Long duration mild temperature hyperthermia and brachytherapy

Abstract

Combining long duration mild temperature hyperthermia (LDMH) and low dose-rate (LDR) brachytherapy to enhance therapeutic killing of cancer cells was proposed many years ago. The cellular and tumour research that supports this hypothesis is presented in this review. Research describing LDMH interaction with pulsed brachytherapy and high dose-rate brachytherapy using clinically relevant parameters are compared with LDMH/LDR brachytherapy. The mechanism by which LDMH sensitizes LDR has been established as the inhibition of sublethal damage repair. The molecular mechanisms have been shown to involve DNA repair enzymes, but the exact nature of these processes is still under investigation. The relative differences between LDMH interactions with human and rodent cells are presented to help in the understanding of possible roles of LDMH in clinical application. The role of LDMH in modifying tumour blood flow and its possible role in LDR sensitization of tumours is also presented. The positive aspects of LDMH-brachytherapy for clinical application are sixfold; (1) the thermal goals (temperature, time and volume) are achievable with currently available technology, (2) the hyperthermia by itself has no detectable toxic effects, (3) thermotolerance appears to play a minor if any role in radiation sensitization, (4) TER of around 2 can be expected, (5) hypoxic fraction may be decreased due to blood flow modification and (6) simultaneous chemotherapy may also be sensitized. Combined LDMH and brachytherapy is a cancer therapy that has established biological rationale and sufficient technical and clinical advancements to be appropriately applied. This modality is ripe for clinical testing.

Inhibition of repair of radiation-induced damage by mild temperature hyperthermia, referring to the effect on quiescent cell populations

“…16 However, both in vitro and in vivo, when combined simultaneously with LDR irradiation, MTH had been reported to inhibit effi ciently cell recovery caused by the decrease in the irradiation dose rate. 5 In the current study, the usefulness of MTH as a manipulation for suppressing PLDR and sublethal damage repair (SLDR) in both total and Q tumor cell populations was evaluated by applying MTH right after HDR irradiation and during LDR irradiation using γ-ray radiation, respectively, in terms of the responses of the total and Q-cell populations in solid tumors using our unique method for selectively detecting the response of Q-cell populations in vivo. 10 Two major pathways for the repair of potentially lethal DNA double-stranded breaks (dsbs) exist in mammalian cells.…”

“…3 Meanwhile, the effects of mild temperature hyperthermia (MTH) (39°-42°C for 1-2 h) on tissues are subtle and have been largely ignored until recently. However, the subtle effects of MTH, including heat-mediated tumor reoxygenation 4 and inhibition of sublethal and potentially lethal damage repair, 5 provide a strong rationale for using MTH in combination with radiotherapy.…”

Termoterapia en cáncer de próstata mediante el uso de nanopartículas magnéticas

“…Desde el punto de visto radio-biológico, la aplicación simultánea de calor y radiación es considerada ideal para la termorradioterapia 29 . En concreto, el concepto de combinar la hipertermia suave con la radiación LDR ha sido propuesto de manera prometedora, pero, que nosotros sepamos nunca se ha llevado a cabo clínicamente 30 . Con este fin, hemos comenzado en nuestra institución un estudio de Fase II en pacientes con cán-cer de próstata clínicamente localizado y con criterio de riesgo intermedio (PSA 10-20ng/ml o suma de Gleason 7), que no habían sido tratados previamente.…”

Adverse effect of mild temperature hyperthermia combined with hexamethylenetetramine compared to its effect combined with tirapazamine in the treatment of solid tumors

“…Scc Vii squamous cell carcinomas (department of radiotherapy, Kyoto university) derived from c3h/he mice were maintained in vitro in eagle's minimum essential medium supplemented with 12.5% fetal bovine serum. the cells (1.0x10 5 ) were inoculated subcutaneously into the left hind legs of 8-to 11-week-old syngeneic female c3h/he mice (Japan animal co., ltd., osaka, Japan). after 14 days, tumors with a diameter of ~1 cm were selected for use in the experiments.…”

“…meanwhile, until recently the effects of mild temperature hyperthermia (MTH) (39-42˚C for 1-2 h) on tissue have largely been ignored. however, mth has subtle effects, including heat-mediated tumor reoxygenation (4) and the inhibition of sublethal and potentially lethal damage repair (5), which provide a very strong rationale for using mth in combination with radiotherapy. in addition, the physiological and cellular effects of mth can improve the delivery of drug vehicles (6), activate promoters for heat-mediated gene therapy (7) and increase immune response to tumors through a variety of mechanisms (8).…”