Effect of the antiprogesterone RU-38486 on meningioma implanted into nude mice.

Meningiomas have been shown to have steroid-binding proteins. In vitro, estradiol, progesterone, and the antiestrogen tamoxifen stimulate tumor growth. However, incubation of tumor cells with an antiprogesterone agent results in tumor inhibition. In this investigation, a human meningioma was implanted subcutaneously in athymic nude mice. Two treatment groups were established, one receiving the antiprogesterone agent RU-38486 (10 mg/kg/day in suspension) and the other receiving only vehicle. After 3 months, the tumor growth index (defined as the tumor volume at 3 months divided by the initial tumor volume) was 0.25 +/- 0.46 (mean +/- standard deviation) in the group receiving antiprogesterone and was 1.54 +/- 0.58 in the control group (p = 0.041). Further investigation of the effect of antiprogestational agents on the growth and hormone-binding proteins of other meningiomas will better define the mechanism of their effects.

B16 melanoma in hairless mice: a model for thermographic research.

Little is understood concerning the mechanism of tumor-induced thermographic abnormalities observed in man. An ideal animal model is lacking. In an effort to create such a model we have worked with hairless mice, subcutaneously inoculated with B16 melanoma cells. This report documents the progress of that work and the subsequent development of a totally satisfactory system for the study of such tumors in a hairless animal.

Hormonal manipulation of meningiomas in vitro.

Speculation that meningiomas are subject to endocrine influence is supported by their higher incidence in women, reports of exacerbation of symptoms during pregnancy, and the discovery that these tumors harbor progesterone- and estrogen-binding proteins. To evaluate if these properties could be exploited therapeutically, specimens from three convexity meningiomas were used for estrogen- and progesterone-binding protein assays and establishment of tissue cultures. Each tumor (designated A, B, and C, respectively) was grown in experimental media containing 7.5 X 10(-5) to 10(-12) M 17 beta-estradiol, 2.5 X 10(-4) to 10(-12) M progesterone, 10(-7) to 10(-9) M tamoxifen (an estrogen antagonist), and 10(-6) to 10(-10) M RU486 (a progesterone antagonist). After incubation, cell growth was compared to control preparations by counting the meningioma cells present in each medium. Tumors A, B, and C contained estrogen-binding proteins of 8.45, 13.6, and 26.9 fmol/mg cytosol protein and progesterone-binding proteins of 210, 130, and 126 fmol/mg cytosol protein, respectively. The media containing 17 beta-estradiol and progesterone caused 21% to 36% growth stimulation in Tumors A and B. In Tumor A, the addition of tamoxifen stimulated growth by 35%, while it caused only transient stimulation in Tumor B and had no effect on Tumor C. RU486, the progesterone antagonist, caused inhibition of cell growth in all three tumors, ranging from 18% to 36%. These data suggest that selected meningiomas are subject to hormonal influence in vitro. The inhibition of meningioma growth in vitro by the antiprogesterone, RU486, has not been previously reported, and serves to encourage further development of alternative modes of therapy for recurrent and unresectable meningiomas.

Temperature over tumors in hairless mice.

The question of whether tumors are warmer or colder than surrounding tissue is considered in these experiments which use a highly suitable animal model, the hairless mouse. Temperatures of skin over induced growing subdermal tumors in these mice were monitored by AGA 680 Color Thermovision. The skin over the tumors does not cool over time but on the contrary becomes warmer. This is probably due to an increase in vascularization rather than increased metabolic rate.

Development and characterization of a human ovarian cancer cell line which clones without agar in vitro.

A new human ovarian cancer cell line has been initiated which clones without agar in vitro. The cell line has been characterized by growth of a tumor resembling the primary tumor in a nude mouse, by human lactic dehydrogenase isozyme pattern, by human karyotype, and by lack of contamination by other cell lines. Initial studies have demonstrated the presence of epidermal growth factor receptors in this cell line. The utility of this line for clonogenic studies is demonstrated by dose-response studies with doxorubicin, cisplatinum, and 13-cis-retinoic acid.

Development of a new human breast cancer cell line Ia-270.

A new human breast cancer cell line (Ia-270) has been isolated from a malignant pleural effusion from a woman with metastatic infiltrating ductal carcinoma of the breast. This cell line contains cytoplasmic estrogen (ER) and progesterone (PR) receptors. Following estradiol (E2) administration, PR synthesis is augmented and a higher level of saturation density is reached. In an athymic mouse, the cell line produced a tumor morphologically similar to the primary tumor. The results of isoenzyme and karyotype analyses demonstrate Ia-270 to be of human origin and free of HeLa cell contamination. The cell line has been maintained in continuous culture since April 1982 and may provide a useful in vitro system for studying the biology of human breast cancer.

Establishment and characterization of four new human non-small cell lung cancer cell lines.

Four new human non-small cell lung cancer cell lines have been established in vitro. These cell lines have been characterized by (a) growth of a tumor in nude mice with histopathology similar to that of the primary, (b) isoenzyme patterns phenotypically human and distinct from each other, (c) distinguishing karyotypic findings, (d) growth rate determinations, and (e) presence of epidermal growth factor receptors. Each of the cell lines will form colonies when directly seeded into a flask without soft agar. The development and availability of the four cell lines may facilitate in vitro studies of the biology of this common cancer. Their clonogenic potential may be of value in the study of sensitivity to antineoplastic agents. Their low passage level may mean that their antigens still resemble those of the primary tumor.

A search for malignant cells in peritoneal fluid from patients with colorectal adenocarcinoma.

Cytologic examination of peritoneal fluid aids in staging ovarian malignancies and in selecting gastric adenocarcinoma patients for intraoperative adjuvant chemotherapy. Tissue culture of peritoneal fluid could be potentially valuable in confirming cell viability and establishing sensitivity to a variety of anti-cancer agents. It also could be a more sensitive diagnostic tool than cytologic examination alone. We obtained peritoneal fluid specimens from 29 patients at the time of celiotomy: 22 had colorectal adenocarcinoma and seven were controls. Cytologic examination on a portion of each specimen produced only one positive result for malignant cells. Tissue culture of the remainder of the specimens grew cells from all but one of the patients with colon cancer; however, their morphology was similar to the fibroblasts and mesothelial cells that grew from the seven controls. We speculate that these negative results stem from the absence or reduced number of tumor cells in the specimens. Without additional refinement of our methods of specimen collection and processing, cytologic examination and tissue culture of peritoneal fluid from patients with colorectal cancer are of minimal value. Nevertheless, we believe that, with the necessary refinements, they may eventually become invaluable in the management of these patients.