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)

Fas ligand (FasL) plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis. Since FasL has been implicated in the existence of immunologically privileged body sites by inducing apoptosis of activated T lymphocytes, we investigated the expression of FasL in human colon cancers. We found that two out of seven primary tumors and all four hepatic metastatic tumors of surgically obtained colonic adenocarcinoma expressed FasL mRNA and protein, detected by reverse transcription-coupled PCR and by immunohistochemical staining, respectively. Expression of FasL was not detected in normal colonic epithelial cells. FasL mRNA was also expressed in some human colonic adenocarcinoma cell lines including SW480, SW1116, and LS180 cells. Cell-surface-associated FasL was detected in these human colon cancer cells by fluorescence immunocytochemical staining. In addition, the expressed FasL was demonstrated to be functional, since coculture experiments using FasL-expressing SW480 cells resulted in apoptosis of Jurkat T leukemia cells that are sensitive to Fas-mediated apoptosis, and this process was specifically inhibited by the neutralizing anti-human FasL antibody. Thus, our findings and other data suggest an alternative mechanism that enables tumors to evade immune destruction by inducing apoptosis in activated T lymphocytes. Furthermore, constitutive expression of FasL in hepatic metastatic tumors suggests that FasL may also be important in their colonization in the liver through induction of apoptosis in the surrounding Fas-expressing hepatocytes.
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PMID:Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. 917 33

The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is a potential target for toxin-directed therapy, because it is overexpressed on many leukemias and solid tumors and apparently not on stem cells. To investigate the potential therapeutic use of GM-CSF toxins, we fused human GM-CSF to truncated forms of either Pseudomonas exotoxin (PE) or diphtheria toxin (DT) and tested the cytotoxicity of the resulting GM-CSF-PE38KDEL and DT388-GM-CSF on human gastrointestinal (GI) carcinomas and leukemias. Toward gastric and colon cancer cell lines, GM-CSF-PE38KDEL was much more cytotoxic than DT388-GM-CSF, with IC50s (concentration resulting in 50% inhibition of protein synthesis) of 0.5 to 10 ng/mL compared with 4 to 400 ng/mL, respectively. In contrast, toward leukemia lines and fresh bone marrow cells DT388-GM-CSF was more cytotoxic than GM-CSF-PE38KDEL. The cytotoxicity of both GM-CSF-PE38KDEL and DT388-GM-CSF toward the human cells was specific, because it could be competed by an excess of GM-CSF. Binding studies indicated that human GM-CSF receptors were present on all of the human GI and leukemic cell lines tested, at levels of 540 to 3,700 sites per cell (kd = 0.2 to 2 nmol/L), and the number of sites per cell did not correlate with the cell type. A similar pattern of cytotoxicity was found with recombinant immunotoxins binding to the transferrin receptor, in that anti-TFR(Fv)-PE38KDEL was much more cytotoxic than DT388-anti-TFR(Fv) toward GI cells, but both were similar in their cytotoxic activity toward leukemia cells. The fact that PE is more effective than DT in killing GI but not leukemic tumor cells targeted by GM-CSF indicates a fundamental difference in the way PE or DT gains access to the cytosol in these cells. GM-CSF-PE38KDEL and DT388-GM-CSF deserve further evaluation as possible treatments for selected tumors.
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PMID:Recombinant toxins containing human granulocyte-macrophage colony-stimulating factor and either pseudomonas exotoxin or diphtheria toxin kill gastrointestinal cancer and leukemia cells. 920 60

Following the observation that relatives of cystic fibrosis (CF) patients have an increased mortality due to leukaemia, a study was initiated to determine whether leukaemia patients had an increased prevalence of the delta F508 CF mutation. No increase in carriers were found among leukaemias; however the carrier frequency of the delta F508 mutation appeared to be reduced in patients with malignant melanoma analysed as a control group compared to the normal population. This paper extends our previous study and investigates several other common human tumours, including those of the colon, breast, and lymphoma tissue. Fewer than expected carriers remained among the melanoma group from South Wales. There were fewer than expected carriers among patients with colon cancer compared to the normal population. The prevalence of the delta F508 mutation was normal in lymphomas and leukaemias.
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PMID:The cystic fibrosis delta F508 gene mutation and cancer. 922 59

Selenium is an essential trace element, the deficiency of which is associated with an increased incidence of some human cancers. Dietary supplementation with selenium has been reported to produce a decrease in the incidence of some cancers in humans. Thioredoxin reductase (TR) is a newly discovered homodimeric selenocysteine (SeCys)-containing protein that catalyzes the NADPH-dependent reduction of the redox protein thioredoxin (Trx). Trx is overexpressed by a number of human tumors, and experimental studies have shown that Trx contributes to the growth and to the transformed phenotype of some human cancer cells. Thus, TR, by reducing Trx, could play a role in regulating the growth of normal and cancer cells. We have investigated mechanisms by which selenium, in the form of sodium selenite, added to serum-free growth medium regulates TR activity in cancer cell lines. Selenium caused a dose-dependent increase in cellular TR activity. The increase in TR activity produced by 1 microM Se compared to medium with no added selenium was: for MCF-7 breast cancer cells, 37-fold; for HT-29 colon cancer cells, 19-fold; and for A549 lung cancer cells, 8-fold. In contrast, Jurkat and HL-60 leukemia cells showed no increase in TR activity. The half-life of the time course of induction of TR in HT-29 cells after adding selenium was 10 h. The increase in TR activity was accompanied by an increase in TR protein levels up to 3-fold and an increase in the specific activity of the enzyme of 5-32-fold, depending on the cell line. Studies using 75Se showed that the amount of selenium incorporated into TR increased with increasing selenium concentration up to a ratio of 1 selenium per TR monomer. There was an increase in TR mRNA levels of 2-5-fold at 1 microM selenium and an increase in the stability of TR mRNA with a half-life for degradation of 21 h compared to 10 h in the absence of selenium. Trx mRNA and protein levels and Trx mRNA stability were not affected by selenium. The results of the study show that the increase in TR activity caused by selenium is specific and due to several effects, including an increase in the stability of TR mRNA leading to increased TR mRNA levels, an increase in TR protein, but predominantly to an increase in the specific activity of TR associated with increased incorporation of selenium into the enzyme.
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PMID:Mechanisms of the regulation of thioredoxin reductase activity in cancer cells by the chemopreventive agent selenium. 935 64

Mucin molecules are displayed on most human cancer cell surface, and are different from that expressed on normal epithelial cells. The molecular structure of mucin core peptide (apomucin) was identified recently. However, the function of apomucin is only poorly understood. To further elucidate the role of apomucin in the modulation of cancers, this study was to investigate the immune responses induced by mucin core peptide in mice. The mucin core peptide was isolated from pancreatic cancer cell line SW1990. When mice immunized with this apomucin (10 micrograms/time x 6) plus DETOX, all mice developed delayed-type hypersensitivity (DTH) after challanged with apomucin or synthetic mucin core peptide MUC-2 or MUC-3, while the mice immunized with only apomucin did not develop DTH. No antibodies were detected by ELISA after immunization. When the splenic cells of vaccinated mice were cocultured with this apomucin (10-50 micrograms/ml) and rhIL-2 (50 U/ml) in vitro, the proliferated lymphocytes showed cytotoxicity against human cancer cells, including colon cancer, gastric cancer, pancreatic cancer and leukemia as measured by Cr-51 release assay. The cytotoxicity could be blocked by antibodies against MUC-2 and MUC-3. These results provide a rational basis for the use of apomucin as a vaccine to stimulate anti-tumor immunity.
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PMID:[Anti-tumor activity and immune responses induced by human cancer-associated mucin core peptide]. 938 91

New antitumor substances, designated BE-32030A, B, C, D and E, were isolated from the culture broth of Nocardia sp. A32030. The active principles were extracted from the mycelium by methanol and purified by Sephadex LH-20 and reversed-phase column chromatographies and finally by reversed-phase HPLC. BE-32030A, B, C, D and E inhibited the growth of P388 murine leukemia, DLD-1 human colon cancer, PC-13 human lung cancer and MKN-45 human stomach cancer cell lines.
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PMID:BE-32030 A, B, C, D and E, new antitumor substances produced by Nocardia sp. A32030. 940 85

We evaluated epidemiologic evidence pertaining to the human carcinogenic potential of triazine herbicides in general and of atrazine, the most common triazine. Cancers for which data are available included non-Hodgkin's lymphoma, Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer. The investigations had methodologic limitations, including lack of in-depth exposure measurements and small numbers of subjects with heavy exposure and/or with many years since starting exposure, possibly required for the induction of cancer. The relation between triazines and non-Hodgkin's lymphoma has been assessed in four independent population-based case-control studies, reporting odds ratios ranging from 1.2 to 2.5. However, chance and/or confounding by other agricultural exposures may have produced these weak statistical associations. Furthermore, a pooled analysis of three of the case-control studies and the combined analysis of two retrospective follow-up studies did not demonstrate the types of dose-response or induction time patterns that would be expected if triazines were causal factors. The epidemiologic data pertaining to Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer were inadequate for determining whether associations with atrazine or triazines exist in humans. For each of these cancers, only one or two studies evaluating the relationship were available, and the results of the studies typically were imprecise.
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PMID:A review of epidemiologic studies of triazine herbicides and cancer. 940 33

The antitumor effects of "half-mustard type" phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures. In contrast, propylureas (9, 11) were active against some leukemia cell types. Only two compounds with the butylene [(CH2)4] linker (10, 12) were active against non-small lung cancer cells. Compounds containing the propylene linker were less effective. On colon cancer lines, tumor cells from the central nervous system and on melanoma cells the same compounds were effective, however, having substituents at the 2-position of phenothiazine seems to be important. Surprisingly, the majority of ovarian cancer cell lines (except one type, IGROVI) and five of eight renal cancer lines were not sensitive to these phenothiazine derivatives. The two butylene linked phenothiazine ureas (10, 12) had moderate antiproliferative action on two renal cancer cell lines. The prostate cancer and some breast cancer cell lines were not sensitive. Nevertheless some breast cancer cell lines were apparently sensitive to CF3-substituted phenothiazine alkylureas. On the basis of these experiments one may postulate that in the case of insensitive cells an mdr-gene encoded multidrug resistance efflux pump is responsible for the resistance. The selectivity or organ cell specificity of the effective phenothiazines will be targeted for improvement in further studies, in order to avoid the general cytotoxic effects of "half mustard type" phenothiazines.
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PMID:The primary in vitro antitumor screening of "half-mustard type" phenothiazines. 941 80

The purpose of this study was to elucidate the mechanism of 201Thallium-chloride (201Tl) uptake in tumor cells and its possible relationship to potassium channels. The subcellular biodistribution of 201Tl in tumor cells was examined in colon cancer (LS180) bearing nude mice using sequential centrifugation. The involvement of potassium channels in 201Tl uptake in tumor cells was examined by uptake inhibition with potassium channel blockers (ouabain, bumetanide, and glibenclamide) in cultured leukemia cells (K562). Greater than 90% of 201Tl was found in the soluble cytoplasmic fraction. 201Tl uptake was inhibited by ouabain and bumetanide but not by glibenclamide. These data demonstrate that 201Tl uptake in tumor cells is mediated by the Na(+)-K+ ATPase and the Na(+)-K(+)-2Cl- cotransporter with 201Tl acting as a potassium analogue.
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PMID:Mechanism of 201thallium-chloride uptake in tumor cells and its relationship to potassium channels. 947 Oct 98

Cytochrome P450 CYP2D6 polymorphism is an autosomal recessive trait leading to impaired sparteine/ debrisoquine metabolism in 5-10% of the Caucasian population. Previous studies have associated affected individuals (poor metabolizers = PM) with susceptibility to bladder cancer and various forms of leukemia. In many other cancer forms, the data remain contradictory. A PCR assay allows the convenient screening of about 90% of known mutations resulting in the PM phenotype. Since in patients with neurofibromatosis type 2, we had observed a significantly increased rate of CYP2D6 mutations leading to PM and apparently predisposing for NF2, we extended our investigation to tumor and peripheral blood samples obtained from NF1 patients. Although the number of cases investigated remains low, the study indicated that during tumor formation no changes occurred at the mutational hot spot within the CYP2D6 sequence. Moreover, no loss of heterozygosity was notable. However, the frequency of the mutated allele in the NF1 individuals is comparable to that of neurofibromatosis type 2 and above that observed in breast and colon cancer, or meningiomas.
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PMID:Debrisoquine hydroxylase gene polymorphism in neurofibromatosis type 1. 949 60


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