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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.01 seconds)

Malignant breast tissue is characterized by morphological and metabolic changes when compared with normal breast tissue. In this study, the cytochemical measurement of glucose-6-phosphate dehydrogenase (G6PD) activity was used to detect abnormal metabolism in breast tissue and to determine whether abnormal metabolic activity precedes morphological change during human breast carcinogenesis. Normal and benign breast tissue, morphologically normal tissue from cancer-containing breasts, and malignant breast tissue were studied. In malignant tissue, mean(s.e.m.) G6PD activity was significantly increased when compared with normal and benign tissue (9.69(2.3) versus 27.02(1.7) mean integrated extinction (MIE) x 100, P less than 0.01). G6PD activity was increased in morphologically normal tissue from cancer-containing breasts when compared with normal and benign breast tissue from breasts with no known cancer (27.02(1.7) versus 18.42(2.6) MIE x 100, P less than 0.05). These findings suggest that metabolic abnormalities precede morphological changes in breast carcinogenesis. Abnormal metabolism can be detected widely within a cancer-containing breast. The detection of such abnormality may prove helpful in identifying patients at high risk of developing breast cancer.
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PMID:Premorphological metabolic changes in human breast carcinogenesis. 222 69

Hormonal modulation of glucose-6-phosphate dehydrogenase (G6PD) and of utilization pathways of NADPH generated by G6PD was studied in the MCF-7 human breast cancer cell line, using a quantitative cytochemical method. Our results show that G6PD is increased by 17 beta-estradiol (estradiol) and synthetic progestin (promegestone R5020). The synthetic antiestrogen tamoxifen has no effect on G6PD activity. When it is present in the medium with estradiol, tamoxifen can oppose the stimulatory effect of estradiol on G6PD activity. Mifepristone (RU 38486) has no effect on G6PD activity, but it inhibits the R5020 stimulation of G6PD activity. After MCF-7 pretreatment with estradiol, there is a much stronger stimulation of G6PD activity by R5020. When we studied the effect of the steroid on the two utilization pathways of NADPH generated by G6PD activity, we observed that, in the cells treated with estradiol, there is an increase in reducing equivalents generated by G6PD activity which only affects the NADPH2 pathway, and that there is cell growth stimulation. When tamoxifen is present in the medium, we found no effect on the NADPH utilization pathways, nor on cell growth. In the presence of R5020, the NADPH2 pathway activity is increased but, under our experimental conditions, there was no effect on cell growth. On the other hand, even though RU 38486 is without effect on total G6PD activity, it does cause a modification in the distribution of reducing equivalents: the NADPH2 pathway activity is decreased, while the NADPH1 pathway is stimulated.
Cancer Res 1990 Feb 15
PMID:Sex steroid hormone modulation of NADPH pathways in MCF-7 cells. 229 68

It was found to be possible to distinguish malignant cells from normal cells by using an oxygen-sensitive tetrazolium salt (neotetrazolium) for the histochemical demonstration of glucose-6-phosphate dehydrogenase activity in cryostat sections of human colon. We have studied 12 cases of established adenocarcinoma of the colon in addition to 4 of ulcerative colitis and 4 of adenomatous polyposis (polyposis coli). In a nitrogen atmosphere the activities of malignant and normal cells were similar. However, after incubation in an atmosphere of pure oxygen, only malignant cells gave a positive reaction after 5 min. Three of the four cases of adenomatous polyposis gave a positive reaction for glucose-6-phosphate dehydrogenase activity in oxygen in a manner similar to that of specimens with severe dysplasia. In general, positive foci were histologically indistinguishable from the neighboring tubuli. However, foci of severely dysplastic epithelium usually showed a positive reaction. All three patients eventually developed clear-cut severe dysplasia. The other patient, who showed a negative reaction in oxygen, was diagnosed after 3 years as not suffering from dysplasia. All cases of ulcerative colitis gave a reaction in oxygen comparable with that of normal cells. Therefore, the areas with a positive reaction are considered to be either in the process of malignant transformation or malignant. An explanation for the oxygen insensitivity of cancer cells appeared to be a decrease in the activity of superoxide dismutase (EC 1.15.1.1), as addition of exogenous superoxide dismutase to malignant cells caused a normal reaction. We wish to suggest that this test in combination with the routine histology may be exploited for the diagnosis of polyps in premalignant conditions.
Cancer Res 1990 Aug 15
PMID:Quantitative cytochemical detection of malignant and potentially malignant cells in the colon. 237 74

Adult Oryzias latipes were exposed to 50 mg of diethylnitrosamine per liter of water for 5 wk and then transferred to clean water for an additional 15 wk. Response of the liver during the first 6 wk were analyzed by enzyme histochemistry and by high-resolution light and transmission electron microscopy. After 1 wk, cytotoxicity was apparent at the light microscopic level by piecemeal necrosis and phagocytosis apoptosis by adjacent hepatocytes and resident macrophages. Spongiosis hepatis and inflammation, found as early as wk 3, were not widespread until wk 6. Glycogen depletion and multifocal increases in gamma-glutamyl transpeptidase were found as early as 3 wk. At 5 wk, macrophage infiltration and aggregation and hepatocyte lysosome proliferation were revealed by an increase in cells staining for acid phosphatase. In addition, a subpopulation of macrophages stained positively for glucose-6-phosphate dehydrogenase during wk 6. Other histochemical biomarkers (Mg2(+)-ATPase, DT-diaphorase, uridine diphosphoglucuronyl dehydrogenase) were not altered. Mitotic figures were rare for the entire 6-wk period. At the ultrastructural level, necrotic alterations of some hepatocytes were seen within 24 h. Within 48 h, an apparent reduction of hepatocyte glycogen and cell volume characterized the majority of hepatocytes; this was accompanied by an increase in interhepatocytic space and the length and complexity of the hepatocyte microvillous projections found in the space of Disse. Lipid vacuolar inclusions inhabited space previously occupied by glycogen. Margins of hepatocyte nuclei were irregular, and mitochondria were condensed and their shape altered so that crescentric and elongated profiles were abundant. Lysosomes and residual bodies were increased after 1 wk. The cytoplasmic processes delineating spongiotic lesions were identified as originating from Ito cells. After 4 wk, apparent proliferation of smooth endoplasmic reticulum and retention of transport lipid within its cisternae were seen. The toxic depletion of hepatocytes and the attendant altered cellular environment are discussed in relation to cell-to-cell interactions and the possible contribution of stromal and extracellular matrix changes to liver regeneration and neoplasia.
Cancer Res 1990 Sep 01
PMID:Cytotoxicity phase of diethylnitrosamine-induced hepatic neoplasia in medaka. 238 55

The biological diagnosis of prostatic carcinoma in relation with benign prostatic hypertrophy is essentially realized by the evaluation of plasma PAP or medullar PAP, the increase of which rises to 70% of the cases. This evaluation contains also other biochemical markers such as CK-BB, glucose-6-phosphate dehydrogenase, LDH 5 or alkaline phosphatase. The elevation of urinary polyamines is also correlated with the evolution of carcinoma. Other markers have been recently described such as PSA, useful both by evaluation in serum and by its identification on biopsy in histopathology. This exploration could be completed by the evaluation of androgenic receptors and of circulating androgens.
Bull Cancer 1985
PMID:[Cancer of the prostate: the markers other than prostatic acid phosphatase]. 241

Chronic administration of the estrogen 17 beta-estradiol induces kidney tumors in male Syrian hamsters within 6 months of initial exposure. Although these tumors have previously been studied histologically and histochemically and have been postulated to be derived from proximal tubular and/or interstitial cells, there exists no unambiguous evidence for an epithelial or mesenchymal origin. To elucidate the histogenesis of these neoplasms, kidney sections of hamsters treated with estradiol for 4, 5, and 6 months and age-matched untreated controls were investigated histologically and histochemically. Proliferating foci were observed in kidneys exposed to estradiol for 5 and 6 months. They consisted of clusters of spindle-shaped cells forming solid blocks, cords, or branches located between tubules. These foci were judged to be precursors of larger tumors identified in the latter treatment group. The histological and histochemical profile of foci and tumors matched closely. These lesions were marked by very high activities of alkaline phosphatase, adenyl cyclase, and glucose 6-phosphate dehydrogenase. In contrast, glycogen content and activities of glucose 6-phosphatase, succinate dehydrogenase, and gamma-glutamyl transpeptidase were low or absent. Immunofluorescence of the intermediate filaments revealed that foci and tumors solely expressed vimentin and desmin but not cytokeratin. The morphology, enzyme histochemical pattern, and immunofluorescence strongly support a mesenchymal origin of the estradiol-induced hamster kidney tumors studied. The neoplasms were probably derived from vascular smooth muscle cells of a cell subtype particularly sensitive to hormonal stimulation and transformation.
Cancer Res 1988 Feb 15
PMID:Histochemical analysis of the development of estradiol-induced kidney tumors in male Syrian hamsters. 244 29

Glycophorins C and D (GPC and GPD) are two erythrocyte glycoproteins which originate from the same gene but differ in their NH2-terminal residues. The cell surface expression of these glycoproteins during normal and erythroid differentiation has been investigated with monoclonal and polyclonal antibodies and has been compared to the expression of glycophorin A (GPA), the major sialoglycoprotein of human red cells. Using glycosylation-independent antibodies (monoclonal or polyclonal), GPC or GPD was detected in erythroid and nonerythroid cell lineages. However, a glycosylation-dependent monoclonal antibody (MR4-130) detected an epitope on GPC which appears to be erythroid specific, suggesting that lineage specificity of this glycoprotein is related to some carbohydrate structures. During normal erythroid differentiation, GPC was expressed early at the level of erythroid progenitors (part of erythroid burst-forming unit and erythroid colony-forming unit) as detected with a glycosylation-independent monoclonal antibody (APO 3), whereas GPA is only present during terminal erythroid differentiation. The MR4-130 epitope was not coordinately expressed on the cell surface with the GPC molecule in the erythroid differentiation, since it was detected at the level of the more mature erythroid colony-forming unit slightly later than the GPC polypeptide. In four erythroleukemic patients, blast cells blocked at discrete stages of the erythroid differentiation were also investigated with antibodies and complementary DNA probes for GPA and GPC. GPA was immunologically detected in three of four cases, and its cell surface expression was correlated with the amount of specific mRNA in the cells, as seen by Northern blot analysis. GPC was immunologically detected on the blast cells of all four patients. However, in two cases including one with positive expression of GPA, the MR4-130 epitope was absent from the GPC molecule. By Northern blot analysis, we found that the GPC/GPD mRNA was present at a high level in all four patient samples. Western blot analysis of GPC and GPD in two of these patients revealed that these mRNAs were mostly translated into the GPD molecule, suggesting that these glycoproteins might be differently processed in certain cases of erythroleukemia.
Cancer Res 1989 May 15
PMID:Early expression of glycophorin C during normal and leukemic human erythroid differentiation. 246 35

The effects of oral fructose on hepatocarcinogenesis were investigated with cytomorphological, cytochemical and stereological methods. Carcinogenesis was induced in male Sprague-Dawley rats by application of N-nitrosomorpholine (NNM) for 7 weeks. Afterwards, the animals received fructose in the drinking water (120 g/l) and food ad libitum (group I) or tap water and food ad libitum (group II). The incidence of hepatocellular carcinoma in rats treated with NNM plus fructose was 46% as compared to 24% in animals receiving NNM alone (P less than 0.05). There was no difference in the incidences of other malignancies between the groups (group I: 32.1%, group II: 32.0%). Morphometric evaluation of preneoplastic liver lesions indicated the enhancing effect of the fructose treatment several months before malignant tumors appeared. As early as 6 weeks after treatment the hepatic parenchyma occupied by focal lesions was increased from 6.7% in the animals which had received NNM alone to 8.5% (P less than 0.05) in animals having received NNM plus fructose. This increase was predominantly caused by an increase in glycogen storing foci (P less than 0.0005). In addition, the fructose treatment caused a histochemically detectable increase in the activity of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase in both the hepatocytes of the focal lesions and the surrounding parenchyma. In the NNM plus fructose group the activity of the glucose-6-phosphatase in the foci was frequently approximately equal to the activity in the parenchyma of untreated controls. The striking increase in the activity of this enzyme in the surrounding hepatocytes, however, still sharply demarcated the lesions. The potential mechanisms by which fructose enhances hepatocarcinogenesis are discussed.
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PMID:Enhancement of hepatocarcinogenesis in rats by dietary fructose. 256 39

The effect of cysteamine (2-aminoethanethiol hydrochloride) on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats received alternate-day s.c. injections of cysteamine, and beginning in experimental week 3 were given drinking water containing NNM for 8 weeks. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or glucose-6-phosphate dehydrogenase (G6PD) were examined by histochemical techniques. In week 18, quantitative histological analysis showed that prolonged administration of cysteamine resulted in a significant reduction in the number of GGT-positive and G6PD-positive hepatic lesions. Histologically, hepatocellular carcinomas were significantly fewer and smaller in GGT-positive and G6PD-positive lesions in rats treated with cysteamine than in untreated rats. Administration of cysteamine also caused a significant decrease in the liver norepinephrine concentration and in the labelling indices of pre-neoplastic lesions and the surrounding liver. Our findings indicate that cysteamine inhibits hepatocarcinogenesis; this may be related to its reducing effect on norepinephrine concentration in the liver and its subsequent inhibition of cell proliferation in neoplastic lesions and surrounding hepatocytes.
Int J Cancer 1989 Sep 15
PMID:Inhibition by cysteamine of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. 257 Jul 57

A case-control study was conducted to test the hypothesis whether the genetic condition of glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with a reduced risk of cancer. One hundred and eighty seven male cancer patients admitted to hospitals in Cagliari (Sardinia, Italy), between November 1984 and March 1986, were compared with 186 male patients with other diseases, except hemolytic anemia, admitted to the same hospitals in the same period. In contrast to previous reports, our study found no reduction of cancer risk in G6PD-deficient subjects. The study had sufficient statistical power to detect a 0.5-fold decrease in the risk of cancer. The recent suggestion from other studies that tumoral cells of G6PD-deficient subjects can produce their own G6PD, seems to be consistent with this negative finding. Among those subjects presenting some level of erythrocyte G6PD activity, the average enzyme activity was significantly higher in cancer patients than in controls. This finding is consistent with previous experimental studies suggesting a positive correlation between cell proliferation and G6PD activity.
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PMID:Glucose-6-phosphate dehydrogenase deficiency and cancer in a Sardinian male population: a case-control study. 270 39


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