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)

Random bred Syrian hamsters given s.c. injections of SV40 small t deletion mutants dl883, dl884, and dl890 rapidly develop reticulum cell sarcomas in the abdominal cavity in addition to slowly developing s.c. fibrosarcomas at the site of virus inoculation. Injection of wild type SV40 s.c. induces only fibrosarcomas at the site of inoculation. In an attempt to understand why mutations in the SV40 small t gene should lead to this difference in tumor-inducing capacity in hamsters, we studied cells from 12 abdominal reticulum cell sarcomas which were induced by the s.c. injection of SV40 mutants. Morphological and functional analyses indicate that these tumor cells are derived from MAC-2+ macrophages. They are highly granulated, vacuolated, and multinucleated, and they generally adhere to glass and plastic. In addition, they (a) phagocytose latex beads; (b) express high levels of class II major histocompatibility complex antigens; (c) contain beta-glucuronidase, acid phosphatase, and fluoride-inhibited nonspecific esterase; (d) contain lysozyme and fibronectin; and (e) express cell surface MAC-2 antigens. Thus, the small t deletions in the SV40 genome appear to permit the virus to transform cells that are distant from the site of virus inoculation; at this distant site, the cells transformed are of a specific lineage, MAC-2+ peritoneal macrophages. This specific tropism may reflect a unique characteristic of MAC-2+ cells or their precursors that renders these cells susceptible to SV40 mutants which are otherwise restricted in the range of cells that they can transform.
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PMID:Characterization of hamster tumors induced by simian virus 40 small t deletion mutants as true histiocytic lymphomas. 253 29

Spontaneous malignant fibrous histiocytoma (MFH) of the chest wall was found in a 10-year-old male Japanese white rabbit. Histologically, the MFH consisted mainly of areas of storiform, pleomorphic and myxoid patterns. Positive reactions for acid phosphatase (Ac-P), non-specific esterase (N-SE) and beta-glucuronidase (beta-GL) were demonstrated in fibroblast-like, histiocyte-like and giant cells. Moreover, a strongly positive fibronectin (FN) reaction was observed mainly in histiocyte-like and giant cells. In electron microscopy, tumor cells were composed morphologically of various types of cells such as fibroblast-like, histiocyte-like, undifferentiated and giant cells. This case was quite similar to those reported in man or other animals.
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PMID:Pathology of spontaneous malignant fibrous histiocytoma in a Japanese white rabbit. 254 66

Glucocorticoids exert their actions through a time-dependent, receptor-mediated, protein synthesis- and RNA synthesis-dependent mechanism. We have assessed the effects of 24-h culture of human neutrophils with dexamethasone on degranulation, chemotaxis, binding to vascular endothelium and formation of leukotriene B4. Purified neutrophils contained an average of 2896 [3H]dexamethasone binding sites per cell with a Kd of 4.1 X 10(-9) M for [3H]dexamethasone binding. Cells exposed to dexamethasone (10(-6) M) released equal or greater quantities of the lysosomal enzymes, lysozyme and beta-glucuronidase in response to formylmethionyl-leucyl-phenylalanine, serum activated zymosan, and the tumor promoting phorbol diester 12-O-tetradecanoylphorbol-13-acetate compared to controls. Culture with dexamethasone also did not inhibit neutrophil chemotaxis in response to a range of concentrations of formylmethionyl-leucyl-phenylalanine, or did it inhibit binding of neutrophils to cultured endothelial cells stimulated by either leukocyte activators (formylmethionyl-leucyl-phenylalanine and platelet-activating factor) or endothelial activators (interleukin-1, lipopolysaccharide or 12-O-tetradecanoylphorbol-13-acetate). Spontaneous adherence of neutrophils to endothelial cells was inhibited (82.9 +/- 6.8% of control, P less than .025, n = 18). Neither in vitro or in vivo glucocorticoids inhibited neutrophil leukotriene B4 formation induced by either the calcium ionophore A23187 or serum activated zymosan. We conclude that human neutrophils are not functionally inactivated by glucocorticoids and suggest that the mechanism by which glucocorticoids inhibit neutrophil accumulation at inflammatory sites may be by inhibition of the production of chemoattractants and endothelial activators rather than inhibition of their actions.
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PMID:An assessment of the effects of glucocorticoids on degranulation, chemotaxis, binding to vascular endothelium and formation of leukotriene B4 by purified human neutrophils. 254 40

Although the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), via its interaction with the Ah receptor, is an extremely potent carcinogen and immunosuppressive agent in experimental animals, its possible actions on polymorphonuclear (PMN) function have not been determined. In addition to their importance against infectious organisms, PMNs have been implicated in antitumor resistance. The present studies examined the effects of in vivo exposure to TCDD on PMN function in B6C3F1 (TCDD sensitive, presence of high affinity Ah receptor) and DBA/2N (TCDD resistant at low doses, defective Ah receptor) mice. Animals received a single oral exposure of 5 or 10 micrograms/kg of TCDD and PMNs were obtained 5 days later from the peritoneal cavity following elicitation with sodium caseinate. TCDD reduced the cytolytic and cytostatic activity of PMA-activated PMNs in B6C3F1, but not in DBA/2N mice, suggesting that this response segregates with the Ah locus. Furthermore, TCDD was found to bind specifically to PMNs from Ah-responsive mice. Neither the production of superoxide and hydrogen peroxide nor degranulation, the latter measured by beta-glucuronidase release, was impaired. Supernatants recovered from PMN cell cultures of TCDD-sensitive mice, but not from resistant DBA/2N mice, showed reduced killing capacity for actinomycin D-treated L929 tumor cells, while their ability to bind to tumor cells was not altered. These data suggest that TCDD interferes with PMN-mediated tumor cell killing by altering the production or secretion of a cytolytic factor. Examination of bone marrow stem cells revealed that granulocytic but not monocytic colonies were reduced after TCDD exposure in vivo and in vitro. Although mature PMNs had detectable levels of Ah receptor, exposure in vitro of these cells to TCDD had no effect on antitumor activity. Thus, it is possible that TCDD may affect PMNs at the level of hematopoiesis, via a direct interaction with granulocyte precursor cells, or modulate PMNs at different stages of maturation.
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PMID:Selective inhibition of polymorphonuclear neutrophil activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin. 255 88

1. The interactions of B16-F1 and B16-F10 tumors with their surrounding tissues in terms of enzyme activities such as cathepsin B, hemoglobin(Hb)-hydrolase, acid phosphatase, beta-glucuronidase and plasminogen activator were investigated when said tumors proliferated locally and at secondary sites throughout the host's circulatory system. 2. In the case of B16-F1 and B16-F10 tumor cells proliferating under the skin, statistical differences were not detected between the enzyme activities of the skin surrounding the tumors and control skin, nor between B16-F1 and B16-F10 tumors, except for beta-glucuronidase. 3. In the case of B16-F1 and B16-F10 tumor cells metastasizing to lung, statistical differences were detected between numerous enzyme activities of the lung tissues surrounding the tumors and control lung tissue, and also between B16-F1 and B16-F10 tumors. 4. The activities of cathepsin B and acid phosphatase of lung tissue surrounding B16-F1 tumor were lower than those of the control lung. 5. beta-Glucuronidase activity of lung tissue surrounding B16-F10 tumor was higher than that of the control lung. 6. The activities of cathepsin B, Hb-hydrolase and beta-glucuronidase of the B16-F10 tumor were higher than those of the B16-F1 tumor. 7. Results indicate that metastasized B16 melanoma tumor cells interact with surrounding lung tissues, and that cathepsin B, Hb-hydrolase and beta-glucuronidase might play important roles in the metastasis of the malignant tumor.
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PMID:Interaction of tumor and surrounding tissue of mice inoculated B16 melanoma variants in terms of enzyme activity. 266 66

The effect of feeding psyllium husk, a water-soluble fiber, and cellulose, a water-insoluble fiber, against chemically induced colon cancer was investigated in rats. Adult male rats were fed semipurified diets containing 20% fat, no fiber, or 10% psyllium husk or cellulose for 22 weeks. Tumors were induced in one-half of the rats fed each diet by the gastric intubation of 1,2-dimethylhydrazine (DMH) during Weeks 3-11. In terms of the number of animals with tumors in each group, psyllium strongly reduced the tumorigenicity of DMH and cellulose moderately reduced tumorigenicity, whereas the two fibers did not differ significantly from each other with respect to tumorigenicity. Psyllium-fed rats had the highest fecal aerobic counts, lowest beta-glucuronidase, and highest 7-alpha-dehydroxylase activities. The psyllium diet also resulted in increased fecal output and percent moisture. Rats fed cellulose tended to have greater fecal bulk and lower beta-glucuronidase activity compared with rats fed no fiber and lower 7-alpha-dehydroxylase activity compared with rats fed psyllium husk.
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PMID:Reduction of DMH-induced colon tumors in rats fed psyllium husk or cellulose. 281 29

Activities of a cathepsin B-like cysteine proteinase have previously been observed to correlate with the malignancy of several animal and human tumors. Plasma membrane fractions of some of these tumors have been found to be enriched in cathepsin B-like activity. We have determined the subcellular distribution of this enzyme and three additional lysosomal hydrolases (cathepsin H, beta-hexosaminidase, and beta-glucuronidase) in normal murine liver and six metastatic variants of the B16 melanoma. The tissues were fractionated initially by differential centrifugation followed by Percoll density gradient centrifugation of the light mitochondrial fraction. Two fractions were obtained: an L-2 fraction enriched in all four lysosomal hydrolases; and an L-1 fraction enriched in a marker enzyme for the plasma membrane. Cathepsin B-like and beta-hexosaminidase activities, but not the other hydrolase activities, were also found to be enriched in the L-1 fractions of the metastatic B16 tumors. We explored the nature of the association of the cathepsin B-like activity with the plasma membrane using fractions from the spontaneously metastatic B16 amelanotic melanoma. Activity could not be dissociated from the plasma membrane fraction by washing with a physiological salt solution suggesting that it was not adsorbed to this fraction nonspecifically, nor could it be displaced by mannose 6-phosphate or other sugars which compete for binding to the known lysosomal receptors. High salt concentrations, low concentrations of the mild detergent saponin, mild acidification, or phosphatidylinositol-specific phospholipase C did not elute the cathepsin B-like activity. However, activity was eluted by exposure to 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, a detergent used in the purification of integral membrane proteins. The B16 amelanotic melanoma plasma membrane-associated cathepsin B-like activity had a slightly higher pH optimum and was resistant to inactivation by neutral pH and to inhibition by three low molecular weight inhibitors of cysteine proteinases. The Ki values for inhibition by leupeptin and stefin A were 20-fold higher. The presence of a cathepsin B-like cysteine proteinase at the surface of metastatic tumor cells, particularly in a form which can retain activity at physiological pH and retain activity in the presence of extracellular proteinase inhibitors, may contribute to the focal dissolution of the extracellular matrix observed at sites of contact with invading tumor cells.
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PMID:Properties of a plasma membrane-associated cathepsin B-like cysteine proteinase in metastatic B16 melanoma variants. 282 39

To determine whether the mononuclear cells (MC) and multinucleated giant cells (GC) of giant cell tumor of tendon sheath (GCTTS) exhibit evidence of monocyte/macrophage lineage, we studied their antigenic features (seven cases, paraffin sections; two cases, frozen sections) and enzymatic features in situ (four cases, plastic sections). Both MC and GC expressed a monocyte/macrophage phenotype: HLA-A,B,C+, HLA-DR+, T200+ (leukocyte common antigen), Leu-M3+ and Leu-3+. MC and GC also expressed similar enzymatic phenotypes which resembled that of osteoclasts. Both were rich in acid phosphatase and contained smaller, variable amounts of ATPase, beta-glucuronidase, alpha-naphthyl acetate esterase, and 5'-nucleotidase. Both lacked alkaline phosphatase. Reactive osteoclasts in plastic and paraffin sections were also T200+, a finding strongly supporting their bone marrow derivation and leukocytic differentiation. In plastic sections, osteoclasts were additionally reactive with macrophage antigen EBM11. In aggregate, these data suggest that GCTTS is a true histiocytic lesion of monocyte/macrophage lineage composed of phenotypically similar MC and GC that most closely resemble osteoclasts. We found no evidence that GCTTS cells resemble osteoblasts, fibroblasts, or synovial sarcoma cells. Furthermore, expression of the Ki-67 nuclear antigen by 1-2% of MC but not by GC suggests that the proliferating cells in GCTTS are restricted to its MC component.
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PMID:The cells of giant cell tumor of tendon sheath resemble osteoclasts. 283 1

The effects of 3-amino-1-hydroxy-propylidene-1,1-bisphosphonate (AHPrBP), 1-hydroxyethylidene-1,1-bisphosphonate (HEBP), dichloromethylenebisphosphonate (Cl2MBP) and azacycloheptylidene-2,2-bisphosphonate (AHBP) on bone were examined in organ culture using newborn mice calvaria. AHPrBP, HEBP and Cl2MBP caused a dose-dependent inhibition of PTH-stimulated (10 nmol/l) release of 45Ca from the calvaria, at and above a concentration of 3 mumol/l, whereas AHBP only caused a slight inhibition, at and above 100 mumol/l. AHPrBP inhibited PTH-stimulated release of 3H from bones prelabelled with [3H]-proline. AHPrBP (30 mumol/l) diminished the stimulatory effect of 1 alpha(OH)vitamin D3 (10 nmol/l), prostaglandin E2 (0.1 mumol/l) and renal tumor conditioned media on 45Ca release. AHPrBP and Cl2MBP, at and above 3 mumol/l, decreased PTH-stimulated mobilization of Ca2+ and Pi and in parallel the release of beta-glucuronidase without affecting the release of lactate dehydrogenase. The inhibitory effect of AHPrBP (30 mumol/l) on PTH-induced 45Ca release was irreversible. The inhibition by AHPrBP (30 mumol/l) on spontaneous and PTH-stimulated release of 45Ca can be seen first after 24 h of culture. Similarly the inhibitory effect by HEBP (30 mumol/l) and Cl2MBP (30 mumol/l) was delayed and could be observed after 36 and 24 h of culture, respectively. PTH-stimulated release of Ca2+, Pi, beta-glucuronidase and beta-N-acetylglucosaminidase was reduced by AHPrBP first after 24 h of culture. AHPrBP, HEBP and Cl2MBP, at concentrations which are inhibitory on bone resorption, do not affect protein synthesis and mitotic activities in mouse calvaria. These data show that AHPrBP, HEBP and Cl2MBP inhibit bone resorption in vitro and in parallel decrease lysosomal enzyme release by a mechanism, which is not related to cytotoxicity. In addition, the delayed inhibitory effect on bone resorption and lysosomal enzyme release by all the compounds suggest that bisphosphonates inhibit bone resorption indirectly and not by a direct effect on existing osteoclasts. The delayed inhibition by bisphosphonates on bone resorption may be due to decreased recruitment of new osteoclasts as a consequence of an inhibitory action on mononuclear osteoclast precursor cells.
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PMID:Effects of four bisphosphonates on bone resorption, lysosomal enzyme release, protein synthesis and mitotic activities in mouse calvarial bones in vitro. 295 2

During chemical carcinogenesis Langerhans cells (LC) are depleted from the epidermis, disrupting the normal immunological functions of the skin. Tumor promotors but not initiators, have been shown to deplete adenosine triphosphatase (ATPase)-positive LC from the skin and therefore the cutaneous immune system may be impaired during tumor promotion but not initiation. The present study shows that the tumor promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) but not the initiator urethane depletes Ia-positive LC from BALB/c murine ear epidermis, and beta-glucuronidase-positive LC from C57BL mouse tail skin. Sensitization with 2,4-dinitrofluorobenzene (DNFB) through urethane-treated skin resulted in a normal contact sensitivity response when the mice were challenged 5 days later. In contrast, tolerance resulted from sensitization through TPA-treated skin as a result of the generation of suppressor cells. In addition, TPA but not urethane-treated C57BL mouse tail skin survived for an extended time when grafted onto histoincompatible BALB/c mice. Therefore, impairment of the normal immunological functions of skin resulted from treatment with the tumor promotor TPA but not the tumor initiator urethane, which suggests that a loss of LC during tumor promotion may impair immunological protection against skin tumors.
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PMID:Suppressor cell activation and enhanced skin allograft survival after tumor promotor but not initiator induced depletion of cutaneous Langerhans cells. 296 90


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