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

Like calcium, vitamin D may protect against colorectal neoplasia as it reduces epithelial cell proliferation and induces differentiation. Although its therapeutic use is limited by its effects on calcium metabolism, analogues such as calcipotriol produce little hypercalcaemia. Stathmokinetic and immunohistochemical techniques were used to study the effect of 1,25 (OH)2 D3 and its analogues on cell proliferation in human rectal mucosa and a colon cancer cell line. Paired sigmoidoscopic biopsy specimens were obtained from 17 control patients and five patients with familial adenomatous polyposis. Explants were established in organ culture, with or without the addition of vitamin D. Proliferation was assessed using (1) metaphase arrest to determine the crypt cell production rate (CCPR) and (2) Ki-67 monoclonal antibody directed against an antigen present in proliferating cells. 1,25 (OH)2 D3 in concentrations of 1 microM-100 pM (10(-6)-10(-10) M) reduced the CCPR (cells/crypt/hour) from 4.74 to 2.15-2.67 (p < 0.001), and the Ki-67 labelling index from 7.28-3.74 (p < 0.01). Likewise, vitamin D2, 10 nM (10(-8) M) reduced the CCPR from 4.74-2.74 (p < 0.05) and calcipotriol from 4.86-2.38 (p < 0.05). In familial adenomatous polyposis patients 1,25 (OH)2 D3 100 pM (10(-10) M) halved the CCPR from 8.75-4.22. Calcipotriol (10(-5) M to 10(-9) M) produced a clearcut dose response inhibition of HT-29 cell growth. Thus, vitamin D and its metabolites inhibit proliferation in normal and premalignant rectal epithelium and suppress growth in a colorectal cancer cell line.
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PMID:Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line. 133 58

The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.
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PMID:Heavy water enhances the antineoplastic effect of 5-fluoro-uracil and bleomycin in nude mice bearing human carcinoma. 168 3

The wild-type p53 gene suppresses cell proliferation and induces apoptosis when it is transfected into human colon cancer cell lines. Therefore, mutation of the p53 gene, which correlates closely with p53 protein overexpression, would be predicted to activate cell proliferation and limit apoptosis. We tested this hypothesis by correlating p53 protein expression with cell proliferation and apoptosis in 70 neoplasms (29 adenomas and 41 carcinomas) using p53 and Ki-67 immunohistochemical staining and DNA nick end labelling. The p53 immunoreactivity was independent of the Ki-67 positivity. The apoptotic incidence was less frequent (P < 0.005) in tumours with diffuse p53 protein overexpression than in those with the sporadic overexpression, defined as p53 staining of isolated or scattered expression. In addition, apoptotic incidence only correlated directly (P < 0.05) with Ki-67 positivity in tumours with sporadic p53-protein expression. These results indicate that p53 protein that is expressed sporadically in colorectal neoplasms is probably wild-type protein and induces apoptosis in response to active cell proliferation. In contrast, diffusely overexpressed p53 protein in colorectal neoplasms is probably mutant and correlates with a reduction in apoptotic cell death independently of cell proliferation.
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PMID:Correlation of p53 protein expression with apoptotic incidence in colorectal neoplasia. 755 42

Most studies on colorectal carcinogenesis suggest a field defect, preceding overt development of cancer. The low incidence of adenomatous polyps in the African population, however, suggests that there may be an alternative route for cancer development. The aim of the study was to discover if the difference in incidence of colorectal cancer in Africans compared with the white population is reflected in a different pattern of cell proliferation. Histological normal mucosa from 30 patients (15 white South African (W), 15 South African Africans (A)) with confirmed colon cancer were examined. Proliferating cells were detected using the Ki-67 antigen. In addition, cell proliferation data were obtained, from 30 age matched controls (15 Africans, 15 white South Africans), without colorectal disease. The African controls were significantly younger (mean (SD) (A: 42 (20), W: 66 (13), p < 0.05)) than the white controls. The second control group had a significantly higher mean (SD) total labelling index (W: 11 (3), A: 6 (4), p < 0.05). In addition the proliferative pattern of the white group without evidence of colorectal cancer showed a comparatively large amount of dividing cells in compartment 2, compared with African controls (mean (SD) (W: 21 (8), A: 9 (8), p < 0.05)). Mucosa from Africans with cancer showed a proliferative pattern with the same increased total labelling index (A: 15 (5), W: 16 (6), p = NS, phase II proliferative lesion) and an even more pronounced upward expansion (phase I proliferative lesion) compared with white cancer patients. This suggests that the mechanism of colorectal carcinogenesis is similar in Africans and the white population. The lack of clinical evidence of the adenoma-carcinoma sequence, and the incidence of cancer at a comparatively young age in Africans may be explained by the fact that colorectal cancer in this ethnic group behaves more aggressively and that adenomatous polyps are rapidly converted into overt cancer before detection.
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PMID:Colonic cell proliferation in two different ethnic groups with contrasting incidence of colon cancer: is there a difference in carcinogenesis? 779 18

The role of apoptosis in colon cancer was investigated in terms of control of growth and expression on p53, using the nick-ended-DNA labelling method and immunohistochemistry. The apoptotic labeling index was highest in the T1 stage (24 cases), as was the proliferative activity, assessed in terms of the Ki-67 labeling index. Both labeling indices demonstrated similar overall incidence curves for the total 95 colon cancer cases, and examination of individual cases revealed a statistically significant correlation (P=0.01). However, neither index had any relation to p53. The results thus suggest that apoptosis in colon cancers has a linkage with proliferative activity that can be assessed by Ki-67 labeling, but is not regulated by the p53 system. This might contribute to the diversity of colon cancer growth.
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PMID:Apoptosis of colon cancer: comparison with Ki-67 proliferative activity and expression of p53. 860 65

Both suppressor oncogene and proliferative activity are believed to indicate colon cancer risk. The retinoblastoma (Rb) gene is a suppressor oncogene affecting cell differentiation. Retinoblastoma gene inactivation is associated with tumour development. However, the relation of the Rb protein to cell proliferation and colon tumour formation is unknown. Retinoblastoma protein quantity was correlated with proliferative activity in flat, unaffected mucosa specimens from 36 cancer patients, 21 non-cancer control subjects and in 29 tumour tissue samples from cancer patients. Nuclear Rb protein was measured by using automated CAS-200 image analysis of monoclonal antibody labelled frozen sections from fresh, surgically removed tissue. All colon cells within 15 whole crypts were imaged. Proliferative activity was also measured by using analysis with Ki-67 monoclonal antibody. Retinoblastoma protein content correlated directly with proliferative activity in flat mucosa of non-cancer control subjects (r = 0.63; P < 0.001; n = 21). A significant correlation was also found in flat mucosa specimens of non-metastatic (Duke's stages A and B) cancer patients (r = 0.52; P < 0.01; n = 22). However, Rb protein did not correlate with proliferation in flat mucosa from metastatic (Duke's stages C and D) cancer patients (r = 0.03; NS; n = 14) or in cancer tissue (r = 0.068; NS; n = 29). Mucosal Rb protein in the colon normally increases as proliferation increases. Dissociation between Rb protein and colon proliferation may occur in flat mucosa in patients with a higher risk of metastatic tumour growth. Future studies comparing Rb protein quantity and proliferative activity may help identify high-risk colon cancer patients.
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PMID:Colonic retinoblastoma protein and proliferation in cancer and non-cancer patients. 914 34

We evaluated the effect of sulindac sulfide (SS), which reduces cell number and induces apoptosis in cultured colon cancer cells (CCCs), on expression of the proliferation markers PCNA and Ki-67 in HT-29 and HCT-15 CCCs; only the former express cyclooxygenases. DNA content and PCNA/Ki-67 expression were analyzed by bivariate flow cytometry. SS inhibited cell proliferation, determined by the reduced expression of PCNA and Ki-67, roughly by half at 72 h, and induced apoptosis (accounting for about two-thirds and one-third of the reduction in cell number, respectively). A similar effect of SS occurred in HT-29 and HCT-15 CCCs, and also in non-colonic cells, indicating that this rather general effect of SS on cultured cells is not dependent on inhibition of prostaglandin synthesis.
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PMID:Sulindac sulfide inhibits the proliferation of colon cancer cells: diminished expression of the proliferation markers PCNA and Ki-67. 914 29

Costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are indispensable for T-cell activation. Recently, a paucity of these costimulatory molecules was reported in inflammatory cells in colon cancer, which may permit the immune evasion of the cancer. The present study uses immunohistochemistry to reveal the expression of these molecules in 43 cases of colorectal cancer tissue. B7-2 was expressed in mononuclear calls distributed along the invasive margin in 37 of 43 cases. B7-1 was positive in the same area in 22 cases. In contrast, the expression of B7-1/B7-2 was usually inconspicuous in the stroma within cancer. Most B7-1+ and B7-2+ cells were identified as macrophages because of the coexpression of CD68 antigen or acid phosphatase activity. CD4+ or CD8+ T cells were distributed in the same area and were in close contact to B7-1/B7-2+ cells. Both CD4+ and CD8+ T cells had a proliferative activity with a labeling index of Ki-67 of 1.5% and 2.5%, respectively. Conventional electron microscopy confirmed both the accumulation of macrophages along the invasive margin and the attachment of lymphocytes to them. Immunoelectron microscopy confirmed: (a) localization of B7-2/B7-1 along the cell membrane; (b) abundance of vacuoles and heterophagosomes (a finding indicative of phagocytosis of other cells) in the cytoplasm of these cells; and (c) direct cell-to-cell contact between these macrophages and lymphocytes. The present data, which suggest that an immune reaction occurs along the invasive margin of colorectal cancer, are in accordance with previous clinicopathologic studies suggesting that peritumoral lymphocytic infiltration is one of the favorable prognostic factors in this disease.
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PMID:Expression of costimulatory molecules B7-1 and B7-2 by macrophages along invasive margin of colon cancer: a possible antitumor immunity? 931 47

This study investigates the effects of the anti-metabolite 5-fluorouracil (5-FU) on the human colon cancer line HT29 (10(7) cells per dose) grown subcutaneously in severe combined immunodeficient (SCID) mice. The efficacy of 5-FU was quantitatively evaluated by comparing the tumour weight, mitotic and apoptotic tumour cell indices and the expression of the Ki-67 nuclear antigen in drug-treated animals and control animals. The tumour cell carbohydrates were assessed using a lectin panel. A significant reduction in the tumour weight was found 4 days after initial 5-FU treatment. 5-FU treatment reduced the percentages of mitoses but increased the apoptotic index in the tumour cells. In addition, 5-FU induced an increase in the signet ring cell population and an increased binding for lectins specific for N-acetylgalactosamine and galactose. However, the vast majority of signet ring cells were negative for Ki-67. The results of this study indicate that continuous treatment with 5-FU for 4 days targets metabolic processes relevant for both cell division and apoptosis. The relative increase in the signet ring population can be explained by the fact that the more proliferation-active stem cell population of the tumour is the primary target of the therapy. The lectin-binding patterns reflect these changes and are therefore differentiation linked.
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PMID:The action of 5-fluorouracil on human HT29 colon cancer cells grown in SCID mice: mitosis, apoptosis and cell differentiation. 937 59

We assessed the effect of sulindac sulfide (SS), a colon cancer chemopreventive agent, on the proliferation and apoptosis in the colon cancer cell lines HCT-15 and HT-29. We applied a triparameter flow cytometric analysis that simultaneously determined DNA content, expression of Ki-67 or proliferating cell nuclear antigen (PCNA), and extent of DNA strand breaks by TUNEL (TdT-mediated dUTP nick end labeling). HCT-15 and HT-29 cells were exposed to SS 200 microM and 175 microM, respectively, for up to 72 h. As expected, SS inhibited proliferation and induced apoptosis. SS also induced several subpopulations of cells defined by their expression of proliferation markers and DNA strand breaks. By 72 h the rapidly proliferating cells [PCNA/Ki-67(+)/TUNEL(-)] were reduced from > 90% to about one third. Of the remaining cells, about one third were apoptotic [PCNA/Ki-67(-)/TUNEL(+)] and one third were quiescent [PCNA/Ki-67(-)/TUNEL(-)]. Another subpopulation was detected that was PCNA/Ki-67(+)/TUNEL(+), some had a dominant subdiploid peak and over half were in S or G2/M phases by DNA content. Thus, a subpopulation of apoptotic cells strongly expressed PCNA and Ki-67, suggesting that their specificity as proliferation markers may need reassessment. Similar results were obtained with the HL-60 promyelocytic cell line.
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PMID:Sulindac sulfide induces several subpopulations of colon cancer cells, defined by PCNA/Ki-67 and DNA strand breaks. 943 28


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