Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential modifying effects of testosterone propionate (TP) and high-caloric high-fat diet (20% corn oil, HF) on rat accessory sex gland carcinogenesis were investigated. Male F344 rats were treated five times at 4-week intervals with N-methylnitrosourea (MNU) i.v. or N-nitrosobis(2-oxopropyl)amine (BOP) s.c., each injection following 2 weeks pretreatment with dietary ethinyl estradiol. After completion of this carcinogen administration stage, animal groups received subcutaneous implantation of Silastic tubes filled with 40 mg TP with or without HF for 40 weeks. Carcinomas of the seminal vesicles and/or coagulating glands were induced in 5, 39 and 56% of rats given MNU alone, MNU and TP, and MNU and HF plus TP respectively. No equivalent tumors were found in rats given MNU and HF. In the BOP-treated groups, 11% of animals receiving TP but no HF diet demonstrated seminal vesicle carcinomas and 6% of rats receiving TP plus HF diet had coagulating gland carcinoma. Thus while TP exerted a strong enhancing effect on tumor growth in the seminal vesicles and coagulating glands, high caloric HF did not manifest any significant influence.
Carcinogenesis 1991 Nov
PMID:Induction of invasive carcinomas of the seminal vesicles and coagulating glands of F344 rats by administration of N-methylnitrosourea or N-nitrosobis(2-oxopropyl)amine and followed by testosterone propionate with or without high-fat diet. 193 6

To further understand the molecular mechanisms and the biological indicators of colonic tumorigenesis, the authors examined tyrosine kinase activity in the cytosol and in the particulate fraction of the homogenates of specimens from 20 human colonic carcinomas and compared them with the adjacent normal mucosal tissues. Total protein tyrosine kinase activity could be precisely detected using miniphosphocellulose column purification and a synthetic peptide, Glu-asparagine (Asp)-alanine (Ala)-Glu-tyrosine (Tyr)-Ala-Ala-arginine (Arg)-Arg-Arg-glycine (Gly) (E11-G1), as an artificial substrate. Tyrosine kinase activity of colonic carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity in the particulate fraction was elevated with respect to protein concentration. The average specific activity ratios were 1.95 +/- 0.27 (normal cytosolic/carcinoma cytosolic) and 0.57 +/- 0.01 (normal particulate/carcinoma particulate) for tyrosine kinase activity. Cellular distribution (% cytosol) of tyrosine kinase activity in normal mucosa and in carcinoma varied from 21.0% to 91.2% and from 7.0% to 61.4%, respectively. In nearly all cases the percentage of cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal tissues. There was no difference due to histologic type or the presence of adenomatous components. A significant decrease of cytosolic tyrosine kinases was correlated with Dukes' Stage A. With advancing Dukes' stage, the average specific activity ratios (normal cytosol/carcinoma cytosol) were decreased. This study indicates that colonic carcinogenesis might be associated with alterations in cellular levels of tyrosine kinase activity and that the average specific activity ratio (normal cytosol/carcinoma cytosol) had a possible correlation with colonic tumor growth.
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PMID:Altered protein tyrosine kinase levels in human colon carcinoma. 198 53

Ornithine decarboxylase (ODC) was separated, using diethylamino-ethyl ion-exchange chromatography, into multiple peaks of activity. We investigated the isoforms of ODC during 1,2-dimethylhydrazine-induced colon carcinogenesis and in human colon tumors. ODC in both mouse and human normal-appearing colonic mucosa was consistently separated into two active peaks by diethylaminoethyl-Sepharose CL-6B column chromatography. The major peak (Peak I) contained about 75% of the mouse and 72% of the human colonic mucosal ODC activity. During and after 10 weekly injections of 1,2-dimethylhydrazine (20 mg/kg, i.p.), colonic ODC activity was significantly enhanced with induction of both peaks but with a more significant increase in Peak II. ODC activity in both 1,2-dimethylhydrazine-induced and human colon tumors was significantly higher compared with the normal colon mucosa. The chromatographic profile of tumors showed the predominance of the second peak. Furthermore, the chromatographic profile of ODC after alkaline phosphatase treatment yielded an elution of only one peak coincident with the Peak I and the disappearance of Peak II. The second peak of ODC (the phosphorylated form) may be a specific isoform associated with colon tumorigenesis and tumor growth.
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PMID:Heterogenicity of ornithine decarboxylase during mouse colon carcinogenesis and in human colon tumors. 200 26

The role of cell death as a determinant for tumor growth and regression was studied using an estrogen-dependent, transplantable kidney tumor designated H301. H301 cells were injected s.c. into diethylstilbestrol(DES)-treated male Syrian hamsters and developed solid tumors of 1-2 g within 2-3 weeks. Upon withdrawal of estrogen the tumors regressed by 80-90% within 4 days. Mitoses, necrotic areas and single-cell death indicated by small, condensed cell residues, were counted in hematoxylin and eosin stained histological sections of the tumors. Coincident with tumor regression after DES withdrawal, mitotic activity decreased by approximately 90%; the rate of single-cell death increased (by approximately 2-fold at its maximum). The incidence of necrotic areas was not affected by DES withdrawal. DES re-treatment resulted in reduction of single-cell death by 80% within 8 h. Mitotic activity increased within 24 h to the level observed before DES withdrawal. Again, the incidence of necrotic areas did not change. As a result, tumors re-grew to their previous size within 2 days after resumption of DES treatment. These results led to the following conclusions: (i) DES treatment inhibits and DES withdrawal enhances single-cell death of H301 tumor cells. (ii) Both this functional property and its morphology characterize single-cell death in the tumors as apoptosis. (iii) Estrogen-dependent cell death determines, in addition to mitosis and necrosis, the growth rate of H301 tumors. (iv) This experimental model may provide a useful tool to study the interaction of potential anti-tumor drugs with apoptosis in neoplasia.
Carcinogenesis 1991 May
PMID:Control of cell death (apoptosis) by diethylstilbestrol in an estrogen-dependent kidney tumor. 202 49

The direct antitumoral effects of gonadotropin-releasing hormone (GnRH) analogues on breast tumors have been surmised from clinical observations and in vitro studies. The present study aimed to determine the effects of the GnRH agonist [D-Trp6]GnRH (Decapeptyl) on steps of experimental mammary carcinogenesis, and the mechanisms, other than the chemical castration, involved. We chose a recent model, i.e., mammary tumors induced by wild-type A2 polyoma (Py) virus in BALB/c female nu/nu mice, which displays the following characteristics. Tumors are mammary adenocarcinomas similar to well differentiated breast carcinomas. Tumor promotion period ends 20 days after Py virus inoculation and is estradiol dependent. The first palpable tumors occur 60 days after Py virus inoculation, and tumor growth is ovarian hormone independent. The effects of Decapeptyl treatment on tumor induction and tumor growth were studied in normal or ovariectomized 6-week-old nude mice inoculated with 10(7) plaque-forming units Py virus (day 0 of experiments). Normal mice and ovariectomized mice percutaneously supplemented with 0.6 micrograms 17 beta-estradiol every other day until day 30 (OvE2 mice) were treated with monthly s.c. injections of the sustained release form of Decapeptyl (5 mg/kg) until the end of 180-day experiments. Overall values for latency periods were included within a day 60 to day 130 time interval. Hormone-independent outgrowth was not affected. We focused on tumor progression before the outgrowth. Incidences on tumor appearance kinetics account for effects at this stage. 17 beta-Estradiol repletion strongly antagonized (P less than 0.001) the slowing effect of ovariectomy on the tumor appearance kinetics, indicating that tumor progression is estradiol sensitive in its early stages. [D-Trp6]GnRH treatment antagonized tumor appearance profiles, inducing similar kinetics in both normal and OvE2 mice. In normal mice, the antagonism (P less than 0.01) was concomitant with significant decreases (P less than 0.05) in serum levels of estradiol and prolactin, which are critical hormones for mammary tumor development in mice, suggesting a pituitary-mediated effect. In OvE2 mice, the antagonism (P less than 0.01) occurs independently of estradiol and prolactin, suggesting a direct effect at the mammary cell level. Because of alterations in kinetics, this effect is exerted at the early stages of tumor progression on Py virus-transformed, ovarian hormone-sensitive cells in the mammary tissue. This new animal model of breast cancer is shown to be useful in characterizing direct antitumoral effects of GnRH analogues and studying the basic mechanisms of mammary carcinogenesis.
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PMID:Direct inhibiting effects of [D-Trp6]gonadotropin-releasing hormone on the estrogen-sensitive progression of polyoma virus-induced mammary tumors in athymic mice. 216 84

Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5'-phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age-matched controls. The children with leukemia had significantly lower PLP levels than the controls. In 26 additional leukemia patients and 26 additional controls, a high-performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). The PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness-related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status.
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PMID:Abnormal vitamin B6 status in childhood leukemia. 224

Receptors for several polypeptide hormones have been demonstrated in cells of the gastrointestinal tract and pancreas. Some of these polypeptides stimulate or inhibit cell division. Therefore, these receptors have been sought in carcinomas arising from these tissues, and several examples have been reported. In some instances, stimulation of tumor growth by the corresponding ligand has been demonstrated or blocked by a receptor antagonist. In experimental carcinogenesis, the incidence of tumors has been influenced by some of the same hormones. Receptors and binding proteins for steroid hormones also have been reported in carcinomas of the pancreas. Manipulation of sex steroid hormones has yielded both inhibition and enhancement of growth of human and rat pancreatic cancers. These observations imply that trophic or growth inhibiting polypeptide and steroid hormones may serve as promoters or inhibitors of carcinogenesis in gastrointestinal organs and may influence the growth of established carcinomas. Receptor blockers may provide a clinical approach for slowing the growth of some gastrointestinal cancers.
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PMID:Hormones and receptors in gastrointestinal malignancies. 226 78

Endothelial cells produce and secrete a large number of proteases which are implicated in various disease states. These proteases fall into two classes: serine proteases include plasminogen activators (t-PA) and urokinase (u-PA) and play a major role in fibrinolysis, tissue repair and carcinogenesis; and metalloproteases include collagenases and stromelysine, two enzymes involved in the tissue remodelling that occurs during angiogenesis and tumor growth. The authors have recently identified two other proteases in porcine aortic endothelial cell culture medium. One is an elastase-like enzyme of the metalloprotease group, whereas the other is a new protease whose molecular weight is 85 Kd and whose activity becomes apparent only after exposure of the endothelial cells to platelets. The term Platelet Endothelial Cell Activated Protease accurately describes this enzyme. PECAP degrades casein and fibrinogen. Because PECAP is not inhibited by the usual inhibitors of the various classes of proteases, it remains at present unclassified.
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PMID:[Endothelial cell proteases and their modulation by platelets]. 229 Jun 90

Based upon a large body of experimental and clinical data, it is evident that multiple malignant events are necessary for a normal cell to give rise to a fully malignant cancer cell. A critical issue with regard to human prostatic carcinogenesis is the clinical significance of the large number of cancers that are present histologically in the elderly male prostate gland. A possibility is that these histological prostate cancers already have undergone all of the malignant events necessary to produce clinically manifest cancer and, thus, only further tumor growth is required to produce a clinical tumor. Alternatively, these histological cancers may have undergone some but not all of the events necessary to produce clinical disease and, therefore, despite host longevity the cancer will remain clinically silent as long as no further malignant changes occur. This issue has importance clinically with respect to the diagnosis, therapy and possible prevention of prostatic cancer. Clinical observations and the mathematical relationship between prostate cancer prevalence and host age (time) support the fact that, in addition to growth, histological prostate cancer requires further malignant events to produce clinical disease. A better understanding of the events involved in prostate cancer development will be necessary to have a greater impact on this disease in the future.
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PMID:Clinical evidence for and implications of the multistep development of prostate cancer. 231 98

The study was concerned with evaluation of the parameters of specific binding of 17-beta-estradiol to myometrial plasma membrane in tumor growth versus lipid profile of the membrane and A2 and C phospholipase activity. Tumor growth was shown to involve an increase in the association constant of plasma membrane, changes in the lipid profile and activity of the enzymes. The role of these factors in myometrial carcinogenesis is discussed.
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PMID:[Estradiol binding and lipid metabolism in the plasma membrane of myometrial cells during tumor growth]. 234 90


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