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PubMed1993

Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer.

Activation of the tyrosine kinase of the c-src gene product, pp60c-src, has been shown to occur in nearly every primary colorectal carcinoma, and is found as early as in polyps of high malignant potential. However, no studies have addressed potential pp60c-src changes which occur during progression. To examine this question, we have studied kinase activity and protein levels in 7 colonic polyps, 19 primary lesions, and 19 liver metastases relative to normal colonic mucosa. Significant increases in tyrosine kinase activity were seen as early as in colonic polyps of high malignant potential. Further increases were observed in activity and level in primary tumors. However, the greatest increases in activity and protein levels were observed in liver metastases. Additionally, six metastatic lesions were obtained in which synchronous primary tumor was resected. In each of these liver metastases, pp60c-src activity and level were significantly increased relative to the corresponding primary tumor, as well as to normal colonic mucosa. Our results demonstrate that progression of colon primary tumors to liver metastases correlates with increased pp60c-src kinase activity and protein level.

Adenocarcinoma↗
PubMed2000

Blood polyamine levels after oral ornithine load, a diagnostic marker of hyperproliferative premalignant and malignant stages in a model of colon carcinogenesis.

This study was performed to determine whether a single oral dose of ornithine (Orn), the substrate of ornithine decarboxylase (ODC), increases blood concentrations of polyamines premalignant stage, and whether blood polyamine levels could be used as predictive markers of cancer development. Male Wistar rats were divided into two groups, control and 1,2-dimethylhydrazine (DMH)-treated rats. DMH (20 mg/kg body weight) was injected intraperitoneally once weekly for 10 weeks. Five, 7, and 10 weeks after the last injection when premalignant aberrant crypt foci have developed in the colon, blood levels of putrescine (PUT), spermidine (SPD), and spermine (SPM) were estimated before and after an oral load of ORN. The results showed that after a single oral load of Orn, blood PUT, but not SPD and SPM, concentrations were significantly higher in DMH-treated rats compared with control rats, indicating enhancement of ODC activity. These results support the view that the increased blood concentration of PUT after administration of Orn may be a useful marker to detect hyperproliferative premalignant and malignant stages of cancer development.

1,2-Dimethylhydrazine↗
PubMed2001

Endoscopic mucosal resection of colon polyps.

The term submucosal injection polypectomy (SIP) more accurately describes the technique used for removal of flat colonic polyps and is preferred, in the colon, to endoscopic mucosal resection (a procedure that usually uses a special suction-activated device). Using SIP, most polyps can be removed safely from any part of the colon. The methodology is described in detail and is within the capability of most colonoscopists.

Colonic Neoplasms↗
PubMed1990

[The characteristics of bile acid excretion in patients with cancer of the large intestine].

Marked difference in bile acids excretion (on the same diet) was observed between patients with large bowel cancer and healthy controls. The peak level of the bile acids in feces was registered in female patients 46-59 years of age suffering right-sided cancer. It is suggested that bile acid excretion in man is determined both by nutritional factors and hormonal-metabolic peculiarities of the body. High excretion of the bile acids is associated with risk for colon cancer.

Aging↗
PubMed1987

Immunohistochemical studies of colorectal carcinoma with a monoclonal antibody against carcinoembryonic antigen.

Immunoperoxidase localization of carcinoembryonic antigen (CEA) was performed on tissue sections of colorectal carcinoma using a monoclonal antibody (MAb) against CEA. CEA has been demonstrated in 20 out of 22 rectum carcinomas (90.9%), in all of 23 colonic carcinomas, in none of 4 hyperplastic polyps and in 2 out of 6 adenomatous polyps (33.3%). CEA was found more often, and the intensity of the staining was stronger in well-differentiated carcinomas than in moderately and poorly differentiated carcinomas. No correlation was found between the presence of CEA in colorectal carcinoma and the stages of the disease. The mean values of serum CEA in patients with colorectal carcinoma and polyps with negative, weakly and strongly positive staining were 5.4 +/- 3.9 ng/ml, 28.3 +/- 23.8 ng/ml and 99.8 +/- 145.3 ng/ml respectively. Elevation of serum CEA occurred in 30 out of 39 (78.9%) cases with strongly positive CEA staining, in 4 out of 6 (66.7%) with weakly positive and in 1 out 9 (11.1%) with negative staining. A significant difference was found in serum CEA activity between the group with negative CEA staining and positive CEA staining (P less than 0.01). Our results suggest that the monoclonal antibody (MAb C27) can be used for the localization of CEA in conventionally prepared tissues of colorectal carcinomas by immunoperoxidase techniques for routine immunopathological diagnosis.

Adenocarcinoma↗
PubMedDate not supplied

[Villous and tubulovillous adenomas of the colon and rectum. Results in 30 patients].

UNLABELLED: Colorectal adenomas precede carcinomas as much as they become larger and present villous histology. Since colonoscopic polypectomy cannot remove all polyps, surgical options include local resection as well as segmental colectomy. Significant morbidity and high recurrence rates may occur following individual and polyp-related characteristics. This paper focuses the clinical aspects of colorectal tubulo-villous adenomas and the results of the surgical treatment. PATIENTS AND METHODS: Hospital charts from 30 patients who underwent surgical treatment of colorectal tubulovillous adenomas between 1980 and 1997 were retrospectively reviewed. RESULTS: Rectal bleeding, urgency and mucus discharge were the most frequent clinical findings. Proctologic examination (digital and rigid rectosigmoidoscopy) diagnosed the lesion for the majority of cases. Seventy per cent of the polyps were in the distal rectum and 60% were larger than 4 cm. Transanal resection was the surgical option for one half of the patients and segmental colectomy for the other. Fourty-two per cent of the polyps that were considered benign as result of preoperative biopsy showed malignant transformation when the whole polyp was examined. Recurrence rate was 26.7% and 6.7% for patients who underwent local resection and segmental colectomy respectively. Postoperative complication rate was similar for the two surgical groups. CONCLUSIONS: Recurrence may occur frequently after standard local resection. Preoperative biopsy examination has no role for the diagnosis of malignant transformation. Office proctologic examination diagnoses majority of colorectal polyps that may be elected for surgical resection.

Adenoma, Villous↗
PubMed1988

Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid.

Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5-aminosalicylic acid (5-ASA), and the 5-ASA metabolite N-acetylated-5-ASA (ac-5-ASA)) was tested at therapeutic colonic concentrations of 0.01-10 mM. Leukotriene B4 at a dose of 10 nM was equipotent with casein (5 g litre-1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5-ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mM, respectively. These concentrations are below the lowest concentration of 5-ASA (2 mM) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.

Adult↗
PubMed2001

Chemoprevention of Colon Carcinogenesis by Dietary Non-nutritive Compounds.

In addition to mutagens and/or carcinogens a number of modulators of carcinogenesis are present in our environment. Some of them are contained in our regular foods and therefore dietary factors play a role in the development of some types of cancers including colon cancer. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with reduced risk for a number of common cancers. There are still many unknown constituents and/or factors in foods that could either enhance or reduce the possibility of developing cancer. Animal studies of experimental chemical carcinogenesis have indicated that several non-nutritive components in foods, belonging to different chemical groups, protect against certain types of cancers including colonic neoplasms. These chemicals are known as "chemopreventive agents". Many of them are antioxidants and might suppress carcinogenesis through: (I) inhibiting Phase I enzymes; (ii) induction of Phase II enzymes; (iii) scavenging DNA reactive agents; (iv) suppression of hyper-cell proliferation induced by carcinogens; and/or (v) inhibition of certain properties of neoplastic cells. With the continuing increase in the incidence of colon cancer, there is an ever increasing need to determine the most effective means for prevention and to understand the underlying mechanism(s). Previous studies in our laboratory demonstrated protective effects of several naturally occurring products against rat colon tumorigenesis. This article will introduce our recent studies in our search for chemopreventive effects of flavonoids (diosmin and hesperidin) and other phytochemicals in edible plants on rat colon carcinogenesis.

Journal Article↗
PubMedDate not supplied

Diet and chemoprevention of colon polyps and colorectal cancer.

Clinical trials in colorectal cancer prevention are based on carcinogenesis research and epidemiologic observations that relate certain macronutrients, micronutrients, non-nutritive factors in foods, and synthetic chemicals to colon neoplasms. These factors appear to act at various points along the putative normal mucosa --> adenomatous polyp --> cancer sequence. This gives an opportunity to develop innovative clinical trails, both in agent selection and in the use of intermediate markers. Clinical colorectal cancer prevention trials are not in progress that employ dietary fiber, a variety of vitamins and minerals and several synthetic drugs, especially the NSAIDs. Most of these trials use the adenomatous polyp as a surrogate marker for colon cancer, thereby reducing trial duration, number of subjects required and overall expense. This paper is a brief review of the basic and epidemiologic background for colorectal cancer prevention trials and their current status.

Anti-Inflammatory Agents, Non-Steroidal↗