Matias Perez

Luteal cytoplasmic estradiol and progesterone receptors in human endometrium: in vitro fertilization and normal cycles

Luteal cytoplasmic estradiol (E2) and progesterone (P) receptor levels were measured from the 22nd to the 25th days of the menstrual cycle in endometrial samples obtained from seven patients in an in vitro fertilization (IVF) program who received no embryo replacement after ovarian stimulation with clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin, and from seven normally menstruating women. Serum levels of E2, P, follicle-stimulating hormone, luteinizing hormone, and prolactin (PRL) were measured in blood samples collected at the time of biopsy. The E2 (P

c-K-ras Overexpression Is Characteristic for Metastases Derived from a Methylcholanthrene-Induced Fibrosarcoma

We investigated the relationship between the activation of the c-myc and c-K-ras proto-oncogenes and the acquisition of metastatic potential in a methylcholanthrene-induced BALB/c fibrosarcoma. The murine fibrosarcoma GR9 was originally induced in BALB/c mice following exposure to the carcinogenic chemical 3-methylcholanthrene. To induce spontaneous metastasis, we used two tumor cell clones (B9 and G2) known to differ in their metastatic potential, local tumor growth, H-2 class I expression and sensitivity to natural killer (NK) cells. The metastatic nodes were obtained from the lung, liver and kidney. The results showed: (1) amplification of the c-myc proto-oncogene in original tumor clones as well as in all metastatic nodes; (2) mRNA overexpression without amplification of the K-ras proto-oncogene in the metastatic cells, regardless of their anatomical location; (3) no c-K-ras point mutations at codons 12 and 61, and (4) in general, a statistically significantly reduced in vitro sensitivity of metastatic tumor cells to NK cells as compared with the tumor clones used to induce them (p < 0.05). These results therefore suggest that overexpressed c-K-ras mRNA is important during tumor progression, perhaps rendering metastatic tumor cells more resistant to lysis by NK cells.

Effect of in vivo activation of natural killer (NK) cells by a tilorone analogue on the survival of mice injected intravenously with different experimental murine tumours.

We studied the effect of a tilorone analogue (RMI 10,874DA) and anti‐asialo GM1 serum on the survival of BALB/c and C57B1/6 mice after i.v. injections of different syngeneic murine tumour cells. Tumour lines used were different clones from chemically (GR9 wild type, GR9.B9, B7.1.B4, B7.1.B5, B7.2.38), and ultraviolet light (GRUV3)‐induced sarcomas; B16 melanoma and LSTRA and YC8 lymphomas. Pretreatment of mice with tilorone inhibited metastatic colonization and increased survival significantly in all cases. In some tumour systems, the effect was attenuated when high numbers of cells were injected. Abrogation of NK cells with anti‐asialo GM1 serum significantly decreased (in all tumours and at different cell doses) survival in comparison with untreated mice injected with tumours, regardless of cell dose used. These results clearly suggest that NK cell activation in vivo by the tilorone analogue we tested prolongs survival and inhibits metastasis formation in mice, even when pretreatment consists of a single dose of the analogue.

In vivo activation of NK cells induces inhibition of lung colonization of H-2 positive and H-2 negative fibrosarcoma tumor clones

The role of different tilorone analogs in the abrogation of the metastatic spread of H-2 positive and H-2 negative tumor clones was studied. Pre-treatment of BALB/c mice with RMI 10,874DA compound completely abolished lung colonization of an H-2 negative (GR9.B9) MCA-induced fibrosarcoma clone in an experimental metastasis assay. This effect was also evident when clones were treated with other tilorone analogs (R11,567DA or R11,513DA). Other H-2 positive and H-2 negative chemically induced fibrosarcoma clones were also tested. The effect was not due to direct toxicity of the tilorone analog on tumor cells, but instead was dependent on NK cells; this was suggested by the finding that treatment of mice with anti-asialo GM1 abrogated the effect of the tilorone analog (RMI 10,874DA compound). Interestingly, the inhibition of lung colonization after intravenous injection was again observed regardless of the H-2 phenotype of the tumor clones, and H-2+ and H-2− clones were similarly inhibited.In vitro assays of NK sensitivity of tumor clones showed that lysis varied depending on the H-2 phenotype of tumor clones, indicating an absence of correlation betweenin vivo andin vitro results.

Luteal Cytoplasmic Estradiol and Progesterone Receptors in Human Endometrium: In Vitro Fertilization and Normal Cycles

Luteal cytoplasmic estradiol (E2) and progesterone (P) receptor levels were measured from the 22nd to the 25th days of the menstrual cycle in endometrial samples obtained from seven patients in an in vitro fertilization (IVF) program who received no embryo replacement after ovarian stimulation with clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin, and from seven normally menstruating women. Serum levels of E2, P, follicle-stimulating hormone, luteinizing hormone, and prolactin (PRL) were measured in blood samples collected at the time of biopsy. The E2 (P less than 0.01) and PRL (P less than 0.001) levels were higher in stimulated than in spontaneous cycles. The level of cytoplasmic P receptor was decreased in endometrium in stimulated cycles, but cytoplasmic E2 receptor remained unchanged. These alterations in the luteal phase of cytoplasmic P receptor in the endometrium could be involved in the low rate of success following the IVF program.

Syngeneic Monoclonal Antibodies Against Chemically Induced Tumors

It has been demonstrated that humoral as well as cellular immune responses take place against chemically induced tumors (Lennox et al. 1981; Ogata et al. 1986). Indeed, syngeneic monoclonal antibodies (McAbs) and antitumor cytotoxic T-lymphocyte responses can be used to define cell surface structures that may be involved in tumor rejection (Simrell and Klein 1979; Fernandez Cruz et al. 1987; Wortzel et al. 1983).