Treatment of Murine SCC VII Tumors with Localized Hyperthermia and Temperature-Sensitive Liposomes Containing Cisplatin

Nishimura, Yasumasa; Ono, Koji; Hiraoka, Masahiro; Masunaga, S.; Jo, Sooyeon; Shibamoto, Yuta; Sasai, Keisuke; Abe, Mitsuyuki; Iga, Kanji; Ogawa, Yasuaki

doi:10.2307/3577601

Cited by 52 publications

(31 citation statements)

References 12 publications

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“…Additionally, it has been reported that this level of modest hyperthermia cannot delay tumour growth (Nishimura et al, 1990) or draw direct thermal radiosensitization (Dewey, 1994).…”

Section: Discussionmentioning

confidence: 99%

Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations

Masunaga

Ono²,

Akaboshi³

et al. 1997

Br J Cancer

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Summary C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted miniosmotic pumps in order to label all proliferating (P) cells. The tumours were then heated at 400C for 60 min. At various time points after heating, tumour-bearing mice were irradiated while alive or after being killed. Immediately after irradiation, the tumours were excised, minced and trypsinized. The tumour cell suspensions obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling, which could be regarded as quiescent (Q) cells, was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. The MN frequency of BrdU unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total (P+Q) tumour cells. In general, Q cells contained a greater hypoxic fraction (HF) than the total tumour cell population. Mild heating decreased the HF of Q cells more markedly than in the total cell population, and the minimum values of HFs of both total and Q cell populations were obtained 6 h after heating. Two days after heating, the HF of total tumour cells returned to almost that of unheated tumours. In contrast, the HF of Q cells did not return to the HF level of unheated tumours until 1 week after heating. It was thought that irradiation within 12 h after mild heating might be a potentially promising therapeutic modality for controlling radioresistant Q tumour cells.Keywords: quiescent cell; hypoxic fraction; mild hyperthermia; immunofluorescence staining; micronucleus assay; 5-bromo-2'-deoxyuridine Tumour hypoxia is clearly an important problem, and improved patient responses to radiotherapy can be achieved by treatments that overcome tumour radiation resistance resulting from the presence of hypoxic cells (Overgaard, 1989). It has been firmly established that hypoxic cells impair the radiation responsiveness of almost all animal tumours thus far investigated (Coleman, 1988).The effectiveness of hyperthermia as an adjuvant modality to radiotherapy has been demonstrated (Overgaard et al, 1995). Laboratory experiments using animal tumours showed that heating for 30 to 60 min at relatively high temperatures, i.e. > 43 to 44°C, damages intratumour blood vessels and kills tumour cells (Vaupel, 1990). Additionally, hyperthermia causes direct cellular radiosensitization (Dewey, 1994). However, currently available hyperthermia devices have been ineffective in raising the temperature of human tumours sufficiently to cause such effects. Furthermore, according to clinical results of thermoradiotherapy, correlations between response to hyperthermia and lowest temperatures in tumours have been reported, and the prognostically important temperatures have been < 41C (Valdagni et ...

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“…Additionally, it has been reported that this level of modest hyperthermia cannot delay tumour growth (Nishimura et al, 1990) or draw direct thermal radiosensitization (Dewey, 1994).…”

Section: Discussionmentioning

confidence: 99%

Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations

Masunaga

Ono²,

Akaboshi³

et al. 1997

Br J Cancer

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“…Hyperthermia-mediated, targeted drug delivery of cisplatin or methotrexate encapsulated in temperature-sensitive liposomes to murine tumors has been shown to result in similar enhancement of antitumor efficacy [49][50][51]. Overgaard et al…”

Section: Discussionmentioning

confidence: 99%

Enhanced Antitumor Effect of Radiation in Combination with Heat-Sensitive Liposome-Encapsulated Drug and Hyperthermia on Murine Tumors.

Tamiz

Ralhan

1995

J. Clin. Biochem. Nutr.

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SummaryAdjuvant hyperthermia enhances the response of melanoma to irradiation or antineoplastic drugs. Radiation in combination with a targeted drug delivery system combining a thermosensitive Liposome-encapsulated antitumor drug with hyperthermia may thus result in enhancement of therapeutic efficacy for more effective management of melanoma. The present study was based on this rationale. The therapeutic effect of radiation alone, or in combination with thermosensitive liposome-encapsulated melphalan and hyperthermia, was determined on B16F10 murine melanoma transplanted into C57B1/6 mice. This multimodality regimen resulted in marked enhancement of the antitumor efficacy in treated animals, as determined by significant tumor growth regression (p < 0.001) and prolongation of survival, compared with the level of enhancement seen in animals receiving single-modality treatment. The results suggest that radiothermochemotherapy using radiation in combination with heat-mediated selective delivery of liposomal melphalan to tumor tissue would result in more effective management of melanoma.

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“…We employed the same heating method as reported previously. 12) Temperatures at the tumor center equilibrated within 3 to 4 min after immersion in the water bath and remained 0.2-0.3°C below the water bath temperature. The temperature difference between the tumor center and the periphery was within 0.1°C.…”

Section: )mentioning

confidence: 99%

Usefulness of Tirapazamine as a Combined Agent in Chemoradiation and Thermo‐chemoradiation Therapy at Mild Temperatures: Reference to the Effect on Intratumor Quiescent Cells

Masunaga

Ono

Suzuki

et al. 2000

Japanese Journal of Cancer Research

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Treatment of Murine SCC VII Tumors with Localized Hyperthermia and Temperature-Sensitive Liposomes Containing Cisplatin

Cited by 52 publications

References 12 publications

Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations

Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations

Enhanced Antitumor Effect of Radiation in Combination with Heat-Sensitive Liposome-Encapsulated Drug and Hyperthermia on Murine Tumors.

Usefulness of Tirapazamine as a Combined Agent in Chemoradiation and Thermo‐chemoradiation Therapy at Mild Temperatures: Reference to the Effect on Intratumor Quiescent Cells

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