Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Metabolic substrate utilization by a tumour cell line which induces cachexia in vivo. 377 4

Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was investigated under aerobic, acute hypoxic (after 4 hr in 95% N2, 5% CO2 < 0.01% O2), and chronic intermittent hypoxic (after 4 hr hypoxia/day x 7 days) conditions. Acute hypoxia induced topo II alpha mRNA and protein, effects that were more pronounced in HT-29 cells. Chronic intermittent hypoxia caused a decrease in topo alpha mRNA and protein, changes that were again more pronounced in HT-29 cells. The observed changes in topo II alpha protein were associated with parallel changes in topo II activity under all conditions tested. Topo II beta mRNA was expressed at a very low level in both cell lines under aerobic and hypoxic conditions. Compared with cells under aerobic conditions, HT-29 cells were more sensitive to MMC under acute hypoxia but more resistant under chronic intermittent hypoxia. In contrast, the senstivity of HT-29R13 cells was unchanged under acute hypoxia, but the cells were more resistant under chronic intermittent hypoxia. Under all conditions tested, the degree of cytotoxicity corresponded to the frequency of MMC-induced DNA cross-links and topo II alpha protein levels and activity. Our results demonstrated that MMC cytotoxicity in hypoxic cells is highly dependent upon the type of hypoxia and the cell type. Hypoxia has significant effects on topo II alpha expression in HT-29 and HT-29R13 cells which correlate with MMC cytotoxicity.
 ...
PMID:Effect of acute and chronic intermittent hypoxia on DNA topoisomerase II alpha expression and mitomycin C-induced DNA damage and cytotoxicity in human colon cancer cells. 875 40

Port site metastasis has been a surprising event after laparoscopic procedures in cancer patients. No clear data exist about this phenomenon. The aim of this study is to summarize current epidemiologic knowledge about the risk of this complication. A review of all case reports about port site recurrences was undertaken. To date, 164 cases of port site metastases after videoscopic procedures have been reported in 90 papers. We found 108 cases of implantation after laparoscopy for digestive tumors, 23 after thoracoscopy, 29 after gynecological and 4 after urological laparoscopy. Analysis of the current literature confirms that laparoscopy is associated with abdominal cell mobilization to the trocars and instruments. Also low-staged and highly differentiated tumors have been reported to cause post-laparoscopy tumor seeding. The temporary data of the CAE registry 'port site metastases' (Workgroup for Surgical Endoscopy of the German Society of Surgery) are also reported. The analysis of 80 histologically confirmed cases of port site recurrence shows a particular frequency after laparoscopic cholecystectomy for unsuspected gallbladder cancer (n = 59). Postoperative specimen examination revealed a T1 carcinoma in 9 cases (15%), T2 carcinoma in 33 (21%), T3 in 3 (5%) and T4 in 1 case (1.7%). The mean time to clinical tumor relapse was 6 months. Similar patterns were found in a lower number of port site metastases after laparoscopy for colon cancer (n = 2) and for other cancers (n = 9). Clinical evidence that laparoscopy with CO2 pneumoperitoneum can enhance tumor dissemination is given. Port site metastases seem to be secondary to multiple factors including the gas used, local trauma, tumor manipulation, biologic properties of the tumor, and individual surgical skills.
 ...
PMID:Port site recurrences after laparoscopic surgery. A review. 984 74

The determination of cellular content of octadecylphosphocholine (D-19391) and hexadecylphosphocholine (HePC, D-18506), two anticancer agents of the alkylphosphocholine group, using capillary gas chromatography is described. The compounds' cytotoxicity was first determined by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium] assay, being indicative for the concentration used in the uptake and retention measurements. D-19391 was added to the SK-BR-3 breast cancer cell line and HePC to the Molt-4 leukemia cell line in concentrations of, respectively, 18.6 and 15.0 microM, during a 36-h incubation period at 37 degrees C, 5% CO2. HePC uptake in the leukemia cells was followed by a 24-h reversibility test in drug-free medium. Subsequently, sample clean-up was performed on a weak cation-exchange column. For the quantitative analysis, HePC was used as internal standard for the D-19391 measurements and vice versa. Derivatization of the samples with trimethylsilylbromide was followed by capillary gas chromatographic analysis. From these data we conclude that our uptake results are quite similar with those of a previous study of HePC cellular uptake in the more resistant Caco-2T colon cancer cell line. Without having investigated the mechanism that underlies the cellular uptake results obtained, our study points to no direct correlation between the compounds' cellular uptake and their cytotoxic effects.
 ...
PMID:Cellular uptake and retention measurements of alkylphosphocholines in the SK-BR-3 breast cancer and Molt-4 leukemia cell line using capillary gas chromatography. 1038 Jan 24

Acarbose inhibits starch digestion in the human small intestine. This increases the amount of starch available for microbial fermentation to acetate, propionate, and butyrate in the colon. Relatively large amounts of butyrate are produced from starch by colonic microbes. Colonic epithelial cells use butyrate as an energy source, and butyrate causes the differentiation of colon cancer cells. In this study we investigated whether colonic fermentation pathways changed during treatment with acarbose. We examined fermentations by fecal suspensions obtained from subjects who participated in an acarbose-placebo crossover trial. After incubation with [1-13C]glucose and 12CO2 or with unlabeled glucose and 13CO2, the distribution of 13C in product C atoms was determined by nuclear magnetic resonance spectrometry and gas chromatography-mass spectrometry. Regardless of the treatment, acetate, propionate, and butyrate were produced from pyruvate formed by the Embden-Meyerhof-Parnas pathway. Considerable amounts of acetate were also formed by the reduction of CO2. Butyrate formation from glucose increased and propionate formation decreased with acarbose treatment. Concomitantly, the amounts of CO2 reduced to acetate were 30% of the total acetate in untreated subjects and 17% of the total acetate in the treated subjects. The acetate, propionate, and butyrate concentrations were 57, 20, and 23% of the total final concentrations, respectively, for the untreated subjects and 57, 13, and 30% of the total final concentrations, respectively, for the treated subjects.
 ...
PMID:Changes of fermentation pathways of fecal microbial communities associated with a drug treatment that increases dietary starch in the human colon. 1038 68

Port-site recurrences of cancer have drawn attention to the potential risks of laparoscopy for the diagnosis and treatment of digestive cancers. The first observations concerned unsuspected gallbladder cancers shown by laparoscopic cholecystectomy for lithiasis. Seventeen cases in patients with advanced or early colon cancer followed. It eventually became clear that all cancers could be the origin of such recurrences, which present as apparently isolated nodules embedded in the wall. These parietal recurrences were well known in open surgery, having been reported for most cancers, but they drew little attention because they usually occur in the context of carcinosis. It must be remembered that digestive cancers in general have a high potential for dissemination and that nearly 30% of patients have micrometastases in the bloodstream, the lymph nodes, the peritoneum, or even the bone marrow. The mechanism of tumor implantation is analogous to development of an inflammatory reaction. Under these conditions, laparoscopic surgery is susceptible to cause neoplastic dissemination for a number of mechanical reasons: CO2 insufflation, tumor manipulation, failure to isolate the tumor, forceful extraction of the surgical specimen, and exsufflation. Multiinstitutional trials of well-defined laparoscopic protocols based on the same oncologic principles as in open surgery should reduce the frequency of tumor cell dissemination and the incidence of port-site recurrences.
 ...
PMID:Port-Site Recurrence of Cancer Associated With Laparoscopic Diagnosis and Resection: The European Experience. 1040 Oct 81

Cell pH regulation was investigated in the T84 cell line derived from epithelial colon cancer. Cell pH was measured by ratiometric fluorescence microscopy using the fluorescent probe BCECF. Basal pH was 7.17 +/- 0.023 (n = 48) in HEPES Ringer. After acidification by an ammonium pulse, cell pH recovered toward normal at a rate of 0.13 +/- 0.011 pH units/min in the presence of Na+, but in the absence of this ion or after treatment with 0.1 mm hexamethylene amiloride (HMA) no significant recovery was observed, indicating absence of Na+ independent H+ transport mechanisms in HEPES Ringer. In CO2/HCO3- Ringer, basal cell pH was 7.21 +/- 0.020 (n = 35). Changing to HEPES Ringer, a marked alkalinization was observed due to loss of CO2, followed by return to the initial pH at a rate of -0.14 +/- 0.012 (n = 8) pH/min; this return was retarded or abolished in the absence of Cl- or after addition of 0.2 mm DIDS, suggesting extrusion of bicarbonate by Cl-/HCO3- exchange. This exchange was not Na+ dependent. When Na+ was added to cells incubated in 0 Na+ Ringer while blocking Na+/H+ exchange by HMA, cell alkalinization by 0.19 +/- 0.04 (n = 11) pH units was observed, suggesting the presence of Na+/HCO3- cotransport carrying HCO3- into these cells, which was abolished by DIDS. These experiments, thus, show that Na+/H+ and Cl-/HCO3- exchange and Na+/HCO3- cotransport participate in cell pH regulation in T84 cells.
 ...
PMID:Control of cell pH in the T84 colon cell line. 1100 89

Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origins. As part of our program on natural products we have examined a number of herbal and botanical products in the aberrant crypt foci (ACF) assay including Korean red ginseng powder, green tea catechins, curcumin from the Indian culinary spice, tumeric, compounds from garlic and onion, resveratrol from red grapes, among others. In the ginseng experiments groups of 10 F344 rats were fed ginseng powder at a dose of 0.5 g/kg or 2 mg/kg for 5 weeks. During weeks 2 and 3 rats were injected with 10 mg/kg azoxymethane to induce ACF. Controls (n=10) did not receive azoxymethane (AOM). Rats were killed by CO2 overdose and ACF counted in the rat colon. In 8 week post-initiation experiments ginseng powder inhibited the progression of established ACF, indicating a cytostatic effect. This may be due to an anti-inflammatory effect. There is a body of literature that suggests that compounds in wine, tumeric, and tea inhibit cyclooxygenases, thus reducing prostaglandin-mediated effects on the colon. As colon tumors have been shown to highly express COX-2 protein, and given, that many NSAID drugs also suppress COX-1, it is tempting to speculate that herbal products that inhibit one or both forms of the COX enzyme will be effective agents for the prevention of cancer in man.
 ...
PMID:Colon cancer chemoprevention with ginseng and other botanicals. 1174 82

Many papers suggested that laparoscopic treatment of cancer could be achieved and taught safely. Although cases reports about trocar site metastasis and national survey about inadequate management of early ovarian cancer suggested that laparoscopic management of cancer may be dangerous. The current literature may be summarized as follows. An inadequate surgical management performed by laparoscopy as well as by laparotomy may worsen the prognosis of an early ovarian cancer. If the abdominal wall is protected with a bag and the tumour is not morcellated, the incidence of trocar site site metastasis is about 1%. Animal studies demonstrated that the laparoscopic management of cancer has both advantages and disadvantages. Preliminary results from prospective randomised trials in the treatment of colon cancer suggested that the survival rate is similar after laparoscopy and after laparotomy. The risk of dissemination appears high when a large number of malignant cells are present in patients operated using an increased abdominal pressure and a CO2 pneumoperitoneum. These data suggest that laparoscopic treatment of gynaecologic cancer is not dangerous if an adequate surgical technique is used. However morcellation of suspicious solid tumours, treatment of adnexal tumours with external vegetations but without peritoneal dissemination and of bulky lymph nodes should be considered as contra-indications to CO2 laparoscopy, puncture of an ovarian tumour with intracystic vegetations is a high risk situation which should be avoided whenever possible.
 ...
PMID:[Laparoscopy and gynecologic cancer: is it still necessary to debate or only convince the incredulous?]. 1219 54

Recent reports have demonstrated that hypoxia induces the up-regulation of transferrin receptor expression in tumour cells. Tumour cells take up 67Ga in the form of a 67Ga-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on 67Ga uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO2 or 95% N2/5% CO2 for 1 h at 37 degrees C. Cellular uptake of 67Ga citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the 67Ga-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on 67Ga binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of 67Ga citrate in N2 gas in comparison to that in air (P < 0.0001). Hypoxia more prominently influenced cellular uptake of Ga-transferrin relative to that of 67Ga citrate (P < 0.0001). Hypoxia did not affect the percentages of 67Ga radioactivity bound to protein in medium supplemented with fetal calf serum, indicating that the results were not caused by the alteration of 67Ga-transferrin formation. These findings suggest the role of tissue hypoxia with respect to accumulation of 67Ga in tumours, which is likely mediated by transferrin receptors.
 ...
PMID:Hypoxia as a factor for 67Ga accumulation in tumour cells. 1506 Dec 64


1 2 3 Next >>