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)

By separating 5'-nucleotide phosphodiesterase isoenzyme-V (5'-NPD-V) as a fast-moving isoenzyme by polyacrylamide electrophoresis, the determination of serum 5'-NPD-V was performed in 302 preoperative patients with gastric and colorectal cancers to assess the clinical usefulness for suspecting liver metastases. Serum levels of CEA, alpha-fetoprotein and tumor markers were simultaneously measured. Angiography, CT scan and echo were also performed preoperatively. The normal values of serum 5'-NPD-V in 67 healthy subjects except heavy smokers were less than 3.0mm. 5'NPD-V values determined in patients with and without liver metastases were as follows: In gastric cancer 1.5 +/- 2.0mm and 8.6 +/- 9.0mm, and in colorectal cancer 2.2 +/- 3.3mm and 5.8 +/- 5.3mm, respectively, indicating a significant difference (p less than 0.05). The sensitivity of 5'-NPD-V in gastric cancer was 0.682, the specificity was 0.892, the predictability was 0.518, and the accuracy was 0.862. The results in colorectal cancer were 0.600, 0.958, 0.805 and 0.800, respectively. Serum 5'-NPD-V value was elevated progressively in accordance with extent of liver involvement. When assessed by 5'-NPD-V and CEA, 80.9% of patients with liver metastases proved to be correctly diagnosed. The results suggest that 5'-NPD-V is clinically a useful marker in that the isoenzyme provides the rationale for the further detection of tumor localization in the liver.
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PMID:[Clinical study on serum 5'-nucleotide phosphodiesterase isoenzyme-V as a predictor of liver metastases in patients with gastric and colorectal cancers]. 301 74

Insulin (INS) stimulates, and diabetes inhibits, low Km cAMP phosphodiesterase (PDE). This mechanism, at least in part, accounts for the lowering of cyclic AMP levels in plasma and tissue of diabetic patients and animals. Phorbol, a tumor-promoting agent known to act through protein kinase C and calcium translocation, exhibits a powerful effect stimulating PDE in rat adipose tissue. Nifedipine, a calcium channel blocker, inhibits insulin, but not phorbol stimulated PDE. These data demonstrate new effects of inositide diacylglycerol-Ca++ pathway components on PDE and suggest some common pathways of activation of low Km cAMP PDE through insulin and phorbol esters.
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PMID:Activation of cyclic AMP phosphodiesterase by phorbol and protein kinase C pathway. 301 37

1,5-Dihydro-7-(1-piperidinyl)-imidazo[2,1-b]quinazolin-2(3H)-one dihydrochloride hydrate (DN-9693), a new c-AMP: phosphodiesterase inhibitor was examined for its inhibitory effects on platelet aggregation induced by metastasizing tumor cells and on blood-borne metastases of these tumors. 1-3 microM of DN-9693 completely inhibited platelet aggregation induced by B16 melanoma subline BL6 and Lewis lung carcinoma (3LL) cells. Platelets prepared from mice intravenously or orally administered with DN-9693 failed to aggregate after the addition of BL6 cells. Intravenous injection of DN-9693 was effective in protecting the mice inoculated with 1 X 10(6) BL6 cells against acute pulmonary embolic death. Either intravenous or oral administration of DN-9693 (1-10 mg/kg) sufficiently suppressed thrombus formation and subsequent pulmonary metastasis caused by intravenously inoculated BL6 or 3LL cells. Spontaneous pulmonary metastasis of 3LL was also inhibited by DN-9693. Continuous administration of DN-9693 during and after surgical excision of the primary tumors was the most effective treatment against the development of pulmonary metastases of 3LL.
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PMID:Effects of DN-9693, a new metastasis inhibitor, on murine hematogenous metastasis. 301 18

Studies with the pyrimido-pyrimidine analogue RA 233 (Rapenton) suggest that its antimetastatic action may not be mediated entirely by inhibition of platelet function. Little is known about its direct effects on tumor cells. We investigated the in vitro effects of RA 233 on clones MTLn3 and MTC of differing metastatic potentials, isolated from the 13762NF rat mammary adenocarcinoma. The results indicated that RA 233 is cytostatic (EC50 of approximately 140 microM and approximately 180 microM for MTLn3 and MTC cells, respectively) rather than cytotoxic by determining changes in viable cell number, thymidine uptake, and incorporation of thymidine and methionine. In both clones RA 233 inhibited cAMP-dependent phosphodiesterase activity and affected cAMP accumulation in intact cells. In contrast, clonal heterogeneity in drug-induced morphological changes, such as vacuole formation and altered organization of cytoskeletal structures, as well as increased tumor cell growth at 50 microM RA 233 was observed between clones MTLn3 and MTC. These data could explain the conflicting results obtained with RA 233 when evaluated as an antimetastatic agent.
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PMID:Direct effects of the pyrimido-pyrimidine derivative RA 233 (Rapenton) on rat 13762NF mammary tumor cell clones in vitro. 302 16

We have recently demonstrated that diethylstilbestrol (DES) significantly suppresses macrophage (M phi) activation by Propionibacterium acnes. Because the initial activation of M phi by P. acnes appears to involve the close interaction of the killed bacteria with inflammatory neutrophils (PMN) and resident M phi in the peritoneal cavity, we investigated whether the DES inhibition of M phi activation was associated with inhibition of the PMN response. Our data demonstrate that treatment of mice with DES did not interfere with the acute inflammatory peritoneal PMN influx 5 h after P. acnes injection. DES treatment also did not affect development of the early (day 4) tumor cytotoxic activity of P. acnes activated M phi; this M phi activity has been shown to be mediated by the acute PMN influx. DES treatment, however, did reduce M phi activation as evidenced by alterations in other markers typically associated with M phi activation by P. acnes, including the characteristic reductions in alkaline phosphodiesterase (APD) ectoenzyme activity and the total RNA synthesis, as well as the characteristic persistence of the peritoneal PMN response seen on days 4 and 7 after P. acnes injection. In addition, M phi activity 7 days after P. acnes injection was inhibited in DES treated mice, as evidenced by reduced antitumor activity, and alteration of the markers mentioned above. As a second approach to elucidate the involvement of the acute and persistent PMN response in the M phi activation process, we depleted mice of circulating PMN by treatment of mice with 89Sr before administration of P. acnes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutrophil involvement in effects of diethylstilbestrol and strontium 89 on macrophage activation by Propionibacterium acnes. 336 12

This study examined the platelet-aggregating and procoagulant activities of two hematogenously disseminating tumors, a mouse lymphoblastic leukemia (L5178Y) and a mouse renal adenocarcinoma (RAG). Tumor-induced human platelet aggregation was inhibited by addition of the following agents to platelet-rich plasma (PRP): a calcium channel blocker (verapamil), a chelator of divalent cations (EDTA), stimulators of adenylate cyclase (2-fluoroadenosine and forskolin), and inhibitors of cAMP phosphodiesterase (oxagrelate and papaverine). The platelet-aggregating activities of both cell lines were completely blocked by treatment of the cells with heat, sonication, phospholipase A2, and Triton X-100. These data suggest that L5178Y and RAG cell-induced human platelet aggregation are dependent on a heat-labile phospholipid component of the tumor cell membrane. L5178Y cells had greater platelet-aggregating activity in human plasma than in rat or mouse plasma, whereas RAG cells had greater procoagulant activity in rat or mouse plasma than in human plasma. The procoagulant activity of RAG cells in rat and mouse plasma was demonstrated by three lines of evidence: RAG cells induced heparinized PRP to clot; the thrombin inhibitor DAPA lengthened of the clotting time and the lag time before aggregation; and RAG cells shortened of the recalcification time of the plasma. The above data indicate that RAG cell-induced murine platelet aggregation and coagulation is dependent on thrombin generation.
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PMID:Murine tumor-induced platelet aggregation and coagulation: mechanisms, inhibitors, and species differences. 359 Jan 14

The pyrimido-pyrimidine derivatives RA 233 and RX-RA 85, which are potent inhibitors of platelet and tumor phosphodiesterase, were developed as antitumor agents. When tested by us, these drugs were cytostatic at low concentrations and produced dramatic changes in cell shape and organization of cytoskeletal structures in cultured MTF7 cells derived from the rat 13762NF mammary adenocarcinoma. At high concentrations (up to 600 micrograms/ml) RA 233 was cytostatic but not cytotoxic to MTF7 cells during a 24 hr incubation in vitro, whereas RX-RA 85 was cytotoxic at concentrations above 4 micrograms/ml. These drugs caused MTF7 cells to elongate and form numerous vacuoles, which surrounded the cell nucleus. Treatment of MTF7 cells with RA 233 or RX-RA 85 enhanced microtubular organization concomitant with a decrease in microfilament organization. In contrast, treatment of MTF7 cells with 1 mM dibutyryl cAMP resulted in an enhanced organization of microtubules but had no effect on microfilament organization. Previous studies suggested that RA 233 and RX-RA 85 increase cAMP levels in 2 other cell clones of rat 13762NF mammary adenocarcinoma by inhibiting phosphodiesterases. However, additional sites of drug action should also be considered based on the effects of these drugs on microfilament systems and cell vacuoles.
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PMID:The pyrimido-pyrimidine derivatives RA 233 and RX-RA 85 affect growth and cytoskeletal organization of rat mammary adenocarcinoma cells. 367 21

Putrescine, spermidine, spermine and two unknowns designated as A and B were detected in first seedling leaves of barley (Hordeum vulgare L. var. Wolfe). The levels of these polyamines in first seedling leaves from 4-day-old barley plants grown in darkness or in light were comparable and did not change significantly after exposure of dark grown plants to light for 24 h. No significant consistent changes in the amounts of above polyamines, except perhaps decline in spermidine, were noted during senescence of intact or excised first seedling leaves of barley and this spermidine decline was suppressed during retardation of senescence of excised leaves by 10 mg/l kinetin in the dark. In addition, putrescine, spermidine, spermine, cadaverine and diaminopropane (0.2 mM, 1 mM, 10 mM) had no effect on senescence of excised barley leaves in the dark and both spermine and spermidine induced bleaching of the leaves in the light. Both spermine and spermidine (approx. 10 mM) inhibited RNase and DNase activities but stimulated phosphodiesterase activity (assayed with bis-p-nitrophenyl phosphate as substrate) in crude soluble extracts from barley leaves. Purified snake venom phosphodiesterase activity assayed with RNA as substrate was, however, stimulated by 300-400% by 7-14 mM spermine or spermidine indicating similar possibilities for barley phosphodiesterase. These results together with the presence of multiple species of these enzymes and a decline in net soluble RNase and DNase activities during senescence in barley leaves reported previously, make it unlikely that inhibition of RNase activity in vitro by polyamines could be correlated with their effect on senescence. Putrescine, spermidine and spermine were detected in normal and crown gall tumor tissue cultures of tobacco (Nicotiana tabacum var Wisconsin 38) and in tobacco mosaic virus (TMV)-infected freshly excised pith tissue from tobacco which represented non-proliferating tissue. The level of all three polyamines was several-fold higher in cultured tissues compared to the non-dividing freshly excised pith tissue and the tumor cultures had several-fold higher spermidine and putrescine respectively compared to normal tissue cultures. These results indicate high levels of polyamines in growing tissues but no consistent pivotal changes in polyamines during senescence. The results also do not support polyamines being natural anti-senescent compounds in plants or that their anti-senescent compounds effect could result from inhibition of RNase activity.
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PMID:Polyamine changes during senescence and tumorogenesis in plants. 369 90

Hematoporphyrin derivative (HPD) plus photoradiation caused the inactivation of DNA polymerases from calf thymus and R3230AC rat mammary tumor. Photosensitization of purified DNA polymerase-alpha as well as two forms of DNA polymerase-delta (I and II) from calf thymus were evaluated. Although all polymerase enzyme forms were inactivated at 70 micrograms HPD/ml, DNA polymerase-delta II was the most sensitive, displaying a 90% inactivation under conditions that did not cause significant inactivation of the other polymerase forms. Unlike DNA polymerase-alpha, the delta-forms have an associated 3'- to 5'-exonuclease activity. The exonuclease associated with DNA polymerase-delta II was uniquely sensitive to a low level of HPD and light exposure. DNA polymerase-delta II can be distinguished from other polymerase forms in cell extracts by its relative insensitivity to the polymerase inhibitor N2-(p-n-butylphenyl)deoxyadenosine 5'-triphosphate. In cytosols prepared from calf thymus and R3230AC rat mammary tumors, DNA polymerase-delta II was preferentially inhibited by HPD plus light. Furthermore, in experiments in which tumor-bearing rats were administered HPD prior to preparation of tumor cytosols, DNA polymerase-delta II was specifically inactivated by exposure to light. These results are discussed in view of their possible role in cancer therapy, and the potential use of HPD as a specific inhibitory agent of DNA polymerase-delta II is suggested.
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PMID:Inhibition of mammalian DNA polymerases by hematoporphyrin derivative and photoradiation. 394 Jan 88

Culture fluids from mouse peritoneal exudate cells inhibited [(3)H]thymidine incorporation by, and proliferation of, EL-4 leukemia cells, 3T3 cells, and mitogen-stimulated spleen lymphocytes. Inhibited EL-4 leukemia cells recovered their normal proliferative capacity when washed and incubated in normal medium. The inhibitory activity resided in a low-molecular-weight substance that could be absorbed by incubation with the tumor cells. This substance was dialyzable and resistant to tryptic digestion and phosphodiesterase treatment. The mononuclear phagocytes in the peritoneal exudate seemed to be the source of the inhibitor. The inhibitory material was found in the same amounts in exudates of normal mice or mice injected with peptone or infected with Listeria monocytogenes; spleen cells adherent to plastic released the inhibitor but in lesser amount. We suggest that this inhibitor may contribute to the deleterious effects found when various cells, including neoplastic ones, are cultured in the presence of macrophages.
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PMID:An inhibitor of cell proliferation released by cultures of macrophages. 421 17


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