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)

Urine specimens obtained from 19 patients with primary brain tumors were examined for the activity of transforming growth factors (TGF's). Urine was assayed for TGF's by soft agar colony formation and iodine-125 (125I)-epidermal growth factor (EGF)-binding competition. Two nontransformed cell lines, clonal NRK49F and BALB/3T3 A31-1-1 cells, were used as indicator cells for the soft agar colony assay, while EGF receptor-rich A431 cells were used for 125I-EGF-binding competition assay. Urine samples were dialyzed against acetic acid, then lyophilized, prepared with gel-permeation chromatography, and assayed. All 19 patients and a control group of healthy individuals showed high levels of alpha-type TGF's with low molecular weight (4 to 8 kD) in all urine samples. In addition, alpha-type TGF's of high molecular weight (20 to 50 kD) were detected at high levels in urine from all 10 patients with high-grade astrocytoma; at intermediate levels in urine from one of two patients with low-grade astrocytoma and from two of four patients with meningioma; and at low levels in urine from one of two patients with low-grade astrocytoma, from two of four patients with meningioma, from one patient with oligodendroglioma, from two patients with neurinoma, and from all healthy control individuals. The high level of alpha-type TGF's with high molecular weight detected in urine from patients with high-grade astrocytoma could be useful as a tumor marker.
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PMID:Transforming growth factors in urine from patients with primary brain tumors. 325 33

The investigational drug flavone-8-acetic acid (FAA) potently augments NK activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner after i.v. or i.p. administration. Augmented NK activity peaks by 24 h after FAA injection and returns to normal after 6 days. Combined treatment of established murine renal cancer with FAA and rIL-2 results in up to 80% long term survival whereas FAA or rIL-2 alone were unable to induce any long term survivors. The optimal dose of rIL-2 required for use with FAA was in the range of 10,000 to 30,000 U/day. Further studies demonstrated that the regimen of FAA plus rIL-2 administration that was effective in treating established murine renal cancer also induced a more potent augmentation of NK activity than did either FAA or rIL-2 alone. Subsequent studies revealed that the therapeutic effectiveness of FAA plus rIL-2 was significantly reduced when tumor-bearing mice were treated with anti-asialo GM1 serum. These results are consistent with a role for augmented NK activity in the therapeutic effects of FAA plus rIL-2 murine renal cancer. In addition, these studies demonstrate that FAA and rIL-2 is a useful approach for cancer treatment in that subtoxic doses of rIL-2 can be used and significant anti-tumor efficacy occurs even without accompanying adoptive immunotherapy.
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PMID:Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer. 325 94

White-type polysaccharide preparation (WPS) obtained from Serratia marcescens bacteria by hot 0.2 N acetic acid extraction was shown to have antitumor effects. These were manifested by enhanced resistance to the take of TA3 transplantable murine adenocarcinoma and by the induction of regression of Meth A sarcoma in mice. Optimal conditions for the liberation and isolation of these substances were sought to achieve the highest antitumor activity and the lowest endotoxin (ET) content. Simultaneously, the activities of the WPS preparations were tested in various tests which are frequently used as in vitro correlates of in vivo antitumor effects, such as the activation of macrophage cytotoxicity, activation of natural killer (NK) cells, and tumor necrosis factor (TNF) generation. We found that the enhanced resistance to the take of TA3 tumor correlated with ET content of the WPS preparations. Preparations with reduced or no ET content showed diminishing activity in this assay or were without any measurable effect. The induction of TNF production and NK activation did not show such close relationship with the ET content. This was particularly evident if testing WPS samples obtained after 60 or 120 min hydrolysis at 90 degrees C. The greatest discrepancy was found between ET content and the Meth A regression induction. Samples with no detectable ET content and no activity in the macrophage, NK, or TNF tests were potent inducers of Meth A regression. Partial purification of such WPS samples could be achieved and a preparation was obtained with high Meth A regression capacity. Preliminary chemical analysis of this preparation showed 25.5% amino acid, 53.7% neutral carbohydrate, less than 0.4% KDO, 0.8% hexosamine, less than 0.1% phosphorous, and less 1.0% long-chain carboxylic acid content. The above chemical analytical data are not consistent with designating such preparations as ET or ET derivatives, such as Lipid A or its split products. This conclusion was confirmed by the lack of endotoxic properties as determined by biological assays on this preparation.
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PMID:Isolation of a nonendotoxic antitumor preparation from Serratia marcescens. 329 7

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.
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PMID:Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging. 331 95

Flavone-8-acetic acid (FAA), a new antitumor agent currently undergoing clinical trial, fails to inhibit the growth of early stage Lewis lung (LL) tumors growing in the lung. However, the growth of advanced subcutaneous tumors, arising from inoculation of either the original in vivo LL line or a tissue culture-adapted cell line (LLTC) derived from the LL line was delayed significantly by FAA treatment. Comparison, by clonogenic survival assays, of the cytotoxic effect of FAA on LLTC cells demonstrated that most cell killing occurred between 2 and 8 hours following in vivo exposure but occurred to a much lesser extent and at later times following in vitro exposure. FAA was inactive against LLTC cells growing in vivo in diffusion chambers, suggesting that a host cellular component was necessary for activity. FAA was found to induce hemorrhagic necrosis in the advanced LL tumors, as well as in a number of human tumor xenografts growing in athymic mice. The human cell lines from which the xenografts were derived, as well as the LL tumor lines and P388 leukemia lines, were inhibited by FAA in vitro. However, the ranking of FAA activity in vivo did not parallel that observed in vitro. Together, these observations strongly suggest that FAA has an indirect mode of antitumor action.
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PMID:Effect of flavone acetic acid on Lewis lung carcinoma: evidence for an indirect effect. 335 60

Ethanol was found to alter functioning and numbers of lymphoid cells of the cellular immune system in humans and rats. In in-vitro studies on human lymphocytes, a higher than 0.1% concentration of ethanol and acetaldehyde and acetic acid, the metabolites of ethanol, caused a decrease in the formation of E-rosettes. Methanol and propanol also resulted in a decrease in E-rosette formation. The natural killer (NK) cells varied in their ability to lyse tumor cells. In vitro, the NK-cell activity declined at higher than 0.2% concentration of ethanol. The NK activity in cells isolated from spleen and thymus of rats fed 1 g/dl or 7 g/dl ethanol did not differ significantly from the controls. Sprague Dawley rats fed 1 g/dl or 7 g/dl ethanol for 12 weeks had a significantly smaller thymus compared to the controls. Alveolar macrophages isolated from the rats exhibited impaired phagocytic activity. In agreement with other investigators, ethanol was found to result in a loss of T-cell population in the spleens of rats fed ethanol for 13 months. On the other hand, the T-helper cells and the proportion of T-helper to T-suppressor cells were found to increase in the splenocytes from these rats. This latter occurrence, apparently, is to compensate for the general loss of T-cell population observed in the body that occurs with ethanol ingestion. It is hypothesized that immunosuppression and the transient imbalances in the components of the cellular immunity induced by ethanol lead to an increased risk of pathogenesis associated with alcohol consumption.
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PMID:Functional and numerical alterations induced by ethanol in the cellular immune system. 337 29

The probe--mediated intragastric injection of 50 mg/kg ethyl ether of N-nitrososarcosine (EENS) 5 times a week for 6 months was followed by the development of multiple tumors in 91.8% of 120 noninbred male rats supplied by a local animal farm: esophagus--85.7%, fore-stomach--73.4% and throat--22.4%. The lesions in the esophagus and the fore-stomach entry were similarly frequent (61.2-75.5%) which was matched by a much lower incidence rate (22.4%) for the remaining parts of the fore-stomach. The combined intragastric injection of 3% acetic acid (0.5 ml thrice a week) for 8 months and EENS for 6 months boosted the total frequency of neoplasms to 100% and resulted in increased multiplicity of tumor--from 9.8--10.7 for EENS alone to 14.5 for EENS + acetic acid. Most lesions occurred in the fore-stomach entry as far as the level of tumor (squamous cell carcinoma and papilloma) development, frequency and relative risk (number of tumors. v. actual number of animals) are concerned. A long--term treatment with 3% acetic acid alone was followed by chronic inflammation of the esophageal mucosa rather than tumor development.
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PMID:[Stimulating effects of 3% acetic acid on the induction of esophageal tumors in rats]. 338 1

Tumor cells produce a variety of hormones and growth factors that are associated with modulation of the growth pattern of malignant cells. Hs294T human malignant melanoma cells produce a monolayer mitogen, melanoma growth stimulatory activity (MGSA), that stimulates the growth of Hs294T cultures in serum-free medium. MGSA has been purified to homogeneity from conditioned medium of Hs294T human malignant melanoma cells using acetic acid extraction of the crude conditioned medium followed by three chromatographic processes, including gel-filtration, heparin-Sepharose, and reverse-phase HPLC. MGSA was eluted from the heparin-Sepharose resin with 0.1-0.3 M NaCl. The binding affinity is similar to that of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) but much less than many endothelial cell-derived growth factors which require significantly higher salt concentrations for elution. These procedures resulted in a final yield of purified MGSA that was significantly greater than yields obtained using previously reported procedures. The homogeneous 16,000 and 13,000 molecular weight moieties obtained by means of these procedures exhibited similar bioactivities (stimulating a 2- to 3-fold increase in Hs294T cell growth) over a 0.06-6 ng concentration range. This bioactivity was progressively inactivated during storage at -80 degrees C. These results indicate that the combination of heparin-Sepharose chromatography and reverse phase-HPLC provides a more efficient means of purification of MGSA.
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PMID:High yield purification of melanoma growth stimulatory activity. 339 57

The investigational drug flavone acetic acid (FAA) systemically augments natural killer (NK) cell activity in normal and tumor-bearing mice and in human cancer patients. The results from the present investigation demonstrate that in vivo administration of FAA induces in a dose-dependent manner high levels of serum interferon (IFN) within 4 hours in BALB/c, C57BL/6, and BALB/c nude mice. Antibody neutralization studies indicated that FAA induced IFN of the alpha/beta type, while molecular hybridization studies demonstrated that FAA rapidly stimulated the production of IFN alpha mRNA in splenic leukocytes. In vivo administration of anti-IFN alpha/beta antibodies to FAA-treated mice inhibited the FAA-induced augmentation of splenic NK cell activity at 4 hours. These results suggest that FAA mediates its anti-tumor effects indirectly by immunomodulation as well as directly by antiproliferative or cytotoxic activity.
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PMID:Immunomodulation of natural killer cell activity by flavone acetic acid: occurrence via induction of interferon alpha/beta. 341 28

The transfer of specific Ti (tumor-inducing) plasmid sequences, the T-DNA, from Agrobacterium tumefaciens to a wide range of plants results in the formation of crown gall tumors. These tissues differ from most plant cells in that they can be grown in vitro in the absence of added phytohormones. Here, data are presented that offer an explanation for the auxin-independent phenotype of crown gall tissues. It is shown that crude cell-free extracts prepared from three bacterial species harboring pTiA6 gene 1 could convert L-tryptophan to indole-3-acetamide; control extracts lacking gene 1 could not carry out the reaction. Other reports indicate that the pTiA6 gene 2 product can convert indole-3-acetamide to indole-3-acetic acid, a naturally occurring auxin of plants. It is concluded that the auxin-independent phenotype of crown gall tissue involves the introduction of Ti plasmid sequences encoding a two-step pathway for auxin synthesis.
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PMID:Molecular basis for the auxin-independent phenotype of crown gall tumor tissues. 351 28


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