Human tumour xenografts in athymic rats and their age dependence

Maruo, Koji; Ueyama, Yoshito; Kuwahara, Yoshikazu; Hioki, K.; Saito, Mitsuhiro; Nomura, Takeshi; Tamaoki, Norikazu

doi:10.1038/bjc.1982.122

Cited by 36 publications

(20 citation statements)

References 4 publications

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“…The slow growth oftumors in the young animals and the lack of growth in older animals is consistent with observations that nude rats have elevated natural killer cell activity and extrathymic Tcell differentiation that occurs in an age-related fashion 24,25 Prior reports have shown that whole-body irradiation significantly increases take rates for subcutaneous tumor xenografts in nude rats. 26 To improve acceptance of the Fischer 11-45 tumor implantation in athymic nude rats, we further immunosuppressed these animals with 500 cGy of whole-body irradiation on the day of tumor implantation.…”

Section: Adenoviral Vectorssupporting

confidence: 64%

The Role of Immunosuppression in the Efficacy of Cancer Gene Therapy Using Adenovirus Transfer of the Herpes Simplex Thymidine Kinase Gene

et al. 1995

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Section: Adenoviral Vectorssupporting

confidence: 64%

The Role of Immunosuppression in the Efficacy of Cancer Gene Therapy Using Adenovirus Transfer of the Herpes Simplex Thymidine Kinase Gene

et al. 1995

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“…The take rates for cells from previously serially transplantable tumour lines or from primary explants have been reported to be equal in rats and mice (Sawada et al, 1982;Matthews et al, 1982). However, in a few studies the take rates have been observed to be lower in nude rats (Maruo et al, 1982;Giovanella et al, 1984). In addition, the take rate (Sawada et al, 1982;Maruo et al, 1982;Drewinko et al, 1986) and growth rate (Maruo et al, 1982) of xenografts in nude rats have been observed to decrease with increasing age in the animal.…”

Section: Discussionmentioning

confidence: 94%

“…However, in a few studies the take rates have been observed to be lower in nude rats (Maruo et al, 1982;Giovanella et al, 1984). In addition, the take rate (Sawada et al, 1982;Maruo et al, 1982;Drewinko et al, 1986) and growth rate (Maruo et al, 1982) of xenografts in nude rats have been observed to decrease with increasing age in the animal. This decrease of take rate and growth rate is thought to be related to the observed increase of host NK cell activity with ageing in the nude rat (Lotzova et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Progressive growth of a human pleural mesothelioma xenografted to athymic rats and mice

Lindén

Johansson²

1988

Br J Cancer

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Summary A human malignant pleural mesothelioma was xenografted serially in athymic nude Rowett rats for 27 passages during 33 months. After the two initial passages (P), the take rate during P3-9 was 100% (192/192). The tumour grew progressively during P3-9 in 99% (190/192) and regressed totally in 1% (2/192). The take rate for the tumour xenografted to athymic BALB/c mice was also 100% (17/17) and no regressions were observed. During serial passaging in nude rats, the tumour-volume doubling time (TD) decreased from 6 days in P2 to 3 days in P8-9 (P<0.001) and then remained around 3 days during P10-25. A TD of 11 days in P1 (man-mouse) for tumours grown in mice decreased during 10 passages in rats to 4 days (P<0.005) when the tumour was transplanted to mice in P11. Light microscopic morphology of the tumour was retained in rats and mice. We believe that our experimental tumour model using the nude rat as a carrier of the xenograft will be useful for studies of human mesothelioma.Malignant human pleural mesothelioma (MHPM) is a rare tumour with a poor prognosis. The evaluation of chemoand radiotherapy is difficult in MHPM owing to difficulties in measuring the tumour volume, lack of a generally accepted staging system (Dimitrov et al., 1983) and different prognoses in the three main histologic subtypes of this tumour (Elmes & Simpson, 1976).Growth of human tumour xenografts in athymic nude mice or artificially immunosuppressed mice is regarded as the best currently available experimental model for studying the response of human tumours to drugs (Pihl, 1986). Most human malignant tumours, including pleural mesotheliomas (Chahinian et al., 1980;Linden et al., 1982), have been xenografted to athymic mice.Festing et al. (1978) described an athymic nude rat with an immunodeficiency state comparable to that of the athymic mouse, suggested to be more robust for certain experimental situations, e.g., for experiments requiring surgical manipulations and frequent blood sampling.Experience with the athymic rat is sparse compared to that with the athymic mouse, but many human malignant tumours, including one human malignant pleural mesothelioma (Linden et al., 1982), have been successfully xenografted to rats.In the present study we transplanted another MHPM to both athymic rats and mice and studied the long-term growth pattern of this tumour line in nude rats. We also compared the growth pattern of the tumour in athymic mice and rats. Materials and methods TumourA 66-year old man was found to have an epithelial pleural mesothelioma at thoracoscopic biopsy of the parietal pleura.The tumour was treated with irradiation to a total dose of 40 Gy. About 2 weeks after the completion of the radiotherapy against the diseased hemithorax, an implantation metastasis was noted in the former needle tracks. This tumour nodule was excised and used for establishing this (AKG) tumour cell line. The patient was treated further with 3 courses of combined chemotherapy consisting of doxorubicin and cyclophosphamide, but in spite of this trea...

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“…In most previously published orthotopic animal models of human GBM (Rana et al 1977;Bradley et al 1978;Shapiro et al 1979;Bullard et al 1981;Horten et al 1981;Jones et al 1981;Basler and Shapiro 1982;Marno et al 1982;De Armond et al 1994), the tumors were implanted not in solid pieces but by stereotaxic injection of cell suspensions. The cell suspension methods of grafting have the distinctive advantage of limited surgical trauma.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Tissue Chimerism in Nude Mouse Brain and Abdominal Xenograft Models of Human Glioblastoma Multiforme: What Does It Tell Us About the Models and About Glioblastoma Biology and Therapy?

Antunes

Angioï-Duprez

Bracard

et al. 2000

J Histochem Cytochem.

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S U M M A R YIn situ hybridization coupled to immunohistochemistry for antigens of interest allows unequivocal identification of tumor cells from reactive stroma cells and normal adjacent structures in human glioblastoma multiforme grafts transplanted into nude mice. With this methodology, we have explored the development of glioblastoma multiforme solid grafts transplanted into nude mouse brains or flanks. The brain transplants closely resembled the human situation, particularly in relation to differentiation and growth patterns. The morphological features of peritumoral reactive gliosis were similar to those observed in humans. A mouse glial stroma within the main tumor masses was also demonstrated. Kinetic studies showed that the compartment of isolated tumor cells that infiltrated host brains and the reactive gliosis constituted two cycling cell populations. Despite VEGF protein expression by tumor cells and some reactive astrocytes, the abnormally permeable microvascular beds were not hyperplastic. The observation of a non-infiltrative pattern of growth when grafts were established in host flanks demonstrated that the organ-specific environment plays a determining role in the growth and invasive properties of glioblastoma. The phylogenetic distance between man and mouse and the recipient immunoincompetence should not impose serious limitations on the use of this model for studying malignant glioma biology and therapy in vivo.

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Human tumour xenografts in athymic rats and their age dependence

Abstract: Images Fig. 1

Cited by 36 publications

References 4 publications

The Role of Immunosuppression in the Efficacy of Cancer Gene Therapy Using Adenovirus Transfer of the Herpes Simplex Thymidine Kinase Gene

The Role of Immunosuppression in the Efficacy of Cancer Gene Therapy Using Adenovirus Transfer of the Herpes Simplex Thymidine Kinase Gene

Progressive growth of a human pleural mesothelioma xenografted to athymic rats and mice

Analysis of Tissue Chimerism in Nude Mouse Brain and Abdominal Xenograft Models of Human Glioblastoma Multiforme: What Does It Tell Us About the Models and About Glioblastoma Biology and Therapy?

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