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

This paper discussed the significance of the activities of purine and pyrimidine salvage enzymes in cancer cells and the targeting against them of chemotherapy. 1. The activities of salvage enzymes in the rat liver were orders of magnitude higher than those of the rate-limiting enzymes of de novo biosynthesis. A similar relationship was observed in rat hepatomas of different growth rates and in primary colon carcinoma in human. 2. The concentrations of nucleosides and nucleobases were measured in plasma, liver and hepatoma 3924A in the rat. The freeze-clamp method was required to determine the concentrations of these precursors in rat liver and hepatoma in a reliable and precise fashion because ischemia markedly altered the concentrations of nucleosides, nucleobases and, as shown earlier, nucleotides in these tissues. The results indicated that the liver markedly concentrated the purine precursors, hypoxanthine, guanine and adenine, but not thymidine, which was one-third that of the plasma. Uridine and deoxycytidine occurred in the same concentration as in plasma, but cytidine was 3-fold higher in liver. In the hepatoma in comparison to the liver the concentrations of the nucleosides and bases were altered and for some of the changes the enzymic differences between liver and hepatoma appeared to be accountable. 3. Kinetic parameters for purine and pyrimidine synthetic enzymes and for the substrates and co-factors were determined in liver and hepatoma 3924A. When enzymic activities were calculated at the tissue steady-state concentrations of the various ligands, the activities of the salvage enzymes were markedly higher than those of the rate-limiting enzymes. 4. Hepatoma cells were highly sensitive to the action of the transport inhibitor, dipyridamole, in lag and log phases. However, plateau phase cells lost their sensitivity to dipyridamole. 5. Amphotericin B rendered plateau phase cells sensitive to the inhibitory action of dipyridamole for the incorporation of thymidine. 6. Amphotericin B enhanced cytotoxicity of dipyridamole in hepatoma and human colon cancer HT-29 cells. 7. In these studies we discovered the decreased responsiveness to dipyridamole of plateau phase cells and the ability of amphotericin B to restore the sensitivity. Moreover, dipyridamole and amphotericin B were synergistic in their cytotoxic action in rat hepatoma cells and human colon cancer cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Salvage pathways as targets of chemotherapy. 367 9

Fourteen patients with diffuse tumors of the liver were treated with temporary occlusion of the hepatic artery (HA) by an external tourniquet followed by infusion and systemic chemotherapy. Three patients had primary neoplasms (one hepatocarcinoma and two cholangiocarcinomas) and eleven had metastatic disease (nine from carcinoma of the colon and rectum, one from retroperitoneal liposarcoma, and one from pulmonary small cell cancer). Infusion chemotherapy in all patients was based on 5-FU, Mitomycin and Vincristine. Systemic chemotherapy was FIVB in metastatic carcinoma and Adriamycin in primary liver tumors. All patients showed improvement of the performance status according to the Karnofsky Index. Objective response (OR) was present in 54% of cases. At present, median survival time in 12.5 months. Aggressive treatment combining hepatic ischemia with infusion and systemic polychemotherapy seems to provide an effective method of palliation in diffuse tumors of the liver. Delayed occlusion by an external tourniquet appears safer than intraoperative ligation of the HA.
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PMID:Temporary occlusion of the hepatic artery plus infusion and systemic chemotherapy for inoperable cancer of the liver. 616 63

Rats with carcinoma of the colon implanted into the liver were subjected to hepatic arterial occlusion for 30-120 min. Regrowth of the tumour after reperfusion was evaluated by immunohistological determination of S-phase activity after injection of bromodeoxyuridine. Levels of RNA and nucleotides, and energy charge, were also examined. DNA synthesis was observed in the entire tumour except in necrotic areas of controls and after 30-min ischaemia with 2-h reflow. Almost all tumoral DNA synthesis was abolished by 2 h of ischaemia, except in a few cells in the tumour periphery, which after reperfusion for 22 and 40 h grew into a band-like concentric layer. Levels of energy charge, adenosine, uridine and guanosine 5'-triphosphates, and RNA were unchanged in liver tissue after hepatic arterial occlusion but decreased in the tumour. In conclusion 30 min of ischaemia did not damage the tumour cells substantially. Ischaemia for 2 h seemed able to kill the tumour cells except those in the periphery in areas nourished by the portal vein where tumour regrowth was seen. The liver tissue was not damaged.
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PMID:Tumour S-phase activity, nucleotide profile and RNA levels after hepatic artery occlusion and reperfusion in an experimental model of secondary liver carcinoma. 764 21

The role of conventional CT scan and conventional MR imaging in assessing patients with colorectal tumors is now well established. Because both techniques have an unacceptably low accuracy for identifying the early stages of primary colorectal cancers (T1, T2N0 or N1 and early T3N0 or N1, or Dukes stage A, B1 and 2, and C1), their routine use for preoperative staging is not recommended. This low staging accuracy is related to the fact that neither method can assess the depth of tumor infiltration within the bowel wall and both have difficulty in diagnosing malignant adenopathy. These distinctions are necessary in order to determine correctly patient prognosis and tumor resectability. If the various publications on CT scan and MR imaging staging of primary colon tumors are summarized, a mean overall accuracy of approximately 70% can be established. The sensitivity for lymph node detection of malignant lymphadenopathy is only about 45%. The sensitivity for detection of positive lymph nodes is better for rectal tumors because any adenopathy in the perirectal area can be considered malignant because benign adenopathy is not seen in this area. For the early stages of colon cancer or recurrent tumor at the anastomotic site, endoscopic ultrasound or TRUS is the method of choice. Both TRUS and MR imaging with endorectal coils can demonstrate the various layers of the rectal wall, but the ultrasonographic examination can be performed at lower cost and is less time-consuming. Despite these limitations CT scan and MR imaging are useful for assessing patients suspected of having extensive disease, including invasion of fat or neighboring organs or metastatic spread to distant sites including, liver, adrenals, lung, and so forth. CT scan and MR imaging are also helpful in the following ways: in determining whether a patient will benefit from preoperative radiation or whether a patient with rectal cancer can undergo a sphincter-saving procedure; for designing radiation ports; and for detecting complications related to the neoplasm, such as perforation with abscess formation or preobstructive ischemia in patients with complete obstruction by tumor. In these cases, management often is based on CT scan and MR imaging findings and cross-sectional follow-up studies can establish the success of treatment. CT scan and MR imaging have a premier role in the detection of recurrent colorectal cancer. CT scan and MR imaging are superior to colonoscopy for diagnosing extrinsic mass-like tumor recurrences and they are the only methods by which patients with total AP resection can be fully evaluated. The overall accuracy of CT scan and MR imaging for detecting recurrent colorectal tumors ranges from 90% to 95%. Following AP resection, CT scan cannot reliably determine whether a soft tissue density in the surgical bed represents recurrent tumor, and it is important to obtain CT scan baseline studies 4 months after surgery and to repeat this examination at 6-month intervals. Scar tissue, even if initially masslike, shrinks over time and after 1 year should be smaller and its margins more sharply defined. Any apparent increase in size of a mass or any demonstration of adenopathy must be considered an indication for biopsy. Recurrent tumors that do not extend to the pelvis or abdominal sidewalls or invade bone or nerves can be resected. Subtle tumor recurrence or tumor foci in small nodes can be detected by PET scan and immunoscintigraphy, but their future role in the diagnostic imaging of colorectal cancer patients depends on the results of ongoing studies. Helical CT scan has the advantages of fast volume scanning associated with optimal bolus delivery, absence of artifacts related to motion, absence of missed slices, and availability of reformations in multiple planes and three-dimensional reconstruction (virtual reality). The role of this technique in patients with colorectal neoplasms has not been defined. (ABSTRACT TRUNCATED)
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PMID:Colorectal cancer. Radiologic staging. 908 14

Ischemic colitis is the most common manifestation of gastrointestinal ischemia. The presumed etiologies are numerous; however, it typically develops spontaneously. It is classified into the transient type, stricture type, and gangrenous type. The majority of patients with ischemic colitis, excluding the gangrenous type, follow a benign clinical course in the absence of major vasculature occlusion. It usually presents as an acute abdominal illness with bloody diarrhea. Diagnosis is confirmed by colonoscopy and/or barium enema. Nongangrenous ischemic colitis usually requires only conservative therapy, including repeated careful assessment, pain control, and fluid replacement, and is associated with a good prognosis. It may lead to the sequela of persistent segmental colitis or colonic strictures, occasionally requiring surgery. Urgent surgery and high morbidity and mortality rates are hallmarks of the gangrenous type. Special consideration must be given to those patients in whom ischemic colitis develops in the context of colon cancer or obstructive colonic lesions. Successful management of a patient with ischemic colitis requires a high degree of clinical suspicion, early diagnosis, careful follow-up, and prompt recognition of persistent disease.
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PMID:[Pathophysiology and diagnosis of ischemic colitis]. 1041 55

Circulating endothelial progenitor cells (EPCs) have been isolated in peripheral blood of adult species. To determine the origin and role of EPCs contributing to postnatal vasculogenesis, transgenic mice constitutively expressing beta-galactosidase under the transcriptional regulation of an endothelial cell-specific promoter (Flk-1/LZ or Tie-2/LZ) were used as transplant donors. Localization of EPCs, indicated by flk-1 or tie-2/lacZ fusion transcripts, were identified in corpus luteal and endometrial neovasculature after inductive ovulation. Mouse syngeneic colon cancer cells (MCA38) were implanted subcutaneously into Flk-1/LZ/BMT (bone marrow transplantation) and Tie-2/LZ/BMT mice; tumor samples harvested at 1 week disclosed abundant flk-1/lacZ and tie-2/lacZ fusion transcripts, and sections stained with X-gal demonstrated that the neovasculature of the developing tumor frequently comprised Flk-1- or Tie-2-expressing EPCs. Cutaneous wounds examined at 4 days and 7 days after skin removal by punch biopsy disclosed EPCs incorporated into foci of neovascularization at high frequency. One week after the onset of hindlimb ischemia, lacZ-positive EPCs were identified incorporated into capillaries among skeletal myocytes. After permanent ligation of the left anterior descending coronary artery, histological samples from sites of myocardial infarction demonstrated incorporation of EPCs into foci of neovascularization at the border of the infarct. These findings indicate that postnatal neovascularization does not rely exclusively on sprouting from preexisting blood vessels (angiogenesis); instead, EPCs circulate from bone marrow to incorporate into and thus contribute to postnatal physiological and pathological neovascularization, which is consistent with postnatal vasculogenesis.
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PMID:Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. 1043 64

Microarray gene expression technology has recently made it feasible to characterize the RNA expression of thousands of genes across numerous tissue samples. We hypothesized that the warm ischemia commonly associated with the surgical extirpation of human tissue would have significant effects on gene expression profiles. To quantitate the effects of warm ischemia on human tissue, we rapidly dissected normal mucosa from a human colon cancer specimen. The specimen was divided and maintained at room temperature until snap-frozen in liquid nitrogen. Aliquots of tissue were frozen at times 5, 10, 15, 20, 40, and 60 min after extirpation. Spotted microarrays composed of 2400 distinct elements were used to assay mRNA derived from each time point in triplicate. Eisen's hierarchical clustering methodology and Bayesean statistical methods were then used to assay the effects of warm ischemia on gene expression. Application of time-course statistical models suggest that three patterns were induced by ischemia, accounting for 68.2, 17.8, and 13.4% of the evaluable genes, respectively. Pattern I corresponds to an average change of 27% over 60 min from 5 min baseline level of expression and 63.8% of the genes with at least 80% probability of membership in this pattern show average increases in expression over 60 min. The remainder decrease on average. Pattern II genes show the least ischemia-related effects, demonstrating an average change of only 12% over 60 min. In contrast to pattern I, we find that 67.5% of the genes with at least 80% probability of membership in this pattern are decreasing in expression on average over time. The remaining 32.5% in this pattern increase an average of 12% over 60 min. Finally, pattern III genes (13.4% of the sample) show the greatest sensitivity to ischemia, changing an average of 50% over 60 min, with about the same number increasing as are decreasing. Fold changes in RNA over- or under-expression were observed up to greater than 20-fold. Warm ischemia associated with the surgical extirpation of human tissues has significant effects on gene expression. These data support the careful monitoring of ischemic time for tissues harvested for the purpose of gene profiling.
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PMID:Effects of ischemia on gene expression. 1146 90

The present paper summarizes the various themes of research which have been developed in the department of medical gastroenterology since it was created in 1977. These include: in pancreatology, the study of chronic pancreatitis pathogenesis, acute pancreatitis pathogenesis and immunomodulation, endoscopic treatment of chronic pancreatitis, the development of new imaging techniques of the bile ducts and the pancreas, as well as the treatment of pancreatic cancer and benign or malignant biliary diseases. in hepatology, the immunomodulation of liver cirrhosis, especially alcoholic liver disease, the modulation of experimental acute and chronic hepatitis, the study of liver ischemia-reperfusion. Clinical hepatology has focused on liver transplantation, prognosis factors of chronic liver disease and treatment of portal hypertension and viral hepatitis. in gut diseases, the treatment of gastro-oesophageal reflux and its complications, the therapeutic endoscopy of the upper and lower GI and the prevention, as well as the treatment, of colon cancer, the pathogenesis and the immunopharmacology of inflammatory bowel diseases and the clinical enteral and parenteral nutrition.
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PMID:[The medical gastroenterology department]. 1258 14

A rat colonic adenocarcinoma was implanted subcutaneously in female nude (C57BL/6JBom-nu) mice. After 7 days, the animals were divided into different groups. One group received triple therapy with octreotide, galanin, and serotonin, 10 microg/kg body weight of each, twice daily. The second group served as controls and received only saline solution. Three groups received 10 microg/kg body weight twice daily of octreotide, galanin, or serotonin. The last group consisted of controls that received only saline solution. The treatment lasted for 5 days. The tumour volume, wet weight, and relative volume density of blood vessels were significantly decreased after the triple treatment, as compared to controls. Apoptotic index was significantly increased, but the proliferation index was not affected in the group of mice that received triple therapy. There was no significant difference between controls and mice treated with octreotide, galanin, or serotonin regarding tumour volume or weight. The relative volume density of blood vessels was decreased in tumours treated with galanin, but not with octreotide or serotonin. There was no statistical difference in the proliferation index between controls and animals treated with octreotide, galanin, or serotonin, as compared with controls. Tumour necrosis and increased apoptosis may be responsible for the reduction in the volume and weight of the tumour after triple therapy. Tumour necrosis may be caused by the induction of tumour ischemia due to a reduction in tumour blood flow, which is caused by decreased incidence of tumour-feeding blood vessels, and by constriction of tumour-feeding arterioles. These results are promising and may offer treatment for colon cancer.
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PMID:Triple therapy with octreotide, galanin, and serotonin reduces the size and blood vessel density and increases apoptosis of a rat colon carcinoma. 1260 62

Gastrointestinal complications are frequent in renal transplant recipients and can include oral lesions, esophagitis, peptic ulcer, diarrhea, colon disorders and malignancy. Oral lesions may be caused by drugs such as cyclosporine and sirolimus, by virus or fungal infections. Leukoplakia may develop in patients with Epstein-Barr virus (EBV) infection. The commonest esophageal disorder is represented by fungal esophagitis usually caused by candida. A number of patients may suffer from nausea, vomiting and gastric discomfort. These disorders are more frequent in patients treated with mycophenolate mofetil (MMF). Peptic ulcer is more rare than in the past. Patients with a history of peptic ulcer are particularly prone to this complication. Other gastroduodenal disorders are caused by cytomegalovirus (CMV) and herpes simplex infection. Diarrhea is a frequent disorder which may be caused by pathogen microorganisms or by immunosuppressive agents. The differential diagnosis may be difficult. Colon disorders mainly consist of hemorrhage, usually sustained by CMV infection, or perforation which may be caused by diverticulitis or intestinal ischemia. Colon cancer, anal carcinoma, and EBV-associated lymphoproliferative disorders are particularly frequent in transplant recipients. A particular gastric lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the eradication of Helicobacter pylori.
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PMID:Gastrointestinal complications in renal transplant recipients. 1591 Feb 87


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