Tumorigenicity of embryonal carcinoma as an assay to study control of malignancy by the murine blastocyst.

Pierce, G. Barry; Lewis, S H; Miller, Gary J.; Moritz, Elisabeth A.; Miller, Paul H.

doi:10.1073/pnas.76.12.6649

Cited by 51 publications

(30 citation statements)

References 16 publications

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“…The embryo was destroyed in 6-9 days by the ensuing homnograft rejection (a technique used successfully in the assay for blastocyst control of tumor formation of embryonal carcinoma) (20). The cancer cells, isologous with the host, survived and formed tumors unless their tumor-forming ability was adversely affected by the embryonic tissues.…”

Section: Methodsmentioning

confidence: 99%

“…The techniques used for injection of embryos with cells were similar to those described previously (20,21). Embryos were oriented on a holding pipette by gentle suction and five neuroblastoma cells were placed in the second somite on the *To whom reprint requests should be addressed.…”

Section: Methodsmentioning

confidence: 99%

“…In an attempt to understand the mechanism of this regulation, an assay, based on the ability of the blastocyst to regulate tumor formation of embryonal carcinoma cells, was developed (20). In this assay, the incidence of tumors obtained when single embryonal carcinoma cells were injected into suitable animals was compared with that when the cancer cells were incorporated into blastocysts that were then placed in the same site in the animal.…”

mentioning

confidence: 99%

“…Suspensions of tumor cells were obtained using standard trypsinization techniques and after testing for viability by trypan blue exclusion were placed with an appropriate number of embryos in a drop of medium under mineral oil. All tissue cultures were fed Ham's F-12 medium/10% fetal calf serum containing antibiotics and were incubated at 37°C.The techniques used for injection of embryos with cells were similar to those described previously (20,21). Embryos were oriented on a holding pipette by gentle suction and five neuroblastoma cells were placed in the second somite on the *To whom reprint requests should be addressed.…”

mentioning

confidence: 99%

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The neurula stage mouse embryo in control of neuroblastoma.

Podestà¹,

Mullins²,

Pierce³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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The purpose of this study was to determine whether the neurula stage mouse embryo can regulate tumor formation of C-1300-3 neuroblastoma cells. Five neuroblastoma cells were injected into the second somite of neurula stage embryos, and their ability to form tumors was tested, 24 hr later, by transplanting the portion of the embryo containing the cancer cells into the testes of adult mice. Only one-third the number of tumors was obtained in comparison with controls in which (i) five neuroblastoma cells were injected into blocks of liver tissue that were then transplanted into the testes of adult animals or (ii) five C-1300-3 neuroblastoma cells were injected directly into the testes. When five C-1300-3 cells were injected into somites, which had been dissected from embryos, and the injected somites were placed in animals, significantly fewer tumors were obtained in relationship with controls. Although it is not known whether the neuroblastoma cells are induced to differentiate or are killed by the embryonic tissue, the effect appeared to be specific because the tumor-forming ability of L1210 leukemia, B-16 melanoma, embryonal carcinoma 247, and a parietal yolk sac carcinoma was unaffected by somites.Cancer cells can differentiate into benign if hot normal cells: observations were made first with teratocarcinomas (1-3), and subsequently have been made with neuroblastoma (4, 5), leukemias (6, 7), squamous cell carcinomas (8), and adenocarcinomas of the breast and colon (9). Differentiation has been induced in tumors by irradiation (10), chemicals (11), analogues of vitamins (12), and growth factors that control physiologic responses of normal hematopoietic and leukemic cells (13). Clearly, direction of the naturally occurring differentiation of neoplasms could result in a noncytotoxic treatment for cancer (14).Important in this regard is the observation that the mouse blastocyst can regulate embryonal carcinoma cells to the point that they and their offspring take part in normal embryonic development leading to the production of chimeric mice (15)(16)(17)(18)(19). In an attempt to understand the mechanism of this regulation, an assay, based on the ability of the blastocyst to regulate tumor formation of embryonal carcinoma cells, was developed (20). In this assay, the incidence of tumors obtained when single embryonal carcinoma cells were injected into suitable animals was compared with that when the cancer cells were incorporated into blastocysts that were then placed in the same site in the animal. Two of three embryonal carcinomas tested produced tumors in significantly fewer numbers than in control situations, and the reaction had a degree of specificity because the tumor-forming ability of B-16 melanoma cells, sarcoma 180 cells, and L1210 leukemias was not affected by the blastocyst (21). A small but significant degree of abrogation of tumor formation was always observed when C-1300-3 neuroblastoma cells were tested in the assay. This was an unexpected observation because C-1300-3 neuroblastoma cells, ...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The neurula stage mouse embryo in control of neuroblastoma.

Podestà¹,

Mullins²,

Pierce³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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“…However, the results are less decisive when several cells are injected together or when B16 melanoma cells are used [24].…”

Section: Regulatory Factors In Embryonic Cellsmentioning

confidence: 99%

Differentiation Therapy by Extracts of Embryo Cells: A Possibility for Cancer Treatment

Berger¹,

Frayssinet²,

Berger³

et al. 2017

Enliven Genet Mol Cell Biol

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Various chemical and biochemical differentiation compounds have been shown to revert to normal state several kinds of cancer cells. As embryonic and cancer cells present similarities of behavior and phenotype and as regulatory factors in young embryos have been found, a treatment of cancer cells by embryo cell extracts could be possible. These factors were prepared from rat and mouse embryonic cell nuclei and partially purified by high performance liquid chromatography. They inhibited up to 90% DNA synthesis of LFCl2A, an established cell line from a hepatocarcinoma and of Raji, a B cell line at the stage blast 1 from a Burkitt lymphoma. They prolonged the survival time of rats injected with LFCl2A and increased the percentage of survivors at one month. In the same way, the inhibitory and apoptotic effects of Zebra fish proteins on human colon cancer cells and hepatocellular carcinoma have been reported by Italian researchers. As these factors were not cytotoxic and were active at low concentration, they could be used repeatedly on the remaining cancer cells, after surgery, radiotherapy or chemotherapy.

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Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules

Miller

1981

Cancer

697

275

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Studies on a variety of chemical carcinogens have demonstrated that their ultimate reactive and carcinogenic forms are strong electrophiles. Some carcinogens, such as alkylating agents, are in their ultimate forms as administered, but most require metabolism to these active derivatives. The ultimate carcinogens react, usually non-enzymatically, with nucleophilic constituents in vivo. Of particular interest in regard to their possible importance in carcinogenesis have been the covalent interactions of these electrophilic reactants with cellular informational macromolecules, the DNAs, RNAs, and proteins. Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens. The nature of the carcinogen metabolite(s) involved in the promotion phase has not been determined, but there appears to be no requirement that they be electrophilic. The development of the concept of ultimate chemical carcinogens as strong electrophilic reactants is reviewed, especially with respect to the studies carried in the authors' laboratory.

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Tumorigenicity of embryonal carcinoma as an assay to study control of malignancy by the murine blastocyst.

Cited by 51 publications

References 16 publications

The neurula stage mouse embryo in control of neuroblastoma.

The neurula stage mouse embryo in control of neuroblastoma.

Differentiation Therapy by Extracts of Embryo Cells: A Possibility for Cancer Treatment

Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules

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