Representativity of Xenografts for Clinical Cancer. Tumor and Host Characteristics as Variables of Tumor Take Rate

Fodstad, Øystein

doi:10.1007/978-3-642-73252-2_3

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…Bomholtgaard, Ry, Denmark. NMRI and triple immune-defective NIH I11 (Fodstad, 1987) nude mice were bred in our own nude mouse facility. Animals were kept in laminar air-flow rooms at constant temperature (24-26°C) and humidity (30-50%).…”

Section: Micementioning

confidence: 99%

“…The availability of athymic nude mice means that the biology and chemosensitivity of human tumors can be studied in vivo (Rygaard and Povlsen, 1969;Giovanella et al, 1974Giovanella et al, , 1983Sordat et al, 1974;Shimosato et al, 1976;Ovejera et al, 1978;Fodstad et al, 1977Fodstad et al, , 1980Kyriazis et al, 1978Kyriazis et al, , 1981Bellet et al, 1979;Povlsen et al, 1982), since xenografted tumors usually have a close resemblance to the tumor of origin in morphology and in most biochemical characteristics (Sordat et al, 1974;Fodstad, 1979Fodstad, , 1987Bellet et al, 1979;Kyriazis et al, 1981;Povlsen et al, 1982;Giovanella et al, 1983;Sharkey and Fogh, 1984). A shortcoming of the model is that spontaneous metastases do not occur ordinarily in nude mice (Sharkey and Fogh, 1979;Sordat et al, 1982).…”

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confidence: 99%

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A new experimental metastasis model in athymic nude mice, the human malignant melanoma lox

Fodstad

Aamdal

McMenamin

et al. 1988

Intl Journal of Cancer

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The human tumor line LOX was established as an s.c. xenograft in nude mice from a lymph-node metastasis of a patient with malignant melanoma. I.v. injection into adult nude mice of single-cell suspensions prepared from xenografts resulted in progressively growing lung tumor colonies that killed the animals. No difference in colony formation was seen between cells taken from lung colonies and s.c. xenografts. An in vitro cell line, LOX-L, was established from lung colonies, and the monolayer cells, detached with EDTA, retained the same ability to form experimental lung metastases. In a total of 14 experiments, 82 of 89 mice receiving 1 X 10(6) viable tumor cells died with a mean survival time of 34.1 +/- 4.8 days. Long-term passaging in vivo and in vitro did not result in any alteration of the lung-colonizing potential of the LOX cells, whereas trypsinization of the cells before i.v. injection reduced lung colony formation. The life span was inversely related to the number of LOX cells injected, permitting estimation of the cell kill caused by chemotherapy. Mice injected i.v. with the LOX cells showed the same relative response to cis-diamminedichloroplatinum (CDDP) and mitozolomide (MZA) as did animals carrying s.c. xenografts. The LOX cells have shown a remarkable stability and similarity to the cells of the patient's tumor with respect to morphology, karyotype and chemosensitivity. The LOX model may be useful for testing effects of therapy on lung micro- and macrometastases, and the activity of antimetastatic agents, as well as for studying mechanisms involved in the metastatic process.

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Section: Micementioning

confidence: 99%

mentioning

confidence: 99%

A new experimental metastasis model in athymic nude mice, the human malignant melanoma lox

Fodstad

Aamdal

McMenamin

et al. 1988

Intl Journal of Cancer

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“…Studies have shown that subcutaneous xenograft models can emulate clinical behavior [72±74], although recently some authors have questioned the accuracy of this data when applied to human drug trials [75]. These models have some disadvantages, however, including: (1) a low tumor take-rate for fresh clinical specimens [72,76], (2) tumor growth in an unusual tissue compartment (the subcutis), the microenvironment of which might influence study results, and (3) the lack of consistent invasion and metastasis [72,77,78], properties that are closely linked to clinical outcome in humans.…”

Section: Human Lung Tumor Xenograftsmentioning

confidence: 99%

Laboratory Models of Lung Cancer

Liu

Johnston

Tumors of the Chest

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Lung cancer is a devastating disease that is associated with significant morbidity and mortality. Most patients die of progressive metastatic disease despite aggressive local and systemic therapies [1]. The pathogenesis of lung cancer remains highly elusive due to its aggressive biologic nature and considerable heterogeneity as compared to other cancers. These circumstances substantially impede study of the disease in humans and necessitate the use of experimental models that can be used under more uniform, controlled conditions than those achievable in clinical settings. The development of animal models of lung cancer may aid in our understanding of lung tumor biology and facilitate the development and testing of novel therapeutic approaches and methods for early diagnosis. To this end, animal models should mimic both the genetic alterations found in human lung tumors and their histological characteristics.Humans are one of only a few species that are susceptible to the spontaneous development of lung cancer. Lung tumors in domestic animals were periodically observed by veterinarians, but Livingood's histologic description 100 years ago of a papillary tumor in a mouse [2] initiated the idea of using animals as experimental tools. There are currently several types of animal models that are widely used for experimental lung cancer research. These include chemically induced lung tumors, transgenic mouse models, and human tumor xenografts.A single model system that faithfully reflects the whole process of lung cancer carcinogenesis and progression is unlikely to be developed. Lung cancer models that accurately reflect the different aspects of the disease are necessary to properly investigate its myriad of complexities. Tumorigenesis, proliferation, invasion, angiogenesis, metastasis, prevention, and therapy are all areas where specific models are required to ensure proper experimental design. To reflect the anticipated biological process being studied, model systems may require certain deviations from the human disease. Thus, we should interpret results of studies utilizing model systems with caution and with an appropriate understanding of their limitations. The purpose of this review is to summarize the various lung cancer model systems in use today and to define both their utility and limitations. As Siemann stated, it is best to ª. . . choose the model to address the question rather than force the question on the tumor modelº [3]. General PrinciplesTumor±host interactions, including immunologic effects, vascular and stromal effects, and host-related pharmacologic and pharmacokinetic effects, are poorly modeled in vitro. Animal models to study these areas can be broadly divided into spontaneous or induced tumors, and transplanted tumors. The former group consists of those induced by some extrinsic chemical or carcinogen and animals genetically modified to express genes that lead to lung tumor development. The latter group includes the widely used heterograft and xenograft models. We will briefly describe all of t...

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Tumorigenicity of cerebellar primitive neuro-ectodermal tumors in athymic mice correlates with poor prognosis in children

et al. 1996

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The histogenesis of medulloblastoma, also described as a cerebellar primitive neuro-ectodermal tumor (PNET), remains controversial and unresolved. In addition, genetic markers which characterize cerebellar PNETs with poor prognosis in children have not been identified. Since xenografts can be valuable tools for better understanding the genetic events involved in cerebellar PNETs, small fragments of tumor samples from I 7 children with newly diagnosed cerebellar PNETs were transplanted S.C. into female athymic Swiss mice. Eleven were non-metastatic and 6 were metastatic PNETs. Eight tumors (47%) were tumorigenic. Histological analysis showed 6 typical medulloblastomas, I PNET with melanin pigment and I PNET with a rhabdoid phenotype. Wide heterogeneity was observed in tumor growth, with a doubling time ranging from 8 to 8 I days after the first passage. Tumorigenicity was correlated with the metastatic phenotype of the tumor (p < 0.00 I). All the patients but one with a tumorigenic tumor relapsed and died. The survival of patients with a non-tumorigenic PNET (67%) was significantly higher than that of patients with a tumorigenic PNET (I 3%) (p < 0.02). None of the xenografts or tumors from patients exhibited N-myc-gene alteration. Only one xenograft showed c-myc amplification, with an abnormal 15-kilobase fragment. None of the I 7 tumors from patients showed amplification or c-myc-gene rearrangement. In conclusion, tumorige-nicity of cerebellar PNETs strongly correlates both with the metastatic phenotype of the tumors and with the disease-free survival of the patients. In addition, genetic events other than c-myc-gene amplification might be involved in cerebellar PNETs with poor prognosis. o 1996 Wilty-Liss, Inc.

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Representativity of Xenografts for Clinical Cancer. Tumor and Host Characteristics as Variables of Tumor Take Rate

Cited by 4 publications

References 20 publications

A new experimental metastasis model in athymic nude mice, the human malignant melanoma lox

A new experimental metastasis model in athymic nude mice, the human malignant melanoma lox

Laboratory Models of Lung Cancer

Tumorigenicity of cerebellar primitive neuro-ectodermal tumors in athymic mice correlates with poor prognosis in children

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