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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new therapy for the progesterone receptor positive mammary carcinoma may be the treatment with progesterone antagonists. This new class of antihormones causes a strong inhibition of tumor growth comparable to the potency of ovariectomy in a panel of experimental mammary carcinomas. The mechanisms of the strong tumor-inhibiting action of progesterone antagonists on experimental mammary carcinomas mainly depends on a progesterone receptor mediated process leading to induction of terminal differentiation and a blockade of the cell cycle. To further characterize the antitumor mechanism of progesterone antagonists we analyzed the effects of Onapristone and ZK 112.993 on DMBA- and MNU-mammary tumors of the rat and MXT-tumors of the mouse after different therapy intervals. These hormone-dependent mammary tumors normally display intraductal growth in papillary, cribiform or solid formation, whereas after treatment periods of 2-6 weeks with progesterone antagonists they displayed dysplastic ductal and acinous formations, usually filled with secretory material. Whereas tumor size, mitotic index, and the grade of tumor malignancy decreased distinctly, the volume fraction of glandular structures in the tumors as well as the appearance of apoptosis increased 3-fold compared to the controls. In addition, the mammary glands of progesterone antagonist treated animals showed the morphological features of differentiation with the appearance of secretory activity. Interestingly, the staining pattern of some of the lectins used, especially UEA 1 binding pattern, fits to the concept of differentiation since recent studies revealed a higher degree of fucosylation only in benign lesions of human breast cancers. Therefore, these data underline the concept of a differentiation potential of progesterone antagonists on progesterone receptor positive mammary carcinomas.
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PMID:The antitumor potency of progesterone antagonists is due to their differentiation potential. 152 61

The histogenesis of mouse lung adenomas is currently being investigated in several laboratories. Based upon studies of a limited number of carcinogens in different mouse strains, some investigators suggest that all lung adenomas in mice are derived from alveolar type II cells, whereas others suggest a Clara cell origin for a majority of the tumors. This report differs from previous investigations in that 12 different carcinogens were evaluated for the types of lung tumor growth patterns they induced in a single mouse strain (strain A mice). The carcinogens aflatoxin B1 (AFB1), benzo(a)pyrene (BP), 1,2-dimethylhydrazine (DMH), 3-methylcholanthrene (MCA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosomethylurea (MNU) induced tumors with a predominantly solid/alveolar growth pattern, whereas N-nitrosodiethylamine (NDEA) induced predominantly papillary tumors. Most of the other carcinogens induced a higher proportion of lung tumors with the solid/alveolar growth pattern than with the papillary growth pattern; however, ratios between the 2 growth patterns varied. If, as suggested by others, solid tumors are derived from alveolar type II cells and papillary tumors from Clara cells, then carcinogens may differ with respect to their ability to transform one cell type or the other.
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PMID:Strain A/J mouse lung adenoma growth patterns vary when induced by different carcinogens. 177 69

The biological role of transforming growth factor-alpha (TGF-alpha) in basal and hormone-stimulated proliferation of primary human and rat mammary tumor cells was studied using antibodies against TGF-alpha and its receptor. A monoclonal antibody, MAb-425 against human EGF receptor was added to in vitro soft agar, clonogenic cultures of human breast carcinoma cells under basal and estradiol(E2)-stimulated conditions. The antibody had an antagonist effect on colony growth in 4 of 10 tumors and an agonist effect in 4 (72 and 153% of control). E2-stimulated colony growth in 5 tumors (167% of control) and the antibody blocked E2-stimulation in 3 of the 5. Inhibition of E2-stimulated growth in 3 and basal growth in 4 other tumors by the EGF receptor antibody suggest that endogenously secreted TGF-alpha has a role as an autocrine/paracrine growth factor in constitutive and E2-stimulated tumor cell proliferation in a majority of human tumors. A polyclonal antibody against TGF-alpha was used to study the role of TGF-alpha in E2-, prolactin(Prl)- and progesterone(Prog)-stimulated proliferation of NMU(nitrosomethylurea)-induced rat mammary tumor cells under similar culture conditions. TGF-alpha, E2, Prl and Prog stimulated colony growth equally to 176, 187, 168 and 181% of control. The antibody produced significant and similar inhibition of TGF-alpha and E2-stimulated growth (95 and 83%). In contrast, inhibition of Prl- and Prog-stimulated growth by the antibody was only 24 and 37%. The TGF-alpha ligand antibody did not have an agonist or antagonist effect when added alone. Thus, TGF-alpha seems to be a major stimulatory growth factor mediating E2-induced tumor cell proliferation in rat mammary tumors. It is less important in Prl- and Prog-induced tumor growth and not essential for basal growth in these tumors. We conclude that TGF-alpha is a biologically important autocrine/paracrine growth factor in primary human breast cancer cell proliferation and in E2-induced rat mammary tumor growth.
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PMID:Role of transforming growth factor-alpha (TGF-alpha) in basal and hormone-stimulated growth by estradiol, prolactin and progesterone in human and rat mammary tumor cells: studies using TGF-alpha and EGF receptor antibodies. 206 83

The progesterone antagonists Onapristone (ZK 98.299) and Mifepristone (RU 486) proved to be strong inhibitors of various rodent mammary tumors. Therefore, a further potent antiprogestin, ZK 112.993, and 11 beta-(4-acetyl-phenyl)-analog of Mifepristone, with a high progesterone receptor affinity was tested in experimental rodent and human breast cancer models. In the hormone-dependent MXT(+) mammary tumor of the mouse, treatment of tumors immediately after implantation with 5 mg/kg for 6 weeks led to an inhibition of growth by 95%, being significantly superior to that caused by tamoxifen, diethylstilbestrol and Onapristone. Treatment of established MXT(+) tumors by ZK 112.993 at doses of 0.5, 1.0 and 2.0 mg/kg led to a strong inhibition that equalled that of ovariectomy and surpassed that of Onapristone in the lower doses. In the human, receptor positive mammary carcinoma T61 implanted in male, castrated nude mice, ZK 112.993 (10 mg/kg) significantly retarded tumor growth. Its effect was again superior to Onapristone though weaker than that of tamoxifen. The NMU-induced mammary carcinoma of the rat (established tumors) was inhibited by ZK 112.993 (5 and 10 mg/kg) in a dose-dependent manner slightly superior to Onapristone but weaker than after ovariectomy. Due to its strong antitumor activity and because of the innovative mechanism of action of antiprogesterones in tumor treatment, ZK 112.993 could be of great value for the treatment of breast cancer.
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PMID:Tumor-inhibiting potential of ZK 112.993, a new progesterone antagonist, in hormone-sensitive, experimental rodent and human mammary tumors. 236 83

Magnetic resonance spectroscopy (MRS) uniquely provides noninvasive access to chemistry in vivo. 31P MRS can be used to monitor the high energy phosphates--phosphocreatine (PCr) and ATP, and their breakdown product--Pi, in situ in animals or patients. In several experimental tumor lines in animals it has been shown that the PCr/ATP and other related ratios steadily decline as the tumor increases in size, and that this effect is reversed when the tumor is treated with a therapeutic modality to which it responds. Acid extracts of freeze-clamped tumors at different stages of growth have confirmed these MRS observations and give additional information on related compounds such as creatine and ADP. Results show that, in the tumors studied, at least 80% of the ADP and about 40% of the Pi are bound and not in solution in the cytosol. Histological sections have indicated that the MRS response to endocrine therapy, in an NMU-induced estrogen-sensitive mammary tumor model, precedes any histological changes or any measurable regression. If these findings can be translated into a clinical setting, this may mean that MRS can be used in the clinic as an early predictor of tumor responsiveness to treatment. In untreated tumor growth, the cause of the decrease in PCr and ATP relative to Pi is probably due to the tumors outgrowing their blood supply and the cells becoming increasingly hypoxic. The PCr is lost more rapidly than ATP, indicating that the equilibrium in the creatine kinase reaction is maintained in these tumors. When the tumor is treated, cellular growth ceases and the requirement for oxygen and other nutrients is greatly reduced. This would allow the cellular energy reserves to be repleted and thus lead to the paradoxical improvement in the high energy phosphate status of a tumor that is about to regress.
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PMID:Monitoring tumor growth and regression by 31P magnetic resonance spectroscopy. 240 32

The effectiveness to reduce tumor growth by 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)- 1-nitrosourea (SLCNU) and N,N,N,'N'- bis(1,2-ethanediyl)-N"-(1-oxyl-2,2,6,6-tetramethyl- 2-piperidinylaminocarbonyl)-phosphoric triamide (SLDU) was studied in osteosarcoma and MNU-induced mammary carcinoma in the SD-rat. Both compounds elicited neither an inhibitory effect on these tumors nor an increase in the mean/median life span as compared to the control group.
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PMID:Evaluation of spin labeled TEPA and CCNU analogs against osteosarcoma and MNU-induced mammary carcinoma of the SD-rat. 247 94

The antitumor activities of the antiprogesterones ZK 98.299 and RU 38.486 (RU 486) were tested in the hormone-dependent MXT(+) mammary tumor model of the mouse and the DMBA- and MNU-induced mammary tumor models of the rat. In the MXT(+)-tumor model, treatment with the two antiprogesterones (1-10 mg/kg daily) starting on day 1 after tumor implantation led to an almost complete inhibition of tumor growth identical to that accomplished with tamoxifen. Treatment of established MXT(+) tumors with ZK 98.299 (1, 10 and 50 mg/mg) resulted in a strong, dose-dependent inhibition of tumor growth. At the 10 and 50 mg doses, the effect of ZK 98.299 was superior to that of tamoxifen (4 mg/kg) and equal to that of ovariectomy and of RU 486, whereas megestrol acetate and medroxyprogesterone acetate had no significant effect. In contrast to the massive induction of cell degeneration and cytolysis in the MXT mammary tumors resulting from ovariectomy, the treatment with the two progesterone antagonists seems rather to trigger differentiation of the mitotically active polygonal tumor cells towards glandular structures and acini with secretory activity as well as towards the development of spindle-shaped necrobiotic cell populations. The weights of the ovaries were increased after therapy with ZK 98.299 and RU 486. Due to this inhibition of the negative feedback and an 'unopposed estrogen effect', uterine weight was also significantly increased. In the DMBA-induced mammary carcinoma, ZK 98.299 (10 mg/kg) caused strong tumor-inhibiting activity almost comparable to that of ovariectomy. The inhibition was very uniform and in this regard superior to RU 486. The MNU-induced mammary carcinoma of the rat was significantly inhibited by ZK 98.299, whereas RU 486 showed only a weak effect. In the light of these results antiprogesterones can be considered to be a very promising new class of mammary tumor inhibitors.
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PMID:Antitumor activity of the progesterone antagonists ZK 98.299 and RU 38.486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA- and the MNU-induced mammary tumor models of the rat. 249 18

Mammary tumor burden, in rats fed either normal or high fat diets related positively to the level of protein in the diet. This relationship existed with either a direct (NMU) or indirect carcinogen (DMBA). Significant differences in body growth, sexual maturation, morphologic structures in the mammary duct, and hormone activities during the estrous cycle probably contributed to lower tumor burden in the low protein-normal fat (LP-NF) group. Animals fed a high protein-normal fat (HP-NF) diet throughout their entire life have, with the exception of early sexual maturation, no distinctive characteristics compared to the control group. Inspite of these physical and physiologic similarities, increased dietary protein enhanced the effect of administered carcinogens. Animals fed a high protein-high fat (HP-HF) diet were compared to rats fed a normal protein-high fat (NP-HF) diet. Increased dietary protein further enhanced the effect of the high fat diet resulting in an increased carcinogen-induced tumor burden. These studies indicate that the design of the animal model, i.e. age of initiation of a test diet, appears to have a significant bearing on mammary tumor development. The biologic mechanisms which respond to diet modifications and which may influence breast tumor growth have not been thoroughly elaborated and require additional study.
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PMID:Fat-protein interaction, defined 2-generation studies. 309 54

NMU-1 is a lung adenocarcinoma induced by N-nitroso-N-methyl-urea in a BALB/c Lac Dp mouse and maintained in vivo by sc passages of tumor fragments. No spontaneous regressions have been observed. After sc implantation, NMU-1 metastasizes to the lung as shown by a bioassay. Seven established antitumoral drugs were used to evaluate the chemosensitivity of this neoplasm. Mitomycin, cyclophosphamide, and cisplatin statistically affected tumor growth, as evaluated by three end points (ie, tumor weight, increase in lifespan, and tumor growth delay). 5-FU, doxorubicin, and vincristine showed significant activity on two end points. Carmustine did not affect any end points.
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PMID:NMU-1, a new transplantable mouse lung tumor: biological and chemosensitivity properties in vivo. 397 93

The action of a number of active anticancer agents belonging to the alkylnitrosoureas (MNU, DMNU, ADEKO, BCNU, CCMU, MeCCNU), as well as the effectiveness of a combined use of DMMU and ADEKO with cyclophosphamide was assessed on experimental tumors transplanted by inocula of different size. A mathematical model of the connection between survival of tumor-bearing animals with the kinetics of tumor growth was proposed to analyze the treatment effect. The contribution of lethal and cytostatic factors to the resultant effect of the drugs was evaluated. A combination of DMNU and cyclophosphamide was found to possess an additive effect. The synergism of the therapeutic action shown in a combined application of ADEKO and cyclophosphamide was stipulated by the potentiation of the lethal effect of these drugs on tumor cells.
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PMID:Assessment of lethal and cytostatic effects of alkylnitrosoureas on the cells of experimental tumors. 650 11


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