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

The local recurrence, after radical exeresis of a large intestinal cancer represents until now an extremely interesting question, taking into consideration that it represents the cause of death in 50% of operated patients. Frequency is higher after an exeresis of a rectal cancer, with a range of 2.6-83% in the different case histories, than after a surgical intervention on a colon cancer, whose incidence is lower than 5%. The early diagnosis of rectum cancer recurrence is the first step towards the favourable issue of treatment. Surgical treatment of loco-regional recurrences of rectum cancer can be curative when it is possible to perform a total resection of the recurrences and of the infiltrated structures, without microscopic residuals of disease, or palliative, aiming to reset the intestinal and urinary functions or to reduce pain. At the Department of Surgery of the University of Perugia, from January 1984 to December 1983, 153 patients with rectal cancer-79 males (52%) and 74 females (48%)-were treated. The operations, all involved total removal of the affected segment and were in 88 cases (58%) an anterior resection and in 65 cases (42%) an abdomino-perineal amputation. The analysis was made of 128 patients with a follow-up of at least five years; the local recurrence incidence was 12.5%. The authors adopted a follow-up protocol based on clinical examination, CEA antigen and routine Lab tests, chest X-rays, colonoscopy, abdominal ultrasonography, pelvic CT scan; these procedures are performed starting 3 months after operation.
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PMID:Surgery of local recurrence in rectal cancer. 908 32

A considerable amount of evidence collected from several different experimental systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal tumorigenesis. Large epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in persons taking aspirin or other nonsteroidal antiinflammatory drugs on a regular basis. One property shared by all of these drugs is their ability to inhibit COX, a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans and rodents. In this study, we selected two transformed human colon cancer cell lines for studies on the role of COX-2 in intestinal tumorigenesis. We evaluated HCA-7 cells which express high levels of COX-2 protein constitutively and HCT-116 cells which lack COX-2 protein. Treatment of nude mice implanted with HCA-7 cells with a selective COX-2 inhibitor (SC-58125), reduced tumor formation by 85-90%. SC-58125 also inhibited colony formation of cultured HCA-7 cells. Conversely, SC-58125 had no effect on HCT-116 implants in nude mice or colony formation in culture. Here we provide evidence that there may be a direct link between inhibition of intestinal cancer growth and selective inhibition of the COX-2 pathway.
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PMID:Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. 915 99

The incidence of colon cancer has increased during the last 30 years in Norway and is now the second most common newly diagnosed type of cancer in women and the third in men. Familial adenomatous polyposis, hereditary colorectal cancer, is caused primarily by inactivation of the tumour suppressor gene adenomatous polyposis coli (APC). The protein coded for by this gene has a possible role in cell-cell signalling or adhesion by binding to catenins which bind to the cell adhesion molecule E-cadherin, or in anchoring the cytoskeleton. Both germ-line and somatic APC gene mutations result in a truncated protein, due to introduction of a stop codon. The positions of the germ-line mutations seem to correlate with the seriousness of polyposis. The food mutagen PhIP causes specific mutations in the Apc gene in rats, and is a possible environmental mutagen also in humans. The Min mouse with mutated Apc-gene is a good model for studies of both induction and prevention of inherited and sporadic intestinal cancer.
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PMID:[Genetic and environmental factors in colorectal cancer. Mutations in the familial adenomatous polyposis gene]. 923 86

Non-traumatic gas gangrene is extremely rare. It is commonly associated with perforation of an occult gastro-intestinal cancer. The patient's course is usually fulminant. We report a case of subcutaneous emphysema and myonecrosis of the lower extremity due to a perforated carcinoma of the large bowel. The diagnosis of colonic cancer was suspected but treatment was regrettably delayed leading to the perforation and subsequent lower extremity gas gangrene. The patient survived following a femoral amputation.
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PMID:An unnecessary femoral amputation? 965 84

The Min (multiple intestinal neoplasia) strain of the laboratory mouse and its derivatives permit the fundamental study of factors that regulate the transition between normal and neoplastic growth. A gene of central importance in mediating these alternative patterns of growth is Apc, the mouse homologue of the human adenomatous polyposis coli (APC) gene. When adenomas form in the Min mouse, both copies of the Apc gene must be inactivated. One copy is mutated by the nonsense Apc allele carried in heterozygous form in this strain. The other copy can be silenced by any of several mechanisms. These range from loss of the homologue bearing the wild-type Apc allele; to interstitial deletions surrounding the wild-type allele; to intragenic mutation, including nonsense alleles; and finally, to a reduction in expression of the locus, perhaps owing to mutation in a regulatory locus. Each of these proposed mechanisms may constitute a two-hit genetic process as initially posited by Knudson; however, apparently the two hits could involve either a single locus or two loci. The kinetic order for the transition to adenoma may be still higher than two, if polyclonal adenomas require stronger interactions than passive fusion. The severity of the intestinal neoplastic phenotype of the Min mouse is strongly dependent upon loci other than Apc. One of these, Mom1, has now been rigorously identified at the molecular level as encoding an active resistance conferred by a secretory phospholipase. Mom1 acts locally within a crypt lineage, not systemically. Within the crypt lineage, however, its action seems to be non-autonomous: when tumours arise in Mom1 heterozygotes, the active resistance allele is maintained in the tumour (MOH or maintenance of heterozygosity). Indeed, the secretory phospholipase is synthesized by post-mitotic Paneth cells, not by the proliferative cells that presumably generate the tumour. An analysis of autonomy of modifier gene action in chimeric mice deserves detailed attention both to the number of genetic factors for which an animal is chimeric and to the clonal structure of the tissue in question. Beyond Mom1, other loci can strongly modify the severity of the Min phenotype. An emergent challenge is to find ways to identify the full set of genes that interact with the intestinal cancer predisposition of the Min mouse strain. With such a set, one can then work, using contemporary mouse genetics, to identify the molecular, cellular and organismal strategies that integrate their functions. Finally, with appropriately phenotyped human families, one can investigate by a candidate approach which modifying factors influence the epidemiology of human colon cancer. Even if a candidate modifier does not explain any of the genetic epidemiology of colon cancer in human populations, modifier activities discovered by mouse genetics provide candidates for chemopreventive and/or therapeutic modalities in the human.
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PMID:The intestinal epithelium and its neoplasms: genetic, cellular and tissue interactions. 968 89

Cancer predisposition in hereditary non-polyposis colon cancer (HNPCC) is caused by defects in DNA mismatch repair (MMR). Mismatch recognition is attributed to two heterodimeric protein complexes: MutSalpha (refs 2, 3, 4, 5), a dimer of MutS homologues MSH2 and MSH6; and MutSbeta (refs 2,7), a dimer of MSH2 and MSH3. These complexes have specific and redundant mismatch recognition capacity. Whereas MSH2 deficiency ablates the activity of both dimers, causing strong cancer predisposition in mice and men, loss of MSH3 or MSH6 (also known as GTBP) function causes a partial MMR defect. This may explain the rarity of MSH6 and absence of MSH3 germline mutations in HNPCC families. To test this, we have inactivated the mouse genes Msh3 (formerly Rep3 ) and Msh6 (formerly Gtmbp). Msh6-deficient mice were prone to cancer; most animals developed lymphomas or epithelial tumours originating from the skin and uterus but only rarely from the intestine. Msh3 deficiency did not cause cancer predisposition, but in an Msh6 -deficient background, loss of Msh3 accelerated intestinal tumorigenesis. Lymphomagenesis was not affected. Furthermore, mismatch-directed anti-recombination and sensitivity to methylating agents required Msh2 and Msh6, but not Msh3. Thus, loss of MMR functions specific to Msh2/Msh6 is sufficient for lymphoma development in mice, whereas predisposition to intestinal cancer requires loss of function of both Msh2/Msh6 and Msh2/Msh3.
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PMID:HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. 1054 54

Increased cell surface expression of the Thomsen-Friedenreich antigen (TF antigen, Galbeta1-3GalNAcalpha-) is a common feature in malignant and pre-malignant epithelia. Our previous studies have shown that dietary TF-binding lectins from peanut (Arachis hypogea) and edible mushroom (Agaricus bisporus) produce marked but different effects on human intestinal epithelial cell proliferation. This study investigates the proliferative effects of the other two known dietary TF-binding lectins: jacalin (Artocarpus integrifolia, JAC) and amaranth lectin (Amaranthus caudatus, ACA). JAC produced dose-dependent and non-cytotoxic inhibition of proliferation in HT29 human colon cancer cells with maximal effects of 46 +/- 4% at 20 microg/ml, whereas ACA produced dose-dependent stimulation of proliferation with maximal effects of 22 +/- 3% at 20 microg/ml when assessed both by incorporation of [3H]thymidine into DNA and by cell counting. The lectin-mediated effects were inhibitable by the presence of appropriate Galbeta1-3GalNAc-expressing glycoproteins but differences existed between JAC and ACA in their patterns of inhibition by such substances. Ligand binding equilibrium studies using iodinated lectins revealed different Kd of the two lectins for HT29 cell surface glycoproteins. Lectin blots of cell membrane extracts showed different binding patterns in all the four TF-binding lectins. These results provide further evidence that dietary TF-binding lectins can have marked effects on the proliferation of human malignant gastro-intestinal epithelial cells and hence may play a role in intestinal cancer development, and also show that the biological effects of dietary lectins cannot be predicted solely from their carbohydrate binding properties.
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PMID:Opposite effects on human colon cancer cell proliferation of two dietary Thomsen-Friedenreich antigen-binding lectins. 1116 64

Arachidonic acid is an important polyunsaturated fatty acid involved in cell signaling. It is derived primarily from dietary linoleic acid, and the rate-limiting step in its biosynthesis is the initial desaturation of linoleic acid via Delta-6 desaturase. Evidence suggests that downstream metabolic products of arachidonic acid, e.g. prostaglandins, are involved in colorectal cancer, but involvement of the biosynthetic pathway of arachidonic acid has not been previously investigated. In the present study, we report the effects of a novel selective Delta-6 desaturase inhibitor, SC-26196, on tumorigenesis in two in vivo models of intestinal cancer. SC-26196 treatment resulted in 36-37% fewer tumors in Apc(Min/+) mice and 35% decrease in primary tumor size in nude mice bearing HT-29 human colon cancer cell xenografts (P<0.05). As expected, SC-26196 treatment resulted in significantly higher linoleic acid levels in tissue phospholipids and lower levels of arachidonic acid. The effects on both tissue fatty acid composition and tumorigenesis in Apc(Min/+) mice were abrogated by concomitant treatment with dietary arachidonic acid, indicating that the observed effects were due to interference with the biosynthetic pathway of arachidonic acid.
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PMID:Selective inhibition of Delta-6 desaturase impedes intestinal tumorigenesis. 1174 43

Multiple intestinal neoplasia (Min) mice are a good model for the investigation of the effects of dietary alterations in a genetic model for intestinal cancer. Previous studies have shown that selenium-enriched broccoli is protective against chemically induced colon cancer susceptibility. This study investigated whether selenium-enriched broccoli would be protective against intestinal cancer susceptibility in Min mice. Five-week-old heterozygotic male Min mice were fed an AIN-93-based diet containing either low-selenium broccoli or an equivalent amount of high-selenium broccoli for 10 wk. Mice fed the selenium-enriched broccoli had fewer (P < 0.02) small intestinal (46.4 +/- 3.7 vs. 65.6 +/- 6.1) and large intestinal (0.43 +/- 0.17 vs. 1.93 +/- 0.27) tumors than those fed an equivalent amount of unenriched broccoli. Min mice fed the selenium-enriched broccoli had small but significant (P < 0.0001) increases in plasma and liver selenium concentrations and red blood cell glutathione peroxidase activity. These results extend previous observations that selenium-enriched broccoli is protective against chemically induced mammary and colon cancer in rats.
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PMID:Selenium-enriched broccoli decreases intestinal tumorigenesis in multiple intestinal neoplasia mice. 1182 96

Our data suggest that lymph-node size is not a reliable indicator for lymph-node metastasis in gastric, esophageal, and colon cancer. Despite a significant difference in diameter of metastatic and non-metastatic nodes, the accurate evaluation of lymph-node metastasis in gastro-intestinal carcinoma cannot be determined by nodal size, because the majority of counted lymph nodes is ?5 mm and the frequency of small lymph-node metastases is high. Therefore imaging techniques using the size as criterion of nodal infiltration can not exactly assess the nodal status of patients with gastro-intestinal carcinomas. For rational lymphadenectomy, the value of sentinel node biopsy in gastro-intestinal cancer is now discussed. At the moment it is too early to apply sentinel node biopsy in order to reduce the extent of lymphadenectomy in these carcinomas [11]. Recent interest has focused on PET scanning in the detection of lymph-node metastases. PET represents a potentially ideal imaging modality for malignancy. It allows a quick and simultaneous assessment of both local and distant sites and, as a result of avid uptake of the glucose moiety, may potentially identify small tumor loads. There are only limited experience in detecting lymph-node metastases in gastro-intestinal carcinoma and the results of the published reports are controversially discussed [12, 13]. Our data demonstrate a high frequency of small lymph-node metastases in gastro-intestinal carcinoma and suggest that a careful histological search for small lymph-node metastases should be undertaken to avoid false-negative lymph-node staging. These results emphasize that a reliable pathological staging of gastro-intestinal cancer must be based on a standardized systematic lymphadenectomy because lymph-node sampling based on lymph-node size is not sufficient.
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PMID:Preoperative lymph-node staging in gastrointestinal cancer--correlation between size and tumor stage. 1223 85


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