Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of fluorocarbon-based oxygen carriers has experienced rapid progress over the past few years. Fluosol has been approved for use during percutaneous transluminal coronary angioplasty (PTCA) for high-risk patients. Its clinical evaluation is being pursued as an adjunct to cancer therapy and for treatment of myocardial infarction in conjunction with thrombolytic therapy. O2-delivery efficacy has been achieved with the development of the new highly concentrated (4 to 5 times more concentrated than Fluosol), fluid, emulsions of perfluorooctyl bromide (perflubron), trade-named Oxygen. The stability of fluorocarbon emulsions has also improved considerably and the new emulsions can be stored unfrozen and are ready for use. The side-effect profile of these emulsions has been characterized as being the normal response of the body's phagocytes to the injection of particles, a response that is considered physiological rather than pathological in nature; it involves some products of arachidonic acid metabolism and can be controlled pharmacologically. Means of further stabilizing fluorocarbon emulsions, involving molecular-diffusion-controlling additives or fluorinated surfactants, including mixed fluorocarbon-hydrocarbon compounds, have been devised. Increased control over in vivo particle recognition, intravascular persistence and side effects, and at adapting emulsion characteristics to specific applications, is being investigated. The range of therapeutic applications is expanding. The concentrated emulsions will be able to serve as a temporary red blood cell substitute in many situations. Acute normovolemic hemodilution with fluorocarbon emulsions, used in conjunction with homologous predonation and other blood-sparing techniques, should afford greater flexibility, increase the margin of safety, and reduce or alleviate the need for autologous blood transfusion during surgical procedures. Fluorocarbon applications in the cardiovascular field include use during PTCA, for cardioplegia and reperfusion, and the treatment of myocardial infarction. Significant tumor growth delay has been achieved when concentrated emulsions are used in conjunction with cancer radio- or chemotherapy. Liquid ventilation has potential as a unique treatment for the adult and infant respiratory distress syndromes and for drug delivery. The radiopaque and versatile perflubron can also be used in contrast agents for diagnosis with computed X-ray tomography, magnetic resonance imaging and ultrasound, allowing the early detection and staging of cancer. Other potential applications investigated include the treatment of cerebral ischemia, organ and limb preservation, use as a tamponade during retinal repair, etc.
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PMID:Overview of progress in the fluorocarbon approach to in vivo oxygen delivery. 139 34

Many anticancer drugs require oxygen to be cytotoxic or are selectively cytotoxic toward cells under oxygenated conditions. The effects of the dilute perfluorochemical emuolsion Fluosol with a wide variety of chemotherapeutic agents have been explored; however, it has not been possible to determine the optimal level of circulating perfluorochemical emulsion with anticancer drugs because the volume of Fluosol that may be administered is limiting. Using a new concentrated perfluorochemical emulsion, a wide range of perfluorochemical doses has been examined in combination with melphalan, cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in the FSaIIC fibrosarcoma. When the perfluorochemical emulsion was administered by injection i.v. just prior to the injection of melphalan (10 mg/kg), cyclophosphamide (150 mg/kg) or BCNU (50 mg/kg), the greatest tumor growth delays were obtained with dosage levels between 4 g and 12 g of the perfluorochemical perfluorooctyl bromide/kg. With each drug the greatest tumor growth delays were obtained when the drug was prepared in the emulsion and the combination injected i.v. In each case, each dose of drug was followed by 6 h of breathing carbogen. The addition of the perfluorochemical emulsion/carbogen breathing to treatment with melphalan, BCNU or cyclophosphamide resulted in significant increases in the killing of tumor cells by these drugs without a concomitant increase in toxicity to bone marrow granulocyte/macrophage-colony-forming units. In each case, preparing the drug in the perfluorochemical emulsion was most effective. These results indicate that clinical trial of this perfluorochemical emulsion/carbogen breathing in combination with cancer chemotherapy may be warranted.
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PMID:A new concentrated perfluorochemical emulsion and carbogen breathing as an adjuvant to treatment with antitumor alkylating agents. 162 42

There is no effective therapy for human malignant mesothelioma, and its susceptibility to recombinant cytokines has not been studied extensively. Recombinant human tumor necrosis factor alpha (rHuTNF alpha) was evaluated for its in vitro and in vivo antitumor activity using a human malignant mesothelioma cell line [DeH128(m)], both in culture and heterotransplanted in nude mice. In vitro, rHuTNF alone had no direct antimesothelioma activity assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, but in combination with the transcription inhibitor, dactinomycin (AD), mesothelioma cell metabolic activity was inhibited (80% of control). The effects of this combination of agents were studied on DeH128(m) cells heterotransplanted as subcutaneous tumors in nude mice. In vivo there was no significant inhibition of tumor growth by combined rHuTNF alpha and AD therapy, but the combination produced marked cachexia in doses at which each component (rHuTNF alone or AD alone) was well tolerated. The authors conclude that the well-described in vitro interaction between AD and rHuTNF also operates in vivo to produce cachexia and that the combination of these two agents is likely to have a low therapeutic index in malignant mesothelioma.
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PMID:Interaction between dactinomycin and tumor necrosis factor in mesothelioma. Cachexia without oncolysis. 201 49

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.
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PMID:[Antitumor effect of a benzoylphenylurea derivative HO-221]. 226 Aug 71

Inhibition of angiogenesis offers an alternative approach to cancer chemotherapy, since solid tumor growth has an absolute dependency on angiogenesis. We have previously shown that 8,9-dihydroxy-7-methyl-benzo [b]quinolizinium bromide (GPA1734) is a basement membrane synthesis inhibitor, and that this compound acts as an antiangiogenic agent in the chick chorioallantoic membrane. When a piece of 10 mg from a Walker 256 carcinoma was implanted into the peritoneal cavity of rats, tumor grew to about 15 g within nine days after transplant. Daily treatment of Walker 256 carcinoma bearing animals with GPA1734, at doses 10-100 mg/kg intraperitoneally, restrained tumor growth in a dose dependent manner. Macroscopic examination showed tumor cells growing in spherical masses 5-8 mm in diameter, indicative of absence of neovascularization. GPA1734 at 300 microM had no direct effect on Walker 256 carcinoma cell culture growth. The antitumor effect of this agent on Walker 256 carcinoma may be related to its antiangiogenic properties.
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PMID:Antitumor effect of GPA1734 in rat Walker 256 carcinoma. 238 1

alpha-Carboline and its several derivatives have been synthesized and evaluated for their antitumor activity against L1210 lymphoid leukemia, P388 lymphocytic leukemia and Sarcoma 180. It was found that of these compounds only alpha-carboline and its derivatives substituted in C-4 position with a methyl group or in 6-C position with a methyl group and fluorine or chlorine atoms caused moderate inhibition of the tumor growth of Sarcoma 180. The introduction of bromide, iodide atoms, hydroxy-, amino-groups or some other substituents in C-6 position of alpha-carboline molecule reduced significantly the biological activity of the tested compounds against Sarcoma 180. Additionally, the introduction of an ethyl or ethoxycarbonyl group to the pyrrole ring at N-9 also obliterated antitumor properties of these analogues. None of the tested compounds displayed a significant activity against murine leukemias. In the cytotoxicity test of KB cells all the compounds were inactive.
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PMID:Antineoplastic activity of azacarbazoles. I. Synthesis and antitumor properties of alpha-carboline and its selected derivatives. 359 35

The reaction of nucleophilic substitution of 14-bromine derivatives of carminomycin and rubomycin with respective nitrogen-containing heterocycles yielded six novel derivatives of carminomycin and rubomycin: 14-N-imidazolyl-carminomycin, 14-carminomycyl-N-pyridinium bromide, 14-carminomycyl-N-(3-aminocarbonyl)-pyridinium chloride, 14-rubomycyl-N-(3-amino-carbonyl)-pyridinium chloride, 14-N-succinimidocarminomycin and 14-N-succinimidorubomycin. In vitro and in vivo antitumor activity of the above derivatives and three other derivatives described earlier: 14-rubomycyl-N-pyridinium bromide, 14-N-imidazolylrubomycin and 14-N-phthalimidorubomycin was studied. It was shown that in vitro all the 9 semisynthetic derivatives had a lower (by 1.5-6 times) cytostatic action on murine lymphadenosis cells NK/LI as compared to the initial antibiotics. The in vivo experiments on mice revealed that by acute toxicity the rubomycin derivatives administered intravenously were close to rubomycin, whereas the toxicity of the analogous derivatives of carminomycin was 5-17 times lower. The in vivo experiments also showed that seven out of the nine 14-N-substituted derivatives of carminomycin and rubomycin were practically deprived of antitumor activity (strain LIO-1), while 14-carminomycyl-N-pyridinium bromide and 14-N-succinimidocarminomycin inhibited the tumor growth by 40-60 per cent.
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PMID:[Synthesis and antitumor action of 14-N-substituted derivatives of rubomycin and karminomycin]. 363 31

A new artificial blood substitute, FOB, which has been shown to be a good solvent for oxygen, contains a Bromine atom within its molecule. FOB is taken up in tumor macrophages and the Bromine shows opacity on X-ray film by absorbance of X-rays. In this study, tumor imaging possibilities were studied using conventional roentgenograms, on mice bearing transplanted Ehrlich ascites tumors on the right leg and which were given a 1-ml injection of 50 w/v % FOB. The results obtained follows: Solid Ehrlich tumors were imaged clearly wih injected FOB. X-ray films showed persisting homogeneous tumor staining, and irregular linear and plaque opacities. Larger tumors (more than 5,000 mm3 in volume) were imaged less clearly than smaller ones (about 1,000 mm3 in volume), because of superimposition of X-ray absorbance of the FOB taken up and of the larger tumor mass itself. The patterns of FOB taken up into the transplanted tumor were different according to various tumor growth time. Tumor imaging effect was enhanced by double time injection of 1 ml FOB. Histological features of Ehrlich tumors injected with FOB showed that FOB was phagocytosed by macrophages in the tumor tissue. The radiosensitization effect of FOB has already been reported by us. These results suggested that FOB acts not only as a sensitizer in radiation therapy, but also as a tumor imaging agent for diagnosis of the localization of malignancy in radiotherapeutic planning.
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PMID:[Tumor imaging with conventional X-ray using a new artificial blood substitute (perfluoroctylbromide emulsion, FOB)]. 648 37

A promising new therapeutic modality for skin cancer, administration of the heme precursor 5-aminolevulinic acid followed by light irradiation, is known as photodynamic therapy. Photofrin, the only clinically approved sensitizer, has an absorption maximum at 630 nm, the wavelength used in most experimental and clinical trials with 5-aminolevulinic acid. We investigated photodynamic efficacy of irradiation with coherent light at wavelengths ranging from 622 to 649 nm in vitro and in vivo as well as the content and distribution of intracellular porphyrin after administration of 5-aminolevulinic acid. HaCaT immortalized human keratinocytes were sensitized with 30 micrograms/ml 5-aminolevulinic acid for 24 h in vitro. By cell viability determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, the best cell-killing effects were observed after irradiation at 635 nm. Using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, we confirmed these results in vivo: tumor growth was markedly delayed in animals treated with 100 mg/kg 5-aminolevulinic acid intravenously and irradiated with coherent light at 635 nm as compared to animals irradiated at 630 nm. This photodynamic effect is probably mediated by large amounts of the photosensitizing porphyrin, protoporphyrin IX, localized in cell membranes as visualized by confocal laser scan microscopy and as determined by high pressure liquid chromatography in vitro. The results suggest that irradiation at 635 nm with a coherent light source is more effective than irradiation at 630 nm for photodynamic therapy with 5-aminolevulinic acid.
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PMID:Wavelength dependency of photodynamic effects after sensitization with 5-aminolevulinic acid in vitro and in vivo. 759 42

Basement membrane (BM) exerts profound influence on endothelial cell (EC) behavior. In addition BM is a structural element of blood vessels; in fact at some point of their formation blood vessels are bare EC tubes lined with the BM produced by these EC. We thought, therefore, that a quantitative relationship must exist between the rate of BM synthesis and angiogenesis, and that interfering with BM synthesis must have an effect on angiogenesis. This was found experimentally in the chick chorioallantoic membrane (CAM) system. It was shown that the rate of BM collagen biosynthesis can serve as a biochemical index of angiogenesis and that inhibitors of BM synthesis prevent angiogenesis. GPA 1734 (8,9-dihydroxy-70-methyl-benzo(b)quinolizinium bromide), which inhibits proline and lysine hydroxylations in type IV collagen formation, suppresses angiogenesis in the CAM. Similarly, D609 (tricyclodecan-9-yl-xanthate), which inhibits BM synthesis by an as yet unknown mechanism, also prevents angiogenesis. Structurally related analogs of GPA 1734 and D609 that have no effect on BM biosynthesis are also without effect on angiogenesis. The aforementioned inhibitors of angiogenesis GPA 1734 and D609 have a dose-dependent inhibitory effect on tumor growth in rats bearing Walker 256 carcinosarcoma, without any obvious toxic effects. This effect is probably related to angiosuppression, since structurally related analogs that do not inhibit angiogenesis are without antitumor properties. Also GPA 1734 and D609 have no direct cytotoxic effects on Walker 256 cells in vitro. These results suggest that a search for agents that are specific inhibitors of BM synthesis may provide novel angiosuppressors with potential application in tumor chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Basement membrane biosynthesis as a target for developing inhibitors of angiogenesis with anti-tumor properties. 767 56


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