Upregulation of heat shock proteins and the promotion of damage-associated molecular pattern signals in a colorectal cancer model by modulated electrohyperthermia

Andócs, Gábor; Meggyesházi, Nóra; Balogh, Lajos; Spisák, Sándor; Maros, Máté E.; Balla, Péter; Kiszner, Gergő; Teleki, Ivett; Csaba, Kovago; Krenács, Tibor

doi:10.1007/s12192-014-0523-6

Cited by 72 publications

(97 citation statements)

References 40 publications

(90 reference statements)

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“…4). This delayed effect of the treatment may be associated with mEHT, which is known to elicit delayed apoptotic reactions (41,42) and to improve immunity (43,44), as well as with the TCM. TCM herbal medicines increase the sensitivity of cancer to mEHT and, vice versa, mEHT increases the anticancer effect of herbal medicines (9).…”

Section: Discussionmentioning

confidence: 99%

Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of peritoneal carcinomatosis with malignant ascites: A phase II randomized trial

Pang¹,

Zhang²,

Wang³

et al. 2017

Molecular and Clinical Oncology

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Abstract. The purpose of this study was to develop a safe and non-toxic alternative to the conventional conservative treatment of peritoneal carcinomatosis with malignant ascites (PCMA) by investigating the efficacy and safety of local modulated electro-hyperthermia (mEHT) combined with the traditional Chinese medicine (TCM) 'Shi Pi' herbal decoction, compared with standard intraperitoneal chemoinfusion (IPCI). A randomized, controlled, single-center, open-label clinical trial (phase II) with two parallel groups (allocation ratio, 1:1) was conducted to investigate the efficacy and safety of mEHT+TCM (study group, SG) vs. standard IPCI (control group, CG) in patients with PCMA by intention-to-treat analysis. A total of 260 patients with PCMA were randomly allocated into the two groups (130/130); mEHT was applied for 60 min per session every second day for 4 weeks, for a total of 14 sessions. The TCM decoction was administered orally, at 400 ml daily. In CG, occlusive IPCI with cisplatin (30-60 mg) and fluorouracil (500-600 mg/m 2 ) was applied twice, biweekly. The objective response rate (ORR), quality of life (QoL) and adverse event rate (AER) in the two groups were evaluated 1 month after treatment, analyzed and compared. The present study is registered on ClinicalTrials.gov (NCT02638051). No case was lost or excluded (0/260). The ORR in SG was 77.69% (101/130) vs. 63.85% (73/130) in CG (P<0.05). The QoL in SG was 49.23% vs. 32.3% in CG (P<0.05). The AER in SG was 2.3% (3/130) vs. 12.3% (16/130) in CG (P<0.05). All the adverse events were grade I. In conclusion, the combination of mEHT with TCM achieves better control of PCMA compared with standard IPCI, with less toxicity. Both components of the combination are non-toxic treatments easily tolerated by patients. Thus, this combined treatment may be preferred due to the better benefit-harm balance.

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Section: Discussionmentioning

confidence: 99%

Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of peritoneal carcinomatosis with malignant ascites: A phase II randomized trial

Pang¹,

Zhang²,

Wang³

et al. 2017

Molecular and Clinical Oncology

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“…In the case of well-applied excitations, these create a spatiotemporal production of particular molecules (damage-associated molecular pattern, DAMP), and its consequence could be immunogenic cell-death (ICD), [46]. The high energy absorption at membrane raft appears in cellular level also.…”

Section: Discussionmentioning

confidence: 99%

Energy Absorption by the Membrane Rafts in the Modulated Electro-Hyperthermia (mEHT)

Papp¹,

Vancsik²,

Kiss³

et al. 2017

OJBIPHY

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Aim: Heating by nanoparticles, which are located in the tissue to be treated, is a well-recognized method in hyperthermic oncology. Our objective is to investigate selective, nanoscopic heating without concentrating extra artificial nanoparticles. We have in silico calculation to study the heating of the transmembrane protein clusters (rafts) on cell-membrane. The transmembrane protein domains have significantly higher dielectric constant than their lipid neighborhood in the membrane. This difference causes a local gradient in the Specific Absorption Rate (SAR), which could be a factor of heating of the membranes locally, as well as exciting the receptors for various signal transduction in the cells. We suppose that this process determines the observed cellular effects of modulated electro-hyperthermia (mEHT, trade-name: oncothermia). Materials and Methods: In silico models with highly specialized software (Computer Simulation Technology (CST), Darmstadt, Germany) were performed visualizing the selectivity for the membrane domains. Local raft models were created to simulate the electromagnetic (EM) effect of a 13.56 MHz excitation between two perfect electrical conductor plates, simulating the equipotential conditions of the sides of the membrane in the vicinity of the raft. The simulations were performed with near-field (EQS) solver of CST. The electric field, current density, and electric loss density were monitored by the simulations. The applied material properties and parameters refer to the recent literature. Results: In silico models show ten times higher energy-absorption of the transmembrane domains than that of its lipid-membrane surrounding, and intra-and extracellular neighborhood. Depending on the size, orientation, and location of the membrane rafts, the value of SAR varies, but we use only two simplified models to see the absorption properties. Taking into account the characteristics of the EM field effects we showed that the selective energy-absorption increased further by the cell-cell interactions. The The heated protein-clusters (membrane rafts) are used the same way as the artificial nanoparticles, while these absorbers are natural parts of the biological system.

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“…HSP70 is expressed on the membrane and extracellularly liberated [119] HMGB1, calreticulin, and small vehicles like apoptotic bodies and exosomes are involved. These are members of the damage-associated molecular pattern, which could play an immunogenic role in the further development of complexity [120]. The mechanism involves destroying the malignant cells by mEHT, using immunogenic cell death as the basis of the immune effects, Figure 13.…”

Section: Modulated Electro-hyperthermia (Meht)mentioning

confidence: 99%

Heating Preciosity—Trends in Modern Oncological Hyperthermia

Szász¹,

Szász²,

Minnaar³

et al. 2017

OJBIPHY

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The use of hyperthermia as a treatment in oncology is a common topic for debate. Some researchers expect a breakthrough in oncological treatments with hyperthermia, whereas others have disregarded the method. Serious questions concerning hyperthermia have arisen. Should homogeneous (isothermal) or heterogeneous (selective) heating being used? When we use selective heating (heterogeneity), should the entire tumour be targeted or should the malignant cells be individually selected? Does the mechanism involve thermal cell death or thermally-assisted cell death? Is the goal necrosis or apoptosis? Is hyperthermia safe as a monotherapy or does it have to be combined with conventional treatments? When the selection is local, how do we act on disseminated cells that represent a high risk of life threatening metastases? When local heating is the focus, how should it be carried out with measured and controlled? Our objective is to show how precise, selective heat transfer is necessary to remove malignant cells and, consequently, how hyperthermia as part of the immune-oncology can change the game in this promising field of oncological therapies.

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Upregulation of heat shock proteins and the promotion of damage-associated molecular pattern signals in a colorectal cancer model by modulated electrohyperthermia

Cited by 72 publications

References 40 publications

Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of peritoneal carcinomatosis with malignant ascites: A phase II randomized trial

Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of peritoneal carcinomatosis with malignant ascites: A phase II randomized trial

Energy Absorption by the Membrane Rafts in the Modulated Electro-Hyperthermia (mEHT)

Heating Preciosity—Trends in Modern Oncological Hyperthermia

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