Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial infiltrative fibromatosis (desmoid tumor) is a recognized complication of familial adenomatous polyposis (FAP) but has not been described in families without colonic polyposis. The authors describe a unique family in which a predisposition to infiltrative fibromatosis and nonpolyposis colon cancer was inherited dominantly through four generations. This report expands the range of phenotypic variation described for the hereditary nonpolyposis colon cancer (HNPCC) syndrome and adds to the extracolonic complications that are common with FAP and HNPCC.
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PMID:Phenotypic variation in hereditary nonpolyposis colon cancer syndrome. Association with infiltrative fibromatosis (desmoid tumor). 154 13

A 43-year-old woman with familial polyposis coli (FPC) and adenocarcinoma of the rectosigmoid was treated by total colectomy, mucosal proctectomy and construction of an ileal pouch with ileoanal anastomosis. A year after operation she developed a huge retroperitoneal desmoid tumor which on exploratory laparotomy was found to be nonresectable. A 21-month course of indomethacin followed by tamoxifen failed to induce regression of the tumor. Desmoid tumors appear in 3.5-29.0% of patients with FPC, mostly after colectomy. This possibility must be considered in the differential diagnosis of recurrent carcinoma of the colon. The preferred treatment of abdominal and retroperitoneal desmoid tumors is conservative, and includes the use of non-steroidal antiinflammatory drugs, ascorbic acid and tamoxifen.
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PMID:[Retroperitoneal desmoid tumor and familial polyposis coli]. 254 78

Colorectal cancer is the second most common cancer in the United Kingdom and other developed countries in the West. Although it is usually not familial, there is a rare dominantly inherited susceptibility to colon cancer, familial adenomatous polyposis (FAP; also often previously called familial polyposis coli). During adolescence affected individuals develop from a few hundred to over a thousand adenomatous polyps in their large bowel. These are sufficiently likely to give rise to adenocarcinomas to make prophylactic removal of the colon usual in diagnosed FAP individuals. Adenomas may occur elsewhere in the gastrointestinal tract and the condition is often associated with other extracolonic lesions, such as epidermoid cysts, jaw osteomata and fibrous desmoid tumours. Adenomata have been suggested to be precancerous states for most colorectal tumours. Knudson has suggested that the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumour cells, and that the same gene may be involved in both familial and non-familial cases of a given tumour. Following up a case report of an interstitial deletion of chromosome 5 in a mentally retarded individual with multiple developmental abnormalities and FAP, we have now shown that the FAP gene is on chromosome 5, most probably near bands 5q21-q22.
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PMID:Localization of the gene for familial adenomatous polyposis on chromosome 5. 303 73

Familial adenomatous polyposis (FAP) is a dominantly inherited genetic disorder predisposing to colon cancer through the early development of multiple adenomatous polyps in the large bowel. FAP is not restricted to the colon and rectum, but is a more complex disease which can potentially affect almost any organ not only with benign tumours but also with life threatening carcinomas. Desmoid tumours and gastroduodenal polyps and cancer are the two more worrying extracolonic manifestations of FAP. Recent advances in FAP knowledge, such as the report of congenital hypertrophy of the retinal pigment epithelium (CHRPE) or the APC gene identification, are very useful for screening and long-term follow-up of the patients through regional or national registries. Nutritional and pharmacological intervention trials are under way to assess potential new medical treatments of FAP. Surgery is still the only effective treatment for colorectal cancer prevention in FAP. The choice of a surgical procedure is controversial, but the introduction of total proctocolectomy with ileal pouch-anal anastomosis can be considered as a major advance in surgical treatment of FAP during the last decade.
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PMID:The clinical [corrected] background of familial adenomatous polyposis. History, epidemiology, diagnosis and treatment. 757 88

In humans, tumor necrosis factor (TNF) treatment has been associated with characteristic changes in circulating white blood cell populations (leukopenia followed by leukocytosis) and increased cell-surface expression of integrins. A similar pattern of effects on leukocytes occurs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF treatment. To determine whether these effects were caused directly by TNF or as a result of secondary CSF release, G-GM-, and M-CSF levels were measured after TNF infusion (9.6 x 10(6) U/mg protein; < 5.0 endotoxin U/mg protein) in cancer patients during two phase I trials of TNF. One patient with aggressive fibromatosis was treated with TNF alone (200 micrograms/m2, days 1-5 every third week) and 10 patients (four colon cancer, four head and neck cancer; one melanoma; one sarcoma) received mitomycin C (15 mg/m2, day 1) followed by TNF (60-180 micrograms/m2, days 1-3) every sixth week. All treatments were given IV, mitomycin C over 5 minutes and TNF over 2 hours. Serum samples were collected at times 0 (before mitomycin C and TNF) and 1, 2, 4, 6, 12, and 24 hours after TNF initiation on day 1 and at similar times on subsequent treatment days. M-CSF samples were analyzed by radioimmunoassay (RIA) and G-CSF and GM-CSF by ELISA. The mean baseline M-CSF levels in normal control subjects (n = 12) was 158.4 +/- 36.2 (SD) U/mL, and in pretreatment cancer patients (n = 10) 235.7 +/- 60.9 U/mL (p = 0.004, Wilcoxon test). M-CSF levels increased 4 hours after TNF initiation (mean 354.7 +/- 96.3 U/mL; p = 0.020), remained elevated at 6 hours (305.6 +/- 45.4 U/mL; p = 0.004, Wilcoxon signed-rank test), and subsequently declined. This pattern was seen in all patients treated with TNF, whether treatment was TNF alone or TNF with mitomycin C. In patients treated with mitomycin C and TNF, G-CSF levels increased at 4 hours after TNF initiation (mean 3886 +/- 2009 pg/mL; p = 0.004), remained elevated at 6 hours (mean 2140 +/- 1131 pg/mL; p = 0.004), and subsequently declined. GM-CSF levels were not measurable before or after treatment with TNF. The changes in all three endogenous cytokines were not temporally related to the previously described leukopenia and integrin upregulation on circulating leukocytes and, therefore, appear to be unrelated to this event. However, release of endogenous G-CSF and M-CSF under the influence of TNF does temporally coincide with the previously described leukocytosis, suggesting a possible role for these endogenous cytokines in the release of bone marrow cellular stores.
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PMID:Tumor necrosis factor administration is associated with increased endogenous production of M-CSF and G-CSF but not GM-CSF in human cancer patients. 853 92

The management of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis (FAP) is very difficult. Non-steroidal anti-inflammatory drugs (NSAIDs), anti-estrogenic agents, and steroids are most commonly used, because surgical removal of these tumors may result in severe morbidity, with local recurrence being common. We report a patient with FAP and intra-abdominal desmoid tumors that regressed markedly after prednisolone therapy. The patient, a 38-year-old woman, had undergone total colectomy and ileorectal anastomosis with a diagnosis of FAP with colon cancer. Approximately 17 months after the surgery, she noticed an elastic firm lump in the abdominal wall. She also experienced lower abdominal distension. Computed tomography (CT) of the lower abdomen showed an invasive heterogenous low-density mass occupying the intra-abdominal space. She was treated with sulindac, NSAID, at 300 mg/day, the diagnosis being intra-abdominal desmoid tumors. She exhibited an intestinal obstruction about 9 months after the initiation of sulindac therapy. We changed the treatment and began prednisolone (initial dose, 40 mg/day). This treatment was continued for two years; subsequently, the lesions regressed markedly. She is currently well, more than 3 years after the withdrawal of prednisolone.
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PMID:Prednisolone therapy for intra-abdominal desmoid tumors in a patient with familial adenomatous polyposis. 908 78

Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues. In some cases, this is caused by a somatic mutation resulting in a truncated APC protein.
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PMID:Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). 925 Jan 46

We investigated whether the therapeutic action of sulindac, used for the treatment of familial adenomatous polyposis, desmoid tumors, and against colon cancer, could be mediated by its active metabolite, sulindac sulfide, in cell growth and apoptosis on cell lines derived from abdominal neoplasms. Sulindac sulfide actions on cell growth and apoptosis were evaluated in epithelial human colon tumor 8 (HCT8) cell line and mesenchymal cell lines (bovine bone endothelial (BBE) cell line, desmoid tumor-derived cells, human colorectal cancer-derived fibroblasts). Sulindac sulfide (0.1-60 microg/ml) induced a dose-dependent inhibition of cell proliferation of all cell lines tested. Apoptosis was induced at doses of 20 and 40 microg/ml, respectively, in BBE and HCT8 cells with no effect on desmoid tumor cells and colorectal cancer-derived fibroblasts. Since mesenchymal cells respond to clinically effective concentrations of the compound, its preferential action on the stromal compartment of intestinal polyps, desmoid tumors and colon cancer can be proposed, with consequent regression of the tumor.
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PMID:Apoptosis induced by sulindac sulfide in epithelial and mesenchymal cells from human abdominal neoplasms. 984 79

Defects in APC and DNA mismatch repair genes are associated with a strong predisposition to colon cancer in humans, and numerous mouse strains with mutations in these genes have been generated. In this report we describe the phenotype of Min/+ Mlh1-/- mice. We find that these doubly mutant mice develop more than three times the number of intestinal adenomas compared to Min/+ Mlh1+/+ or +/- mice but that these tumors do not show advanced progression in terms of tumor size or histological appearance. Full length Apc protein was not detected in the tumor cells from Min/+ Mlh1-/- mice. Molecular analyses indicated that in many tumors from Min/+ Mlh1-/- mice, Apc was inactivated by intragenic mutation. Mlh1 deficiency in Min/+ mice also led to an increase in cystic intestinal crypt multiplicity as well as enhancing desmoid tumorigenesis and epidermoid cyst development. Thus, Mlh1 deficiency influences the somatic events involved in the development of most of the phenotypes associated with the Min mutation. Oncogene (2000).
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PMID:Mlh1 deficiency enhances several phenotypes of Apc(Min)/+ mice. 1085 Oct 78

Familial adenomatous polyposis (FAP) is an autosomal dominant condition characterized by diffuse intestinal polyposis, specific gene mutation, and predisposition for developing colon cancer. Left untreated, patients with FAP will develop colorectal carcinoma during early adulthood. Hence, early detection and surgical intervention are of the utmost importance. Colectomy is required and may include an ileal pouch with ileoanal anastomosis, which eliminates the colon and rectal disease while preserving fecal continence and avoidance of a permanent ileostomy. Advances in the treatment of FAP with associated reduction in mortality from colorectal carcinoma make extracolonic manifestations of the disease more common and life-long surveillance is mandatory. The most life-threatening extracolonic manifestations of FAP are periampullary carcinoma and desmoid tumors. The upper gastrointestinal tract should be monitored endoscopically at the time of diagnosis and assessed regularly thereafter. Duodenal adenomas should be resected so as to avoid the devastating effects of invasive periampullary carcinoma. Additionally, the development of desmoid tumors needs to be monitored (by CT or MRI), so as to avoid the severe complications of local invasion. Further research is indicated in the development of effective screening and treatment for this condition.
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PMID:Familial adenomatous polyposis: a case report and review of the literature. 1144 92


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