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

Within human carcinomas, there is often an infiltration of lymphocytes and other cells of the immune system. A variety of cytokines are produced by such cells that could have a paracrine influence on the growth of tumor epithelium. The effect of one of these cytokines, interleukin-4 (IL-4), on human breast and colon cancer cell lines was therefore examined. IL-4 inhibited the growth of human colon (HT 29) and breast [MCF-7 wild type (MCF-7 WT), MCF-7 Adriamycin-resistant (MCF-7r), MDA-MB-231, and MDA-MB-468] carcinoma cells in culture. Competitive binding of 125I-IL-4 demonstrated the presence of 2000 high affinity IL-4-binding sites on HT 29 cells. The Kd for specific binding of 125I-IL-4 to HT 29 cells was 77 pM. Further studies were conducted on the estrogen-dependent MCF-7 WT and estrogen-independent MDA-MB-231 breast carcinoma lines. Concentrations of IL-4 of 10-100 nM were required to significantly inhibit growth of these carcinoma cell lines; e.g., with MCF-7 WT cells, half-maximal inhibition of growth occurred at 20 nM IL-4. Specific binding of 125I-IL-4 was detected to MCF-7 WT and MDA-MB-231 cells, but the low level of binding precluded Scatchard analysis. IL-4 inhibited 90% of the 17 beta-estradiol-stimulated growth of MCF-7 WT cells in a dose-dependent manner but without a change in estrogen receptor expression. Inhibition of growth by IL-4 was less in the absence of estrogens. Combined treatment with IL-4 and other known inhibitors of breast carcinoma cell growth [transforming growth factor-beta 1 (TGF-beta 1) and the antiestrogen tamoxifen] showed additive inhibition. The hormone-independent cell lines MCF-7r and MDA-MB-231 were additively inhibited by IL-4 and TGF-beta 1. This was not the case with MDA-MB-468 cells in which inhibition by IL-4 and TGF-beta 1 was of similar magnitude but no significantly greater effect was observed on combined treatment. No secretion of IL-4 was detected from these cell lines either basally or on treatment with TGF-beta 1 or tamoxifen, and we conclude that IL-4 is a nonautocrine inhibitor of breast carcinoma cell growth.
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PMID:Inhibition of colon and breast carcinoma cell growth by interleukin-4. 172 1

The ER-D5 antigen is a protein associated with the estrogen receptor that is present only in estrogen receptor-positive tissues. To clarify the estrogen receptor in colon cancer, the localization of ER-D5 was studied immunohistochemically. Forty-three of 171 (25.1%) specimens of colon cancer showed reactivity for ER-D5. Reactivity was seen only in the cytoplasm. No reactivity was seen in cancer limited to the mucosa or in adenoma, but submucosal cancers showed a rate of positivity similar to cancers that involved lamina muscularis and beyond. Estradiol staining was done on serial sections from 56 specimens. There was a significant relationship between reactivity for estradiol and that for ER-D5. In the 15 specimens where both ER-D5 and estradiol were positive, the distribution of estradiol was similar to that of ER-D5. It was concluded that the immunohistochemical localization of ER-D5 indirectly shows that of the estrogen receptor in colorectal cancer tissues.
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PMID:An immunohistochemical study with an estrogen receptor-related protein (ER-D5) in human colorectal cancer. 173 82

Established human colon cancer cells with distinct degrees of differentiation (LoVo, well-differentiated; SW620, intermediate differentiation; and SW1116, poorly differentiated) were used to produce monoclonal antibodies (MoAbs) by standard hybridoma techniques. Specificity was tested by an enzyme-linked immunosorbent assay against human foreskin cells, 7 established human colon cancer lines, a panel of 17 established human tumor lines of different histological origins, purified carcinoembryonic antigen, panels of red blood cells, and a suspension of lymphocytes obtained from 30 random normal donors. MoAb LoVo-F4 3E4/1A1/2E10 (MoAb F4/2E10) reacted with five colon cancer lines and only slightly with MCF-7 cells (estrogen receptor positive breast carcinoma). MoAb LoVo-F4 3E4/1A1/5C10 also reacted with the previous five colon cancer lines and with two gastric cancer lines. A MoAb obtained with a LoVo 3 M KCl membrane extract reacted exclusively with LoVo cells. MoAb SW620-F1 4E5/1A3 reacted with only three colon cancer cell lines and an estrogen receptor negative breast cancer line. MoAb SW1116-F2 1E3/1A1 reacted with four colon carcinoma cell lines, one gastric cancer line, MCF-7 cells, and a lung cancer line. MoAb SW1116-F2 1F3/1B1 reacted intensely with purified carcinoembryonic antigen and with every carcinoembryonic antigen-producing cell line available in our laboratory. Further studies concentrated on the immunoglobulin G1 MoAb F4/2E10. We demonstrated that the purified MoAb did not inhibit binding of MoAb CA19-9 to any colon Ca lines and reacted with fresh human colon carcinoma specimens regardless of whether they were processed by cryostat or paraffin embedding after fixation in formalin for 24 through 96 h. Using the peroxidase-antiperoxidase technique, MoAb F4/2E10 did not react with 23 normal adult and 18 fetal (less than 3 months old) human tissue specimens. When tested on 312 specimens of diverse histological origins and diseases, the MoAb was positive in 57 of 62 colorectal cancers, in 12 of 19 villous adenomas, in 5 of 7 adenomatous polyps, and in 10 of 12 cases of ulcerative colitis. With the exception of 2 of 15 cases of Crohn's disease that were slightly positive, all tissues from nonmalignant diseases (regardless of histological origin) were consistently negative. There was only weak reactivity in 2 of 18 breast cancers, 7 of 21 squamous cell carcinomas, 4 of 27 lung tumors, 1 of 13 kidney carcinomas and in 7 miscellaneous tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New monoclonal antibodies against colon cancer-associated antigens. 242 73

We previously reported that the combination of cis-diamminedichloroplatinum (CDDP) and 1-beta-D-arabinofuranosylcytosine (ara-C) induced a remarkable synergistic killing effect on an established human colon carcinoma cell line, LoVo. The current study investigated whether this effect was LoVo specific or could be extended to other colon cancer cell lines as well as to cell lines of different histological origins, including an estrogen receptor-positive breast cancer cell line (MCF7), an ovarian cancer cell line (OV1225), and an esophageal cancer cell line (Hcu18). The six human colorectal cancer cell lines included in this study represent three biological groups with distinct phenotypic properties. Group 1 (well-differentiated) consisted of LoVo and SW48; group 2 (intermediately differentiated) comprised SW480 and SW620; and group 3 (undifferentiated) was represented by SW403 and SW1116. No significant synergistic cytotoxicity was noted after the breast and ovarian cancer cells were treated. However, synergistic lethal effects were observed in all of the six colon cancer cell lines as well as the esophageal cancer cell line. The synergistic effect on the gastrointestinal cancer cell lines was related to the concentration of ara-C and CDDP during treatment. Our results suggest that the cytotoxic synergism between ara-C and CDDP may be tissue-type specific and that synergism may depend on the histological origin of the cancer.
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PMID:Synergism of 1-beta-D-arabinofuranosylcytosine and cis-diamminedichloroplatinum in their lethal efficacies against seven established cancer cell lines of gastrointestinal origin. 270 47

A detailed retrospective analysis was undertaken of the effect of perioperative blood transfusion on long-term survival of 113 patients with Dukes' Stages A, B and C1 cancer of the colon and 383 patients with invasive cancer of the breast who were treated in our institution between 1973 and 1978 and followed for 5 to 10 years. In the patients with colon cancer, a significant adverse effect of transfusion on long-term survival was seen. In this group there was a cumulative 5-year overall survival of 48% for the transfused and 74% for the nontransfused patients (P = 0.007, log-rank test). Perioperative blood transfusion was associated with a relative risk of 3.42 for all deaths (P = 0.005) and 4.25 for death due to cancer (P = 0.03), after adjustment for other important variables such as age, sex, stage, location of tumor, surgical procedure, and preoperative hemoglobin level. In contrast, in our study group of patients with breast cancers, who all underwent a modified radical mastectomy, no effect of blood transfusion on long-term survival was seen. Multivariate analysis adjusting for size of tumor, number of positive regional lymph nodes, menopausal status, estrogen receptor status and the addition or absence of chemotherapy, did not show any increased risk in all deaths or death due to cancer associated with blood transfusion. Although no definite explanation is available, our data show that there seems to be a difference in the relationship between perioperative blood transfusion and survival for colon and breast cancer patients.
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PMID:Perioperative blood transfusion and cancer prognosis. Different effects of blood transfusion on prognosis of colon and breast cancer patients. 380 42

We examined the cytosolic estrogen receptor (ER) level in tumor tissue from 77 patients: 36 meningiomas, 20 gliomas (12 glioblastomas, 2 cerebellar astrocytomas, 2 ependymomas, and 4 medulloblastomas), 8 neurinomas, 7 pituitary adenomas (2 prolactin-producing adenomas, 1 growth hormone-producing adenoma, and 4 nonfunctioning adenomas), and 6 metastatic brain tumors (1 from breast cancer, 4 from lung cancers, and 1 from colon cancer). Nuclear ER levels were assayed in 11 meningiomas and 2 glioblastomas. ER was determined by the dextran-coated charcoal method and calculated by Scatchard analysis. Cytosolic ER was detected in 100% of the pituitary adenomas, 50% of the meningiomas, 50% of the metastatic brain tumors, 25% of the neurinomas, and 15% of the gliomas. In gliomas, only medulloblastomas had ER activity. Nuclear ER was found in three premenopausal women with meningioma. The dissociation constant of the ER complex was, in each case, less than 10(-9) M. These observations suggest that some brain tumors may be responsive to estrogen via the cellular ER.
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PMID:Estrogen receptors in brain tumors. 650 47

In vivo and epidemiological data suggest a mitogenic role for estrogens (E) in colon cancer. The presence of estrogen receptor (ER) and ER mRNA in colonic epithelium and colon cancer cells, make it necessary to explore the possible direct effects of E on colon cancer growth. In this study, a 15-mer oligodoxynucleotide (oligo) antisense to the region of the translation start codon of estrogen receptor mRNA inhibited ER expression in a mouse colon cancer cell line (MC-26), as determined by receptor binding assay. Antisense oligo also decreased ER mRNA levels in MC-26 cells. The growth-stimulatory effect of E was abolished by antisense oligo treatment, demonstrating that the ER is directly involved in the regulation of colon cancer cell growth.
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PMID:Estrogen receptor-mediated direct stimulation of colon cancer cell growth in vitro. 785 26

Instability at microsatellite repeat sequences (MI) has been observed in endometrial carcinomas (EC) arising sporadically or in association with the hereditary colon cancer syndrome. However, the clinical and pathological features of the EC with MI have not been characterized. DNA of 42 patients with EC was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. Microsatellite loci on chromosomes 4, 5, 10, 12, 17, and 18 were amplified by polymerase chain reaction. MI was defined by a mobility shift in the tumor DNA as compared with normal DNA. Results were correlated with the clinical and pathological features of the tumors. MI at three or more loci was detected in 12 of 42 cases (28%). There were no significant differences between EC with and without MI with regard to age of presentation, stage, evidence of estrogenic stimulation, mucinous differentiation, estrogen receptor, c-erbB2, or p53 immunostaining. However, MI was more frequent in endometrioid (11/33, 33.3%) than in nonendometrioid (1/9, 11%) carcinomas. Only one papillary serous carcinomas showed MI. MI was found in one of two cases of endometrial hyperplasia adjacent to EC. It was concluded that MI is a common genetic abnormality of endometrial carcinoma and appears to be more frequent in endometrioid than in nonendometrioid tumors.
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PMID:Microsatellite instability in endometrial carcinomas: clinicopathologic correlations in a series of 42 cases. 978 37

The interaction between beta-catenin and LEF-1/TCF transcription factors plays a pivotal role in the Wnt-1 signaling pathway. The level of beta-catenin is regulated by partner proteins, including glycogen synthase kinase-3beta (GSK-3beta) and the adenomatous polyposis coli (APC) tumor suppressor protein. Genetic defects in APC are responsible for a heritable predisposition to colon cancer. APC protein and GSK-3beta bind beta-catenin, retain it in the cytoplasm, and facilitate the proteolytic degradation of beta-catenin. Abrogation of this negative regulation allows beta-catenin to translocate to the nucleus and to form a transcriptional activator complex with the DNA-binding protein lymphoid-enhancing factor 1 (LEF-1). This complex is thought to be involved in tumorigenesis. Here we show that covalent linkage of LEF-1 to beta-catenin and to transcriptional activation domains derived from the estrogen receptor or the herpes simplex virus protein VP16 generates transcriptional regulators that induce oncogenic transformation of chicken embryo fibroblasts. The chimeras between LEF-1 and beta-catenin or VP16 are constitutively active, whereas fusions of LEF-1 to the estrogen receptor are regulatable by estrogen. These experiments document the oncogenicity of transactivating LEF-1 and show that the transactivation domain normally provided by beta-catenin can be replaced by heterologous activation domains. These results suggest that the transactivating function of the LEF-1/beta-catenin complex is critical for tumorigenesis and that this complex transforms cells by activating specific LEF-1 target genes.
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PMID:Nuclear endpoint of Wnt signaling: neoplastic transformation induced by transactivating lymphoid-enhancing factor 1. 987 85

Antiestrogen tamoxifen (Tam) is the most prescribed drug for the treatment of estrogen receptor (ER)-positive breast cancers. It is also used in long-term clinical trials with encouraging preliminary results as a chemopreventive agent for breast cancer. The effect of Tam on ER-negative cancers, however, is unclear. Here we reported that paclitaxel and 4-hydroxytamoxifen (4-HT) have a synergistic cytotoxic effect on the ER-negative colon cancer cell line HCT15, which is refractory to paclitaxel alone. Our results showed that 4-HT at submicromolar concentrations effectively enhanced the antiproliferative effect of paclitaxel. In addition, at 1/10 of the paclitaxel concentrations used for HCT15, 4-HT and paclitaxel also showed synergistic effect on NCI H460, an ER-negative lung cancer cell line. For both cell lines, the effective concentration for paclitaxel to inhibit cell growth was 1 log lower in the combination treatment than the concentration used in the single treatment. Cell cycle analysis showed that the combination of paclitaxel and 4-HT increased the G2/M population and resulted in the increase of apoptosis in both cell lines. Enhanced early release of cytochrome c from mitochondria may be the apoptotic pathway activated in the combination treatment in HCT15 cells.
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PMID:Synergistic effect of paclitaxel and 4-hydroxytamoxifen on estrogen receptor-negative colon cancer and lung cancer cell lines. 1063 Mar 57


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