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

The influence of hyperthermia (42.5 degrees C) on the viability and morphology of L1A2 ascites cells incubated at various pH levels (6.4-7.2) was studied. In contrast to unheated cells, increased extracellular acidity in hyperthermically treated tumor cells was associated with markedly reduced viability of the tumor cells exposed to hyperthermia. The cells heated at neutral pH underwent ultrastructural nuclear changes; the most prominent were the appearance of filamentous bundles and increased perichromatin granules. The cells heated under more acid conditions had an increased lysosomal activity and intense cell lysis resulting in lethal damage to the entire cell population within 6 hours after treatment. The active mechanism was not clear, but cell membrane lesions combined with the increased lysosome activity seemed of major importance in the mechanism of heat-induced damage to tumor cells kept in an acid milieu.
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PMID:Influence of extracellular pH on the viability and morphology of tumor cells exposed to hyperthermia. 1 50

Colony formation of JB-1-E tumor cells was studied after hyperthermic treatment (42.5 degrees C) at a pH of 6.4 or 7.2 under hypoxic and euoxic conditions. At a pH of 7.2 and normal oxygen tension, there was a moderate decrease in colony formation with increasing duration of hyperthermic treatment (To = 65 min.). This effect was slightly enhanced under hypoxic conditions (To = 36 min.). The hyperthermic effect was enhanced to a considerably greater degree when treatment was performed at a pH of 6.4 (To = 19 min.), with no observable difference between hypoxia and euoxia. These findings indicate that environmental acidity is a determining factor in the hyperthermic effect. The hypoxic effect at a pH of 7.2 is probably due to a slight decrease in the intracellular pH caused by increased production of lactic acid.
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PMID:The influence of hypoxia and acidity on the hyperthermic response of malignant cells in vitro. 1

A significant tumor damaging effect (growth inhibition) on transplanted syngeneic sarcoma in mouse was obtained by means of pH-dependent activation of a transport form of a cancerostatic drug by an enzyme foreign to the organism. This effect was achieved by combined administration of 8-0-(alpha-L-arabinofuranosyl)beta-peltatin-A as a transport form of beta-peltatin-A and the exogenous enzyme alpha-L-arabinofuranosidase from Aspergillus niger and additional increase of the acidity of the tumor by injection of glucose. The combined application of the transport form plus enzyme showed a more favorable effect on selectivity than free peltatin when a quantitative comparison was made between the tumor growth inhibition and the damage to the blood picture.
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PMID:Experiments to increase the selectivity of tumor chemotherapy by means of in vivo activation of transport forms of cancerostatics by exogenous enzymes. 2 45

1. The operative technique and the postoperative results of the original pylorus-preserving gastrectomy (PPG) and those of the Maki procedure as applied to cases of total gastrectomy are reported briefly. 2. The essence of these operations is to retain the pyloric cuff of 1.0-1.5 cm in length in order to preserve sphincteric function without the use of the drainage procedure. Ingested food was seen to empty gradually and rhythmically through the pyloric ring into the duodenum thereby avoiding dumping syndrome and reflux esophagitis. 3. As gastric acidity is reduced sufficiently by PPG, this method is to be recommended for treatment of intractable gastric ulcer cases and other benign lesions in which the foci are located in the distal half of the stomach. Though the method seems to be also useful in selected cases of duodenal ulcer, stenosis at the level of the pylorus and duodenum may preclude the application of the method. 4. The Maki procedure with jejunal interposition following nearly-total proximal gastrectomy is recommended in patients whose pylorus and its surroundings have remained free of tumor.
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PMID:Pylorus-preserving procedure in partial and total gastrectomy. 32 97

The relevant literature is reviewed in an attempt to clarify the mechanism of heat-dependent tumor cell destruction in vivo. Malignant cells in vivo appear to be selectively destroyed by hyperthermia in the range of 41-43 degrees C. Heat evidently affects nuclear function, expressed by an inhibited RNA, DNA and protein synthesis and characteristic arrest or delay of cells in certain locations of the cell cycle. However, as these effects appear to be reversible and are observed in normal cells as well as malignant cells, they probably do not explain the hyperthermic induced selective in vivo destruction of malignant cells. Heat-induced cytoplasmic damage appears to be of more importance. Increased lysosomal activation is observed, and is further intensified by a relatively increased anaerobic glycolysis which develops selectively in tumor cells. A hypothesis is proposed and discussed which explains the marked and selective in vivo tumor cell destruction as a consequence of the enhancing effect on the cytoplasmic damage of certain environmental factors (e.g. increased acidity, hypoxia and insufficient nutrition.
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PMID:Effect of hyperthermia on malignant cells in vivo. A review and a hypothesis. 87 62

The ultrastructural changes following local hyperthermic therapy was studied in a solid murine mammary carcinoma. A few hr after treatment, a pronounced lysosomal activity was observed in the cytoplasm of the tumor cells, together with mitochondrial destruction and disaggregation of the polyribosomes. Later, more destructive changes with intense cell shrinkage and cytoplasmic lysis occurred, and within 24 hr the entire cytoplasm of all the tumor cells was completely destroyed. In the nuclei shrinkage and condensation of heterochromatin were early features. The nucleoli were gradually degranulated, but with preservation of the fibrillary component. However, here, too, complete destruction occurred within the first few days after treatment. Cells in mitosis were also arrested and destroyed in the same way. The nonmalignant cells of the tumor tissue presented only minor reversible morphological changes, and within a few days the tumor area was replaced by ingrowth of fibroblasts and macrophages. The morphological changes are discussed in the light of our present knowledge of the hyperthermic effect on tumor cells. As regards the mechanism of hyperthermic destruction of solid tumors in vivo, the hypothesis is advanced that a primary, lysosomally conditioned, selective destruction of the malignant cells occurs and that this reaction is intensified by a high acidity in the tumor milieu.
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PMID:Ultrastructure of a murine mammary carcinoma exposed to hyperthermia in vivo. 125 86

Radiotherapy in patients with squamous cell lung cancer produced an increase of urinary magnesium and calcium secretion. This is probably due to the cytolysis of malignant cells and shifting of the acid--base balance toward acidity values. This interpretation is justified by the significant correlation between the regression of tumor and increased secretion of the intercellular cation--magnesium.
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PMID:[Urinary excretion of magnesium and calcium in patients with pulmonary squamous cell carcinoma treated by ionizing radiation]. 129 Sep 74

Studies with mouse tumors have shown that the effectiveness of certain chemotherapeutic agents can be enhanced if they are used in appropriate combination with an anti-hypertensive drug such as hydralazine. This results in reduced tumor blood flow with, among other things, a consequent decrease in oxygenation and increase in acidity in the tumor tissue. The purpose of the present work was to determine to what extent hypoxia and low pH are involved in the mechanism of this effect for chlorambucil. V79-WNRE cells were exposed to various drug concentrations under aerobic or hypoxic conditions, pH 6.4 or 7.4. Measurements of cell survival following 1 hr exposure at 37 degrees C showed that pH 6.4 produced a large potentiation of cell killing by chlorambucil (ER = 4 approx.); hypoxia, on the other hand, had little effect. The potentiation was shown to be greatest for pH values below 7.0. HPLC measurements of drug uptake were made since it was anticipated that chlorambucil, a weak acid, might tend to accumulate in cells under conditions of low extracellular pH. It was found that at an extracellular pH of 6.4 the ratio of the intracellular (Ci) and extracellular (Ce) drug concentrations was increased 4.5 and 3.6 fold for aerobic and hypoxic conditions, respectively. This probably explains most, if not all, of the cell killing potentiation observed at low pH.
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PMID:The effect of hypoxia and low pH on the cytotoxicity of chlorambucil. 154 46

The migration of lymphocytes through extracellular matrix (ECM) is an essential feature of the infiltration process. In the course of their extravasation into poorly perfused neoplastic lesions, lymphocytes often encounter regions of acidified ECM. This study was designed to determine whether lymphocyte adherence and motility in ECM are influenced by ambient pH. Murine splenic lymphocytes, activated by culture with high-titer IL-2, were allowed to migrate into three-dimensional gels of Type I collagen, a major component of interstitial stroma, or into Matrigel, a basement membrane model. After 18 hr at pH 7.1, the leading cell front traveled a mean distance of approx 475 microM into Type I collagen gel. Approx 50% of the cells remained nonadherent, 25% adhered to the gel surface, and 25% were motile (penetrated beneath the surface). At pH 6.7, the leading-front distance increased significantly, by a factor of 1.4X, but there was little change in the proportion of cells exhibiting nonadherence, surface adherence, or motility. The relative motilities of CD3+ and AsGM1+ subsets were also unaltered. It therefore appears that acidification of collagen matrix increases the locomotory activity of motile lymphocytes, but causes little recruitment of nonmotile lymphocytes into the motile pool. Similar results were obtained in experiments with Matrigel. The increased motility observed at pH 6.7 did not reflect breakdown or relaxation of matrix lattices, as measured by the passive diffusion of latex beads of defined diameter. Preincubation of lymphocytes at pH 6.7 did not alter their subsequent motility in pH 7.1 gels. The findings establish ambient pH as a microenvironmental variable which can influence lymphocyte migration through ECM. The weak acidity characteristic of certain tumor microenvironments may be a factor which encourages lymphocyte infiltration through tissue matrix. Treatments which alter intratumor pH could potentially be used to manipulate the infiltration process for immunotherapeutic benefit.
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PMID:Motility of IL-2-stimulated lymphocytes in neutral and acidified extracellular matrix. 173 11

It is a known fact that pH in rodent tumors decline significantly upon heating most likely due to breakdown of the tumor blood circulation. We recently observed that tumor blood vessels become thermotolerant after being heated with a sublethal thermal dose. The purpose of the present study was to reveal whether heating can reduce intratumor pH when the tumor vessels are thermotolerant. When the SCK tumors of A/J mice were heated at 42.5 degrees C for 1 h, the tumor vessels became most thermotolerant at 18 h postheating, as measured with the 86Rb uptake method. The intratumor pH in the control SCK tumors was 7.05 +/- 0.14 (SD), and it significantly decreased to 6.70 +/- 0.08 (P less than 0.001) after heating at 44.5 degrees C for 1 h. However, when the tumor vessels were thermotolerant, i.e., 18 h after heating at 42.5 degrees C for 1 h, reheating at 44.5 degrees C for 1 h could not reduce the intratumor pH. We concluded that such a failure to increase tumor acidity by a second heating at temperatures as high as 44.5 degrees C was due to vascular thermotolerance developed by the first heating.
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PMID:Changes in intratumor pH by two heatings. 222 45


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