Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug toxicity testing is required by the U.S. Food and Drug Administration in bitches of beagle dogs for 7 years and in female rhesus monkeys for 10 years at 25-50 times the human dosage. Progesterone, medroxyprogesterone acetate, megesterol acetate, chlormadinone acetate, chloroethynl norethisterone and chloroethynyl norgestrel are some compounds which have induced tumors in beagle dogs. However, the endocrinology of the beagles is unlike that of a woman and binding affinity of synthetic progestogens to breast cytoplasmic progesterone receptors of the beagle and women have striking differences. Some progestogen compounds which do not produce neoplasia in dogs because of too low a dose are most potent in women. Both the WHO and the Committee on Safety of Medicines concluded that progestogen-induced breast tumors in beagles are unhelpful in predicting possible breast cancer in women who use oral contraceptives.
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PMID:Hounding the pill. 31 66

Retinoic acid (RA), a vitamin A derivative with anti-tumor activity, was assayed for its effects on the immune system in mice. High doses of this compound (1000 microgram/mouse/day) have toxic effects and cause depletion on the peripheral lymphoid organs (spleen, thymus) while leaving the bone marrow cells unaffected. Both the in vivo and in vitro induction of cell-mediated cytotoxicity (CMC) to allogeneic tumor cells is stimulated at least tenfold by low doses (25--300 microgram/mouse/day) of RA while high doses suppress CMC induction. RA is shown to be a specific adjuvant for the induction of cytotoxic thymus-derived lymphocytes (T cells) and not a general T cell mitogen or adjuvant. It does not enhance the proliferative response in the mixed lymphocyte culture nor does it stimulate lymphocyte proliferation in response to the mitogens concanavalin A and phytohemagglutinin. The induction of cooperating T cells and the delayed-type hypersensitivity reaction are also not stimulated by RA. In contrast to the reported stimulatory effects of retinyl palmitate and retinyl acetate, RA does not stimulate the humoral response to erythrocytes. The strong adjuvant effects that RA has on the induction of CMC at low doses may be responsible for its anti-tumor activity.
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PMID:Effects of retinoic acid on the immune system: stimulation of T killer cell induction. 34 57

Patients with metastatic renal cell cancer have an overall 5-year survival rate of only 28% to 40% in spite of aggressive surgical treatment. A prospective randomized study conducted by the Eastern Cooperative Oncology Group used methyl--CCNU (meCCNU), vinblastine, and meCCNU-medroxyprogesterone acetate (MPA) to treat 165 patients with advanced renal cancer. The antitumor activity of the single-agent and/or combination therapy is analyzed. Patients were classified (as to grade of anaplasia of tumor; age; performance status; primary site of metastatic disease; and previous treatment with a progestational agent) and randomly assigned to various treatment protocols as described. Crossover randomization to one of alternate single-agent or combination regimens was carried out after failure with initial therapy. 2 meCCNU regimens were associated with severe hematologic toxicity, vinblastine regimens with neurotoxicity. All regimens except the vinblastine-MPA resulted in substantial vomiting. Response rate is low (11%) with each regimen. There were no statistically significant differences in treatment variables or factors among the various regimens. Patients capable of normal activity had a significantly higher response rate and longer survival period than nonambulatory or poor performance status patients. A relatively long symptom-free interval from primary tumor to metastatic disease was also associated with better survival rate. More than 50% of patients exhibited disease progression with 3 months of initiating the regimens.
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PMID:Phase II study of vinblastine, methyl-CCNU, and medroxyprogesterone in advanced renal cell cancer. 35 71

Phorbol myristate acetate (PMA), a tumor-promoter capable of influencing biologic functions of many cell systems, has been demonstrated to augment glucose-initiated insulin release from isolated rat islets of Langerhans. PMA caused a 2-fold increase in insulin release. This effect of PMA did not alter the sigmoidal relationship of insulin released to glucose concentration. The effect of PMA on insulin secretion from the islet beta-cells persists and a challenge with glucose alone, subsequent to a pulse of PMA, elicits an augmented insulin release response.
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PMID:Phorbol myristate acetate: effect of a tumor promoter on insulin release from isolated rat islets of Langerhans. 36 26

The increase in interfollicular epidermal ribosomes on the backs of mice initiated with 7,12-dimethylbenz(a)-anthracene and promoted with 12-0-tetradecanoyl-phorbol-13-acetate was disproportionate to the increase in epidermal wet weight, protein, and DNA. Whereas ribosome numbers increased five- to sixfold 48 hr after the first, fourth, or eight application of 12-3-tetradecanoyl-phorbol-13-acetate, epidermal tissue increased only two- to threefold at these times. This disproportionate increase was due to the fact that, concurrent with the increased amount of interfollicular epidermal tissue and cells, ribosomes per g epidermis and per mg DNA increased two to three times normal. The tissue concentration and cellular content of ribosomes were also increased in the epidermal component of induced squamous papillomas. The work of others has demonstrated that, during growth of other tissues and organs, ribosome accumulation is proportionate to accumulation of tissue and/or cells. The results of our study indicate that the epidermis may have unique kinetics of ribosome accumulation during induced growth. Furthermore, these findings suggest the interesting possibility that other tumor-prone surface epithelia, such as the linings of the respiratory and gastrointestinal tracts, have similar kinetics of ribosome accumulation during induced growth.
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PMID:Epidermal ribosome accumulation during two-stage skin tumorigenesis. 40 79

The formation of new hair follicles was quantitatively demonstrated in the tail skin of adult mice in the course of a two-stage carcinogenesis experiment with 7,12-dimethylbenz(a)anthracene as an initiator and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as a promoter, as well as in experiments with 12-O-tetradecanoylphorbol-13-acetate alone. Two kinds of follicular neogenesis could be distinguished. The most frequently encountered type was characterized by the organization of new follicles from the upper neck and orifice regions of already existing follicles. During their development, these new follicles remained in close apposition to the original follicles but, after having reached a critical size, split off to form fully independent follicles. In the second, type of follicular neogenesis, which occurred very rarely, the new follicles seemed to arise directly from the epidermis between two sets of hair triads; however, these follicles never reached their final stage and did not produce hairs. The formation of new hair follicles may be explained by a "dedifferentiation" of epidermal cells caused by the tumor promoter. Because of the paucity and advanced stage of the papillomas formed in tail skin after long-term treatment with 12-O-tetradecanoylphorbol-13-acetate, no reliable comment as to whether the papillomas derive from the hair follicles can be made.
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PMID:Induction of the formation of new hair follicles in mouse tail epidermis by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. 40 92

12-O-Tetradecanoylphorbol-13-acetate, a highly active tumor-promoting agent and lymphocyte comitogen, rapidly accelerates the transport of alpha-aminoisobutyric acid in cultured bovine lymphocytes. Structure-activity studies show that the ability of phorbol diesters to accelerate alpha-aminoisobutyric acid uptake runs parallel to their potency as lymphocyte comitogens and as tumor promoters in mouse skin. This phorbol ester-accelerated, amino acid transport is largely insensitive to the inhibition of RNA and protein synthesis by actinomycin D and cycloheximide, respectively, and is insensitive to the inhibition of membrane movement by cytochalasin B and colchicine. Retinoic acid, an antagonist of the tumor-promoting and comitogenic actions of phorbol esters also inhibits the acceleration of amino acid uptake by 12-O-tetradecanoylphorbol-13-acetate; however, the epoxy derivatives of retinoic acid and structurally related analogs, which are potent antagonists of the other aspects of phorbol ester activation of lymphocytes, are inactive in blocking amino acid uptake. Comparative studies in lymphocytes show that this phorbol ester elicits a number of metabolic responses which appear to originate at the cell membrane and that these are differentially antagonized by retinoic acid, the 5,6-epoxide of retinoic acid, and related retinoid analogs.
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PMID:Inhibition of phorbol ester-accelerated amino acid transport in bovine lymphocytes. 44 91

A 21-year-old female underwent a hysterectomy with the finding of an endometrial stromal sarcoma (7-9 mitoses/10 HPF) confined to the uterus. However, within 30 months of hysterectomy, metastases occurred in the spinal cord, femur and lungs. Treatment consisted of surgery and irradiation for the spinal cord metastases and ten courses of combination chemotherapy, Adriamycin, vincristine, cyclophosphamide (6 courses) and megestrol acetate (continuous since course 7). This therapy resulted in a complete clinical remission which has been maintained for eight months since completion of chemotherapy. It is suggested that this regimen be employed in patients with this rare and lethal tumor.
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PMID:Complete remission of widely metastatic endometrial stromal sarcoma following combination chemotherapy. 44 21

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence of absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone also inhibited thymidine kinase activity multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.
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PMID:Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture. 44 41

Treatment of cultured human HO melanoma cells with the mouse skin tumor promoter phorbol-12-myristate-13-acetate (PMA) at 5 x 10(-10) to 5 x 10(-7) M resulted in a dose-related inhibition of growth and a stimulation of differentiated functions. These included melanin synthesis and formation of dendrite-like structures. Higher doses of phorbol dibutyrate, a less potent tumor promoter, were required to produce an effect comparable to that of PMA for dendrite induction. Phorbol and two other phorbol esters, which lack tumor-promoting activity, were either inactive or elicited a poor response. In addition to morphological changes, treatment with PMA altered glucosamine incorporation into membrane gangliosides. After PMA treatment, glucosamine incorporation increased 8- to 10-fold in the GM3 ganglioside and decreased 2-fold in the GM1 ganglioside, as compared to phorbol or untreated control. Inhibition of cell growth and stimulation of melanin synthesis were also observed after treatment of the HO cells with dimethyl sulfoxide. Unlike the tumor-promoting agents, dimethyl sulfoxide did not induce the formation of dendrite-like structures in the cells. These findings indicate that HO melanoma cells can be stimulated into terminally differentiated cells after treatment with tumor-promoting agents such as phorbol diesters.
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PMID:Stimulation of differentiated functions in human melanoma cells by tumor-promoting agents and dimethyl sulfoxide. 44 63


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