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)

Female 3-month-old C3H mice were given sc injections of 5-mg pieces of mammary adenocarcinoma and fed a linoleate-containing (15% corn oil) diet in the presence or absence of eicosa-5,8,11,14-tetraynoic acid (TYA), an inhibitor of prostaglandin synthesis. After 6 weeks, the weights of tumors of mice fed the TYA-free linoleate diet were three to five times greater than those of mice fed the TYA-containing linoleate diet. Dietary TYA caused a reduction in the levels of arachidonate and an elevation in the levels of linoleate in mammary tumors and livers. Aspirin, another known inhibitor of prostaglandin synthesis, when added to the linoleate diet, did not affect the tumor size or the composition of fatty acids in the tumors and livers. Thus we concluded that a) the growth of mammary tumors was not related to prostaglandin synthesis but was related to the availability of arachidonate, and b) TYA was an effective inhibitor for the conversion of linoleate to arachidonate.
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PMID:Reduced growth rate of transplantable mammary adenocarcinoma in C3H mice fed eicosa-5,8,11,14-tetraynoic acid. 83 90

Oral daily administration of aspirin or indomethacin retarded growth of experimental tumors in mouse. Aspirin treatment, 150 mg/kg twice daily, inhibited growth of a transplantable mast-cell ascites tumor (P815) by 39-43% (p less than 0.001) and of a s.c. transplanted Lewis lung carcinoma by 52% (p less than 0.025) without adversely affecting body growth. The total serotonin, histamine and histidine decarboxylase content of the ascites tumor was also reduced as was the urinary excretion of the amines. Treatment with 3 and 5 mg/kg indomethacin resulted in 40% (p less than 0.01) and 80% (p less than 0.001) reduction, respectively, in ascites tumor growth. With the higher dose of indomethacin, no tumor was observed in half of the animals inoculated with tumor, although signs of indomethacin toxicity (reduced body growth, gastric lesion) was evident in the animals.
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PMID:Alteration of tumor growth by aspirin and indomethacin: studies with two transplantable tumors in mouse. 95 14

A review of posterior fossa myelography at St. Joseph Hospital within the past 5 years is presented. Three false positive diagnoses have been found. Two of the cases were proved to have arachnoiditis, while one demonstrated a knuckle of artery in the canal. One case with large acoustic neuromas causing nonfilling of the contralateral canal is presented. One case with Type I intracanalicular tumor out of 40 acoustic neuromas in the series was diagnosed prior to surgery. The indication for posterior fossa myelography are discussed with a review of the literature.
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PMID:Filling defects and nonfilling of the internal auditory canal in posterior fossa myelography. 107 96

The influence of aspirin (ASA) on 1,2-dimethylhydrazine (1,2-DMH)-induced colonic carcinogenesis was examined in weanling Sprague-Dawley rats. The incidence of adenocarcinomas in response to a single dose of 1,2-DMH was reduced 60% in rats receiving ASA for 1 week before and after the carcinogen. However, ASA had no effect on tumor incidence when initiated 4 weeks after a single dose of 1,2-DMH and continuing until the animals were killed at 36 weeks. The doses of ASA employed suppressed by 95% or more ex vivo colonic prostaglandin E2 (PGE2) production and reduced colonic mucosal cAMP levels in both rats exposed to 1,2-DMH and in age-matched controls. Proliferative activity of colonic mucosa as assessed from tritiated thymidine ([3H]dThd) incorporation into mucosal DNA was increased at 1 week but suppressed by 36 weeks after 1,2-DMH exposure. ASA significantly increased colonic mucosal DNA synthesis, suppressed colonic PGE2 production and reduced mucosal cAMP levels at both 1 and 36 weeks in rats given the 1,2-DMH vehicle. However, ASA failed to alter the enhanced mucosal DNA synthesis observed at 1 week or the suppressed DNA synthesis observed at 36 weeks after a single dose of 1,2-DMH, despite significant inhibition of colonic PGE2 production and reduction in mucosal cAMP levels by ASA. Treatment of rats for 1 week with ASA significantly inhibited basal and arachidonate stimulated decomposition of the 1,2-DMH intermediary metabolite methylazoxy-methanol, assessed ex vivo in colonic mucosal homogenates. Thus, while other mechanisms are not excluded, suppression of 1,2-DMH induced colonic carcinoma by concurrent administration of ASA may be linked in part to altered metabolic activation of this carcinogen via cyclooxygenase-dependent co-oxidation. By contrast, the previously reported suppression of the promotional phase of colonic carcinogenesis in rats by the delayed introduction of cyclooxygenase inhibitors may not be linked to inhibition of local colonic prostanoid production, since (i) inhibition of colonic prostanoid synthesis by ASA did not mimic this antipromotional effect, and (ii) the doses of non-steroidal anti-inflammatory drugs employed in some earlier studies may not significantly inhibit colonic prostanoid synthesis.
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PMID:Effects of aspirin on 1,2-dimethylhydrazine-induced colonic carcinogenesis. 131 25

SV-40 transformed human lung fibroblasts and HT 1080 fibrosarcoma cells secrete a 92-kDa type IV collagenase (in addition to 72-kDa type IV collagenase identical to that found in macrophages, phorbol ester differentiated U937 cells, and keratinocytes. The expression of this protease is induced by the tumor promoter TPA, and interleukin-1 and was not detected in the parental human lung fibroblast. The 92-kDa preproenzyme has a predicted Mr of 78,426, including a 19 amino acid long hydrophobic signal peptide. The apparent discrepancy between the predicted molecular weight and the molecular weight of the secreted protein is due to a post-translational modification of the enzyme through glycosylation. The 92-kDa type IV collagenase consists of five distinct domains, including a unique 54 amino acid long collagen--like domain, and is a member of the secreted ECM metalloprotease gene family. Both the 72 and 92-kDa type IV collagenase contain a fibronectin-like collagen binding domain. The mosaic structure of the secreted ECM metalloproteases is a result of a recruitment of the functional units from ECM structural macromolecules into an enzyme protein in the process of evolution. The 92-kDa and 72-kDa type IV collagenase proenzymes form a noncovalent complex with inhibitors, which is activatable by APMA, yielding an enzymes with similar if not identical substrate specificity profile. Our results demonstrate that while the 92-kDa type IV collagenase forms a stoichiometric complex with TIMP, the 72-kDa type IV collagenase, purified from the same starting material, contains a novel 24-kDa inhibitor-TIMP-2.
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PMID:Mosaic structure of the secreted ECM metalloproteases and interaction of the type IV collagenases with inhibitors. 133 9

In this review we have presented overwhelming evidence that platelets play an important enhancing role in tumor cell-vasculature interactions and cancer metastasis. Tumor cells employ a host of mechanisms to induce platelet aggregation; vice versa, platelets make use of a spectrum of mechanisms to modulate tumor cell-EC and tumor cell-ECM interactions. Various COX and LOX metabolites are closely involved in this bidirectional modulation, thus providing us with a very promising therapeutic avenue by modifying the actions of these metabolites. On the other hand, adhesion molecules are mediators of tumor cell-platelet-EC interactions; therefore interference with these adhesion molecules and various adhesive processes either by soluble peptides, nonpeptidic analogues, or specific antibodies holds great investigational and clinical appeal.
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PMID:Platelets and cancer metastasis: more than an epiphenomenon. 147 Sep 27

The major cause of failure in the treatment of patients with solid malignancies is failure to prevent or control the spread of metastases. The metastatic process is a series of interrelated steps that must be accomplished before distant tumour foci can be established. Tumour cell motility is a complex process, which is involved in many of these steps. The mechanisms by which motility is stimulated and physically generated are complex and as yet poorly understood. Viewing the cell as a chemomechanical engine that relies on a tension based system for movement allows us to design chemotherapeutic strategies to inhibit tumour cell motility directly. Chemotherapeutic agents that block stimulation, interfere with cell-ECM interactions and interfere with cytoskeletal mechanics are already being tested. Further studies will be needed to define their efficacy.
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PMID:Cell motility as a chemotherapeutic target. 168 57

Multiple clinical trials have demonstrated that thrombolytic treatment early in the course of acute myocardial infarction significantly reduces mortality. Patients under 75 years of age who have had chest pain for no longer than six hours and who demonstrate ST-segment elevation on electrocardiogram are the best candidates for this therapy. Recent studies suggest that there is little difference in effectiveness among streptokinase, alteplase and anistreplase. However, streptokinase is 10 times less expensive than the other agents and causes fewer intracranial bleeds, the major serious adverse effect of thrombolytic therapy. An advantage of anistreplase is that it can be given in a five-minute bolus injection, compared with a one-hour infusion for streptokinase and a three-hour infusion for alteplase. Thrombolytic therapy is contraindicated in patients with known pregnancy, active internal bleeding, uncontrolled hypertension, aortic dissection, intracranial neoplasm or a history of hemorrhagic stroke. Heparin should be administered with both alteplase and streptokinase. Aspirin, beta blockers, nitrates and lidocaine are useful adjunctive therapies in the setting of an acute myocardial infarction.
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PMID:Thrombolytic therapy in acute myocardial infarction. 173 49

We hypothesize that early events in the development of at least some human breast cancers involve faulty epithelial-mesenchymal interactions and that the stromal cells themselves play an active role in this abnormal process. In contrast, later events accelerating breast tumor progression may occur in association with genetic changes involving only the malignant epithelial cells. These conclusions arise from a review of the literature, our comparative studies of HA metabolism in fibroblasts cultured from either normal or malignant breast tissues, and from molecular-genetic studies performed on sequential specimens from a single patient and on a wide variety of human breast tumor samples. HA is a proteoglycan component of the ECM which is known to stimulate epithelial cell detachment and motility and is most abundant in fetal and rapidly growing tissues. We find that many breast cancer-derived fibroblasts are stimulated to produce HA in response to TGF-beta under conditions where HA accumulation by normal tissue fibroblasts is almost uniformly inhibited. In a single patient, we had the opportunity to examine three malignant effusions that occurred sequentially to identify genetic changes associated with the later stages of breast cancer progression. Although, common cytogenetic abnormalities were found in all the effusion samples, only the last effusion exhibited a loss of heterozygosity at the c-Ha-ras locus. In this case, the allelic loss correlated with improved growth in vitro of the primary cells and with ability to become a permanently established cell line.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early and late events in the development of human breast cancer. 181 93

Gliomas are known to express over a hundred antigens, and no doubt make many more unknown antigens. Major categories of glioma cell antigens include glial antigens, ECM antigens, muscle antigens, melanoma antigens, "tumor-specific" antigens, and cellular proliferation antigens. A strikingly low number of cultured gliomas express glial antigens. They commonly express not only ectodermal, but also mesenchymal ECM antigens. Tumor-specific antigens have been an elusive goal of neuro-oncologists, but there are bright new prospects in need of further study. These include direct screening of hybridoma supernatants on glioma tissue and targeting glycolipids, glycoproteins, and oncogene products. Cellular proliferation antigens will become increasingly important in predicting prognosis of gliomas. Proliferation antigens of cultured gliomas are under intense scrutiny at present. The extent and evolution of antigenic heterogeneity of neoplastic cells in gliomas raise basic biologic questions with profound clinical ramifications. Individual glioma cell lines may generate more than 30 subtypes of cells with minor to major differences in antigen expression. These include expression of antigens representing multiple different cell lineages. Mesenchymal drift is the tendency of gliomas to progressively lose glial and gain mesenchymal features. Models of in vivo mesenchymal drift occur in glioma cell culture where mechanisms are more easily investigated than in situ. Neither exogenous protein absorption nor fibroblast overgrowth explain the phenomenon. Cells with the mesenchymal marker, fibronectin, overgrow GFAP-positive cells during explanation of gliomas. Many of these fibronectin-positive cells express cytologic and growth characteristics of neoplasia. The source of these cells is unknown. A leading candidate for the source of these neoplastic fibronectin-positive cells is the proliferation of vascular and mesenchymal cell elements of glioma tissue commonly called "endothelial proliferations". However, these elements in tissue do not display the same abnormalities of neoplasia as the fibronectin-positive cells in culture. Understanding this "tissue/explant paradox" may solve the conundrum of mesenchymal drift. In the absence of a counterpart in tissue of these neoplastic fibronectin-positive cells so abundant in glioma cell cultures, mechanisms of mesenchymal drift other than overgrowth of neoplastic mesenchyme must be considered. The occurrence of "dual cells" which express antigenic markers of entirely different cellular lineages suggests the possibility that neoplastic glia generate mesenchymal drift by altered gene expression. Various studies which suggest the capacity of cultured gliomas to alter phenotypic expression of their genes are critically examined and their relevance to mesenchymal drift discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Patterns of antigenic expression of human glioma cells. 193 88


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