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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor agent flavone-8-acetic acid (FAA) is remarkable because it induces hemorrhagic necrosis, altered tumor blood flow, and cytokine synthesis. We show here that FAA and structurally related analogues increase plasma nitrite plus nitrate (NO2-/NO3-) levels in mice. Dose-dependent increases in plasma NO2-/NO3- concentrations, which reached maximum levels at 12 h, were found following administration of FAA. Furthermore, the presence of a palpable s.c. Colon 38 tumor significantly enhanced the response. Tumor-dependent increases were also observed with the active FAA analogues xanthenone-4-acetic acid, 5-methyl XAA, and 5,6-dimethyl XAA, while the inactive analogue 8-methyl XAA failed to increase plasma NO2-/NO3- concentrations substantially above basal levels. Increased plasma NO2-/NO3- levels were also observed in response to endotoxin (100 micrograms/mouse) and to recombinant human tumor necrosis factor alpha (4 to 16 micrograms/mouse). NO2-/NO3- levels may signify nitric oxide production as a result of stimulation of the L-arginine-dependent pathway in activated macrophages. The tumor dependence of the response may reflect the immunological stimulus imposed by tumor implantation. A clear relationship was found between increased plasma NO2-/NO3- levels and tumor growth delays induced by FAA and xanthenone-4-acetic acid analogues. It is suggested that nitric oxide may contribute to tumor cell death by two mechanisms, alteration of blood flow contributing to tumor ischemia and direct tumor cell killing. Plasma NO2-/NO3- concentrations may be a sensitive indication of the antitumor response to this class of compounds.
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PMID:Tumor-dependent increased plasma nitrate concentrations as an indication of the antitumor effect of flavone-8-acetic acid and analogues in mice. 198 9

We have developed an isolated perfused tumor model to study the metabolism of solid tumors by nuclear magnetic resonance spectroscopy. Morris hepatomas (7777) were implanted in the inguinal region of Buffalo rats, such that they developed an isolated blood supply. These tumors were perfused with a RBC perfusate, removed from the animal, and studied by 31P nuclear magnetic resonance spectroscopy. ATP levels, as determined from the spectra, were stable for as long as the tumors were maintained in the magnet (7 h) only if the perfusate contained inosine, adenosine, and insulin. The adenosine and inosine were also required for recovery from ischemia. Under these conditions, ischemia did not result in a change in tumor pH. The gamma nucleoside triphosphate resonance was significantly larger than the beta nucleoside triphosphate resonance in spectra of some of the perfused tumors, suggesting that ADP above about 300 nmol/g wet weight was not complexed in these tumors. The adenylate levels determined from extracts, O2 consumption, histology, and 31P nuclear magnetic resonance spectra of extracts of perfused tumors and tumors in situ were all similar, indicating the perfused tumor is a reasonable model of the tumor in vivo.
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PMID:An ex vivo model for the study of tumor metabolism by nuclear magnetic resonance: characterization of the phosphorus-31 spectrum of the isolated perfused Morris hepatoma 7777. 198 24

Three isomeric series of 2-(aryloxy)-2-methylpropionic acids were prepared and studied for their ability to decrease the oxygen affinity of human hemoglobin A. The isomeric aryloxy groups included 4-[[(aryloyl)amino]methyl]phenoxy, 4-(arylacetamido)phenoxy, and 4-[[(arylamino)carbonyl]methyl]phenoxy. A total of 20 compounds were synthesized and tested. Structure-activity relationships are presented. Several of the new compounds were found to be strong allosteric effectors of hemoglobin. The two most active compounds are 2-[4-[[(3,5-dichloroanilino)carbonyl]-methyl]phenoxy]- 2-methylpropionic acid and the corresponding 3,5-dimethyl derivative. The latter two compounds have been compared to other known potent allosteric effectors in the same assay and show greater activity. Both compounds also exhibit a right shift in the oxygen equilibrium curve when incubated with whole blood. The new compounds may be of interest in clinical or biological areas that require or would benefit from a reversal of depleted oxygen supply (i.e., ischemia, stroke, tumor radiotherapy, blood storage, blood substitutes, etc.). They are also structurally related to several marketed antilipidemic agents.
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PMID:Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents. 199 97

Blood flow was measured in intratumoral tissue, the cerebral hemispheres and particularly in the peritumoral area of 12 patients with intracranial meningiomas using the stable xenon-enhanced computed tomographic scan. Tumor blood flow frequently showed a heterogeneous pattern of enhancement with high flow at the tumor periphery and a central area of hypoperfusion. Blood flow values were on average 28% lower in the peritumoral area than in the ipsilateral cerebral hemisphere. In individual cases, blood flow values in the peritumoral edematous area were very low. These findings suggest that the hypodense area surrounding meningiomas does not solely represent vasogenic edema, but may actually represent tumor pressure ischemia.
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PMID:Peritumoral blood flow in intracranial meningiomas. 201 Dec 22

Starting from the assumption that tumor cells constantly experience transient ischemia and anoxia, and that this results in metabolic stress which is reflected above all, on the concentration of ATP, ADP and AMP, in other words, the adenine nucleotide pool (AdN), the aim of our research was to study the degradation and resynthesis kinetics of that pool on two types of malignant cells. All experiments were conducted in vitro with cells of the transplantable tumors of Ehrlich's ascitic carcinoma and the AS 30D hepatoma, and metabolite analyses were carried out enzymatically or by way of the HPLC chromatography method. It was found that immediately after the setting on of anoxia, there comes not only to a fall in ATP, but also to a fall in the complete adenine nucleotide pool for about 50%. The further maintenance of anaerobiosis does not have a significant influence on the AdN pool. The adenine nucleotide pool resynthesis is very rapid in the examined cells, and in the presence of glutamine and inosine, there comes to an occurrence of its significant growth. Evidence is given that the resynthesis in Ehrlich's ascitic carcinoma cells is made possible through the purine nucleotide cycle, which probably brings about the intensive glutamine oxidation and aspartate production, while in the AS 30D hepatoma cells it develops by means of adenosine kinase. The AS 30D hepatoma cells maintain a high ATP level in the absence of oxygen for a long time, provided that iodine-acetate is not added, which points to the fact that they have some other kind of energetic reserve aside from ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Kinetics of degradation and resynthesis of the adenine-nucleotide pool in tumor cells]. 209 81

Hepatic metastases rather than the primary neoplasm usually dictate the course of the disease and patient's survival. For unresectable disease, intraarterial infusion of chemotherapy, embolization, and chemoembolization are viable alternatives. Intraarterial therapy for hepatic metastases is based on the dual blood supply of the normal liver (portal vein, 75%, and hepatic artery, 25%) and that of the tumors (hepatic artery, 90%). Intraarterial infusion delivers a higher concentration of chemotherapy, whereas chemoembolization adds ischemia and increased contact time with the tumor. Selective vascular occlusion for infusion, redistribution of the blood supply and pulsatile flow enhance the delivery of therapeutic agents to the liver.
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PMID:Hepatic artery infusion and chemoembolization in the management of liver metastases. 212 43

So far two methods for prolonging the tolerance of renal ischemia are available: 1) surface cooling with crushed ice and 2) perfusion cooling with an extracellular-like solution. Both methods use only the principle of reducing metabolism through cooling. While rewarming during surgery the ischemic protection is lost, or the kidney must be cooled once again. Therefore, a new preservation solution should reduce energy consumption due to its composition in addition to cooling. For open heart surgery, the HTK solution by Bretschneider is already used clinically. In 71 dog kidney experiments, the ischemic time kidneys could tolerate was prolonged by this solution from 15 to 120 min at 35 degrees C and from 45 to 360 min at 25 degrees C. After 2 h of ischemia at 30 degrees C glomerular filtration rate was about 20 ml/min.100gww within 3 h of reperfusion. After six postoperative days the filtration rate was 40 ml/min.100 gww. No ischemic damage could be recognized by histological investigations. The clinical effectiveness of this method was shown in 7 clinical applications. Ischemic duration lasted up to 113 min, and blood creatinine was between 0.8 and 2.4 mg% at the 6th postoperative day. Use of this preservation technique thus leads to improved kidney function immediately following operation. Longer ischemia can be tolerated by a kidney thus protected, and using this technique excellent visibility can be achieved during intrarenal surgery, simplifying, for example, tumor extirpation.
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PMID:A new method for conservative renal surgery--experimental and first clinical results. 212 22

Arterial tumor embolism is a rare occurrence. We report such an embolus causing acute limb ischemia which was the first indication of malignancy in a patient who subsequently proved to have malignant melanoma.
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PMID:Acute limb ischemia due to arterial embolism of tumor. 212 95

The acute effects of photoradiation after administering hematoporphyrin derivative (Hpd) on capillary blood flow were studied in intrahepatic tumors and normal liver. The tumors were solitary Walker carcinosarcomas implanted within the livers of Sprague-Dawley rats. Capillary flow was measured by a laser doppler monitor with its probe positioned over the tumor or over normal liver. Within a minute after intraportal Hpd injection (1.7 mg), capillary flow in the tumors began to decrease. Minimal levels of flow were maintained for as long as 15 minutes after Hpd injection with no observed recovery of flow back to control levels. Ratio of minimal flow/control flow averaged 0.36. Similar results were seen in studies on normal liver tissue. These studies demonstrate the extremely rapid vasoactive effects caused by photoradiation of Hpd. Vasoconstriction, vascular stasis and ischemia have proven to be important mechanisms in producing tumor cell destruction by photodynamic therapy.
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PMID:The acute effects of hematoporphyrin derivative photoradiation on tumor and liver capillary blood flow. 214 62

Excitotoxin-induced neural tissue damage is mediated through specific receptors. We studied the in vivo effect of two selective N-methyl-D-aspartate receptor antagonists on the compressed spinal cord segments of rats harboring a thoracolumbar epidural tumor. The effect of a single intramuscular treatment with either MK-801 (3 mg/kg) or ketamine (110 mg/kg) given at the onset of paraplegia was evaluated 30 hours later. In saline-treated control animals, significant increases in water content, prostaglandin E2, and 6-keto-prostaglandin F1 alpha were evident. Treatment with either agent resulted in a normal water content in the compressed segments but had no effect on prostaglandin synthesis. Evaluation of the effect of treatment on the course of the disease required dose reduction by 45% for ketamine and by 30% for MK-801, to avoid the excessive sedative effect. Treatment was started at the first appearance of neurological dysfunction (Grade 1) and continued to paraplegia (Grade 5). The mean time interval between Grades 1 and 5 was 2.1 +/- 0.3 days in saline-treated control animals, and it was not significantly altered by either ketamine or MK-801. Our study indicates that in the end stage of epidural compression, when ischemia is present, excitotoxins probably participate in the evolution of a cytotoxic edema. It is suggested that treatment initiated at the onset of paraplegia may still reduce the cytotoxic edema, but its potential clinical value requires further investigations.
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PMID:Experimental neoplastic spinal cord compression: effect of ketamine and MK-801 on edema and prostaglandins. 216 98


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