The effect of toremifene on the expression of genes in a rat mammary adenocarcinoma.

Toremifene, apart from its partial estrogen antagonism, exerts multiple and varied effects on a variety of genes involved in the control of signalling and apoptosis. After three weeks of exposure of R3230AC hosting rats to therapeutical oral doses of toremifene distinct changes in steroid receptors, P-glycoprotein, p53 and Bc1-2 expression and protein S100 levels occurred, which may contribute to our understanding of the mechanisms of action of this antiestrogen.

Immunohistochemical determination of P-glycoprotein in a rat mammary tumour treated with tamoxifen.

The effect of treatment with the antiestrogen Tamoxifen on the distribution and localization of P-glycoprotein was determined by immunohistochemistry in a rat mammary tumour model, the R3230AC. Both in the untreated and the treated tumours, P-glycoprotein is unevenly expressed with numerous negative tumour cells and located predominantly in the cytoplasmic membranes. Administration of Tamoxifen significantly lowers P-glycoprotein content of the tumour studied.

Antimetastatic effect of amiloride in an animal tumour model.

The diuretic Amiloride competitively inhibits the catalytic activity of the urokinase-type plasminogen activator on plasminogen in vitro. This effect was tested on a rat adenocarcinoma model and its invasive potential in the host lung. While the inhibitory effect on intact cell cultures of the tumour was slight, continuous exposure of tumour-injected animals to the drug completely prevented the formation of lung metastasis.

Single-chain, urokinase-type plasminogen activator in a tumor model linked to metastatic potential.

Single-chain urokinase-like plasminogen activators have been determined by an indirect method (after activation to urokinase by plasmin and chromogenic assay with S 2444) in the cytosol of a rat tumor model. Variants of the R 3230 AC rat mammary adenocarcinoma were studied, including a subline with increased metastatic potential established by lung colony assay. The cellular content of the UK precursor was found to be significantly higher in the metastatic variant. Plasminogen activator-mediated invasion and collagenolysis of cells with the metastatic phenotype may be regulated by the release of the precursor which lacks reactivity with inhibitors, its transient activation and subsequent inhibition of the urokinase formed.

Effects of antibodies to choriogonadotropin in malignant growth. II. Solid transplantable rat tumors.

We have studied the effects of preimmunization with a conjugate of beta-subunit of choriogonadotropin and tetanus toxoid (CG beta-tt) on the growth of the implanted R 3230 AC mammary adenocarcinoma (in Fischer 344 rats) and the implanted 5123 1-1 hepatoma (in Buffalo rats) after 20 days, in order to determine if the in vivo production of antibodies against CG could modify the relationship between host and malignant growth. The results obtained demonstrated that active immunization against CG retarded significantly (P less than 0.01) the growth of the two transplantable tumors. Anti-CG antibodies were also determined and constantly found in the sera of all the preimmunized rats of both strains while no antibodies to CG were found in the control animals.

Antitumor activity of tilorone hydrochloride on a transplantable rat adenocarcinoma.

Tilorone HCL, administered in drinking water, retarded and slowed significantly the growth of the transplantable R3230 AC rat adenocarcinoma in Fischer 344 rats. This effect is dose-related; from the average three dosage levels studied, daily intake of 30 mg/kg rat/day was found to be optimal. However, Stadie slices of tumors from Tilorone-treated animals when transplanted, took, and showed a growth curve similar to tumors from untreated rats. Exposure to Tilorone does not select tumor cell clones of lesser malignancy or different histopathology.

Effect of alpha-difluoromethyl ornithine on the transplantable rat hepatoma 5123, 1-1.

Oral treatment with alpha-difluoromethyl ornithine (2.75 g/kg rat/day) simultaneous with subscapular implantation in Buffalo rats of the 5213, 1-1 hepatoma, retarded significantly the tumor growth rate for 20 days. The regimen also decreased tumor ornithine decarboxylase activity (ODC); however, the tumors growing despite treatment, maintained their malignant characteristics and ODC activity when re-transplanted into normal animals.

Patterns of in vivo lymphoid responses to tumour specific antigens.

A tumour-derived antigen complex injected induced a different cellular immune response in tumour-bearing mice when compared with unprimed controls. A different statistical approach, namely the linear correlation, allowed us to discern significant differences in the response pattern.

Transplantation resistance to mouse ependymoblastoma following immunization with dehistonized syngeneic tumor chromatin.

Female C57BL/J6 mice pretreated with dehistonized ependymoblastoma chromatin rejected 5 x 10(4) or 10(5) s.c.-implanted syngeneic ependymoblastoma cells. Control mice that received Freund's adjuvant containing dehistonized chromatin from normal mouse brain developed palpable tumor nodules in 90% and 35 to 45% of the animals, respectively. Increased binding of spleen lymphocytes from mice pretreated with dehistonized tumor chromatin to Sepharose 4B coupled with components of dehistonized tumor chromatin was observed. This provides initial evidence for the presence of "committed" lymphocytes in mice pretreated with dehistonized chromatin from this mouse ependymoblastoma.