetic hyperthermia. In particular, the combination of lethal-7a microRNA (let-7a), which targets a number of the survival pathways that typically limit the effectiveness of hyperthermia, with magnetic hyperthermia greatly enhances apoptosis in brain cancer cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

PubMed

Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

2016-01-01

MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

PubMed Central

Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

2016-01-01

MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results. PMID:26105141

Photoacoustic-Based-Close-Loop Temperature Control for Nanoparticle Hyperthermia.

PubMed

Xiaohua, Feng; Fei, Gao; Yuanjin, Zheng

2015-07-01

Hyperthermia therapy requires tight temperature control to achieve selective killing of cancerous tissue with minimal damage on surrounding healthy tissues. To this end, accurate temperature monitoring and subsequent heating control are critical. However, an economic, portable, and real-time temperature control solution is currently lacking. To bridge this gap, we present a novel portable close-loop system for hyperthermia temperature control, in which photoacoustic technique is proposed for noninvasive real-time temperature measurement. Exploiting the high sensitivity of photoacoustics, the temperature is monitored with an accuracy of around 0.18 °C and then fed back to a controller implemented on field programmable gate array (FPGA) for temperature control. Dubbed as portable hyperthermia feedback controller (pHFC), it stabilizes the temperature at preset values by regulating the hyperthermia power with a proportional-integral-derivative (PID) algorithm; and to facilitate digital implementation, the pHFC further converts the PID output into switching values (0 and 1) with the pulse width modulation (PWM) algorithm. Proof-of-concept hyperthermia experiments demonstrate that the pHFC system is able to bring the temperature from baseline to predetermined value with an accuracy of 0.3° and a negligible temperature overshoot. The pHFC can potentially be translated to clinical applications with customized hyperthermia system design. This paper can facilitate future efforts in seamless integration of close-loop temperature control solution and various clinical hyperthermia systems.

Ultrastructure of rabbit embryos exposed to hyperthermia and anti-Hsp 70.

PubMed

Olexikova, L; Makarevich, A V; Pivko, J; Chrenek, P

2013-08-01

The aim of the study was to determine the effect of short-term hyperthermia and Hsp70 blockage on ultrastructural changes in cell organelles and nucleoli of rabbit preimplantation embryos. The embryos were cultured either at 37.5°C (control, C) or 41.5°C (hyperthermia, HT) during 6 h. The antibody against Hsp70 was added into the culture medium (4 μg/ml) of morula stage embryos from C and HT groups. After termination of the culture, the embryos were processed for transmission electron microscopy. The embryos exposed to hyperthermia showed increased volume of lipid droplets, considerable occurrence of cellular debris in the perivitelline space and slight changes in the occurrence of microvilli on the surface of trophoblastic cells. In the embryos exposed to anti-Hsp 70 at 37.5°C, there were considerable changes in mitochondria morphology, decreased volume of dense bodies in the cytoplasm and considerable changes in the occurrence of microvilli on the surface of trophoblastic cells. In the group of embryos exposed simultaneously to hyperthermia and anti-Hsp 70, mitochondria were also expanded and swollen; the volume of flocculent vesicles and lipid droplets was increased and the volume of dense bodies in the cytoplasm was diminished. General organization of the cytoplasm in groups with anti-Hsp70 was characterized by cell organelle segregation. Averaged size of the nucleolar area was significantly increased in the embryos exposed to hyperthermia, whereas in the group exposed to the anti-Hsp70 without hyperthermia it was significantly diminished. Hyperthermia also caused disintegration of compact status of the nucleoli. In presence of anti-Hsp 70, the structural changes, described within the nucleoli during hyperthermia, were not observed. In conclusion, these results document ultrastructural changes in cell organelles of rabbit preimplantation embryo caused by hyperthermia, and also changes in the nucleolar structures, at which presence of Hsp-70 inhibit these changes. © 2012 Blackwell Verlag GmbH.

Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy

PubMed Central

Marangon, Iris; Silva, Amanda A. K.; Guilbert, Thomas; Kolosnjaj-Tabi, Jelena; Marchiol, Carmen; Natkhunarajah, Sharuja; Chamming's, Foucault; Ménard-Moyon, Cécilia; Bianco, Alberto; Gennisson, Jean-Luc; Renault, Gilles; Gazeau, Florence

2017-01-01

Tumor stiffening, stemming from aberrant production and organization of extracellular matrix (ECM), has been considered a predictive marker of tumor malignancy, non-invasively assessed by ultrasound shear wave elastography (SWE). Being more than a passive marker, tumor stiffening restricts the delivery of diagnostic and therapeutic agents to the tumor and per se could modulate cellular mechano-signaling, tissue inflammation and tumor progression. Current strategies to modify the tumor extracellular matrix are based on ECM-targeting chemical agents but also showed deleterious systemic effects. On-demand excitable nanomaterials have shown their ability to perturb the tumor microenvironment in a spatiotemporal-controlled manner and synergistically with chemotherapy. Here, we investigated the evolution of tumor stiffness as well as tumor integrity and progression, under the effect of mild hyperthermia and thermal ablation generated by light-exposed multi-walled carbon nanotubes (MWCNTs) in an epidermoid carcinoma mouse xenograft. SWE was used for real-time mapping of the tumor stiffness, both during the two near infrared irradiation sessions and over the days after the treatment. We observed a transient and reversible stiffening of the tumor tissue during laser irradiation, which was lowered at the second session of mild hyperthermia or photoablation. In contrast, over the days following photothermal treatment, the treated tumors exhibited a significant softening together with volume reduction, whereas non-treated growing tumors showed an increase of tumor rigidity. The organization of the collagen matrix and the distribution of CNTs revealed a spatio-temporal correlation between the presence of nanoheaters and the damages on collagen and cells. This study highlights nanohyperthermia as a promising adjuvant strategy to reverse tumor stiffening and normalize the mechanical tumor environment. PMID:28042338

The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation.

PubMed

Gavva, Narender R; Bannon, Anthony W; Surapaneni, Sekhar; Hovland, David N; Lehto, Sonya G; Gore, Anu; Juan, Todd; Deng, Hong; Han, Bora; Klionsky, Lana; Kuang, Rongzhen; Le, April; Tamir, Rami; Wang, Jue; Youngblood, Brad; Zhu, Dawn; Norman, Mark H; Magal, Ella; Treanor, James J S; Louis, Jean-Claude

2007-03-28

The vanilloid receptor TRPV1 (transient receptor potential vanilloid 1) is a cation channel that serves as a polymodal detector of pain-producing stimuli such as capsaicin, protons (pH <5.7), and heat. TRPV1 antagonists block pain behaviors in rodent models of inflammatory, neuropathic, and cancer pain, suggesting their utility as analgesics. Here, we report that TRPV1 antagonists representing various chemotypes cause an increase in body temperature (hyperthermia), identifying a potential issue for their clinical development. Peripheral restriction of antagonists did not eliminate hyperthermia, suggesting that the site of action is predominantly outside of the blood-brain barrier. Antagonists that are ineffective against proton activation also caused hyperthermia, indicating that blocking capsaicin and heat activation of TRPV1 is sufficient to produce hyperthermia. All TRPV1 antagonists evaluated here caused hyperthermia, suggesting that TRPV1 is tonically activated in vivo and that TRPV1 antagonism and hyperthermia are not separable. TRPV1 antagonists caused hyperthermia in multiple species (rats, dogs, and monkeys), demonstrating that TRPV1 function in thermoregulation is conserved from rodents to primates. Together, these results indicate that tonic TRPV1 activation regulates body temperature.

Effective elimination of cancer stem cells by magnetic hyperthermia.

PubMed

Sadhukha, Tanmoy; Niu, Lin; Wiedmann, Timothy Scott; Panyam, Jayanth

2013-04-01

Cancer stem cells (CSCs) are a subpopulation of cancer cells that have stem cell-like properties and are thought to be responsible for tumor drug resistance and relapse. Therapies that can effectively eliminate CSCs will, therefore, likely inhibit tumor recurrence. The objective of our study was to determine the susceptibility of CSCs to magnetic hyperthermia, a treatment that utilizes superparamagnetic iron oxide nanoparticles placed in an alternating magnetic field to generate localized heat and achieve selective tumor cell kill. SPIO NPs having a magnetite core of 12 nm were used to induce magnetic hyperthermia in A549 and MDA-MB-231 tumor cells. Multiple assays for CSCs, including side population phenotype, aldehyde dehydrogenase expression, mammosphere formation, and in vivo xenotransplantation, indicated that magnetic hyperthermia reduced or, in some cases, eliminated the CSC subpopulation in treated cells. Interestingly, conventional hyperthermia, induced by subjecting cells to elevated temperature (46 °C) in a water bath, was not effective in eliminating CSCs. Our studies show that magnetic hyperthermia has pleiotropic effects, inducing acute necrosis in some cells while stimulating reactive oxygen species generation and slower cell kill in others. These results suggest the potential for lower rates of tumor recurrence after magnetic hyperthermia compared to conventional cancer therapies.

Magnetomotive Optical Coherence Elastography for Magnetic Hyperthermia Dosimetry Based on Dynamic Tissue Biomechanics

PubMed Central

Huang, Pin-Chieh; Pande, Paritosh; Ahmad, Adeel; Marjanovic, Marina; Spillman, Darold R.; Odintsov, Boris; Boppart, Stephen A.

2016-01-01

Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively. MNPs have also been independently used for magnetic hyperthermia treatments, enabling therapeutic functions such as killing tumor cells. It is well known that the localized tissue heating during hyperthermia treatments result in a change in the biomechanical properties of the tissue. Therefore, we propose a novel dosimetric technique for hyperthermia treatment based on the viscoelasticity change detected by MM-OCE, further enabling the theranostic function of MNPs. In this paper, we first review the basic principles and applications of MM-OCT, MM-OCE, and magnetic hyperthermia, and present new preliminary results supporting the concept of MM-OCE-based hyperthermia dosimetry. PMID:28163565

A Study for Cryosurgery-Hyperthermia Treatment System

NASA Astrophysics Data System (ADS)

Takahashi, Daishi; Takahashi, Tomoya; Sone, Kazuya; Fukumoto, Ichiro

Cryosurgical system utilizing liquid nitrogen and argon gas as cryogens has been used for the treatment of malignant tumors. Those devices fail to cool the tissues to the low temperatures that completely destroy the bulky tumors. It is of course difficult for the low power cooling devices using Peltier effect, to destroy the large tumors. Therefore adjunctive treatment such as hyperthermia treatment is needed to intensify the tissue destruction. Actually, hyperthermia has been clinically used to destroy tumors, but it is unclear that the hyperthermia enhances the tissue injury in cryosurgery because there have been few studies of the combination use of hyperthermia and cryosurgery. The purposes of this study are to produce the cryosurgery-hyperthermia treatment system utilizing Peltier device and Stirling cooler and to evaluate the effects of hyperthermia treatment immediately after thawing in cryosurgery onto the living normal liver tissue of mouse. In the no-load running test of our system, the minimum temperature of the cryoprobe reached -74.0 degrees C in 30 minutes. The findings of the stained tissues suggested that the combination treatment of both was effective to destroy the tissue and the higher temperature applied immediately after freezing and thawing in cryosurgery might reinforce the tissue destruction.

EFFECTS OF HYPERTHERMIA AND HYPERTHERMIA PLUS MICROWAVES ON RAT BRAIN ENERGY METABOLISM

EPA Science Inventory

The effects of hyperthermia, alone and in conjunction with microwave exposure, on brain energetics were studied in anesthetized male Sprague-Dawley rats. The effects of temperature on adenosine triphosphate concentration (ATP) and creatine phosphate concentration (CP) was determi...

Optimized Hyperthermia Treatment of Prostate Cancer Using a Novel Intracavitary Ultrasound Array

DTIC Science & Technology

2006-01-01

Overgaard J, Gonzalez GD, Hulshof MC, Arcangeli G, Dahl O, Mella O, et al. 1995. Randomised trial of hyperthermia as adjuvant to radiotherapy for...Gonzalez, G. D., Hulshof , M. C., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S. M., "Hyperthermia as an adjuvant to radiation therapy of recurrent or...25 pp. 79-85, 1993. 9. Overgaard, J., Gonzalez, G. D., Hulshof , M. C., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S. M.: Hyperthermia as an

Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

PubMed Central

LIU, JIAYI; LI, NING; LI, LI; LI, DANYE; LIU, KAI; ZHAO, LINGYUN; TANG, JINTIAN; LI, LIYA

2013-01-01

Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment. PMID:24260045

Ultra-small superparamagnetic iron oxide mediated magnetic hyperthermia in treatment of neck lymph node metastasis in rabbit pyriform sinus VX2 carcinoma.

PubMed

Wang, Peng; Xie, Xiaofeng; Wang, Jian; Shi, Yuan; Shen, Na; Huang, Xinsheng

2015-09-01

Lymph node metastasis of rabbit VX2 pyriform sinus carcinoma can be enhanced by MR scanning after injecting ultra-small superparamagnetic iron oxide (USPIO) into the submucosa beside the tumor. The metastasis lymph node which fit in with the diagnostic criteria will be placed into the alternating magnetic field after MR scanning. Then, magnetic particles can be heated to the effective therapeutic temperature. And it evaluates the possibility of diagnosis together with therapy in cervical metastasis of pyriform sinus carcinoma. Twenty rabbits bearing VX2 tumor in pyriform sinuses were randomly divided into hyperthermia group and control group after USPIO MR scanning; each group contained 10 rabbits. The hyperthermia for the experimental group was conducted by the alternating magnetic field. After hyperthermia, the detection of apoptosis for the two groups was tested by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL), transmission electron microscopy (TEM), and the expression of Bcl-2 and Bax evaluated by immunohistochemical analysis. The apoptosis rate detected by TUNEL in hyperthermia group was 100 %, while the control group was only 20 % (p < 0.05). TEM observation showed that cell chromatin condensation and clumping, condensed cytoplasm, endoplasmic reticulum membrane fusion with loose change, and the formation of a bubble could be seen in the hyperthermia group. However, the control group showed a more complete cytoplasm and nucleus. Bcl-2 protein expression in the hyperthermia group was lower than the control group, and Bax protein expression in hyperthermia group was higher (p < 0.05). USPIO indirect lymphography could localize the metastatic lymph nodes for hyperthermia. And it could make the metastatic cervical lymph nodes apoptosis when placed into the alternating magnetic field.

Regulation of body temperature and nociception induced by non-noxious stress in rat.

PubMed

Vidal, C; Suaudeau, C; Jacob, J

1984-04-09

The effects of 3 different non-noxious stressors on body temperature (Tb) were investigated in the rat: (1) loose restraint in cylinders, (2) removal of the rats from cylinders, exposure to a novel environment and replacement in cylinders, a stressor called here 'novelty', and (3) gentle holding of the rats by the nape of the neck. Loose restraint and 'novelty' produced hyperthermia. On the contrary, holding induced hypothermia. Hypophysectomy (HX) reduced basal Tb, abolished restraint hyperthermia and reduced both 'novelty' hyperthermia and holding hypothermia. Dexamethasone ( DEXA ) had no effect upon either restraint or novelty hyperthermia but reduced the hypothermia. Naloxone (Nx) produced a slight fall in basal Tb accounting for its reduction of restraint and 'novelty' hyperthermias ; it did not affect holding hypothermia. The inhibitory effects of HX suggest a participation of the pituitary in the hyperthermias ; the neurointermediate lobe would be involved as the hyperthermias were not affected by DEXA , which is known to block the stress-induced release of pituitary secretions from the anterior lobe but not from the neurointermediate lobe. In contrast, substances from the anterior lobe might participate in hypothermia due to holding since it is reduced by HX and DEXA . As to the effects of Nx, endogenous opioids would not be significantly involved in the thermic effects of the stressors used in this study; they might play, if any, only a minor role in the regulation of basal Tb. These results are compared with those previously obtained on nociception using the same non-noxious stressors. It emerges that, depending on the stressor, different types of association between thermoregulation and nociception may occur, i.e. hyperthermia with analgesia, hyperthermia with hyperalgesia and hypothermia with hyperalgesia.

The effects of hyperthermia on the immunomodulatory properties of human umbilical cord vein mesenchymal stem cells (MSCs).

PubMed

Hesami, Shilan; Mohammadi, Mehdi; Rezaee, Mohamad Ali; Jalili, Ali; Rahmani, Mohammad Reza

2017-11-01

Hyperthermia can modulate inflammation and the immune response. Based on the recruitment of mesenchymal stem cells (MSCs) to inflamed tissues and the immunomodulatory properties of these cells, the aim of this study was to examine the effects of hyperthermia on the immunomodulatory properties of MSCs in a mixed lymphocyte reaction (MLR). Passages 4-6 of human umbilical cord vein mesenchymal stem cells were co-cultured in a two-way MLR. Cells in the hyperthermia groups were incubated at 41 °C for 45 min. A colorimetric assay was employed to examine the effects of MSCs on cell proliferation. The levels of IL-4 and TNF-α proteins in the cell culture supernatant were measured, and non-adherent cells were used for RNA extraction, which was then used for cDNA synthesis. RT-PCR was utilised to assess levels of IL-10, IL-17A, IL-4, TNF-α, TGF-β1, FOX P 3 , IFN-γ, CXCL12 and β-actin mRNA expression. UCV-MSCs co-cultured in an MLR reduced lymphocyte proliferation at 37 °C, whereas hyperthermia attenuated this effect. Hyperthermia increased expression of IL-10, TGF-β1 and FOXP3 mRNAs in co-culture; however, no effects on IL-17A and IFN-γ were observed, and it reduced CXCL12 expression. In co-culture, IL-4 mRNA and protein increased at 37 °C, an effect that was reduced by hyperthermia. No considerable change in TNF-α mRNA expression was found in hyperthermia-treated cells. Hyperthermia increases cell proliferation of the peripheral blood mononuclear cells and modifies the cytokine profile in the presence of UCV-MSCs.

Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection.

PubMed

Bear, Joseph C; Patrick, P Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J; Pankhurst, Quentin A; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P; Mayes, Andrew G

2016-09-27

Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it's drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.

Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.

PubMed

Alvarez-Berríos, Merlis P; Castillo, Amalchi; Rinaldi, Carlos; Torres-Lugo, Madeline

2014-01-01

The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.

Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

PubMed Central

Seminerio, Michael J.; Robson, Matthew J.; McCurdy, Christopher R.; Matsumoto, Rae R.

2013-01-01

Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced doseand time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression. PMID:22820108

Magnetic nanoparticles for medical applications: Progress and challenges

NASA Astrophysics Data System (ADS)

Doaga, A.; Cojocariu, A. M.; Constantin, C. P.; Hempelmann, R.; Caltun, O. F.

2013-11-01

Magnetic nanoparticles present unique properties that make them suitable for applications in biomedical field such as magnetic resonance imaging (MRI), hyperthermia and drug delivery systems. Magnetic hyperthermia involves heating the cancer cells by using magnetic particles exposed to an alternating magnetic field. The cell temperature increases due to the thermal propagation of the heat induced by the nanoparticles into the affected region. In order to increase the effectiveness of the treatment hyperthermia can be combined with drug delivery techniques. As a spectroscopic technique MRI is used in medicine for the imaging of tissues especially the soft ones and diagnosing malignant or benign tumors. For this purpose ZnxCo1-xFe2O4 ferrite nanoparticles with x between 0 and 1 have been prepared by co-precipitation method. The cristallite size was determined by X-ray diffraction, while the transmission electron microscopy illustrates the spherical shape of the nanoparticles. Magnetic characterizations of the nanoparticles were carried out at room temperature by using a vibrating sample magnetometer. The specific absorption rate (SAR) was measured by calorimetric method at different frequencies and it has been observed that this value depends on the chemical formula, the applied magnetic fields and the frequency. The study consists of evaluating the images, obtained from an MRI facility, when the nanoparticles are dispersed in agar phantoms compared with the enhanced ones when Omniscan was used as contrast agent. Layer-by-layer technique was used to achieve the necessary requirement of biocompatibility. The surface of the magnetic nanoparticles was modified by coating it with oppositely charged polyelectrolites, making it possible for the binding of a specific drug.

Hyperthermia with implanted electrodes.

PubMed

Brezovich, I A; Young, J H

1981-01-01

A general solution is given for the steady state form of the heat conduction equation applied to a simple tumor model which is imagined as being heated by means of electrical currents flowing between metallic electrodes. The model assumes a homogeneous tumor with no bloodflow. The solution for the special case of constant temperature and potential at the surface of the heated volume is examined in detail. The solution shows that there exists, independent of the particular tumor and electrode geometry, a close relationship between the steady state temperature distribution and the electrical potential. Among the more important implications of this relationship are that equipotential surfaces within the heated volume are also isothermal surfaces and that no areas of excessive heat at or near any sharp edges or corners of the electrodes should develop, despite the high electric field intensity. Based on the theory, a procedure is outlined which might greatly facilitate the determination of temperature distributions in phantoms. Finally, the usefulness and the limitations of the theoretical models in clinical hyperthermia are discussed.

Skull and cerebrospinal fluid effects on microwave radiation propagation in human brain

NASA Astrophysics Data System (ADS)

Ansari, M. A.; Zarei, M.; Akhlaghipour, N.; Niknam, A. R.

2017-12-01

The determination of microwave absorption distribution in the human brain is necessary for the detection of brain tumors using thermo-acoustic imaging and for removing them using hyperthermia treatment. In contrast to ionizing radiation, hyperthermia treatment can be applied to remove tumors inside the brain without the concern of including secondary malignancies, which typically form from the neuronal cells of the septum pellucidum. The aim of this study is to determine the microwave absorption distribution in an adult human brain and to study the effects of skull and cerebrospinal fluid on the propagation of microwave radiation inside the brain. To this end, we simulate the microwave absorption distribution in a realistic adult brain model (Colin 27) using the mesh-based Monte Carlo (MMC) method. This is because in spite of there being other numerical methods, the MMC does not require a large memory, even for complicated geometries, and its algorithm is simple and easy to implement with low computational cost. The brain model is constructed using high-resolution (1 mm isotropic voxel) and low noise magnetic resonance imaging (MRI) scans and its volume contains 181×217×181 voxels, covering the brain completely. Using the MMC method, the radiative transport equation is solved and the absorbed microwave energy distribution in different brain regions is obtained without any fracture or anomaly. The simulation results show that the skull and cerebrospinal fluid guide the microwave radiation and suppress its penetration through deep brain compartments as a shielding factor. These results reveal that the MMC can be used to predict the amount of required energy to increase the temperature inside the tumour during hyperthermia treatment. Our results also show why a deep tumour inside an adult human brain cannot be efficiently treated using hyperthermia treatment. Finally, the accuracy of the presented numerical method is verified using the signal flow graph technique.

MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment.

PubMed

Kiyatkin, Eugene A; Ren, Suelynn E

2017-01-01

Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA-induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential dangers of MDMA in humans and the development of pharmacological tools to alleviate drug-induced hyperthermia - potentially saving the lives of highly intoxicated individuals.

Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice

PubMed Central

Sanchez-Alavez, Manuel; Bortell, Nikki; Galmozzi, Andrea; Conti, Bruno; Marcondes, Maria Cecilia G.

2014-01-01

Hyperthermia is a potentially lethal side effect of Methamphetamine (Meth) abuse, which involves the participation of peripheral thermogenic sites such as the Brown Adipose Tissue (BAT). In a previous study we found that the anti-oxidant N-acetyl cysteine (NAC) can prevent the high increase in temperature in a mouse model of Meth-hyperthermia. Here, we have further explored the ability of NAC to modulate Meth-induced hyperthermia in correlation with changes in BAT. We found that NAC treatment in controls causes hypothermia, and, when administered prior or upon the onset of Meth-induced hyperthermia, can ameliorate the temperature increase and preserve mitochondrial numbers and integrity, without affecting locomotor activity. This was different from Dantrolene, which decreased motor activity without affecting temperature. The effects of NAC were seen in spite of its inability to recover the decrease of mitochondrial superoxide induced in BAT by Meth. In addition, NAC did not prevent the Meth-induced decrease of BAT glutathione. Treatment with S-adenosyl-L-methionine, which improves glutathione activity, had an effect in ameliorating Meth-induced hyperthermia, but also modulated motor activity. This suggests a role for the remaining glutathione for controlling temperature. However, the mechanism by which NAC operates is independent of glutathione levels in BAT and specific to temperature. Our results show that, in spite of the absence of a clear mechanism of action, NAC is a pharmacological tool to examine the dissociation between Meth-induced hyperthermia and motor activity, and a drug of potential utility in treating the hyperthermia associated with Meth-abuse. PMID:26346736

Magnetic hyperthermia properties of nanoparticles inside lysosomes using kinetic Monte Carlo simulations: Influence of key parameters and dipolar interactions, and evidence for strong spatial variation of heating power

NASA Astrophysics Data System (ADS)

Tan, R. P.; Carrey, J.; Respaud, M.

2014-12-01

Understanding the influence of dipolar interactions in magnetic hyperthermia experiments is of crucial importance for fine optimization of nanoparticle (NP) heating power. In this study we use a kinetic Monte Carlo algorithm to calculate hysteresis loops that correctly account for both time and temperature. This algorithm is shown to correctly reproduce the high-frequency hysteresis loop of both superparamagnetic and ferromagnetic NPs without any ad hoc or artificial parameters. The algorithm is easily parallelizable with a good speed-up behavior, which considerably decreases the calculation time on several processors and enables the study of assemblies of several thousands of NPs. The specific absorption rate (SAR) of magnetic NPs dispersed inside spherical lysosomes is studied as a function of several key parameters: volume concentration, applied magnetic field, lysosome size, NP diameter, and anisotropy. The influence of these parameters is illustrated and comprehensively explained. In summary, magnetic interactions increase the coercive field, saturation field, and hysteresis area of major loops. However, for small amplitude magnetic fields such as those used in magnetic hyperthermia, the heating power as a function of concentration can increase, decrease, or display a bell shape, depending on the relationship between the applied magnetic field and the coercive/saturation fields of the NPs. The hysteresis area is found to be well correlated with the parallel or antiparallel nature of the dipolar field acting on each particle. The heating power of a given NP is strongly influenced by a local concentration involving approximately 20 neighbors. Because this local concentration strongly decreases upon approaching the surface, the heating power increases or decreases in the vicinity of the lysosome membrane. The amplitude of variation reaches more than one order of magnitude in certain conditions. This transition occurs on a thickness corresponding to approximately 1.3 times the mean distance between two neighbors. The amplitude and sign of this variation is explained. Finally, implications of these various findings are discussed in the framework of magnetic hyperthermia optimization. It is concluded that feedback on two specific points from biology experiments is required for further advancement of the optimization of magnetic NPs for magnetic hyperthermia. The present simulations will be an advantageous tool to optimize magnetic NPs heating power and interpret experimental results.

nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice.

PubMed

Itzhak, Y; Martin, J L; Ail, S F

2000-09-11

Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity.

Characteristics of hyperthermia-induced hyperventilation in humans

PubMed Central

Tsuji, Bun; Hayashi, Keiji; Kondo, Narihiko; Nishiyasu, Takeshi

2016-01-01

ABSTRACT In humans, hyperthermia leads to activation of a set of thermoregulatory responses that includes cutaneous vasodilation and sweating. Hyperthermia also increases ventilation in humans, as is observed in panting dogs, but the physiological significance and characteristics of the hyperventilatory response in humans remain unclear. The relative contribution of respiratory heat loss to total heat loss in a hot environment in humans is small, and this hyperventilation causes a concomitant reduction in arterial CO2 pressure (hypocapnia), which can cause cerebral hypoperfusion. Consequently, hyperventilation in humans may not contribute to the maintenance of physiological homeostasis (i.e., thermoregulation). To gain some insight into the physiological significance of hyperthermia-induced hyperventilation in humans, in this review, we discuss 1) the mechanisms underlying hyperthermia-induced hyperventilation, 2) the factors modulating this response, and 3) the physiological consequences of the response. PMID:27227102

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kok, H. Petra, E-mail: H.P.Kok@amc.uva.nl; Crezee, Johannes; Franken, Nicolaas A.P.

2014-03-01

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy{sup −1}) and β (Gy{sup −2}) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normalmore » tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.« less

Transcriptome Analysis of Neonatal Larvae after Hyperthermia-Induced Seizures in the Contractile Silkworm, Bombyx mori

PubMed Central

Nie, Hongyi; Liu, Chun; Zhang, Yinxia; Zhou, Mengting; Huang, Xiaofeng; Peng, Li; Xia, Qingyou

2014-01-01

The ability to respond quickly and efficiently to transient extreme environmental conditions is an important property of all biota. However, the physiological basis of thermotolerance in different species is still unclear. Here, we found that the cot mutant showed a seizure phenotype including contraction of the body, rolling, vomiting gut juice and a momentary cessation of movement, and the heartbeat rhythm of the dorsal vessel significantly increases after hyperthermia. To comprehensively understand this process at the molecular level, the transcriptomic profile of cot mutant, which is a behavior mutant that exhibits a seizure phenotype, was investigated after hyperthermia (42°C) that was induced for 5 min. By digital gene expression profiling, we determined the gene expression profile of three strains (cot/cot ok/ok, +/+ ok/ok and +/+ +/+) under hyperthermia (42°C) and normal (25°C) conditions. A Venn diagram showed that the most common differentially expressed genes (DEGs, FDR<0.01 and log2 Ratio≥1) were up-regulated and annotated with the heat shock proteins (HSPs) in 3 strains after treatment with hyperthermia, suggesting that HSPs rapidly increased in response to high temperature; 110 unique DEGs, could be identified in the cot mutant after inducing hyperthermia when compared to the control strains. Of these 110 unique DEGs, 98.18% (108 genes) were up-regulated and 1.82% (two genes) were down-regulated in the cot mutant. KEGG pathways analysis of these unique DEGs suggested that the top three KEGG pathways were “Biotin metabolism,” “Fatty acid biosynthesis” and “Purine metabolism,” implying that diverse metabolic processes are active in cot mutant induced-hyperthermia. Unique DEGs of interest were mainly involved in the ubiquitin system, nicotinic acetylcholine receptor genes, cardiac excitation–contraction coupling or the Notch signaling pathway. Insights into hyperthermia-induced alterations in gene expression and related pathways could yield hints for understanding the relationship between behaviors and environmental stimuli (hyperthermia) in insects. PMID:25423472

New Experiences of Treatment in Multiple Tumors with HIFU Ablation and Whole Body Hyperthermia

NASA Astrophysics Data System (ADS)

Takeuchi, Akira; Gondo, Hideki; Iijima, Norio; Xia, Yuantian; Takeuchi, Takashi

2007-05-01

We have performed some 5000 whole body hyperthermia (WBH) treatments using far-infrared equipment (RHD 7500: Enthermics medical systems, USA) in 1000 cancer patients since 1991 at Luke Hospital & Clinic (Nakano, Japan). Hyperthermia is a natural treatment whereby patients are heated within the fever temperature range of 41-42 C. However, this therapy alone is poorly suited to advanced cancer patients, where regional tumor control is needed. The potential of HIFU therapy for theses cases deserves further investigation. We have treated 20 times in 12 advanced cancer patients, since importing a new HIFU device (Sonic CZ901: Mianyang some electronic Ltd: China) last December and are able to report some interesting results of combination treatment with HIFU and WBH. Our first experience was a 20-year old female pharyngeal cancer patient with lung and multiple liver metastases. Her lung tumor reduced following WBH (given weekly, 4 times in total) and her liver tumor clearly reduced following HIFU treatment. Our second experience of combinative treatment was in a 65-year old male suffering from a neck tumor with bone metastasis. He received WBH after HIFU treatment into 7th lib bone metastasis. After 10 days, his neck tumor grew with evidence of internal necrosis, and finally ruptured. CT images showed necrotic changes in the focus of the neck tumor and also lib bone metastasis. We believe that this new thermal combinative therapy shows great promise.

Thermometry system development for thermoradiotherapy of deep-seated tumours

NASA Astrophysics Data System (ADS)

Fadeev, A. M.; Ivanov, S. M.; Perelstein, E. A.; Polozov, S. M.

2017-12-01

Therapeutic hyperthermia (including RF hyperthermia) in combination with radiotherapy (called thermoradiotherapy) is one of widely used contemporary cancer treatment methods. The independent electron linac and RF system or their combinations are necessary for effective therapy. Whole-body hyperthermia is used for treatment of metastatic cancer that was spread throughout the body, regional one is used for treatment of part of the body (for instance leg or abdominal cavity). Local hyperthermia with characteristic size of heating volume of 20-100 mm permits to heat tumour without overheating of healthy tissues. The thermometry of deep suited tissues during the hyperthermia process is an important and complex task. Invasive methods as thermistors, optical sensors or thermo-couples can not be widely used because all of them are able to transport tumor cells to the healthy region of the patient body. Distant methods of the temperature measurement such, as radiothermometry and acoustic thermometry can not be used for tissues seated deeper than 5-7 cm. One of possible ways to solve the problem of temperature measurement of the deep suited tissues is discussed in this article: it was proposed to use the same electrodes for RF hyperthermia and thermometry. As known electrodynamics characteristics of tissues are sufficiently depends on temperature. It was proposed to use this effect for active radiothermometry in local hyperthermia. Two opposite RF dipoles can be used as generator and receiver of pick-up signal.

Novel Magnetic Fluids for Breast Cancer Therapy

DTIC Science & Technology

2008-01-01

technology, in particular. The last one gave birth to the magnetic fluid hyperthermia (MFH) - an important tool for cancer treatment . Hyperthermia is...MODELING WORK In order to theoretically demonstrate the advantage of the novel magnetic nanoparticles for hyperthermia , we have developed a...AD_________________ Award Number: DAMD17-03-1-0176 TITLE: Novel Magnetic Fluids for Breast Cancer

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

PubMed

Ranieri, Girolamo; Ferrari, Cristina; Di Palo, Alessandra; Marech, Ilaria; Porcelli, Mariangela; Falagario, Gianmarco; Ritrovato, Fabiana; Ramunni, Luigi; Fanelli, Margherita; Rubini, Giuseppe; Gadaleta, Cosmo Damiano

2017-07-06

As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal ( n = 16), ovarian ( n = 5), and breast ( n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (<6, 6, 12, >12), number of hyperthermia sessions (<12, 12, 24, >24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles ( p = 0.015) and to number of HT sessions ( p < 0.001) performed. Both overall survival (OS) and time to progression (TTP) were influenced by the number of chemotherapy cycles ( p < 0.001) and HT sessions ( p < 0.001) performed. Our preliminary data, that need to be confirmed in larger studies, suggest that the combined treatment of bevacizumab-based chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

Magnetic Microspheres for Therapeutical Applications

NASA Technical Reports Server (NTRS)

Mazuruk, K.; Ramachandran, N.; Curreri, Peter A. (Technical Monitor)

2002-01-01

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady. The basic obstacle of the present heating methods are non-uniform thermal properties of the tissue. Our approach is to develop a novel class of magnetic fluids which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as a suitable nano-particle material. The objective is to synthesize, characterize and evaluate the efficacy of TRMF for hyperthermia therapy.

Localised hyperthermia in rodent models using an MRI-compatible high-intensity focused ultrasound system

PubMed Central

Bing, Chenchen; Nofiele, Joris; Staruch, Robert; Ladouceur-Wodzak, Michelle; Chatzinoff, Yonatan; Ranjan, Ashish; Chopra, Rajiv

2015-01-01

Purpose Localised hyperthermia in rodent studies is challenging due to the small target size. This study describes the development and characterisation of an MRI-compatible high-intensity focused ultrasound (HIFU) system to perform localised mild hyperthermia treatments in rodent models. Material and methods The hyperthermia platform consisted of an MRI-compatible small animal HIFU system, focused transducers with sector-vortex lenses, a custom-made receive coil, and means to maintain systemic temperatures of rodents. The system was integrated into a 3T MR imager. Control software was developed to acquire images, process temperature maps, and adjust output power using a proportional-integral-derivative feedback control algorithm. Hyperthermia exposures were performed in tissue-mimicking phantoms and in a rodent model (n = 9). During heating, an ROI was assigned in the heated region for temperature control and the target temperature was 42 °C; 30 min mild hyperthermia treatment followed by a 10-min cooling procedure was performed on each animal. Results 3D-printed sector-vortex lenses were successful at creating annular focal regions which enables customisation of the heating volume. Localised mild hyperthermia performed in rats produced a mean ROI temperature of 42.1 ± 0.3 °C. The T10 and T90 percentiles were 43.2 ± 0.4 °C and 41.0 ± 0.3 °C, respectively. For a 30-min treatment, the mean time duration between 41–45 °C was 31.1 min within the ROI. Conclusions The MRI-compatible HIFU system was successfully adapted to perform localised mild hyperthermia treatment in rodent models. A target temperature of 42 °C was well-maintained in a rat thigh model for 30 min. PMID:26540488

Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model.

PubMed

Petryk, Alicia A; Giustini, Andrew J; Gottesman, Rachel E; Trembly, B Stuart; Hoopes, P Jack

2013-12-01

The purpose of this study was to compare the efficacy of iron oxide/magnetic nanoparticle hyperthermia (mNPH) and 915 MHz microwave hyperthermia at the same thermal dose in a mouse mammary adenocarcinoma model. A thermal dose equivalent to 60 min at 43 °C (CEM60) was delivered to a syngeneic mouse mammary adenocarcinoma flank tumour (MTGB) via mNPH or locally delivered 915 MHz microwaves. mNPH was generated with ferromagnetic, hydroxyethyl starch-coated magnetic nanoparticles. Following mNP delivery, the mouse/tumour was exposed to an alternating magnetic field (AMF). The microwave hyperthermia treatment was delivered by a 915 MHz microwave surface applicator. Time required for the tumour to reach three times the treatment volume was used as the primary study endpoint. Acute pathological effects of the treatments were determined using conventional histopathological techniques. Locally delivered mNPH resulted in a modest improvement in treatment efficacy as compared to microwave hyperthermia (p = 0.09) when prescribed to the same thermal dose. Tumours treated with mNPH also demonstrated reduced peritumoral normal tissue damage. Our results demonstrate similar tumour treatment efficacy when tumour heating is delivered by locally delivered mNPs and 915 MHz microwaves at the same measured thermal dose. However, mNPH treatments did not result in the same type or level of peritumoral damage seen with the microwave hyperthermia treatments. These data suggest that mNP hyperthermia is capable of improving the therapeutic ratio for locally delivered tumour hyperthermia. These results further indicate that this improvement is due to improved heat localisation in the tumour.

Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors

NASA Astrophysics Data System (ADS)

Giustini, Andrew J.; Petryk, Alicia A.; Hoopes, Paul J.

2011-03-01

Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 +/- 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.

FDTD analysis of a noninvasive hyperthermia system for brain tumors.

PubMed

Yacoob, Sulafa M; Hassan, Noha S

2012-08-14

Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40-45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

Inflammation, edema and poor outcome are associated with hyperthermia in hypertensive intracerebral hemorrhages.

PubMed

Iglesias-Rey, Ramón; Rodríguez-Yáñez, Manuel; Arias, Susana; Santamaría, María; Rodríguez-Castro, Emilio; López-Dequidt, Iria; Hervella, Pablo; Sobrino, Tomás; Campos, Francisco; Castillo, José

2018-05-11

The deleterious effect of hyperthermia on intracerebral hemorrhage (ICH) has been studied, however the results are not completely conclusive and new studies are needed to elucidate clinical factors that condition the poor outcome. The aim of this study was to identify the clinical factors (including ICH etiology) that influence the poor outcome associated with hyperthermia on ICH. We additionally tried to identify potential mechanisms involved in hyperthermia during ICH. From a prospective registry, we conducted a retrospective study enrolling non-traumatic ICH patients. We used logistic regression models to analyze the influence of hyperthermia in relation to different inflammatory and endothelial dysfunction markers, hematoma growth and edema volume in hypertensive and non-hypertensive ICH patients. We included 887 ICH patients: 433 hypertensive, 50 amyloid, 117 by anticoagulants and 287 by other causes. Patients with hypertensive ICH showed the higher body temperature (37.5±0.8°C) as well as the maximum increase in temperature (0.9±0.1°C) within the first 24 hours. ICH patients with hypertensive etiologic origin, who presented hyperthermia, showed a 5.3 fold-higher risk to have poor outcome at 3 months. We found a positive relationship (r=0.717, P<0.0001) between edema volume and hyperthermia during the first 24 hours but only in ICH patients with hypertensive etiologic origin, and this relationship seems to be mediated by inflammatory markers. Our data suggest that hyperthermia, together with inflammation and edema is associated with poor outcome only in ICH from hypertensive etiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer

NASA Astrophysics Data System (ADS)

Hervault, Aziliz; Thanh, Nguyêl; N. Thé, Kim

2014-09-01

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

Magnetic nanoparticles for enhancing the effectiveness of ultrasonic hyperthermia

NASA Astrophysics Data System (ADS)

Józefczak, A.; Kaczmarek, K.; Hornowski, T.; Kubovčíková, M.; Rozynek, Z.; Timko, M.; Skumiel, A.

2016-06-01

Ultrasonic hyperthermia is a method of cancer treatment in which tumors are exposed to an elevated cytotoxic temperature using ultrasound (US). In conventional ultrasonic hyperthermia, the ultrasound-induced heating in the tumor is achieved through the absorption of wave energy. However, to obtain appropriate temperature in reasonable time, high US intensities, which can have a negative impact on healthy tissues, are required. The effectiveness of US for medical purposes can be significantly improved by using the so-called sonosensitizers, which can enhance the thermal effect of US on the tissue by increasing US absorption. One possible candidate for such sonosensitizers is magnetic nanoparticles with mean sizes of 10-300 nm, which can be efficiently heated because of additional attenuation and scattering of US. Additionally, magnetic nanoparticles are able to produce heat in the alternating magnetic field (magnetic hyperthermia). The synergetic application of ultrasonic and magnetic hyperthermia can lead to a promising treatment modality.

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer.

PubMed

Hervault, Aziliz; Thanh, Nguyen Th Kim

2014-10-21

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

Current Status and Perspectives of Hyperthermia in Cancer Therapy

NASA Astrophysics Data System (ADS)

Hiraoka, Masahiro; Nagata, Yasushi; Mitsumori, Michihide; Sakamoto, Masashi; Masunaga, Shin-ichiro

2004-08-01

Clinical trials of hyperthermia in combination with radiation therapy or chemotherapy undertaken over the past decades in Japan have been reviewed. Originally developed heating devices were mostly used for these trials, which include RF (radiofrequency) capacitive heating devices, a microwave heating device with a lens applicator, an RF intracavitary heating device, an RF current interstitial heating device, and ferromagnetic implant heating device. Non-randomized trials for various cancers, demonstrated higher response rate in thermoradiotherapy than in radiotherapy alone. Randomized trials undertaken for esophageal cancers also demonstrated improved local response with the combined use of hyperthermia. Furthermore, the complications associated with treatment were not generally serious. These clinical results indicate the benefit of combined treatment of hyperthermia and radiotherapy for various malignancies. On the other hand, the presently available heating devices are not satisfactory from the clinical viewpoints. With the advancement of heating and thermometry technologies, hyperthermia will be more widely and safely used in the treatment of cancers.

Cancer hyperthermia using magnetic nanoparticles.

PubMed

Kobayashi, Takeshi

2011-11-01

Magnetic-nanoparticle-mediated intracellular hyperthermia has the potential to achieve localized tumor heating without any side effects. The technique consists of targeting magnetic nanoparticles to tumor tissue followed by application of an external alternating magnetic field that induces heat through Néel relaxation loss of the magnetic nanoparticles. The temperature in tumor tissue is increased to above 43°C, which causes necrosis of cancer cells, but does not damage surrounding normal tissue. Among magnetic nanoparticles available, magnetite has been extensively studied. Recent years have seen remarkable advances in magnetite-nanoparticle-mediated hyperthermia; both functional magnetite nanoparticles and alternating-magnetic-field generators have been developed. In addition to the expected tumor cell death, hyperthermia treatment has also induced unexpected biological responses, such as tumor-specific immune responses as a result of heat-shock protein expression. These results suggest that hyperthermia is able to kill not only local tumors exposed to heat treatment, but also tumors at distant sites, including metastatic cancer cells. Currently, several research centers have begun clinical trials with promising results, suggesting that the time may have come for clinical applications. This review describes recent advances in magnetite nanoparticle-mediated hyperthermia. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williams, B. A.

1983-01-01

The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl normetazocine and an agonist at both kappa and sigma receptors, pentazocine, was found to induce hyperthermia in guinea pigs. The similar administration of peptide opioids like beta endorphin, methionine endkephalin, leucine endkephaline, and several of their synthetic analogues was also found to cause hyperthermia. Only the liver-like transport system of the three anion transport systems (iodide, hippurate, and liver-like) present in the choroid plexus was determined to be important to the central inactivation of beta-endorphin and two synthetic analogues. Prostaglandins and norepinephrine (NE) as well as cAMP were not involved in peptide and nonpeptide opioid-induced hyperthermia. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine and beta-endorphin, while hyperthermic responses to ketocyclazocine, N-allyl normetazocine, pentazocine, Met-enkephalin, Leu-enkephalin, and two of the synthetic analogues were not antagonized by nalozone. The lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP, and NE-induced hyperthermia shows that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.

Hypo-fractionated radiation, magnetic nanoparticle hyperthermia and a viral immunotherapy treatment of spontaneous canine cancer

NASA Astrophysics Data System (ADS)

Hoopes, P. Jack; Moodie, Karen L.; Petryk, Alicia A.; Petryk, James D.; Sechrist, Shawntel; Gladstone, David J.; Steinmetz, Nicole F.; Veliz, Frank A.; Bursey, Alicea A.; Wagner, Robert J.; Rajan, Ashish; Dugat, Danielle; Crary-Burney, Margaret; Fiering, Steven N.

2017-02-01

It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component. Two tumors received all three therapeutic modalities, one tumor received radiation and hyperthermia, two tumors received radiation and VLP, and three tumors received only mNP hyperthermia. The treatment regimen is conducted over a 14-day period. All patients tolerated the treatments without complication and have had local and distant tumor responses that significantly exceed responses observed following conventional therapy (surgery and/or radiation). The results suggest that both hypofractionated radiation and hyperthermia have effective immune responses that are enhanced by the intratumoral VLP treatment. Molecular data from these tumors suggest Heat Shock Protein (HSP) 70/90, calreticulin and CD47 are targets that can be exploited to enhance the local and systemic (abscopal effect) immune potential of radiation and hyperthermia cancer treatment.

A printed Yagi-Uda antenna for application in magnetic resonance thermometry guided microwave hyperthermia applicators

NASA Astrophysics Data System (ADS)

Paulides, M. M.; Mestrom, R. M. C.; Salim, G.; Adela, B. B.; Numan, W. C. M.; Drizdal, T.; Yeo, D. T. B.; Smolders, A. B.

2017-03-01

Biological studies and clinical trials show that addition of hyperthermia stimulates conventional cancer treatment modalities and significantly improves treatment outcome. This supra-additive stimulation can be optimized by adaptive hyperthermia to counteract strong and dynamic thermoregulation. The only clinically proven method for the 3D non-invasive temperature monitoring required is by magnetic resonance (MR) temperature imaging, but the currently available set of MR compatible hyperthermia applicators lack the degree of heat control required. In this work, we present the design and validation of a high-frequency (433 MHz ISM band) printed circuit board antenna with a very low MR-footprint. This design is ideally suited for use in a range of hyperthermia applicator configurations. Experiments emulating the clinical situation show excellent matching properties of the antenna over a 7.2% bandwidth (S 11  <  -15 dB). Its strongly directional radiation properties minimize inter-element coupling for typical array configurations (S 21  <  -23 dB). MR imaging distortion by the antenna was found negligible and MR temperature imaging in a homogeneous muscle phantom was highly correlated with gold-standard probe measurements (root mean square error: RMSE  =  0.51 °C and R 2  =  0.99). This work paves the way for tailored MR imaging guided hyperthermia devices ranging from single antenna or incoherent antenna-arrays, to real-time adaptive hyperthermia with phased-arrays.

A numerical study on dual-phase-lag model of bio-heat transfer during hyperthermia treatment.

PubMed

Kumar, P; Kumar, Dinesh; Rai, K N

2015-01-01

The success of hyperthermia in the treatment of cancer depends on the precise prediction and control of temperature. It was absolutely a necessity for hyperthermia treatment planning to understand the temperature distribution within living biological tissues. In this paper, dual-phase-lag model of bio-heat transfer has been studied using Gaussian distribution source term under most generalized boundary condition during hyperthermia treatment. An approximate analytical solution of the present problem has been done by Finite element wavelet Galerkin method which uses Legendre wavelet as a basis function. Multi-resolution analysis of Legendre wavelet in the present case localizes small scale variations of solution and fast switching of functional bases. The whole analysis is presented in dimensionless form. The dual-phase-lag model of bio-heat transfer has compared with Pennes and Thermal wave model of bio-heat transfer and it has been found that large differences in the temperature at the hyperthermia position and time to achieve the hyperthermia temperature exist, when we increase the value of τT. Particular cases when surface subjected to boundary condition of 1st, 2nd and 3rd kind are discussed in detail. The use of dual-phase-lag model of bio-heat transfer and finite element wavelet Galerkin method as a solution method helps in precise prediction of temperature. Gaussian distribution source term helps in control of temperature during hyperthermia treatment. So, it makes this study more useful for clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intra-Peritoneal Hyperthermia Combining α-Galactosylceramide in the Treatment of Ovarian Cancer

PubMed Central

Hsu, Yun-Ting; Huang, Jung-Tang; Wu, T. -C; Hung, Chien-Fu; Yang, Yuh-Cheng; Chang, Chih-Long

2013-01-01

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8+/IFN-γ+ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer. PMID:23935988

A case of malignant hyperthermia captured by an anesthesia information management system.

PubMed

Maile, Michael D; Patel, Rajesh A; Blum, James M; Tremper, Kevin K

2011-04-01

Many cases of malignant hyperthermia triggered by volatile anesthetic agents have been described. However, to our knowledge, there has not been a report describing the precise changes in physiologic data of a human suffering from this process. Here we describe a case of malignant hyperthermia in which monitoring information was frequently and accurately captured by an anesthesia information management system.

Magnetic nanoparticles for medical applications: Progress and challenges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doaga, A.; Cojocariu, A. M.; Constantin, C. P.

2013-11-13

Magnetic nanoparticles present unique properties that make them suitable for applications in biomedical field such as magnetic resonance imaging (MRI), hyperthermia and drug delivery systems. Magnetic hyperthermia involves heating the cancer cells by using magnetic particles exposed to an alternating magnetic field. The cell temperature increases due to the thermal propagation of the heat induced by the nanoparticles into the affected region. In order to increase the effectiveness of the treatment hyperthermia can be combined with drug delivery techniques. As a spectroscopic technique MRI is used in medicine for the imaging of tissues especially the soft ones and diagnosing malignantmore » or benign tumors. For this purpose Zn{sub x}Co{sub 1−x}Fe{sub 2}O{sub 4} ferrite nanoparticles with x between 0 and 1 have been prepared by co-precipitation method. The cristallite size was determined by X-ray diffraction, while the transmission electron microscopy illustrates the spherical shape of the nanoparticles. Magnetic characterizations of the nanoparticles were carried out at room temperature by using a vibrating sample magnetometer. The specific absorption rate (SAR) was measured by calorimetric method at different frequencies and it has been observed that this value depends on the chemical formula, the applied magnetic fields and the frequency. The study consists of evaluating the images, obtained from an MRI facility, when the nanoparticles are dispersed in agar phantoms compared with the enhanced ones when Omniscan was used as contrast agent. Layer-by-layer technique was used to achieve the necessary requirement of biocompatibility. The surface of the magnetic nanoparticles was modified by coating it with oppositely charged polyelectrolites, making it possible for the binding of a specific drug.« less

Thermoregulatory disorders and illness related to heat and cold stress.

PubMed

Cheshire, William P

2016-04-01

Thermoregulation is a vital function of the autonomic nervous system in response to cold and heat stress. Thermoregulatory physiology sustains health by keeping body core temperature within a degree or two of 37°C, which enables normal cellular function. Heat production and dissipation are dependent on a coordinated set of autonomic responses. The clinical detection of thermoregulatory impairment provides important diagnostic and localizing information in the evaluation of disorders that impair thermoregulatory pathways, including autonomic neuropathies and ganglionopathies. Failure of neural thermoregulatory mechanisms or exposure to extreme or sustained temperatures that overwhelm the body's thermoregulatory capacity can also result in potentially life-threatening departures from normothermia. Hypothermia, defined as a core temperature of <35.0°C, may present with shivering, respiratory depression, cardiac dysrhythmias, impaired mental function, mydriasis, hypotension, and muscle dysfunction, which can progress to cardiac arrest or coma. Management includes warming measures, hydration, and cardiovascular support. Deaths from hypothermia are twice as frequent as deaths from hyperthermia. Hyperthermia, defined as a core temperature of >40.5°C, may present with sweating, flushing, tachycardia, fatigue, lightheadedness, headache, and paresthesia, progressing to weakness, muscle cramps, oliguria, nausea, agitation, hypotension, syncope, confusion, delirium, seizures, and coma. Mental status changes and core temperature distinguish potentially fatal heat stroke from heat exhaustion. Management requires the immediate reduction of core temperature. Ice water immersion has been shown to be superior to alternative cooling measures. Avoidance of thermal risk and early recognition of cold or heat stress are the cornerstones of preventive therapy. Copyright © 2016 The Author. Published by Elsevier B.V. All rights reserved.

Simultaneous hyperthermia and doxorubicin delivery from polymer-coated magnetite nanoparticles

NASA Astrophysics Data System (ADS)

Iglesias, G. R.; Delgado, A. V.; González-Caballero, F.; Ramos-Tejada, M. M.

2017-06-01

In this work, the hyperthermia response, (i.e., heating induced by an externally applied alternating magnetic field) and the simultaneous release of an anti-cancer drug (doxorubicin) by polymer-coated magnetite nanoparticles have been investigated. After describing the setup for hyperthermia measurements in suspensions of magnetic nanoparticles, the hyperthermia (represented by the rate of suspension heating and, ultimately, by the specific absorption rate or SAR) of magnetite nanoparticles (both bare and polymer-coated as drug nanocarriers) is discussed. The effect of the applied ac magnetic field on doxorubicin release is also studied, and it is concluded that the field does not interfere with the release process, demonstrating the double functionality of the investigated particles.

Low-density lipoprotein transport through an arterial wall under hyperthermia and hypertension conditions--An analytical solution.

PubMed

Iasiello, Marcello; Vafai, Kambiz; Andreozzi, Assunta; Bianco, Nicola

2016-01-25

An analytical solution for Low-Density Lipoprotein transport through an arterial wall under hyperthermia conditions is established in this work. A four-layer model is used to characterize the arterial wall. Transport governing equations are obtained as a combination between Staverman-Kedem-Katchalsky membrane equations and volume-averaged porous media equations. Temperature and solute transport fields are coupled by means of Ludwig-Soret effect. Results are in excellent agreement with numerical and analytical literature data under isothermal conditions, and with numerical literature data for the hyperthermia case. Effects of hypertension combined with hyperthermia, are also analyzed in this work. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Malignant hyperthermia - problem in dental surgery. An introductory report].

PubMed

Kamińska, Ewa; Janas, Anna; Osica, Piotr

2014-01-01

Malignant hyperthermia is a genetic defect of uncontrolled hypermetabolic skeletal muscle response to anesthetic triggering drugs. Some congenital myopathies are regarded as risk increasing factors. The use of volatile anaesthetics or suxamethonium (succinylcholine) in patients who are predisposed to malignant hyperthermia leads to an increase in Ca2+ release from sarcoplasmic reticulum, which in turn causes a set of biochemical and clinical symptoms, which can be a cause of death, if dantrolene is not administered adequately. The aim of the study was to draw attention to the problem of malignant hyperthermia, which is hardly ever described in Polish literature, and requires the necessity of intensifying the cooperation between the dentist and specialists from other medical fields. The origin of the article was a case of congenital myopathy with recognized malignant hyperthermia in an 18-year-old patient, in whom surgical extraction of teeth was indicated. The course of diagnostics and treatment showed once more that contemporary medicine is in need of holistic approach, and in consequence, promising and effective cooperation of many specialists.

Predicting thermal history a-priori for magnetic nanoparticle hyperthermia of internal carcinoma

NASA Astrophysics Data System (ADS)

Dhar, Purbarun; Sirisha Maganti, Lakshmi

2017-08-01

This article proposes a simplistic and realistic method where a direct analytical expression can be derived for the temperature field within a tumour during magnetic nanoparticle hyperthermia. The approximated analytical expression for thermal history within the tumour is derived based on the lumped capacitance approach and considers all therapy protocols and parameters. The present method is simplistic and provides an easy framework for estimating hyperthermia protocol parameters promptly. The model has been validated with respect to several experimental reports on animal models such as mice/rabbit/hamster and human clinical trials. It has been observed that the model is able to accurately estimate the thermal history within the carcinoma during the hyperthermia therapy. The present approach may find implications in a-priori estimation of the thermal history in internal tumours for optimizing magnetic hyperthermia treatment protocols with respect to the ablation time, tumour size, magnetic drug concentration, field strength, field frequency, nanoparticle material and size, tumour location, and so on.

An overview of interstitial brachytherapy and hyperthermia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandt, B.B.; Harney, J.

Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combinationmore » with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references.« less

CDRH RF phantom for hyperthermia systems evaluations.

PubMed

Allen, S; Kantor, G; Bassen, H; Ruggera, P

1988-01-01

The National Cancer Institute (NCI) sponsored clinical evaluations of investigational 'regional' hyperthermia systems at four clinical institutions. To support this project, the Center for Devices and Radiological Health (CDRH) developed a series of test instruments to evaluate the magnitude and repeatability of the induced heating by radiofrequency (RF) systems. Data from three institutions using the same model hyperthermia system have been analyzed. After heating, the average temperature from measurements taken at several points in the test phantom at each institution agree within +/- 0.002 degrees C. These differences are about equal to the measurement uncertainty. Thus, this technique can be used for preclinical evaluation and quality control of the total system operation. After one of the institutions relocated its hyperthermia system, a subsequent set of data showed inconsistencies compared to their earlier data. Investigation traced this to cable loss and power meter interference. From the analysis of the data from the three institutions, the utility of the CDRH RF phantom for hyperthermia systems evaluation is demonstrated.

Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells.

PubMed

Yuan, Guang-Jin; Deng, Jun-Jian; Cao, De-Dong; Shi, Lei; Chen, Xin; Lei, Jin-Ju; Xu, Xi-Ming

2017-08-14

To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism. Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species (ROS) were quantified using the fluorescent probe DCFH-DA. Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation. Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.

Immunohistochemistry of catecholamines in the hypothalamic-pituitary-adrenal system with special regard to fatal hypothermia and hyperthermia.

PubMed

Ishikawa, Takaki; Yoshida, Chiemi; Michiue, Tomomi; Perdekamp, Markus Grosse; Pollak, Stefan; Maeda, Hitoshi

2010-05-01

Catecholamines are involved in various stress responses. Previous studies have suggested applicability of the postmortem blood levels to investigations of physical stress responses or toxic/hyperthermic neuronal dysfunction during death process. The present study investigated cellular immunopositivity for adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) in the hypothalamus, adenohypophysis and adrenal medulla with special regard to fatal hypothermia (cold exposure) and hyperthermia (heat stroke) to examine forensic pathological significance. Medicolegal autopsy cases (n=290, within 3 days postmortem) were examined. The proportions of catecholamine (Adr, Nad and DA)-positive cells (% positivity) in each tissue were quantitatively estimated using immunostaining. Hyperthermia cases (n=12) showed a lower neuronal DA-immunopositivity in the hypothalamus than hypothermia cases (n=20), while Nad- and DA-immunopositivities in the adrenal medulla were higher for hyperthermia than for hypothermia. Rates of Nad-immunopositivity in the adrenal medulla were very low for hypothermia. No such difference between hypothermia and hyperthermia was seen in the adenohypophysis. In hypothermia cases, cellular Nad-immunopositivity in the adrenal medulla correlated with the Nad level in cerebrospinal fluid (r=0.591, p<0.01). These observations suggest a characteristic immunohistochemical pattern of systemic stress response to fatal hypothermia and hyperthermia, involving the hypothalamus and adrenal medulla. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Modeling the thermo-acoustic effects of thermal-dependent speed of sound and acoustic absorption of biological tissues during focused ultrasound hyperthermia.

PubMed

López-Haro, S A; Gutiérrez, M I; Vera, A; Leija, L

2015-10-01

To evaluate the effects of thermal dependence of speed of sound (SOS) and acoustic absorption of biological tissues during noninvasive focused ultrasound (US) hyperthermia therapy. A finite element (FE) model was used to simulate hyperthermia therapy in the liver by noninvasive focused US. The model consisted of an ultrasonic focused transducer radiating a four-layer biological medium composed of skin, fat, muscle, and liver. The acoustic field and temperature distribution along the layers were obtained after 15 s of hyperthermia therapy using the bio-heat equation. The model solution was found with and without the thermal dependence of SOS and acoustic absorption of biological tissues. The inclusion of the thermal dependence of the SOS generated an increment of 0.4 mm in the longitudinal focus axis of the acoustic field. Moreover, results indicate an increment of the hyperthermia area (zone with temperature above 43 °C), and a maximum temperature difference of almost 3.5 °C when the thermal dependence of absorption was taken into account. The increment of the achieved temperatures at the treatment zone indicated that the effects produced by the thermal dependence of SOS and absorption must be accounted for when planning hyperthermia treatment in order to avoid overheating undesired regions.

Factors associated with high risk of marginal hyperthermia in elderly patients living in an institution.

PubMed Central

Vassallo, M.; Gera, K. N.; Allen, S.

1995-01-01

The elderly, the very young, and the sick are known to be adversely affected by high environmental temperatures. In a retrospective open case-note review of 872 patients in a large institution during a hot summer we identified characteristics in the elderly that increase the risk of marginal hyperthermia. Women were more likely to be affected than men (25.6% vs 16.9%). We found an age-related increase in marginal hyperthermia, 15.7% of those below 60 years developed a hyperthermia compared to 18.9% in those between 70-79 years (non-significant), 28.3% in those between 80-89 years (p = 0.01) and 50% in those above 90 years (p < 0.01). There was also a direct relationship between the incidence of hyperthermia and the ambient temperature (29% in the warmer wards, compared to 17.2% in cooler ones; p < 0.01) and with the level of dependence (42.3% of the bedridden group, p < 0.01, and 20.4% of the semi-dependent, p < 0.01, compared to 11.1% of the mobile group). These factors were more significant as predictors of risk than the diagnosis. Identifying high risk patients early and taking appropriate measures to avoid hyperthermia and dehydration is important to try to decrease mortality during heatwaves. PMID:7784280

Graphene Quantum Dots-Capped Magnetic Mesoporous Silica Nanoparticles as a Multifunctional Platform for Controlled Drug Delivery, Magnetic Hyperthermia, and Photothermal Therapy.

PubMed

Yao, Xianxian; Niu, Xingxing; Ma, Kexin; Huang, Ping; Grothe, Julia; Kaskel, Stefan; Zhu, Yufang

2017-01-01

A multifunctional platform is reported for synergistic therapy with controlled drug release, magnetic hyperthermia, and photothermal therapy, which is composed of graphene quantum dots (GQDs) as caps and local photothermal generators and magnetic mesoporous silica nanoparticles (MMSN) as drug carriers and magnetic thermoseeds. The structure, drug release behavior, magnetic hyperthermia capacity, photothermal effect, and synergistic therapeutic efficiency of the MMSN/GQDs nanoparticles are investigated. The results show that monodisperse MMSN/GQDs nanoparticles with the particle size of 100 nm can load doxorubicin (DOX) and trigger DOX release by low pH environment. Furthermore, the MMSN/GQDs nanoparticles can efficiently generate heat to the hyperthermia temperature under an alternating magnetic field or by near infrared irradiation. More importantly, breast cancer 4T1 cells as a model cellular system, the results indicate that compared with chemotherapy, magnetic hyperthermia or photothermal therapy alone, the combined chemo-magnetic hyperthermia therapy or chemo-photothermal therapy with the DOX-loaded MMSN/GQDs nanosystem exhibits a significant synergistic effect, resulting in a higher efficacy to kill cancer cells. Therefore, the MMSN/GQDs multifunctional platform has great potential in cancer therapy for enhancing the therapeutic efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhalable Magnetic Nanoparticles for Targeted Hyperthermia in Lung Cancer Therapy

PubMed Central

Sadhukha, Tanmoy; Wiedmann, Timothy Scott; Panyam, Jayanth

2015-01-01

Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. PMID:23591395

Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy.

PubMed

Sadhukha, Tanmoy; Wiedmann, Timothy S; Panyam, Jayanth

2013-07-01

Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Role for D1 Dopamine Receptors in Striatal Methamphetamine-Induced Neurotoxicity

PubMed Central

Friend, Danielle M.; Keefe, Kristen A.

2015-01-01

Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 Dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Importantly, METH-induced hyperthermia is tightly associated with the neurotoxicity, such that simply cooling animals during METH exposure protects against the neurotoxicity. Therefore, it is difficult to determine whether D1 DA receptors per se play an important role in METH-induced neurotoxicity or whether the protection observed simply resulted from a mitigation of METH-induced hyperthermia. To answer this important question, the current study infused a D1 DA receptor antagonist into striatum during METH exposure while controlling for METH-induced hyperthermia. Here we found that even when METH-induced hyperthermia is maintained, the coadministration of a D1 DA receptor antagonist protects against METH-induced neurotoxicity, strongly suggesting that D1 DA receptors play an important role in METH-induced neurotoxicity apart from the mitigation of METH-induced hyperthermia. PMID:23994061

Physical mechanism and modeling of heat generation and transfer in magnetic fluid hyperthermia through Néelian and Brownian relaxation: a review.

PubMed

Suriyanto; Ng, E Y K; Kumar, S D

2017-03-23

Current clinically accepted technologies for cancer treatment still have limitations which lead to the exploration of new therapeutic methods. Since the past few decades, the hyperthermia treatment has attracted the attention of investigators owing to its strong biological rationales in applying hyperthermia as a cancer treatment modality. Advancement of nanotechnology offers a potential new heating method for hyperthermia by using nanoparticles which is termed as magnetic fluid hyperthermia (MFH). In MFH, superparamagnetic nanoparticles dissipate heat through Néelian and Brownian relaxation in the presence of an alternating magnetic field. The heating power of these particles is dependent on particle properties and treatment settings. A number of pre-clinical and clinical trials were performed to test the feasibility of this novel treatment modality. There are still issues yet to be solved for the successful transition of this technology from bench to bedside. These issues include the planning, execution, monitoring and optimization of treatment. The modeling and simulation play crucial roles in solving some of these issues. Thus, this review paper provides a basic understanding of the fundamental and rationales of hyperthermia and recent development in the modeling and simulation applied to depict the heat generation and transfer phenomena in the MFH.

A role for D1 dopamine receptors in striatal methamphetamine-induced neurotoxicity.

PubMed

Friend, Danielle M; Keefe, Kristen A

2013-10-25

Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Importantly, METH-induced hyperthermia is tightly associated with the neurotoxicity, such that simply cooling animals during METH exposure protects against the neurotoxicity. Therefore, it is difficult to determine whether D1 DA receptors per se play an important role in METH-induced neurotoxicity or whether the protection observed simply resulted from a mitigation of METH-induced hyperthermia. To answer this important question, the current study infused a D1 DA receptor antagonist into striatum during METH exposure while controlling for METH-induced hyperthermia. Here we found that even when METH-induced hyperthermia is maintained, the coadministration of a D1 DA receptor antagonist protects against METH-induced neurotoxicity, strongly suggesting that D1 DA receptors play an important role in METH-induced neurotoxicity apart from the mitigation of METH-induced hyperthermia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.

PubMed

Garami, Andras; Shimansky, Yury P; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Romanovsky, Andrej A

2010-01-27

Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.

Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia

PubMed Central

Garami, Andras; Shimansky, Yury P.; Pakai, Eszter; Oliveira, Daniela L.; Gavva, Narender R.; Romanovsky, Andrej A.

2010-01-01

Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We have found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia. PMID:20107070

Shape-controlled fabrication of magnetite silver hybrid nanoparticles with high performance magnetic hyperthermia.

PubMed

Ding, Qi; Liu, Dongfang; Guo, Dawei; Yang, Fang; Pang, Xingyun; Che, Renchao; Zhou, Naizhen; Xie, Jun; Sun, Jianfei; Huang, Zhihai; Gu, Ning

2017-04-01

Superparamagnetic Fe 3 O 4 nanoparticles (NPs)-based hyperthermia is a promising non-invasive approach for cancer therapy. However, the heat transfer efficiency of Fe 3 O 4 NPs is relative low, which hinders their practical clinical applications. Therefore, it is promising to improve the magnetic hyperthermia efficiency by exploring the higher performance magnetic NPs-based hybrid nanostructures. In the current study, it presents a straightforward in situ reduction method for the shape-controlled preparation of magnetite (Fe 3 O 4 ) silver (Ag) hybrid NPs designed as magnetic hyperthermia heat mediators. The magnetite silver hybrid NPs with core-shell (Fe 3 O 4 @Ag) or heteromer (Fe 3 O 4 -Ag) structures exhibited a higher biocompatibility with SMMC-7721 cells and L02 cells than the individual Ag NPs. Importantly, in the magnetic hyperthermia, with the exposure to alternating current magnetic field, the Fe 3 O 4 @Ag and Fe 3 O 4 -Ag hybrid NPs indicated much better tumor suppression effect against SMMC-7721 cells than the individual Fe 3 O 4 NPs in vitro and in vivo. These results demonstrate that the hybridisation of Fe 3 O 4 and Ag NPs could greatly enhance the magnetic hyperthermia efficiency of Fe 3 O 4 NPs. Therefore, the Fe 3 O 4 @Ag and Fe 3 O 4 -Ag hybrid NPs can be used to be as high performance magnetic hyperthermia mediators based on a simple and effective preparation approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

Magnetic Microspheres and Tissue Model Studies for Therapeutical Applications

NASA Technical Reports Server (NTRS)

Ramachandran, N.; Mazuruk, K.

2003-01-01

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia breast therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady for an extended period (2-3 hours). The basic shortcomings of the presently utilized heating methods stem from the non-uniform thermal properties of the tissue and the point heating characteristics of the techniques without any thermal control. Our approach is to develop a novel class of magnetic fluids, which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as suitable nano to micron-size particle material. The objective is to synthesize, characterize and evaluate the efficacy of Thermo Regulating Magnetic Fluids (TRMF) for hyperthermia therapy. The development of a tissue model and testing the fluid dynamics of particle motion, settling, distribution in the tissue matrix and heat generation will be discussed.

Effector CD8+ T cell IFN-γ production and cytotoxicity are enhanced by mild hyperthermia

PubMed Central

Mace, Thomas A.; Zhong, Lingwen; Kokolus, Kathleen M.; Repasky, Elizabeth A.

2012-01-01

Purpose Clinical trials combining hyperthermia with radiation and/or chemotherapy for cancer treatment have resulted in improved overall survival and control of local recurrences. The contribution of thermally enhanced anti-immune function in these effects is of considerable interest, but not understood; studies on the fundamental effects of elevated temperature on immune effector cells are needed. The goal of this study is to investigate the potential of mild hyperthermia to impact tumor antigen-specific (Ag) effector CD8+ T cell functions. Method Pmel-1 Ag-specific CD8+ T cells were exposed to mild hyperthermia and tested for changes in IFN-γ production and cytotoxicity. Additionally, overall plasma membrane organization and the phosphorylation of signaling proteins were also investigated following heat treatment. Results Exposing effector Pmel-1 specific CD8+ T cells to mild hyperthermia (39.5°C) resulted in significantly enhanced Ag-specific IFN-γ production and tumor target cell killing compared to that seen using lower temperatures (33 and 37°C). Further, inhibition of protein synthesis during hyperthermia did not reduce subsequent Ag-induced IFN-γ production by CD8+ T cells. Correlated with these effects, we observed a distinct clustering of GM1+ lipid microdomains at the plasma membrane and enhanced phosphorylation of LAT and PKCθ which may be related to an observed enhancement of Ag-specific effector CD8+ T cell IFN-γ gene transcription following mild hyperthermia. However, mitogen–mediated production of IFN-γ, which bypasses T cell receptor activation with antigen, was not enhanced. Conclusions Antigen-dependent effector T cell activity is enhanced following mild hyperthermia. These effects could potentially occur in patients being treated with thermal therapies. These data also provide support for the use of thermal therapy as an adjuvant for immunotherapies to improve CD8+ effector cell function. PMID:22235780

Repressive effects of a capacitive-resistive electric transfer (CRet) hyperthermic apparatus combined with provitamin C on intracellular lipid-droplets formation in adipocytes.

PubMed

Kato, Shinya; Saitoh, Yasukazu; Miwa, Nobuhiko

2013-01-01

The aim of this study was to evaluate inhibitory effects of L-ascorbic acid-2-O-phosphate-Na(2) (APS), a pro-vitamin C, combined with hyperthermia on adipogenic differentiation of mouse stromal cells, OP9. OP9 preadipocytes were differentiated with serum replacement, administered with APS, and simultaneously treated with hyperthermia using a capacitive-resistive electric transfer (CRet) apparatus, which was conducted repeatedly twice a day. After 2 days, intracellular lipid droplets were stained with Oil Red O, then observed by microscopy and assessed spectrophotometrically. After stimulation by serum replacement for 2 days, lipid droplets were accumulated surrounding nucleus of OP9 cells. When APS of 0.15-0.6 mM was administered without hyperthermia, the amount of lipid droplets was markedly suppressed to 50.5%∼-11.3% versus the undifferentiated control, and diminished huge aggregates of lipid droplets. In OP9 cells treated by hyperthermia at 42°C for 0.5 min, 1 min or 3 min in the absence of APS, adipogenesis was suppressed abruptly in a time-dependent manner to 95.4%, 18.7% or -5.5%, respectively. Whereas, the percentage of adipogenesis was 96.8% in OP9 cells treated by mild hyperthermia alone at 41°C for 1 min. The simultaneous application of APS and hyperthermia at 41°C for 1 min markedly suppressed the accumulation of lipid droplets to 25.7%∼-66.2%. By scanning electron microscopy (SEM) observation, the surface of OP9 cells treated with APS and hyperthermia appeared to have the morphological property of undifferentiated OP9 cells. Combined treatment of APS and mild hyperthermia suppresses adipogenesis in OP9 cells, particularly in lipid droplets accumulation during spontaneous differentiation of OP9 preadipocytes.

Evaluation of The Combined Effects of Hyperthermia, Cobalt-60 Gamma Rays and IUdR on Cultured Glioblastoma Spheroid Cells and Dosimetry Using TLD-100

PubMed Central

Neshasteh-Riz, Ali; Rahdani, Rozhin; Mostaar, Ahmad

2014-01-01

Objective In radiation treatment, the irradiation which is effective enough to control the tumors far exceeds normal-tissues tolerance. Thus to avoid such unfavourable outcomes, some methods sensitizing the tumor cells to radiation are used. Iododeoxyuridine (IUdR) is a halogenated thymidine analogue that known to be effective as a radiosensitizer in human cancer therapy. Improving the potential efficacy of radiation therapy after combining to hyperthermia depends on the magnitude of the differential sensitization of the hyperthermic effects or on the differential cytotoxicity of the radiation effects on the tumor cells. In this study, we evaluated the combined effects of IUdR, hyperthermia and gamma rays of 60Co on human glioblastoma spheroids culture. Materials and Methods In this experimental study,the cultured spheroids with 100µm diameter were treated by 1 µM IUdR, 43°C hyperthermia for an hour and 2 Gy gamma rays, respectively. The DNA damages induced in cells were compared using alkaline comet assay method, and dosimetry was then performed by TLD-100. Comet scores were calculated as mean ± standard error of mean (SEM) using one-way ANOVA. Results Comparison of DNA damages induced by IUdR and hyperthermia + gamma treatment showed 2.67- and 1.92-fold enhancement, respectively, as compared to the damages induced by radiation alone or radiation combined IUdR. Dosimetry results showed the accurate dose delivered to cells. Conclusion Analysis of the comet tail moments of spheroids showed that the radiation treatments combined with hyperthermia and IUdR caused significant radiosensitization when compared to related results of irradiation alone or of irradiation with IUdR. These results suggest a potential clinical advantage of combining radiation with hyperthermia and indicate effectiveness of hyperthermia treatment in inducing cytotoxicity of tumor cells. PMID:24611138

Hyperthermia increases interleukin-6 in mouse skeletal muscle

PubMed Central

Welc, Steven S.; Phillips, Neil A.; Oca-Cossio, Jose; Wallet, Shannon M.; Chen, Daniel L.

2012-01-01

Skeletal muscles produce and contribute to circulating levels of IL-6 during exercise. However, when core temperature is reduced, the response is attenuated. Therefore, we hypothesized that hyperthermia may be an important and independent stimulus for muscle IL-6. In cultured C2C12 myotubes, hyperthermia (42°C) increased IL-6 gene expression 14-fold after 1 h and 35-fold after 5 h of 37°C recovery; whereas exposure to 41°C resulted in a 2.6-fold elevation at 1 h. IL-6 protein was secreted and significantly elevated in the cell supernatant. Similar but reduced responses to heat were seen in C2C12 myoblasts. Isolated soleus muscles from mice, exposed ex vivo to 41°C for 1 h, yielded similar IL-6 gene responses (>3-fold) but without a significant effect on protein release. When whole animals were exposed to passive hyperthermia, such that core temperature increased to 42.4°C, IL-6 mRNA in soleus increased 5.4-fold compared with time matched controls. Interestingly, TNF-α gene expression was routinely suppressed at all levels of hyperthermia (40.5–42°C) in the isolated models, but TNF-α was elevated (4.2-fold) in the soleus taken from intact mice exposed, in vivo, to hyperthermia. Muscle HSP72 mRNA increased as a function of the level of hyperthermia, and IL-6 mRNA responses increased proportionally with HSP72. In cultured C2C12 myotubes, when heat shock factor was pharmacologically blocked with KNK437, both HSP72 and IL-6 mRNA elevations, induced by heat, were suppressed. These findings implicate skeletal muscle as a “heat stress sensor” at physiologically relevant hyperthermia, responding with a programmed cytokine expression pattern characterized by elevated IL-6. PMID:22673618

FDTD analysis of a noninvasive hyperthermia system for brain tumors

PubMed Central

2012-01-01

Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors. PMID:22891953

Identification of infusion strategy for achieving repeatable nanoparticle distribution and quantification of thermal dosage using micro-CT Hounsfield unit in magnetic nanoparticle hyperthermia.

PubMed

LeBrun, Alexander; Joglekar, Tejashree; Bieberich, Charles; Ma, Ronghui; Zhu, Liang

2016-01-01

The objective of this study was to identify an injection strategy leading to repeatable nanoparticle deposition patterns in tumours and to quantify volumetric heat generation rate distribution based on micro-CT Hounsfield unit (HU) in magnetic nanoparticle hyperthermia. In vivo animal experiments were performed on graft prostatic cancer (PC3) tumours in immunodeficient mice to investigate whether lowering ferrofluid infusion rate improves control of the distribution of magnetic nanoparticles in tumour tissue. Nanoparticle distribution volume obtained from micro-CT scan was used to evaluate spreading of the nanoparticles from the injection site in tumours. Heating experiments were performed to quantify relationships among micro-CT HU values, local nanoparticle concentrations in the tumours, and the ferrofluid-induced volumetric heat generation rate (q(MNH)) when nanoparticles were subject to an alternating magnetic field. An infusion rate of 3 µL/min was identified to result in the most repeatable nanoparticle distribution in PC3 tumours. Linear relationships have been obtained to first convert micro-CT greyscale values to HU values, then to local nanoparticle concentrations, and finally to nanoparticle-induced q(MNH) values. The total energy deposition rate in tumours was calculated and the observed similarity in total energy deposition rates in all three infusion rate groups suggests improvement in minimising nanoparticle leakage from the tumours. The results of this study demonstrate that micro-CT generated q(MNH) distribution and tumour physical models improve predicting capability of heat transfer simulation for designing reliable treatment protocols using magnetic nanoparticle hyperthermia.

Controllable in vivo hyperthermia effect induced by pulsed high intensity focused ultrasound with low duty cycles

PubMed Central

Tu, Juan; Ha Hwang, Joo; Chen, Tao; Fan, Tingbo; Guo, Xiasheng; Crum, Lawrence A.; Zhang, Dong

2012-01-01

High intensity focused ultrasound (HIFU)-induced hyperthermia is a promising tool for cancer therapy. Three-dimensional nonlinear acoustic-bioheat transfer-blood flow-coupling model simulations and in vivo thermocouple measurements were performed to study hyperthermia effects in rabbit auricular vein exposed to pulsed HIFU (pHIFU) at varied duty cycles (DCs). pHIFU-induced temperature elevations are shown to increase with increasing DC. A critical DC of 6.9% is estimated for temperature at distal vessel wall exceeding 44 °C, although different tissue depths and inclusions could affect the DC threshold. The results demonstrate clinic potentials of achieving controllable hyperthermia by adjusting pHIFU DCs, while minimizing perivascular thermal injury. PMID:23112347

It Takes Time to Be Cool: On the Relationship between Hyperthermia and Body Cooling in a Migrating Seaduck

PubMed Central

Guillemette, Magella; Polymeropoulos, Elias T.; Portugal, Steven J.; Pelletier, David

2017-01-01

The large amount of energy expended during flapping flight is associated with heat generated through the increased work of the flight muscles. This increased muscle work rate can manifest itself in core body temperature (Tb) increase of 1–2°C in birds during flight. Therefore, episodic body cooling may be mandatory in migratory birds. To elucidate the thermoregulatory strategy of a short-distance migrant, common eiders (Somateria mollissima), we implanted data loggers in the body cavity of wild birds for 1 year, and report information on Tb during their entire migration for 19 individuals. We show that the mean body temperature during flight (TbMean) in the eiders was associated with rises in Tb ranging from 0.2 to 1.5°C, largely depending on flight duration. To understand how eiders are dealing with hyperthermia during migration, we first compare, at a daily scale, how Tb differs during migration using a before-after approach. Only a slight difference was found (0.05°C) between the after (40.30°C), the before (40.41°C) and the migration (40.36°C) periods, indicating that hyperthermia during flight had minimal impact at this time scale. Analyses at the scale of a flight cycle (flight plus stops on the water), however, clearly shows that eiders were closely regulating Tb during migration, as the relationship between the storage of heat during flight was highly correlated (slope = 1) with the level of heat dumping during stops, at both inter-individual and intra-individual levels. Because Tb at the start of a flight (TbStart) was significantly and positively related to Tb at the end of a flight (TbEnd), and the maximal attained Tb during a flight (TbMax), we conclude that in absence of sufficient body cooling during stopovers, eiders are likely to become increasingly hyperthermic during migration. Finally, we quantified the time spent cooling down during migration to be 36% of their daily (24 h) time budget, and conclude that behavioral body cooling in relation to hyperthermia represents an important time cost. PMID:28790930

Passive heat stress reduces circulating endothelial and platelet microparticles.

PubMed

Bain, Anthony R; Ainslie, Philip N; Bammert, Tyler D; Hijmans, Jamie G; Sekhon, Mypinder; Hoiland, Ryan L; Flück, Daniela; Donnelly, Joseph; DeSouza, Christopher A

2017-06-01

What is the central question of this study? Does passive heat stress of +2°C oesophageal temperature change concentrations of circulating arterial endothelial- and platelet-derived microparticles in healthy adults? What is the main finding and its importance? Concentrations of circulating endothelial- and platelet-derived microparticles were markedly decreased in heat stress. Reductions in circulating microparticles might indicate favourable vascular changes associated with non-pathological hyperthermia. Interest in circulating endothelial- and platelet-derived microparticles (EMPs and PMPs, respectively) has increased because of their potential pathogenic role in vascular disease and as biomarkers for vascular health. Hyperthermia is commonly associated with a pro-inflammatory stress but might also provide vascular protection when the temperature elevation is non-pathological. Circulating microparticles might contribute to the cellular adjustments and resultant vascular impacts of hyperthermia. Here, we determined whether circulating concentrations of arterial EMPs and PMPs are altered by passive heat stress (+2°C oesophageal temperature). Ten healthy young men (age 23 ± 3 years) completed the study. Hyperthermia was achieved by circulating ∼49°C water through a water-perfused suit that covered the entire body except the hands, feet and head. Arterial (radial) blood samples were obtained immediately before heating (normothermia) and in hyperthermia. The mean ± SD oesophageal temperature in normothermia was 37.2 ± 0.1°C and in hyperthermia 39.1 ± 0.1°C. Concentrations of circulating EMPs and PMPs were markedly decreased in hyperthermia. Activation-derived EMPs were reduced by ∼30% (mean ± SD; from 61 ± 8 to 43 ± 7 microparticles μl -1 ; P < 0.05) and apoptosis-derived EMPs by ∼45% (from 46 ± 7 to 23 ± 3 microparticles μl -1 ; P < 0.05). Likewise, circulating PMPs were reduced by ∼75% in response to hyperthermia (from 256 ± 43 to 62 ± 14 microparticles μl -1 ). These beneficial reductions in circulating EMPs and PMPs in response to a 2°C increase in core temperature might partly underlie the reported vascular improvements following therapeutic bouts of physiological hyperthermia. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Synergistic administration of photothermal therapy and chemotherapy to cancer cells using polypeptide-based degradable plasmonic matrices

PubMed Central

Huang, Huang-Chiao; Yang, Yoonsun; Nanda, Alisha; Koria, Piyush; Rege, Kaushal

2012-01-01

Aim Resistance of cancer cells to hyperthermic temperatures and spatial limitations of nanoparticle-induced hyperthermia necessitates the identification of effective combination treatments that can enhance the efficacy of this treatment. Here we show that novel polypeptide-based degradable plasmonic matrices can be employed for simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment that can overcome cancer cell resistance to hyperthermia. Method Novel gold nanorod elastin-like polypeptide matrices were generated and characterized. The matrices were also loaded with the heat-shock protein (HSP)90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), currently in clinical trials for different malignancies, in order to deliver a combination of hyperthermia and chemotherapy. Results Laser irradiation of cells cultured over the plasmonic matrices (without 17-AAG) resulted in the death of cells directly in the path of the laser, while cells outside the laser path did not show any loss of viability. Such spatial limitations, in concert with expression of prosurvival HSPs, reduce the efficacy of hyperthermia treatment. 17-AAG–gold nanorod–polypeptide matrices demonstrated minimal leaching of the drug to surrounding media. The combination of hyperthermic temperatures and the release of 17-AAG from the matrix, both induced by laser irradiation, resulted in significant (>90%) death of cancer cells, while ‘single treatments’ (i.e., hyperthermia alone and 17-AAG alone) demonstrated minimal loss of cancer cell viability (<10%). Conclusion Simultaneous administration of hyperthermia and HSP inhibitor release from plasmonic matrices is a powerful approach for the ablation of malignant cells and can be extended to different combinations of nanoparticles and chemotherapeutic drugs for a variety of malignancies. PMID:21542685

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models.more » In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.« less

The independent influences of heat strain and dehydration upon cognition.

PubMed

van den Heuvel, Anne M J; Haberley, Benjamin J; Hoyle, David J R; Taylor, Nigel A S; Croft, Rodney J

2017-05-01

Many researchers have addressed the potential effects of hyperthermia and dehydration on cognition, often revealing contradictory outcomes. A possible reason for this inconsistency is that experiments may have been inadequately designed for such effects. In this study, the impact of hyperthermia, dehydration and their combination on cognition were evaluated in eight young males, after accounting for a range of experimental limitations. Passive heating and thermal clamping at two mean body temperatures (36.5, 38.5 °C) were performed under three hydration states (euhydrated, 3 and 5% dehydrated) to assess their effects on difficulty-matched working memory and visual perception tasks, and on a difficulty manipulated perceptual task. Data were analysed according to signal detection theory to isolate changes in response sensitivity, bias and speed. Neither moderate hyperthermia (P = 0.141) nor dehydration (P > 0.604) modified response sensitivity, nor did they significantly interact (P > 0.698). Therefore, the ability to distinguish correct from incorrect responses was unaffected. Nevertheless, hyperthermia, but not dehydration (P = 0.301), reduced the response bias (-0.08 versus 2.2 [normothermia]; P = 0.010) and reaction time (mean reduction 49 ms; P < 0.001), eliciting more liberal and faster responses (P = 0.010). Response bias was reduced for the memory relative to the perceptual task (P = 0.037), and this effect was enhanced during hyperthermia (P = 0.031). These observations imply that, once potentially confounding influences were controlled, moderate hyperthermia, significant dehydration and their combined effects had insufficient impact to impair cognition within the memory and perceptual domains tested. Nonetheless, moderate hyperthermia elicited more liberal and rapid responses.

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

PubMed

Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

2004-01-01

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external sphincterotomy followed by condom catheter drainage is recommended. However, if external urethral sphincterotomy fails to reduce residual urine and detrusor pressure, urinary diversion or bladder reconstruction may be necessary.

Hyperthermically induced changes in high spectral and spatial resolution MR images of tumor tissue—a pilot study

NASA Astrophysics Data System (ADS)

Foxley, Sean; Fan, Xiaobing; River, Jonathan; Zamora, Marta; Markiewicz, Erica; Sokka, Shunmugavelu; Karczmar, Gregory S.

2012-05-01

This pilot study investigated the feasibility of using MRI based on BOLD (blood-oxygen-level-dependent) contrast to detect physiological effects of locally induced hyperthermia in a rodent tumor model. Nude mice bearing AT6.1 rodent prostate tumors inoculated in the hind leg were imaged using a 9.4 T scanner using a multi-gradient echo pulse sequence to acquire high spectral and spatial resolution (HiSS) data. Temperature increases of approximately 6 °C were produced in tumor tissue using fiber-optic-guided light from a 250 W halogen lamp. HiSS data were acquired over three slices through the tumor and leg both prior to and during heating. Water spectra were produced from these datasets for each voxel at each time point. Time-dependent changes in water resonance peak width were measured during 15 min of localized tumor heating. The results demonstrated that hyperthermia produced both significant increases and decreases in water resonance peak width. Average decreases in peak width were significantly larger in the tumor rim than in normal muscle (p = 0.04). The effect of hyperthermia in tumor was spatially heterogeneous, i.e. the standard deviation of the change in peak width was significantly larger in the tumor rim than in normal muscle (p = 0.005). Therefore, mild hyperthermia produces spatially heterogeneous changes in water peak width in both tumor and muscle. This may reflect heterogeneous effects of hyperthermia on local oxygenation. The peak width changes in tumor and muscle were significantly different, perhaps due to abnormal tumor vasculature and metabolism. Response to hyperthermia measured by MRI may be useful for identifying and/or characterizing suspicious lesions as well as guiding the development of new hyperthermia protocols.

High pressure enhances the effect of hyperthermia in intraperitoneal chemotherapy with oxaliplatin: an experimental study.

PubMed

Facy, Olivier; Al Samman, Sophie; Magnin, Guy; Ghiringhelli, Francois; Ladoire, Sylvain; Chauffert, Bruno; Rat, Patrick; Ortega-Deballon, Pablo

2012-12-01

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) achieve good results in selected patients with peritoneal carcinomatosis. High intra-abdominal pressure could enhance the penetration of chemotherapy drugs. The aim of this study was to compare the effects of high pressure and hyperthermia when used separately and when combined in terms of blood and tissue absorption of oxaliplatin in a swine model of intraperitoneal chemotherapy. Four groups of 5 pigs each underwent laparotomy and open intraperitoneal chemotherapy with oxaliplatin at a constant concentration (150 mg/L) for 30 minutes in normothermia and atmospheric pressure (group 1), or hyperthermia (42°C) and atmospheric pressure (group 2), or normothermia and high pressure (25 cm H2O) (group 3), or hyperthermia and high pressure (group 4). High pressure was achieved thorough a water column over the abdomen. Systemic absorption and abdominal tissue mapping of the penetration of oxaliplatin in each group were studied. Blood concentrations of oxaliplatin were similar in the different groups. Hyperthermia achieved higher concentrations in visceral surfaces (P = 0.0014), but not in parietal surfaces. High pressure enhanced diffusion of the drug in both the visceral and parietal peritoneum (P = 0.0058 and P = 0.0044, respectively). The combination of hyperthermia and high pressure significantly increased the penetration of oxaliplatin and achieved the highest tissue concentrations (10.39 mg/kg vs 5.48 mg/kg; P = 0.00001 in the visceral peritoneum, and 66.16 mg/kg vs 35.62 mg/kg; P = 0.0003 in the parietal peritoneum). Open high-pressure HIPEC with oxaliplatin is feasible in the pig. Hyperthermia enhances diffusion in the visceral peritoneum, whereas high pressure is effective in the visceral and parietal peritoneum. The combination of the two achieves the highest tissue concentrations of oxaliplatin.

Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents.

PubMed

Albers, D S; Sonsalla, P K

1995-12-01

Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental animals. Damage sustained to dopaminergic nerve terminals by this stimulant can be reduced by environmental cooling or by pharmacological manipulation which attenuates the hyperthermia. Many pharmacological agents with very diverse actions protect against METH-induced neuropathology. Several of these compounds, as well as drugs which do not protect, were investigated to determine if there was a relationship between protection and METH-induced hyperthermia. Mice received METH with or without concurrent administration of other drugs and core (i.e., colonic) temperature was monitored during treatment. The animals were sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and dopamine were measured. Core temperature was significantly elevated (> or = 2 degrees C) in mice treated with doses of METH which produced > or = 90% losses in striatal dopamine but not in mice less severally affected (only 50% loss of dopamine). Concurrent treatment of mice with METH and pharmacological agents which protected partially or completely from METH-induced toxicity also prevented the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine, dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and propranol). These findings are consistent with the hypothesis that the hyperthermia produced by METH contributes to its neuropathology. However, studies with reserpine, a compound which dramatically lowers core temperature, demonstrated that hyperthermia per se is not a requirement for METH-induced neurotoxicity. Although core temperature was elevated in reserpinized mice treated with METH as compared with reserpinized control mice, their temperatures remained significantly lower than in nonreserpinized control mice. However, the hypothermic state produced in the reserpinized mice did not provide protection from METH-induced toxicity. These data demonstrate that hyperthermia per se contributes to but is not solely responsible for the METH-induced neuropathology.

Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood salvage but preserves the function of erythrocytes.

PubMed

Yang, Jin-ting; Tang, Li-hui; Liu, Yun-qing; Wang, Yin; Wang, Lie-ju; Zhang, Feng-jiang; Yan, Min

2015-05-01

The safe use of intraoperative blood salvage (IBS) in cancer surgery remains controversial. Here, we investigated the killing effect of cisplatin combined with hyperthermia on human hepatocarcinoma (HepG2) cells and erythrocytes from IBS in vitro. HepG2 cells were mixed with concentrated erythrocytes and pretreated with cisplatin (50, 100, and 200 μg/ml) alone at 37 °C for 60 min and cisplatin (25, 50, 100, and 200 μg/ml) combined with hyperthermia at 42 °C for 60 min. After pretreatment, the cell viability, colony formation and DNA metabolism in HepG2 and the Na(+)-K(+)-ATPase activity, 2,3-diphosphoglycerate (2,3-DPG) concentration, free hemoglobin (Hb) level, osmotic fragility, membrane phosphatidylserine externalization, and blood gas variables in erythrocytes were determined. Pretreatment with cisplatin (50, 100, and 200 μg/ml) combined with hyperthermia (42 °C) for 60 min significantly decreased HepG2 cell viability, and completely inhibited colony formation and DNA metabolism when the HepG2 cell concentration was 5×10(4) ml(-1) in the erythrocyte (P<0.01). Erythrocytic Na(+)-K(+)-ATPase activity, 2,3-DPG level, phosphatidylserine externalization, and extra-erythrocytic free Hb were significantly altered by hyperthermia plus high concentrations of cisplatin (100 and 200 μg/ml) (P<0.05), but not by hyperthermia plus 50 μg/ml cisplatin (P>0.05). In conclusion, pretreatment with cisplatin (50 μg/ml) combined with hyperthermia (42 °C) for 60 min effectively eliminated HepG2 cells from IBS but did not significantly affect erythrocytes in vitro.

Numerical modeling for an electric-field hyperthermia applicator

NASA Technical Reports Server (NTRS)

Wu, Te-Kao; Chou, C. K.; Chan, K. W.; Mcdougall, J.

1993-01-01

Hyperthermia, in conjunction with radiation and chemotherapy for treatment of cancers, is an area of current concern. Experiments have shown that hyperthermia can increase the potency of many chemotherapy drugs and the effectiveness of radiation for treating cancer. A combination of whole body or regional hyperthermia with chemotherapy or radiation should improve treatment results. Conventional methods for inducing whole body hyperthermia, such as exposing a patient in a radiant cabinet or under a hot water blanket, conduct heat very slowly from the skin to the body core. Thus a more efficient system, such as the three-plate electric-field hyperthermia applicator (EHA), is developed. This three-plate EHA has one top plate over and two lower plates beneath the patient. It is driven at 27.12 MHz with 500 Watts through a matching circuit. Using this applicator, a 50 kg pig was successfully heated to 42 C within 45 minutes. However, phantom and animal studies have indicated non-uniform heating near the side of the body. In addition, changes in the size and distance between the electrode plates can affect the heating (or electromagnetic field) pattern. Therefore, numerical models using the method of moments (MOM) or the finite difference time domain (FDTD) technique are developed to optimize the heating pattern of this EHA before it is used for human trials. The accuracy of the numerical modeling has been achieved by the good agreement between the MOM and FDTD results for the three-plate EHA without a biological body. The versatile FDTD technique is then applied to optimize the EHA design with a human body. Both the numerical and measured data in phantom blocks will be presented. The results of this study will be used to design an optimized system for whole body or regional hyperthermia.

Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

PubMed Central

Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

2017-01-01

Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors. PMID:28287120

Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model.

PubMed

Ware, Matthew J; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A; Corr, Stuart J

2017-03-13

Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature.

PubMed

Kong, G; Braun, R D; Dewhirst, M W

2001-04-01

The efficacy of novel cancer therapeutics can be hampered by inefficient delivery of agents to the tumor at effective concentrations. Liposomes have been used as a method to overcome some delivery issues and, in combination with hyperthermia, have been shown to increase drug delivery to tumors. This study investigates the effects of a range of temperatures (34-42 degrees C) and hyperthermia treatment scheduling (time between hyperthermia and drug administration as well as between consecutive hyperthermia treatments) on the extravasation of nanoparticles (100-nm liposomes) from tumor microvasculature in a human tumor (SKOV-3 ovarian carcinoma) xenograft grown in athymic nude mouse window chambers. Under normothermic conditions (34 degrees C) and at 39 degrees C, nanoparticles were unable to extravasate into the tumor interstitium. From 40 to 42 degrees C, nanoparticle extravasation increased with temperature, reaching maximal extravasation at 42 degrees C. Temperatures higher than 42 degrees C led to hemorrhage and stasis in tumor vessels. Enhanced nanoparticle extravasation was observed several hours after heating, decaying back to baseline at 6 h postheating. Reheating (42 degrees C for 1 h) 8 h after an initial heating (42 degrees C for 1 h) did not result in any increased nanoparticle extravasation, indicating development of vascular thermotolerance. The results of this study have implications for the application and scheduling of hyperthermia combined with other therapeutics (e.g., liposomes, antibodies, and viral vectors) for the treatment of cancer.

Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

NASA Astrophysics Data System (ADS)

Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

2017-03-01

Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

Hydroxyapatite Coated Iron Oxide Nanoparticles: A Promising Nanomaterial for Magnetic Hyperthermia Cancer Treatment.

PubMed

Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Nguyen, Van Tu; Kim, Hye Hyun; Nam, Seung Yun; Lee, Kang Dae; Oh, Junghwan

2017-12-04

Targeting cancer cells without injuring normal cells is the prime objective in treatment of cancer. In this present study, solvothermal and wet chemical precipitation techniques were employed to synthesize iron oxide (IO), hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and 40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic field at room temperature (300 K). The magnetic hyperthermia study that was performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia temperature (~45 °C) was reached within 3 min, which shows a very high efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells within 30 min exposure. These results could potentially open new perceptions for biomaterials that are aimed for anti-cancer therapies based on magnetic hyperthermia.

Hydroxyapatite Coated Iron Oxide Nanoparticles: A Promising Nanomaterial for Magnetic Hyperthermia Cancer Treatment

PubMed Central

Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Nguyen, Van Tu; Kim, Hye Hyun; Nam, Seung Yun; Lee, Kang Dae; Oh, Junghwan

2017-01-01

Targeting cancer cells without injuring normal cells is the prime objective in treatment of cancer. In this present study, solvothermal and wet chemical precipitation techniques were employed to synthesize iron oxide (IO), hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and 40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic field at room temperature (300 K). The magnetic hyperthermia study that was performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia temperature (~45 °C) was reached within 3 min, which shows a very high efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells within 30 min exposure. These results could potentially open new perceptions for biomaterials that are aimed for anti-cancer therapies based on magnetic hyperthermia. PMID:29207552

Design of optimal hyperthermia protocols for prostate cancer by controlling HSP expression through computer modeling (Invited Paper)

NASA Astrophysics Data System (ADS)

Rylander, Marissa N.; Feng, Yusheng; Diller, Kenneth; Bass, J.

2005-04-01

Heat shock proteins (HSP) are critical components of a complex defense mechanism essential for preserving cell survival under adverse environmental conditions. It is inevitable that hyperthermia will enhance tumor tissue viability, due to HSP expression in regions where temperatures are insufficient to coagulate proteins, and would likely increase the probability of cancer recurrence. Although hyperthermia therapy is commonly used in conjunction with radiotherapy, chemotherapy, and gene therapy to increase therapeutic effectiveness, the efficacy of these therapies can be substantially hindered due to HSP expression when hyperthermia is applied prior to these procedures. Therefore, in planning hyperthermia protocols, prediction of the HSP response of the tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of overall tissue response. In this paper, we present a highly accurate, adaptive, finite element tumor model capable of predicting the HSP expression distribution and tissue damage region based on measured cellular data when hyperthermia protocols are specified. Cubic spline representations of HSP27 and HSP70, and Arrhenius damage models were integrated into the finite element model to enable prediction of the HSP expression and damage distribution in the tissue following laser heating. Application of the model can enable optimized treatment planning by controlling of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

How gastrin-releasing peptide receptor (GRPR) and αvβ3 integrin expression reflect reorganization features of tumors after hyperthermia treatments.

PubMed

Hallasch, Sandra; Frick, Sindy; Jung, Maximilian; Hilger, Ingrid

2017-07-31

The outcome of tumor treatment via hyperthermia in the clinic has been reported to be heterogeneous. Here, we assessed how the presence of gastrin-releasing peptide receptor (GRPR) and α v β 3 integrin together with the morphology of the vascularization reflects the growth behavior of tumors after hyperthermia treatment. MDA-MB-231 tumor bearing mice were treated either with high (46 °C) or low dose (42 °C) water hyperthermia for 60 min. Changes of GRPR and α v β 3 integrin expression were assessed via multiplexed optical imaging. Vascularization was reconstructed and quantified by µCT imaging after contrast agent injection. We found that high dose hyperthermia is capable of increasing the expression of GRPR, α v β 3 integrin, CD31, and Ki67 in tumors. Also the morphology of tumor vasculature changed (increased relative blood volume and small-diameter vessel density, decreased expression of α-SMA). Low dose hyperthermia induced comparatively moderate effects on the investigated protein expression pattern and vascular remodeling. We conclude that under defined circumstances, specific temperature doses affect the reorganization of tumor regrowth, which is triggered by residual "dormant" cells even though tumor volumes are transiently decreasing. Further on, GRPR, α v β 3 integrin expression are versatile tools to surveil potential tumor regrow during therapy, beyond the conventional determination of tumor volumes.

Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus

PubMed Central

Zaretsky, Dmitry V; Zaretskaia, Maria V; Durant, Pamela J; Rusyniak, Daniel E

2015-01-01

The contribution of exercise to hyperthermia mediated by MDMA is not known. We recently showed that inhibiting the dorsomedial hypothalamus (DMH) attenuated spontaneous locomotion and hyperthermia and prevented deaths in rats given MDMA in a warm environment. The goal of this study was to confirm that restoring locomotion through a treadmill would reverse these effects thereby confirming that locomotion mediated by the DMH contributes to MDMA-mediated hyperthermia. Rats were randomized to receive bilateral microinjections, into the region of the DMH, of muscimol (80 pmol/100nl) or artificial CSF followed by a systemic dose of either MDMA (7.5 mg/kg, i.v.) or saline. Immediately after the systemic injection, rats were placed on a motorized treadmill maintained at 32°C. Rats were exercised at a fixed speed (10 m/min) until their core temperature reached 41°C. Our results showed that a fixed exercise load abolished the decreases in temperature and mortality, seen previously with inhibition of the DMH in freely moving rats. Therefore, locomotion mediated by neurons in the DMH is critical to the development of hyperthermia from MDMA. PMID:25725382

Enhancement of Thermal Damage to Adenocarcinoma Cells by Iron Nanoparticles Modified with MUC1 Aptamer.

PubMed

Guo, Fangqin; Hu, Yan; Yu, Lianyuan; Deng, Xiaoyuan; Meng, Jie; Wang, Chen; Yang, Xian-Da

2016-03-01

Hyperthermia cancer treatment is an adjunctive therapy that aims at killing the tumor cells with excessive heat that is usually generated by metal contrasts exposed to alternating magnetic field. The efficacy of hyperthermia is often limited by the heat damage to normal tissue due to indiscriminate distribution of the metal contrasts within the body. Tumor-targeting metal contrasts may reduce the toxicity of hyperthermia and improve the efficacy of thermotherapy against cancer. MUC1 is a glycoprotein over expressed in most adenocarcinomas, and represents an attractive therapeutic target. In this study, a MUC1 aptamer is conjugated with iron nanoparticles to construct adenocarcinoma-targeting metal contrasts. DNA hybridization studies confirmed that the aptamers were conjugated to the iron nanoparticles. Importantly, more aptamer-modified nanoparticles attached to the MUC1-positive cancer cells compared with the unmodified nanoparticles. Moreover, aptamer-modified nanoparticles significantly enhanced the targeted hyperthermia damage to MUC1-positive cancer cells in vitro (p < 0.05). The results suggest that MUC1 aptamer-modified metal particles may have potential in development of targeted hyperthermia therapy against adenocarcinomas.

Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillette, S.M.; Gillette, E.L.; Dawson, C.A.

1997-02-01

The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0{degrees}C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for andmore » occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological change were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study. 17 refs., 3 figs., 2 tabs.« less

Hyperthermia treatment of spontaneously occurring oral cavity tumors using a computer-controlled Nd:YAG laser system

NASA Astrophysics Data System (ADS)

Panjehpour, Masoud; Overholt, Bergein F.; Frazier, Donita L.; Klebanow, Edward R.

1991-05-01

Conventional hyperthermia treatment of superficial tumors in the oral cavity is difficult due to inability in accessing the lesion. A new hyperthermia technique employing near infrared Nd:YAG irradiation delivered through an optical fiber is introduced for heating oral and nasal tumors in animals. This system consisted of an Nd:YAG laser, a He-Ne laser, a computer controlled optical shutter, an interstitial thermometer, computer and a printer. The tumors were heated via surface illumination of the lesion. A thermocouple implanted in the base of the tumor provided temperature feedback for laser energy regulation. Three spontaneously occurring canine (two squamous cell carcinoma on the gum, one pigmented melanoma on the hard palate) and one feline tumor (squamous cell carcinoma on the nose) have been treated with the Nd:YAG laser-induced hyperthermia delivered following radiation therapy. The tumor temperature was maintained between 43.2-43.5 degree(s)C for one hour. Nd:YAG hyperthermia allowed efficient delivery of heat to veterinary oral and nasal lesions otherwise impossible to treat with conventional heating techniques.

Circulatory failure during severe hyperthermia in dog.

PubMed

Miki, K; Morimoto, T; Nose, H; Itoh, T; Yamada, S

1983-01-01

The effect of acute hyperthermia on circulatory function was studied in 6 mongrel dogs. At a core temperature of about 40 degrees C, central venous pressure and stroke volume were maintained at almost normal level. Cardiac output significantly increased (26 ml/(kg . min)) while systemic vascular resistance significantly decreased (1.2 mmHg . sec/ml). In addition, significant decrease in vascular compliance by 40% was observed. When body temperature was raised further (severe hyperthermia), an abrupt fall of arterial pressure was observed at the rectal temperature of about 41-42 degrees C. Concomitant decreases in central venous pressure (3 mmHg), stroke volume (2.1 ml/beat) and cardiac output (29 ml/(kg . min)) were observed while heart rate increased (48 beats/min). These results suggest that the decrease in cardiac output during severe hyperthermia is due to the fall of central venous pressure, and the fall was attributed to the increase in unstressed vascular volume of systemic circulation due to the heat-induced cutaneous vasodilation. The observed decrease in systemic vascular compliance is considered to have a significant role in the maintenance of central venous pressure under hyperthermia.

Weather, geography, and vehicle-related hyperthermia in children.

PubMed

Grundstein, Andrew; Null, Jan; Meentemeyer, Vernon

2011-01-01

Vehicle-related hyperthermia is an unfortunate tragedy that leads to the accidental deaths of children each year. This research utilizes the most extensive dataset of child vehicle-related hyperthermia deaths in the United States, including 414 deaths between 1998 and 2008. Deaths follow a seasonal pattern, with a peak in July and no deaths in December or January. Also, deaths occurred over a wide range of temperature and radiation levels and across virtually all regions, although most of them took place across the southern United States. In particular, the Phoenix, Houston, Dallas, and Las Vegas metropolitan areas had the greatest number of deaths. We utilize our vehicle hyperthermia index (vhi) to compare expected deaths versus actual deaths in a metropolitan area, based on the number of children in the area who are under the age of five and on the frequency of hot days in the area. The vhi indicates that the Memphis, West Palm Beach-Boca Raton, and Las Vegas metropolitan areas are the most dangerous places for vehicle-related hyperthermia. We conclude by discussing several recommendations with public health policy implications.

Social factors modulate restraint stress induced hyperthermia in mice.

PubMed

Watanabe, Shigeru

2015-10-22

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

The Dartmouth Center for Cancer Nanotechnology Excellence: magnetic hyperthermia.

PubMed

Baker, Ian; Fiering, Steve N; Griswold, Karl E; Hoopes, P Jack; Kekalo, Katerina; Ndong, Christian; Paulsen, Keith; Petryk, Alicea A; Pogue, Brian; Shubitidze, Fridon; Weaver, John

2015-01-01

The Dartmouth Center for Cancer Nanotechnology Excellence - one of nine funded by the National Cancer Institute as part of the Alliance for Nanotechnology in Cancer - focuses on the use of magnetic nanoparticles for cancer diagnostics and hyperthermia therapy. It brings together a diverse team of engineers and biomedical researchers with expertise in nanomaterials, molecular targeting, advanced biomedical imaging and translational in vivo studies. The goal of successfully treating cancer is being approached by developing nanoparticles, conjugating them with Fabs, hyperthermia treatment, immunotherapy and sensing treatment response.

Temperature distribution in the human body under various conditions of induced hyperthermia

NASA Technical Reports Server (NTRS)

Korobko, O. V.; Perelman, T. L.; Fradkin, S. Z.

1977-01-01

A mathematical model based on heat balance equations was developed for studying temperature distribution in the human body under deep hyperthermia which is often induced in the treatment of malignant tumors. The model yields results which are in satisfactory agreement with experimental data. The distribution of temperature under various conditions of induced hyperthermia, i.e. as a function of water temperature and supply rate, is examined on the basis of temperature distribution curves in various body zones.

Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer.

PubMed

Gözen, Ali Serdar; Umari, Paolo; Scheitlin, Walter; Su, Fuat Ernis; Akin, Yigit; Rassweiler, Jens

2017-06-30

Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC) is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC) instillation in patients with high-risk recurrent NMIBC. Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT) system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel). The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria) score system. Mean age was 72 (32-87) years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period). 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3%) were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

Genetics Home Reference: malignant hyperthermia

MedlinePlus

... Genetic and Rare Diseases Information Center (2 links) King Denborough syndrome Malignant hyperthermia Educational Resources (4 links) ... 19 [updated 2013 Jan 31]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean ...

Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

NASA Astrophysics Data System (ADS)

Yuan, Chenyan; An, Yanli; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng

2014-08-01

Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression.

Monitoring nanoparticle-mediated cellular hyperthermia with a high-sensitivity biosensor

PubMed Central

Mukherjee, Amarnath; Castanares, Mark; Hedayati, Mohammad; Wabler, Michele; Trock, Bruce; Kulkarni, Prakash; Rodriguez, Ronald; Getzenberg, Robert H; DeWeese, Theodore L; Ivkov, Robert; Lupold, Shawn E

2014-01-01

Aim To develop and apply a heat-responsive and secreted reporter assay for comparing cellular response to nanoparticle (NP)- and macroscopic-mediated sublethal hyperthermia. Materials & methods Reporter cells were heated by water bath (macroscopic heating) or iron oxide NPs activated by alternating magnetic fields (nanoscopic heating). Cellular responses to these thermal stresses were measured in the conditioned media by secreted luciferase assay. Results & conclusion Reporter activity was responsive to macroscopic and nanoparticle heating and activity correlated with measured macroscopic thermal dose. Significant cellular responses were observed with NP heating under doses that were insufficient to measurably change the temperature of the system. Under these conditions, the reporter response correlated with proximity to cells loaded with heated nanoparticles. These results suggest that NP and macroscopic hyperthermia may be distinctive under conditions of mild hyperthermia. PMID:24547783

Superparamagnetic MFe2O 4 (M = Ni, Co, Zn, Mn) nanoparticles: synthesis, characterization, induction heating and cell viability studies for cancer hyperthermia applications.

PubMed

Sabale, Sandip; Jadhav, Vidhya; Khot, Vishwajeet; Zhu, Xiaoli; Xin, Meiling; Chen, Hongxia

2015-03-01

Superparamagnetic nanoferrites are prepared by simple and one step refluxing in polyol synthesis. The ferrite nanoparticles prepared by this method exhibit particle sizes below 10 nm and high degree of crystallinity. These ferrite nanoparticles are compared by means of their magnetic properties, induction heating and cell viability studies for its application in magnetic fluid hyperthermia. Out of all studied nanoparticles in present work, only ZnFe2O4 and CoFe2O4 MNPs are able to produce threshold hyperthermia temperature. This rise in temperature is discussed in detail in view of their magneto-structural properties. Therefore ZnFe2O4 and CoFe2O4 MNPs with improved stability, magnetic induction heating and cell viability are suitable candidates for magnetic hyperthermia.

A study on thermal damage during hyperthermia treatment based on DPL model for multilayer tissues using finite element Legendre wavelet Galerkin approach.

PubMed

Kumar, Dinesh; Rai, K N

2016-12-01

Hyperthermia is a process that uses heat from the spatial heat source to kill cancerous cells without damaging the surrounding healthy tissues. Efficacy of hyperthermia technique is related to achieve temperature at the infected cells during the treatment process. A mathematical model on heat transfer in multilayer tissues in finite domain is proposed to predict the control temperature profile at hyperthermia position. The treatment technique uses dual-phase-lag model of heat transfer in multilayer tissues with modified Gaussian distribution heat source subjected to the most generalized boundary condition and interface at the adjacent layers. The complete dual-phase-lag model of bioheat transfer is solved using finite element Legendre wavelet Galerkin approach. The present solution has been verified with exact solution in a specific case and provides a good accuracy. The effect of the variability of different parameters such as lagging times, external heat source, metabolic heat source and the most generalized boundary condition on temperature profile in multilayer tissues is analyzed and also discussed the effective approach of hyperthermia treatment. Furthermore, we studied the modified thermal damage model with regeneration of healthy tissues as well. For viewpoint of thermal damage, the least thermal damage has been observed in boundary condition of second kind. The article concludes with a discussion of better opportunities for future clinical application of hyperthermia treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Real-time temperature feedback for nanoparticles based tumor thermal treatment (Conference Presentation)

NASA Astrophysics Data System (ADS)

Steinberg, Idan; Tamir, Gil; Gannot, Israel

2017-02-01

Systemic hyperthermia therapy exploits the fact that cancer cells are more sensitive to elevated temperatures than healthy tissue. Systemic application of hyperthermia externally usually leads to low efficiency treatment. Recently, our group and others have proposed an antibody conjugated magnetic nanoparticles (MNPs) approach to overcome the limitation of systemic hyperthermia. MNPs can bind specifically to the tumor sites, thus delivering internal highly effective targeted hyperthermia. However, such internal mechanism requires more complicated controls and monitoring. This current work presents a deep tissue temperature monitoring method to control hyperthermia effectiveness and minimize collateral damage to surrounding tissues. A low-frequency narrowband modulation of the RF field used for MNP heating leads to the generation of diffused thermal waves which propagate to the tissue surface and captured by a thermal camera. A Fourier domain, analytical heat transfer model is used for temperature monitoring algorithm. The ill-posed thermal inverse problem is solved efficiently by iterating over the source power until both the amplitude and phase match the recorded thermal image sequence. The narrow bandwidth thermal stimulation enables acquiring deep signals with high SNR. We show that thermal transverse resolution improves as the stimulation frequency increases even slightly above DC, enabling better heat source transverse separation and margin identification in the case of distributed tumors. These results can be used as a part of an overall image and treat system for efficient detection of tumors, manipulation of MNPs and monitoring MNP based hyperthermia.

Effects of hyperthermia on enzymes and electrolytes in blood and cerebrospinal fluid in dogs

NASA Astrophysics Data System (ADS)

Deswal, K.; Chohan, I. S.

1981-09-01

The effects of exposure to various degrees of heat stress on serum glutamate—oxaloacetate transaminase (SGOT), serum glutamate-pyruvate transaminase (SGPT), alkaline phosphatase (ALK-P-ase), calcium and chlorides have been studied on 75 dogs. Rectal temperature (Tre) was recorded before and after exposure to heat stress. These dogs were divided into 5 groups, according to the Tre level attained after exposure to heat stress. Rectal temperature was raised from normal to 39.45±0.47‡C in the first group, to 40.93±0.17‡C in the second group, to 41.87±0.22‡C in the third group, to 42.90 ± 0.21‡C in the fourth group and to 43.93±0.19‡C in the fifth group. The concentration of enzymes SGOT, SGPT and ALK-P-ase in blood and cerebrospinal fluid (CSF) increased significantly with hyperthermia. Calcium and chlorides concentrations in blood and in CSF tended to increase in hyperthermia. The integrity of the blood brain barrier for these enzymes and calcium is maintained under mild hyperthermia but it breaks down partially under influence of more severe hyperthermia. Core temperature above 41‡C results in damage to tissues and consequential rise of plasma enzymes. This degree of hyperthermia also seems to mark the beginning of injury to blood brain barrier. Critical core temperature tolerated by 50% of animals was 44‡C.

Central dopaminergic neurotransmission plays an important role in thermoregulation and performance during endurance exercise.

PubMed

Zheng, Xinyan; Hasegawa, Hiroshi

2016-10-01

Dopamine (DA) has been widely investigated for its potential role in determining exercise performance. It was originally thought that DA's ergogenic effect was by mediating psychological responses. Recently, some studies have also suggested that DA may regulate physiological responses, such as thermoregulation. Hyperthermia has been demonstrated as an important limiting factor during endurance exercise. DA is prominent in the thermoregulatory centre, and changes in DA concentration have been shown to affect core temperature regulation during exercise. Some studies have proposed that DA or DA/noradrenaline (NA) reuptake inhibitors can improve exercise performance, despite hyperthermia during exercise in the heat. DA/NA reuptake inhibitors also increase catecholamine release in the thermoregulatory centre. Intracerebroventricularly injected DA has been shown to improve exercise performance through inhibiting hyperthermia-induced fatigue, even at normal ambient temperatures. Further, caffeine has been reported to increase DA release in the thermoregulatory centre and improves endurance exercise performance despite increased core body temperature. Taken together, DA has been shown to have ergogenic effects and increase heat storage and hyperthermia tolerance. The mechanisms underlying these effects seem to involve limiting/overriding the inhibitory signals from the central nervous system that result in cessation of exercise due to hyperthermia.

The role of size polydispersity in magnetic fluid hyperthermia: average vs. local infra/over-heating effects.

PubMed

Munoz-Menendez, Cristina; Conde-Leboran, Ivan; Baldomir, Daniel; Chubykalo-Fesenko, Oksana; Serantes, David

2015-11-07

An efficient and safe hyperthermia cancer treatment requires the accurate control of the heating performance of magnetic nanoparticles, which is directly related to their size. However, in any particle system the existence of some size polydispersity is experimentally unavoidable, which results in a different local heating output and consequently a different hyperthermia performance depending on the size of each particle. With the aim to shed some light on this significant issue, we have used a Monte Carlo technique to study the role of size polydispersity in heat dissipation at both the local (single particle) and global (macroscopic average) levels. We have systematically varied size polydispersity, temperature and interparticle dipolar interaction conditions, and evaluated local heating as a function of these parameters. Our results provide a simple guide on how to choose, for a given polydispersity degree, the more adequate average particle size so that the local variation in the released heat is kept within some limits that correspond to safety boundaries for the average-system hyperthermia performance. All together we believe that our results may help in the design of more effective magnetic hyperthermia applications.

Molecular mechanisms of hyperthermia-induced apoptosis enhanced by withaferin A.

PubMed

Cui, Zheng-Guo; Piao, Jin-Lan; Rehman, Mati U R; Ogawa, Ryohei; Li, Peng; Zhao, Qing-Li; Kondo, Takashi; Inadera, Hidekuni

2014-01-15

Hyperthermia is a good therapeutic tool for non-invasive cancer therapy; however, its cytotoxic effects are not sufficient. In the present study, withaferin A (WA), a steroidal lactone derived from the plant Withania somnifera Dunal, has been investigated for its possible enhancing effects on hyperthermia-induced apoptosis. In HeLa cells, treatment with 0.5 or 1.0μM WA at 44°C for 30min induced significant apoptosis accompanied by decreased intracellular GSH/GSSG ratio and caspase-3 activation, while heat or WA alone did not induce such changes. The upregulation in apoptosis was significantly inhibited by glutathione monoethyl ester, a cell permeable glutathione precursor. Mitochondrial transmembrane potentials were dramatically decreased by the combined treatment, with increases in pro-apoptotic Bcl-2-family proteins tBid and Noxa, and downregulation of antiapoptotic Bcl-2 and Mcl-1. Combined treatment with hyperthermia and WA induced significant increases in JNK phosphorylation (p-JNK), and decreases in the phosphorylation of ERK (p-ERK) compared with either treatment alone. These results suggest that WA enhances hyperthermia-induced apoptosis via a mitochondria-caspase-dependent pathway; its underlying mechanism involves elevated intracellular oxidative stress, mitochondria dysfunction, and JNK activation. © 2013 Elsevier B.V. All rights reserved.

Radiotherapy and hyperthermia in the treatment of fibrosarcomas in the dog.

PubMed

Brewer, W G; Turrel, J M

1982-07-15

Ten dogs with oral or external nasal fibrosarcoma were treated sequentially with orthovoltage radiation and radiofrequency (RF)-induced hyperthermia. Total radiation doses ranged from 3,200 to 4,800 rad given in 8 to 12 fractions of 400 rad. Immediately after 2 to 4 radiation treatments, hyperthermia was given. Six oral fibrosarcomas were heated to 50 C for 30 sec, using a hand-held RF generator. Four nasomaxillary fibrosarcomas were heated to 43 C for 30 minutes, using a 500-kHz RF generator. Hyperthermia of 50 C resulted in tumor necrosis and infection in 3 dogs and fatal septicemia in 1 dog. Nine of 10 tumors responded to therapy. One year after therapy, 5 dogs were free of disease. Tumor regrowth occurred in 5 dogs. Mean time to tumor regrowth and mean survival time of all dogs were 343 and 398 days, respectively. The results suggested that sequential radiation-hyperthermia is an effective therapeutic regimen for canine fibrosarcoma. It was concluded that this modality not only may be beneficial in the treatment of canine tumors but may be useful for designing new therapeutic approaches to similar tumors in man.

Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus.

PubMed

Zaretsky, Dmitry V; Zaretskaia, Maria V; Durant, Pamela J; Rusyniak, Daniel E

2015-05-22

The contribution of exercise to hyperthermia mediated by MDMA is not known. We recently showed that inhibiting the dorsomedial hypothalamus (DMH) attenuated spontaneous locomotion and hyperthermia and prevented deaths in rats given MDMA in a warm environment. The goal of this study was to confirm that restoring locomotion through a treadmill would reverse these effects thereby confirming that locomotion mediated by the DMH contributes to MDMA-mediated hyperthermia. Rats were randomized to receive bilateral microinjections, into the region of the DMH, of muscimol (80pmol/100nl) or artificial CSF followed by a systemic dose of either MDMA (7.5mg/kg, i.v.) or saline. Immediately after the systemic injection, rats were placed on a motorized treadmill maintained at 32°C. Rats were exercised at a fixed speed (10m/min) until their core temperature reached 41°C. Our results showed that a fixed exercise load abolished the decreases in temperature and mortality, seen previously with inhibition of the DMH in freely moving rats. Therefore, locomotion mediated by neurons in the DMH is critical to the development of hyperthermia from MDMA. Copyright © 2015 Elsevier B.V. All rights reserved.

On the temperature control in self-controlling hyperthermia therapy

NASA Astrophysics Data System (ADS)

Ebrahimi, Mahyar

2016-10-01

In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paudel, Nava Raj, E-mail: nrpaudel@yahoo.com; Shvydka, Diana; Parsai, E. Ishmael

Purpose: Gold nanoparticles (GNPs) are known to be effective mediators in microwave hyperthermia. Interaction with an electromagnetic field, large surface to volume ratio, and size quantization of nanoparticles (NPs) can lead to increased cell killing beyond pure heating effects. The purpose of this study is to explore the possibility of free radical generation by GNPs in aqueous media when they are exposed to a microwave field. Methods: A number of samples with 500 mM 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in 20 ppm GNP colloidal suspensions were scanned with an electron paramagnetic resonance (EPR)/electron spin resonance spectrometer to generate and detect free radicals.more » A fixed (9.68 GHz) frequency microwave from the spectrometer has served for both generation and detection of radicals. EPR spectra obtained as first derivatives of intensity with the spectrometer were double integrated to get the free radical signal intensities. Power dependence of radical intensity was studied by applying various levels of microwave power (12.5, 49.7, and 125 mW) while keeping all other scan parameters the same. Free radical signal intensities from initial and final scans, acquired at the same power levels, were compared. Results: Hydroxyl radical (OH⋅) signal was found to be generated due to the exposure of GNP–DMPO colloidal samples to a microwave field. Intensity of OH⋅ signal thus generated at 12.5 mW microwave power for 2.8 min was close to the intensity of OH⋅ signal obtained from a water–DMPO sample exposed to 1.5 Gy ionizing radiation dose. For repeated scans, higher OH⋅ intensities were observed in the final scan for higher power levels applied between the initial and the final scans. Final intensities were higher also for a shorter time interval between the initial and the final scans. Conclusions: Our results observed for the first time demonstrate that GNPs generate OH⋅ radicals in aqueous media when they are exposed to a microwave field. If OH⋅ radicals can be generated close to deoxyribonucleic acid of cells by proper localization of NPs, NP-aided microwave hyperthermia can yield cell killing via both elevated temperature and free radical generation.« less

A novel property of gold nanoparticles: Free radical generation under microwave irradiation.

PubMed

Paudel, Nava Raj; Shvydka, Diana; Parsai, E Ishmael

2016-04-01

Gold nanoparticles (GNPs) are known to be effective mediators in microwave hyperthermia. Interaction with an electromagnetic field, large surface to volume ratio, and size quantization of nanoparticles (NPs) can lead to increased cell killing beyond pure heating effects. The purpose of this study is to explore the possibility of free radical generation by GNPs in aqueous media when they are exposed to a microwave field. A number of samples with 500 mM 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in 20 ppm GNP colloidal suspensions were scanned with an electron paramagnetic resonance (EPR)/electron spin resonance spectrometer to generate and detect free radicals. A fixed (9.68 GHz) frequency microwave from the spectrometer has served for both generation and detection of radicals. EPR spectra obtained as first derivatives of intensity with the spectrometer were double integrated to get the free radical signal intensities. Power dependence of radical intensity was studied by applying various levels of microwave power (12.5, 49.7, and 125 mW) while keeping all other scan parameters the same. Free radical signal intensities from initial and final scans, acquired at the same power levels, were compared. Hydroxyl radical (OH⋅) signal was found to be generated due to the exposure of GNP-DMPO colloidal samples to a microwave field. Intensity of OH⋅ signal thus generated at 12.5 mW microwave power for 2.8 min was close to the intensity of OH⋅ signal obtained from a water-DMPO sample exposed to 1.5 Gy ionizing radiation dose. For repeated scans, higher OH⋅ intensities were observed in the final scan for higher power levels applied between the initial and the final scans. Final intensities were higher also for a shorter time interval between the initial and the final scans. Our results observed for the first time demonstrate that GNPs generate OH⋅ radicals in aqueous media when they are exposed to a microwave field. If OH⋅ radicals can be generated close to deoxyribonucleic acid of cells by proper localization of NPs, NP-aided microwave hyperthermia can yield cell killing via both elevated temperature and free radical generation.

Toxicokinetics and biodistribution of dextran stabilized iron oxide nanoparticles in rats

NASA Astrophysics Data System (ADS)

Easo, S. L.; Neelima, R.; Mohanan, P. V.

2015-07-01

Dextran stabilized iron oxide nanoparticles (DIONPs) synthesized and characterized for hyperthermia application were tested for toxicokinetics and biodistribution in order to analyze the prospect of safety and biocompatibility of these particles for advanced use. Rats were administered a single dose of DIONPs at a concentration of 10 mg kg-1 by intravenous injection with a post-exposure period of 1, 7, 14 and 28 days. Liver, spleen, kidney, blood, urine and feces were examined for iron content by inductively coupled plasma atomic emission spectroscopy. At 24 h, greater amounts of nanoparticles were deposited in liver and spleen. Maximum absorption of iron in blood occurred at day 7 and excess iron appeared to be eliminated by liver, seemingly via biliary excretion. Serum hematology and biochemistry analysis revealed an overall lack of systemic toxicity due to metabolism of DIONPs. Additionally, pathological changes associated with repeated exposure to DIONPs with a post exposure period of 28 days were also assessed. Although no significant pathological alterations were seen in spleen or kidney, slight morphological deviations from normal were observed in liver. Further progression in the analysis of biological response towards DIONPs will be determined in long-term studies in the presence of an alternating magnetic field in the context of hyperthermia application.

Strategies to Improve Cancer Photothermal Therapy Mediated by Nanomaterials.

PubMed

de Melo-Diogo, Duarte; Pais-Silva, Cleide; Dias, Diana R; Moreira, André F; Correia, Ilídio J

2017-05-01

The deployment of hyperthermia-based treatments for cancer therapy has captured the attention of different researchers worldwide. In particular, the application of light-responsive nanomaterials to mediate hyperthermia has revealed promising results in several pre-clinical assays. Unlike conventional therapies, these nanostructures can display a preferential tumor accumulation and thus mediate, upon irradiation with near-infrared light, a selective hyperthermic effect with temporal resolution. Different types of nanomaterials such as those based on gold, carbon, copper, molybdenum, tungsten, iron, palladium and conjugated polymers have been used for this photothermal modality. This progress report summarizes the different strategies that have been applied so far for increasing the efficacy of the photothermal therapeutic effect mediated by nanomaterials, namely those that improve the accumulation of nanomaterials in tumors (e.g. by changing the corona composition or through the functionalization with targeting ligands), increase nanomaterials' intrinsic capacity to generate photoinduced heat (e.g. by synthesizing new nanomaterials or assembling nanostructures) or by optimizing the parameters related to the laser light used in the irradiation process (e.g. by modulating the radiation wavelength). Overall, the development of new strategies or the optimization and combination of the existing ones will surely give a major contribution for the application of nanomaterials in cancer PTT. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Dartmouth Center for Cancer Nanotechnology Excellence: magnetic hyperthermia

PubMed Central

Baker, Ian; Fiering, Steve N; Griswold, Karl E; Hoopes, P Jack; Kekalo, Katerina; Ndong, Christian; Paulsen, Keith; Petryk, Alicea A; Pogue, Brian; Shubitidze, Fridon; Weaver, John

2015-01-01

The Dartmouth Center for Cancer Nanotechnology Excellence – one of nine funded by the National Cancer Institute as part of the Alliance for Nanotechnology in Cancer – focuses on the use of magnetic nanoparticles for cancer diagnostics and hyperthermia therapy. It brings together a diverse team of engineers and biomedical researchers with expertise in nanomaterials, molecular targeting, advanced biomedical imaging and translational in vivo studies. The goal of successfully treating cancer is being approached by developing nanoparticles, conjugating them with Fabs, hyperthermia treatment, immunotherapy and sensing treatment response. PMID:26080693

Phencyclidine-induced malignant hyperthermia causing submassive liver necrosis.

PubMed

Armen, R; Kanel, G; Reynolds, T

1984-07-01

This report describes three male patients arrested for aggressive and combative behavior, characteristic of phencyclidine intoxication, in whom severe hyperthermia, respiratory failure, and coma developed. Two days after the malignant hyperthermic event, serum transaminase levels rose acutely to extremely high levels with concomitant elevations in bilirubin levels and a fall in prothrombin activity. Liver biopsy specimens in two patients showed marked perivenular necrosis and collapse. No specific treatment was directed at the phencyclidine intoxication. Two of the three patients survived. Submassive liver necrosis caused by malignant hyperthermia is an unusual complication of phencyclidine abuse.

Nanoparticle-mediated hyperthermia in cancer therapy

PubMed Central

Chatterjee, Dev Kumar; Diagaradjane, Parmeswaran; Krishnan, Sunil

2011-01-01

A small rise in tumor temperature (hyperthermia) makes cancer cells more susceptible to radiation and chemotherapy. The means of achieving this is not trivial, and traditional methods have certain drawbacks. Loading tumors with systematically asministered energy-transducing nanoparticles can circumvent several of the obstacles to achieve tumor hyperthermia. However, nanoparticles also face unique challenges prior to clinical implementation. This article summarizes the state-of-the-art current technology and discusses the advantages and challenges of the three major nanoparticle formulations in focus: gold nanoshells and nanorods, superparamagnetic iron oxide particles and carbon nanotubes. PMID:22506095

Analysis of clinical data to determine the minimum number of sensors required for adequate skin temperature monitoring of superficial hyperthermia treatments.

PubMed

Bakker, Akke; Holman, Rebecca; Rodrigues, Dario B; Dobšíček Trefná, Hana; Stauffer, Paul R; van Tienhoven, Geertjan; Rasch, Coen R N; Crezee, Hans

2018-04-27

Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients. Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm 2 ). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (ΔT) between subsets and complete sets of sensors were evaluated in terms of overall minimum (T min ) and maximum (T max ) temperature, as well as T90 and T10. Eighty patients were included yielding a total of 400 hyperthermia sessions. Median ΔT was <0.01 °C for T90, its 95% confidence interval (95%CI) decreased to ≤0.5 °C when >50 sensors were used. Subsets of <10 sensors result in underestimation of T max up to -2.1 °C (ΔT 95%CI), which decreased to -0.5 °C when >50 sensors were used. Thermal profiles (8-21 probes) yielded a median ΔT < 0.01 °C for T90 and T max , with a 95%CI of -0.2 °C and 0.4 °C, respectively. The detection rate of T max  ≥43 °C is ≥85% while using >50 stationary sensors or thermal profiles. Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of >50 stationary sensors per 400 cm 2 applicator. Thermal mapping is a valid alternative.

Analysis of the effects on body temperature of intracerebroventricular injection in anaesthetized dogs of gamma-aminobutyric acid

PubMed Central

Dhumal, V.R.; Gulati, O.D.; Raghunath, P.R.; Sivaramakrishna, N.

1974-01-01

1 The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro-spinal fluid (CSF) at a rate of 0.4-0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum. 2 γ-Aminobutyric acid (GABA) 0.1-5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia. 3 Intraventricular perfusion with 2-bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea-pig isolated superfused ileum for the possible release, respectively, of 5-hydroxytryptamine or acetylcholine by GABA were negative. 4 When tested for the presence of prostaglandin E(PGE)-like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA-induced hyperthermia to hypothermia and blocked the release of PGE-like substances. 5 Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent. 6 Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs. 7 Perfusion with calcium-free solution blocked both the noradrenaline-releasing and hypothermic actions of GABA. 8 It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE-like substance and hypothermia is due to the release of noradrenaline. PMID:4155652

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, William, E-mail: William.Chu@sunnybrook.ca; Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario; Staruch, Robert M.

Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh weremore » evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.« less

Feasibility of on-line temperature-based hyperthermia treatment planning to improve tumour temperatures during locoregional hyperthermia.

PubMed

Kok, H P; Korshuize-van Straten, L; Bakker, A; de Kroon-Oldenhof, R; Westerveld, G H; Versteijne, E; Stalpers, L J A; Crezee, J

2017-11-16

The effectiveness of hyperthermia is strongly dependent on the achieved tumour temperatures. Phased-array systems allow flexible power steering to realise good tumour heating while avoiding excessive heating in normal tissue, but the limited quantitative accuracy of pre-treatment planning complicates realising optimal tumour heating. On-line hyperthermia treatment planning could help to improve the heating quality. This paper demonstrates the feasibility of using on-line temperature-based treatment planning to improve the heating quality during hyperthermia in three patients. Hyperthermia treatment planning was performed using the Plan2Heat software package combined with a dedicated graphical user interface for on-line application. Electric fields were pre-calculated to allow instant update and visualisation of the predicted temperature distribution for user-selected phase-amplitude settings during treatment. On-line treatment planning using manual variation of system settings for the AMC-8 hyperthermia system was applied in one patient with a deep-seated pelvic melanoma metastasis and two cervical cancer patients. For a clinically relevant improvement the increase in average target temperature should be at least 0.2 °C. With the assistance of on-line treatment planning a substantial improvement in tumour temperatures was realised for all three patients. In the melanoma patient, the average measured target temperature increased from 38.30 °C to 39.15 °C (i.e. +0.85 °C). In the cervical cancer patients, the average measured target temperature increased from 41.30 °C to 42.05 °C (i.e. +0.75 °C) and from 41.70 °C to 42.80 °C (i.e. +1.1 °C), respectively. On-line temperature-based treatment planning is clinically feasible to improve tumour temperatures. A next, worthwhile step is automatic optimisation for a larger number of patients.

Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats

PubMed Central

Shi, Yaoping; Zhang, Feng; Bai, Zhibin; Wang, Jianfeng; Qiu, Longhua; Li, Yonggang; Meng, Yanfeng; Valji, Karim

2017-01-01

Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire–mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy on esophageal squamous cell cancers. © RSNA, 2016 PMID:27404050

Efficient treatment of breast cancer xenografts with multifunctionalized iron oxide nanoparticles combining magnetic hyperthermia and anti-cancer drug delivery.

PubMed

Kossatz, Susanne; Grandke, Julia; Couleaud, Pierre; Latorre, Alfonso; Aires, Antonio; Crosbie-Staunton, Kieran; Ludwig, Robert; Dähring, Heidi; Ettelt, Volker; Lazaro-Carrillo, Ana; Calero, Macarena; Sader, Maha; Courty, José; Volkov, Yuri; Prina-Mello, Adriele; Villanueva, Angeles; Somoza, Álvaro; Cortajarena, Aitziber L; Miranda, Rodolfo; Hilger, Ingrid

2015-05-13

Tumor cells can effectively be killed by heat, e.g. by using magnetic hyperthermia. The main challenge in the field, however, is the generation of therapeutic temperatures selectively in the whole tumor region. We aimed to improve magnetic hyperthermia of breast cancer by using innovative nanoparticles which display a high heating potential and are functionalized with a cell internalization and a chemotherapeutic agent to increase cell death. The superparamagnetic iron oxide nanoparticles (MF66) were electrostatically functionalized with either Nucant multivalent pseudopeptide (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6LDOX). Their cytotoxic potential was assessed in a breast adenocarcinoma cell line MDA-MB-231. Therapeutic efficacy was analyzed on subcutaneous MDA-MB-231 tumor bearing female athymic nude mice. All nanoparticle variants showed an excellent heating potential around 500 W/g Fe in the alternating magnetic field (AMF, conditions: H=15.4 kA/m, f=435 kHz). We could show a gradual inter- and intracellular release of the ligands, and nanoparticle uptake in cells was increased by the N6L functionalization. MF66-DOX and MF66-N6LDOX in combination with hyperthermia were more cytotoxic to breast cancer cells than the respective free ligands. We observed a substantial tumor growth inhibition (to 40% of the initial tumor volume, complete tumor regression in many cases) after intratumoral injection of the nanoparticles in vivo. The proliferative activity of the remaining tumor tissue was distinctly reduced. The therapeutic effects of breast cancer magnetic hyperthermia could be strongly enhanced by the combination of MF66 functionalized with N6L and DOX and magnetic hyperthermia. Our approach combines two ways of tumor cell killing (magnetic hyperthermia and chemotherapy) and represents a straightforward strategy for translation into the clinical practice when injecting nanoparticles intratumorally.

Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3 pN0 M0.

PubMed

Tilly, Wolfgang; Gellermann, Johanna; Graf, Reinhold; Hildebrandt, Bert; Weissbach, Lothar; Budach, Volker; Felix, Roland; Wust, Peter

2005-01-01

Since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. From 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pN0 M0 and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate- specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. Mean maximum temperatures along the urethra of 41.4 degrees C (41.0 degrees C for the recurrences), and mean T(90) values of 40.7 degrees C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. Regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile.

TRPV1 deletion exacerbates hyperthermic seizures in an age-dependent manner in mice.

PubMed

Barrett, Karlene T; Wilson, Richard J A; Scantlebury, Morris H

2016-12-01

Febrile seizures (FS) are the most common seizure disorder to affect children. Although there is mounting evidence to support that FS occur when children have fever-induced hyperventilation leading to respiratory alkalosis, the underlying mechanisms of hyperthermia-induced hyperventilation and links to FS remain poorly understood. As transient receptor potential vanilloid-1 (TRPV1) receptors are heat-sensitive, play an important role in adult thermoregulation and modulate respiratory chemoreceptors, we hypothesize that TRPV1 activation is important for hyperthermia-induced hyperventilation leading to respiratory alkalosis and decreased FS thresholds, and consequently, TRPV1 KO mice will be relatively protected from hyperthermic seizures. To test our hypothesis we subjected postnatal (P) day 8-20 TRPV1 KO and C57BL/6 control mice to heated dry air. Seizure threshold temperature, latency and the rate of rise of body temperature during hyperthermia were assessed. At ages where differences in seizure thresholds were identified, head-out plethysmography was used to assess breathing and the rate of expired CO 2 in response to hyperthermia, to determine if the changes in seizure thresholds were related to respiratory alkalosis. Paradoxically, we observed a pro-convulsant effect of TRPV1 deletion (∼4min decrease in seizure latency), and increased ventilation in response to hyperthermia in TRPV1 KO compared to control mice at P20. This pro-convulsant effect of TRPV1 absence was not associated with an increased rate of expired CO 2 , however, these mice had a more rapid rise in body temperature following exposure to hyperthermia than controls, and the expected linear relationship between body weight and seizure latency was absent. Based on these findings, we conclude that deletion of the TRPV1 receptor prevents reduction in hyperthermic seizure susceptibility in older mouse pups, via a mechanism that is independent of hyperthermia-induced respiratory alkalosis, but possibly involves impaired development of thermoregulatory mechanisms, although at present the mechanism remain unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

Cardiopulmonary and arterial baroreceptor unloading during passive hyperthermia does not contribute to hyperthermia-induced hyperventilation

PubMed Central

Lucas, Rebekah A. I.; Pearson, James; Schlader, Zachary J.; Crandall, Craig G.

2016-01-01

This study tested the hypothesis that baroreceptor unloading during passive hyperthermia contributes to increases in ventilation and decreases in end-tidal partial pressure of carbon dioxide (PET,CO2) during that exposure. Two protocols were performed, in which healthy subjects underwent passive hyperthermia (increasing intestinal temperature by ~1.8°C) to cause a sustained increase in ventilation and reduction in PET,CO2. Upon attaining hyperthermic hyperventilation, in protocol 1 (n = 10; three females) a bolus (19 ± 2 ml kg−1) of warm (~38°C) isotonic saline was rapidly (5–10 min) infused intravenously to restore reductions in central venous pressure, whereas in protocol 2 (n = 11; five females) phenylephrine was infused intravenously (60–120 μg min−1) to return mean arterial pressure to normothermic levels. In protocol 1, hyperthermia increased ventilation (by 2.2 ± 1.7 l min−1, P < 0.01), while reducing PET,CO2 (by 4 ± 3 mmHg, P = 0.04) and central venous pressure (by 5 ± 1 mmHg, P <0.01). Saline infusion increased central venous pressure by 5 ± 1 mmHg (P < 0.01), restoring it to normothermic values, but did not change ventilation or PET,CO2 (P > 0.05). In protocol 2, hyperthermia increased ventilation (by 5.0 ± 2.7l min−1, P <0.01) and reduced PET ,CO2 (by 5 ± 2 mmHg, P < 0.01) and mean arterial pressure (by 9 ± 7 mmHg, P <0.01). Phenylephrine infusion increased mean arterial pressure by 12 ± 3 mmHg (P < 0.01), restoring it to normothermic values, but did not change ventilation or PET,CO2 (P > 0.05). The absence of a reduction in ventilation upon reloading the cardiopulmonary and arterial baroreceptors to pre-hyperthermic levels indicates that baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. PMID:26299270

THREE-DIMENSIONAL MODEL FOR HYPERTHERMIA CALCULATIONS

EPA Science Inventory

Realistic three-dimensional models that predict temperature distributions with a high degree of spatial resolution in bodies exposed to electromagnetic (EM) fields are required in the application of hyperthermia for cancer treatment. To ascertain the thermophysiologic response of...

Mean-field and linear regime approach to magnetic hyperthermia of core-shell nanoparticles: can tiny nanostructures fight cancer?

PubMed

Carrião, Marcus S; Bakuzis, Andris F

2016-04-21

The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy.

A case report of suspected malignant hyperthermia where patient survived the episode.

PubMed

Iqbal, Asif; Badoo, Shoaib; Naqeeb, Ruqsana

2017-01-01

Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000-100,000 and mortality rate is estimated to be <5% in the presence of standard care. In India, there is no center where in vitro halothane caffeine contraction test is performed to confirm diagnosis in suspected cases. Second, dantrolene drug of choice for this condition is not freely available in market in India and is stored only in some hospitals in few major cities. Among the cases reported of suspected of malignant hyperthermia in India almost 50% have survived the condition despite nonavailability of dantrolene emphasizing role of early detection and aggressive management in these cases.

A case report of suspected malignant hyperthermia where patient survived the episode

PubMed Central

Iqbal, Asif; Badoo, Shoaib; Naqeeb, Ruqsana

2017-01-01

Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000–100,000 and mortality rate is estimated to be <5% in the presence of standard care. In India, there is no center where in vitro halothane caffeine contraction test is performed to confirm diagnosis in suspected cases. Second, dantrolene drug of choice for this condition is not freely available in market in India and is stored only in some hospitals in few major cities. Among the cases reported of suspected of malignant hyperthermia in India almost 50% have survived the condition despite nonavailability of dantrolene emphasizing role of early detection and aggressive management in these cases. PMID:28442967

A Reconstruction Method for the Estimation of Temperatures of Multiple Sources Applied for Nanoparticle-Mediated Hyperthermia.

PubMed

Steinberg, Idan; Tamir, Gil; Gannot, Israel

2018-03-16

Solid malignant tumors are one of the leading causes of death worldwide. Many times complete removal is not possible and alternative methods such as focused hyperthermia are used. Precise control of the hyperthermia process is imperative for the successful application of such treatment. To that end, this research presents a fast method that enables the estimation of deep tissue heat distribution by capturing and processing the transient temperature at the boundary based on a bio-heat transfer model. The theoretical model is rigorously developed and thoroughly validated by a series of experiments. A 10-fold improvement is demonstrated in resolution and visibility on tissue mimicking phantoms. The inverse problem is demonstrated as well with a successful application of the model for imaging deep-tissue embedded heat sources. Thereby, allowing the physician then ability to dynamically evaluate the hyperthermia treatment efficiency in real time.

[Mitomycin C HIVEC. Update and results in high risk patients.

PubMed

Guerrero-Ramos, Félix; Castellano-Gauna, Daniel; García-Rojo, Esther; Duarte-Ojeda, José Manuel; de la Rosa-Kehrmann, Federico; Villacampa-Aubá, Felipe

2018-05-01

Adjuvant endovesical treatment is a research field in constant exploration with the aim to minimize the risk of recurrence and progression of non muscle invasive bladder tumors. Over the last years, the administration of chemotherapy in a chemo hyperthermia regimen has been added to the existing regimens. There are various systems for its administration, but this article focus on HIVEC (Hyperthermic IntraVEsical Chemotherapy) and its current status. In this review article we update the results of this system in the case-scenarios it has been used (preoperative with ablative intention and as adjuvant therapy with prophylactic purposes), tolerance and security issues, on-going clinical trials and future perspectives.

Dantrolene, a treatment for Alzheimer disease?

PubMed

Liang, Li; Wei, Huafeng

2015-01-01

Alzheimer disease (AD) is a fatal progressive disease and the most common form of dementia without effective treatments. Previous studies support that the disruption of endoplasmic reticulum Ca through overactivation of ryanodine receptors plays an important role in the pathogenesis of AD. Normalization of intracellular Ca homeostasis could be an effective strategy for AD therapies. Dantrolene, an antagonist of ryanodine receptors and an FDA-approved drug for clinical treatment of malignant hyperthermia and muscle spasms, exhibits neuroprotective effects in multiple models of neurodegenerative disorders. Recent preclinical studies consistently support the therapeutic effects of dantrolene in various types of AD animal models and were summarized in the current review.

Magnetic solid lipid nanoparticles in hyperthermia against colon cancer.

PubMed

Muñoz de Escalona, María; Sáez-Fernández, Eva; Prados, José C; Melguizo, Consolación; Arias, José L

2016-05-17

A reproducible double emulsion/solvent evaporation procedure is developed to formulate magnetic solid lipid nanoparticles (average size≈180 nm) made of iron oxide cores embedded within a glyceryl trimyristate solid matrix. The physicochemical characterization of the nanocomposites ascertained the efficacy of the preparation conditions in their production, i.e. surface properties (electrokinetic and thermodynamic data) were almost indistinguishable from those of the solid lipid nanomatrix, while electron microscopy characterizations and X-ray diffraction patterns confirmed the satisfactory coverage of the magnetite nuclei. Hemocompatibility of the particles was established in vitro. Hysteresis cycle determinations defined the appropriate magnetic responsiveness of the nanocomposites, and their heating characteristics were investigated in a high frequency alternating gradient of magnetic field: a constant maximum temperature of 46 °C was obtained within 40 min. Finally, in vitro tests performed on human HT29 colon adenocarcinoma cells demonstrated a promising decrease in cell viability after treatment with the nanocomposites and exposure to that alternating electromagnetic field. To the best of our knowledge, this is the first time that such type of nanoformulation with very promising hyperthermia characteristics has been developed for therapeutic aims. Copyright © 2016 Elsevier B.V. All rights reserved.

Si nanoparticles as sensitizers for radio frequency-induced cancer hyperthermia

NASA Astrophysics Data System (ADS)

Kabashin, A. V.; Tamarov, K. P.; Ryabchikov, Yu. V.; Osminkina, L. A.; Zinovyev, S. V.; Kargina, J. V.; Gongalsky, M. B.; Al-Kattan, A.; Yakunin, V. G.; Sentis, M. L.; Ivanov, A. V.; Nikiforov, V. N.; Kanavin, A. P.; Zavestovskaya, I. N.; Timoshenko, V. Y.

2016-03-01

We review our recently obtained data on the employment of Si nanoparticles as sensitizers of radiofrequency (RF) - induced hyperthermia for mild cancer therapy tasks. Such an approach makes possible the heating of aqueous suspensions of Si nanoparticles by tens of degrees Celsius under relatively low intensities (1-5 W/cm2) of 27 MHz RF radiation. The heating effect is demonstrated for nanoparticles synthesized by laser ablation in water and mechanical grinding of porous silicon, while laser-ablated nanoparticles demonstrate a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations. The observed RF heating effect can be explained in the frame of a model considering the polarization of Si NPs and electrolyte in the external oscillating electromagnetic field and the corresponding release of heat by electric currents around the nanoparticles. Our tests evidence relative safety of Si nanostructures and their efficient dissolution in physiological solutions, suggesting potential clearance of nanoparticles from a living organism without any side effects. Profiting from Si nanoparticle-based heating, we finally demonstrate an efficient treatment of Lewis Lung carcinoma in vivo. The obtained data promise a breakthrough in the development of mild, non-invasive methods for cancer therapy.

The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

NASA Astrophysics Data System (ADS)

Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

2017-02-01

It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia.

PubMed

Li, Li; ten Hagen, Timo L M; Bolkestein, Michiel; Gasselhuber, Astrid; Yatvin, Jeremy; van Rhoon, Gerard C; Eggermont, Alexander M M; Haemmerich, Dieter; Koning, Gerben A

2013-04-28

Accumulation of nanoparticles in solid tumors depends on their extravasation. However, vascular permeability is very heterogeneous within a tumor and among different tumor types, hampering efficient delivery. Local hyperthermia at a tumor can improve nanoparticle delivery by increasing tumor vasculature permeability, perfusion and interstitial fluid flow. The aim of this study is to investigate hyperthermia conditions required to improve tumor vasculature permeability, subsequent liposome extravasation and interstitial penetration in 4 tumor models. Tumors are implanted in dorsal skin flap window chambers and observed for liposome (~85 nm) accumulation by intravital confocal microscopy. Local hyperthermia at 41°C for 30 min initiates liposome extravasation through permeable tumor vasculature in all 4 tumor models. A further increase in nanoparticle extravasation occurs while continuing heating to 1h, which is a clinically relevant duration. After hyperthermia, the tumor vasculature remains permeable for 8h. We visualize gaps in the endothelial lining of up to 10 μm induced by HT. Liposomes extravasate through these gaps and penetrate into the interstitial space to at least 27.5 μm in radius from the vessel walls. Whole body optical imaging confirms HT induced extravasation while liposome extravasation was absent at normothermia. In conclusion, a thermal dose of 41°C for 1h is effective to induce long-lasting permeable tumor vasculature for liposome extravasation and interstitial penetration. These findings hold promise for improved intratumoral drug delivery upon application of local mild hyperthermia prior to administration of nanoparticle-based drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Design of a compact antenna with flared groundplane for a wearable breast hyperthermia system.

PubMed

Curto, Sergio; Prakash, Punit

2015-01-01

Currently available microwave hyperthermia systems for breast cancer treatment do not conform to the intact breast and provide limited control of heating patterns, thereby hindering an effective treatment. A compact patch antenna with a flared groundplane that may be integrated within a wearable hyperthermia system for the treatment of the intact breast disease is proposed. A 3D simulation-based approach was employed to optimise the antenna design with the objective of maximising the hyperthermia treatment volume (41 °C iso-therm) while maintaining good impedance matching. The optimised antenna design was fabricated and experimentally evaluated with ex vivo tissue measurements. The optimised compact antenna yielded a -10 dB bandwidth of 90 MHz centred at 915 MHz, and was capable of creating hyperthermia treatment volumes up to 14.4 cm(3) (31 mm × 28 mm × 32 mm) with an input power of 15 W. Experimentally measured reflection coefficient and transient temperature profiles were in good agreement with simulated profiles. Variations of + 50% in blood perfusion yielded variations in the treatment volume up to 11.5%. When compared to an antenna with a similar patch element employing a conventional rectangular groundplane, the antenna with flared groundplane afforded 22.3% reduction in required power levels to reach the same temperature, and yielded 2.4 times larger treatment volumes. The proposed patch antenna with a flared groundplane may be integrated within a wearable applicator for hyperthermia treatment of intact breast targets and has the potential to improve efficiency, increase patient comfort, and ultimately clinical outcomes.

Diagnosis of human prostate carcinoma cancer stem cells enriched from DU145 cell lines changes with microscopic texture analysis in radiation and hyperthermia treatment using run-length matrix.

PubMed

Abbasian Ardakani, Ali; Rajaee, Jila; Khoei, Samideh

2017-11-01

Hyperthermia and radiation have the ability to induce structural and morphological changes on both macroscopic and microscopic level. Normal and damage cells have a different texture but may be perceived by human eye, as having the same texture. To explore the potential of texture analysis based on run-length matrix, a total of 32 sphere images for each group and treatment regime were used in this study. Cells were subjected to the treatment with different doses of 6 MeV electron radiation (0 2, 4 and 6 Gy), hyperthermia (at 43° C in 0, 30, 60 and 90 min) and radiation + hyperthermia (at 43 °C in 30 min with 2, 4 and 6 Gy dose), respectively. Twenty run-length matrix (RLM) features were extracted as descriptors for each selected region of interest for texture analysis. Linear discriminant analysis was employed to transform raw data to lower-dimensional spaces and increase discriminative power. The features were classified by the first nearest neighbor classifier. RLM features represented the best performance with sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 100% between 0 and 6 Gy radiation, 0 and 6 Gy radiation + hyperthermia, 0 and 90 min and 30 and 90 min hyperthermia groups. The area under receiver operating characteristic curve was 1 for these groups. RLM features have a high potential to characterize cell changes during different treatment regimes.

MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method

PubMed Central

Al-Bataineh, Osama M; Collins, Christopher M; Park, Eun-Joo; Lee, Hotaik; Smith, Nadine Barrie

2006-01-01

Background Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43°C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. Methods A 3D acoustical prostate model was created using photographic data from the Visible Human Project®. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 × 20 elements phased array were 1 × 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin® plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. Results Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0°C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 ± 0.38°C and 43.1 ± 0.80°C, respectively, for 20 minutes of heating. Conclusion Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield in large scale, 3D, inhomogeneous and coarse grid tissue models. Noninvasive MRI thermometry supports the efficacy of this probe and the feedback controller in an in vivo hyperthermia treatment of canine prostate. PMID:17064421

MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method.

PubMed

Al-Bataineh, Osama M; Collins, Christopher M; Park, Eun-Joo; Lee, Hotaik; Smith, Nadine Barrie

2006-10-25

Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43 degrees C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. A 3D acoustical prostate model was created using photographic data from the Visible Human Project. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 x 20 elements phased array were 1 x 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0 degrees C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 +/- 0.38 degrees C and 43.1 +/- 0.80 degrees C, respectively, for 20 minutes of heating. Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield in large scale, 3D, inhomogeneous and coarse grid tissue models. Noninvasive MRI thermometry supports the efficacy of this probe and the feedback controller in an in vivo hyperthermia treatment of canine prostate.

CT-guided thermocouple placement for hyperthermia treatment.

PubMed

Banerian, K G; Roberts, J L; Borrego, J C; Martinez, A

1990-05-01

There is a well-documented synergistic cytotoxic effect when heat is combined with ionizing radiation. An integral component of hyperthermia treatments is the placement of thermocouple probes used for thermal dosimetry. With the surge in interest in the clinical use of hyperthermia, our department is performing an increasing number of thermocouple placements under computed tomographic (CT) guidance. We describe our technique for CT-guided thermocouple placement with two different systems: a trocar introduction system and a peel-away needle introduction system. We discuss the rationale for thermocouple placement, our early experience with this technique, and some potential complications.

[Chemotherapy in combination with laser coagulation or interstitial hyperthermia--effective combined therapy for disseminated skin melanoma].

PubMed

Akimov, M A; Gel'fond, M L; Gershanovich, M L; Barchuk, A S

2003-01-01

Thirty-eight patients with disseminated skin melanoma received chemotherapy in conjunction with laser coagulation or interstitial hyperthermia of intra- or subcutaneous metastases. Use of combination therapy was followed by a rise to 37% in total response and 16%--complete regression, respectively. Most effectiveness was attained when the dacarbazine + cisplatin + BCNU + tamoxifen regime was employed. In this group of 16 patients (46%), total response was 56% and, what is most significant, 31% in complete regression. In all cases of apparent response, polychemotherapy was administered both before and after laser coagulation or interstitial hyperthermia.

Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria

PubMed Central

Chen, Changyou; Chen, Linjie; Yi, Yong; Chen, Chuanfang

2016-01-01

Staphylococcus aureus is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing S. aureus cells in vitro and in vivo through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The S. aureus suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h. S. aureus viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the S. aureus cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and S. aureus increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of S. aureus both in vitro and in vivo, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for S. aureus-induced skin or wound infections. PMID:26873320

Developing Antitumor Magnetic Hyperthermia: Principles, Materials and Devices.

PubMed

Tishin, Alexander M; Shtil, Alexander A; Pyatakov, Alexander P; Zverev, Vladimir I

2016-01-01

Methods of local or loco-regional anticancer treatment are of the utmost importance because the therapeutic 'power' is applied directly to the disease site. Consequently, general toxicity is minimized. Hyperthermia, that is, a sustained increase of intratumoral temperature up to 45oC, has been investigated as a perspective treatment modality alone and/or in combination with ionizing radiation or chemotherapy. Still, the surrounding tissues can be damaged by the external heat. Development of new materials and devices gave rise to methods of inducing hyperthermia by a high frequency magnetic or electromagnetic field applied to the tumor with exogenous nanosized particles captured within it. The idea of this approach is the release of local heat in the vicinity of the magnetic nanoparticle in a time-varying magnetic field due to transfer of external magnetic field energy into the heat. Therefore, tumor cells are heated whereas the peritumoral non-malignant tissues are spared. This review analyzes recent advances in understanding physical principles that underlie magnetic hyperthermia as well as novel approaches to obtain nanoparticles with optimized physico-chemical, toxicological and tumoricidal properties. Special focus is made on the construction of devices for therapeutic purposes. The review covers recent patents and general literature sources regarding magnetic hyperthermia, the developing approach to treat otherwise intractable malignancies. </p><p>.

Marshall J. Edwards: discoverer of maternal hyperthermia as a human teratogen.

PubMed

Graham, John M

2005-11-01

In a series of animal studies performed over a career spanning 40 years at the University of Sydney, Professor Marshall J. Edwards investigated the hypothesis that maternal hyperthermia during gestation can be teratogenic to the developing fetus. He is one of few investigators to have discovered a known human teratogen primarily through animal studies. In 1970 he earned his Ph.D. from the University of Sydney, writing a doctoral thesis entitled "A Study of Some Factors Affecting Fertility of Animals with Particular Reference to the Effects of Hyperthermia on Gestation and Prenatal Development of the Guinea-Pig." He went on to prove that hyperthermia-induced malformations in animals involve many organs and structures, particularly the central nervous system. Other defects include craniofacial anomalies, heart defects and hypodactyly, cataracts and coloboma, kyphoscoliosis, renal anomalies, dental agenesis, and abdominal wall defects. In a series of carefully planned and executed experiments, he demonstrated that the type of defect is related to the timing of the hyperthermic insult, and analyzed the underlying mechanisms. Cell death, membrane disruption, vascular disruption, and placental infarction were all implicated in causing embryonic damage. This special article reviews the scientific discoveries and personal philosophy of Marshall J. Edwards, the discoverer of maternal hyperthermia as a human teratogen.

Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells

PubMed Central

Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J.

2012-01-01

Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately 10-fold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. PMID:22174016

Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells.

PubMed

Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J

2012-05-01

Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately tenfold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization, and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases, and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. Copyright © 2011 Wiley Periodicals, Inc.

Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles

NASA Astrophysics Data System (ADS)

Jordan, Andreas; Scholz, Regina; Wust, Peter; Fähling, Horst; Felix, Roland

1999-07-01

The story of hyperthermia with small particles in AC magnetic fields started in the late 1950s, but most of the studies were unfortunately conducted with inadequate animal systems, inexact thermometry and poor AC magnetic field parameters, so that any clinical implication was far behind the horizon. More than three decades later, it was found, that colloidal dispersions of superparamagnetic (subdomain) iron oxide nanoparticles exhibit an extraordinary specific absorption rate (SAR [ W/ g]), which is much higher at clinically tolerable H 0 f combinations in comparison to hysteresis heating of larger multidomain particles. This was the renaissance of a cancer treatment method, which has gained more and more attention in the last few years. Due to the increasing number of randomized clinical trials preferentially in Europe with conventional E-field hyperthermia systems, the general medical and physical experience in hyperthermia application is also rapidly growing. Taking this increasing clinical experience carefully into account together with the huge amount of new biological data on heat response of cells and tissues, the approach of magnetic fluid hyperthermia (MFH) is nowadays more promising than ever before. The present contribution reviews the current state of the art and some of the future perspectives supported by advanced methods of the so-called nanotechnology.

A facile microwave synthetic route for ferrite nanoparticles with direct impact in magnetic particle hyperthermia.

PubMed

Makridis, A; Chatzitheodorou, I; Topouridou, K; Yavropoulou, M P; Angelakeris, M; Dendrinou-Samara, C

2016-06-01

The application of ferrite magnetic nanoparticles (MNPs) in medicine finds its rapidly developing emphasis on heating mediators for magnetic hyperthermia, the ever-promising "fourth leg" of cancer treatment. Usage of MNPs depends largely on the preparation processes to select optimal conditions and effective routes to finely tailor MNPs. Microwave heating, instead of conventional heating offers nanocrystals at significantly enhanced rate and yield. In this work, a facile mass-production microwave hydrothermal synthetic approach was used to synthesize stable ferromagnetic manganese and cobalt ferrite nanoparticles with sizes smaller than 14 nm from metal acetylacetonates in the presence of octadecylamine. Prolonging the reaction time from 15 to 60 min, led to ferrites with improved crystallinity while the sizes are slight increased. The high crystallinity magnetic nanoparticles showed exceptional magnetic heating parameters. In vitro application was performed using the human osteosarcoma cell line Saos-2 incubated with manganese ferrite nanoparticles. Hyperthermia applied in a two cycle process, while AC magnetic field remained on until the upper limit of 45 °C was achieved. The comparative results of the AC hyperthermia efficiency of ferrite nanoparticles in combination with the in vitro study coincide with the magnetic features and their tunability may be further exploited for AC magnetic hyperthermia driven applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Iron oxide nanoparticles with controlled morphology for advanced hyperthermia

NASA Astrophysics Data System (ADS)

Nemati Porshokouh, Zohreh; Khurshid, Hafsa; Alonso Messa, Javier; Phan, Manh-Huong; Srikanth, Hariharan

2015-03-01

Magnetic nanoparticles (NPs) are interesting for a wide range of applications. In biomedicine, they have been exploited for use in drug delivery, magnetic resonance imaging, and magnetic hyperthermia. While magnetic hyperthermia, using NPs to convert electromagnetic energy into heat to destroy the cancer cells, represents a novel cancer treatment technique, a poor heating conversion efficiency of the existing NPs restricts its practical use. Different strategies have been proposed to overcome this limitation, mainly by tuning the size, saturation magnetization and effective anisotropy of the NPs. Here we report a magnetic hyperthermia study on Fe3O4 NPs, where the effective anisotropy was tuned by varying particle morphology from the spherical to octopod shape. The Fe3O4 NPs were synthesized using a thermal decomposition method. Transmission electron microscopy (TEM) and high-resolution TEM images show high crystalline monodisperse nanoparticles. X-ray diffraction patterns confirm the presence of Fe3O4 phase. Hyperthermia experiments indicate that the octopods possess a higher SAR as compared to their spherical counterpart. Our findings provide an effective approach to improve the SAR of NPs by manipulating the shape anisotropy of the nanoparticles. Research was supported by USAMRMC through Grant Numbers W81XWH-07-1-0708 and W81XWH1020101/3349.

Thermal tolerance reduces hyperthermia-induced disruption of working memory: a role for endogenous opiates?

PubMed

Mickley, G A; Cobb, B L

1998-03-01

Previous reports indicate that microwave-induced hyperthermia can impair learning and memory. Here, we report that preexposure to a single 20-min period of hyperthermia can produce thermal tolerance and, thereby, attenuate future physiological and behavioral reactions to heating. Because endogenous opioids have been implicated in thermoregulation and reactions to microwave exposure, we also determined how opioid receptor antagonism might modulate these effects. In an initial experiment, rats were exposed daily, over 5 successive days, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. In animals exposed to microwaves, thermal tolerance was evidenced by declining rectal temperatures over time. Temperature reductions following microwave exposure were prominent after a single previous exposure. Therefore, in a second study, a single hyperthermic episode was used to induce thermal tolerance. On Day 1, rats were either exposed, over a 20-min period, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. Just prior to radiation/sham-radiation treatment, rats received either saline or naltrexone (0.1 or 10 mg/kg, intraperitoneally (i.p.)). The following day (Day 2), rats were either microwave or sham exposed and tested on a task which measures the relative time subjects explore a familiar versus a novel stimulus object. Normothermic rats spend significantly more time in contact with new environmental components and less time with familiar objects. Brain (dura) and rectal temperatures were recorded on both days of the study. Microwave exposure produced a reliable hyperthermia which was significantly lower (on Day 2) in rats receiving repeated treatments (tolerant group). On the behavioral test, rats exposed only once to microwave-induced hyperthermia (nontolerant group) exhibited significantly different patterns of object discrimination than did tolerant or sham-exposed animals. Sham-exposed and tolerant animals showed a distinct preference for the new object whereas the nontolerant animals did not. Naltrexone (10 mg/kg) antagonized the hyperthermia-induced disruption of the object discrimination task (in nontolerant rats) and produced patterns of object exploration that were similar to those of sham-irradiated and thermal-tolerant rats, suggesting that endogenous opioids play a role in the organism's response to heating. Taken together, these data are consistent with the conclusions that 1) microwave-induced hyperthermia can cause a dose-dependent disruption of the normal discrimination between new and familiar objects, 2) physiological reactions to a single hyperthermic episode can produce a thermotolerance that expresses itself in both reduced levels of hyperthermia and attenuated behavioral disruptions following microwave exposure, and 3) opioid antagonism can partially reverse some of the behavioral effects of microwave-induced hyperthermia.

Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment

NASA Astrophysics Data System (ADS)

Quinto, Christopher A.; Mohindra, Priya; Tong, Sheng; Bao, Gang

2015-07-01

Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy. Electronic supplementary information (ESI) available: Core size distribution; temperature increase for specific absorption rate calculations; effect of DOX loading on zeta potential; combined effect of hyperthermia and free DOX; cell morphology following DOX/hyperthermia treatment. See DOI: 10.1039/c5nr02718g

Administration of ondansetron is associated with lethal outcome.

PubMed

Gener, Blanca; Burns, Jarrett M; Griffin, Susanne; Boyer, Edward W

2010-06-01

We report here the case of a child with a known muscular abnormality and susceptibility to malignant hyperthermia who abruptly died after receiving a therapeutic dose of ondansetron. Also, we discuss the pharmacodynamic relationship of ondansetron to malignant hyperthermia in a susceptible host.

Repeated nitrous oxide exposure in rats causes a thermoregulatory sign-reversal with concurrent activation of opposing thermoregulatory effectors

PubMed Central

Ramsay, Douglas S; Woods, Stephen C; Kaiyala, Karl J

2014-01-01

Initial administration of 60% nitrous oxide (N2O) to rats at an ambient temperature of 21°C decreases core temperature (Tc), primarily via increased heat loss (HL). Over repeated N2O administrations, rats first develop tolerance to this hypothermia and subsequently exhibit hyperthermia (a sign-reversal) due primarily to progressive increases in heat production (HP). When rats initially receive 60% N2O in a thermal gradient, they become hypothermic while selecting cooler ambient temperatures that facilitate HL. This study investigated whether rats repeatedly administered 60% N2O in a thermal gradient would use the gradient to behaviorally facilitate, or oppose, the development of chronic tolerance and a hyperthermic sign-reversal. Male Long-Evans rats (N = 16) received twelve 3-h administrations of 60% N2O in a gas-tight, live-in thermal gradient. Hypothermia (Sessions 1–3), complete chronic tolerance (Sessions 4–6), and a subsequent transient hyperthermic sign-reversal (Sessions 7–12) sequentially developed. Despite the progressive recovery and eventual hyperthermic sign-reversal of Tc, rats consistently selected cooler ambient temperatures during all N2O administrations. A final 60% N2O administration in a total calorimeter indicated that the hyperthermic sign-reversal resulted primarily from increased HP. Thus, rats did not facilitate chronic tolerance development by moving to warmer locations in the gradient, and instead selected cooler ambient temperatures while simultaneously increasing autonomic HP. The inefficient concurrent activation of opposing effectors and the development of a sign-reversal are incompatible with homeostatic models of drug-adaptation and may be better interpreted using a model of drug-induced allostasis. PMID:25938127

Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance

PubMed Central

Ren, Yanyan; Zhang, Haijun; Chen, Baoan; Cheng, Jian; Cai, Xiaohui; Liu, Ran; Xia, Guohua; Wu, Weiwei; Wang, Shuai; Ding, Jiahua; Gao, Chong; Wang, Jun; Bao, Wen; Wang, Lei; Tian, Liang; Song, Huihui; Wang, Xuemei

2012-01-01

Background Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe3O4 magnetic nanoparticles (Fe3O4-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia. Methods Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe3O4-MNP, and Fe3O4-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe3O4-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance. Results Fe3O4-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe3O4-MNP and Fe3O4-MNP-DNR-5-BrTet groups, especially in the Fe3O4-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe3O4-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression. Conclusion Fe3O4-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia. PMID:22619560

Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis.

PubMed

Datta, Niloy R; Rogers, Susanne; Ordóñez, Silvia Gómez; Puric, Emsad; Bodis, Stephan

2016-01-01

A systematic review and meta-analysis was conducted to evaluate the outcome of controlled clinical trials in head and neck cancers (HNCs) using hyperthermia and radiotherapy versus radiotherapy alone. A total of 498 abstracts were screened from four databases and hand searched as per the PRISMA guidelines. Only two-arm studies treating HNCs with either radiotherapy alone, or hyperthermia and radiotherapy without concurrent chemotherapy or surgery were considered. The evaluated end point was complete response (CR). Following a detailed screening of the titles, abstracts and full text papers, six articles fulfilling the above eligibility criteria were considered. In total 451 clinical cases from six studies were included in the meta-analysis. Five of six trials were randomised. The overall CR with radiotherapy alone was 39.6% (92/232) and varied between 31.3% and 46.9% across the six trials. With thermoradiotherapy, the overall CR reported was 62.5% (137/219), (range 33.9-83.3%). The odds ratio was 2.92 (95% CI: 1.58-5.42, p = 0.001); the risk ratio was 1.61 (95% CI: 1.32-1.97, p < 0.0001) and the risk difference was 0.25 (95% CI: 0.12-0.39, p < 0.0001), all in favour of combined treatment with hyperthermia and radiotherapy over radiotherapy alone. Acute and late grade III/IV toxicities were reported to be similar in both the groups. Hyperthermia along with radiotherapy enhances the likelihood of CR in HNCs by around 25% compared to radiotherapy alone with no significant additional acute and late morbidities. This level I evidence should justify the integration of hyperthermia into the multimodality therapy of HNCs.

Hysteresis losses and specific absorption rate measurements in magnetic nanoparticles for hyperthermia applications.

PubMed

Coïsson, Marco; Barrera, Gabriele; Celegato, Federica; Martino, Luca; Kane, Shashank N; Raghuvanshi, Saroj; Vinai, Franco; Tiberto, Paola

2017-06-01

Magnetic hysteresis loops areas and hyperthermia on magnetic nanoparticles have been studied with the aim of providing reliable and reproducible methods of measuring the specific absorption rate (SAR). The SAR of Fe 3 O 4 nanoparticles with two different mean sizes, and Ni 1-x Zn x Fe 2 O 4 ferrites with 0 ≤ x ≤ 0.8 has been measured with three approaches: static hysteresis loops areas, dynamic hysteresis loops areas and hyperthermia of a water solution. For dynamic loops and thermometric measurements, specific experimental setups have been developed, that operate at comparable frequencies (≈ 69kHz and ≈ 100kHz respectively) and rf magnetic field peak values (up to 100mT). The hyperthermia setup has been fully modelled to provide a direct measurement of the SAR of the magnetic nanoparticles by taking into account the heat exchange with the surrounding environment in non-adiabatic conditions and the parasitic heating of the water due to ionic currents. Dynamic hysteresis loops are shown to provide an accurate determination of the SAR except for superparamagnetic samples, where the boundary with a blocked regime could be crossed in dynamic conditions. Static hysteresis loops consistently underestimate the specific absorption rate but can be used to select the most promising samples. A means of reliably measure SAR of magnetic nanoparticles by different approaches for hyperthermia applications is presented and its validity discussed by comparing different methods. This work fits within the general subject of metrological traceability in medicine with a specific focus on magnetic hyperthermia. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. Copyright © 2016 Elsevier B.V. All rights reserved.

Anticancer effects of β-elemene with hyperthermia in lung cancer cells

PubMed Central

Wu, Zhibing; Wang, Ting; Zhang, Yanmei; Zheng, Zhishuang; Yu, Shuhuan; Jing, Saisai; Chen, Sumei; Jiang, Hao; Ma, Shenglin

2017-01-01

β-elemene is a novel, plant-derived anticancer drug, which has been used to target multiple solid tumor types. Hyperthermia is an adjuvant therapeutic modality to treat cancer. However, the underlying mechanisms associated with the efficacy of these two treatments are largely unknown. The aim of the present study was to evaluate the effects of β-elemene combined with hyperthermia in lung cancer cell lines. An MTT assay was used to determine cell viability. The cell cycle and apoptosis were analyzed using flow cytometry. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of P21, survivin, caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax) mRNA were detected using quantitative polymerase chain reaction. β-elemene with hyperthermia treatment significantly inhibited the viability and increased the apoptosis rate of A549 cells compared with β-elemene treatment alone (P<0.01), and significantly decreased the proportion of cells in S phase compared with the control (P<0.01). Morphological observation using transmission electron microscopy indicated cross-sectional features of apoptosis: Chromatin condensation, reduced integrity of the plasma membrane, increased cellular granularity, nuclear collapse and the formation of apoptotic bodies. β-elemene with hyperthermia treatment significantly promoted P21 and Bax mRNA expression (P<0.01) and significantly decreased caspase-9, Bcl-2 and survivin mRNA expression (P<0.01) in A549 cells. In conclusion, β-elemene with hyperthermia has a significant inhibitory effect on A549 cells. This occurs through reducing S phase and inducing apoptosis, via an increase in P21 and Bax expression and a decrease in caspase-9, Bcl-2 and survivin expression. PMID:28588670

Chronic Stress Enhances the Corticosterone Response and Neurotoxicity to +3,4-Methylenedioxymethamphetamine (MDMA): The Role of Ambient Temperature

PubMed Central

Johnson, Bethann N.

2010-01-01

Stress facilitates drug abuse by humans. In rodents, stress enhances the neurochemical, neuroendocrine, and behavioral responses to psychostimulants. Although chronic unpredictable stress (CUS) enhances the acute hyperthermic and long-term monoamine-depleting effects of the psychostimulant +3,4-methylenedioxymethamphetamine (MDMA), the roles of hyperthermia and corticosterone (CORT) in mediating the stress-induced enhancement of MDMA-induced serotonin (5-HT) and dopamine (DA) depletions are unknown. Rats were exposed to 10 days of CUS and then challenged with MDMA (5 mg/kg i.p. once every 2 h for a total of four injections). Prior exposure to CUS augmented MDMA-induced hyperthermia and plasma CORT secretion and the long-term depletions in 5-HT content in striatum, hippocampus, and frontal cortex and DA content in striatum. A reduced ambient temperature of 21°C attenuated the hyperthermia, CORT secretion, and 5-HT decreases after MDMA in nonstressed rats. The lower ambient temperature also prevented the augmented hyperthermia, CORT secretion, and enhanced 5-HT and DA depletions after MDMA in chronically stressed rats to levels exhibited by nonstressed, MDMA-treated rats. To investigate the role of CORT on monoamine depletions in response to MDMA, stressed and nonstressed rats were treated with the CORT synthesis inhibitor metyrapone during exposure to MDMA. Metyrapone prevented CORT secretion in both stressed and nonstressed rats but did not modify 5-HT or DA depletions in any brain region examined. This study suggests that enhanced CORT is a consequence of enhanced hyperthermia and the CUS-induced enhancements of MDMA-induced monoamine depletions may be mediated by hyperthermia but not CORT. PMID:20634423

Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance.

PubMed

Ren, Yanyan; Zhang, Haijun; Chen, Baoan; Cheng, Jian; Cai, Xiaohui; Liu, Ran; Xia, Guohua; Wu, Weiwei; Wang, Shuai; Ding, Jiahua; Gao, Chong; Wang, Jun; Bao, Wen; Wang, Lei; Tian, Liang; Song, Huihui; Wang, Xuemei

2012-01-01

Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe(3)O(4) magnetic nanoparticles (Fe(3)O(4)-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia. Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe(3)O(4)-MNP, and Fe(3)O(4)-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe(3)O(4)-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance. Fe(3)O(4)-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe(3)O(4)-MNP and Fe(3)O(4)-MNP-DNR-5-BrTet groups, especially in the Fe(3)O(4)-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression. Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia.

Ag-doped manganite nanoparticles: new materials for temperature-controlled medical hyperthermia.

PubMed

Melnikov, O V; Gorbenko, O Yu; Markelova, M N; Kaul, A R; Atsarkin, V A; Demidov, V V; Soto, C; Roy, E J; Odintsov, B M

2009-12-15

The purpose of this study was to introduce newly synthesized nanomaterials as an alternative to superparamagnetic ironoxide based particles (SPIO) and thus to launch a new platform for highly controllable hyperthermia cancer therapy and imaging. The new material that forms the basis for this article is lanthanum manganite particles with silver ions inserted into the perovskite lattice: La(1-x)Ag(x)MnO(3+delta). Adjusting the silver doping level, it is possible to control the Curie temperature (T(c)) in the hyperthermia range of interest (41-44 degrees C). A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) is suggested. New nanoparticles are stable, and their properties were not affected by the typical ambient conditions in the living tissue. It is possible to monitor the particle uptake and retention by MRI. When these particles are placed into an alternating magnetic field, their temperature increases to the definite value near T(c) and then remains constant if the magnetic field is maintained. During the hyperthermia procedure, the temperature can be restricted, thereby preventing the necrosis of normal tissue. A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) was suggested. Ag-doped perovskite manganites particles clearly demonstrated the effect of adjustable Curie temperature necessary for highly controllable cellular hyperthermia. The magnetic relaxation properties of the particles are comparable with that of SPIO, and so we were able to monitor the particle movement and retention by MRI. Thus, the new material combines the MRI contrast enhancement capability with targeted hyperthermia treatment.

Effect of short-term scrotal hyperthermia on spermatological parameters, testicular blood flow and gonadal tissue in dogs.

PubMed

Henning, H; Masal, C; Herr, A; Wolf, K; Urhausen, C; Beineke, A; Beyerbach, M; Kramer, S; Günzel-Apel, A-R

2014-02-01

The objective was to assess the effect of a short-term scrotal hyperthermia in dogs on quantitative and qualitative ejaculate parameters, testicular blood flow and testicular and epididymal histology. After a control period, the scrotum of seven normospermic adult beagle dogs was insulated with a self-made suspensory for 48 h. Nine weeks later, two animals were castrated, while in five animals, scrotal hyperthermia was repeated. Dogs were castrated either 10 or 40 days thereafter. In each phase of scrotal insulation, average scrotal surface temperature increased by 3.0°C. Semen was collected twice weekly throughout the experiment. Total sperm count did not change after the first hyperthermia, but it slightly decreased after the second (p < 0.05). Profiles of sperm morphology and velocity parameters (CASA) rather indicated subtle physiological variations in sperm quality than effects of a local heat stress. Chromatin stability of ejaculated spermatozoa as indicated by SCSA remained constant throughout the experiment. Perfusion characteristics of the gonads, that is, systolic peak velocity, pulsatility and resistance index at the marginal location of the testicular artery, did not change due to hyperthermia (p > 0.05). Histological examination of excised testes and epididymides for apoptotic (TUNEL and activated caspase-3) and proliferating cells (Ki-67 antigen) indicated only marginal effects of scrotal insulation on tissue morphology. In conclusion, a mild short-term scrotal hyperthermia in dogs does not cause substantial changes in sperm quantity and quality. In contrast to other species, canine testes and epididymides may have a higher competence to compensate such thermal stress. © 2013 Blackwell Verlag GmbH.

Impact of Ambient Temperature on Hyperthermia Induced by (±)3,4-Methylenedioxymethamphetamine in Rhesus Macaques

PubMed Central

Von Huben, Stefani N.; Lay, Christopher C.; Crean, Rebecca D.; Davis, Sophia A.; Katner, Simon N.; Taffe, Michael A.

2007-01-01

The ambient temperature (TA) under which rodents are exposed to (±)3,4-methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the body temperature response, and the degree of hypo/hyperthermia generated in subjects can modify the severity of lasting brain changes in “neurotoxicity” models. The thermoregulatory effects of MDMA have not been well described in nonhuman primates and it is unknown if TA has the potential to affect acute hyperthermia and therefore other lasting consequences of MDMA. The objective of this study was to determine if the temperature alteration produced by MDMA in nonhuman primates depends on TA as it does in rats and mice. Body temperature and spontaneous home cage activity were monitored continuously in six male rhesus monkeys via radiotelemetry. The subjects were challenged intramuscularly with 0.56-2.4 mg/kg (±)MDMA under each of three TA conditions (18°C, 24°C, 30°C) in a randomized order. Temperature was significantly elevated following injection with all doses of MDMA under each ambient temperature. The magnitude of mean temperature change was ~1°C in most conditions suggesting a closely controlled thermoregulatory response in monkeys across a range of doses and ambient temperatures. Activity levels were generally suppressed by MDMA, however a 50% increase over vehicle was observed after 0.56 MDMA under the 30°C condition. It is concluded that MDMA produces very a similar degree of hyperthermia in rhesus monkeys across a range of TA conditions which result in hypothermia or exaggerated hyperthermia in rodents. Monkey temperature responses to MDMA appear to be more similar to humans than to rodents and therefore the monkey may offer an improved model of effects related to MDMA-induced hyperthermia. PMID:16641942

Effect of intra-tumoral magnetic nanoparticle hyperthermia and viral nanoparticle immunogenicity on primary and metastatic cancer

NASA Astrophysics Data System (ADS)

Hoopes, P. Jack; Mazur, Courtney M.; Osterberg, Bjorn; Song, Ailin; Gladstone, David J.; Steinmetz, Nicole F.; Veliz, Frank A.; Bursey, Alicea A.; Wagner, Robert J.; Fiering, Steven N.

2017-02-01

Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia. Based on the prior experience of our research group including; cancer-based heat therapy, magnetic nanoparticle (mNP) hyperthermia, radiation biology, cancer immunology and Cowpea Mosaic Virus that has been engineered to over express antigenic proteins without RNA or DNA (eCPMV/VLP). This research was designed to determine if and how the intra-tumoral delivery of mNP hyperthermia and VLP can work together to improve local and systemic tumor treatment efficacy. Using the C3H mouse/MTG-B mammary adenocarcinoma cell model and the C57-B6 mouse/B-16-F10 melanoma cancer cell model, our data suggests the appropriate combination of intra-tumoral mNP heat (e.g. 43°C /30-60 minutes) and VLP (100 μg/200 mm3 tumor) not only result in significant primary tumor regression but the creation a systemic immune reaction that has the potential to retard secondary tumor growth (abscopal effect) and resist tumor rechallenge. Molecular data from these experiments suggest treatment based cell damage and immune signals such as Heat Shock Protein (HSP) 70/90, calreticulin, MTA1 and CD47 are potential targets that can be exploited to enhance the local and systemic (abscopal effect) immune potential of hyperthermia cancer treatment

Association of hyperglycemia, systolic and diastolic hypertension, and hyperthermia relative to baseline in the acute phase of stroke with poor outcome after intravenous thrombolysis.

PubMed

Forlivesi, Stefano; Micheletti, Nicola; Tomelleri, Giampaolo; Bovi, Paolo; Cappellari, Manuel

2018-03-01

: In the acute phase of ischemic stroke, the trend of some physiological variables, such as blood glucose (BG), blood pressure, and body temperature (BT), might influence outcome. We aimed to assess the association of hyperglycemia, systolic and diastolic hypertension, and hyperthermia relative to baseline BG, systolic blood pressure, diastolic blood pressure and BT, respectively, in the first 12 h with poor outcome after intravenous thrombolysis (IVT). We conducted a retrospective analysis of data prospectively collected from 200 consecutive anterior ischemic stroke patients treated with IVT. Outcome measures were no neurological improvement at 24 h (National Institutes of Health Stroke Scale (NIHSS) score at 24 h ≥NIHSS score at baseline), and unfavorable functional outcome [modified Rankin Scale (mRS) score 3-6] at 3 months. No neurological improvement at 24 h was noted in 52 (26%) patients and mRS 3-6 at 3 months in 68 (34%) patients. The multivariate analyses showed that odds ratios (ORs) for no neurological improvement at 24 h were higher in patients with hyperglycemia relative to baseline [OR 3.50, 95% confidence interval (CI) 1.43-8.57, P = 0.006], and hyperthermia relative to baseline (OR 2.88, 95% CI 1.20-6.91, P = 0.018). OR for 3-month mRS score 3-6 was higher in patients with hyperthermia relative to baseline (OR 3.05, 95% CI 1.20-7.74, P = 0.019). Hyperglycemia and hyperthermia relative to baseline in the first 12 h after IVT are associated with no neurological improvement at 24 h. Hyperthermia relative to baseline is also associated with unfavorable functional outcome at 3 months.

The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives

PubMed Central

Docherty, JR; Green, AR

2010-01-01

Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters [5-hydroxytryptamine (5-HT), dopamine and noradrenaline], both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5-HT release is not directly responsible for hyperthermia, but 5-HT receptors are involved in modulating the hyperthermic response. Impairing 5-HT function with a neurotoxic dose of MDMA or p-chlorophenylalanine alters the subsequent MDMA-induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central α2A-adrenoceptors and peripheral α1-adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and β3-adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem. PMID:20590597

Mechanisms of Hypothermia, Delayed Hyperthermia and Fever Following CNS Injury

EPA Science Inventory

Central nervous system (CNS) damage is often associated with robust body temperature changes, such as hypothermia and delayed hyperthermia. Hypothermia is one of the most common body temperature changes to CNS insults in rodents and is often associated with improved outcome. Alth...

Simulation techniques in hyperthermia treatment planning

PubMed Central

Paulides, MM; Stauffer, PR; Neufeld, E; Maccarini, P; Kyriakou, A; Canters, RAM; Diederich, C; Bakker, JF; Van Rhoon, GC

2013-01-01

Clinical trials have shown that hyperthermia (HT), i.e. an increase of tissue temperature to 39-44°C, significantly enhance radiotherapy and chemotherapy effectiveness (1). Driven by the developments in computational techniques and computing power, personalized hyperthermia treatment planning (HTP) has matured and has become a powerful tool for optimizing treatment quality. Electromagnetic, ultrasound, and thermal simulations using realistic clinical setups are now being performed to achieve patient-specific treatment optimization. In addition, extensive studies aimed to properly implement novel HT tools and techniques, and to assess the quality of HT, are becoming more common. In this paper, we review the simulation tools and techniques developed for clinical hyperthermia, and evaluate their current status on the path from “model” to “clinic”. In addition, we illustrate the major techniques employed for validation and optimization. HTP has become an essential tool for improvement, control, and assessment of HT treatment quality. As such, it plays a pivotal role in the quest to establish HT as an efficacious addition to multi-modality treatment of cancer. PMID:23672453

High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

PubMed

Laorden, M L; Miralles, F S; Puig, M M

1988-03-01

The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

A Parallel 2D Numerical Simulation of Tumor Cells Necrosis by Local Hyperthermia

NASA Astrophysics Data System (ADS)

Reis, R. F.; Loureiro, F. S.; Lobosco, M.

2014-03-01

Hyperthermia has been widely used in cancer treatment to destroy tumors. The main idea of the hyperthermia is to heat a specific region like a tumor so that above a threshold temperature the tumor cells are destroyed. This can be accomplished by many heat supply techniques and the use of magnetic nanoparticles that generate heat when an alternating magnetic field is applied has emerged as a promise technique. In the present paper, the Pennes bioheat transfer equation is adopted to model the thermal tumor ablation in the context of magnetic nanoparticles. Numerical simulations are carried out considering different injection sites for the nanoparticles in an attempt to achieve better hyperthermia conditions. Explicit finite difference method is employed to solve the equations. However, a large amount of computation is required for this purpose. Therefore, this work also presents an initial attempt to improve performance using OpenMP, a parallel programming API. Experimental results were quite encouraging: speedups around 35 were obtained on a 64-core machine.

Hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3 nanoparticles: in vivo studies

PubMed Central

Haghniaz, Reihaneh; Umrani, Rinku D; Paknikar, Kishore M

2016-01-01

Purpose The aim of this study was to evaluate radiofrequency-induced dextran-coated lanthanum strontium manganese oxide nanoparticles-mediated hyperthermia to be used for tumor regression in mice. Materials and methods Nanoparticles were injected intra-tumorally in melanoma-bearing C57BL/6J mice and were subjected to radiofrequency treatment. Results Hyperthermia treatment significantly inhibited tumor growth (~84%), increased survival (~50%), and reduced tumor proliferation in mice. Histopathological examination demonstrated immense cell death in treated tumors. DNA fragmentation, increased terminal deoxynucleotidyl transferase-dUTP nick end labeling signal, and elevated levels of caspase-3 and caspase-6 suggested apoptotic cell death. Enhanced catalase activity suggested reactive oxygen species-mediated cell death. Enhanced expression of heat shock proteins 70 and 90 in treated tumors suggested the possible development of “antitumor immunity”. Conclusion The dextran-coated lanthanum strontium manganese oxide-mediated hyperthermia can be used for the treatment of cancer. PMID:27175076

Biphasic magnetic nanoparticles-nanovesicle hybrids for chemotherapy and self-controlled hyperthermia.

PubMed

Gogoi, Manashjit; Sarma, Haladhar D; Bahadur, Dhirendra; Banerjee, Rinti

2014-05-01

The aim was to develop magnetic nanovesicles for chemotherapy and self-controlled hyperthermia that prevent overheating of tissues. Magnetic nanovesicles containing paclitaxel and a dextran-coated biphasic suspension of La0.75Sr0.25MnO3 and Fe3O4 nanoparticles (magnetic nanoparticles) were developed. Encapsulation efficiencies of magnetic nanoparticles and paclitaxel were 67 ± 5 and 83 ± 3%, respectively. Sequential release performed at 37°C for 1 h followed by 44°C for another 1 h (as expected for intratumoral injection), showed a cumulative release of 6.6% (109.6 µg), which was above the IC50 of the drug. In an alternating current magnetic field, the temperature remained controlled at 44°C and a synergistic cytotoxicity of paclitaxel and hyperthermia was observed in MCF-7 cells. Magnetic nanovesicles containing biphasic suspensions La0.75Sr0.25MnO3 and Fe3O4 nanoparticles encapsulating paclitaxel have potential for combined self-controlled hyperthermia and chemotherapy.

Radio frequency induced hyperthermia mediated by dextran stabilized LSMO nanoparticles: in vitro evaluation of heat shock protein response

NASA Astrophysics Data System (ADS)

Bhayani, K. R.; Rajwade, J. M.; Paknikar, K. M.

2013-01-01

Dextran stabilized La0.7Sr0.3MnO3 (Dex-LSMO) is an alternative cancer hyperthermia agent holding considerable promise. Here, we have carried out a comparative study on radio frequency (˜264 kHz) induced Dex-LSMO mediated heating and extraneous heating (mimicking generalized hyperthermia) in terms of changes in the morphology, proliferation pattern and induction of heat shock proteins in a human melanoma cell line (A375). Our results clearly show that the cellular effects seen with extraneous heating (60 min at 43 °C) could be reproduced by just six minutes of radio frequency induced Dex-LSMO mediated heating. More importantly, the observed enhanced levels of HSP 70 and 90 (molecular markers of heat shock that trigger favorable immunological reactions) seen with Dex-LSMO mediated heating were comparable to extraneous heating. These results suggest the possible utility of Dex-LSMO as a cancer hyperthermia agent.

Magnetic hyperthermia in water based ferrofluids: Effects of initial susceptibility and size polydispersity on heating efficiency

NASA Astrophysics Data System (ADS)

Lahiri, B. B.; Ranoo, Surojit; Muthukumaran, T.; Philip, John

2018-04-01

The effects of initial susceptibility and size polydispersity on magnetic hyperthermia efficiency in two water based ferrofluids containing phosphate and TMAOH coated superparamagnetic Fe3O4 nanoparticles were studied. Experiments were performed at a fixed frequency of 126 kHz on four different concentrations of both samples and under different external field amplitudes. It was observed that for field amplitudes beyond 45.0 kAm-1, the maximum temperature rise was in the vicinity of 42°C (hyperthermia limit) which indicated the suitability of the water based ferrofluids for hyperthermia applications. The maximum temperature rise and specific absorption rate were found to vary linearly with square of the applied field amplitudes, in accordance with theoretical predictions. It was further observed that for a fixed sample concentration, specific absorption rate was higher for the phosphate coated samples which was attributed to the higher initial static susceptibility and lower size polydispersity of phosphate coated Fe3O4.

Magnetic, structural and magnetocaloric properties of Ni-Si and Ni-Al thermoseeds for self-controlled hyperthermia.

PubMed

Pandey, Sudip; Quetz, Abdiel; Aryal, Anil; Dubenko, Igor; Mazumdar, Dipanjan; Stadler, Shane; Ali, Naushad

2017-11-01

Self-controlled hyperthermia is a non-invasive technique used to kill or destroy cancer cells while preserving normal surrounding tissues. We have explored bulk magnetic Ni-Si and Ni-Al alloys as a potential thermoseeds. The structural, magnetic and magnetocaloric properties of the samples were investigated, including saturation magnetisation, Curie temperature (T C ), and magnetic and thermal hysteresis, using room temperature X-ray diffraction and magnetometry. The annealing time, temperature and the effects of homogenising the thermoseeds were studied to determine the functional hyperthermia applications. The bulk Ni-Si and Ni-Al binary alloys have Curie temperatures in the desired range, 316 K-319 K (43 °C-46 °C), which is suitable for magnetic hyperthermia applications. We have found that T C strictly follows a linear trend with doping concentration over a wide range of temperature. The magnetic ordering temperature and the magnetic properties can be controlled through substitution in these binary alloys.

alpha-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia.

PubMed

Cappon, G D; Broening, H W; Pu, C; Morford, L; Vorhees, C V

1996-10-01

Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P < 0.01 vs. Sal-Sal). MA with PBN pretreatment (PBN-MA) at 36 or 60 mg/kg reduced neostriatal DA by 36 and 22%, respectively (P < 0.05 and P < 0.01 vs Sal-MA) indicating partial protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis

PubMed Central

Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

2006-01-01

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2–0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the Ih current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes. PMID:16819552

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

PubMed

Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

2006-07-01

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

Design of a Subtarsal Ultrasonic Transducer for Mild Hyperthermia Treatment of Dry Eye Disease.

PubMed

Hynes, Michael B; Bujak, Matthew C; Chérin, Emmanuel; Sade, Shachar; Foster, F Stuart

2016-01-01

Dry eye disease is a disorder of the ocular surface that causes pain and low vision in a significant portion of the adult population. A common cause is obstructive Meibomian gland dysfunction, whereby the Meibomian glands secrete abnormal meibum with a melting point elevated by 3°C-4°C; hence, hyperthermia is the typical treatment. A design is proposed for an ultrasound hyperthermia device made of a transducer contained inside a contact lens with an internal air gap. The transducer heats the posterior of the tarsus, and the air gap provides an air backing to the transducer, preventing direct heating of the cornea. A prototype device was built, and hyperthermia experiments were performed on a porcine subject in vivo. A therapeutic temperature rise of 5°C-7°C was achievable in 10-15 min. The temperature of the cornea did not rise more than 2°C during any of the experiments. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Design and characterisation of miniaturised cavity-backed patch antenna for microwave hyperthermia.

PubMed

Chakaravarthi, Geetha; Arunachalam, Kavitha

2015-01-01

The aim of this study was to describe the design and characterisation of a miniaturised 434 MHz patch antenna enclosed in a metal cavity for microwave hyperthermia treatment of cancer. Electromagnetic (EM) field distribution in the near field of a microstrip patch irradiating body tissue was studied using finite element method (FEM) simulations. Antenna miniaturisation was achieved through dielectric loading with very high permittivity, metal enclosure, patch folding and shorting post. Frequency dependent electrical properties of materials were incorporated wherever appropriate using dispersion model and measurements. Antenna return loss and specific absorption rate (SAR) at 434 MHz were measured on muscle phantoms for characterisation. The design was progressively optimised to yield a compact 434 MHz patch (22 mm × 8.8 mm × 10 mm) inside a metal cavity (40 mm × 12 mm) with integrated coupling water bolus (35 mm). The fabricated antenna with integrated water bolus was self resonant at 434 MHz without load, and has better than -10 dB return loss (S11) with 13-20 MHz bandwidth on two different phantoms. SAR at 434 MHz measured using an infrared (IR) thermal camera on split phantoms indicated penetration depth for -3 dB SAR as 8.25 mm compared to 8.87 mm for simulation. The simulated and measured SAR coverage along phantom depth was 3.09 cm(2) and 3.21 cm(2) respectively at -3 dB, and 6.42 cm(2) and 9.07 cm(2) respectively at -6 dB. SAR full width at half maximum (FWHM) at 5 mm and 20 mm depths were 54.68 mm and 51.18 mm respectively in simulation, and 49.47 mm and 43.75 mm respectively in experiments. Performance comparison of the cavity-backed patch indicates more than 89% co-polarisation and higher directivity which resulted in deeper penetration compared to the patch applicators of similar or larger size proposed for hyperthermia treatment of cancer. The fabricated cavity-backed applicator is self-resonant at 434 MHz with a negligible shift in resonance when coupled to different phantoms, Δf/f0 less than 1.16%. IR thermography-based SAR measurements indicated that the -3 dB SAR of the cavity-backed aperture antenna covered the radiating aperture surface at 5 mm and 20 mm depths. It can be concluded that the compact cavity-backed patch antenna has stable resonance, higher directivity and low cross polarisation, and is suitable for design of microwave hyperthermia array applicators with adjustable heating pattern for superficial and/or deep tissue heating.

Glucocorticoid effects on sheep peripheral blood mononuclear cell proliferation and cytokine production under in vitro hyperthermia.

PubMed

Caroprese, M; Ciliberti, M G; De Palo, P; Santillo, A; Sevi, A; Albenzio, M

2018-06-27

The present experiment aimed at understanding the effects of cortisol levels on sheep peripheral blood mononuclear cell (PBMC) proliferation and cytokine production during hyperthermia. To mimic stress related to the exposition of high ambient temperatures, PBMC were cultured at 43°C for 12 h, and subsequently at 39°C for additional 12 h. Cells in normothermia were cultured at 39°C for 24 h. Phytohemagglutinin-stimulated PBMC were cultured with different cortisol levels: 0 ng/mL; 100 ng/mL, representing the physiological cortisol concentration simulating stress condition (Cort100); and 1,000 ng/mL, representing the hyperactivated hypothalamic-pituitary-adrenal axis (Cort1000). Phytohemagglutinin-stimulated PBMC with 0 ng/mL of cortisol concentration represented the positive control, whereas nonstimulated PBMC without cortisol represented the negative control (NC). The free cell supernatants were collected for the determination of IL-6, IL-1β, and IL-10 by ELISA. Bromodeoxyuridine assay was performed on cells to determine cell proliferation. Exposition to hyperthermia negatively affected cell proliferation, IL-6, IL-1β, and IL-10 concentrations in cell supernatants. The interaction of hyperthermia and cortisol level affected both cell proliferation and IL-10 production. Both PBMC proliferation and IL-10 production in positive control, Cort100, and Cort100 decreased at 43°C as compared with 39°C NC. On average, the Cort100 treatment displayed higher concentrations of IL-6 than NC. The present experiment demonstrated that the action of cortisol concentration simulating stress condition on cell proliferation and cytokine production was a permissive/stimulatory action during normothermia, whereas it was a suppressive action during hyperthermia. These data confirmed that cortisol concentration simulating stress condition could have a role in the immune system of sheep via mediating cellular homeostasis in the condition of hyperthermia. The negative effects of hyperthermia on sheep immune responses were apparent when performing an immunological challenge. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Mean-field and linear regime approach to magnetic hyperthermia of core-shell nanoparticles: can tiny nanostructures fight cancer?

NASA Astrophysics Data System (ADS)

Carrião, Marcus S.; Bakuzis, Andris F.

2016-04-01

The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy.The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy. Electronic supplementary information (ESI) available: Unit cells per region calculation; core-shell Hamiltonian; magnetisation description functions; energy argument of Brillouin function; polydisperse models; details of experimental procedure; LRT versus core-shell model; model calculation software; and shell thickness study. See DOI: 10.1039/C5NR09093H

The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels.

PubMed

Franke, Karolin; Kettering, Melanie; Lange, Kathleen; Kaiser, Werner A; Hilger, Ingrid

2013-01-01

The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 μg Fe/cm(2)) or mitomycin C (up to 1.5 μg/cm(2), 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop new treatment strategies by repressing mechanisms that actively export drugs from the target cell, thereby improving the therapeutic outcome in oncology.

Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors.

PubMed

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2015-02-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity.

The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels

PubMed Central

Franke, Karolin; Kettering, Melanie; Lange, Kathleen; Kaiser, Werner A; Hilger, Ingrid

2013-01-01

Purpose The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. Methods BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 μg Fe/cm2) or mitomycin C (up to 1.5 μg/cm2, 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Results When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. Discussion The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop new treatment strategies by repressing mechanisms that actively export drugs from the target cell, thereby improving the therapeutic outcome in oncology. PMID:23378758

Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors

PubMed Central

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2014-01-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity. PMID:25446678

Obese type 2 diabetics have a blunted hypotensive response to acute hyperthermia therapy that does not affect the perception of thermal stress or physiological strain compared to healthy adults.

PubMed

Rivas, Eric; Newmire, Dan E; Ben-Ezra, Vic

2016-10-15

The objective of this study was to test the hypothesis that a hyperthermia-hypotensive challenge via whole body hot water immersion would alter the perception of hyperthermia and physiological strain in obese type 2 diabetics (T2DM) compared to healthy non-obese (HC) individuals. Additionally, we hypothesize that the mechanisms would be attributed to impaired blood pressure adjustments and afferent signals (via changes in internal and mean skin temperatures). In random order, eleven obese T2DM (50±12y, 45±7% fat mass, 7.5±1.8% HbA1c) and nine similar aged (41±14y, P>0.05) HC non-obese (33±8% fat mass, P<0.01) non-diabetic (5.3±0.4% HbA1c, P<0.01) underwent a 60min bout of whole body passive hyperthermia followed by 60min of recovery or a 2h resting control condition. The perception of thermal sensation (TS, scale range: 1-13), calculated physiological strain (PSI), internal (Tre, rectal) and mean skin (Tsk) temperatures, heart rate (HR) and blood pressures (BP) were the primary dependent variables. Hyperthermia similarly increased Tre by 1.4±0.4°C, Tsk by 6.5±0.8°C and HR by 34±8bpm in both groups (P>0.5). Hyperthermia reduced diastolic BP (27% in T2DM and 33% in HC, P<0.05) and mean arterial BP (reduced by 15% in T2DM and by 19% in HC) relative to control conditions (P<0.05). The reduction of mean arterial BP area under the curve was attenuated in T2DM (12%) compared to HC (30%) (group×condition, P<0.01). TS and PSI during hyperthermia were not different between groups. Pearson product correlation reported strong correlations (r=0.69-0.89) with Tre and Tsk with TS in both populations. The linear stepwise regression analysis revealed similar relative contributions for Tre (~60%) and Tsk (~40%) on TS for both groups. These data indicate that obese T2DM with moderate metabolic control have an attenuated hyperthermia-hypotensive response that does not affect TS and PSI. This also may suggest behavioral thermoregulation is intact in this study group. Copyright © 2016 Elsevier Inc. All rights reserved.

Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats

PubMed Central

2018-01-01

Background Initial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations. Methods This study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C—38°C) to assess each adapted group’s thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration. Results In phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia. Conclusions Acquired N2O hyperthermia in rats is remarkably robust, and occurs even despite the availability of ambient temperatures that might fully counter the hyperthermia. Increased locomotion in the gradient may contribute to hyperthermia. Our data are consistent with an allostatic dis-coordination of autonomic and behavioral thermoregulatory mechanisms during drug administration. Our results have implications for research on N2O abuse as well as research on the role of allostasis in drug addiction. PMID:29672605

Thermosensitive Nanostructured Media for imaging and Hyperthermia Cancer Treatment

NASA Astrophysics Data System (ADS)

Martirosyan, Karen

2011-03-01

Hyperthermia has been used for many years to treat a wide variety of tumors in patients. The most commonly applied method of hyperthermia is capacitive heating by using microwave. Magnetic fluids based on iron oxide (Fe3O4), stabilized by biocompatible surfactants are typically used as heating agent. However, significant limitations of using commercial available magnetic particles are non-selectivity and overheating of surrounding normal tissues. To improve the efficacy of hyperthermia treatment we intend to develop Curie temperature (Tc)-tuned nanostructured media having T2 relaxation response on MRI for selective and self-controlled hyperthermia cancer treatment. As an active part of this media we fabricated superparamagnetic, biocompatible and dextran coated ferrite nanoparticles Mg1+xTixFe2(1-x)O4 at 0.3 x < 0.5 with low Curie temperature. To tune Tc we produced a large number of ferrites powders with x = 0.05 by aqueous combustion synthesis. This process typically involves a reaction in a solution containing metal nitrates and different fuels, which are classified based on the type of reactive groups (e.g., amino, hydroxyl, carboxyl) connected to a hydrocarbon chain, such as glycine, hydrazine, or urea. Our experiments revealed that ferrite with formula Mg1.35Ti0.35Fe1.3O4 appears with Curie temperature within 46-50rC. NSF, grant # 0933140.

Similarities and differences in ablative and non-ablative iron oxide nanoparticle hyperthermia cancer treatment

NASA Astrophysics Data System (ADS)

Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Mazur, Courtney M.; Petryk, James D.; Hoopes, P. Jack

2015-03-01

The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. It has been demonstrated by many research groups that ablative temperatures and cytotoxicity can be produced with locally NP-based hyperthermia. Such ablative NP techniques have demonstrated the potential for success. Much attention has also been given to the fact that NP may be administered systemically, resulting in a broader cancer therapy approach, a lower level of tumor NP content and a different type of NP cancer therapy (most likely in the adjuvant setting). To use NP based hyperthermia successfully as a cancer treatment, the technique and its goal must be understood and utilized in the appropriate clinical context. The parameters include, but are not limited to, NP access to the tumor (large vs. small quantity), cancer cell-specific targeting, drug carrying capacity, potential as an ionizing radiation sensitizer, and the material properties (magnetic characteristics, size and charge). In addition to their potential for cytotoxicity, the material properties of the NP must also be optimized for imaging, detection and direction. In this paper we will discuss the differences between, and potential applications for, ablative and non-ablative magnetic nanoparticle hyperthermia.

Study of the therapeutic effect of 188Re labeled folate targeting albumin nanoparticle coupled with cis-diamminedichloroplatinum cisplatin on human ovarian cancer.

PubMed

Tang, Qiusha; Chen, Daozhen

2014-01-01

This paper aimed to investigate the treatment efficiency of 188Re labeled folate targeting albumin nanoparticles with cis-Diamminedichloroplatinum Cisplatin (188Re-folate-CDDP/HAS MNP) on human ovarian cancer. SKOV3 cells or tumor-bearing mice were divided into different groups and treated as follow: (A) negative control; (B) chemotherapy; (C) radiotherapy; (D) hyperthermia; (E) chemotherapy and radiotherapy; (F) chemotherapy and hyperthermia; (G) radiotherapy and hyperthermia; (H) chemotherapy, radiotherapy and hyperthermia. Treatment of B to H inhibited proliferation of SKOV3 cells, with the greatest inhibition being observed in group H (P<0.05). Obvious apoptotic hypodiploid peak appeared beside G1 phase in groups of B to H. The apoptotic rates of SKOV3 cells in groups of A to H were 0.08%, 7.56%, 8.64%, 17.14%, 21.64%, 23.77%, 33.94% and 57.16%, respectively. Our findings in vivo study showed that the mass of tumor in each group of B to H was significantly lower than that in the negative control (p <0.05). In addition, compared with each group of B to G, group H showed highest inhibition of tumor growth (p<0.05). In conclusion, the combination of magnetic induced hyperthermia, chemotherapy and targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer, which indicates a potential applications in ovarian cancer treatment.

Simultaneous hyperthermia-chemotherapy with controlled drug delivery using single-drug nanoparticles.

PubMed

Sato, Itaru; Umemura, Masanari; Mitsudo, Kenji; Fukumura, Hidenobu; Kim, Jeong-Hwan; Hoshino, Yujiro; Nakashima, Hideyuki; Kioi, Mitomu; Nakakaji, Rina; Sato, Motohiko; Fujita, Takayuki; Yokoyama, Utako; Okumura, Satoshi; Oshiro, Hisashi; Eguchi, Haruki; Tohnai, Iwai; Ishikawa, Yoshihiro

2016-04-22

We previously investigated the utility of μ-oxo N,N'- bis(salicylidene)ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF), and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide, and thus cannot exhibit anti-cancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells, and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor, and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.

Canine blood volume and cardiovascular function during hyperthermia.

PubMed

Miki, K; Morimoto, T; Nose, H; Itoh, T; Yamada, S

1983-08-01

The effect of acute hyperthermia on hemodynamic functions and blood volume regulation was examined on eight splenectomized dogs. Elevation of core body temperature by 2 degrees C over 90 min caused significant increase in cardiac output (11.2 +/- 12.5 ml X min-1 X kg-1 or about 10%) and significant decrease in total peripheral resistance (TPR; -1.3 +/- 1.0 mmHg X s X ml-1 or about 20%), whereas blood volume (BV), plasma oncotic pressure, and intravascular protein mass remained unchanged. Thus the raised core temperature caused peripheral vasodilation with decreased TPR and compensatory increase in cardiac output. Because BV remained unchanged during warming, mobilization of extravascular fluid did not occur; only the redistribution of blood to the vasodilated cutaneous circulation took place. To assess the effects of heat stress on transvascular fluid equilibrium, Ringer solution (10.7 ml X kg-1 X 10 min-1) was infused under normothermic and hyperthermic conditions. The volume of fluid retained within the intravascular space under equilibrium state was 33.5% in hyperthermia and 9.4% in normothermia. In hyperthermia, the transvascular fluid shift and urinary output were decreased both during and after infusion. The role of preferential fluid retention within the intravascular space observed during hyperthermia was discussed in relation to the mechanism to maintain cardiovascular function and BV under heat stress.

Cardiopulmonary and arterial baroreceptor unloading during passive hyperthermia does not contribute to hyperthermia-induced hyperventilation.

PubMed

Lucas, Rebekah A I; Pearson, James; Schlader, Zachary J; Crandall, Craig G

2015-11-01

What is the central question of this study? Does baroreceptor unloading during passive hyperthermia contribute to increases in ventilation and decreases in end-tidal carbon dioxide during that exposure? What is the main finding and its importance? Hyperthermic hyperventilation is not mitigated by expanding central blood volume and reloading the cardiopulmonary baroreceptors via rapid saline infusion or by reloading the arterial baroreceptors via phenylephrine administration. The absence of a reduction in ventilation upon reloading the baroreceptors to pre-hyperthermic levels indicates that cardiopulmonary and arterial baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. This study tested the hypothesis that baroreceptor unloading during passive hyperthermia contributes to increases in ventilation and decreases in end-tidal partial pressure of carbon dioxide (P ET ,CO2) during that exposure. Two protocols were performed, in which healthy subjects underwent passive hyperthermia (increasing intestinal temperature by ∼1.8°C) to cause a sustained increase in ventilation and reduction in P ET ,CO2. Upon attaining hyperthermic hyperventilation, in protocol 1 (n = 10; three females) a bolus (19 ± 2 ml kg(-1) ) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to restore reductions in central venous pressure, whereas in protocol 2 (n = 11; five females) phenylephrine was infused intravenously (60-120 μg min(-1) ) to return mean arterial pressure to normothermic levels. In protocol 1, hyperthermia increased ventilation (by 2.2 ± 1.7 l min(-1) , P < 0.01), while reducing P ET ,CO2 (by 4 ± 3 mmHg, P = 0.04) and central venous pressure (by 5 ± 1 mmHg, P <0.01). Saline infusion increased central venous pressure by 5 ± 1 mmHg (P < 0.01), restoring it to normothermic values, but did not change ventilation or P ET ,CO2 (P > 0.05). In protocol 2, hyperthermia increased ventilation (by 5.0 ± 2.7 l min(-1) , P <0.01) and reduced P ET ,CO2 (by 5 ± 2 mmHg, P < 0.01) and mean arterial pressure (by 9 ± 7 mmHg, P <0.01). Phenylephrine infusion increased mean arterial pressure by 12 ± 3 mmHg (P < 0.01), restoring it to normothermic values, but did not change ventilation or P ET ,CO2 (P > 0.05). The absence of a reduction in ventilation upon reloading the cardiopulmonary and arterial baroreceptors to pre-hyperthermic levels indicates that baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Laserthermia on head and neck malignancies--experimental and clinical studies.

PubMed

Ohyama, M; Nobori, T; Moriyama, I; Furuta, S; Shima, T

1988-01-01

In recent years, remarkable progress has been made in thermotherapy. However, there is little information on localized laser hyperthermia (laserthermia) or on conventional hyperthermia technique applied to head and neck cancers. We have developed a ceramic probe to insert into tumor tissue and irradiate the Nd:YAG laser omnidirectionally. This probe can heat a spherical range of 1.5 cm to 43 degrees C. This paper concerns experimental and clinical studies on the effectiveness of laserthermia using our technique in the tumor of head and neck regions. The results obtained were as follows: histological findings and biochemical studies of arachidonic acid metabolites on normal rabbit tongue after laserthermia showed very slight effect and relatively short duration of the concomitant inflammation. The combination of laserthermia and CDDP chemotherapy was found to give a much better cytocidal effect on the tumor tissue in nude mice implanted with human thyroid cancer cells. In a clinical study on 21 cases with head and neck cancers, four cases showed complete and 13 cases showed partial remission after combined treatments of laserthermia and radiochemotherapy. Both basic experimental and clinical results have indicated a role for laserthermia in the treatment of head and neck cancer. Possible uses include the treatment of early cancer as well as advanced or recurrent cancer, where its therapeutic effect may be increased by combination with radiotherapy or chemotherapy.

Methotrexate-conjugated magnetic nanoparticles for thermochemotherapy and magnetic resonance imaging of tumor

NASA Astrophysics Data System (ADS)

Gao, Fuping; Yan, Zixing; Zhou, Jing; Cai, Yuanyuan; Tang, Jintian

2012-10-01

There is significant interest in recent years in developing magnetic nanoparticles (MNPs) having multifunctional characteristics with complimentary roles. In this study, methotrexate (MTX) was conjugated on the iron oxide magnetic nanoparticles surface via a poly(ethyleneimine) self-assembled monolayer (MTX-MNPs). The novel platform combined cancer chemotherapy, hyperthermia and potential monitoring of the progression of disease through magnetic resonance imaging (MRI). The conjugation of MTX on the magnetite surface was confirmed by Fourier transform infrared spectroscopy and change of zeta potential. Transmission electron microscope (TEM) showed that MTX-MNPs were morphologically spherical. The average diameter of MTX-MNPs was 30.1 ± 5.2 nm determined by dynamic light scattering. Magnetic measurements revealed that the saturation magnetization of MTX-MNPs reached 68.8 emu/g and the nanoparticles were superparamagnetic. The MTX-MNPs had good heating properties in an alternating magnetic field. TEM results showed that a larger number of MTX-MNPs were internalized into the MCF-7 cellular cytoplasm compared with the MNPs. The MTX-MNPs demonstrated highly synergistic antiproliferative effects of simultaneous chemotherapy and hyperthermia in MCF-7 breast cancer cells. A significant negative contrast enhancement was observed with magnetic resonance phantom imaging for MCF-7 cells over L929cells, when both were cultured with the nanoconjugate. The MTX-MNPs with combined characteristics of thermochemotherapy and MRI could be of high clinical significance in the treatment of tumor.

A PERIPHERAL CHOLINERGIC PATHWAY MODULATES STRESS-INDUCED HYPERTHERMIA IN THE RAT EXPOSED TO AN OPEN FIELD.

EPA Science Inventory

Exposure to an open-field is psychologically stressful and leads to an elevation in core temperature (Tc). This increase in Tc associated with open-field is usually referred to as stress-induced hyperthermia (SIH) and can be blocked centrally with cyclooxygenase inhibitors suc...

EFFECTS OF HYPERTHERMIA AND BORIC ACID ON SKELETAL DEVELOPMENT IN RAT EMBRYOS

EPA Science Inventory

BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have previously been reported. Both cause an increased incidence of axial skeletal defects including a decrease in the total number of ribs and vertebrae. Because of th...

Is Limb Salvage With Microwave-induced Hyperthermia Better Than Amputation for Osteosarcoma of the Distal Tibia?

PubMed

Han, Kang; Dang, Peiye; Bian, Na; Chen, Xiang; Yang, Tongtao; Fan, QingYu; Zhou, Yong; Zhao, Tingbao; Wang, Pingshan

2017-06-01

Amputation has been the standard surgical treatment for distal tibia osteosarcoma owing to its unique anatomic features. Preliminary research suggested that microwave-induced hyperthermia may have a role in treating osteosarcoma in some locations of the body (such as the pelvis), but to our knowledge, no comparative study has evaluated its efficacy in a difficult-to-treat location like the distal tibia. Does microwave-induced hyperthermia result in (1) improved survival, (2) decreased local recurrence, (3) improved Musculoskeletal Tumor Society (MSTS) scores, or (4) fewer complications than amputation in patients with a distal tibial osteosarcoma? Between 2000 and 2015, we treated 79 patients for a distal tibia osteosarcoma without metastases. Of those, 52 were treated with microwave-induced hyperthermia, and 27 with amputation. Patients were considered eligible for microwave-induced hyperthermia if they had an at least 20-mm available distance from the tumor edge to the articular surface, good clinical and imaging response to neoadjuvant chemotherapy, and no pathologic fracture. Patients not meeting these indications were treated with amputation. In addition, if neither the posterior tibial artery nor the dorsalis pedis artery was salvageable, the patients were treated with amputation and were not included in any group in this study. A total of 13 other patients were treated with conventional limb-salvage resections and reconstructions (at the request of the patient, based on patient preference) and were not included in this study. All 79 patients in this retrospective study were available for followup at a minimum of 12 months (mean followup in the hyperthermia group, 79 months, range 12-158 months; mean followup in the amputation group, 95 months, range, 15-142 months). With the numbers available, the groups were no different in terms of sex, age, tumor grade, tumor stage, or tumor size. All statistical tests were two-sided, and a probability less than 0.05 was considered statistically significant. Survival to death was evaluated using Kaplan-Meier analysis. Complications were recorded from the patients' files and graded using the classification of surgical complications described by Dindo et al. In the limb-salvage group, Kaplan Meier survival at 6 years was 80% (95% CI, 63%-90%), and this was not different with the numbers available from survivorship in the amputation group at 6 years (70%; 95% CI, 37%-90%; p = 0.301).With the numbers available, we found no difference in local recurrence (six versus 0; p = 0.066). However mean ± SD MSTS functional scores were higher in patients who had microwave-induced hyperthermia compared with those who had amputations (85% ± 6% versus 66% ± 5%; p = 0.008).With the numbers available, we found no difference in the proportion of patients experiencing complications between the two groups (six of 52 [12%] versus three of 27 [11%]; p = 0.954). We were encouraged to find no early differences in survival, local recurrence, or serious complications between microwave-induced hyperthermia and amputation, and a functional advantage in favor of microwave-induced hyperthermia. However, these findings should be replicated in larger studies with longer mean duration of followup, and in studies that compare microwave-induced hyperthermia with conventional limb-sparing approaches. Level III, therapeutic study.

A rat model of spontaneous myopathy and malignant hyperthermia.

PubMed Central

Gonzalez, L. E.; Meléndez-Vásquez, C. V.; Gregson, N. A.; File, S. E.

1998-01-01

Malignant hyperthermia is a main cause of death during general anesthesia, particularly in children. However, research has been hampered by the lack of a convenient animal model, the only one available being a special strain of pig. In this study, we describe spontaneous myopathy and a fatal syndrome of generalized muscle rigidity triggered by halothane in an outbred strain of rat. Histological examination of skeletal muscle reveals severe abnormalities indicating chronic underlying myopathy. The association of histological abnormalities with an acute, fatal syndrome clinically resembling malignant hyperthermia provides a strong basis for a new and extremely useful animal model to study this fatal disorder. Images Figure 1 Figure 2 PMID:9546371

Clinical applications of magnetic nanoparticles for hyperthermia.

PubMed

Thiesen, Burghard; Jordan, Andreas

2008-09-01

Magnetic fluids are increasingly used for clinical applications such as drug delivery, magnetic resonance imaging and magnetic fluid hyperthermia. The latter technique that has been developed as a cancer treatment for several decades comprises the injection of magnetic nanoparticles into tumors and their subsequent heating in an alternating magnetic field. Depending on the applied temperature and the duration of heating this treatment either results in direct tumor cell killing or makes the cells more susceptible to concomitant radio- or chemotherapy. Numerous groups are working in this field worldwide, but only one approach has been tested in clinical trials so far. Here, we summarize the clinical data gained in these studies on magnetic fluid induced hyperthermia.

Thermal potentiation of chemotherapy by magnetic nanoparticles

PubMed Central

Torres-Lugo, Madeline; Rinaldi, Carlos

2014-01-01

Clinical studies have demonstrated the effectiveness of hyperthermia as an adjuvant for chemotherapy and radiotherapy. However, significant clinical challenges have been encountered, such as a broader spectrum of toxicity, lack of patient tolerance, temperature control and significant invasiveness. Hyperthermia induced by magnetic nanoparticles in high-frequency oscillating magnetic fields, commonly termed magnetic fluid hyperthermia, is a promising form of heat delivery in which thermal energy is supplied at the nanoscale to the tumor. This review discusses the mechanisms of heat dissipation of iron oxide-based magnetic nanoparticles, current methods and challenges to deliver heat in the clinic, and the current work related to the use of magnetic nanoparticles for the thermal-chemopotentiation of therapeutic drugs. PMID:24074390

Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report.

PubMed

Huo, Wei; Di, Zheng-Hong; Xiao, Bi-Huan; Qi, Rui-Qun; Weiland, Matthew; Gao, Xing-Hua

2014-01-01

Genital warts acquired during pregnancy tend to grow fast, and management is challenging. We treated two cases of primipara with extensive genital warts by local hyperthermia at 44°C for 30 minutes a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical regression. The warty lesions in the patients resolved in 5 and 7 weeks, respectively. There was no sign of recurrence during a 6-month follow-up. This suggests that local hyperthermia seems to be a promising method for treating genital warts in pregnant women. © 2013 China Medical University. ; Dermatologic Therapy © 2013 Wiley Periodicals, Inc.

A study of effects of hyperthermia on large, short-haired male dogs : a simulated air transport environmental stress.

DOT National Transportation Integrated Search

1977-03-01

When dogs are shipped by air transport, they can encounter environmental temperatures as high as 130.0 F during the summer months. Heat- induced hyperthermia can be a major problem in dogs. : To assess some aspects of the heat stress problem, 20 dogs...

Delaware Consortium for Undergraduate Minority Training in Prostate Cancer

DTIC Science & Technology

2008-02-01

Nanoparticle Hyperthermia Induced Wound-Healing Assay in Prostate Cancer Cells. Adaire T. Heady, Michael J. Bonder, Ph.D., David J. DeGraff, M.S., Robert...6 Development of Magnetic Nanoparticle Hyperthermia ...George C. Hadjipanayis, Ph.D., Delaware State University, Dover, DE, USA, University of Delaware, Neware, DE, USA The use of magnetic nanoparticle

Intra-operative hyperthermia in a young Angus bull with a fatal outcome.

PubMed

Skelding, Alicia; Valverde, Alexander

2017-06-01

A healthy, 9-month-old black Angus bull was presented for elective penile-preputial translocation and caudal epididymectomy. After premedication and induction, general anesthesia was maintained with inhalant anesthetic. Over an hour into the anesthetic period the bull developed severe hyperthermia and hypercapnia that resulted in fatality despite treatment efforts.

High permittivity patch radiator for single and multi-element hyperthermia applicators.

PubMed

Andreuccetti, D; Bini, M; Ignesti, A; Olmi, R; Priori, S; Vanni, R

1993-07-01

This paper describes a compact, low-profile patch radiator which is the base element for efficient, small-size applicators suitable for superficial hyperthermia. The design criteria and the technological processes involved are presented. The electromagnetic characteristics of the patch element are outlined, and possible application of the radiator are discussed.

Calcific tendinopathy of the rotator cuff. Conservative management with 434 Mhz local microwave diathermy (hyperthermia): a case study.

PubMed

Di Cesare, Annalisa; Giombini, Arrigo; Dragoni, Stefano; Agnello, Luciano; Ripani, Maurizio; Saraceni, Vincenzo Maria; Maffulli, Nicola

2008-01-01

To report the effects of local microwave diathermy (hyperthermia) at 434 Mhz on calcific tendinopathy of the shoulder in two middle aged patients. Two middle-aged women with calcific tendinopathy of the shoulder were treated with local microwave diathermy (hyperthermia) at 434 Mhz three times a week for four weeks. Plain radiographs and ultrasonography demonstrated calcific deposits in the area of infraspinatus or supraspinatus. Shoulder Pain and Disability Index (SPADI) and passive Range of Motion (ROM) were used to assess the response to treatment. At the end of the treatment period, the improvement as measured by the SPADI score was respectively 30% for the first patient and 40% for the second patient with an improvement of the shoulder passive ROM for both patients. The calcific deposits seen on the initial radiographs and ultrasonography were no longer visible. At 1 year follow-up, both patients continued to be symptom free. Hyperthermia is a safe option in the management of calcific tendinopathy of the shoulder. Prospective randomized controlled studies with long term assessment are needed to further document its therapeutic efficacy.

Effect of tumor properties on energy absorption, temperature mapping, and thermal dose in 13.56-MHz radiofrequency hyperthermia.

PubMed

Prasad, Bibin; Kim, Subin; Cho, Woong; Kim, Suzy; Kim, Jung Kyung

2018-05-01

Computational techniques can enhance personalized hyperthermia-treatment planning by calculating tissue energy absorption and temperature distribution. This study determined the effect of tumor properties on energy absorption, temperature mapping, and thermal dose distribution in mild radiofrequency hyperthermia using a mouse xenograft model. We used a capacitive-heating radiofrequency hyperthermia system with an operating frequency of 13.56 MHz for in vivo mouse experiments and performed simulations on a computed tomography mouse model. Additionally, we measured the dielectric properties of the tumors and considered temperature dependence for thermal properties, metabolic heat generation, and perfusion. Our results showed that dielectric property variations were more dominant than thermal properties and other parameters, and that the measured dielectric properties provided improved temperature-mapping results relative to the property values taken from previous study. Furthermore, consideration of temperature dependency in the bio heat-transfer model allowed elucidation of precise thermal-dose calculations. These results suggested that this method might contribute to effective thermoradiotherapy planning in clinics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Localized thermo-cisplatin therapy: a pilot study in spontaneous canine and feline tumours.

PubMed

Théon, A P; Madewell, B R; Moore, A S; Stephens, C; Krag, D N

1991-01-01

Local hyperthermia combined with intralesional cisplatin chemotherapy is a logical and potentially effective therapeutic approach for localized cancers. A trial using outbred animals with spontaneously occurring tumours was initiated to evaluate the toxicity and efficacy of this approach. Treatment consisted of injection of a colloidal suspension of cisplatin into the tumour prior to hyperthermia once a week for 4 weeks. Immediately after intratumoral injection of a mixture of cisplatin and collagen, thermotherapy was given. The goal temperature was 42 +/- 1 degrees C for 30 min. Ten animals (nine dogs and one cat) with soft tissue neoplasms were treated with one to four hyperthermia and cisplatin sessions for a total of 30 treatment sessions. Complete responses occurred in 4/10 cases (one carcinoma, two sarcomas, one melanoma). One dog with haemangiopericytoma had partial response. The lack of systemic toxicity and the minimal local normal tissue reactions indicate that the treatments were well tolerated. These data provide preliminary evidence that a combination of local hyperthermia and intratumoral cisplatin chemotherapy is a safe and effective method for the treatment of selected localized neoplasms.

The in vivo performance of biomagnetic hydroxyapatite nanoparticles in cancer hyperthermia therapy.

PubMed

Hou, Chun-Han; Hou, Sheng-Mou; Hsueh, Yu-Sheng; Lin, Jinn; Wu, Hsi-Chin; Lin, Feng-Huei

2009-08-01

Hyperthermia therapy for cancer has drawn more and more attention these days. In this study, we conducted an in vivo cancer hyperthermia study of the new magnetic hydroxyapatite nanoparticles by a mouse model. The magnetic hydroxyapatite nanoparticles were first made by co-precipitation method with the addition of Fe(2+). Then, magnetic-HAP powder (mHAP) or pure HAP powder (HAP) was mixed with phosphate buffer solution (PBS), respectively. The mixture was injected around the tumor. In order to achieve hyperthermia, the mice were placed into an inductive heater with high frequency and alternating magnetic field. Only the mice which were injected with mHAP and had been treated inside the magnetic field showed dramatic reduction of tumor volume, in the 15-day observation period. No local recurrence was noted. The blood test of mice proved that mHAP powders possessed good biocompatibility and little toxicity when injected subcutaneously. Therefore, our new magnetic hydroxyapatite nanoparticles have demonstrated therapeutic effect in a mouse model with little toxicity. Further study should be done before its application inside the human body.

Targeted Delivery of Hyaluronan-Immobilized Magnetic Ceramic Nanocrystals.

PubMed

Wu, Hsi-Chin; Wang, Tzu-Wei; Hsieh, Shun-Yu; Sun, Jui-Sheng; Kang, Pei-Leun

2016-01-01

Effective cancer therapy relies on delivering the therapeutic agent precisely to the target site to improve the treatment outcome and to minimize side effects. Although surgery, chemotherapy, and radiotherapy are the standard methods commonly used in clinics, hyperthermia has been developed as a new and promising strategy for cancer therapy. In this study, magnetic bioceramic hydroxyapatite (mHAP) nanocrystals have been developed as heat mediator for intracellular hyperthermia. Hyaluronic acid (HA) modified mHAP nanocrystals are synthesized by a wet chemical precipitation process to achieve active targeting. The results demonstrate that the HA targeting moiety conjugated by a poly(ethylene glycol) (PEG) spacer arm is successfully immobilized on the surface of mHAP. The HA-modified mHAP possesses relatively good biocompatibility, an adequate biodegradation rate and superparamagnetic properties. The HA-modified mHAP could be localized and internalized into HA receptor-overexpressed malignant cells (e.g., MDA-MB-231 cell) and used as the heat generating agent for intracellular hyperthermia. The results from this study indicate that biocompatible HA-modified mHAP shows promise as a novel heat mediator and a specific targeting nanoagent for intracellular hyperthermia cancer therapy.

Hyperthermia phased arrays pre-treatment evaluation.

PubMed

Bardati, Fernando; Tognolatti, Piero

2016-12-01

In the hyperthermia treatment of deep-seated tumours by a phased array of radiofrequency (RF) antennas, heatability will be investigated in terms of power-to-tumour and other figures-of-merit of hyperthermia treatments to be optimised. The assumption is that each source is individually constrained to not exceed a maximal nominal power. The nominal power may differ from a source to another as a physical limit or an operative modality. Under such constraint, new procedures for the maximisation of (i) power-to-tumour, (ii) heating efficiency and, in general, (iii) power ratios as tumour-heating selectivity are proposed. (iv) The problem whether a tumour is equally heatable after turning off some antennas is addressed as array thinning. An array of eight dipoles arranged on two lines around a head/neck is introduced to perform a numerical analysis. The achievable power-to-tumour according to the new optimizations and other performance indices adopted from the literature is tested against values of power that can be found to be sufficient for heating tumours to clinical temperatures. New solutions to data rendering in hyperthermia heating are proposed.

Ultrasonic phased array controller for hyperthermia applications.

PubMed

Benkeser, P J; Pao, T L; Yoon, Y J

1991-01-01

Multiple and mechanically scanned ultrasound transducer systems have demonstrated the efficacy of using ultrasound to produce deep localized hyperthermia. The use of ultrasonic phased arrays has been proposed as an alternative to these systems. A phased array offers a more flexible approach to heating tumours in that the size, shape, and position of its focal region can be altered during the course of treatment in order to achieve the desired temperature distribution. This added flexibility comes at the cost of increased complexity of the hardware necessary to drive the transducer because each element requires its own amplifer with both phase and amplitude control. In order for phased arrays with large numbers of elements to be feasible for hyperthermia applications, the complexity of this circuitry must be minimized. This paper describes a circuit design which simplifies the electronics required to control a phased array transducer system for hyperthermia applications. The design is capable of controlling virtually any type of phased array transducer operating at frequencies less than 2 MHz. The system performance was verified through beam profile measurements using a 48-element tapered phased array transducer.

In-vivo optical molecular imaging for laser hyperthermia

NASA Astrophysics Data System (ADS)

Zeng, Shaoqun; Zhang, Zhihong; Zhou, Wei; Luo, Qingming

2002-04-01

Green fluorescent protein (GFP) transfected Hela cell was planted in naked mice, to construct an in vivo model for monitoring the therapeutic effect of laser hyperthermia in real time. A cooled CCD fluorescence imaging system was used to record the tumor fluorescence image during the hyperthermia process. Primary experimental results were presented in this paper. To make sure the fluorescent probe GFP does not have strong effect on the biologic function of the host tumor cell (Hela cell), several conventional biological processes were observed in real time. First, neurons, which are much more tender than tumor cells, were transfected with GFP (cameleons). No morphological inhomogenities were observed, and normal functional responses of the neurons were observed when stimulated with histamine. In the second step, the mitosis process of cultured Hela cell was monitored. The features observed during mitosis confirmed that the transfection does not ruin the mitosis process of the tumor cell. At last, naked mice with tumor cell was constructed, which emit fluorescence in the tumor region when excited with faint laser. This presentation provides an in vivo biological model for quick monitoring of the therapeutic results of tumor hyperthermia.

Modeling the heat transfer problem for the novel combined cryosurgery and hyperthermia system.

PubMed

Zhao, Gang; Bai, Xue-Fei; Luo, Da-Wei; Gao, Da-Yong

2006-01-01

A multidimensional, finite element analysis (FEA) for the freezing, holding, rewarming and heating processes of biological tissues during the cryosurgery process of the new Combined Cryosurgery/Hyperthermia System is presented to theoretically test its validity. The tissues are treated as nonideal materials freezing over a temperature range, and the thermophysical properties of which are temperature dependent. The enthalpy method is applied to solve the highly nonlinear problem. It was found that when the same boundary condition and the same target tissue presented, the novel Cryosurgery/Hyperthermia System could supply the target tissue an approximative cooling rate, a much lower minimal temperature, a much greater warming rate, and a much greater thermal gradients compared with that of the simplified Endocare system. The numerical simulation indicates that the novel combined cryosurgery and hyperthermia system can provide an excellent curative effect in the corresponding cryotherapy. And the most attractive feature of this FEA framework is that it can be easily mastered by the surgeon without in-depth theory of heat transfer to analyze the cryosurgery process beforehand due to the friendly GUI (graphical user interface) of Ansys software.

Body temperature changes are associated with outcomes following in-hospital cardiac arrest and return of spontaneous circulation.

PubMed

Suffoletto, Brian; Peberdy, Mary Anne; van der Hoek, Terry; Callaway, Clifton

2009-12-01

Spontaneous changes in body temperature after return of circulation (ROSC) from cardiac arrest are common, but the association of these changes with outcomes in hospitalized patients who survive to 24h post-ROSC is not known. We tested the hypothesis that adults who experience temperature lability in the first 24h have worse outcomes compared with those who maintain normothermia. A prospective observational study from a multicenter registry of cardiac arrests (National Registry of Cardiopulmonary Resuscitation) from 355 US and Canadian hospitals. 14,729 adults with return of circulation from a pulseless cardiac arrest. We excluded those who died or were discharged before 24h post-event, those made Do-Not-Resuscitate (DNR) within 24h of event, those that had a preceding trauma, and those with multiple cardiac arrests. Finally, we included only subjects that had both a lowest (T(min)) and highest (T(max)) body temperature value recorded during the first 24-h after ROSC, resulting in a study sample of 3426 patients. After adjustment for potential covariates, there was a lower odds of survival in those having an episode of hypothermia (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.48-0.80), those having an episode of hyperthermia (OR, 0.67; 95% CI, 0.48-0.80), and those having an episode of both (OR, 0.59; 95% CI, 0.39-0.91). Among those who survived to discharge, there was also a lower odds of favorable neurologic performance in those who had an episode of hyperthermia (OR, 0.71; 95% CI, 0.51-0.98). Episodes of temperature lability following in-hospital resuscitation from cardiac arrest are associated with lower odds of surviving to discharge. Hyperthermia is also associated with fewer patients leaving the hospital with favorable neurologic performance. Further studies should identify whether therapeutic control over changes in body temperature after in-hospital cardiac arrest improves outcomes.

Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement Disorder in Progressed Stages of Late-Infantile CLN2 Disease.

PubMed

Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas

2016-06-01

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. Georg Thieme Verlag KG Stuttgart · New York.

Prolonged environment-induced hyperthermia alters autophagy in oxidative skeletal muscle in Sus scrofa.

PubMed

Ganesan, Shanthi; Brownstein, Alexandra J; Pearce, Sarah C; Hudson, Matthew B; Gabler, Nicolas K; Baumgard, Lance H; Rhoads, Robert P; Selsby, Joshua T

2018-05-01

Prolonged heat stress represents a continuing threat to human health and agricultural production. Despite the broad, negative impact of prolonged hyperthermia little is known about underlying pathological mechanisms leading to negative health outcomes, which has limited the development of etiological interventions and left clinicians and producers with only cooling and rehydration strategies. The purpose of this investigation was to determine the extent to which prolonged environment-induced hyperthermia altered autophagy in oxidative skeletal muscle in a large animal model, serving the dual purpose of accurately modeling human physiology as well as agricultural production. We hypothesized that prolonged hyperthermia would induce autophagy in skeletal muscle, independent of the accompanying caloric restriction. To test this hypothesis pigs were treated as follows: thermoneutral (20 °C), heat stress (35 °C), or were held under thermoneutral conditions but pair-fed to the heat stress group for seven days. Upon euthanasia the red portion of the semitendinosus was collected. We found that prolonged hyperthermic exposure increased oxidative stress without a corresponding change in antioxidant enzyme activities. Hyperthermia prevented initiation of autophagy despite increased markers of nucleation, elongation and autophagosome formation. However, p62 relative protein abundance, which is inversely correlated with autophagic degradation, was strongly increased suggesting suppressed degradation of autophagosomes. Markers of mitophagy and mitochondrial abundance were largely similar between groups. These data indicate that faulty autophagy plays a key role in hyperthermic muscle dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hyperthermia increases accumulation of technetium-99m-labeled liposomes in feline sarcomas.

PubMed

Matteucci, M L; Anyarambhatla, G; Rosner, G; Azuma, C; Fisher, P E; Dewhirst, M W; Needham, D; Thrall, D E

2000-09-01

The effect of hyperthermia on the accumulation of technetium-99m-labeled liposomes was studied in feline sarcomas. Each cat received two separate injections of liposomes. The first was used to quantify the amount of technetium-99m-labeled liposomes within the tumor under normothermic conditions. The second injection was made at the beginning of a 60-min hyperthermia procedure. Planar scintigraphy was used to measure the activity of technetium-99m-labeled liposomes within the tumor at predetermined times up to 18 h after injection. Regions of interest were drawn for the tumor, lungs, liver, kidney, and aorta. Counts in the regions of interest were decay corrected. Counts/pixel in the tumor under normothermic and hyperthermic conditions were normalized to aorta counts/pixel. A total of 16 cats were eligible for the study. In two of the 16 cats, incomplete count data precluded analysis. In the remaining 14 cats, hyperthermia resulted in a significant increase in liposome accumulation in the tumor (P = 0.001). Tumor volume ranged from 1.2 to 236.2 cm3, and thermal dose ranged from 2.0 to 243.3 CEM43CT90 (equivalent time that the 10th percentile temperature was equal to 43 degrees C). There was not a relationship between either tumor volume or hyperthermia dose on the magnitude of increased liposome accumulation, suggesting that this method has application across a range of tumor volumes and degrees of heatibility.

Acute whole-body cooling for exercise-induced hyperthermia: a systematic review.

PubMed

McDermott, Brendon P; Casa, Douglas J; Ganio, Matthew S; Lopez, Rebecca M; Yeargin, Susan W; Armstrong, Lawrence E; Maresh, Carl M

2009-01-01

To assess existing original research addressing the efficiency of whole-body cooling modalities in the treatment of exertional hyperthermia. During April 2007, we searched MEDLINE, EMBASE, Scopus, SportDiscus, CINAHL, and Cochrane Reviews databases as well as ProQuest for theses and dissertations to identify research studies evaluating whole-body cooling treatments without limits. Key words were cooling, cryotherapy, water immersion, cold-water immersion, ice-water immersion, icing, fanning, bath, baths, cooling modality, heat illness, heat illnesses, exertional heatstroke, exertional heat stroke, heat exhaustion, hyperthermia, hyperthermic, hyperpyrexia, exercise, exertion, running, football, military, runners, marathoner, physical activity, marathoning, soccer, and tennis. Two independent reviewers graded each study on the Physiotherapy Evidence Database (PEDro) scale. Seven of 89 research articles met all inclusion criteria and a minimum score of 4 out of 10 on the PEDro scale. After an extensive and critical review of the available research on whole-body cooling for the treatment of exertional hyperthermia, we concluded that ice-water immersion provides the most efficient cooling. Further research comparing whole-body cooling modalities is needed to identify other acceptable means. When ice-water immersion is not possible, continual dousing with water combined with fanning the patient is an alternative method until more advanced cooling means can be used. Until future investigators identify other acceptable whole-body cooling modalities for exercise-induced hyperthermia, ice-water immersion and cold-water immersion are the methods proven to have the fastest cooling rates.

Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

PubMed Central

Yang, Rui; Tang, Qiusha; Miao, Fengqin; An, Yanli; Li, Mengfei; Han, Yong; Wang, Xihui; Wang, Juan; Liu, Peidang; Chen, Rong

2015-01-01

Purpose To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods CD90+ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results CD90+ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90+ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia. Conclusion The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo. PMID:26677324

Barium titanate core--gold shell nanoparticles for hyperthermia treatments.

PubMed

FarrokhTakin, Elmira; Ciofani, Gianni; Puleo, Gian Luigi; de Vito, Giuseppe; Filippeschi, Carlo; Mazzolai, Barbara; Piazza, Vincenzo; Mattoli, Virgilio

2013-01-01

The development of new tools and devices to aid in treating cancer is a hot topic in biomedical research. The practice of using heat (hyperthermia) to treat cancerous lesions has a long history dating back to ancient Greece. With deeper knowledge of the factors that cause cancer and the transmissive window of cells and tissues in the near-infrared region of the electromagnetic spectrum, hyperthermia applications have been able to incorporate the use of lasers. Photothermal therapy has been introduced as a selective and noninvasive treatment for cancer, in which exogenous photothermal agents are exploited to achieve the selective destruction of cancer cells. In this manuscript, we propose applications of barium titanate core-gold shell nanoparticles for hyperthermia treatment against cancer cells. We explored the effect of increasing concentrations of these nanoshells (0-100 μg/mL) on human neuroblastoma SH-SY5Y cells, testing the internalization and intrinsic toxicity and validating the hyperthermic functionality of the particles through near infrared (NIR) laser-induced thermoablation experiments. No significant changes were observed in cell viability up to nanoparticle concentrations of 50 μg/mL. Experiments upon stimulation with an NIR laser revealed the ability of the nanoshells to destroy human neuroblastoma cells. On the basis of these findings, barium titanate core-gold shell nanoparticles resulted in being suitable for hyperthermia treatment, and our results represent a promising first step for subsequent investigations on their applicability in clinical practice.

Barium titanate core – gold shell nanoparticles for hyperthermia treatments

PubMed Central

FarrokhTakin, Elmira; Ciofani, Gianni; Puleo, Gian Luigi; de Vito, Giuseppe; Filippeschi, Carlo; Mazzolai, Barbara; Piazza, Vincenzo; Mattoli, Virgilio

2013-01-01

The development of new tools and devices to aid in treating cancer is a hot topic in biomedical research. The practice of using heat (hyperthermia) to treat cancerous lesions has a long history dating back to ancient Greece. With deeper knowledge of the factors that cause cancer and the transmissive window of cells and tissues in the near-infrared region of the electromagnetic spectrum, hyperthermia applications have been able to incorporate the use of lasers. Photothermal therapy has been introduced as a selective and noninvasive treatment for cancer, in which exogenous photothermal agents are exploited to achieve the selective destruction of cancer cells. In this manuscript, we propose applications of barium titanate core–gold shell nanoparticles for hyperthermia treatment against cancer cells. We explored the effect of increasing concentrations of these nanoshells (0–100 μg/mL) on human neuroblastoma SH-SY5Y cells, testing the internalization and intrinsic toxicity and validating the hyperthermic functionality of the particles through near infrared (NIR) laser-induced thermoablation experiments. No significant changes were observed in cell viability up to nanoparticle concentrations of 50 μg/mL. Experiments upon stimulation with an NIR laser revealed the ability of the nanoshells to destroy human neuroblastoma cells. On the basis of these findings, barium titanate core–gold shell nanoparticles resulted in being suitable for hyperthermia treatment, and our results represent a promising first step for subsequent investigations on their applicability in clinical practice. PMID:23847415

THC Prevents MDMA Neurotoxicity in Mice.

PubMed

Touriño, Clara; Zimmer, Andreas; Valverde, Olga

2010-02-10

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4) were pretreated with THC (3 mg/kg x 4) at room (21 degrees C) and at warm (26 degrees C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1) receptor antagonist AM251 and the CB(2) receptor antagonist AM630, as well as in CB(1), CB(2) and CB(1)/CB(2) deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1) receptor antagonist AM251, neither in CB(1) and CB(1)/CB(2) knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2) cannabinoid antagonist and in CB(2) knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1) receptor, although CB(2) receptors may also contribute to attenuate neuroinflammation in this process.

THC Prevents MDMA Neurotoxicity in Mice

PubMed Central

Touriño, Clara; Zimmer, Andreas; Valverde, Olga

2010-01-01

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg ×4) were pretreated with THC (3 mg/kg ×4) at room (21°C) and at warm (26°C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB1 receptor antagonist AM251 and the CB2 receptor antagonist AM630, as well as in CB1, CB2 and CB1/CB2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB1 receptor antagonist AM251, neither in CB1 and CB1/CB2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB2 cannabinoid antagonist and in CB2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB1 receptor, although CB2 receptors may also contribute to attenuate neuroinflammation in this process. PMID:20174577

Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakker, Akke, E-mail: akke.bakker@amc.uva.nl; Kolff, M. Willemijn; Holman, Rebecca

Purpose: To investigate the relationship of thermal skin damage (TSD) to time–temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. Methods and Materials: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Results: Sixty-eight patients (26%) developed 79more » sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. Conclusion: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time–temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.« less

Thermal therapy of pancreatic tumors using endoluminal ultrasound: parametric and patient-specific modeling

PubMed Central

Adams, Matthew S.; Scott, Serena J.; Salgaonkar, Vasant A.; Sommer, Graham; Diederich, Chris J.

2016-01-01

Purpose To investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumors using 3D acoustic and biothermal finite element models. Materials and Methods Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1–5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumor models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (>240 EM43°C) and moderate hyperthermia (40–45 °C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70–80 °C for ablation and 45 °C for hyperthermia in target regions. Results Parametric studies indicated that 1–3 MHz planar transducers are most suitable for volumetric ablation, producing 5–8 cm3 lesion volumes for a stationary 5 minute sonication. Curvilinear-focused geometries produce more localized ablation to 20–45 mm depth from the GI tract and enhance thermal sparing (Tmax<42 °C) of the luminal wall. Patient anatomy simulations show feasibility in ablating 60.1–92.9% of head/body tumor volumes (4.3–37.2 cm3) with dose <15 EM43°C in the luminal wall for 18–48 min treatment durations, using 1–3 applicator placements in GI lumen. For hyperthermia, planar and radial-diverging transducers could maintain up to 8 cm3 and 15 cm3 of tissue, respectively, between 40–45 °C for a single applicator placement. Conclusions Modeling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumor tissue. PMID:27097663

Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique.

PubMed

Johannsen, M; Gneveckow, U; Eckelt, L; Feussner, A; Waldöfner, N; Scholz, R; Deger, S; Wust, P; Loening, S A; Jordan, A

2005-11-01

The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0-18 kA m(-1)). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0-5.0 kA m(-1) were 48.5 degrees C and 40.0 degrees C during the 1st treatment and 42.5 degrees C and 39.4 degrees C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors' knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.

Rapid cooling after acute hyperthermia alters intestinal tissue morphology and increases the systemic inflammatory response in pigs

USDA-ARS?s Scientific Manuscript database

Acute hyperthermia can result in mortality if recovery is not appropriately managed. The study objective was to determine the effects of heatstroke recovery methods on the physiological response in pigs. In four repetitions, 36 male pigs (88.7 ± 1.6 kg BW) were exposed to thermoneutral conditions (T...

An Acremonium endophyte of Lolium perenne associated with hyperthermia of cattle in Pacific County, Washington

Treesearch

A. D. Wilson; C.C. Gay; S.C. and Fransen

1992-01-01

Clavicipitaceous endophytes are well known for causing maladies of livestock. Recent studies of a new syndrome causing hyperthermia of cattle in Pacific County, Washington, prompted surveys of endophytes in pasture grasses of seven affected paddocks. Cattle removed from affected pastures and fed alfalfa became normothermic within 3 days, suggesting a pyrogenic factor...

THE EFFECTS OF HYPERTHERMIA ON SPERMATOGENESIS, APOPTOSIS, GENE EXPRESSION AND FERTILITY IN ADULT MALE MICE

EPA Science Inventory

The effects of hyperthermia on spermatogenesis, apoptosis, gene expression and fertility in adult male mice
John C. Rockett1, Faye L. Mapp1, J. Brian Garges1, J. Christopher Luft1, Chisato Mori2 and David J. Dix1.
1Reproductive Toxicology Division, National Health and Envir...

Novel Interventions for Heat/Exercise Induced Sudden Death and Fatigue

DTIC Science & Technology

2013-10-01

mutations associated with enhanced susceptibility to Exertional Heat Stroke (EHS), Exertional Rhabdomyolysis (ER), and Malignant Hyperthermia (MH) by...reduces the probability of a hypermetabolic response in YS mice. 15. SUBJECT TERMS: Exertional Heat Stroke, Exertional Rhabdomyolysis ...and exertional rhabdomyolysis (ER) have been reported in subjects with diagnosis of Malignant Hyperthermia (MH). MH is a life- threatening

A microangiographic study of the effect of hyperthermia on the rabbit bladder

NASA Technical Reports Server (NTRS)

Hietala, S. O.; Howells, R.; Hazra, I. A.

1978-01-01

A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

The effect of hyperthermia on the radiation response of crypt cells in mouse jejunum

NASA Technical Reports Server (NTRS)

Wilson, J. D.

1978-01-01

The effect of hyperthermia and/or gamma-radiation on the survival of intestinal crypt cells was studied in BDF sub 1 mice using a microcolony assay. Hyperthermia treatments, which in themselves caused no detectable cell lethality, inhibited the capacity of crypt cells to repair sublethal radiation damage. In addition, heat applied either before or after single radiation exposures potentiated lethal damage to crypt cells; the degree of enhancement was dependent on the time interval between treatments. At the levels of heating employed, DNA synthesis in the intestinal epithelium was significantly reduced immediately following exposure, but returned rapidly to normal levels. No further disturbances in cellular kinetics were observed for up to 10 days after heating.

Heating characteristics of the TRIPAS hyperthermia system for deep seated malignancy.

PubMed

Surowiec, A; Bicher, H I

1995-01-01

A deep heating hyperthermia device TRIPAS (a triapplicator system) consisting of three independent, dielectrically loaded horn applicators operating in phase at 300 MHz was investigated. The heating characteristics produced by this hyperthermia system were analyzed by means of thermochromic liquid-crystal cards and a modified CDRH (Center for Devices and Regulatory Health) elliptical phantom. Both homogenous and inhomogeneous phantoms were used, simulating high and low permittivity tissues (muscle and lung). These equivalent tissues were made of polyacrylamide gel. The semiquantitative heating pattern analysis showed a central heating of 1/3 of maximum heating at a depth of 10 cm in both homogenous (muscle) and heterogenous (muscle/fat) phantoms. Also more uniform temperature/SAR distributions were generated in muscle equivalent material than those in lung.

Triple Therapy of HER2+ Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.

PubMed

Zolata, Hamidreza; Afarideh, Hossein; Davani, Fereydoun Abbasi

2016-11-01

By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2 + cells and tumor (HER2 + )-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3) 111 In-labeled, antibody-conjugated surface-modified SPIONs; and (4) 111 In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.

Physical exercise-induced changes in the core body temperature of mice depend more on ambient temperature than on exercise protocol or intensity

NASA Astrophysics Data System (ADS)

Wanner, Samuel Penna; Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Cardoso, Valbert Nascimento; Coimbra, Cândido Celso

2014-08-01

The mechanisms underlying physical exercise-induced hyperthermia may be species specific. Therefore, the present study aimed to investigate the effects of exercise intensity and ambient temperature on the core body temperature ( T core) of running mice, which provide an important experimental model for advancing the understanding of thermal physiology. We evaluated the influence of different protocols (constant- or incremental-speed exercises), treadmill speeds and ambient temperatures ( T a) on the magnitude of exercise-induced hyperthermia. To measure T core, a telemetric sensor was implanted in the abdominal cavity of male adult Swiss mice under anesthesia. After recovering from the surgery, the animals were familiarized to running on a treadmill and then subjected to the different running protocols and speeds at two T a: 24 °C or 34 °C. All of the experimental trials resulted in marked increases in T core. As expected, the higher-temperature environment increased the magnitude of running-induced hyperthermia. For example, during incremental exercise at 34 °C, the maximal T core achieved was increased by 1.2 °C relative to the value reached at 24 °C. However, at the same T a, neither treadmill speed nor exercise protocol altered the magnitude of exercise-induced hyperthermia. We conclude that T core of running mice is influenced greatly by T a, but not by the exercise protocols or intensities examined in the present report. These findings suggest that the magnitude of hyperthermia in running mice may be regulated centrally, independently of exercise intensity.

Arrhenius thermodynamics and birth defects: chemical teratogen synergy. Untested, testable, and projected relevance.

PubMed

Miller, Morton W; Church, Charles C

2013-03-01

This article addresses the issue of hyperthermia-induced birth defects with an accompanying additional teratogen, be it a chemical or a physical agent (i.e., a simultaneous "combinational" exposure to two teratogens, one of which is hyperthermia). Hyperthermia per se is a recognized human and animal teratogen. An excellent example of such combinational exposures is an epileptic woman who becomes pregnant while taking valproic acid (VPA) to control seizures. VPA is a recognized chemical teratogen, and fever (hyperthermia) is not an uncommon event during pregnancy. While VPA also may occasionally induce fever as a side effect, we are concerned here with fevers arising from other, unrelated causes. There is a small but internally consistent literature on these combinational-teratogen exposures involving hyperthermia plus a chemical teratogen; in each instance, the effect level has been observed to be synergistically elevated above levels induced by the separate teratogenic components. The data were empirical. The observed synergy is, however, consistent with Arrhenius thermodynamics, a well-known chemical rate equation. The need for information about combinational teratogen exposures is acute; fever is a common occurrence during pregnancy; and there are many instances whereby there is also the simultaneous presence of some other teratogen(s). Given that the rate of autism spectrum disorders in the United States was recently presented as 1 in 88 births, it seems reasonable to suspect that such combinational regimens are much more prevalent than previously thought. Our hypothesis is that synergistic birth defect levels from combinational regimens are consistent with Arrhenius thermodynamics. Copyright © 2013 Wiley Periodicals, Inc.

Functional studies of RYR1 mutations in the skeletal muscle ryanodine receptor using human RYR1 complementary DNA.

PubMed

Sato, Keisaku; Pollock, Neil; Stowell, Kathryn M

2010-06-01

Malignant hyperthermia is associated with mutations within the gene encoding the skeletal muscle ryanodine receptor, the calcium channel that releases Ca from sarcoplasmic reticulum stores triggering muscle contraction, and other metabolic activities. More than 200 variants have been identified in the ryanodine receptor, but only some of these have been shown to functionally affect the calcium channel. To implement genetic testing for malignant hyperthermia, variants must be shown to alter the function of the channel. A number of different ex vivo methods can be used to demonstrate functionality, as long as cells from human patients can be obtained and cultured from at least two unrelated families. Because malignant hyperthermia is an uncommon disorder and many variants seem to be private, including the newly identified H4833Y mutation, these approaches are limited. The authors cloned the human skeletal muscle ryanodine receptor complementary DNA and expressed both normal and mutated forms in HEK-293 cells and carried out functional analysis using ryanodine binding assays in the presence of a specific agonist, 4-chloro-m-cresol, and the antagonist Mg. Transiently expressed human ryanodine receptor proteins colocalized with an endoplasmic reticulum marker in HEK-293 cells. Ryanodine binding assays confirmed that mutations causing malignant hyperthermia resulted in a hypersensitive channel, while those causing central core disease resulted in a hyposensitive channel. The functional assays validate recombinant human skeletal muscle ryanodine receptor for analysis of variants and add an additional mutation (H4833Y) to the repertoire of mutations that can be used for the genetic diagnosis of malignant hyperthermia.

Effects of elevated core temperature and normoxic 30% nitrous oxide on human ventilation during short duration, high intensity exercise.

PubMed

Yogev, A; Hall, A M; Jay, O; White, M D

2015-01-15

It was hypothesized that normoxic 30% nitrous oxide (N2O) would suppress and hyperthermia would increase exercise ventilation during short duration, high intensity exercise. Thirteen males (24.2±0.8y; mean±SE), of normal physique (BMI, 23.8±1.0kgm(-2)), performed 4 separate 30s Wingate tests on a cycle ergometer. Exercise ventilation and its components, as well as mean skin and esophageal temperature (TES), were assessed in 2 way experimental design with factors of Thermal State (Normothermia or Hyperthermia) and Gas Type (Air or 30% Normomoxic N2O). In the 2 hyperthermic tests TES was elevated to ∼38.5°C in a 40°C bath. The main results indicated a significant interaction (F=7.14, P=0.02) between Gas Type and Thermal state for the exercise-induced increase in ventilation (ΔV˙E). During both the normothermia and hyperthermia conditions with AIR breathing, the exercise ΔV˙E was ∼80Lmin(-1) and it was significantly decreased to 73.1±24.1Lmin(-1) in the normothermia condition with N2O breathing relative to that of 92.0±25.0Lmin(-1) in the hyperthermia condition with N2O breathing. In conclusion, normoxic N2O breathing suppressed high intensity exercise ventilation during normothermia relative to that during hyperthermia on account of decreases in the tidal volume and this led CO2 retention. Copyright © 2014 Elsevier B.V. All rights reserved.

Feasibility of chemohyperthermia with docetaxel-embedded magnetoliposomes as minimally invasive local treatment for cancer.

PubMed

Yoshida, Motohira; Watanabe, Yuji; Sato, Mitsunori; Maehara, Tsunehiro; Aono, Hiromichi; Naohara, Takashi; Hirazawa, Hideyuki; Horiuchi, Atsushi; Yukumi, Shungo; Sato, Koichi; Nakagawa, Hiromichi; Yamamoto, Yuji; Sugishita, Hiroki; Kawachi, Kanji

2010-04-15

Hyperthermia is a minimally invasive approach to cancer treatment, but it is difficult to heat only the tumor without damaging surrounding tissue. To solve this problem, we studied the effectiveness of chemohyperthermia with docetaxel-embedded magnetoliposomes (DMLs) and an applied alternating current (AC) magnetic field. Human MKN45 gastric cancer cells were implanted in the hind limb of Balb-c/nu/nu mice. Various concentrations of docetaxel-embedded DMLs were injected into the tumors and exposed to an AC magnetic field (n = 6, each). For comparison with hyperthermia alone, magnetite-loaded liposome (ML)-injected tumors were exposed to an AC magnetic field. Furthermore, the results of DML without AC treatment and docetaxel diluted into PBS with AC treatment were also compared (n = 10, each). Tumor surface temperature was maintained between 42 and 43 degrees C. Tumor volume was reduced in the DML group with a docetaxel concentration > 56.8 microg/ml, while a docetaxel concentration > 568.5 microg/ml was required for tumor reduction without hyperthermia. Statistically significant differences in tumor volume and survival rate were observed between the DML group exposed to the magnetic field and the other groups. The tumor disappeared in 3 mice in the DML group exposed to the magnetic field; 2 mice survived over 6 months after treatment, whereas all mice of the other groups died by 15 weeks. Histologically, hyperthermia with DML damaged tumor cells and DML diffused homogeneously. To the best of our knowledge, this is the first report to show that hyperthermia using chemotherapeutic agent-embedded magnetoliposomes has an anticancer effect.

Preparation of magnetic mesoporous silica nanoparticles as a multifunctional platform for potential drug delivery and hyperthermia

NASA Astrophysics Data System (ADS)

Yu, Xia; Zhu, Yufang

2016-01-01

We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with the potential multifunctionality of drug delivery and magnetic hyperthermia. Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat mesoporous silica shells for the formation of the core-shell structured MMS nanoparticles (MCN@C/mSiO2), and the rattle-type structured MMS nanoparticles (MCN/mSiO2) were obtained after the removal of the carbon layers from MCN@C/mSiO2 nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles were investigated. The results revealed that the MCN@C/mSiO2 and MCN/mSiO2 nanoparticles had spherical morphology and average particle sizes of 390 and 320 nm, respectively. The MCN@C/mSiO2 nanoparticles exhibited higher magnetic hyperthermia ability compared to the MCN/mSiO2 nanoparticles, but the MCN/mSiO2 nanoparticles had higher drug loading capacity. Both MCN@C/mSiO2 and MCN/mSiO2 nanoparticles had similar drug release behavior with pH-controlled release and temperature-accelerated release. Furthermore, the MCN@C/mSiO2 and MCN/mSiO2 nanoparticles showed low cytotoxicity and could be internalized into HeLa cells. Therefore, the MCN@C/mSiO2 and MCN/mSiO2 nanoparticles would be promising for the combination of drug delivery and magnetic hyperthermia treatment in cancer therapy.

Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer.

PubMed

Stocke, Nathanael A; Sethi, Pallavi; Jyoti, Amar; Chan, Ryan; Arnold, Susanne M; Hilt, J Zach; Upreti, Meenakshi

2017-03-01

Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles or magnetic nanocomposites (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/mL) caused significant increase in cellular death/damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of magnetic mesoporous silica nanoparticles as a multifunctional platform for potential drug delivery and hyperthermia.

PubMed

Yu, Xia; Zhu, Yufang

2016-01-01

We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with the potential multifunctionality of drug delivery and magnetic hyperthermia. Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat mesoporous silica shells for the formation of the core-shell structured MMS nanoparticles (MCN@C/mSiO 2 ), and the rattle-type structured MMS nanoparticles (MCN/mSiO 2 ) were obtained after the removal of the carbon layers from MCN@C/mSiO 2 nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles were investigated. The results revealed that the MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles had spherical morphology and average particle sizes of 390 and 320 nm, respectively. The MCN@C/mSiO 2 nanoparticles exhibited higher magnetic hyperthermia ability compared to the MCN/mSiO 2 nanoparticles, but the MCN/mSiO 2 nanoparticles had higher drug loading capacity. Both MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles had similar drug release behavior with pH-controlled release and temperature-accelerated release. Furthermore, the MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles showed low cytotoxicity and could be internalized into HeLa cells. Therefore, the MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles would be promising for the combination of drug delivery and magnetic hyperthermia treatment in cancer therapy.

Physical exercise-induced changes in the core body temperature of mice depend more on ambient temperature than on exercise protocol or intensity.

PubMed

Wanner, Samuel Penna; Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Cardoso, Valbert Nascimento; Coimbra, Cândido Celso

2014-08-01

The mechanisms underlying physical exercise-induced hyperthermia may be species specific. Therefore, the present study aimed to investigate the effects of exercise intensity and ambient temperature on the core body temperature (T core) of running mice, which provide an important experimental model for advancing the understanding of thermal physiology. We evaluated the influence of different protocols (constant- or incremental-speed exercises), treadmill speeds and ambient temperatures (T a) on the magnitude of exercise-induced hyperthermia. To measure T core, a telemetric sensor was implanted in the abdominal cavity of male adult Swiss mice under anesthesia. After recovering from the surgery, the animals were familiarized to running on a treadmill and then subjected to the different running protocols and speeds at two T a: 24 °C or 34 °C. All of the experimental trials resulted in marked increases in T core. As expected, the higher-temperature environment increased the magnitude of running-induced hyperthermia. For example, during incremental exercise at 34 °C, the maximal T core achieved was increased by 1.2 °C relative to the value reached at 24 °C. However, at the same T a, neither treadmill speed nor exercise protocol altered the magnitude of exercise-induced hyperthermia. We conclude that T core of running mice is influenced greatly by T a, but not by the exercise protocols or intensities examined in the present report. These findings suggest that the magnitude of hyperthermia in running mice may be regulated centrally, independently of exercise intensity.

'Smart' gold nanoshells for combined cancer chemotherapy and hyperthermia.

PubMed

Liang, Zhongshi; Li, Xingui; Xie, Yegui; Liu, Shunying

2014-04-01

Nanomaterials that circulate in the body have great potential in the diagnosis and treatment of diseases. Here we report that 'smart' gold nanoshells can carry a drug payload, and that their intrinsic near-infrared (NIR) plasmon resonance enables the combination of chemotherapeutic and hyperthermia therapies. The 'smart' gold nanoshells (named DOX/A54@GNs) consist of (a) gold nanoshells (GNs) with NIR plasmon resonance, which not only act as nanoblocks but also produce local heat to allow hyperthermia; (b) an anticancer drug, doxorubicin (DOX), which was conjugated onto the nanoblocks by pH-dependent biodegradable copolymer thiol poly(ethylene glycol) derivatives via carbamate linkage; and (c) the targeting peptide A54 (AGKGTPSLETTP) to facilitate its orientation to liver cancer cells and enhance cellular uptake. The conjugated DOX was released from the DOX/A54@GNs much more rapidly in an acidic environment (pH 5.3) than in a neutral environment (pH 7.4), which is a desirable characteristic for intracellular tumor drug release. DOX-modified GNs showed pH-dependent release behavior, and the in vitro cell uptake experiment using ICP-AES and microscopy showed greater internalization of A54-modified GNs in the human liver cancer cell line BEL-7402 than of those without A54. Flow cytometry and fluoroscopy analysis were conducted to reveal the enhanced cell apoptosis caused by the A54-modified GNs under combined chemotherapeutic and hyperthermia therapies. These results imply that DOX/A54@GNs could be used as a multifunctional nanomaterial system with pH-triggered drug-releasing properties for tumor-targeted chemotherapy and hyperthermia.

Hyperthermia promotes and prevents respiratory epithelial apoptosis through distinct mechanisms.

PubMed

Nagarsekar, Ashish; Tulapurkar, Mohan E; Singh, Ishwar S; Atamas, Sergei P; Shah, Nirav G; Hasday, Jeffrey D

2012-12-01

Hyperthermia has been shown to confer cytoprotection and to augment apoptosis in different experimental models. We analyzed the mechanisms of both effects in the same mouse lung epithelial (MLE) cell line (MLE15). Exposing MLE15 cells to heat shock (HS; 42°C, 2 h) or febrile-range hyperthermia (39.5°C) concurrent with activation of the death receptors, TNF receptor 1 or Fas, greatly accelerated apoptosis, which was detectable within 30 minutes and was associated with accelerated activation of caspase-2, -8, and -10, and the proapoptotic protein, Bcl2-interacting domain (Bid). Caspase-3 activation and cell death were partially blocked by inhibitors targeting all three initiator caspases. Cells expressing the IκB superrepessor were more susceptible than wild-type cells to TNF-α-induced apoptosis at 37°C, but HS and febrile-range hyperthermia still increased apoptosis in these cells. Delaying HS for 3 hours after TNF-α treatment abrogated its proapoptotic effect in wild-type cells, but not in IκB superrepressor-expression cells, suggesting that TNF-α stimulates delayed resistance to the proapoptotic effects of HS through an NF-κB-dependent mechanism. Pre-exposure to 2-hour HS beginning 6 to16 hours before TNF-α treatment or Fas activation reduced apoptosis in MLE15 cells. The antiapoptotic effects of HS pretreatment were reduced in TNF-α-treated embryonic fibroblasts from heat shock factor-1 (HSF1)-deficient mice, but the proapoptotic effects of concurrent HS were preserved. Thus, depending on the temperature and timing relative to death receptor activation, hyperthermia can exert pro- and antiapoptotic effects through distinct mechanisms.

Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers.

PubMed

Das, R; Rinaldi-Montes, N; Alonso, J; Amghouz, Z; Garaio, E; García, J A; Gorria, P; Blanco, J A; Phan, M H; Srikanth, H

2016-09-28

Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

[Mathematical apparatus of the circuit theory in modeling of heat transfer upon extreme heating of an organism].

PubMed

2010-01-01

The mathematical model of heat transfer in whole-body hyperthermia, developed earlier by the author, has been refined using the mathematical apparatus of the circuit theory. The model can be used to calculate the temperature of each organ, which can increase the efficacy and safety of the immersion-convection technique of whole-body hyperthermia.

Application of hyperthermia for cancer treatment: recent patents review.

PubMed

Soares, Paula I P; Ferreira, Isabel M M; Igreja, Rui A G B N; Novo, Carlos M M; Borges, Joao P M R

2012-01-01

Cancer is one of the main causes of death in the world and its incidence increases every day. Current treatments are insufficient and present many breaches. Hyperthermia is an old concept and since early it was established as a cancer treatment option, mainly in superficial cancers. More recently the concept of intracellular hyperthermia emerged wherein magnetic particles are concentrated at the tumor site and remotely heated using an applied magnetic field to achieve hyperthermic temperatures (42-45°C). Many patents have been registered in this area since the year 2000. This review presents the most relevant information, organizing them according to the hyperthermic method used: 1) external Radio-Frequency devices; 2) hyperthermic perfusion; 3) frequency enhancers; 4) apply heating to the target site using a catheter; 5) injection of magnetic and ferroelectric particles; 6) injection of magnetic nanoparticles that may carry a pharmacological active drug. The use of magnetic nanoparticles is a very promising treatment approach since it may be used for diagnostic and treatment. An ideal magnetic nanoparticle would be able to detect and diagnose the tumor, carry a pharmacological active drug to be delivered in the tumor site, apply hyperthermia through an external magnetic field and allow treatment monitoring by magnetic resonance imaging.

Effects of MDMA on body temperature in humans

PubMed Central

Liechti, Matthias E

2014-01-01

Hyperthermia is a severe complication associated with the recreational use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). In this review, the clinical laboratory studies that tested the effects of MDMA on body temperature are summarized. The mechanisms that underlie the hyperthermic effects of MDMA in humans and treatment of severe hyperthermia are presented. The data show that MDMA produces an acute and dose-dependent rise in core body temperature in healthy subjects. The increase in body temperature is in the range of 0.2-0.8°C and does not result in hyperpyrexia (>40°C) in a controlled laboratory setting. However, moderately hyperthermic body temperatures >38.0°C occur frequently at higher doses, even in the absence of physical activity and at room temperature. MDMA primarily releases serotonin and norepinephrine. Mechanistic clinical studies indicate that the MDMA-induced elevations in body temperature in humans partially depend on the MDMA-induced release of norepinephrine and involve enhanced metabolic heat generation and cutaneous vasoconstriction, resulting in impaired heat dissipation. The mediating role of serotonin is unclear. The management of sympathomimetic toxicity and associated hyperthermia mainly includes sedation with benzodiazepines and intravenous fluid replacement. Severe hyperthermia should primarily be treated with additional cooling and mechanical ventilation. PMID:27626046

Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

PubMed

Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

2018-04-02

Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Specific loss power in superparamagnetic hyperthermia: nanofluid versus composite

NASA Astrophysics Data System (ADS)

Osaci, M.; Cacciola, M.

2017-01-01

Currently, the magnetic hyperthermia induced by nanoparticles is of great interest in biomedical applications. In the literature, we can find a lot of models for magnetic hyperthermia, but many of them do not give importance to a significant detail, such as the geometry of nanoparticle positions in the system. Usually, a nanofluid is treated by considering random positions of the nanoparticles, geometry that is actually characteristic to the composite nanoparticles. To assess the error which is frequently made, in this paper we propose a comparative analysis between the specific loss power (SLP) in case of a nanofluid and the SLP in case of a composite with magnetic nanoparticles. We are going to use a superparamagnetic hyperthermia model based on the improved model for calculating the Néel relaxation time in a magnetic field oblique to the nanoparticle magnetic anisotropy axes, and on the improved theoretical model LRT (linear response theory) for SLP. To generate the nanoparticle geometry in the system, we are going to apply a Monte Carlo method to a nanofluid, by minimising the interaction potentials in liquid medium and, for a composite environment, a method for generating random positions of the nanoparticles in a given volume.

Immobility and hyperthermia in the tail suspension test: association with the Porsolt test and the reflex startle reaction in 11 inbred mouse strains and the effects of genetic knockout of MAO A.

PubMed

Popova, N K; Tibeikina, M A

2010-06-01

Immobility and hyperthermia induced by unavoidable stress imposed by the tail suspension test (TST) and the acoustic startle reaction were assessed in mice of 11 inbred strains and in Tg8 mice, which have genetic knockout of MAO A. Sharp genotypic differences in immobility were seen, while there was no correlation with the hyperthermic response to the TST. A correlation was found between the extent of immobility in the TST and the startle reaction. Studies of 11 strains of mice revealed a positive correlation between the duration of immobility in the TST and the Porsolt "despair test." Genetic knockout of MAO A, one of the key enzymes in catecholamine and serotonin metabolism in the brain, weakened the startle reaction and TST-induced hyperthermia but had no significant effect on the immobility of Tg8 mice, which provides evidence of differences in the neurochemical regulation of these reactions. These data provide grounds for using the TST as a "dry" Porsolt test and identify TST-induced hyperthermia as a model for reactions to unavoidable stress.

Theoretical analysis, design and development of a 27-MHz folded loop antenna as a potential applicator in hyperthermia treatment.

PubMed

Kouloulias, Vassilis; Karanasiou, Irene; Giamalaki, Melina; Matsopoulos, George; Kouvaris, John; Kelekis, Nikolaos; Uzunoglu, Nikolaos

2015-02-01

A hyperthermia system using a folded loop antenna applicator at 27 MHz for soft tissue treatment was investigated both theoretically and experimentally to evaluate its clinical value. The electromagnetic analysis of a 27-MHz folded loop antenna for use in human tissue was based on a customised software tool and led to the design and development of the proposed hyperthermia system. The system was experimentally validated using specific absorption rate (SAR) distribution estimations through temperature distribution measurements of a muscle tissue phantom after electromagnetic exposure. Various scenarios for optimal antenna positioning were also performed. Comparison of the theoretical and experimental analysis results shows satisfactory agreement. The SAR level of 50% reaches 8 cm depth in the tissue phantom. Thus, based on the maximum observed SAR values that were of the order of 100 W/kg, the antenna specified is suitable for deep tumour heating. Theoretical and experimental SAR distribution results as derived from this study are in agreement. The proposed folded loop antenna seems appropriate for use in hyperthermia treatment, achieving proper planning and local treatment of deeply seated affected areas and lesions.

Clinical implementation of electrical impedance tomography with hyperthermia.

PubMed

Moskowitz, M J; Ryan, T P; Paulsen, K D; Mitchell, S E

1995-01-01

We describe the use of electrical impedance tomography (EIT) for non-invasive thermal imaging in conjunction with a clinical treatment of a superficial scalp lesion utilizing a spiral microstrip antenna. This is our first reported use of EIT with a clinical hyperthermia treatment and perhaps the first world-wide. The thermal measurements recorded during treatment compare favourably with the images reconstructed from impedance data gathered during heating. A linear relation, measured in phantom material, between the change in temperature with the change in reconstructed impedance was assumed. The average discrepancy between the measured temperature changes with the temperatures reconstructed from the impedance changes was 1.4 degrees C, with the maximum being 8.9 degrees C. These preliminary data suggest that impedance changes can be measured during hyperthermia delivery and temperature estimates based on these observed changes are possible in the clinical setting. These findings also point to the complex, yet critical nature of the impedance versus temperature relationship for tissue in vivo. The reconstructed thermal images may provide complementary information about the overall thermal damage imposed during heating. Based on this initial clinical experience we feel that EIT has great potential as a viable clinical aid in imaging the temperature changes imposed during hyperthermia.

Multifunctional magnetic nanostructured hardystonite scaffold for hyperthermia, drug delivery and tissue engineering applications.

PubMed

Farzin, Ali; Fathi, Mohammadhossein; Emadi, Rahmatollah

2017-01-01

Hyperthermia and local drug delivery have been proposed as potential therapeutic approaches for killing cancer cells. The development of bioactive materials such as Hardystonite (HT) with magnetic and drug delivery properties can potentially meet this target. This new class of magnetic bioceramic can replace the widely used magnetic iron oxide nanoparticles, whose long-term biocompatibility is not clear. Magnetic HT can be potentially employed to develop new ceramic scaffolds for bone surgery and anticancer therapies. With this in mind, a synthesis procedure was developed to prepare multifunctional bioactive scaffold for tissue engineering, hyperthermia and drug delivery applications. To this end, iron (Fe 3+ )-containing HT scaffolds were prepared. The effect of Fe on biological, magnetic and drug delivery properties of HT scaffolds were investigated. The results showed that obtained Fe-HT is bioactive and magnetic with no magnetite or maghemite as secondary phases. The Fe-HT scaffolds obtained also possessed high specific surface areas and demonstrated sustained drug delivery. These results potentially open new aspects for biomaterials aimed at regeneration of large-bone defects caused by malignant bone tumors through a combination of hyperthermia, local drug delivery and osteoconductivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment.

PubMed

Quinto, Christopher A; Mohindra, Priya; Tong, Sheng; Bao, Gang

2015-08-07

Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.

Precise determination of the heat delivery during in vivo magnetic nanoparticle hyperthermia with infrared thermography

NASA Astrophysics Data System (ADS)

Rodrigues, Harley F.; Capistrano, Gustavo; Mello, Francyelli M.; Zufelato, Nicholas; Silveira-Lacerda, Elisângela; Bakuzis, Andris F.

2017-05-01

Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal’s surface. The results indicate that temperature errors as large as 7~\\circ C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.

Anisotropic Magnetic Nanostructures For Enhanced Hyperthermia

NASA Astrophysics Data System (ADS)

Torres, D.; Das, R.; Alonso, J.; Phan, M. H.; Srikanth, H.

Magnetic nanoparticles assisted hyperthermia is one of the most promising techniques for cancer treatment. By the use of magnetic nanoparticles in an external AC magnetic field, one can target a specific tumor location and deliver toxic doses of heat to the tumor area without damaging the surrounding healthy tissue. Magnetite is typically used in biomedical applications due to its biocompatibility, but the heating efficiency of the commonly used magnetite nanoparticles is not enough to obtain the best results in cancer treatment. Therefore, novel magnetic nanostructures are required in order to improve the heating efficiency. Recently, it has been proposed by different groups that it is possible to increase the heating efficiency of the nanoparticles by tuning their effective anisotropy. Considering this, we have synthesized high aspect ratio magnetic nanorods with increased effective anisotropy. A thorough structural and magnetic characterization has revealed high crystallinity and optimal magnetic properties of these nanorods. The hyperthermia response shows that by increasing the aspect ratio from 5 to 11, their heating efficiency is increased by 150%. In addition, we have observed that a good alignment of the nanorods with the magnetic field ensures the best heating results. Hence, these nanorods appear to be promising candidates for cancer treatment with magnetic hyperthermia.

Precise determination of the heat delivery during in vivo magnetic nanoparticle hyperthermia with infrared thermography.

PubMed

Rodrigues, Harley F; Capistrano, Gustavo; Mello, Francyelli M; Zufelato, Nicholas; Silveira-Lacerda, Elisângela; Bakuzis, Andris F

2017-05-21

Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal's surface. The results indicate that temperature errors as large as [Formula: see text]C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.

Survival and characteristics of murine leukaemic and normal stem cells after hyperthermia: a murine model for human bone marrow purging.

PubMed

Gidáli, J; Szamosvölgyi, S; Fehér, I; Kovács, P

1990-01-01

The effect of hyperthermia in vitro on the survival and leukaemogenic effectiveness of WEHI 3-B cells and on the survival and transplantation efficiency of bone marrow cells was compared in a murine model system. Normal murine clonogenic haemopoietic cells (day 9 CFU-S and CFU-GM) proved to be significantly less sensitive to 42.5 degrees C hyperthermia (Do values: 54.3 and 41.1 min, respectively) than leukaemic clonogenic cells (CFU-L) derived from suspension culture or from bone marrow of leukaemic mice (Do: 17.8 min). Exposure for 120 min to 42.5 degrees C reduced the surviving fraction of CFU-L to 0.002 and that of CFU-S to 0.2. If comparable graft sizes were transplanted from normal or heat exposed bone marrow, 60-day survival of supralethally irradiated mice was similar. Surviving WEHI 3-B cells were capable of inducing leukaemia in vivo. The two log difference in the surviving fraction of CFU-L and CFU-S after 120 min exposure to 42.5 degrees C suggests that hyperthermia ex vivo may be a suitable purging method for autologous bone marrow transplantation.

Clinical and immunologic results of local hyperthermia at 44 °C for extensive genital warts in patients with diabetes mellitus.

PubMed

Huo, Wei; Li, Gui-Hua; Qi, Rui-Qun; Zhang, Li; Yan, Xiao-Xia; Chen, Hong-Duo; Gao, Xing-Hua

2013-01-01

Genital warts are more extensive and difficult to treat in patients with diabetes mellitus due to defective immune responses. Our aim was to confirm the suitability of local hyperthermia for the treatment of genital warts in patients with diabetes mellitus and to investigate the immune cells in lesional areas at different time intervals after treatment. We treated three diabetic patients with extensive genital warts by local hyperthermia at 44 °C for 30 min a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical clearance. Immunohistochemical profile was described on serial biopsies from a patient with confluent plaques. The warty lesions in the patients resolved in 6, 4 and 9 weeks, respectively. Immunohistochemical staining in the regressing warts revealed abundant infiltrating CD4+ T and CD8+ T lymphocytes (P < 0.01), as well as macrophages and CD1a+ dendritic cells. This preliminary study suggested that local hyperthermia was a safe and effective single modality in the treatment of genital warts in diabetic patients and could induce a rapid immune response in lesional skin.

Exposure to heavy charged particles affects thermoregulation in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kandasamy, S.B.; Hunt, W.A.; Dalton, T.K.

1994-09-01

Rats exposed to 0.1-5 Gy of heavy particles ({sup 56}Fe, {sup 40}Ar, {sup 20}Ne or {sup 4}He) showed dose-dependent changes in body temperature. Lower doses of all particles produced hyperthermia, and higher doses of {sup 20}Ne and {sup 56}Fe produced hypothermia. Of the four HZE particles, {sup 56}Fe particles were the most potent and {sup 4}He particles were the least potent in producing changes in thermoregulation. The {sup 20}Ne and {sup 40}Ar particles produced an intermediate level of change in body temperature. Significantly greater hyperthermia was produced by exposure to 1 Gy of {sup 20}Ne, {sup 40}Ar and {sup 56}Femore » particles than by exposure to 1 Gy of {sup 60}Co {gamma} rays. Pretreating rats with the cyclo-oxygenase inhibitor indomethacin attenuated the hyperthermia produced by exposure to 1 Gy of {sup 56}Fe particles, indicating that prostaglandins mediate {sup 56}Fe-particle-induced hyperthermia. The hypothermia produced by exposure to 5 Gy of {sup 56}Fe particles is mediated by histamine and can be attenuated by treatment with the antihistamines mepyramine and cimetidine. 15 refs., 4 figs.« less

Hyperthermia in low aspect-ratio magnetic nanotubes for biomedical applications

NASA Astrophysics Data System (ADS)

Gutierrez-Guzman, D. F.; Lizardi, L. I.; Otálora, J. A.; Landeros, P.

2017-03-01

A simple model for the magnetization reversal process of low aspect-ratio ferromagnetic nanotubes (MNTs) is presented. Because of advantages over other geometries, these structures are interesting for biomedical applications, such as magnetic hyperthermia cancer therapy, where the heat released during magnetic reversal is used to destroy tumors. For example, the tubular geometry provides two independent functional surfaces that may be selectively manipulated and also gives a storage cavity. Owing to their large surface to weight ratio and low mass density, MNTs are not decanted by gravity. We calculated magnetic phase diagrams, energy barriers, nucleation fields, and the amount of dissipated heat and specific absorption rate for magnetite nanotubes. The geometrical parameters were varied, and simple formulae were used to optimize the tube response under alternating excitation, as required for magnetic hyperthermia applications.

Irradiation-hyperthermia in canine hemangiopericytomas: large-animal model for therapeutic response.

PubMed

Richardson, R C; Anderson, V L; Voorhees, W D; Blevins, W E; Inskeep, T K; Janas, W; Shupe, R E; Babbs, C F

1984-11-01

Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.

Thermoseeds for interstitial magnetic hyperthermia: from bioceramics to nanoparticles

NASA Astrophysics Data System (ADS)

Baeza, A.; Arcos, D.; Vallet-Regí, M.

2013-12-01

The development of magnetic materials for interstitial hyperthermia treatment of cancer is an ever evolving research field which provides new alternatives to antitumoral therapies. The development of biocompatible magnetic materials has resulted in new biomaterials with multifunctional properties, which are able to adapt to the complex scenario of tumoral processes. Once implanted or injected in the body, magnetic materials can behave as thermoseeds under the effect of AC magnetic fields. Magnetic bioceramics aimed to treat bone tumors and magnetic nanoparticles are among the most studied thermoseeds, and supply different solutions for the different scenarios in cancerous processes. This paper reviews some of the biomaterials used for bone cancer treatment and skeletal reinforcing, as well as the more complex topic of magnetic nanoparticles for intracellular targeting and hyperthermia.

Thermoseeds for interstitial magnetic hyperthermia: from bioceramics to nanoparticles.

PubMed

Baeza, A; Arcos, D; Vallet-Regí, M

2013-12-04

The development of magnetic materials for interstitial hyperthermia treatment of cancer is an ever evolving research field which provides new alternatives to antitumoral therapies. The development of biocompatible magnetic materials has resulted in new biomaterials with multifunctional properties, which are able to adapt to the complex scenario of tumoral processes. Once implanted or injected in the body, magnetic materials can behave as thermoseeds under the effect of AC magnetic fields. Magnetic bioceramics aimed to treat bone tumors and magnetic nanoparticles are among the most studied thermoseeds, and supply different solutions for the different scenarios in cancerous processes. This paper reviews some of the biomaterials used for bone cancer treatment and skeletal reinforcing, as well as the more complex topic of magnetic nanoparticles for intracellular targeting and hyperthermia.

Magnetic nanoparticles-based drug and gene delivery systems for the treatment of pulmonary diseases.

PubMed

El-Sherbiny, Ibrahim M; Elbaz, Nancy M; Sedki, Mohammed; Elgammal, Abdulaziz; Yacoub, Magdi H

2017-02-01

Magnetic nanoparticles (MNPs) have gained much attention due to their unique properties such as biocompatibility and biodegradability as well as magnetic and heat-medicated characteristics. Due to these inherent properties, MNPs have been widely used in various biomedical applications including targeted drug delivery and hyperthermia-based therapy. Hyperthermia is a promising approach for the thermal activation therapy of several diseases, including pulmonary diseases. Additionally, due to their large loading capacity and controlled release ability, several MNP-based drug delivery systems have been emerged for treatment of cystic fibrosis and lung cancer. This review provides an overview on the unique properties of MNPs and magnetic-mediated hyperthermia with emphasis on the recent biomedical applications of MNPs in treatment of both lung cancer and cystic fibrosis.

High-performance iron oxide nanoparticles for magnetic particle imaging - guided hyperthermia (hMPI)

NASA Astrophysics Data System (ADS)

Bauer, Lisa M.; Situ, Shu F.; Griswold, Mark A.; Samia, Anna Cristina S.

2016-06-01

Magnetic particle imaging (MPI) is an emerging imaging modality that allows the direct and quantitative mapping of iron oxide nanoparticles. In MPI, the development of tailored iron oxide nanoparticle tracers is paramount to achieving high sensitivity and good spatial resolution. To date, most MPI tracers being developed for potential clinical applications are based on spherical undoped magnetite nanoparticles. For the first time, we report on the systematic investigation of the effects of changes in chemical composition and shape anisotropy on the MPI performance of iron oxide nanoparticle tracers. We observed a 2-fold enhancement in MPI signal through selective doping of magnetite nanoparticles with zinc. Moreover, we demonstrated focused magnetic hyperthermia heating by adapting the field gradient used in MPI. By saturating the iron oxide nanoparticles outside of a field free region (FFR) with an external static field, we can selectively heat a target region in our test sample. By comparing zinc-doped magnetite cubic nanoparticles with undoped spherical nanoparticles, we could show a 5-fold improvement in the specific absorption rate (SAR) in magnetic hyperthermia while providing good MPI signal, thereby demonstrating the potential for high-performance focused hyperthermia therapy through an MPI-guided approach (hMPI).Magnetic particle imaging (MPI) is an emerging imaging modality that allows the direct and quantitative mapping of iron oxide nanoparticles. In MPI, the development of tailored iron oxide nanoparticle tracers is paramount to achieving high sensitivity and good spatial resolution. To date, most MPI tracers being developed for potential clinical applications are based on spherical undoped magnetite nanoparticles. For the first time, we report on the systematic investigation of the effects of changes in chemical composition and shape anisotropy on the MPI performance of iron oxide nanoparticle tracers. We observed a 2-fold enhancement in MPI signal through selective doping of magnetite nanoparticles with zinc. Moreover, we demonstrated focused magnetic hyperthermia heating by adapting the field gradient used in MPI. By saturating the iron oxide nanoparticles outside of a field free region (FFR) with an external static field, we can selectively heat a target region in our test sample. By comparing zinc-doped magnetite cubic nanoparticles with undoped spherical nanoparticles, we could show a 5-fold improvement in the specific absorption rate (SAR) in magnetic hyperthermia while providing good MPI signal, thereby demonstrating the potential for high-performance focused hyperthermia therapy through an MPI-guided approach (hMPI). Electronic supplementary information (ESI) available: Detailed IONP synthetic methods, description of magnetic particle relaxometer set-up, TEM of reference IONP (Senior Scientific PrecisionMRX™ 25 nm oleic acid-coated nanoparticles), concentration dependent PSF of all IONP samples, PSF and SAR of Zn-Sph and Zn-Cube mixture sample, upper right quadrant of field-dependent hysteresis curve labelled with static field strengths, and the magnetic hyperthermia temperature profiles with and without the presence of external magnetic fields. See DOI: 10.1039/c6nr01877g

Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

DTIC Science & Technology

2013-10-01

ABSTRACT Based upon the results obtained from these studies, we can draw the following conclusions: 1) Airway hyperresponsiveness developed in Ova ...hyperthermia in Ova -sensitized rats. The manuscript reporting the results obtained frim this study has been accepted for publication by the Journal of...to increasing airway temperature. Our results showed: 1) In Brown-Norway rats actively sensitized by ovalbumin ( Ova ), isocapnic hyperventilation with

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

PubMed

Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

2016-02-01

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Online Adaptive Hyperthermia Treatment Planning During Locoregional Heating to Suppress Treatment-Limiting Hot Spots.

PubMed

Kok, H Petra; Korshuize-van Straten, Linda; Bakker, Akke; de Kroon-Oldenhof, Rianne; Geijsen, Elisabeth D; Stalpers, Lukas J A; Crezee, Johannes

2017-11-15

Adequate tumor temperatures during hyperthermia are essential for good clinical response, but excessive heating of normal tissue should be avoided. This makes locoregional heating using phased array systems technically challenging. Online application of hyperthermia treatment planning could help to improve the heating quality. The aim of this study was to evaluate the clinical benefit of online treatment planning during treatment of pelvic tumors heated with the AMC-8 locoregional hyperthermia system. For online adaptive hyperthermia treatment planning, a graphical user interface was developed. Electric fields were calculated in a preprocessing step using our in-house-developed finite-difference-based treatment planning system. This allows instant calculation of the temperature distribution for user-selected phase-amplitude settings during treatment and projection onto the patient's computed tomographic scan for online visualization. Online treatment planning was used for 14 treatment sessions in 8 patients to reduce the patients' reports of hot spots while maintaining the same level of tumor heating. The predicted decrease in hot spot temperature should be at least 0.5°C, and the tumor temperature should decrease less than 0.2°C. These predictions were compared with clinical data: patient feedback about the hot spot and temperature measurements in the tumor region. In total, 17 hot spot reports occurred during the 14 sessions, and the alternative settings predicted the hot spot temperature to decrease by at least 0.5°C, which was confirmed by the disappearance of all 17 hot spot reports. At the same time, the average tumor temperature was predicted to change on average -0.01°C (range, -0.19°C to 0.34°C). The measured tumor temperature change was on average only -0.02°C (range, -0.26°C to 0.31°C). In only 2 cases the temperature decrease was slightly larger than 0.2°C, but at most it was 0.26°C. Online application of hyperthermia treatment planning is reliable and very useful to reduce hot spots without affecting tumor temperatures. Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial variation in hyperthermia emergency department visits among those with employer-based insurance in the United States - a case-crossover analysis.

PubMed

Saha, Shubhayu; Brock, John W; Vaidyanathan, Ambarish; Easterling, David R; Luber, George

2015-03-04

Predictions of intense heat waves across the United States will lead to localized health impacts, most of which are preventable. There is a need to better understand the spatial variation in the morbidity impacts associated with extreme heat across the country to prevent such adverse health outcomes. Hyperthermia-related emergency department (ED) visits were obtained from the Truven Health MarketScan(®) Research dataset for 2000-2010. Three measures of daily ambient heat were constructed using meteorological observations from the National Climatic Data Center (maximum temperature, heat index) and the Spatial Synoptic Classification. Using a time-stratified case crossover approach, odds ratio of hyperthermia-related ED visit were estimated for the three different heat measures. Random effects meta-analysis was used to combine the odds ratios for 94 Metropolitan Statistical Areas (MSA) to examine the spatial variation by eight latitude categories and nine U.S. climate regions. Examination of lags for all three temperature measures showed that the odds ratio of ED visit was statistically significant and highest on the day of the ED visit. For heat waves lasting two or more days, additional statistically significant association was observed when heat index and synoptic classification was used as the temperature measure. These results were insensitive to the inclusion of air pollution measures. On average, the maximum temperature on the day of an ED visit was 93.4°F in 'South' and 81.9°F in the 'Northwest' climatic regions of United States. The meta-analysis showed higher odds ratios of hyperthermia ED visit in the central and the northern parts of the country compared to the south and southwest. The results showed spatial variation in average temperature on days of ED visit and odds ratio for hyperthermia ED visits associated with extreme heat across United States. This suggests that heat response plans need to be customized for different regions and the potential role of hyperthermia ED visits in syndromic surveillance for extreme heat.

Biocompatibility and therapeutic evaluation of magnetic liposomes designed for self-controlled cancer hyperthermia and chemotherapy.

PubMed

Gogoi, Manashjit; Jaiswal, Manish K; Sarma, Haladhar Dev; Bahadur, Dhirendra; Banerjee, Rinti

2017-06-19

Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La 0.75 Sr 0.25 MnO 3 (LSMO) and iron oxide (Fe 3 O 4 ) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm 3 ) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm 3 ) compared to their corresponding control (mean tumour volume 3782 ± 515 mm 3 ). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of the body, suggesting again the potential of the novel magnetic liposomes formulation for possibility of developing as an effective modality for treatment of drug resistant or physiologically vulnerable cancer.

Experimental and theoretical investigation of intratumoral nanoparticle distribution to enhance magnetic nanoparticle hyperthermia

NASA Astrophysics Data System (ADS)

Attaluri, Anilchandra

Magnetic nanoparticles have gained prominence in recent years for use in clinical applications such as imaging, drug delivery, and hyperthermia. Magnetic nanoparticle hyperthermia is a minimally invasive and effective approach for confined heating in tumors with little collateral damage. One of the major problems in the field of magnetic nanoparticle hyperthermia is irregular heat distribution in tumors which caused repeatable heat distribution quite impossible. This causes under dosage in tumor area and overheating in normal tissue. In this study, we develop a unified approach to understand magnetic nanoparticle distribution and temperature elevations in gel and tumors. A microCT imaging system is first used to visualize and quantify nanoparticle distribution in both tumors and tissue equivalent phantom gels. The microCT based nanoparticle concentration is related to specific absorption rate (SAR) of the nanoparticles and is confirmed by heat distribution experiments in tissue equivalent phantom gels. An optimal infusion protocol is identified to generate controllable and repeatable nanoparticle distribution in tumors. In vivo animal experiments are performed to measure intratumoral temperature elevations in PC3 xenograft tumors implanted in mice during magnetic nanoparticle hyperthermia. The effect of nanofluid injection parameters on the resulted temperature distribution is studied. It shows that the tumor temperatures can be elevated above 50°C using very small amounts of ferrofluid with a relatively low magnetic field. Slower ferrofluid infusion rates result in smaller nanoparticle distribution volumes in the tumors, however, it gives the much required controllability and repeatability when compared to the higher infusion rates. More nanoparticles occupy a smaller volume in the vicinity of the injection site with slower infusion rates, causing higher temperature elevations in the tumors. Based on the microCT imaging analyses of nanoparticles in tumors, a mass transport model is developed to simulate nanoparticle convection and diffusion in tumors, heat-induced tumor structural changes, as well as nanoparticle re-distribution during nanoparticle hyperthermia procedures. The modeled thermal damage induced nanoparticle redistribution predicts a 20% increase in the radius of the spherical tissue region containing nanoparticles. The developed model has demonstrated the feasibility of enhancing nanoparticle dispersion from injection sites using targeted thermal damage.

Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of locally advanced cancer of the prostate and cervix

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Wootton, Jeff; Prakash, Punit; Salgaonkar, Vasant; Juang, Titania; Scott, Serena; Chen, Xin; Cunha, Adam; Pouliot, Jean; Hsu, I. C.

2011-03-01

A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions.

Intratumoral iron oxide nanoparticle hyperthermia and radiation cancer treatment

NASA Astrophysics Data System (ADS)

Hoopes, P. J.; Strawbridge, R. R.; Gibson, U. J.; Zeng, Q.; Pierce, Z. E.; Savellano, M.; Tate, J. A.; Ogden, J. A.; Baker, I.; Ivkov, R.; Foreman, A. R.

2007-02-01

The potential synergism and benefit of combined hyperthermia and radiation for cancer treatment is well established, but has yet to be optimized clinically. Specifically, the delivery of heat via external arrays /applicators or interstitial antennas has not demonstrated the spatial precision or specificity necessary to achieve appropriate a highly positive therapeutic ratio. Recently, antibody directed and possibly even non-antibody directed iron oxide nanoparticle hyperthermia has shown significant promise as a tumor treatment modality. Our studies are designed to determine the effects (safety and efficacy) of iron oxide nanoparticle hyperthermia and external beam radiation in a murine breast cancer model. Methods: MTG-B murine breast cancer cells (1 x 106) were implanted subcutaneous in 7 week-old female C3H/HeJ mice and grown to a treatment size of 150 mm3 +/- 50 mm3. Tumors were then injected locally with iron oxide nanoparticles and heated via an alternating magnetic field (AMF) generator operated at approximately 160 kHz and 400 - 550 Oe. Tumor growth was monitored daily using standard 3-D caliper measurement technique and formula. specific Mouse tumors were heated using a cooled, 36 mm diameter square copper tube induction coil which provided optimal heating in a 1 cm wide region in the center of the coil. Double dextran coated 80 nm iron oxide nanoparticles (Triton Biosystems) were used in all studies. Intra-tumor, peri-tumor and rectal (core body) temperatures were continually measured throughout the treatment period. Results: Preliminary in vivo nanoparticle-AMF hyperthermia (167 KHz and 400 or 550 Oe) studies demonstrated dose responsive cytotoxicity which enhanced the effects of external beam radiation. AMF associated eddy currents resulted in nonspecific temperature increases in exposed tissues which did not contain nanoparticles, however these effects were minor and not injurious to the mice. These studies also suggest that iron oxide nanoparticle hyperthermia is more effective than non-nanoparticle tumor heating techniques when similar thermal doses are applied. Initial electron and light microscopy studies of iron oxide nanoparticle and AMF exposed tumor cells show a rapid uptake of particles and acute cytotoxicity following AMF exposure.

Jim Peters' collapse in the 1954 Vancouver Empire Games marathon.

PubMed

Noakes, Tim; Mekler, Jackie; Pedoe, Dan Tunstall

2008-08-01

On 7 August 1954, the world 42 km marathon record holder, Jim Peters, collapsed repeatedly during the final 385 metres of the British Empire and Commonwealth Games marathon held in Vancouver, Canada. It has been assumed that Peters collapsed from heatstroke because he ran too fast and did not drink during the race, which was held in windless, cloudless conditions with a dry-bulb temperature of 28 degrees C. Hospital records made available to us indicate that Peters might not have suffered from exertional heatstroke, which classically produces a rectal temperature > 42 degrees C, cerebral effects and, usually, a fatal outcome without vigorous active cooling. Although Peters was unconscious on admission to hospital approximately 60 minutes after he was removed from the race, his rectal temperature was 39.4 degrees C and he recovered fully, even though he was managed conservatively and not actively cooled. We propose that Peters' collapse was more likely due to a combination of hyperthermia-induced fatigue which caused him to stop running; exercise-associated postural hypotension as a result of a low peripheral vascular resistance immediately he stopped running; and combined cerebral effects of hyperthermia, hypertonic hypernatraemia associated with dehydration, and perhaps undiagnosed hypoglycaemia. But none of these conditions should cause prolonged unconsciousness, raising the possibility that Peters might have suffered from a transient encephalopathy, the exact nature of which is not understood.

Hyperthermia in bone generated with MR imaging-controlled focused ultrasound: control strategies and drug delivery.

PubMed

Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

2012-04-01

To evaluate the feasibility of achieving image-guided drug delivery in bone by using magnetic resonance (MR) imaging-controlled focused ultrasound hyperthermia and temperature-sensitive liposomes. Experiments were approved by the institutional animal care committee. Hyperthermia (43°C, 20 minutes) was generated in 10-mm-diameter regions at a muscle-bone interface in nine rabbit thighs by using focused ultrasound under closed-loop temperature control with MR thermometry. Thermosensitive liposomal doxorubicin was administered systemically during heating. Heating uniformity and drug delivery were evaluated for control strategies with the temperature control image centered 10 mm (four rabbits) or 0 mm (five rabbits) from the bone. Simulations estimated temperature elevations in bone. Drug delivery was quantified by using the fluorescence of doxorubicin extracted from bone marrow and muscle and was compared between treated and untreated thighs by using the one-sided Wilcoxon signed rank test. With ultrasound focus and MR temperature control plane 0 mm and 10 mm from the bone interface, average target region temperatures were 43.1°C and 43.3°C, respectively; numerically estimated bone temperatures were 46.8°C and 78.1°C. The 10-mm offset resulted in thermal ablation; numerically estimated muscle temperature was 66.1°C at the bone interface. Significant increases in doxorubicin concentration occurred in heated versus unheated marrow (8.2-fold, P = .002) and muscle (16.8-fold, P = .002). Enhancement occurred for 0- and 10-mm offsets, which suggests localized drug delivery in bone is possible with both hyperthermia and thermal ablation. MR imaging-controlled focused ultrasound can achieve localized hyperthermia in bone for image-guided drug delivery in bone with temperature-sensitive drug carriers. © RSNA, 2012.

Uncoupling of oxidative phosphorylation and ATP synthase reversal within the hyperthermic heart

PubMed Central

Power, Amelia; Pearson, Nicholas; Pham, Toan; Cheung, Carlos; Phillips, Anthony; Hickey, Anthony

2014-01-01

Abstract Heart failure is a common cause of death with hyperthermia, and the exact cause of hyperthermic heart failure appears elusive. We hypothesize that the energy supply (ATP) of the heart may become impaired due to increased inner‐mitochondrial membrane permeability and inefficient oxidative phosphorylation (OXPHOS). Therefore, we assessed isolated working heart and mitochondrial function. Ex vivo working rat hearts were perfused between 37 and 43.5°C and showed break points in all functional parameters at ~40.5°C. Mitochondrial high‐resolution respirometry coupled to fluorometry was employed to determine the effects of hyperthermia on OXPHOS and mitochondrial membrane potential (ΔΨ) in vitro using a comprehensive metabolic substrate complement with isolated mitochondria. Relative to 37 and 40°C, 43°C elevated Leak O2 flux and depressed OXPHOS O2 flux and ∆Ψ. Measurement of steady‐state ATP production from mitochondria revealed decreased ATP synthesis capacity, and a negative steady‐state P:O ratio at 43°C. This approach offers a more powerful analysis of the effects of temperature on OXPHOS that cannot be measured using simple measures such as the traditional respiratory control ratio (RCR) or P:O ratio, which, respectively, can only approach 1 or 0 with inner‐membrane failure. At 40°C there was only a slight enhancement of the Leak O2 flux and this did not significantly affect ATP production rate. Therefore, during mild hyperthermia (40°C) there is no enhancement of ATP supply by mitochondria, to accompany increasing cardiac energy demands, while between this and critical hyperthermia (43°C), mitochondria become net consumers of ATP. This consumption may contribute to cardiac failure or permanent damage during severe hyperthermia. PMID:25263202

Transient Mild Hyperthermia Induces E-selectin Mediated Localization of Mesoporous Silicon Vectors in Solid Tumors

PubMed Central

Kirui, Dickson K.; Mai, Juahua; Palange, Anna-Lisa; Qin, Guoting; van de Ven, Anne L.; Liu, Xuewu; Shen, Haifa; Ferrari, Mauro

2014-01-01

Background Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs). We also determined the optimal time window at which maximal accumulation occur. Results In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm2) amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm) adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. Conclusions Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy. PMID:24558362

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

PubMed Central

Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

2014-01-01

MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats.

PubMed

Nyhuis, Tara J; Masini, Cher V; Taufer, Kirsten L; Day, Heidi E W; Campeau, Serge

2016-01-01

The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 min of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-h intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-min to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similar attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress.

Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia.

PubMed

Kim, Dong-Hyun; Kim, Kyoung-Nam; Kim, Kwang-Mahn; Lee, Yong-Keun

2009-01-01

The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia. 2008 Wiley Periodicals, Inc.

A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

PubMed

Kleiter, Miriam M; Yu, Daohai; Mohammadian, Lenore A; Niehaus, Nelsen; Spasojevic, Ivan; Sanders, Linda; Viglianti, Benjamin L; Yarmolenko, Pavel S; Hauck, Marlene; Petry, Neil A; Wong, Terence Z; Dewhirst, Mark W; Thrall, Donald E

2006-11-15

A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)-labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

Thermometric analysis of intra-cavitary hyperthermia for esophageal cancer.

PubMed

Qi, C; Li, D J

1999-01-01

Thermometric analysis was carried out in 51 patients with esophageal cancer treated with intra-cavitary hyperthermia combined with radio chemotherapy, to test whether temperature index (T20, T50) and T90) could be used as an indicator for tumour control. Hyperthermia was administered by intra-cavitary microwave applicator. The T20, T50 and T90 were deducted from the temperature sensors T0 and T3 situated at the center of the tumour surface and 3cm from it. Eighteen patients with local control > or =36 months were named long term control patients (LC), 24 patients with local recurrence within 24 months (LR) (there were no events occurring between 24 and 36 months) and nine patients died of metastasis without local recurrence (DM). The overall survival rates were 80.4 +/- 5.6% at 1 year, 38.3 +/- 6.9% at 3 years and 31 +/- 6.7% at 5 years, respectively. Chi-square test showed no influence of the number of hyperthermia sessions on the local control (p > 0.25). The 5-year local control rate was 18.8% for the patients with T90 < 43 degrees C and 45% for those with T90 > or = 43 degrees C (p < 0.01). The average T90 was 43.76 +/- 0.74 degrees C for the LC patients and 43.17 +/- 0.57 degrees C for those LR (p = 0.024). The mean T90 was higher than 43 degrees C in 94.4% of LC, whereas in 58.8% of LR. The study suggested that T90 was a good parameter for thermal dose in the intracavitary hyperthermia for the treatment of esophageal cancer.

Measurement of Thermal Conductivity of Porcine Liver in the Temperature Range of Cryotherapy and Hyperthermia (250~315k) by A Thermal Sensor Made of A Micron-Scale Enameled Copper Wire.

PubMed

Jiang, Z D; Zhao, G; Lu, G R

　　BACKGROUND: Cryotherapy and hyperthermia are effective treatments for several diseases, especially for liver cancers. Thermal conductivity is a significant thermal property for the prediction and guidance of surgical procedure. However, the thermal conductivities of organs and tissues, especially over the temperature range of both cryotherapy and hyperthermia are scarce. To provide comprehensive thermal conductivity of liver for both cryotherapy and hyperthermia. A hot probe made of stain steel needle and micron-sized copper wire is used for measurement. To verify data processing, both the least square method and the Monte Carlo inversion method are used to determine the hot probe constants, respectively, with reference materials of water and 29.9 % Ca 2 Cl aqueous solution. Then the thermal conductivities of Hanks solution and pork liver bathed in Hanks solution are measured. The effective length for two methods is nearly the same, but the heat capacity of probe calibrated by the Monte Carlo inversion is temperature dependent. Fairly comprehensive thermal conductivity of porcine liver measured with these two methods in the target temperature range is verified to be similar. We provide an integrated thermal conductivity of liver for cryotherapy and hyperthermia in two methods, and make more accurate predictions possible for surgery. The least square method and the Monte Carlo inversion method have their advantages and disadvantages. The least square method is available for measurement of liquids that not prone to convection or solids in a wide temperature range, while the Monte Carlo inversion method is available for accurate and rapid measurement.

Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats

PubMed Central

Nyhuis, Tara J.; Masini, Cher V.; Taufer, Kirsten L.; Day, Heidi E.W.; Campeau, Serge

2016-01-01

The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 minutes of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-hr intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-minutes to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similarly attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress. PMID:26998558

Magnetic hyperthermia enhances cell toxicity with respect to exogenous heating.

PubMed

Sanz, Beatriz; Calatayud, M Pilar; Torres, Teobaldo E; Fanarraga, Mónica L; Ibarra, M Ricardo; Goya, Gerardo F

2017-01-01

Magnetic hyperthermia is a new type of cancer treatment designed for overcoming resistance to chemotherapy during the treatment of solid, inaccessible human tumors. The main challenge of this technology is increasing the local tumoral temperature with minimal side effects on the surrounding healthy tissue. This work consists of an in vitro study that compared the effect of hyperthermia in response to the application of exogenous heating (EHT) sources with the corresponding effect produced by magnetic hyperthermia (MHT) at the same target temperatures. Human neuroblastoma SH-SY5Y cells were loaded with magnetic nanoparticles (MNPs) and packed into dense pellets to generate an environment that is crudely similar to that expected in solid micro-tumors, and the above-mentioned protocols were applied to these cells. These experiments showed that for the same target temperatures, MHT induces a decrease in cell viability that is larger than the corresponding EHT, up to a maximum difference of approximately 45% at T = 46 °C. An analysis of the data in terms of temperature efficiency demonstrated that MHT requires an average temperature that is 6 °C lower than that required with EHT to produce a similar cytotoxic effect. An analysis of electron microscopy images of the cells after the EHT and MHT treatments indicated that the enhanced effectiveness observed with MHT is associated with local cell destruction triggered by the magnetic nano-heaters. The present study is an essential step toward the development of innovative adjuvant anti-cancer therapies based on local hyperthermia treatments using magnetic particles as nano-heaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Halothane and halothane/succinylcholine induced malignant hyperthermia (porcine stress syndrome) in a population of Ontario boars.

PubMed

Seeler, D C; McDonell, W N; Basrur, P K

1983-07-01

This paper recounts a study of the prevalence of malignant hyperthermia in a population of boars entering the Record of Performance Test Station at New Hamburg, Ontario over a period of ten months. The literature is briefly reviewed and an account of the present status of malignant hyperthermia (porcine stress syndrome) in Ontario boars using the halothane or halothane/succinylcholine screening tests is presented. It was determined in this population of boars that there was a 1.5% prevalence rate of malignant hyperthermia susceptible boars. This was based on a five minute halothane challenge carried out on 786 boars from 107 herds. The halothane reactors came from a total of eight herds or 7.5% of the total number of herds. A majority of 58.3% of the animals reacted after the three minute mark of the halothane challenge. In contrast, an 18.0% prevalence rate was determined using halothane/succinylcholine challenge on 123 boars. This further identified an additional eight herds with the problem, bringing the total to 16 or 15% of the total number of herds. It is suggested that the prevalence of malignant hyperthermia in Ontario breeding herds is much higher than was originally thought and that the halothane challenge is an inadequate screening test for this trait if the intention is to remove the genetic trait from the breeding herd. At the same time halothane challenge testing will identify those animals which have a strong susceptibility to the trait and if used on key breeding stock will help to maintain some control on the condition until a more definitive test is readily available.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo optimisation study for multi-baseline MR-based thermometry in the context of hyperthermia using MR-guided high intensity focused ultrasound for head and neck applications.

PubMed

Pichardo, Samuel; Köhler, Max; Lee, Justin; Hynnyen, Kullervo

2014-12-01

In this in vivo study, the feasibility to perform hyperthermia treatments in the head and neck using magnetic resonance image-guided high intensity focused ultrasound (MRgHIFU) was established using a porcine acute model. Porcine specimens with a weight between 17 and 18 kg were treated in the omohyoid muscle in the neck. Hyperthermia was applied with a target temperature of 41 °C for 30 min using a Sonalleve MRgHIFU system. MR-based thermometry was calculated using water-proton resonance frequency shift and multi-baseline look-up tables indexed by peak-to-peak displacement (Dpp) measurements using a pencil-beam navigator. Three hyperthermia experiments were conducted at different Dpp values of 0.2, 1.0 and 3.0 mm. An optimisation study was carried out to establish the optimal parameters controlling the multi-baseline method that ensured a minimisation of spatial-average peak-to-peak temperature (TSA-pp) and temperature direct current bias (TSA-DC). The multi-baseline technique reduced considerably the noise on both TSA-pp and TSA-DC. The reduction of noise was more important when Dpp was higher. For Dpp = 3 mm the average (±standard deviation (SD)) of TSA-pp and TSA-DC was reduced from 4.5 (± 2.5) and 2.5 (±0.6) °C, respectively, to 0.8 (± 0.7) and 0.09 (± 0.2) °C. This in vivo study showed the level of noise in PRFS-based thermometry introduced by respiratory motion in the context of MRgHIFU hyperthermia treatment for head and neck and the feasibility of reducing this noise using a multi-baseline technique.

Dopamine D(1) receptor deletion strongly reduces neurotoxic effects of methamphetamine.

PubMed

Ares-Santos, S; Granado, N; Oliva, I; O'Shea, E; Martin, E D; Colado, M I; Moratalla, R

2012-02-01

Methamphetamine (METH) is a potent, highly addictive psychostimulant consumed worldwide. In humans and experimental animals, repeated exposure to this drug induces persistent neurodegenerative changes. Damage occurs primarily to dopaminergic neurons, accompanied by gliosis. The toxic effects of METH involve excessive dopamine (DA) release, thus DA receptors are highly likely to play a role in this process. To define the role of D(1) receptors in the neurotoxic effects of METH we used D(1) receptor knock-out mice (D(1)R(-/-)) and their WT littermates. Inactivation of D(1)R prevented METH-induced dopamine fibre loss and hyperthermia, and increases in gliosis and pro-inflammatory molecules such as iNOS in the striatum. In addition, D(1)R inactivation prevented METH-induced loss of dopaminergic neurons in the substantia nigra. To explore the relationship between hyperthermia and neurotoxicity, METH was given at high ambient temperature (29 °C). In this condition, D(1)R(-/-) mice developed hyperthermia following drug delivery and the neuroprotection provided by D(1)R inactivation at 23 °C was no longer observed. However, reserpine, which empties vesicular dopamine stores, blocked hyperthermia and strongly potentiated dopamine toxicity in D(1)R(-/-) mice, suggesting that the protection afforded by D(1)R inactivation is due to both hypothermia and higher stored vesicular dopamine. Moreover, electrical stimulation evoked higher DA overflow in D(1)R(-/-) mice as demonstrated by fast scan cyclic voltammetry despite their lower basal DA content, suggesting higher vesicular DA content in D(1)R(-/-) than in WT mice. Altogether, these results indicate that the D(1)R plays a significant role in METH-induced neurotoxicity by mediating drug-induced hyperthermia and increasing the releasable cytosolic DA pool. Copyright © 2011. Published by Elsevier Inc.

Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats.

PubMed

Goñi-Allo, Beatriz; Puerta, Elena; Hervias, Isabel; Di Palma, Richard; Ramos, Maria; Lasheras, Berta; Aguirre, Norberto

2007-05-21

Amiloride and several of its congeners known to block the Na(+)/Ca(2+) and/or Na(+)/H(+) antiporters potentiate methamphetamine-induced neurotoxicity without altering methamphetamine-induced hyperthermia. We now examine whether amiloride also exacerbates 3,4-methylenedioxymethamphetamine (MDMA)-induced long-term serotonin (5-HT) loss in rats. Amiloride (2.5 mg/kg, every 2 h x 3, i.p.) given at ambient temperature 30 min before MDMA (5 mg/kg, every 2 h x 3, i.p.), markedly exacerbated long-term 5-HT loss. However, in contrast to methamphetamine, amiloride also potentiated MDMA-induced hyperthermia. Fluoxetine (10 mg/kg i.p.) completely protected against 5-HT depletion caused by the MDMA/amiloride combination without significantly altering the hyperthermic response. By contrast, the calcium channel antagonists flunarizine or diltiazem did not afford any protection. Findings with MDMA and amiloride were extended to the highly selective Na(+)/H(+) exchange inhibitor dimethylamiloride, suggesting that the potentiating effects of amiloride are probably mediated by the blockade of Na(+)/H(+) exchange. When the MDMA/amiloride combination was administered at 15 degrees C hyperthermia did not develop and brain 5-HT concentrations remained unchanged 7 days later. Intrastriatal perfusion of MDMA (100 microM for 8 h) in combination with systemic amiloride caused a small depletion of striatal 5-HT content in animals made hyperthermic but not in the striatum of normothermic rats. These data suggest that enhancement of MDMA-induced 5-HT loss caused by amiloride or dimethylamiloride depends on their ability to enhance MDMA-induced hyperthermia. We hypothesise that blockade of Na(+)/H(+) exchange could synergize with hyperthermia to render 5-HT terminals more vulnerable to the toxic effects of MDMA.

Nitric oxide is not permissive for cutaneous active vasodilatation in humans.

PubMed

Wilkins, Brad W; Holowatz, Lacy A; Wong, Brett J; Minson, Christopher T

2003-05-01

The precise role of nitric oxide (NO) in cutaneous active vasodilatation in humans is unknown. We tested the hypothesis that NO is necessary to permit the action of an unknown vasodilator. Specifically, we investigated whether a low-dose infusion of exogenous NO, in the form of sodium nitroprusside (SNP), would fully restore vasodilatation in an area of skin in which endogenous NO was inhibited during hyperthermia. This finding would suggest a 'permissive' role for NO in active vasodilatation. Eight subjects were instrumented with three microdialysis fibres in forearm skin. Sites were randomly assigned to (1) Site A: control site; (2) Site B: NO synthase (NOS) inhibition during established hyperthermia; or (3) Site C: NOS inhibition throughout the protocol. Red blood cell flux was measured using laser-Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was normalized to maximal vasodilatation at each site. In Site B, NG-nitro-L-arginine methyl ester (L-NAME) infusion during hyperthermia reduced CVC by approximately 32 % (65 +/- 4 % CVCmax vs. 45 +/- 4 % CVCmax; P < 0.05). Vasodilatation was not restored to pre-NOS inhibition values in this site following low-dose SNP infusion (55 +/- 4 % CVCmax vs. 65 +/- 4 % CVCmax; P < 0.05). CVC remained significantly lower than the control site with low-dose SNP infusion in Site C (P < 0.05). The rise in CVC with low-dose SNP (deltaCVC) was significantly greater in Site B and Site C during hyperthermia compared to normothermia (P < 0.05). No difference in deltaCVC was observed between hyperthermia and normothermia in the control site (Site A). Thus, NO does not act permissively in cutaneous active vasodilatation in humans but may directly mediate vasodilatation and enhance the effect of an unknown active vasodilator.

Adjuvant properties of thermal component of hyperthermia enhanced transdermal immunization: effect on dendritic cells.

PubMed

Joshi, Neha; Duhan, Vikas; Lingwal, Neelam; Bhaskar, Sangeeta; Upadhyay, Pramod

2012-01-01

Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential.

Fe3O4@Au composite magnetic nanoparticles modified with cetuximab for targeted magneto-photothermal therapy of glioma cells.

PubMed

Lu, Qianling; Dai, Xinyu; Zhang, Peng; Tan, Xiao; Zhong, Yuejiao; Yao, Cheng; Song, Mei; Song, Guili; Zhang, Zhenghai; Peng, Gang; Guo, Zhirui; Ge, Yaoqi; Zhang, Kangzhen; Li, Yuntao

2018-01-01

Thermoresponsive nanoparticles have become an attractive candidate for designing combined multimodal therapy strategies because of the onset of hyperthermia and their advantages in synergistic cancer treatment. In this paper, novel cetuximab (C225)-encapsulated core-shell Fe 3 O 4 @Au magnetic nanoparticles (Fe 3 O 4 @Au-C225 composite-targeted MNPs) were created and applied as a therapeutic nanocarrier to conduct targeted magneto-photothermal therapy against glioma cells. The core-shell Fe 3 O 4 @Au magnetic nanoparticles (MNPs) were prepared, and then C225 was further absorbed to synthesize Fe 3 O 4 @Au-C225 composite-targeted MNPs. Their morphology, mean particle size, zeta potential, optical property, magnetic property and thermal dynamic profiles were characterized. After that, the glioma-destructive effect of magnetic fluid hyperthermia (MFH) combined with near-infrared (NIR) hyperthermia mediated by Fe 3 O 4 @Au-C225 composite-targeted MNPs was evaluated through in vitro and in vivo experiments. The inhibitory and apoptotic rates of Fe 3 O 4 @Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group were significantly higher than other groups in vitro and the marked upregulation of caspase-3, caspase-8, and caspase-9 expression indicated excellent antitumor effect by inducing intrinsic apoptosis. Furthermore, Fe 3 O 4 @Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group exhibited significant tumor growth suppression compared with other groups in vivo. Our studies illustrated that Fe 3 O 4 @Au-C225 composite-targeted MNPs have great potential as a promising nanoplatform for human glioma therapy and could be of great value in medical use in the future.

Fe3O4@Au composite magnetic nanoparticles modified with cetuximab for targeted magneto-photothermal therapy of glioma cells

PubMed Central

Tan, Xiao; Zhong, Yuejiao; Yao, Cheng; Song, Mei; Song, Guili; Zhang, Zhenghai; Peng, Gang; Guo, Zhirui; Ge, Yaoqi; Zhang, Kangzhen; Li, Yuntao

2018-01-01

Background Thermoresponsive nanoparticles have become an attractive candidate for designing combined multimodal therapy strategies because of the onset of hyperthermia and their advantages in synergistic cancer treatment. In this paper, novel cetuximab (C225)-encapsulated core-shell Fe3O4@Au magnetic nanoparticles (Fe3O4@Au-C225 composite-targeted MNPs) were created and applied as a therapeutic nanocarrier to conduct targeted magneto-photothermal therapy against glioma cells. Methods The core-shell Fe3O4@Au magnetic nanoparticles (MNPs) were prepared, and then C225 was further absorbed to synthesize Fe3O4@Au-C225 composite-targeted MNPs. Their morphology, mean particle size, zeta potential, optical property, magnetic property and thermal dynamic profiles were characterized. After that, the glioma-destructive effect of magnetic fluid hyperthermia (MFH) combined with near-infrared (NIR) hyperthermia mediated by Fe3O4@Au-C225 composite-targeted MNPs was evaluated through in vitro and in vivo experiments. Results The inhibitory and apoptotic rates of Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group were significantly higher than other groups in vitro and the marked upregulation of caspase-3, caspase-8, and caspase-9 expression indicated excellent antitumor effect by inducing intrinsic apoptosis. Furthermore, Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group exhibited significant tumor growth suppression compared with other groups in vivo. Conclusion Our studies illustrated that Fe3O4@Au-C225 composite-targeted MNPs have great potential as a promising nanoplatform for human glioma therapy and could be of great value in medical use in the future. PMID:29719396

Thermoregulation During Spaceflight

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Fortney, Suzanne M.

1992-01-01

The purpose of this flight proposal is to investigate human thermoregulatory parameters during exercise in microgravity. The hypothesis to be tested is that microgravity-adopted astronauts will exhibit accentuated increases in their core temperature (excess hyperthermia) during exercise because of altered heat loss responses due to reduced sweating and/or accentuated vasodilation. The specific aims are (1) to compare core and skin temperature responses during moderate exercise before flight and inflight; (2) to determine whether the hypothesized inflight excessive hyperthermia is due to increased heat production, reduced, sweating, impaired peripheral vasodilation, or to some combination of these factors; and (3) to determine whether heat production at an exercise load of 60 percent of the maximal working capacity is similar preflight and inflight. It is expected that the astronauts will exhibit excessive hyperthermia during exposure to microgravity which will be caused by decreased sweating and decreased skin blood flow.

Magnetic hyperthermia performance of magnetite nanoparticle assemblies under different driving fields

NASA Astrophysics Data System (ADS)

Wu, Kai; Wang, Jian-Ping

2017-05-01

The heating performance of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) is dependent on several factors. Optimizing these factors improves the heating efficiency for cancer therapy and meanwhile lowers the MNP treatment dosage. AMF is one of the most easily controllable variables to enhance the efficiency of heat generation. This paper investigated the optimal magnetic field strength and frequency for an assembly of magnetite nanoparticles. For hyperthermia treatment in clinical applications, monodispersed NPs are forming nanoclusters in target regions where a strong magnetically interactive environment is anticipated, which leads to a completely different situation than MNPs in ferrofluids. Herein, the energy barrier model is revisited and Néel relaxation time is tailored for high MNP packing densities. AMF strength and frequency are customized for different magnetite NPs to achieve the highest power generation and the best hyperthermia performance.

Magnetic nanoparticles-based acoustical detection and hyperthermic treatment of cancer, in vitro and in vivo studies

NASA Astrophysics Data System (ADS)

Shoval, Asaf; Tepper, Michal; Tikochkiy, Jenny; Gur, Leah Ben; Markovich, Gil; Keisari, Yona; Gannot, Israel

2016-07-01

This paper describes a minimally invasive method for detection and growth inhibition of tumors that utilizes the unique properties of super paramagnetic nanoparticles. To demonstrate the feasibility of this method, dimercaptosuccinic acid-coated magnetite nanoparticles were successfully fabricated and used. Those nanoparticles were simultaneously used for magnetoacoustic detection of tumors and for specific hyperthermia treatment in C57BL/J mice injected with Lewis lung carcinoma cells. The in vivo acoustic signal attributed to the nanoparticles was 4.4 dB, while the single session hyperthermia treatment caused a reduction of 50% in tumor growing rate. In addition, a thermography-based method was applied to monitor the efficacy of the hyperthermia treatment. The presented method has the potential to revolutionize current cancer treatment by enabling diagnosis and treatment under real-time feedback in one session.

Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

DTIC Science & Technology

2012-10-01

conclusions: 1) Airway hyperresponsiveness developed in Ova-sensitized mice was less pronounced in TRPV1 -null mice, indicating an important role of TRPV1 ...expression of the transient receptor potential vanilloid type 1 ( TRPV1 ) channel is up-regulated in the airway mucosa of patients with mild asthma... TRPV1 channel in triggering the bronchoconstriction caused by airway hyperthermia, and to determine whether this acute bronchoconstrictive effect was

Hyperthermia apparatus

DOEpatents

Larsen, Lawrence E.

2000-01-01

A hyperthermia apparatus, suitable for transurethral application, has an energy radiating element comprising a leaky-wave antenna. The leaky wave antenna radiation pattern is characterized by a surface wave which propagates along an aperture formed by openings (small in comparison to a wavelength) in the outer conductor of a transmission line. Appropriate design of the leaky wave antenna produces a uniform, broadside pattern of temperature elevation that uniformly heats all or part of the periurethral tissues.

Differences in the Onset and Severity of Symptoms of Malignant Hyperthermia with Different Inhalational Anesthetics

DTIC Science & Technology

1999-10-01

patients had also received succinylcholine (Fu, Scharf, Mangar & Miller, 1996;Michalek- Sauberer , Fricker, Gradwohl, & Gilly, 1997). The case reported...In the case reported by Michaelek- Sauberer and colleagues (1997), a pediatric patient received desflurane. After 90 minutes of surgery, the...Malignant Hyperthermia 61 biopsy (Fu et al., 1996; Michalek- Sauberer et al., 1997). In both case reports, there was a wide

Changes in ryanodine-induced contractures by stimulus frequency in malignant hyperthermia susceptible and malignant hyperthermia nonsusceptible dog skeletal muscle.

PubMed

Sudo, R T; Nelson, T E

1997-09-01

Elective diagnosis of malignant hyperthermia depends on halothane and caffeine contracture testing of biopsied skeletal muscle. Ryanodine-induced contractures may provide greater sensitivity and specificity for malignant hyperthermia (MH) diagnosis. This study investigated the effects of ryanodine concentration and stimulus frequency to distinguish between MH susceptible (MHS) and MH non-susceptible (MHN) dogs. Increasing ryanodine concentrations (1, 2.5 and 5 microM) increased peak isometric contracture tension, but similar responses in MHS and MHN muscle precluded use for diagnosis. Time to tension onset and to peak tension decreased with increasing ryanodine concentration, and these times were shorter in MH skeletal muscle. Increasing stimulus frequency (0.1, 0.5 and 1 Hz) decreased the time to tension onset and to peak tension, but the effect was greater in MHN muscle which decreased the difference between MHN and MHS muscle responses. When ryanodine contracture tension onset time was selected to detect MHS muscle, combinations of either 0.1 Hz and 1 microM ryanodine or 0.5 Hz and 1 microM ryanodine reduced the probabilty of a false diagnosis to less than 1%. Similar studies performed on human muscle might identify optimal stimulus frequency and ryanodine concentration for detecting MH in patients.

Preparation of Multifunctional Fe@Au Core-Shell Nanoparticles with Surface Grafting as a Potential Treatment for Magnetic Hyperthermia.

PubMed

Chung, Ren-Jei; Shih, Hui-Ting

2014-01-24

Iron core gold shell nanoparticles grafted with Methotrexate (MTX) and indocyanine green (ICG) were synthesized for the first time in this study, and preliminarily evaluated for their potential in magnetic hyperthermia treatment. The core-shell Fe@Au nanoparticles were prepared via the microemulsion process and then grafted with MTX and ICG using hydrolyzed poly(styrene-alt-maleic acid) (PSMA) to obtain core-shell Fe@Au-PSMA-ICG/MTX nanoparticles. MTX is an anti-cancer therapeutic, and ICG is a fluorescent dye. XRD, TEM, FTIR and UV-Vis spectrometry were performed to characterize the nanoparticles. The data indicated that the average size of the nanoparticles was 6.4 ± 09 nm and that the Au coating protected the Fe core from oxidation. MTX and ICG were successfully grafted onto the surface of the nanoparticles. Under exposure to high frequency induction waves, the superparamagnetic nanoparticles elevated the temperature of a solution in a few minutes, which suggested the potential for an application in magnetic hyperthermia treatment. The in vitro studies verified that the nanoparticles were biocompatible; nonetheless, the Fe@Au-PSMA-ICG/MTX nanoparticles killed cancer cells (Hep-G2) via the magnetic hyperthermia mechanism and the release of MTX.

Thermosensitive Ni-based magnetic particles for self-controlled hyperthermia applications

NASA Astrophysics Data System (ADS)

Pandey, Sudip; Quetz, Abdiel; Aryal, Anil; Dubenko, Igor; Mazumdar, Dipanjan; Stadler, Shane; Ali, Naushad

2017-04-01

A number of ferromagnetic alloys in the bulk-form "thermoseeds" have been investigated for localized self-controlled hyperthermia treatment of cancer by substituting V, Mo, Cu, and Ga for Ni. The samples were prepared by arc-melting technique and annealed at 1223 K (950 °C) for 12 h in sealed quartz tubes. The structural, magnetic, and magnetocaloric properties of the samples were studied, using room temperature X-ray diffraction and a Superconducting Quantum Interference Device (SQUID) magnetometer. The magnetocaloric parameters (magnetic entropy changes, refrigeration capacity (RC), and hysteretic effects) have been calculated. It has been shown that recrystallization, i.e., annealing time and temperature, is crucial for controlling the heating characteristics of the seeds. A linear decrease in Curie temperature (TC) from 380 K (107 °C) to 200 K (-73 °C) was observed with increasing substitution of Ni by V, Mo, Cu, and Ga, while the magnetization value remained nearly constant for all substitutions. The optimal composition of these Ni-based alloys has been determined in order to allow self-controlling hyperthermia, implying a Curie temperature near the therapeutic level, 315-318 K (41-45 °C). The results showed that an extraordinary self-regulating heating effect has been achieved in Ni-based magnetic materials, which may create new vistas for hyperthermia cancer treatment.

Single dose x irradiation and concomitant hyperthermia on a murine fibroscarcoma. [Sensitizing effects of hyperthermia on tumors in mice subjected to local radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, E.W.; Alfieri, A.A.; Kim, J.H.

1978-12-01

The objectives of this study were to quantitate the effects of local tumor hyperthermia (LTH) and concomitant x irradiation (RAD) on a moderately radioresistant murine fibrosarcoma in situ. Comparisons were made to the combined treatment response on the Ridgway osteogenic sarcoma, a radiosensitive tumor previously used in this laboratory and to establish the Meth-A fibrosarcoma as a model system for combined modality studies. 1.0 cm/sup 3/ tumors were exposed to single doses of RAD ranging from 0.5 to 3.8 krad alone or 0.5 to 2.3 krad in combination with LTH (water bath at 43.1 +- .05 C for 20 minutes)more » applied immediately postirradiation. LTH significantly enhanced the action of radiation as measured by tumor volume analysis, mean survival time and cures. The ratio of radiation doses vs. RAD + LTH required to produce an equivalent response ranged from 1.4 to 2.5 depending upon the endpoints evaluated. These findings are consistent with single dose studies on the radiosensitive Ridgway osteogenic sarcoma and suggest that the tumoricidal effectiveness of combination radiation and hyperthermia cannot be predicted on the basis of the radiation alone responsiveness of tumor.« less

Pharmacological evaluation of SN79, a sigma (σ) receptor ligand, against methamphetamine-induced neurotoxicity in vivo

PubMed Central

Kaushal, Nidhi; Seminerio, Michael J.; Robson, Matthew J.; McCurdy, Christopher R.; Matsumoto, Rae R.

2013-01-01

Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (σ) receptors in the brain at physiologically relevant concentrations, where it acts in part as an agonist. SN79 (6-acetyl-3-(4-(4-(4-florophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one) was synthesized as a putative σ receptor antagonist with nanomolar affinity and selectivity for σ receptors over 57 other binding sites. SN79 pretreatment afforded protection against methamphetamine-induced hyperthermia and striatal dopaminergic and serotonergic neurotoxicity in male, Swiss Webster mice (measured as depletions in striatal dopamine and serotonin levels, and reductions in striatal dopamine and serotonin transporter expression levels). In contrast, di-o-tolylguanidine (DTG), a well established σ receptor agonist, increased the lethal effects of methamphetamine, although it did not further exacerbate methamphetamine-induced hyperthermia. Together, the data implicate σ receptors in the direct modulation of some effects of methamphetamine such as lethality, while having a modulatory role which can mitigate other methamphetamine-induced effects such as hyperthermia and neurotoxicity. PMID:22921523

Microstrip-antenna design for hyperthermia treatment of superficial tumors.

PubMed

Montecchia, F

1992-06-01

Microstrip antennas have many different advantages over other RF/MW radiative applicators employed for superficial hyperthermia treatment. This is mainly due to their compact and body-conformable structure as well as to printed circuit board techniques, both of which allow a wide design flexibility for superficial tumor heating. Among the wide variety of radiator configurations, three microstrip antennas of increasing complexity with electromagnetic and heating characteristics potentially suitable as applicators for superficial hyperthermia have been designed, developed, and tested in different radiative conditions: a microstrip disk, a microstrip annular-slot, and a microstrip spiral. Electromagnetic design criteria are presented together with the determinations of the applicator return loss versus frequency and thermograms of the near-field heating pattern in muscle-like phantom. The results are in good agreement with theory and indicate that: i) the operating frequency is either single or multiple according to the applicator-mode, "resonant" or "traveling-wave," and can be chosen in the useful frequency range for hyperthermia (200-1000 MHz) according to the tumor cross-section and depth; ii) the heating pattern flexibility increases going from the simple geometry disk to the annular-slot and spiral applicators; iii) a distilled-water bolus is required; iv) the annular-slot applicator exhibits the highest efficiency, while the spiral applicator provides the best performance.

Duality of Iron Oxide Nanoparticles in Cancer Therapy: Amplification of Heating Efficiency by Magnetic Hyperthermia and Photothermal Bimodal Treatment.

PubMed

Espinosa, Ana; Di Corato, Riccardo; Kolosnjaj-Tabi, Jelena; Flaud, Patrice; Pellegrino, Teresa; Wilhelm, Claire

2016-02-23

The pursuit of innovative, multifunctional, more efficient, and safer treatments is a major challenge in preclinical nanoparticle-mediated thermotherapeutic research. Here, we report that iron oxide nanoparticles have the dual capacity to act as both magnetic and photothermal agents. We further explore every key aspect of this magnetophotothermal approach, choosing iron oxide nanocubes for their high efficiency for the magnetic hyperthermia modality itself. In aqueous suspension, the nanocubes' exposure to both: an alternating magnetic field and near-infrared laser irradiation (808 nm), defined as the DUAL-mode, amplifies the heating effect 2- to 5-fold by comparison with magnetic stimulation alone, yielding unprecedented heating powers (specific loss powers) up to 5000 W/g. In cancer cells, the laser excitation restores the optimal efficiency of magnetic hyperthermia, otherwise inhibited by intracellular confinement, resulting in a remarkable heating efficiency in the DUAL-mode (up to 15-fold amplification), with respect to the magnetophotothermal mode. As a consequence, the dual action yielded complete apoptosis-mediated cell death. In solid tumors in vivo, single-mode treatments (magnetic or laser hyperthermia) reduced tumor growth, while DUAL-mode treatment resulted in complete tumor regression, mediated by heat-induced tumoral cell apoptosis and massive denaturation of the collagen fibers, and a long-lasting thermal efficiency over repeated treatments.

Vasomotor response of the human face: laser-Doppler measurements during mild hypo- and hyperthermia.

PubMed

Rasch, W; Cabanac, M

1993-04-01

The skin of the face is reputed not to vasoconstrict in response to cold stress because the face skin temperature remains steady during hypothermia. The purpose of the present work was to measure the vasomotor response of the human face to whole-body hypothermia, and to compare it with hyperthermia. Six male subjects were immersed in cold and in warm water to obtain the two conditions. Skin blood flow, evaporation, and skin temperature (Tsk) were recorded in three loci of the face, the forehead, the infra orbital area, and the cheek. Tympanic (Tty) and oesophageal (Toes) temperatures were also recorded during the different thermal states. Normothermic measurements served as control. Blood flow was recorded with a laser-Doppler flowmeter, evaporation measured with an evaporimeter. Face Tsk remained stable between normo-, hypo-, and hyperthermia. Facial blood flow, however, did not follow the same pattern. The facial blood flow remained at minimal vasoconstricted level when the subjects' condition was changed from normo- to hypothermia. When the condition changed from hypo- to hyperthermia a 3 to 9-fold increase in the blood flow was recorded. From these results it was concluded that a vasoconstriction seems to be the general vasomotor state in the face during normothermia.

Implantable chemothermal brachytherapy seeds: A synergistic approach to brachytherapy using polymeric dual drug delivery and hyperthermia for malignant solid tumor ablation.

PubMed

Aguilar, Ludwig Erik; Thomas, Reju George; Moon, Myeong Ju; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

2018-08-01

Chemothermal brachytherapy seeds have been developed using a combination of polymeric dual drug chemotherapy and alternating magnetic field induced hyperthermia. The synergistic effect of chemotherapy and hyperthermia brachytherapy has been investigated in a way that has never been performed before, with an in-depth analysis of the cancer cell inhibition property of the new system. A comprehensive in vivo study on athymic mice model with SCC7 tumor has been conducted to determine optimal arrays and specifications of the chemothermal seeds. Dual drug chemotherapy has been achieved via surface deposition of polydopamine that carries bortezomib, and also via loading an acidic pH soluble hydrogel that contains 5-Fluorouracil inside the chemothermal seed; this increases the drug loading capacity of the chemothermal seed, and creates dual drug synergism. An external alternating magnetic field has been utilized to induce hyperthermia conditions, using the inherent ferromagnetic property of the nitinol alloy used as the seed casing. The materials used in this study were fully characterized using FESEM, H 1 NMR, FT-IR, and XPS to validate their properties. This new approach to experimental cancer treatment is a pilot study that exhibits the potential of thermal brachytherapy and chemotherapy as a combined treatment modality. Copyright © 2018 Elsevier B.V. All rights reserved.

Application and possible mechanisms of combining LLLT (low level laser therapy), infrared hyperthermia and ionizing radiation in the treatment of cancer

NASA Astrophysics Data System (ADS)

Abraham, Edward H.; Woo, Van H.; Harlin-Jones, Cheryl; Heselich, Anja; Frohns, Florian

2014-02-01

Benefit of concomitant infrared hyperthermia and low level laser therapy and ionizing radiation is evaluated in this study. The purpose/objectives: presentation with locally advanced bulky superficial tumors is clinically challenging. To enhance the efficacy of chemotherapy and IMRT (intensity-modulated radiation therapy) and/or electron beam therapy we have developed an inexpensive and clinically effective infrared hyperthermia approach that combines black-body infrared radiation with halogen spectrum radiation and discrete wave length infrared clinical lasers LLLT. The goal is to produce a composite spectrum extending from the far infrared to near infrared and portions of the visible spectrum with discrete penetrating wavelengths generated by the clinical infrared lasers with frequencies of 810 nm and/or 830 nm. The composite spectrum from these sources is applied before and after radiation therapy. We monitor the surface and in some cases deeper temperatures with thermal probes, but use an array of surface probes as the limiting safe thermal constraint in patient treatment while at the same time maximizing infrared entry to deeper tissue layers. Fever-grade infrared hyperthermia is produced in the first centimeters while non-thermal infrared effects act at deeper tissue layers. The combination of these effects with ionizing radiation leads to improved tumor control in many cancers.

Thermo-sensitively and magnetically ordered mesoporous carbon nanospheres for targeted controlled drug release and hyperthermia application.

PubMed

Chen, Lin; Zhang, Huan; Zheng, Jing; Yu, Shiping; Du, Jinglei; Yang, Yongzhen; Liu, Xuguang

2018-03-01

A multifunctional nanoplatform based on thermo-sensitively and magnetically ordered mesoporous carbon nanospheres (TMOMCNs) is developed for effective targeted controlled release of doxorubicin hydrochloride (DOX) and hyperthermia in this work. The morphology, specific surface area, porosity, thermo-stability, thermo-sensitivity, as well as magnetism properties of TMOMCNs were verified by high resolution transmission electron microscopy, field emission scanning electron microscopy, thermo-gravimetric analysis, X-ray diffraction, Brunauer-Emmeltt-Teller surface area analysis, dynamic light scattering and vibrating sample magnetometry measurement. The results indicate that TMOMCNs have an average diameter of ~146nm with a lower critical solution temperature at around 39.5°C. They are superparamagnetic with a magnetization of 10.15emu/g at 20kOe. They generate heat when inductive magnetic field is applied to them and have a normalized specific absorption rate of 30.23W/g at 230kHz and 290Oe, showing good potential for hyperthermia. The DOX loading and release results illustrate that the loading capacity is 135.10mg/g and release performance could be regulated by changing pH and temperature. The good targeting, DOX loading and release and hyperthermia properties of TMOMCNs offer new probabilities for high effectiveness and low toxicity of cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacological evaluation of SN79, a sigma (σ) receptor ligand, against methamphetamine-induced neurotoxicity in vivo.

PubMed

Kaushal, Nidhi; Seminerio, Michael J; Robson, Matthew J; McCurdy, Christopher R; Matsumoto, Rae R

2013-08-01

Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (σ) receptors in the brain at physiologically relevant concentrations, where it "acts in part as an agonist." SN79 (6-acetyl-3-(4-(4-(4-florophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one) was synthesized as a putative σ receptor antagonist with nanomolar affinity and selectivity for σ receptors over 57 other binding sites. SN79 pretreatment afforded protection against methamphetamine-induced hyperthermia and striatal dopaminergic and serotonergic neurotoxicity in male, Swiss Webster mice (measured as depletions in striatal dopamine and serotonin levels, and reductions in striatal dopamine and serotonin transporter expression levels). In contrast, di-o-tolylguanidine (DTG), a well established σ receptor agonist, increased the lethal effects of methamphetamine, although it did not further exacerbate methamphetamine-induced hyperthermia. Together, the data implicate σ receptors in the direct modulation of some effects of methamphetamine such as lethality, while having a modulatory role which can mitigate other methamphetamine-induced effects such as hyperthermia and neurotoxicity. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Fighting fire with fire: the revival of thermotherapy for gliomas.

PubMed

Lee Titsworth, William; Murad, Greg J A; Hoh, Brian L; Rahman, Maryam

2014-02-01

In 1891, an orthopedic surgeon in New York noted the disappearance of an inoperable sarcoma in a patient after a febrile illness. This observation resulted in experiments assessing the utility of heat therapy or thermotherapy for the treatment of cancer. While it initially fell from favor, thermotherapy has recently made a resurgence, sparking investigations into its anticancer properties. This therapy is especially attractive for glioblastoma multiforme (GBM) which is difficult to target due to the blood-brain barrier and recalcitrant to treatment. Here we briefly review the history of thermotherapy and then more methodically present the current literature as it relates to central nervous system malignancies. Recent developments show that heat is preferentially cytotoxic to tumor cells and induces cellular pathways which result in apoptotic and non-apoptotic death. Techniques to induce hyperthermia include regional hyperthermia by water bath, focused ultrasound, radiofrequency microwaves, laser-induced interstitial thermotherapy, and magnetic energy. The recent revival of these therapeutic approaches and their preliminary outcomes in the treatment of GBM is reviewed. From bacterial toxins to infusion of magnetic nanoparticles, hyperthermia has the potential to be an effective and easy-to-execute adjuvant therapy for GBM. Hyperthermia for GBM is a promising therapy as part of a growing armamentarium for malignant glioma treatment.

Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential.

PubMed

Guthrie, T C; Nelson, D A

1995-03-01

In 1890, Uhthoff studied multiple sclerosis (MS) patients who developed amblyopia following exercise, a phenomenon later discovered to be secondary to elevated body temperature from muscular activity. Six decades later, the hot bath test and various other heating reactions (HR) began to be used diagnostically. They were essentially discontinued after 1983, being replaced by more specific and safer tests and procedures. Over 80% of MS patients develop a panoply of neurological signs during hyperthermia, 60% of which are "new" to that patient. The literature contains a number of unexplained paradoxical responses of MS patients during induced hyperthermia. These challenge the current hypothesis that, in MS, hyperthermia induces a heat-linked neuro-blockade of partially demyelinated axons. Some MS patients developed signs before temperature elevations occurred; others showed clearing of signs while temperatures were elevated or were ascending. Several MS patients improved for about 3 hours after being tested, a rebound phenomenon known as "overshoot." Conversely, other MS patients developed persistent neurological deficits after hyperthermia. The etiology of HR may be multifactorial. This includes heat itself, effects of serum calcium, blockade of ion channels, circulatory changes, heat shock proteins, and unidentified humoral substances. Research techniques are suggested to continue investigations into the enigma of HR, hopefully to widen knowledge of demyelination.

State-of-the-Art Materials for Ultrasound-Triggered Drug Delivery

PubMed Central

Sirsi, Shashank; Borden, Mark

2014-01-01

Ultrasound is a unique and exciting theranostic modality that can be used to track drug carriers, trigger drug release and improve drug deposition with high spatial precision. In this review, we briefly describe the mechanisms of interaction between drug carriers and ultrasound waves, including cavitation, streaming and hyperthermia, and how those interactions can promote drug release and tissue uptake. We then discuss the rational design of some state-of-the-art materials for ultrasound-triggered drug delivery and review recent progress for each drug carrier, focusing on the delivery of chemotherapeutic agents such as doxorubicin. These materials include nanocarrier formulations, such as liposomes and micelles, designed specifically for ultrasound-triggered drug release, as well as microbubbles, microbubble-nanocarrier hybrids, microbubble-seeded hydrogels and phase-change agents. PMID:24389162

Utilization of the k-space Computational Method to Design an Intracavitary Transrectal Ultrasound Phased Array Applicator for Hyperthermia Treatment of Prostate Cancer

NASA Astrophysics Data System (ADS)

Al-Bataineh, Osama M.; Collins, Christopher M.; Sparrow, Victor W.; Keolian, Robert M.; Smith, Nadine Barrie

2006-05-01

This research utilizes the k-space computational method to design an intracavitary probe for hyperthermia treatment of prostate cancer. A three-dimensional (3D) photographical prostate model, utilizing imaging data from the Visible Human Project®, was the basis for inhomogeneous acoustical model development. The acoustical model accounted for sound speed, density, and absorption variations. The k-space computational method was used to simulate ultrasound wave propagation of the designed phased array through the acoustical model. To insure the uniformity and spread of the pressure in the length of the array, and the steering and focusing capability in the width of the array, the equal-sized elements of the phased array were 1 × 14 mm. The anatomical measurements of the prostate were used to predict the final phased array specifications (4 × 20 planar array, 1.2 MHz, element size = 1 × 14 mm, array size = 56 × 20 mm). Good agreement between the exposimetry and the k-space results was achieved. As an example, the -3 dB distances of the focal volume were differing by 9.1% in the propagation direction for k-space prostate simulation and exposimetry results. Temperature simulations indicated that the rectal wall temperature was elevated less than 2°C during hyperthermia treatment. Steering and focusing ability of the designed probe, in both azimuth and propagation directions, were found to span the entire prostate volume with minimal grating lobes (-10 dB reduction from the main lobe) and least heat damage to the rectal wall. Evaluations of the probe included ex vivo and in vivo controlled experiments to deliver the required thermal dose to the targeted tissue. With a desired temperature plateau of 43.0°C, the MRI temperature results at the steady state were 42.9 ± 0.38°C and 43.1 ± 0.80°C for ex vivo and in vivo experiments, respectively. Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield and temperature rise in sophisticated, large scale, 3D, inhomogeneous and coarse grid models.

Differences in the Onset and Severity of Symptoms of Malignant Hyperthermia With Different Inhalational Anesthetics

DTIC Science & Technology

1999-10-01

also received succinylcholine (Fu, Scharf, Mangar & Miller, 1996;Michalek- Sauberer , Fricker, Gradwohl, & Gilly, 1997). The case reported by Fu and...the case reported by Michaelek- Sauberer and colleagues (1997), a pediatric patient received desflurane. After 90 minutes of surgery, the patient s...Malignant Hyperthermia 61 biopsy (Fu et al., 1996; Michalek- Sauberer et al., 1997). In both case reports, there was a wide variability of

Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route

PubMed Central

Iwasaki, Tomohiro; Nakatsuka, Ryo; Murase, Kenya; Takata, Hiroshige; Nakamura, Hideya; Watano, Satoru

2013-01-01

This paper presents a simple method for the rapid synthesis of magnetite/hydroxyapatite composite particles. In this method, superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride. Immediately following the synthesis, carbonate-substituted (B-type) hydroxyapatite particles are mechanochemically synthesized by wet milling dicalcium phosphate dihydrate and calcium carbonate in a dispersed suspension of magnetite nanoparticles, during which the magnetite nanoparticles are incorporated into the hydroxyapatite matrix. We observed that the resultant magnetite/hydroxyapatite composites possessed a homogeneous dispersion of magnetite nanoparticles, characterized by an absence of large aggregates. When this material was subjected to an alternating magnetic field, the heat generated increased with increasing magnetite concentration. For a magnetite concentration of 30 mass%, a temperature increase greater than 20 K was achieved in less than 50 s. These results suggest that our composites exhibit good hyperthermia properties and are promising candidates for hyperthermia treatments. PMID:23629669

Beyond Traditional Hyperthermia: In Vivo Cancer Treatment with Magnetic-Responsive Mesoporous Silica Nanocarriers.

PubMed

Guisasola, Eduardo; Asín, Laura; Beola, Lilianne; de la Fuente, Jesús M; Baeza, Alejandro; Vallet-Regí, María

2018-04-18

In this study, we present an innovation in the tumor treatment in vivo mediated by magnetic mesoporous silica nanoparticles. This device was built with iron oxide magnetic nanoparticles embedded in a mesoporous silica matrix and coated with an engineered thermoresponsive polymer. The magnetic nanoparticles act as internal heating sources under an alternating magnetic field (AMF) that increase the temperature of the surroundings, provoking the polymer transition and consequently the release of a drug trapped inside the silica pores. By a synergic effect between the intracellular hyperthermia and chemotherapy triggered by AMF application, significant tumor growth inhibition was achieved in 48 h after treatment. Furthermore, the small magnetic loading used in the experiments indicates that the treatment is carried out without a global temperature rise of the tissue, which avoids the problem of the necessity to employ large amounts of magnetic cores, as is common in current magnetic hyperthermia.

Core–Shell Nanoparticle-Based Peptide Therapeutics and Combined Hyperthermia for Enhanced Cancer Cell Apoptosis

PubMed Central

2015-01-01

Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core–shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis. PMID:25133971

Synthesis, characterization and hemolysis studies of Zn(1-x)CaxFe2O4 ferrites synthesized by sol-gel for hyperthermia treatment applications

NASA Astrophysics Data System (ADS)

Jasso-Terán, Rosario Argentina; Cortés-Hernández, Dora Alicia; Sánchez-Fuentes, Héctor Javier; Reyes-Rodríguez, Pamela Yajaira; de-León-Prado, Laura Elena; Escobedo-Bocardo, José Concepción; Almanza-Robles, José Manuel

2017-04-01

The synthesis of Zn(1-x)CaxFe2O4 nanoparticles, x=0, 0.25, 0.50, 0.75 and 1.0, was performed by sol-gel method followed by a heat treatment at 400 °C for 30 min. These ferrites showed nanometric sizes and nearly superparamagnetic behavior. The Zn0.50Ca0.50Fe2O4 and CaFe2O4 ferrites presented a size within the range of 12-14 nm and appropriate heating ability for hyperthermia applications. Hemolysis testing demonstrated that Zn0.50Ca0.50Fe2O4 ferrite was not cytotoxic when using 10 mg of ferrite/mL of solution. According to the results obtained, Zn0.50Ca0.50Fe2O4 is a potential material for cancer treatment by magnetic hyperthermia therapy.

Magnetic mesoporous silica nanoparticles for potential delivery of chemotherapeutic drugs and hyperthermia.

PubMed

Tao, Cuilian; Zhu, Yufang

2014-11-07

Magnetic mesoporous silica (MMS) nanoparticles with controllable magnetization have been synthesized by encapsulating Fe3O4 nanoparticles in a mesoporous silica matrix. The structure, magnetic heating capacity and drug delivery ability of MMS nanoparticles were evaluated. The results showed that MMS nanoparticles had an average particle size of 150 nm and showed low cytotoxicity and efficient cell uptake ability. MMS nanoparticles exhibited a sustained drug release in the medium of pH 5.0, but a very slow release in the medium of pH 7.4. On the other hand, MMS nanoparticles could controllably generate heat to reach the hyperthermia temperature within a short time upon exposure to an alternating magnetic field due to the superparamagnetic behavior and controllable magnetization. Therefore, MMS nanoparticles could provide a promising multifunctional platform for the combination of chemotherapy and hyperthermia for cancer therapy.

Laserthermia: a new computer-controlled contact Nd: YAG system for interstitial local hyperthermia.

PubMed

Daikuzono, N; Suzuki, S; Tajiri, H; Tsunekawa, H; Ohyama, M; Joffe, S N

1988-01-01

Contact Nd:YAG laser surgery is assuming a greater importance in endoscopic and open surgery, allowing coagulation, cutting, and vaporization with greater precision and safety. A new contact probe allows a wider angle of irradiation and diffusion of low-power laser energy (less than 5 watts), using the interstitial technique for producing local hyperthermia. Temperature sensors that monitor continuously can be placed directly into the surrounding tissue or tumor. Using a computer program interfaced with the laser and sensors, a controlled and stable temperature (e.g., 42 degrees C) can be produced in a known volume of tissue over a prolonged period of time (e.g., 20-40 min). This new laserthermia system, using a single low-power Nd:YAG laser for interstitial local hyperthermia, may offer many new advantages in the experimental treatment and clinical management of carcinoma. A multiple system is now being developed.

RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction.

PubMed

Voermans, N C; Snoeck, M; Jungbluth, H

2016-10-01

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide spectrum of inherited myopathies presenting throughout life. Malignant hyperthermia susceptibility (MHS)-related RYR1 mutations have emerged as a common cause of exertional rhabdomyolysis, accounting for up to 30% of rhabdomyolysis episodes in otherwise healthy individuals. Common triggers are exercise and heat and, less frequently, viral infections, alcohol and drugs. Most subjects are normally strong and have no personal or family history of malignant hyperthermia. Heat intolerance and cold-induced muscle stiffness may be a feature. Recognition of this (probably not uncommon) rhabdomyolysis cause is vital for effective counselling, to identify potentially malignant hyperthermia-susceptible individuals and to adapt training regimes. Studies in various animal models provide insights regarding possible pathophysiological mechanisms and offer therapeutic perspectives. Copyright © 2016. Published by Elsevier Masson SAS.

Nanoparticle-induced intraperitoneal hyperthermia and targeted photoablation in treating ovarian cancer

PubMed Central

Wu, Chao-Chih; Yang, Yuh-Cheng; Hsu, Yun-Ting; Wu, T.-C.; Hung, Chien-Fu; Huang, Jung-Tang; Chang, Chih-Long

2015-01-01

Hyperthermic intraperitoneal chemotherapy is effective in treating various intra-abdominal malignancies. However, this therapeutic modality can only be performed during surgical operations and cannot be used repeatedly. We propose repeatedly noninvasive hyperthermia mediated by pegylated silica-core gold nanoshells (pSGNs) in vivo with external near-infrared (NIR) laser irradiation. This study demonstrated that repeated photothermal treatment can effectively eliminate intraperitoneal tumors in mouse ovarian cancer models without damage of normal tissues. By conjugating pSGNs with anti-human CD47 monoclonal antibody, a significant photoablative effect can be achieved using lower amount of pSGNs and shorter NIR laser irradiation. Conjugated pSGNs specifically targeted and bound to cancer cells inside the peritoneal cavity. Our results indicate the possibility of a noninvasive method of repeated hyperthermia and photoablative therapies using nanoparticles. This has substantial clinical potential in treating ovarian and other intraperitoneal cancers. PMID:26318039

Gold Nanoparticle Hyperthermia Reduces Radiotherapy Dose

PubMed Central

Lin, Lynn; Slatkin, Daniel N.; Dilmanian, F. Avraham; Vadas, Timothy M.; Smilowitz, Henry M.

2014-01-01

Gold nanoparticles can absorb near infrared light, resulting in heating and ablation of tumors. Gold nanoparticles have also been used for enhancing the dose of X-rays in tumors during radiotherapy. The combination of hyperthermia and radiotherapy is synergistic, importantly allowing a reduction in X-ray dose with improved therapeutic results. Here we intratumorally infused small 15 nm gold nanoparticles engineered to be transformed from infrared-transparent to infrared-absorptive by the tumor, which were then heated by infrared followed by X-ray treatment. Synergy was studied using a very radioresistant subcutaneous squamous cell carcinoma (SCCVII) in mice. It was found that the dose required to control 50% of the tumors, normally 55 Gy, could be reduced to <15 Gy (a factor of >3.7). Gold nanoparticles therefore provide a method to combine hyperthermia and radiotherapy to drastically reduce the X-ray radiation needed, thus sparing normal tissue, reducing the side effects, and making radiotherapy more effective. PMID:24990355

Physics responsible for heating efficiency and self-controlled temperature rise of magnetic nanoparticles in magnetic hyperthermia therapy.

PubMed

Shaterabadi, Zhila; Nabiyouni, Gholamreza; Soleymani, Meysam

2018-03-01

Magnetic nanoparticles as heat-generating nanosources in hyperthermia treatment are still faced with many drawbacks for achieving sufficient clinical potential. In this context, increase in heating ability of magnetic nanoparticles in a biologically safe alternating magnetic field and also approach to a precise control on temperature rise are two challenging subjects so that a significant part of researchers' efforts has been devoted to them. Since a deep understanding of Physics concepts of heat generation by magnetic nanoparticles is essential to develop hyperthermia as a cancer treatment with non-adverse side effects, this review focuses on different mechanisms responsible for heat dissipation in a radio frequency magnetic field. Moreover, particular attention is given to ferrite-based nanoparticles because of their suitability in radio frequency magnetic fields. Also, the key role of Curie temperature in suppressing undesired temperature rise is highlighted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR-guided endorectal HIFU ablation array

PubMed Central

Salgaonkar, Vasant A.; Prakash, Punit; Rieke, Viola; Ozhinsky, Eugene; Plata, Juan; Kurhanewicz, John; Hsu, I-C. (Joe); Diederich, Chris J.

2014-01-01

Purpose: Feasibility of targeted and volumetric hyperthermia (40–45 °C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy. Methods: The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm2, ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W). Results: Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm2). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13–23 cm3 volumes for sonications with planar or diverging beam patterns at 0.9–1.2 W/cm2, in 4.5–5.8 cm3 volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm2, and in ∼6.0 cm3 for curvilinear (cylindrical) beam patterns at 0.75 W/cm2. Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm2, 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations. Conclusions: The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints. PMID:24593742

Increases in core temperature counterbalance effects of haemoconcentration on blood viscosity during prolonged exercise in the heat.

PubMed

Buono, Michael J; Krippes, Taylor; Kolkhorst, Fred W; Williams, Alexander T; Cabrales, Pedro

2016-02-01

What is the central question of this study? The purpose of the present study was to determine the effects of exercise-induced haemoconcentration and hyperthermia on blood viscosity. What is the main finding and its importance? Exercise-induced haemoconcentration, increased plasma viscosity and increased blood aggregation, all of which increased blood viscosity, were counterbalanced by increased red blood cell (RBC) deformability (e.g. RBC membrane shear elastic modulus and elongation index) caused by the hyperthermia. Thus, blood viscosity remained unchanged following prolonged moderate-intensity exercise in the heat. Previous studies have reported that blood viscosity is significantly increased following exercise. However, these studies measured both pre- and postexercise blood viscosity at 37 °C even though core and blood temperatures would be expected to have increased during the exercise. Consequently, the effect of exercise-induced hyperthermia on mitigating change in blood viscosity may have been missed. The purpose of this study was to isolate the effects of exercise-induced haemoconcentration and hyperthermia and to determine their combined effects on blood viscosity. Nine subjects performed 2 h of moderate-intensity exercise in the heat (37 °C, 40% relative humidity), which resulted in significant increases from pre-exercise values for rectal temperature (from 37.11 ± 0.35 to 38.76 ± 0.13 °C), haemoconcentration (haematocrit increased from 43.6 ± 3.6 to 45.6 ± 3.5%) and dehydration (change in body weight = -3.6 ± 0.7%). Exercise-induced haemoconcentration significantly (P < 0.05) increased blood viscosity by 9% (from 3.97 to 4.33 cP at 300 s(-1)), whereas exercise-induced hyperthermia significantly decreased blood viscosity by 7% (from 3.97 to 3.69 cP at 300 s(-1)). When both factors were considered together, there was no overall change in blood viscosity (from 3.97 to 4.03 cP at 300 s(-1)). The effects of exercise-induced haemoconcentration, increased plasma viscosity and increased red blood cell aggregation, all of which increased blood viscosity, were counterbalanced by increased red blood cell deformability (e.g. red blood cell membrane shear elastic modulus and elongation index) caused by the hyperthermia. Thus, blood viscosity remained unchanged following prolonged moderate-intensity exercise in the heat. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Immunomodulation of Hyperthermia for Recurrent Prostate Cancer

DTIC Science & Technology

2006-03-01

cells treated with Hyperthermia (HT). HT was administered either as incubation in a 43.7oC water bath or by High frequency focused ultrasound ( HIFU ...immunity and improve local and distant tumor regression. B. BODY B.1. HT induced by water bath (43.7C,1hr) in vivo was compared to HIFU in vivo... HIFU induces coagulative tissue necrosis in the focal zone by rapidly elevating tissue temperature in a short exposure (seconds) while keeping the

Targeted Magnetic Hyperthermia for Lung Cancer

DTIC Science & Technology

2013-09-01

REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 2. REPORT TYPE...3. DATES COVERED 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK...been reported to date . Using various in vitro and in vivo assays, we evaluated the ability of SPIO NP-mediated magnetic hyperthermia to effectively

Core-shell nanocapsules stabilized by single-component polymer and nanoparticles for magneto-chemotherapy/hyperthermia with multiple drugs.

PubMed

Hu, Shang-Hsiu; Liao, Bang-Jie; Chiang, Chin-Sheng; Chen, Po-Jung; Chen, I-Wei; Chen, San-Yuan

2012-07-17

Iron-oxide-containing double emulsion capsules carrying both hydrophilic and hydrophobic therapeutic molecules can deliver drugs and energy on demand in vivo. Magneto-chemotherapy/hyperthermia involves a burst-like release of hydrophilic doxorubicin and hydrophobic paclitaxel, remotely triggered by a high frequency magnetic field, which also releases energy via internalized iron oxide nanoparticles, all contributing to cell kill. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lack of effect of dopaminergic denervation on caudate-putamen hyperthermia or hypothermia induced by drugs and mild stressors.

PubMed

Marcangione, Caterina; Constantin, Annie; Clarke, Paul B S

2010-07-01

A number of drugs and psychological stressors induce brain hyperthermia and increase extracellular dopamine in the caudate-putamen. The present study tested whether caudate-putamen hyperthermia produced by such stimuli is dependent on dopaminergic transmission. Rats were infused with 6-hydroxydopamine unilaterally into the medial forebrain bundle, and after a two-week recovery period, removable thermocouples were used to monitor temperature in the depleted and intact caudate-putamen in freely-moving animals. The indirect dopamine agonist d-amphetamine (1 and 2mg/kg s.c.) increased caudate-putamen temperature, whereas a low dose of the direct agonist apomorphine (0.1mg/kg s.c.) reduced it. Gamma-butyrolactone, which strongly inhibits dopamine release at the dose administered (700mg/kg i.p.), initially reduced and then increased caudate-putamen temperature. Brief (5-10min) presentation of mild stressors, including tail pinch, produced a rapid and transient caudate-putamen hyperthermia. Quantitative (125)I-RTI-55 autoradiography in post-mortem tissue revealed a 97-100% loss of binding to dopamine transporters in the lesioned caudate-putamen. Despite this near-total dopamine denervation, neither basal caudate-putamen temperature, nor any of the observed temperature responses to drugs or mild stressors, was altered. We conclude that in the caudate-putamen, endogenous dopamine is unlikely to modulate temperature significantly at a local level. Copyright 2010 Elsevier Inc. All rights reserved.

The development of magnetic degradable DP-Bioglass for hyperthermia cancer therapy.

PubMed

Wang, Tzu-Wei; Wu, Hsi-Chin; Wang, Wei-Ren; Lin, Feng-Huei; Lou, Pei-Jen; Shieh, Ming-Jium; Young, Tai-Horng

2007-12-01

In this study, a novel magnetic degradable material was developed by adding Fe ions into DP-Bioglass (Na(2)O-CaO-P(2)O(5)-SiO(2)) as thermoseed for hyperthermia cancer therapy under an alternating magnetic field. We have investigated the properties of developed magnetic DP-Bioglass including morphology, chemical composition, and magnetism. The degradability was conducted by measuring the released concentrations of Na, Ca, Si, P, and Fe ions. The biocompatibility was analyzed by biological assays, and the functional hyperthermia effect to cancer cells was evaluated by in vitro cell culture test. In the results, the morphology of synthesized magnetic DP-Bioglass was revealed in sphere and rod shape with particle size around 50-100 nm. From the hysteresis loop analysis, it showed that the group of Fe/Bioglass = 0.2 possessed the maximum magnetization property. When cultured with fibroblasts, the magnetic DP-Bioglass had no significant influence on cell viability and mediated low cytotoxicity. The thermal-induced property demonstrated that after exposure to an alternating magnetic field, the cell number of human Caucasian lung carcinoma cells (A549) was significantly decreased when temperature was increasing to 45 degrees C. In brief, successfully incorporated with Fe ions by sol-gel method, this magnetic degradable DP-Bioglass possessed the potential and properties of hyperthermia effect to lung carcinoma cells. Copyright 2007 Wiley Periodicals, Inc.

Magnetic and magnetothermal studies of pure and doped gadolinium silicide nanoparticles for self-controlled hyperthermia applications

NASA Astrophysics Data System (ADS)

Alnasir, M. Hisham; Awan, M. S.; Manzoor, Sadia

2018-03-01

We report on magnetic and magnetothermal properties of undoped and doped gadolinium silicide (Gd5Si4) nanoparticles with the objective of simultaneously attaining high specific absorption rate (SAR) and low Curie temperature (TC) suitable for self-controlled hyperthermia applications for which TC ∼ 315-320 K. Pellets of doped gadolinium silicide Gd5(Si1-xGex)4 and (Gd1-xRx)5Si4 with R = Ho, Nd and Er and 0 ≤ x ≤ 0.35 were made by arc melting and reduced to nanoparticulate form by surfactant assisted ball milling. Structural and morphological studies were done using X-ray diffraction and scanning electron microscopy respectively. All samples show soft magnetic properties. At low fields there is a ferromagnetic to paramagnetic transition that reduces remanance and coercivity to zero making these materials very attractive for biomedical applications. Zero-field-cooled thermal demagnetization measurements showed that TC of these nanoparticles can be lowered to lie within the limits required for self-controlled hyperthermia by varying the dopant concentration. Specific absorption rates (SAR's) were obtained from magnetothermia measurements made in an ac magnetic field of amplitude 10 Oe and frequency 300 kHz. We have identified samples that have SAR values larger or comparable to those of magnetite and several ferrite nanoparticles, while having Curie temperatures that are low enough for self controlled hyperthermia applications.

On-Demand Drug Release from Gold Nanoturf for a Thermo- & Chemo-Therapeutic Esophageal Stent (TES).

PubMed

Lee, Sori; Hwang, Gyoyeon; Kim, Tae Hee; Kwon, S Joon; Kim, Jong Uk; Koh, Kyongbeom; Park, Byeonghak; Hong, Haeleen; Yu, Ki Jun; Chae, Heeyeop; Jung, Youngmee; Lee, Jiyeon; Kim, Tae-Il

2018-06-07

Stimuli-responsive delivery systems for cancer therapy have been increasingly used to promote the on-demand therapeutic efficacy of anticancer drugs, and in some cases, simultaneously generate heat in response to a stimulus, resulting in hyperthermia. However, their application is still limited due to the systemic drawbacks of intravenous delivery, such as rapid clearance from the bloodstream, and the repeat injections required for sustained safe dosage, which can cause over-dosing. Here, we propose a gold (Au)-coated nanoturf structure as an implantable therapeutic interface for near-infrared (NIR)-mediated on-demand hyperthermia chemotherapy. The Au nanoturf possessed long-lasting doxorubicin (DOX) duration, which helps facilitate drug release in a sustained and prolonged manner. Moreover, the Au-coated nanoturf provides reproducible hyperthermia induced by localized surface plasmon resonances (LSPRs) under NIR irradiation. Simultaneously, the NIR-mediated temperature increase can promote on-demand drug release at desired time points. For in vivo analysis, the Au nanoturf structure was applied on an esophageal stent, which needs sustained anticancer treatment to prevent tumor recurrence on the implanted surface. This thermo- and chemo-esophageal stent induced significant cancer cell death with released drug and hyperthermia. These phenomena were also confirmed by theoretical analysis. The proposed strategy provides a solution to achieve enhanced thermo-/chemotherapy, and has broad applications in sustained cancer treatments.

Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.

PubMed

Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E M

2017-04-29

Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3 H )-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32 P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe₃O₄-NPs. Significant dose-response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells

PubMed Central

Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W.; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E. M.

2017-01-01

Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe3O4-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe3O4-NPs. Significant dose–response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death. PMID:28468256

The hyperthermia-enhanced association between tropoelastin and its 67-kDa chaperone results in better deposition of elastic fibers.

PubMed

Murphy, Brooke A; Bunda, Severa; Mitts, Thomas; Hinek, Aleksander

2010-12-17

The results of our in vitro experiments indicate that exposing cultured human aortic smooth muscle cells and dermal fibroblasts to 39 to 41 °C induces a significant up-regulation in the net deposition of elastic fibers, but not of collagen I or fibronectin, and also decreases the deposition of chondroitin sulfate-containing moieties. We further demonstrate that mild hyperthermia also rectifies the insufficient elastogenesis notable in cultures of fibroblasts derived from the stretch-marked skin of adult patients and in cultures of dermal fibroblasts from children with Costello syndrome, which is characterized by the accumulation of chondroitin 6-sulfate glycosaminoglycans that induce shedding and inactivation of the 67-kDa elastin-binding protein. We have previously established that this protein serves as a reusable chaperone for tropoelastin and that its recycling is essential for the normal deposition of elastic fibers. We now report that hyperthermia not only inhibits deposition of chondroitin 6-sulfate moieties and the consequent preservation of elastin-binding protein molecules but also induces their faster recycling. This, in turn, triggers a more efficient preservation of tropoelastin, enhancement of its secretion and extracellular assembly into elastic fibers. The presented results encourage using mild hyperthermia to restore elastic fiber production in damaged adult skin and to enhance elastogenesis in children with genetic elastinopathies.

CT-based patient modeling for head and neck hyperthermia treatment planning: manual versus automatic normal-tissue-segmentation.

PubMed

Verhaart, René F; Fortunati, Valerio; Verduijn, Gerda M; van Walsum, Theo; Veenland, Jifke F; Paulides, Margarethus M

2014-04-01

Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H&N) carcinoma. Hyperthermia treatment planning (HTP) guided H&N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Automatically generated 3D patient models can be introduced in the clinic for H&N HTP. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Induction of cytogenetic damage in human lymphocytes in vitro and of antineoplastic effects in Ehrlich ascites tumor cells in vivo treated by methotrexate, hyperthermia and/or caffeine.

PubMed

Maskaleris, T; Lialiaris, T; Triantaphyllidis, C

1998-12-03

The synergistic effect of methotrexate (at concentrations between 3. 1 and 100 nM) and its combinations with caffeine (618 microM) and/or hyperthermia (42 degreesC for 2 h) on the frequency of sister chromatid exchanges (SCEs), the proliferating rate index and the mitotic index in cultured human lymphocytes, was examined. Also, the in vivo antineoplastic effects of methotrexate (at a concentration of 0.45 microg/g body weight) and its combination with caffeine (120 microg/g body weight), both on the survival time and the increase of the weight of tumor of BALB/c mice inoculated with Ehrlich ascites tumor cells was examined in the present study. The results indicated that: (a) the triple combination of methotrexate, caffeine and hyperthermia synergistically increased the levels of SCEs and exerted cytostatic and cytotoxic action and (b) the combination of methotrexate and caffeine significantly increased the survival span of the mice inoculated with Ehrlich ascites tumor cells and reduced the increase of the weight of their tumors at rates higher than in the case of methotrexate by itself. It is suggested that the above triple combination (methotrexate plus caffeine plus hyperthermia) could achieve increased effectiveness of methotrexate, better therapy results, and could be successfully applied in the treatment of various types of cancer. Copyright 1998 Elsevier Science B.V.

Effect of intravenous administration of d-lysergic acid diethylamide on subsequent protein synthesis in a cell-free system derived from brain.

PubMed

Cosgrove, J W; Clark, B D; Brown, I R

1981-03-01

An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of d-lysergic acid diethylamide (LSD) to rabbits induced a transient inhibition of translation following a brief stimulatory period. Subfractionation of the brain cell-free system into postribosomal supernatant (PRS) and microsome fractions demonstrated that LSD in vivo induced alterations in both of these fractions. In addition to the overall inhibition of translation in the cell-free system, differential effects were noted, i.e., greater than average relative decreases in in vitro labeling of certain brain proteins and relative increases in others. The brain proteins of molecular weights 75K and 95K, which were increased in relative labeling under conditions of LSD-induced hyperthermia, are similar in molecular weight to two of the major "heat shock" proteins reported in tissue culture systems. Injection of LSD to rabbits at 4 degrees C prevented LSD-induced hyperthermia but behavioral effects of the drug were still apparent. The overall decrease in cell-free translation was still observed but the differential labeling effects were not. LSD appeared to influence cell-free translation in the brain at two dissociable levels: (a) an overall decrease in translation that was observed even in the absence of LSD-induced hyperthermia and (b) differential labeling effects on particular proteins that were dependent on LSD-induced hyperthermia.

Sudden infant death syndrome: no significant expression of heat-shock proteins (HSP27, HSP70).

PubMed

Doberentz, Elke; Führing, Sarah; Madea, Burkhard

2016-03-01

In industrialized countries, sudden infant death is the most common cause of death in young children. Although prone sleeping position is a well-known risk factor, hyperthermia might also be important. Pathognomonic findings of premortem hyperthermia do not exist. During stress, including thermal effects, heat-shock protein (HSP) expression increases. This study investigated hyperthermia as a contributing or pathogenic factor for sudden infant death syndrome (SIDS). Immunohistochemical staining for HSP27 and HSP70 in the kidney, heart, and lung from 120 SIDS cases was examined. HSP70 immunostaining was negative in kidney, heart, and lung tissues in all cases and in tissues from the control group. HSP27 staining was positive in the kidney from one case, and was positive in the lungs (respiratory epithelia in 27% of cases; vascular endothelia in 19% of cases) and was negative in the heart. In the control group HSP27 was positive in 8% of renal tubular tissues and in 29% of renal vascular endothelia. Staining for HSP27 in lung tissues was positive in respiratory epithelia in 8% of cases and for vascular endothelia in 29%, whereas tissues from the heart were positive in only 4%. The hypothesis of hyperthermia being a pathogenic factor for SIDS was not supported by immunohistochemical visualization of HSP70 or HSP27.

Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells.

PubMed

Chen, Kaiyun; Zhu, Shuguang; Xiang, Guoan; Duan, Xiaopeng; He, Jiwen; Chen, Guihua

2016-05-01

To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.

Optimizing deep hyperthermia treatments: are locations of patient pain complaints correlated with modelled SAR peak locations?

NASA Astrophysics Data System (ADS)

Canters, R. A. M.; Franckena, M.; van der Zee, J.; van Rhoon, G. C.

2011-01-01

During deep hyperthermia treatment, patient pain complaints due to heating are common when maximizing power. Hence, there exists a good rationale to investigate whether the locations of predicted SAR peaks by hyperthermia treatment planning (HTP) are correlated with the locations of patient pain during treatment. A retrospective analysis was performed, using the treatment reports of 35 patients treated with deep hyperthermia controlled by extensive treatment planning. For various SAR indicators, the average distance from a SAR peak to a patient discomfort location was calculated, for each complaint. The investigated V0.1 closest (i.e. the part of the 0.1th SAR percentile closest to the patient complaint) performed the best, and leads to an average distance between the SAR peak and the complaint location of 3.9 cm. Other SAR indicators produced average distances that were all above 10 cm. Further, the predicted SAR peak location with V0.1 provides a 77% match with the region of complaint. The current study demonstrates that HTP is able to provide a global indication of the regions where hotspots during treatment will most likely occur. Further development of this technology is necessary in order to use HTP as a valuable toll for objective and advanced SAR steering. The latter is especially valid for applications that enable 3D SAR steering.

How does temperature affect the function of tissue macrophages?

NASA Astrophysics Data System (ADS)

Lee, Chen-Ting; Repasky, Elizabeth A.

2011-03-01

Macrophages create a major danger signal following injury or infection and upon activation release pro-inflammatory cytokines, which in turn help to generate febrile conditions. Thus, like other cells of the body, tissue macrophages are often exposed to naturally occurring elevations in tissue temperature during inflammation and fever. However, whether macrophages sense and respond to temperature changes in a specific manner which modulates their function is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of temperatures on macrophage function, and summarize the possible underlying molecular mechanisms which have been identified. Mild, physiological range hyperthermia has been shown to have both pro- and anti-inflammatory roles in regulating macrophage inflammatory cytokine production and at the meeting presentation, we will show new data demonstrating that hyperthermia can indeed exert both positive and negative signals to macrophages. While some thermal effects are correlated with the induction of heat shock factors/heat shock proteins, overall it is not clear how mild hyperthermia can exert both pro- and anti-inflammatory functions. We also summarize data which shows that hyperthermia can affect other macrophage effector functions, including the anti-tumor cytotoxicity. Overall, these studies may help us to better understand the immunological role of tissue temperature and may provide important information needed to maximize the application of heat in the treatment of various diseases including cancer.

Computational evaluation of amplitude modulation for enhanced magnetic nanoparticle hyperthermia.

PubMed

Soetaert, Frederik; Dupré, Luc; Ivkov, Robert; Crevecoeur, Guillaume

2015-10-01

Magnetic nanoparticles (MNPs) can interact with alternating magnetic fields (AMFs) to deposit localized energy for hyperthermia treatment of cancer. Hyperthermia is useful in the context of multimodality treatments with radiation or chemotherapy to enhance disease control without increased toxicity. The unique attributes of heat deposition and transfer with MNPs have generated considerable attention and have been the focus of extensive investigations to elucidate mechanisms and optimize performance. Three-dimensional (3D) simulations are often conducted with the finite element method (FEM) using the Pennes' bioheat equation. In the current study, the Pennes' equation was modified to include a thermal damage-dependent perfusion profile to improve model predictions with respect to known physiological responses to tissue heating. A normal distribution of MNPs in a model liver tumor was combined with empirical nanoparticle heating data to calculate tumor temperature distributions and resulting survival fraction of cancer cells. In addition, calculated spatiotemporal temperature changes were compared among magnetic field amplitude modulations of a base 150-kHz sinusoidal waveform, specifically, no modulation, sinusoidal, rectangular, and triangular modulation. Complex relationships were observed between nanoparticle heating and cancer tissue damage when amplitude modulation and damage-related perfusion profiles were varied. These results are tantalizing and motivate further exploration of amplitude modulation as a means to enhance efficiency of and overcome technical challenges associated with magnetic nanoparticle hyperthermia (MNH).

Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy.

PubMed

Mauro, Nicolò; Scialabba, Cinzia; Cavallaro, Gennara; Licciardi, Mariano; Giammona, Gaetano

2015-09-14

Among the relevant properties of graphene derivatives, their ability of acting as an energy-converting device so as to produce heat (i.e., thermoablation and hyperthermia) was more recently taken into account for the treatment of solid tumors. In this pioneering study, for the first time, the in vitro RGO-induced hyperthermia was assessed and combined with the stimuli-sensitive anticancer effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting to a nanosystem endowed with synergic anticancer effects and high specificity. CJ-PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin. The citraconylamide pendants, used as pH reversible spacer, were exploited to further conjugate doxorubicin, whereas the alkyne moiety was orthogonally functionalized with an azido PEG-biotin derivative by copper(II) catalyzed 1,3-dipolar cycloaddition. DSC measures, AFM, and UV spectrophotometry were employed to systematically investigate adsorption of CJ-PEGBT onto RGO and its physicochemical stability in aqueous media, demonstrating that a stable π-staked nanosystem can be obtained. In vitro tests using cancer breast cells (MCF-7) showed the ability of the RGO/CJ-PEGBT of efficiently killing cancer cells both via a selective laser beam thermoablation and hyperthermia-triggered chemotherapy. If compared with the nonbiotinylated nanosystem, including virgin RGO and the free conjugate, RGO/CJ-PEGBT is endowed with a smart combination of properties which warrant potential as an anticancer nanomedicine.

[Hereditary sensory and autonomic neuropathy type IV: a report on two cases].

PubMed

Achouri, E; Gribaa, M; Bouguila, J; Haddad, S; Souayeh, N; Saad, A; Essoussi, A S

2011-04-01

Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a very rare autosomal recessive disorder characterized by recurrent episodes of unexplained fever, extensive anhidrosis, total insensitivity to pain, hypotonia, and mental retardation. The absence of urticarial reaction to intradermal injection of histamine is a sign of great diagnostic value, but this is common to all types of HSAN. The most frequent complications of this disease are corneal scarring, multiple fractures, joint deformities, osteomyelitis, and disabling self-mutilations. Malignant hyperthermia and sepsis are major causes of mortality. We relate the first observations of two Tunisian children with genetically confirmed HSAN IV. Our goal is to review the clinical aspects of this mysterious neuropathy and to emphasize the peculiarities of its management. These two patients are brothers from 1st-degree consanguineous parents (cousins) with no particular medical history. The 1st patient, the family's 1st child, presented in the 1st h of life with hypotonia and persistent fever, which was refractory to antipyretics. At the age of 8 months, the patient presented recurrent febrile seizures and developed significant self-mutilations of the fingers and tongue. He died 3 months later in a context of multivisceral failure from sepsis and malignant hyperthermia. The 2nd patient, currently aged 4 years, was born after a normal sister. He consulted in the neonatal period for a high fever. The diagnosis of HSAN IV was rapidly suspected and genetically confirmed. In fact, this patient is homozygous for the NTRK1 gene, whereas his sister and both parents are heterozygous. Special predispositions have been taken to improve the course of the disease such as air conditioning to control hyperthermia, a dental tray to reduce the injuries resulting from self-mutilation, regular moistening of the eyes to avoid corneal drying, and chlorpromazine to control hyperactivity and reduce injuries. The good progression with all these predispositions and others underlines the importance of appropriate multidisciplinary management and close monitoring of patients suffering from HSAN IV, especially during the first 3 years of life. Indeed, mortality, behavioral disorders, and mental retardation significantly decrease after this age. New curative treatments are expected in the next decade. Copyright © 2011. Published by Elsevier SAS.

Assessment of the efficacy of laser hyperthermia and nanoparticle-enhanced therapies by heat shock protein analysis

NASA Astrophysics Data System (ADS)

Tang, Fei; Zhang, Ye; Zhang, Juan; Guo, Junwei; Liu, Ran

2014-03-01

Tumor thermotherapy is a method of cancer treatment wherein cancer cells are killed by exposing the body tissues to high temperatures. Successful clinical implementation of this method requires a clear understanding and assessment of the changes of the tumor area after the therapy. In this study, we evaluated the effect of near-infrared laser tumor thermotherapy at the molecular, cellular, and physical levels. We used single-walled carbon nanotubes (SWNTs) in combination with this thermotherapy. We established a mouse model for breast cancer and randomly divided the mice into four groups: mice with SWNT-assisted thermotherapy; mice heat treated without SWNT; mice injected with SWNTs without thermotherapy; and a control group. Tumors were irradiated using a near-infrared laser with their surface temperature remaining at approximately 45 °C. We monitored the tumor body growth trend closely by daily physical measurements, immunohistochemical staining, and H&E (hematoxylin-eosin) staining by stage. Our results showed that infrared laser hyperthermia had a significant inhibitory effect on the transplanted breast tumor, with an inhibition rate of 53.09%, and also significantly reduced the expression of the heat shock protein Hsp70. Furthermore, we have found that protein analysis and histological analysis can be used to assess therapeutic effects effectively, presenting broad application prospects for determining the effect of different treatments on tumors. Finally, we discuss the effects of SWNT-assisted near-infrared laser tumor thermotherapy on tumor growth at the molecular, cellular, and physical levels.

Temperature data analysis for 22 patients with advanced cervical carcinoma treated in Rotterdam using radiotherapy, hyperthermia and chemotherapy: a reference point is needed.

PubMed

Fatehi, D; van der Zee, J; van der Wal, E; Van Wieringen, W N; Van Rhoon, G C

2006-06-01

The growing interest and participation in multi-institutional trials involving deep hyperthermia treatment is an important step towards the further consolidation of hyperthermia as an oncological treatment modality. However, the differences in the clinical procedures of hyperthermia application also raises questions as how to compare the reported temperatures data obtained by the different institutes. In this study our recent developed approach, RHyThM (Rotterdam Hyperthermia Thermal Modulator), has been used for thermal data analysis to investigate the temperature dynamics behaviour of a series of deep hyperthermia treatments. All 22 patients (104 hyperthermia treatments) with locally advanced cervical carcinoma who participated in a feasibility study for treatment with a three-modality therapy were selected. The patients received mega-voltage external beam radiotherapy to the pelvis in daily fractions of 2 Gy five times a week to a total dose of 46 Gy and additional brachytherapy, at least four courses of weekly cisplatin (40 mg m-2) and five sessions of weekly loco regional deep hyperthermia treatments with the BSD2000-3D with the Sigma 60 or the Sigma-eye applicators at frequencies 70-120 MHz. Using RHyThM tissue type was defined along the insertion length, based on the CT scan information in radiotherapy position, for each single treatment. A step change in the slope of the profile of the first temperature map was identified to verify the insertion length of the thermometry catheter and precise location of the transition between in- and outside the body. Data analysis was performed based on the temperature readout provided by RHyThM. The temperature and RF-power data of 97 treatments could be analysed. The intra-vaginal temperature indices were slightly lower than those for bladder and rectum. The average T50 (median temperature) in all lumens, i.e. bladder, vagina and rectum, was 40.4 +/- 0.6 degrees Celsius. The average vagina all lumen T50 was 40.0 +/- 0.8 degrees Celsius. The average bladder and rectum all lumen T50 was 40.6 +/- 0.7 degrees Celsius and 40.5 +/- 0.6, respectively. When the analysis was restricted to the deepest 5 cm of the vagina lumen, the average T50 was 39.8 +/- 0.9 degrees Celsius. Good correlation exists between the various temperature indices like T20, T50 and T90, for all lumen measurements in bladder, vagina and rectum. No correlation was found between temperature indices and treatment number. For the complete patient population, no relationship was found between T50 and net integrated RF-power applied. In an explorative analysis on individual patients a positive correlation coefficient or trend was found in 14 patients between normalized net integrated RF-power and vagina T50. Average all lumen T50 for bladder, vagina and rectum differ less than 1 degrees Celsius, indicating that a large volume was heated relatively homogeneously. The vagina T50 value depends on how many measurement points are included for the analysis. In this group of patients the vagina T50 of the first treatment is not a good measure to discriminate between patients with 'heatable' and 'non-heatable' tumours. In order to compare temperature data reported by different institutes dealing with the same group of patients, one needs a strict and clear agreement on which temperature measurements or reference point(s) that should be included in the analysis.

Real-time infrared thermography detection of magnetic nanoparticle hyperthermia in a murine model under a non-uniform field configuration.

PubMed

Rodrigues, Harley F; Mello, Francyelli M; Branquinho, Luis C; Zufelato, Nicholas; Silveira-Lacerda, Elisângela P; Bakuzis, Andris F

2013-12-01

Magnetic nanoparticle hyperthermia consists of an increase of the temperature of magnetic nanoparticles (heat centres) due to the interaction of their magnetic moments with an alternating magnetic field. In vivo experiments using this method usually use a few fibre-optic thermometers inserted in the animal body to monitor the heat deposition. As a consequence, only a few points of the 3D temperature distribution can be monitored by this invasive procedure. It is the purpose of this work to show that non-invasive infrared thermography is able to detect, in real time, magnetic nanoparticle hyperthermia as well as monitor the harmful field-induced eddy currents in a murine model with a subcutaneous tumour. This surface temperature measurement method has the potential to give information about the intratumoral temperature. The non-invasive magnetic hyperthermia experiments were performed at 300 kHz in non-uniform field configuration conditions in healthy mice and murine tumour induced by sarcoma S180. A soft ferrite-based biocompatible magnetic colloid consisting of manganese-ferrite nanoparticles surface-coated with citric acid were used in the experiments, which were extensively characterised by several techniques (transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM)). The amplitude of the alternating magnetic fields was obtained from measurements using an AC field probe at similar experimental conditions. The temperature measurements were obtained from an infrared thermal camera and a fibre-optic thermometer. Three-minute magnetic hyperthermia experiments revealed surface temperature increase as high as 11 °K in healthy and (5 °K in S180 tumour) animals when injecting subcutaneously 2 mg of magnetic nanoparticles (86 μL of magnetic fluid), in contrast to around 1.5 °K (for healthy) and 2.5 °K (for cancerous) animals in experiments without the colloid due to field-induced eddy currents at the animal surface. The thermographic temperature measurements were found to agree with the fibre-optic measurements within a 5% error, and were associated with the skin emissivity angle of dependence in the experimental set-up. On the other hand, a 30-min magnetic nanoparticle hyperthermia revealed surface temperature increases as high as 12 °K close to the injection site, while above 2-3 cm no significant temperature increase was observed. Curiously, the intratumoral temperature, monitored by a fibre-optic sensor, was found to be almost the same as the thermal camera surface temperature after achieving an equilibrium temperature regime. From the observed isotherms at the animal surface, using an analytical heat conduction model, taking into account surface conductance, we estimate a magnetic heating power of 0.45 W/cm(3) and a specific loss power (SLP) of 85 W/g for a field of the order of only 10 kA/m at the injection site region. The results indicate that infrared thermography may be a promising tool for both early cancer detection and for hyperthermia treatment (at least for subcutaneous tumours), since the method permits access to information about the intratumoral temperature during a real-time magnetic hyperthermia as well as to estimate the in vivo nanoparticles SLP.

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franckena, Martine; Stalpers, Lukas J.A.; Koper, Peter C.M.

2008-03-15

Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a medianmore » total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.« less

Uncoupling of oxidative phosphorylation and ATP synthase reversal within the hyperthermic heart.

PubMed

Power, Amelia; Pearson, Nicholas; Pham, Toan; Cheung, Carlos; Phillips, Anthony; Hickey, Anthony

2014-09-01

Heart failure is a common cause of death with hyperthermia, and the exact cause of hyperthermic heart failure appears elusive. We hypothesize that the energy supply (ATP) of the heart may become impaired due to increased inner-mitochondrial membrane permeability and inefficient oxidative phosphorylation (OXPHOS). Therefore, we assessed isolated working heart and mitochondrial function. Ex vivo working rat hearts were perfused between 37 and 43.5°C and showed break points in all functional parameters at ~40.5°C. Mitochondrial high-resolution respirometry coupled to fluorometry was employed to determine the effects of hyperthermia on OXPHOS and mitochondrial membrane potential (ΔΨ) in vitro using a comprehensive metabolic substrate complement with isolated mitochondria. Relative to 37 and 40°C, 43°C elevated Leak O2 flux and depressed OXPHOS O2 flux and ∆Ψ. Measurement of steady-state ATP production from mitochondria revealed decreased ATP synthesis capacity, and a negative steady-state P:O ratio at 43°C. This approach offers a more powerful analysis of the effects of temperature on OXPHOS that cannot be measured using simple measures such as the traditional respiratory control ratio (RCR) or P:O ratio, which, respectively, can only approach 1 or 0 with inner-membrane failure. At 40°C there was only a slight enhancement of the Leak O2 flux and this did not significantly affect ATP production rate. Therefore, during mild hyperthermia (40°C) there is no enhancement of ATP supply by mitochondria, to accompany increasing cardiac energy demands, while between this and critical hyperthermia (43°C), mitochondria become net consumers of ATP. This consumption may contribute to cardiac failure or permanent damage during severe hyperthermia. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Using thermal energy produced by irradiation of Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression.

PubMed

Tang, Qiu-sha; Zhang, Dong-sheng; Cong, Xiao-ming; Wan, Mei-ling; Jin, Li-qiang

2008-06-01

One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we developed a novel heat-inducible gene expression system in which thermal energy generated by Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) under an alternating magnetic field (AMF) was used to activate gene expression. MZF-NPs, obtained by co-precipitation method, were firstly surface modified with cation poly(ethylenimine) (PEI). Then thermodynamic test of various doses of MZF-NPs was preformed in vivo and in vitro. PEI-MZF-NPs showed good DNA binding ability and high transfection efficiency. In AMF, they could rise to a steady temperature. To analyze the heat-induced gene expression under an AMF, we combined P1730OR vector transfection with hyperthermia produced by irradiation of MZF-NPs. By using LacZ gene as a reporter gene and Hsp70 as a promoter, it was demonstrated that expression of a heterogeneous gene could be elevated to 10 to 500-fold over background by moderate hyperthermia (added 12.24 or 25.81 mg MZF-NPs to growth medium) in tissue cultured cells. When injected with 2.6 or 4.6 mg MZF-NPs, the temperature of tumor-bearing nude mice could rise to 39.5 or 42.8 degrees C, respectively, and the beta-gal concentration could increase up to 3.8 or 8.1 mU/mg proteins accordingly 1 day after hyperthermia treatment. Our results therefore supported hyperthermia produced by irradiation of MZF-NPs under an AMF as a feasible approach for targeted heat-induced gene expression. This novel system made use of the relative low Curie point of MZF-NPs to control the in vivo hyperthermia temperature and therefore acquired safe and effective heat-inducible transgene expression.

Intracavitary ultrasound phased arrays for thermal therapies

NASA Astrophysics Data System (ADS)

Hutchinson, Erin

Currently, the success of hyperthermia and thermal surgery treatments is limited by the technology used in the design and fabrication of clinical heating devices and the completeness of the thermometry systems used for guidance. For both hyperthermia and thermal surgery, electrically focused ultrasound generated by phased arrays provides a means of controlling localized energy deposition in body tissues. Intracavitary applicators can be used to bring the energy source close to a target volume, such as the prostate, thereby minimizing normal tissue damage. The work performed in this study was aimed at improving noninvasive prostate thermal therapies and utilized three research approaches: (1) Acoustic, thermal and optimization simulations, (2) Design and fabrication of multiple phased arrays, (3) Ex vivo and in vivo experimental testing of the heating capabilities of the phased arrays. As part of this study, a novel aperiodic phased array design was developed which resulted in a 30- 45% reduction in grating lobe levels when compared to conventional phased arrays. Measured acoustic fields generated by the constructed aperiodic arrays agreed closely with the fields predicted by the theoretical simulations and covered anatomically appropriate ranges. The power capabilities of these arrays were demonstrated to be sufficient for the purposes of hyperthermia and thermal surgery. The advantage of using phased arrays in place of fixed focus transducers was shown by demonstrating the ability of electronic scanning to increase the size of the necrosed tissue volume while providing a more uniform thermal dose, which can ultimately reduce patient treatment times. A theoretical study on the feasibility of MRI (magnetic resonance imaging) thermometry for noninvasive temperature feedback control was investigated as a means to improve transient and steady state temperature distributions achieved in hyperthermia treatments. MRI guided ex vivo and in vivo experiments demonstrated that the heating capabilities of the constructed phased arrays were adequate for hyperthermia and thermal surgery treatments. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253- 1690.)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schooneveldt, G.; Kok, H.P.; Bakker, A.

Purpose: Hyperthermia combined with Mitomycin C is used for the treatment of non-muscle invasive bladder cancer (NMIBC), using a phased array system of microwave antennas for bladder heating. Often some air is present in the bladder, which effectively blocks the microwave radiation, potentially preventing proper treatment of that part of the bladder. Air can be a relevant fraction of the bladder content and large air pockets are expected to have a noticeable influence on achieved temperatures. Methods: We analysed 14 NMIBC patients treated at our institute with our AMC-4 hyperthermia device with four 70MHz antennas around the pelvis. A CTmore » scan was made after treatment and a physician delineated the bladder on the CT scan. On the same scan, the amount of air present in the bladder was delineated. Using our in-house developed hyperthermia treatment planning system, we simulated the treatment using the clinically applied device settings. We did this once with the air pocket delineated on the CT scan, and once with the same volume filled with bladder tissue. Results: The patients had on average 4.2ml (range 0.8–10.1ml) air in the bladder. The bladder volume was delineated by the physician, that is including air pocket and bladder wall, was on average 253ml (range 93–452ml). The average volume in which changes exceeded 0.25°C was 22ml (range 0–108 ml), with the bladder being up to 2°C cooler when an air pocket was present. Except for extreme cases, there was no evident relation between the quantity of air and the difference in temperature. Conclusion: The effect of an air pocket in the bladder during bladder hyperthermia treatment varies strongly between patients. Generally, this leads to lower temperatures in the bladder, potentially affecting treatment quality, and suggesting that care need be taken to minimise the size of air pockets during hyperthermia treatments. The KWF Dutch Cancer Society financially supported this work, grant UVA 2012-5539.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kok, H. Petra, E-mail: H.P.Kok@amc.uva.nl; Ciampa, Silvia; Department of Civil Engineering and Computer Science, University of Rome Tor Vergata, Rome

Purpose: Hyperthermia is the clinical application of heat, in which tumor temperatures are raised to 40°C to 45°C. This proven radiation and chemosensitizer significantly improves clinical outcome for several tumor sites. Earlier studies of the use of pre-treatment planning for hyperthermia showed good qualitative but disappointing quantitative reliability. The purpose of this study was to investigate whether hyperthermia treatment planning (HTP) can be used more reliably for online adaptive treatment planning during locoregional hyperthermia treatments. Methods and Materials: This study included 78 treatment sessions for 15 patients with non-muscle-invasive bladder cancer. At the start of treatments, temperature rise measurements weremore » performed with 3 different antenna settings optimized for each patient, from which the absorbed power (specific absorption rate [SAR]) was derived. HTP was performed based on a computed tomography (CT) scan in treatment position with the bladder catheter in situ. The SAR along the thermocouple tracks was extracted from the simulated SAR distributions. Correlations between measured and simulated (average) SAR values were determined. To evaluate phase steering, correlations between the changes in simulated and measured SAR values averaged over the thermocouple probe were determined for all 3 combinations of antenna settings. Results: For 42% of the individual treatment sessions, the correlation coefficient between measured and simulated SAR profiles was higher than 0.5, whereas 58% showed a weak correlation (R of <0.5). The overall correlation coefficient between measured and simulated average SAR was weak (R=0.31; P<.001). The measured and simulated changes in average SAR after adapting antenna settings correlated much better (R=0.70; P<.001). The ratio between the measured and simulated quotients of maximum and average SARs was 1.03 ± 0.26 (mean ± SD), indicating that HTP can also correctly predict the relative amplitude of SAR peaks. Conclusions: HTP can correctly predict SAR changes after adapting antenna settings during hyperthermia treatments. This allows online adaptive treatment planning, assisting the operator in determining antenna settings resulting in increased tumor temperatures.« less

Effective heating of magnetic nanoparticle aggregates for in vivo nano-theranostic hyperthermia.

PubMed

Wang, Chencai; Hsu, Chao-Hsiung; Li, Zhao; Hwang, Lian-Pin; Lin, Ying-Chih; Chou, Pi-Tai; Lin, Yung-Ya

2017-01-01

Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe 3 O 4 and cobalt ferrite CoFe 2 O 4 magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10-20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%-25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal heating efficiency in comparison with the optimal size predicted by previous models.

Effective heating of magnetic nanoparticle aggregates for in vivo nano-theranostic hyperthermia

PubMed Central

Wang, Chencai; Hsu, Chao-Hsiung; Li, Zhao; Hwang, Lian-Pin; Lin, Ying-Chih; Chou, Pi-Tai; Lin, Yung-Ya

2017-01-01

Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe3O4 and cobalt ferrite CoFe2O4 magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10–20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%–25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal heating efficiency in comparison with the optimal size predicted by previous models. PMID:28894366

Muscle metaboreceptor modulation of cutaneous active vasodilation

NASA Technical Reports Server (NTRS)

Crandall, C. G.; Stephens, D. P.; Johnson, J. M.

1998-01-01

PURPOSE: Isometric handgrip exercise in hyperthermia has been shown to reduce cutaneous vascular conductance (CVC) by inhibiting the cutaneous active vasodilator system. METHODS: To identify whether this response was initiated by muscle metaboreceptors, in seven subjects two 3-min bouts of isometric handgrip exercise in hyperthermia were performed, followed by 2 min of postexercise ischemia (PEI). An index of forearm skin blood flow (laser-Doppler flowmetry) was measured on the contralateral arm at an unblocked site and at a site at which adrenergic vasoconstrictor function was blocked via bretylium iontophoresis to reveal active cutaneous vasodilator function unambiguously. Sweat rate was measured via capacitance hygrometry, CVC was indexed from the ratio of skin blood flow to mean arterial pressure and was expressed as a percentage of maximal CVC at that site. In normothermia, neither isometric exercise nor PEI affected CVC (P > 0.05). RESULTS: The first bout of isometric handgrip exercise in hyperthermia reduced CVC at control sites and this reduction persisted through PEI (pre-exercise: 59.8 +/- 5.4, exercise: 49.8 +/- 4.9, PEI: 49.7 +/- 5.3% of maximum; both P < 0.05), whereas there were no significant changes in CVC at the bretylium treated sites. The succeeding bout of isometric exercise in hyperthermia significantly reduced CVC at both untreated (pre-exercise: 59.0 +/- 4.8, exercise: 47.3 +/- 4.0, PEI: 50.1 +/- 4.1% of maximum; both P < 0.05) and bretylium treated sites (pre-exercise: 61.4 +/- 7.3, exercise: 50.6 +/- 5.1, PEI: 53.9 +/- 6.0% of maximum, both P < 0.05). At both sites, CVC during PEI was lower than during the pre-exercise period (P < 0.05). Sweat rate rose significantly during both bouts of isometric exercise and remained elevated during PEI. CONCLUSIONS: These data suggest that the reduction in CVC during isometric exercise in hyperthermia, including the inhibition of the active vasodilator system, is primarily mediated by muscle metaboreceptors, whereas central command or muscle mechanoreceptors have less influence.

Synthesis and magnetic hyperthermia studies on high susceptible Fe1-xMgxFe2O4 superparamagnetic nanospheres

NASA Astrophysics Data System (ADS)

Manohar, A.; Krishnamoorthi, C.

2017-12-01

Majority studies on magnetic hyperthermia properties were carried out by modifying the saturation mass magnetization (Ms) of the samples. Here efforts were made to enhance the specific heat generation rate (SHGR) of single domain superparamagnetic (SP) material by modifying its magnetic susceptibility. Well crystallined, inverse spinel structured and close to monosize Fe1-xMgxFe2O4 (x = 0, 0.1, 0.2, 0.3, 0.4, & 0.5) compounds with nanosphere geometry (diameter 10 nm) were synthesized by solvothermal reflux method at ≈ 300 °C . In the literature it is reported that magnesium ferrites synthesized at high temperatures yield mixed (normal & inverse) spinel structures. The inverse spinel structure was confirmed by X-ray powder diffraction (XRPD), lattice vibrations and magnetic characteristics of the compounds. The Ms of the compounds decrease with increase of substituent Mg2+ concentration. Under high excitation energy the inter-valance charge transfer whereas under low excitation energy the intra-valance charge transfer process were predominant. The as-synthesized nanospheres were encapsulated by hydrophobic oleic acid and were exchanged by hydrophilic poly(acrylic acid) by chemical exchange process. Estimated magnetic hyperthermia power or SHGR of the x = 0, 0.3 & 0.5 were 11, 11.4 & 22.4 W per gram of respective compounds, respectively, under 63.4 kA m-1 field amplitude and 126 kHz frequency. The SHGR enhances with Mg2+ concentration though its Ms reduces and is attributed to reduced spin-orbital coupling in the compounds with enhanced Mg2+ concentration. This may pave a new way to develop magnetic hyperthermia material by modifying magnetic susceptibility of the compounds against to the reported Ms modification approach. The obtained high SHGR of the biocompatible compounds could be used in magnetic hyperthermia applications in biomedical field.

A Pilot Study of Catheter-Based Ultrasound Hyperthermia with HDR Brachytherapy for Treatment of Locally Advanced Cancer of the Prostate and Cervix

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Wootton, Jeff; Prakash, Punit; Salgaonkar, Vasant; Juang, Titania; Scott, Serena; Chen, Xin; Cunha, Adam; Pouliot, Jean; Hsu, I. C.

2011-09-01

Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within temporary HDR brachytherapy implants during radiation therapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length×180 deg and 3-4 cm×360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers x dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and four prostate implants. 100% of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions.

Iatrogenic hyperthermia during cardiac magnetic resonance imaging.

PubMed

Kussman, Barry D; Mulkern, Robert V; Holzman, Robert S

2004-10-01

We report the occurrence of accidental hyperthermia in a young child undergoing anesthesia for cardiac magnetic resonance imaging. Although the tendency during anesthesia is to develop hypothermia, the absorbed radiofrequency energy from magnetic resonance scanning is added to metabolic energy and must be balanced by appropriate heat loss to maintain normothermia. In addition to stressing the clinical importance of temperature monitoring, this report suggests that the recommended specific absorption rates to prevent excessive patient heating may need to be revised for infants and young children.

Computational nanomedicine: modeling of nanoparticle-mediated hyperthermal cancer therapy

PubMed Central

Kaddi, Chanchala D; Phan, John H; Wang, May D

2016-01-01

Nanoparticle-mediated hyperthermia for cancer therapy is a growing area of cancer nanomedicine because of the potential for localized and targeted destruction of cancer cells. Localized hyperthermal effects are dependent on many factors, including nanoparticle size and shape, excitation wavelength and power, and tissue properties. Computational modeling is an important tool for investigating and optimizing these parameters. In this review, we focus on computational modeling of magnetic and gold nanoparticle-mediated hyperthermia, followed by a discussion of new opportunities and challenges. PMID:23914967

High skeletal muscle adenylate cyclase in malignant hyperthermia.

PubMed Central

Willner, J H; Cerri, C G; Wood, D S

1981-01-01

Malignant hyperthermia occurs in humans with several congenital myopathies, usually in response to general anesthesia. Commonly, individuals who develop this syndrome lack symptoms of muscle disease, and their muscle lacks specific pathological changes. A biochemical marker for this myopathy has not previously been available; we found activity of adenylate cyclase and content of cyclic AMP to be abnormally high in skeletal muscle. Secondary modification of protein phosphorylation could explain observed abnormalities of phosphorylase activation and sarcoplasmic reticulum function. PMID:6271806

Can magneto-plasmonic nanohybrids efficiently combine photothermia with magnetic hyperthermia?

PubMed

Espinosa, Ana; Bugnet, Mathieu; Radtke, Guillaume; Neveu, Sophie; Botton, Gianluigi A; Wilhelm, Claire; Abou-Hassan, Ali

2015-12-07

Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives.

Solvothermal Synthesis of Magnetic Spinel Ferrites

PubMed Central

Rafienia, Mohammad; Bigham, Ashkan; Hassanzadeh-Tabrizi, Seyed Ali

2018-01-01

At present, solvothermal fabrication method has widely been applied in the synthesis of spinel ferrite nanoparticles (SFNs), which is mainly because of its great advantages such as precise control over size, shape distribution, and high crystallinity that do not require postannealing treatment. Among various SFNs, Fe3O4 nanoparticles have attracted tremendous attention because of their favorable physical and structural properties which are advantageous, especially in biomedical applications, among which the vast application of these materials as targeted drug delivery systems, hyperthermia, and imaging agents in cancer therapy can be mentioned. The main focus of this study is to present an introduction to solvothermal method and key synthesis parameters of SFNs through this synthesis route. Moreover, most recent progress on the potential applications of Fe3O4 nanoparticles as the most important compound among the spinel ferrites family members is discussed. PMID:29928636

Current applications and future prospects of nanomaterials in tumor therapy.

PubMed

Huang, Yu; Fan, Chao-Qiang; Dong, Hui; Wang, Su-Min; Yang, Xiao-Chao; Yang, Shi-Ming

2017-01-01

Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed.

Chemical meningitis related to intra-CSF liposomal cytarabine.

PubMed

Durand, Bénédicte; Zairi, Fahed; Boulanger, Thomas; Bonneterre, Jacques; Mortier, Laurent; Le Rhun, Emilie

2017-10-01

Therapeutic options of leptomeningeal metastases include intra-cerebrospinal fluid (CSF) chemotherapy. Among intra-CSF agents, liposomal cytarabine has advantages but can induce specific toxicities. A BRAF-V600E-mutated melanoma leptomeningeal metastases patient, treated by dabrafenib and liposomal cytarabine, presented after the first injection of liposomal cytarabine with hyperthermia and headaches. Despite sterile CSF/blood analyses, extended intravenous antibiotics were given and the second injection was delayed. The diagnosis of chemical meningitis was finally made. Dose reduction and appropriate symptomatic treatment permitted the administration of 15 injections of liposomal cytarabine combined with dabrafenib. A confirmation of the diagnosis of chemical meningitis is essential in order (1) not to delay intra-CSF or systemic chemotherapy or (2) to limit the administration of unnecessary but potentially toxic antibiotics.

Magnetic and hyperthermia properties of CoxFe3-xO4 nanoparticles synthesized via cation exchange

NASA Astrophysics Data System (ADS)

Mohapatra, Jeotikanta; Xing, Meiying; Liu, J. Ping

2018-05-01

We demonstrate magnetic and hyperthermia properties of CoxFe3-xO4 (x = 0, 0.1, 0.3 and 0.5) nanoparticles synthesized via a simple cation exchange reaction of ˜12 nm Fe3O4 nanoparticles. The substitution of Fe cations with Co2+ ions leads to enhanced magnetocrystalline anisotropy and coercivity of the pristine superparamagnetic Fe3O4 nanoparticles. Hyperthermia measurement shows that by controlling the Co content (x = 0 to 0.5) in CoxFe3-xO4 nanoparticles, their specific absorption rate (SAR) can be greatly improved from 132 to 534 W/g. The strong enhancement in SAR value is attributed to the increased anisotropy and coercivity. Moreover, with the increase of ac magnetic field from 184 to 491 Oe, the SAR values of Fe3O4 and Co0.5Fe2.5O4 nanoparticles increase from 81 to 132 W/g and 220 to 534 W/g, respectively.

Magnetic hyperthermia properties of iron oxide nanoparticles: The effect of concentration

NASA Astrophysics Data System (ADS)

Ebrahimisadr, Saeid; Aslibeiki, Bagher; Asadi, Reza

2018-06-01

We investigated the effect of concentration on magnetic hyperthermia properties of Fe3O4 nanoparticles (NPs). The NPs were synthesized by co-precipitation method at 80 °C. Scanning electron microscope image showed that the mean diameter of NPs is about 18 nm. The XRD pattern indicated that the sample is pure Fe3O4 with spinel structure and the FT-IR spectroscopy confirmed formation of metal-oxygen bonds in the octahedral and tetrahedral spinel sub-lattice which further confirmed crystalline structure of the sample. The hyperthermia property of Fe3O4 NPs was investigated via an induction heater generating alternating magnetic field with frequency of 92 kHz. The temperature rise (ΔT) of suspension in the AC magnetic field was studied on different concentrations of NPs and the specific absorption rate (SAR) was obtained from Box-Lucas equation and linear fitting of ΔT-time curve. The results showed that the ΔT sharply increases with increasing the NPs concentration while the SAR remains almost constant.

Strontium hexaferrite (SrFe12O19) based composites for hyperthermia applications

NASA Astrophysics Data System (ADS)

Rashid, Amin Ur; Southern, Paul; Darr, Jawwad A.; Awan, Saifullah; Manzoor, Sadia

2013-10-01

Mixed phase composites of SrFe12O19/MgFe2O4/ZrO2 were prepared via the citrate gel technique as potential candidate materials for magnetic hyperthermia. Structural and magnetic properties of the samples were studied using powder X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and a vibrating sample magnetometer. XRD and FE-SEM data confirm that magnesium ferrite and zirconium oxide phases increased with increasing Mg and Zr content in the precursors. Magnetization loops for the composites were measured at room temperature and showed significant variation of saturation magnetization, coercivity and remanence depending on the amount of the highly anisotropic Sr-hexaferrite phase. The sample with the highest Mg and Zr content had the lowest coercivity (80 Oe) and saturation magnetization (41 emu/g). The composite samples each were exposed to a 214 kHz alternating magnetic field of amplitude 22 Oe and a significant heating effect was observed in selected samples, which suggests potential for use in magnetic hyperthermia.

Body Temperature Regulation in Hot Environments.

PubMed

Nilsson, Jan-Åke; Molokwu, Mary Ngozi; Olsson, Ola

2016-01-01

Organisms in hot environments will not be able to passively dissipate metabolically generated heat. Instead, they have to revert to evaporative cooling, a process that is energetically expensive and promotes excessive water loss. To alleviate these costs, birds in captivity let their body temperature increase, thereby entering a state of hyperthermia. Here we explore the use of hyperthermia in wild birds captured during the hot and dry season in central Nigeria. We found pronounced hyperthermia in several species with the highest body temperatures close to predicted lethal levels. Furthermore, birds let their body temperature increase in direct relation to ambient temperatures, increasing body temperature by 0.22°C for each degree of increased ambient temperature. Thus to offset the costs of thermoregulation in ambient temperatures above the upper critical temperature, birds are willing to let their body temperatures increase by up to 5°C above normal temperatures. This flexibility in body temperature may be an important mechanism for birds to adjust to predicted increasing ambient temperatures in the future.

Analytical modeling of hyperthermia using magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Bensenane, Mohamed Nassim; Senoudi, Assia Rachida; Benmouna, Reda; Ould-Kaddour, Fouzia

2018-06-01

Hyperthermia using magnetic nanoparticles (MNPs) is one of many techniques to treat cancer causing minimal damage to healthy tissues. In the present work we give an analytical resolution of the bio-heat equation (based on Pennes model) providing the temperature rise as a function of the characteristics of the magnetic nanoparticles, the applied magnetic field and the biological properties of the tissue. The temperature inside the tumor was found to be very sensitive to the frequency f of alternating magnetic field, magnetic field amplitude H0 and volume fraction φ. This study optimizes the intensity of magnetic field to reach ideal hyperthermia conditions. When f varies between 50 and 150 KHz, temperature increases from 39 °C until 53 °C; when H0 is ranged from 5 - 15 kA/m, it increases from 39.5 °C until 49 °C, and when volume fraction φ of MNPs is ranged from 2 × 10-4 to 3 × 10-4 it increases from 44 °C until 48 °C.

Enhanced Energy Localization in Hyperthermia Treatment Based on Hybrid Electromagnetic and Ultrasonic System: Proof of Concept with Numerical Simulations.

PubMed

Nizam-Uddin, N; Elshafiey, Ibrahim

2017-01-01

This paper proposes a hybrid hyperthermia treatment system, utilizing two noninvasive modalities for treating brain tumors. The proposed system depends on focusing electromagnetic (EM) and ultrasound (US) energies. The EM hyperthermia subsystem enhances energy localization by incorporating a multichannel wideband setting and coherent-phased-array technique. A genetic algorithm based optimization tool is developed to enhance the specific absorption rate (SAR) distribution by reducing hotspots and maximizing energy deposition at tumor regions. The treatment performance is also enhanced by augmenting an ultrasonic subsystem to allow focused energy deposition into deep tumors. The therapeutic faculty of ultrasonic energy is assessed by examining the control of mechanical alignment of transducer array elements. A time reversal (TR) approach is then investigated to address challenges in energy focus in both subsystems. Simulation results of the synergetic effect of both modalities assuming a simplified model of human head phantom demonstrate the feasibility of the proposed hybrid technique as a noninvasive tool for thermal treatment of brain tumors.

Fundamental solutions to the bioheat equation and their application to magnetic fluid hyperthermia.

PubMed

Giordano, Mauricio A; Gutierrez, Gustavo; Rinaldi, Carlos

2010-01-01

Methods of predicting temperature profiles during local hyperthermia treatment are very important to avoid damage to healthy tissue. With this aim, fundamental solutions of Pennes' bioheat equation are derived in rectangular, cylindrical, and spherical coordinates. The medium is idealised as isotropic with effective thermal properties. Temperature distributions due to space- and time-dependent heat sources are obtained by the solution method presented. Applications of the fundamental solutions are addressed with emphasis on a particular problem of Magnetic Fluid Hyperthermia (MFH) consisting of a thin shell of magnetic nanoparticles in the outer surface of a spherical solid tumour. It is observed from the solution of this particular problem that the temperature profiles are strongly dependent on the distribution of the magnetic nanoparticles within the tissue. An almost uniform temperature profile is obtained inside the tumour with little penetration of therapeutic temperatures to the outer region of healthy tissue. The fundamental solutions obtained can be used to develop boundary element methods to predict temperature profiles with more complicated geometries.

Effect of magnetic dipolar interactions on nanoparticle heating efficiency: Implications for cancer hyperthermia

PubMed Central

Branquinho, Luis C.; Carrião, Marcus S.; Costa, Anderson S.; Zufelato, Nicholas; Sousa, Marcelo H.; Miotto, Ronei; Ivkov, Robert; Bakuzis, Andris F.

2013-01-01

Nanostructured magnetic systems have many applications, including potential use in cancer therapy deriving from their ability to heat in alternating magnetic fields. In this work we explore the influence of particle chain formation on the normalized heating properties, or specific loss power (SLP) of both low- (spherical) and high- (parallelepiped) anisotropy ferrite-based magnetic fluids. Analysis of ferromagnetic resonance (FMR) data shows that high particle concentrations correlate with increasing chain length producing decreasing SLP. Monte Carlo simulations corroborate the FMR results. We propose a theoretical model describing dipole interactions valid for the linear response regime to explain the observed trends. This model predicts optimum particle sizes for hyperthermia to about 30% smaller than those previously predicted, depending on the nanoparticle parameters and chain size. Also, optimum chain lengths depended on nanoparticle surface-to-surface distance. Our results might have important implications to cancer treatment and could motivate new strategies to optimize magnetic hyperthermia. PMID:24096272

A thermo-fluid analysis in magnetic hyperthermia

NASA Astrophysics Data System (ADS)

Iordana, Astefanoaei; Ioan, Dumitru; Alexandra, Stancu; Horia, Chiriac

2014-04-01

In the last years, hyperthermia induced by the heating of magnetic nanoparticles (MNPs) in an alternating magnetic field received considerable attention in cancer therapy. The thermal effects could be automatically controlled by using MNPs with selective magnetic absorption properties. In this paper, we analyze the temperature field determined by the heating of MNPs, injected in a malignant tissue, subjected to an alternating magnetic field. The main parameters which have a strong influence on temperature field are analyzed. The temperature evolution within healthy and tumor tissues are analyzed by finite element method (FEM) simulations in a thermo-fluid model. The cooling effect produced by blood flow in blood vessels from the tumor is considered. A thermal analysis is conducted under different distributions of MNP injection sites. The interdependence between the optimum dose of the nanoparticles and various types of tumors is investigated in order to understand their thermal effect on hyperthermia therapy. The control of the temperature field in the tumor and healthy tissues is an important step in the healing treatment.

Spherical porous hydroxyapatite granules containing composites of magnetic and hydroxyapatite nanoparticles for the hyperthermia treatment of bone tumor.

PubMed

Kamitakahara, Masanobu; Ohtoshi, Naohiro; Kawashita, Masakazu; Ioku, Koji

2016-05-01

Spherical porous granules of hydroxyapatite (HA) containing magnetic nanoparticles would be suitable for the hyperthermia treatment of bone tumor, because porous HA granules act as a scaffold for bone regeneration, and magnetic nanoparticles generate sufficient heat to kill tumor cells under an alternating magnetic field. Although magnetic nanoparticles are promising heat generators, their small size makes them difficult to support in porous HA ceramics. We prepared micrometer-sized composites of magnetic and HA nanoparticles, and then supported them in porous HA granules composed of rod-like particles. The spherical porous HA granules containing the composites of magnetic and HA nanoparticle were successfully prepared using a hydrothermal process without changing the crystalline phase and heat generation properties of the magnetic nanoparticles. The obtained granules generated sufficient heat for killing tumor cells under an alternating magnetic field (300 Oe at 100 kHz). The obtained granules are expected to be useful for the hyperthermia treatment of bone tumors.

MWCNT-MnFe2O4 nanocomposite for efficient hyperthermia applications

NASA Astrophysics Data System (ADS)

Seal, Papori; Hazarika, Monalisa; Paul, Nibedita; Borah, J. P.

2018-04-01

In this work we present synthesis of multi-walled carbon nanotube (MWCNT)-Manganese ferrite (MnFe2O4) nanocomposite and its probable application in hyperthermia. MnFe2O4 nanoparticles were synthesized by co-precipitation method. X ray diffractogram (XRD) confirms the formation of cubic phase of MnFe2O4 with preferred crystallographic orientation along (311) plane. High resolution electron microscope (HRTEM) image of the composites confirms the presence of MnFe2O4 spherical nanoparticles on the surface of CNT which are bound strongly to the surface. MWCNT-MnFe2O4 nanocomposite were prepared after acid functionalization of MWCNT. Vibrational features of the synthesized samples were confirmed through Fourier transformed infra-red spectroscopy (FTIR). FTIR spectra of acid functionalized MWCNT shows a peak positioned at ˜1620cm-1 which corresponds to C=O functional group of carboxylic acid. Prepared MnFe2O4 nanoparticles and MWCNT-MnFe2O4 nanocomposites were subjected to hyperthermia studies.

Enhanced Energy Localization in Hyperthermia Treatment Based on Hybrid Electromagnetic and Ultrasonic System: Proof of Concept with Numerical Simulations

PubMed Central

Elshafiey, Ibrahim

2017-01-01

This paper proposes a hybrid hyperthermia treatment system, utilizing two noninvasive modalities for treating brain tumors. The proposed system depends on focusing electromagnetic (EM) and ultrasound (US) energies. The EM hyperthermia subsystem enhances energy localization by incorporating a multichannel wideband setting and coherent-phased-array technique. A genetic algorithm based optimization tool is developed to enhance the specific absorption rate (SAR) distribution by reducing hotspots and maximizing energy deposition at tumor regions. The treatment performance is also enhanced by augmenting an ultrasonic subsystem to allow focused energy deposition into deep tumors. The therapeutic faculty of ultrasonic energy is assessed by examining the control of mechanical alignment of transducer array elements. A time reversal (TR) approach is then investigated to address challenges in energy focus in both subsystems. Simulation results of the synergetic effect of both modalities assuming a simplified model of human head phantom demonstrate the feasibility of the proposed hybrid technique as a noninvasive tool for thermal treatment of brain tumors. PMID:28840125

Microchip transponder thermometry for monitoring core body temperature of antelope during capture.

PubMed

Rey, Benjamin; Fuller, Andrea; Hetem, Robyn S; Lease, Hilary M; Mitchell, Duncan; Meyer, Leith C R

2016-01-01

Hyperthermia is described as the major cause of morbidity and mortality associated with capture, immobilization and restraint of wild animals. Therefore, accurately determining the core body temperature of wild animals during capture is crucial for monitoring hyperthermia and the efficacy of cooling procedures. We investigated if microchip thermometry can accurately reflect core body temperature changes during capture and cooling interventions in the springbok (Antidorcas marsupialis), a medium-sized antelope. Subcutaneous temperature measured with a temperature-sensitive microchip was a weak predictor of core body temperature measured by temperature-sensitive data loggers in the abdominal cavity (R(2)=0.32, bias >2 °C). Temperature-sensitive microchips in the gluteus muscle, however, provided an accurate estimate of core body temperature (R(2)=0.76, bias=0.012 °C). Microchips inserted into muscle therefore provide a convenient and accurate method to measure body temperature continuously in captured antelope, allowing detection of hyperthermia and the efficacy of cooling procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micelles driven magnetite (Fe3O4) hollow spheres and a study on AC magnetic properties for hyperthermia application

NASA Astrophysics Data System (ADS)

Goswami, Madhuri Mandal; Dey, Chaitali; Bandyopadhyay, Ayan; Sarkar, Debasish; Ahir, Manisha

2016-11-01

Here we have discussed about designing the magnetic particles for hyperthermia therapy and done some studies in this direction. We have used oleylamine micelles as template to synthesize hollow-nanospheres (HNS) of magnetite by solvo-thermal technique. We have shown that oleylamine plays an important role to generate hollow particles. Structural analysis was done by XRD measurement and morphological measurements like SEM and TEM was performed to confirm the shape and size of hollow sphere particles. The detail magnetic measurements give an idea about the application of these HNS for magnetic heating in hyperthermia therapy. In vitro cytotoxicity studies reveal that tolerable dose rate for these particles can be significantly high and particles are non-toxic in nature. Being hollow in structure and magnetic in nature such materials will also be useful in other application fields like in drug delivery, drug release, arsenic and heavy metal removal by adsorption technique, magnetic separation etc.

Development, characterization, and in vitro trials of chloroaluminum phthalocyanine-magnetic nanoemulsion to hyperthermia and photodynamic therapies on glioblastoma as a biological model

NASA Astrophysics Data System (ADS)

de Paula, L. B.; Primo, F. L.; Jardim, D. R.; Morais, P. C.; Tedesco, A. C.

2012-04-01

A glioblastoma multiforme (GBM) is the highest grade glioma tumor (grade IV) and is the most malignant form of astrocytomas. Grade IV tumors, which are the most malignant and aggressive, affect people between the ages of 45 and 70 years. A GBM exhibits remarkable characteristics that include excessive proliferation, necrosis, genetic instability, and chemoresistance. Because of these characteristics, GBMs are difficult to treat and have a poor prognosis with a median survival of less than one year. New methods to achieve widespread distribution of therapeutic agents across infiltrative gliomas significantly improve brain tumor therapy. Photodynamic therapy (PDT) and hyperthermia (HPT) are well-established tumor therapies with minimal side effects while acting synergistically. This study introduces a new promising nanocarrier for the synergistic application of PDT and magnetic hyperthermia therapy against human glioma cell line T98 G, with cellular viability reduction down to as low as 17% compared with the control.

Proton Relaxivity and Magnetic Hyperthermia Evaluation of Gadolinium Doped Nickel Ferrite Nanoparticles as Potential Theranostic Agents.

PubMed

Yadavalli, Tejabhiram; Raja, Paradeep; Ramaswamy, Shivaraman; Chandrasekharan, Gopalakrishnan; Chennakesavulu, Ramasamy

2017-02-01

This paper outlines the preparation of gadolinium doped nickel ferrite nanoparticles as potential magnetic carriers and longitudinal magnetic resonance imaging contrast agents using hydrothermal method with gadolinium concentration varying from 10% to 40%. A concise effect on the crystal structure was observed at 10% and 20% gadolinium doping, while gadolinium oxide was observed to leach at concentrations exceeding 20%. Further, gadolinium doped nickel ferrites were analyzed for their morphological, magnetic, proton relaxation and magnetic hyperthermia heating properties to understand their potential role as magnetic carrier agents. Low temperature and room temperature magnetic studies conducted on the samples showed comparatively high magnetic saturation with low remanent magnetization. Further, relaxometry studies revealed a high relaxation rate of 6.63 s−1 at a concentration of 0.1 mg/mL. Magnetic hyperthermia studies of the samples at a concentration of 1 mg/mL, assessed that the samples attained a temperature of 68 °C in 240 seconds.

Body Temperature Regulation in Hot Environments

PubMed Central

Nilsson, Jan-Åke; Molokwu, Mary Ngozi; Olsson, Ola

2016-01-01

Organisms in hot environments will not be able to passively dissipate metabolically generated heat. Instead, they have to revert to evaporative cooling, a process that is energetically expensive and promotes excessive water loss. To alleviate these costs, birds in captivity let their body temperature increase, thereby entering a state of hyperthermia. Here we explore the use of hyperthermia in wild birds captured during the hot and dry season in central Nigeria. We found pronounced hyperthermia in several species with the highest body temperatures close to predicted lethal levels. Furthermore, birds let their body temperature increase in direct relation to ambient temperatures, increasing body temperature by 0.22°C for each degree of increased ambient temperature. Thus to offset the costs of thermoregulation in ambient temperatures above the upper critical temperature, birds are willing to let their body temperatures increase by up to 5°C above normal temperatures. This flexibility in body temperature may be an important mechanism for birds to adjust to predicted increasing ambient temperatures in the future. PMID:27548758

Optimal size for heating efficiency of superparamagnetic dextran-coated magnetite nanoparticles for application in magnetic fluid hyperthermia

NASA Astrophysics Data System (ADS)

Shaterabadi, Zhila; Nabiyouni, Gholamreza; Soleymani, Meysam

2018-06-01

Dextran-coated magnetite (Fe3O4) nanoparticles with average particle sizes of 4 and 19 nm were synthesized through in situ and semi-two-step co-precipitation methods, respectively. The experimental results confirm the formation of pure phase of magnetite as well as the presence of dextran layer on the surface of modified magnetite nanoparticles. The results also reveal that both samples have the superparamagnetic behavior. Furthermore, calorimetric measurements show that the dextran-coated Fe3O4 nanoparticles with an average size of 4 nm cannot produce any appreciable heat under a biologically safe alternating magnetic field used in hyperthermia therapy; whereas, the larger ones (average size of 19 nm) are able to increase the temperature of their surrounding medium up to above therapeutic range. In addition, measured specific absorption rate (SAR) values confirm that magnetite nanoparticles with an average size of 19 nm are very excellent candidates for application in magnetic hyperthermia therapy.

Can magneto-plasmonic nanohybrids efficiently combine photothermia with magnetic hyperthermia?

NASA Astrophysics Data System (ADS)

Espinosa, Ana; Bugnet, Mathieu; Radtke, Guillaume; Neveu, Sophie; Botton, Gianluigi A.; Wilhelm, Claire; Abou-Hassan, Ali

2015-11-01

Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives.Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06168g

Reduced-order modeling for hyperthermia control.

PubMed

Potocki, J K; Tharp, H S

1992-12-01

This paper analyzes the feasibility of using reduced-order modeling techniques in the design of multiple-input, multiple-output (MIMO) hyperthermia temperature controllers. State space thermal models are created based upon a finite difference expansion of the bioheat transfer equation model of a scanned focused ultrasound system (SFUS). These thermal state space models are reduced using the balanced realization technique, and an order reduction criterion is tabulated. Results show that a drastic reduction in model dimension can be achieved using the balanced realization. The reduced-order model is then used to design a reduced-order optimal servomechanism controller for a two-scan input, two thermocouple output tissue model. In addition, a full-order optimal servomechanism controller is designed for comparison and validation purposes. These two controllers are applied to a variety of perturbed tissue thermal models to test the robust nature of the reduced-order controller. A comparison of the two controllers validates the use of open-loop balanced reduced-order models in the design of MIMO hyperthermia controllers.

Dopamine D3 receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: Role of hyperthermia

PubMed Central

Baladi, Michelle G.; Newman, Amy H.; Nielsen, Shannon M.; Hanson, Glen R.; Fleckenstein, Annette E.

2014-01-01

Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine-induced changes to dopamine systems. The present study extended these findings by testing the role of the dopamine D3 receptor subtype in mediating the long-term dopaminergic, and for comparison serotonergic, deficits caused by methamphetamine. Results indicate that the dopamine D3 receptor selective antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine-induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by treating rats in a warm ambient environment, PG01037 failed to attenuate the effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate methamphetamine-induced decreases in dopamine and 5HT content. Taken together, the present study demonstrates that dopamine D3 receptors mediate, in part, the long-term deficits in DAT function caused by methamphetamine, and that this effect likely involves an attenuation of methamphetamine-induced hyperthermia. PMID:24685638

Study of non-uniform nanoparticle liposome extravasation in tumour.

PubMed

Liu, P; Zhang, A; Xu, Y; Xu, L X

2005-05-01

The effect of hyperthermia on the nanoparticle extravasation in different tumour regions was investigated in real time using confocal laser scanning microscopy. Murine mammary carcinoma 4T1 was implanted in the nude mice dorsal skin-fold window chamber. Tumour angiogenesis was observed through the window chamber on days 4, 7, 8 and 10 after the implantation. In 10 days, the tumour became 1-2 mm in diameter and 150 microm thick. Most vessels were found to be <15 microm in diameter. Histological examination showed that there were fewer vessels in a more ordered branching pattern inside the tumour than in the tumour periphery. After hyperthermia at 42 degrees C for 1 h, numerous erythrocytes were found in the peripheral region. Extravasation of rhodamine-labelled 100 nm nanoparticles in different tumour regions under both normal and hyperthermic conditions (34 and 42 degrees C) was quantified using confocal fluorescence microscopy. The relative fluorescence intensity hardly changed in tissue at 34 degrees C, but increased by the local hyperthermia at 42 degrees C. In particular, the relative intensity in the tumour periphery was more than 120 as compared to 40 in the tumour centre, after 1 h hyperthermia. Results showed that the thermally induced liposome nanoparticle extravasation was heterogeneous in tumour, owing to the non-uniform distribution of tumour vasculature. Further, the degree of vascular damage was found to be more severe in the tumour periphery, which is likely due to the high thermal sensitivity of newly formed tumour vessels in this region.