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Biomedical subjects

A E Lee

Publications and source records attributed to A E Lee.

9 recordsLinked to original sources
PubMed1992

Phenotypic responses of mouse mammary tumours and normal mammary epithelium cultured in collagen gels: correlation with tumour type and progression.

Mammary tumours in female BR6/Icrf mice and the corresponding contralateral normal mammary glands were disaggregated with collagenase and the epithelial structures released ('organoids') separated from other cellular components by filtration. The organoids were established in primary culture in a collagen matrix and the outgrowths obtained were studied by light microscopy and time-lapse cinemicroscopy. The pattern of three-dimensional outgrowths produced was found to be specific to the original tissue. Organoids from normal tissue formed a characteristic outgrowth designated Pattern A. Normal tissue from pregnant mice formed an additional characteristic outgrowth (Pattern A') which has not been described previously. Pregnancy-dependent tumours produced a distinctive phenotypic outgrowth designated Pattern D, whereas pregnancy-independent tumours gave a different distinctive Pattern B as well as a unique specific outgrowth designated Pattern C. Outgrowths of Pattern D from a pregnancy-dependent tumour were removed from culture and implanted into a syngeneic female mouse. Tumours arising in the host were found to be pregnancy-independent and showed phenotypic outgrowths in subsequent culture of pregnancy-independent Patterns B and C. The results show that the type of outgrowths in these cultures correlates with the biology of the tissue in vivo and that changes in tumour progression in vivo are accompanied by alterations in phenotypic outgrowths in culture.

Animals↗
PubMed1990

Implied consent.

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Informed Consent↗
PubMed1989

Interferons alpha and gamma differ in their ability to cause tumour stasis and regression in vivo.

We have studied the antitumour activity of human lymphoblastoid interferon-alpha [HuIFN-alpha(N)] and human recombinant interferon-gamma (rHuIFN-gamma) on 12 early passage (passages 2-7) human tumour xenografts derived from primary malignancies. Systemic daily therapy of established (approx. 0.5 cm diameter) subcutaneous xenografts with HuIFN-alpha(N) resulted in significant tumour stasis, and occasionally regression, in nine of 12 breast, bowel, and ovarian cancers studied. A significant decrease in tumour mitotic index was seen in three HuIFN-alpha(N) sensitive breast tumours. In contrast, none of nine of the same tumours responded significantly to rHuIFN-gamma therapy. Direct administration of rHuIFN-gamma into the tumour did not improve its therapeutic efficacy. However, when tumour cells from xenografts were dissociated and grown as colonies in soft agar, both IFNs, used at doses that are found circulating in vivo after therapy, inhibited colony development in three of three lines tested. Combinations of rHuIFN-gamma and HuIFN-alpha(N) had no synergistic benefit in four of four xenografts studied.

Animals↗
PubMed1989

Reinfection of virus free mice with mouse mammary tumour virus.

BR6/Icrf mice carrying a milk-transmitted mammary tumour virus (MMTV) develop tumours after several pregnancies. If the mice are freed from MMTV, no tumours develop. In the experiments described in this paper, MMTV was reintroduced into MMTV-free mice by foster nursing, which was least effective if the pups were exposed to the virus only during the first week of life. Exposure for even a short time after that age led to a tumour incidence similar to that found in normally infected mice. Reinfection was also achieved by injection of MMTV-containing milk into weanling or pregnant mice, and was then transmitted naturally to the next generation.

Aging↗
PubMedDate not supplied

Reduction of metastasis in a murine mammary tumour model by heparin and polyinosinic-polycytidylic acid.

A murine mammary tumour model has been used to test the efficacy of a combination of heparin and the interferon inducer, poly I:C on spontaneous metastasis from a s.c. primary tumour and on experimental metastasis following i.v. injection of tumour cells. This treatment has no effect on the growth of primary tumours, but lung metastases arising from these tumours were reduced. When tumour cells were injected i.v. the number of lung colonies was significantly reduced and survival time extended. Short-term treatment did not prevent the subsequent growth of extravasated, but dormant tumour cells, although mice treated for 8 or 12 weeks survived at least 6 months without any sign of lung colonies. Several mechanisms may contribute to the overall effect of this treatment; a reduction in the mitotic indices of lung colonies (observed in poly I:C treated mice) and also NK cells appeared to be important for the effectiveness of poly I:C since the reduction in experimental metastasis was abrogated by concomitant treatment with anti-asialo GM1 serum.

Animals↗
PubMedDate not supplied

Comparison of metastatic cell lines derived from a murine mammary tumour, and reduction of metastasis by heparin.

A murine mammary carcinoma, which had a high potential for metastasis to the lungs, was established in culture, and from the parent line several clonally derived variants were isolated, showing different characteristics including metastatic potential. C1, a high metastatic clone, and C2, a low one, were selected for further study. When tumour cells were injected s.c. the growth rates of the resulting tumours were higher when they developed from the parent line (P2) or C1 cells, than from C2 cells. The numbers of lung colonies seen following i.v. inoculation of tumour cells also varied, C2 cells yielding the lowest score. In vitro C1 cells were more efficient at aggregating platelets than C2, an effect reduced by the addition of heparin. In vivo heparin reduced the number of tumour cells arrested in the lungs after i.v. injection, and also the number lung colonies which subsequently became established. The number of metastases which developed following s.c. injection of tumour cells was also reduced by heparin.

Animals↗
PubMedDate not supplied

Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus.

The induction of tumours by retroviruses lacking transduced oncogenes can involve the transcriptional or functional activation of cellular proto-oncogenes by an integrated provirus. Thus, the two cellular genes int-1 and int-2, identified as common targets for activation by mouse mammary tumour virus (MMTV), may constitute previously unrecognized oncogenes. In tumours, proviral insertion at these loci leads to expression of messenger RNAs which are undetectable in normal mammary glands. Here we report that in a survey of the two transcriptional activity and structural integrity of the two int loci in 30 BR6 mouse mammary tumours, around 50% of the tumours expressed both of these genes, in ostensibly monoclonal cell populations. Our data suggest that int-1 and int-2 may act cooperatively in the genesis of mammary carcinomas. However, because three tumours (10%) involved neither gene, and because in five cases activation occurred in the apparent absence of an adjacent provirus, it is clear that other loci and mechanisms contribute to tumorigenesis.

Animals↗