Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.
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PMID:Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens. 192 98

Recurrent disease from colorectal carcinomas is common. 25 percent of patients have apparent metastases at the time of first detection of the tumor, and at least 50% of patients die from their tumor. The aim of the postoperative follow-up of patients with carcinoma of the colon and rectum is thus to detect recurrent tumor when cure is still possible. Clinical examination and CEA-measurement is widely recommended as a reliable indicator for recurrence and metastases of colonic cancer. This may be combined with regular coloscopic surveillance for detection of anastomotic recurrences or a second colonic cancer. In case of suspicion of a recurrence or metastasis a full range of examinations should be performed to detect the site of recurrent tumor and to exclude wide spread disease. In case of a circumscribed lesion the patients may benefit from local radical resection. Patients with four or less unilateral liver metastases show a five year disease free survival reported of more than 30% and a disease free survival reported of more than 25%. Unfortunately because of wide spread misunderstanding of the potential of hepatic Rx only about 1/3 of potentially curatively resectable patients with liver metastases finally undergo liver surgery. A more active policy towards patients with colorectal disease concerning surveillance may lead to a better survival in selected cases.
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PMID:[Colorectal cancers: therapy of recurrences and metastases]. 192 5

Lactose-binding lectins having Mr values of approximately 14,000 (L-14.5) and approximately 35,000 Da have been found in a variety of vertebrate tissues, including normal intestine and colon, and in several types of tumors such as colon carcinomas. To determine the clinical relevance of such lectins in human colon cancer, specimens from 46 patients with colorectal carcinoma of identified Dukes' stages were selected and analyzed for the presence and amount of lactose-binding lectins by immunoblotting using a polyclonal, rabbit anti-lectin antibody followed by binding of 125I-labeled anti-rabbit IgG. The amount of a lectin having an Mr value of approximately 31,000 Da (L-31) varied among the specimens. The levels of L-31 lectin in colorectal cancer specimens from primary tumors of patients with distant metastases (Dukes' stage D) were significantly higher than were those from patients without detectable metastases (Dukes' stages B1 and B2). In contrast, among the various specimens the variation in the level of the L-14.5 lectin was smaller, and there was no correlation between the amount of this lectin and cancer stage. Immunohistochemical staining of thin sections of colorectal tumor specimens using antibodies specific for either L-31 or L-14.5 lectin revealed that the two were located at different places, the L-31 lectin primarily within the cytoplasm of carcinoma cells, and the L-14.5 lectin associated with secreted material. These results indicated that the relative amount of the L-31 lectin increases as the colorectal cancer progresses to a more malignant stage.
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PMID:Lactose-binding lectin expression in human colorectal carcinomas. Relation to tumor progression. 193 52

The systemic management of patients with colorectal cancer continues to center on the use of 5-fluorouracil (5-FU). In the setting of metastatic disease, parenteral 5-FU has been shown to be superior to oral 5-FU; however, survival duration seems similar regardless of whether parenteral 5-FU is administered in a "loading schedule," weekly, or in a continuous-infusion regimen. The addition of other cytotoxic agents, such as semustine (methyl-CCNU) and/or mitomycin C, to 5-FU does not appear to be beneficial. Recent efforts have been directed toward enhancing the activity of 5-FU by (1) increasing its incorporation into RNA through pretreatment with methotrexate or phosphonoacetyl-L-aspartate (PALA), (2) enhancing DNA synthesis inhibition via the concomitant administration of folinic acid, and (3) an undetermined modulatory action by the addition of alpha-interferon. These pharmacologic approaches are being compared in ongoing cooperative group trials. The results of five randomized trials assessing the value of intra-arterial, hepatic infusions of 5-FU or 5-fluorodeoxyuridine have demonstrated that regional chemotherapy increases the likelihood of a hepatic response when compared with systemic treatment, but has little effect on survival and is associated with significant toxicity. Recent adjuvant chemotherapy trials have indicated both a decrease in recurrence and a prolongation in survival when chemotherapy (5-FU + levamisole) is administered to patients with stage C colon cancer; and combined radiation therapy and chemotherapy is given to patients with stages B2 and C rectal cancer.
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PMID:Systemic therapy for colorectal cancer: an overview. 194 31

The lymphatic system is an important route of spread of hepatic metastatic disease to extrahepatic sites. Although portal and celiac nodes are commonly evaluated both pre- and intraoperatively in patients considered for resection, cephalad sites of drainage of the liver represent a more occult pitfall. We report a case of colon cancer metastatic to the right lobe with an isolated extrahepatic deposit in a mediastinal lymph node. This preoperative diagnosis was confirmed at a subsequent operation, leading to a change in treatment plan. We believe that such occurrences may be unrecognized rather than rare. Careful evaluation of the mediastinum prior to proceeding with hepatic resection may improve patient selection, and hence the outcome, of this procedure.
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PMID:Isolated spread of hepatic metastatic disease to a mediastinal lymph node. Report of a case and review of pertinent anatomy and literature. 195 65

To study the possible role of ras oncogene activation in the dissemination of colon cancer, we determined point mutations in codons 12, 13 and 61 in K- and N-ras in 3 groups of tumors: (A) primary tumors of patients who had undergone surgery for Dukes' B (early-stage) colon cancer, (B) primary tumors and metastases from patients undergoing resection of isolated lung metastases and (C) primary tumors and metastases from patients undergoing resection of isolated liver metastases. In 129 samples from 93 patients, 54 (42%) were positive for point mutations in either K- or N-ras. Most mutations (89%) were found in the K-ras gene. In group A (n = 50) ras point mutations were detected in 16 cases (32%) (15 in K-ras and 1 in N-ras). Thirteen out of 23 cases in group B (57%) were positive for a ras point mutation: 10 in K-ras and 3 in N-ras. In group C (n = 20), point mutations in codon 12 of K-ras, but none in H- or N-ras, were found in 10 cases (50%). In 31 cases the primary tumors from the metastases in groups B and C were available for analysis and 15 contained a ras point mutation (48%). Not all mutations were present in both the primary tumor and the metastasis. In 3 instances, a mutation was detected in the metastasis but not in the primary tumor, whereas in 1 case a mutation was found in the primary tumor.
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PMID:Differential activation of ras genes by point mutation in human colon cancer with metastases to either lung or liver. 195 91

Cytogenetic analyses of human colon cancer cells have revealed a high frequency of chromosome 1p deletions among other chromosomal abnormalities. In order to find out whether these chromosomal alterations are manifestations of loss of genetic material, we surveyed DNA of 62 primary tumors, 7 metastases, and matching peripheral blood cells with a panel of polymorphic DNA probes that detect different loci on chromosome 1p. A portion of the probes was derived from a microclone bank generated by microdissection and microcloning of 1p35----pter DNA. In 42% of the colon carcinomas allelic loss was observed with at least one probe. The deletions were of different sizes but always included a region involving band 1p35, except for two tumors in which allelic loss was detected more proximally. The frequency of 1p deletion in the metastases was higher than in the primary tumors. These data indicate that genetic information related to tumorigenesis is located within or nearby region 1p35 and that deletion of this region occurs later in tumor development. Our results add to the number of genetic changes presumably involved in colon cancerogenesis.
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PMID:Human colorectal cancer: high frequency of deletions at chromosome 1p35. 197 17

Fecal occult blood testing for the detection of colon cancer remains controversial. We performed a mass screening program from January 24, 1988, to February 19, 1988, with intensive media promotion, including 121 minutes of televised air time. A total of 5,000 primary practitioners were notified by mail. Hemoccult-II tests were distributed to 156,000 individuals; 55,051 (35%) were returned. Ninety-five percent of the respondents were informed of the program by television. A total of 3,375 persons (6%) tested positive for fecal occult blood; of these, 2,469 (73%) informed the center that they saw their physician to initiate a work-up. Information from physicians regarding work-ups was returned on only 1,356 (55%) patients. Diagnostic tests numbered 2,227 (1.6 tests per patient). However, 5% had no testing, 16% had a repeat Hemoccult only, and 35% had neither a barium enema nor colonoscopy performed. Thirty-six colorectal cancers and 212 polyps were identified. The predictive value (i.e., number of cancers per number of patients who tested positive) increased directly by decade. Thirty-three of 36 patients (92%) with cancer underwent either a barium enema or colonoscopy versus only 185 of 438 (42%) patients with a "negative" work-up. Cancers found were carcinoma in situ in 10 patients (29%), Dukes A in 12 (35%), Dukes B in 4 (12%), and Dukes C in 8 (24%); distant metastases were not found in any participant. Thirty-six percent of the tumors were located in either the right or transverse colon. We conclude that: (1) Screening identified early cancers. All were potentially curable and 64% were limited to the bowel wall. (2) Massive Hemoccult distribution was possible over a short interval, but patient and physician compliance was disturbingly low. (3) Total colonic evaluation is mandatory, since at least 36% of tumors were beyond the reach of the flexible sigmoidoscope. (4) Many work-ups were unnecessary (repeat Hemoccults) or inadequate, indicating a need for physician education.
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PMID:A critical analysis of the largest reported mass fecal occult blood screening program in the United States. 198 42

Fluorouracil (5-FU) is still the mainstay of adjuvant treatment for colorectal cancer. Two trials have shown a disease-free and overall survival benefit for 5-FU combined with levamisole in patients with node-positive colon cancer. This regimen is fairly well tolerated and devoid of long-term sequelae, and is now considered standard treatment for node-positive colon cancer. One trial showed a modest improvement in disease-free survival for the semustine/vincristine/5-FU combination; the leukemogenicity and renal toxicity caused by semustine have prevented this regimen from being adopted. Although administering 5-FU directly into the portal vein may improve disease-free survival, most trials have failed to demonstrate a reduction in the incidence of hepatic metastases. This technique, therefore, remains investigational. Several trials in rectal cancer show an advantage for 5-FU combined with semustine and radiation therapy in terms of disease-free survival, overall survival, or both; the contribution of semustine has been questioned and is currently being investigated. In patients with metastatic disease, hepatic arterial infusion of floxuridine produces a higher objective response rate than intravenous administration, but has not resulted in a survival benefit; hepatobiliary toxicity limits the duration of therapy. Biochemical modulation of 5-FU with leucovorin increases the response rate produced by 5-FU alone; a survival benefit has also been observed. N-(phosphonacetyl)-L-aspartate has shown initial promise in combination with high-dose 5-FU infusions. Among the many new drugs tested, only tauromustine seems worthy of further study.
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PMID:Current treatment approaches in colorectal cancer. 199 27

Patients with mucinous colorectal cancers characteristically present with advanced disease, however, the relationship between mucin production by colon cancer cells and their metastatic potential remains unclear. We therefore sought to define the relationship between mucin production by human colon cancer cells and metastatic ability by employing animal models of colon cancer metastasis. LS LiM 6, a colon carcinoma cell line with high liver metastasizing ability during cecal growth in nude mice produced twofold more metabolically labeled intracellular mucin and secreted four- to fivefold more mucin into the culture medium compared to poorly metastatic parental line LS174T. This was accompanied by a similar elevation in poly(A)+ RNA detected by blot hybridization with a human intestinal mucin cDNA probe, and increases in mucin core carbohydrate antigens determined immunohistochemically. Variants of LS174T selected for high (HM 7) or low (LM 12) mucin synthesizing capacity also yielded metastases after cecal growth and colonized the liver after splenic-portal injection in proportion to their ability to produce mucin. Inhibition of mucin glycosylation by the arylglycoside benzyl-alpha-N-acetyl-galactosamine greatly reduced liver colonization after splenic-portal injection of the tumor cells. These data suggest that mucin production by human colon cancer cells correlates with their metastatic potential and affects their ability to colonize the liver in experimental model systems.
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PMID:Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis. 199 84


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