ABSTRACT
In prospective clinical trials single octreotide therapy or combined therapy with tamoxifen has improved the quality of life and survival time in patients with pancreatic cancer. In this study we analyzed the influence of octreotide and tamoxifen on tumor growth and liver metastases in chemically induced pancreatic adenocarcinoma in Syrian hamsters. Octreotide alone and the combined therapy (octreotide/tamoxifen) decreased the incidence of macroscopic pancreatic carcinomas as well as the number and size of liver metastases. The combined therapy showed no superior effect to octreotide alone. Furthermore, there was no difference between the tamoxifen and the control group.
Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Liver Neoplasms/secondary , Octreotide/pharmacology , Pancreatic Neoplasms/pathology , Tamoxifen/pharmacology , Animals , Carcinogens , Cricetinae , Incidence , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Male , Mesocricetus , Nitrosamines , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/metabolism , Receptors, Estrogen/metabolism , Receptors, Somatostatin/metabolismABSTRACT
Attempts were made to correlate growth effects induced by oestradiol and tamoxifen with the hormonal regulation of c-erbB-2 protein in experiments in vivo. We report here the responsiveness of four xenotransplanted oestrogen-receptor(ER)-positive and four ER-negative human mammary carcinomas to oestradiol and tamoxifen. Oestradiol in a dose of 0.5 mg/kg significantly increased the growth of the ER-positive mammary carcinomas 3366, MCF-7, 4134 and 4049, but not the ER-negative tumours 4000, 4296 and MT-3. However, within the group of the ER-negative breast carcinomas the tumour 4151 ES deviates from this growth behaviour, as we could prove an estrogen induced growth. The stimulation of tumour growth by oestradiol was always accompanied by a down-regulation of c-erbB-2 protein both in the ER-positive mammary carcinomas and in the ER-negative mammary carcinoma 4151 ES. Tamoxifen significantly inhibited the growth of the ER/PR-positive mammary carcinomas 3366 and MCF-7 but not the ER-positive/PR-negative mammary carcinomas 4049 and 4134. In the group of ER-negative mammary carcinomas only the growth of the oestrogen-responsive tumour 4151 ES was significantly inhibited by tamoxifen. The inhibition of tumour growth by tamoxifen was correlated with a reversion of the oestradiol-induced down-regulation of c-erbB-2, also in the ER-negative/oestradiol-responsive mammary carcinoma 4151 ES. From our results we hypothesize that the oestrogen-dependent growth of ER-negative breast carcinoma 4151 ES could also be correlated with the oestradiol-regulated expression of c-erbB-2 protein.
Subject(s)
Estradiol/pharmacology , Mammary Neoplasms, Experimental/metabolism , Mammary Neoplasms, Experimental/pathology , Receptor, ErbB-2/biosynthesis , Receptors, Estradiol/metabolism , Animals , Base Sequence , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , DNA Primers/chemistry , Estrogen Antagonists/pharmacology , Female , Humans , Mammary Neoplasms, Experimental/drug therapy , Mice , Mice, Nude , Molecular Sequence Data , Neoplasm Transplantation , Polymerase Chain Reaction , RNA, Messenger/biosynthesis , Receptors, Progesterone/metabolism , Tamoxifen/pharmacology , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
Two new human mammary carcinoma lines originating from surgical material were established in nude mice. According to the adopted criteria, the tumor 4049 has been classified as estradiol receptor positive and mammary carcinoma 4296 as estradiol receptor negative. Both tumors proved to be c-erbB-2 protein positive and EGF-receptor negative. In contrast to carcinoma 4296, the in vitro growth and the take rate of mammary carcinoma 4049 in nude mice seems to be dependent on stromal components. Pretreatment of mice with estradiol/peanut oil before tumor engraftment was an essential precondition for the growth of the primary tumor in nude mice. After successful establishment the tumor growth was significantly stimulated by estradiol. The growth rate of mammary carcinoma 4296 was independent of any supplementation of estradiol. The two breast tumors were characterized with regard to their growth behaviour, histology, and sensitivity to cytostatics and antihormones. They are considered suitable tumor models for the testing of antineoplastic substances and for biological experiments.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Squamous Cell/pathology , Connective Tissue/physiology , Estradiol , Neoplasm Proteins/analysis , Receptors, Estradiol/analysis , Tumor Cells, Cultured , Animals , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Cell Division , ErbB Receptors/analysis , Estradiol/administration & dosage , Estradiol/pharmacology , Female , Gene Expression Regulation, Neoplastic/drug effects , Graft Survival/drug effects , Humans , Karyotyping , Male , Mice , Mice, Nude , Neoplasm Transplantation , Neoplasms, Hormone-Dependent/drug therapy , Neoplasms, Hormone-Dependent/metabolism , Neoplasms, Hormone-Dependent/pathology , Peanut Oil , Plant Oils/pharmacology , Postmenopause , Premenopause , Receptor, ErbB-2/analysis , Receptor, ErbB-2/biosynthesis , Receptor, ErbB-2/genetics , Receptors, Progesterone/analysis , Receptors, Progesterone/biosynthesis , Receptors, Progesterone/genetics , Tamoxifen/pharmacology , Transplantation, HeterologousABSTRACT
Two human mammary carcinomas of postmenopausal women were successfully transplanted into nude mice. Both tumours were classified as epidermal-growth-factor-, oestradiol- and progesterone-receptor-negative and c-erbB2-protein-positive. Histological studies of the primary tumours (4000 and 4151) revealed ductal invasive mammary carcinomas. In the first passages the precondition for the growth of breast carcinoma 4000 were pretreatments of the nude mice with oestradiol and peanut oil before transplantation. The mammary carcinomas 4000 and 4151 described here are suitable for in vivo testing of antineoplastic substances and for biological studies.
