Comparison between macroscopic and microscopic evaluation of tumour responsiveness using the subrenal capsule assay

Edelstein, M; Fiebig, Heinz H.; Smink, T.; Putten, L.M. van; Schuchhardt, C.

doi:10.1016/0277-5379(83)90070-6

Cited by 49 publications

(15 citation statements)

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“…Our results differ from those of Edelstein et al (1983) andSeltzer et al (1983) who reported that subrenal human grafts consisted mainly of oedema, inflammatory cells, granulation tissue and necrotic tissue. Part of the discrepancy may be due to the fact that we have used serially transplanted and fairly rapidly growing tumours whereas these authors largely used surgical specimens directly from patients.…”

Section: Discussioncontrasting

confidence: 99%

“…(Figure 8, left panel), indicated that they were inflammatory mouse cells in agreement with previous findings (Edelstein et al, 1983;Aamdal et al, 1984b, c). The mouse origin of these cells follows from the fact that they were not stained by peroxidase in an immunohistochemical method specific for human cells (not shown).…”

Section: Growthsupporting

confidence: 92%

“…The assumption that the cell-mediated responses to a heterograft does not become evident until after the 6-day observation period (Bogden et al, 1979) has not been confirmed (Edelstein et al, 1983;Aamdal et al, 1984b). The present results show that an immune response may appear already after a few days.…”

Section: Discussioncontrasting

confidence: 53%

“…Part of the discrepancy may be due to the fact that we have used serially transplanted and fairly rapidly growing tumours whereas these authors largely used surgical specimens directly from patients. However, this can hardly account for the whole difference as Edelstein et al (1983) studied xenografted tissue as well. Obviously, it is essential that only viable tissue is grafted.…”

Section: Discussionmentioning

confidence: 95%

“…In fact, it has been reported (Seltzer et al, 1983) that the observed increase in implant size resulted from inflammation and oedema rather than from tumour growth, and Edelstein et al (1983) found that most or part of the subrenal grafts on Day 6 was replaced by granulation tissue due to immune-mediated inflammation. In their study no mitoses were observed and the residual tumour cells showed signs of degeneration and necrosis.…”

mentioning

confidence: 93%

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Characteristics of human tumour xenografts transplanted under the renal capsule of immunocompetent mice

Aamdal¹,

Fodstad²,

Nesland³

et al. 1985

Br J Cancer

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Human tumour lines established in athymic nude mice were grafted under the renal capsule of immunocompetent mice. Grafts from 27 human tumour lines comprising 9 malignant melanomas, 10 sarcomas, 2 colon carcinomas, 4 lung carcinomas and 2 mammary carcinomas, grew well under the renal capsule of the immunocompetent mice and retained morphological and functional characteristics of the parent tumours, as judged by light and electron microscopy and immunohistochemical examinations. Numerous mitoses were detected. Granulation tissue and necrosis were not predominant features. After Day 4, the grafts became infiltrated from the periphery by mouse inflammatory cells. The infiltration could be prevented by pretreatment of the animals with cyclophosphamide. Anti-human antibodies were detected after Day 3. Single cell suspensions from the subrenal grafts were able to form colonies in soft agar. and upon reimplantation in nude mice, subcutaneous tumours were formed showing that the grafted tumour tissue had also retained its malignant character. Altogether the results support the view that human tumour xenografts grow well under the renal capsule of immunocompetent mice and that the grafts retain important characteristics of the original tumour. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8

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Section: Discussioncontrasting

confidence: 99%

Section: Growthsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 93%

See 3 more Smart Citations

Characteristics of human tumour xenografts transplanted under the renal capsule of immunocompetent mice

Aamdal¹,

Fodstad²,

Nesland³

et al. 1985

Br J Cancer

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5-fluorouracil and uft-sensitive gastric carcinoma has a high level of thymidylate synthase

Maehara

Kusumoto

et al. 1990

Cancer

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The authors examined the relationship between the level of thymidylate synthase (TS) and the sensitivity to 5-fluorouracil (5-FU) and UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil in a molar ratio of 1:4. For the studies we used the subrenal capsule (SRC) assay and 15 human gastric cancer tissues. The TS levels were assayed by the ligand-binding technique, using [6-3H]FdUMP. The relative variation of tumor size (delta TuS/TuS0) was calculated to be as follows: delta TuS/TuS0 = [(TuS6 - TuS0)/TuS0] x 100 (%), where TuS6 was the tumor size on day 6 and TuS0 on day 0. The chemosensitivity was considered to be positive when delta TuS/TuS0 in the treated group decreased to below -10%. Decrease in tumor size was marked in case of exposure to UFT (-19.8 +/- 13.0%) (mean +/- standard deviation), compared with that to 5-FU (-9.0 +/- 7.2%), with a statistically significant difference (P less than 0.001). The TS level varied from 1.7 to 30.8 pmol/g gastric cancer tissue and the mean was 7.1 +/- 7.2 pmol/g tissue. A correlation was noted between the TS level and decrease in size of the tumor exposed to 5-FU (r = -0.671) or UFT (r = -0.758): gastric cancer tissue with higher level of TS is more sensitive to 5-FU and UFT than is that with a lower TS level. These findings show that the sensitivity to 5-FU and UFT of gastric cancer tissue is related to the TS level and that UFT shows promise for the treatment of patients with gastric cancer.

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Human tumor xenografts transplanted under the renal capsule of conventional mice. Growth rates and host immune response

Aamdal¹,

Fodstad²,

Pihl³

1984

Intl Journal of Cancer

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The growth of 29 different human tumor lines under the renal capsule of immunocompetent mice was investigated. The tumors, previously established in athymic mice, included malignant melanomas, colon carcinomas, soft-tissue sarcomas, lung cancers and a mammary carcinoma. The growth rates of 17 tumors, measured repeatedly over a period of several years, were highly reproducible. The different grafts exhibited distinctly different and individual growth rates for up to 6 days. In animals pretreated with an immunosuppressive dose of cyclophosphamide, the growth rate was the same as in non-pretreated animals, but the growth continued for several more days. In the case of 9 different grafts, the subrenal growth rates were compared with those observed when the same tumors were growing subcutaneously in athymic, nude mice. The relative growth rates of the different tumors were practically the same in the two systems. The results indicate that the growth conditions under the renal capsule permit the grafts to express their inherent growth potentials and that the subrenal grafts do not represent a selected sub-population of the tumor cells. The extent of infiltration of the grafts by mouse inflammatory cells was measured by flow cytometry on single-cell suspension as well as by quantitative analysis of serial histological sections. In most cases the mouse cells occupied 15-25% of the total graft volume on day 6. The results indicate that the effect of mouse cell infiltration on the growth of established tumor lines is slight and that it is unnecessary to use athymic mice as host animals when testing new investigational drugs by the SRC assay. The use of established tumor lines in the SRC assay in immunocompetent mice may be useful also in the study of factors influencing the anti-cancer activity of current drugs.

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Comparison between macroscopic and microscopic evaluation of tumour responsiveness using the subrenal capsule assay

Cited by 49 publications

References 1 publication

Characteristics of human tumour xenografts transplanted under the renal capsule of immunocompetent mice

Characteristics of human tumour xenografts transplanted under the renal capsule of immunocompetent mice

5-fluorouracil and uft-sensitive gastric carcinoma has a high level of thymidylate synthase

Human tumor xenografts transplanted under the renal capsule of conventional mice. Growth rates and host immune response

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