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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MAC 16 is a transplantable murine carcinoma of the colon producing extensive weight loss in tumour-bearing animals. The weight loss is proportional to the size of the tumour and occurs without a reduction in food intake when compared with non tumour-bearing control mice. Weight loss produced by the MAC 16 tumour is accompanied by hypoglycaemia which becomes more extensive as the tumour mass increases. In order to understand the mechanism of the cachexia produced by the MAC 16 tumour the rate of substrate utilization and CO2 formation from both glucose and palmitate has been compared in vitro, with other colon carcinoma cell lines known not to produce cachexia as well as a range of murine and human tumour cell lines. The rate of glucose consumption, lactate production and CO2 formation from both glucose and palmitate is much higher for the MAC 16 than for the other tumour cells. For all cell lines in vitro the consumption of glucose exceeds that of palmitate by a factor of 10(3). Excessive consumption of glucose by the MAC 16 tumour may account for the hypoglycaemic effect on the host. The level of 3 oxo acid CoA transferase, an initiator of ketone body utilization, was found to be much lower in the MAC 16 tumour than non-involved colon. This suggests that the tumour may not be able to metabolize ketone bodies effectively.
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PMID:Metabolic substrate utilization by a tumour cell line which induces cachexia in vivo. 377 4

In order to study the effect of glucose on the differentiation of cultured human colon cancer cells, a subpopulation of HT-29 cells was selected for its capacity to grow in the total absence of sugar. These cells (Glc-cells) exhibit, after confluency, an enterocytic differentiation, in contrast to cells grown with glucose (Glc+ cells), which always remain undifferentiated. The differentiation is characterized by a polarization of the cell layer with apical brush borders and tight junctions, and by the presence of sucrase-isomaltase. The differentiation of Glc- cells is reversible: the addition of glucose to postconfluent cultures of Glc- cells results in an inhibiting effect on the expression of sucrase-isomaltase; switching growing cultures of Glc- cells to the Glc+ medium for several passages results in a progressive reversion to the undifferentiated state, which is completed after seven passages. The dedifferentiation process is associated with a parallel, passage-related, increase in the rates of glucose consumption and lactic acid production, and decreases of intracellular glycogen content, which return to the values of the undifferentiated original Glc+ cells. The values of these metabolic parameters are correlated, at each passage, with the degree of dedifferentiation of the cells. When these dedifferentiated cells, after having been cultured in Glc+ medium for 20 passages, are switched back to the Glc- medium, they readily grow without mortality, and reexpress the same enterocytic differentiation as the parent Glc- cells. These results show that the capacity of this subpopulation to grow and differentiate in the absence of sugar is a stable characteristic. They further suggest that glucose metabolism interferes with the program of differentiation of HT-29 cells.
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PMID:Enterocytic differentiation of a subpopulation of the human colon tumor cell line HT-29 selected for growth in sugar-free medium and its inhibition by glucose. 388 Jul 64

The relationship between the intracellular concentration of various nucleotides as measured by high-performance liquid chromatography analysis, and the differentiation of 2 human colon cancer cell lines was studied. HT-29 cells were induced to undergo both structural and functional enterocytic differentiation (as determined by electron microscopy and the presence of brush-border specific enzymes, respectively) by changing the carbon source or adding Na butyrate to standard tissue culture media. This differentiation occurred after the cells reached confluency when they were cultured in galactose, uridine, inosine, or without nucleosides (all in the absence of glucose) and in the presence of glucose plus Na butyrate. Cells cultured in 25 mM fructose or glucose +/- nucleosides did not differentiate. In all culture conditions where HT-29 cells did not differentite, the intracellular concentrations of 2 compounds which co-migrated with UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine rose approximately equal to 10-fold at confluency and remained elevated throughout the stationary phase, whereas their concentrations remained constant and low after confluency in cells that underwent differentiation. This indicated that the accumulation of these compounds is associated with the inability of these cells to differentiate since other nucleotides and nucleotide sugars did not change in a similar fashion. Purification of the presumed UDP-N-acetylhexosamines, followed by the identification of the products from their chemical and enzymatic hydrolysis, confirmed the identity of these two peaks. Nucleotide analysis of Caco-2 cells, which undergo enterocytic differentiation after they reach confluency even when cultured on glucose, revealed the same pattern of UDP-N-acetylhexosamine levels as differentiated HT-29 cells, with its concentration remaining relatively constant and very low, even after the cells were confluent. The significance of the accumulation of UDP-N-acetylhexosamines in cells unable to differentiate is discussed.
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PMID:The intracellular accumulation of UDP-N-acetylhexosamines is concomitant with the inability of human colon cancer cells to differentiate. 396 44

Chlorozotocin is a glucose-substituted chloroethyl nitrosourea with pharmacologic properties suggesting it is a relatively nonmyelosuppressive cancer chemotherapy drug. Preclinical studies have shown that this drug possesses approximately twice the in vitro alkylating activity of the chloroethyl nitrosoureas BCNU and CCNU. In the L1210 leukemia system, chlorozotocin has curative activity at doses that result in minimal bone marrow toxicity. In vitro studies of human bond marrow stem cells have shown that chlorozotocin is relatively sparing of these cells compared to BCNU. Phase I and phase II trials in man have been performed that show that chlorozotocin's dose-limiting toxicity is thrombocytopenia at doses greater than 120 mg/m2. In the phase II trial, 16% of patients with colon cancer and 20% of patients with malignant melanoma evidenced objective regression of disease. Chlorozotocin is now undergoing phase II evaluation in combination chemotherapy trials in colon and stomach cancer.
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PMID:Preclinical and clinical studies on chlorozotocin, a new nitrosourea with decreased bone marrow toxicity. 644 66

A simple fluorescent microscopic method demonstrated that adriamycin was distributed in two cellular compartments of living rat colon cancer cells. Adriamycin accumulated slowly in cytoplasmic granules, probably lysosomes, where it persisted long after the drug was removed from the medium. On the other hand, adriamycin accumulated rapidly in the nucleus, but was rapidly cleared in adriamycin-free medium. Drug efflux from the nucleus was blocked by sodium azide in glucose-free medium or by verapamil, a calcium-blocking agent. When colon cancer cells were cultivated for 1 day or longer in adriamycin-containing medium no nuclear fluorescence was observed. However, the addition of sodium azide to glucose-free medium or verapamil restores the nuclear fluorescence. The colon cancer cells had low sensitivity to adriamycin, but the addition of verapamil strongly enhanced adriamycin toxicity. Thus adriamycin is permanently cleared from the nucleus of rat colon cancer cells through an energy-dependent efflux mechanism, which is blocked by verapamil. The efficiency of this efflux mechanism is enhanced by exposure of the cell to adriamycin. This mechanism could be involved in the resistance of colon cancer to adriamycin.
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PMID:Cytofluorescence localization of adriamycin in resistant colon cancer cells. 673 40

A hematological picture simulating that seen in cases of leukemia often occurs in a variety of conditions. We recently treated a patient who had a leukemoid reaction in the peripheral blood while he was on parenteral nutrition. Throughout the period of treatment with parenteral nutrition, an abnormal shift towards immaturity in the neutrophilic granulocytes was seen, and the degree of this shift appeared to depend on the caloric intake. Moreover, the hematological picture resembling that seen in cases of leukemia disappeared shortly after discontinuation of the parenteral nutrition, and immature cells were no longer apparent. We assumed that the excess glucose-related calories included in parenteral nutrition produced the leukemoid reaction in this patient who was being surgically treated for carcinoma of the colon with hepatic metastasis.
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PMID:Leukemoid reaction associated with parenteral nutrition. 679 18

1. Changes in liver glycogen and glycolytic intermediates were determined in ten patients undergoing abdominal surgery for carcinoma of the colon. 2. One hour of surgery resulted in a 19% decrease in liver glycogen, together with an increase in hepatic glucose 6-phosphate and glucose concentrations. 3. Blood glucose increased from 5.01 to 6.67 mmol/l during the hour between liver biopsies. 4. We conclude that the hyperglycaemia of surgery is associated with stimulation of hepatic glycogenolysis.
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PMID:Changes in liver glycogen and glycolytic intermediates during abdominal surgery in man. 682 47

Fifty-two patients with resectable carcinoma of the colon and rectum have been monitored by three monthly serial estimations of three APRP (serum protein hexose, transferrin and ceruloplasmin) together with CEA. In 36 patients, subsequent clinical evidence of a recurrence of the disease developed during the study period. Monitoring with APRP can detect a recurrence of the disease at the subclinical stage in the majority of patients and appears to be complimentary to monitoring with CEA. However, due to the low incidence of surgical removal of recurrent carcinoma, this does not give real benefit for patients.
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PMID:Monitoring of patients with carcinoma of the large intestine by use of acute phase proteins and carcinoembryonic antigen. 685 57

Chronochemotherapy was performed in two cases of metastatic liver cancer. One was a 51-year-old woman whose pancreas tumor was incompletely removed six months ago and had a residual pancreas tumor (30 x 20 mm2) with liver metastases in S4. Another was a 54-year-old woman whose sigma colon cancer had been removed 10 months ago. A large metastatic tumor in the fourth section of the liver and multiple daughter tumors in other parts of the liver were seen. The hyperthermic chemotherapy using warmed 5% glucose solution administered intraarterially could not be used for these patients. The variable rate of infusion of 5FU (250 mg/body) and CDDP (3.3 mg/body) (23:19:00-7:00) (1/3:7:00-10:00) as chronotherapy showed more efficacy as an anti-cancer treatment compared to their continuous infusion.
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PMID:[Chronochemotherapy in two cases of metastatic liver cancer]. 757 96

To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate therapy, 22 patients with colon cancer were admitted prospectively to a Clinical Research Center for serial measurement of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation. Combined therapy was associated with a significant reduction in fasting glucose level (98 +/- 2 mg/dL to 94 +/- 2, P < 0.025) without a significant fall in fasting HGP (2.09 +/- 0.11 mg/kg/min versus 2.03 +/- 0.13; P > 0.05). The decreased fasting glucose value was associated with a mild but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (1.34 +/- 0.07 %/min vs 1.47 +/- 0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2 months of therapy (63.3 +/- 3.0 mumol/kg/hr vs 57.1 +/- 3.9 mumol/kg/hr; P < 0.025), but leucine oxidation (11.5 +/- 1.1 mumol/kg/hr vs 11.2 +/- 1.1 mumol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine concentrations significantly increased with therapy, it was not associated with plasma LA. Half of the patients with cancer died 14 +/- 4 months after the study, and the other half were alive 58 +/- 2 months later. Survival time can be estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and insulin concentration. Multiple regression analysis identified that plasma LA was related directly to length of survival time, and baseline HGP, carcino-embryonic antigen, and insulin concentration were related inversely to length of survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered metabolism and mortality in patients with colon cancer receiving chemotherapy. 763 42


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