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)

Lung cancers have become the leading cause of cancer deaths in Japan, claiming more than 55 000 lives annually. Unfortunately, substantial improvement in terms of cure rates has not been achieved over the last two decades, although during the same period of time in-depth basic knowledge of the molecular mechanisms, which underlies carcinogenesis and progression of this deadly group of neoplasms, has accumulated at an amazing pace. It has consequently become evident that they have many shared but also distinct features, when comparisons are made not only with other common epithelial cancers of adults, such as colon cancer, but also within the various histologic types of lung cancers themselves. This review article provides an up-date on cutting-edge research into the following three different topics, from which important new insights have been obtained. The first concerns genetic instability, especially chromosome instability, and checkpoint failure in lung cancers. Second, we deal with EGFR mutations, which shows revealing specificities in various aspects. Finally, advances in the expression profiling analysis of both transcriptomes and proteomes of lung cancers are summarized.
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PMID:Throwing new light on lung cancer pathogenesis: updates on three recent topics. 1572 49

We have prepared the map of regional distribution of cervical cancer in Hungary. Serial HPV genotyping of sexual partners provided evidence for the sexually transmitted infections. Molecular epidemiology studies revealed activating c-kit mutation in bilateral testicular cancers. A cost-effective molecular staging method was introduced to the management of breast cancer patients. Genomic profiling identified the gene signature of Herceptin and taxane sensitivity of breast cancer. In colon cancer patients we have determined the mutational spectrum of hMLH1 and hMSH2 genes in Hungary. The prognostic power of SHMT and MTHFR polymorphism was determined in colorectal cancer patients. In head and neck cancer the gene signature of cisplatin sensitivity and the EGFR polymorphism was determined. We have introduced a cost-effective in vitro assay to determine the drug resistance of pediatric leukemias. The prognostic power of N-myc genotyping was determined in neuroblastoma patients. A phase I trial for gene therapy of brain cancer was started by using a GM-CSF adenoviral vector system. Using global genomic approaches the gene signature of malignant melanoma and its metastatic disease was determined. We have found that Ca-channel blockers and EGFR tyrosine kinase inhibitors are effective in preclinical human melanoma models in breaking the apoptosis resistance of this tumor.
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PMID:[Activity of the National Oncology R&D Consortium in 2004]. 1590 26

Interferon-alpha (IFNalpha) treatment is associated with up-regulation of epidermal growth factor receptor (HER1/EGFR) expression and marked growth inhibition while maintaining the sensitivity of the target colon cancer cells to epidermal growth factor (Gut 2004;53:123). We aimed to determine the effect of combining IFNalpha and Erlotinib (an HER1/EGFR inhibitor) on colon cancer cell line growth. Crystal-violet staining and flow cytometry were used to assess cell proliferation and expression of HER1/EGFR. IFNalpha pre-treatment followed by a combination of IFNalpha plus Erlotinib significantly enhanced the sensitivity of 7/9 of colon cancer cell lines by 7-43%. This approach may have clinical implications for improving treatment based on targeting of HER1/EGFR.
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PMID:Interferon-alpha promotes the anti-proliferative effect of Erlotinib (OSI-774) on human colon cancer cell lines. 1592 58

Progress in the treatment of colon cancer depends on the development of target-based molecules built on an improved understanding of the molecular biology of the disease. Defining end points for chemotherapy resistance is needed as drug resistance develops quickly and patients demonstrate variation in response to chemotherapy. Many techniques that measure a marker's preponderance have been developed including biochemical, immunohistochemical, genomics, proteomics or a combination thereof. However, standardization of these techniques that measure either genes or their protein products is urgently needed. This article reviews several markers (TS,TP, DPD, FT, EGFR, VEGF, CD44v6, TRAIL, microsatellite instability, allelic deletions, oncogenes and suppressor genes [c-myc, Ki-Ras, p53, p21, Topo I, Topo IIalpha, Fos, hMLH1, Bcl-2/Bax and MDR1], MDR-related proteins [Pgp, MRP and LRP], genomic polymorphisms [XPD, ERCC1, GSTP1 and TS 3 -UTR] and COX-;2) that influence DNA metabolism, DNA damage, programmed cell death, the immune or vascular system, or lead to mutations. When combined together and tested by newly developed genomic and proteomic approaches, many of these markers provide a more sensitive indicative predictor of response than when evaluated separately or by older biochemical, immunohistologic or morphologic methods. A global approach involving the simultaneous testing of several predictive multimarkers will provide critical information for improving chemotherapy to alleviate suffering from this disease.
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PMID:Molecular markers that predict response to colon cancer therapy. 1593 13

The IGF/IGF-1R system, which includes the IGF, IGF-1R, and IGFBPs proteins, plays an important role in the development and growth of colorectal cancer. We previously reported that in the HT29 human colon cancer cell line EGCG, the major biologically active component of green tea, inhibits activation of the RTKs EGFR, HER2, and HER3, and that this is associated with inhibition of multiple downstream signaling pathways. Since IGF-1R is also a RTK, in this study we examined the effects of EGCG on the activity of IGF/IGF-1R system in human colon cancer cells. We found that the colon cancer cell lines Caco2, HT29, SW837, and SW480 express high levels of the IGF-1R receptor, and that both SW837 and SW480 cells display constitutive activation of this receptor. Treatment of SW837 cells with 20 microg/ml of EGCG (the IC50 concentration for growth inhibition) caused within 6 h a decrease in the phosphorylated (i.e., activated) form of the IGF-1R protein. At 12 h, there was a decrease in the levels of both IGF-1 protein and mRNA and within 3-6 h there was an increase in the levels of both IGFBP-3 protein and mRNA. The increased expression of the latter protein was sustained for at least 48 h. When SW837 cells were treated with EGCG for a longer time, i.e., 96 h, a very low concentration (1.0 microg/ml) of EGCG also caused inhibition of activation of IGF-1R, a decrease in the IGF-1 protein, and an increase in the IGFBP-3 protein. EGCG also caused a decrease in the levels of mRNAs that encode MMPs-7 and -9, proteins that proteolyze IGFBP-3. In addition, treatment with EGCG caused a transient increase in the expression of TGF-beta2, an inducer of IGFBP-3 expression. These findings expand the roles of EGCG as an inhibitor of critical RTKs involved in cell proliferation, providing further evidence that EGCG and related compounds may be useful in the chemoprevention or treatment of colorectal cancer.
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PMID:EGCG inhibits activation of the insulin-like growth factor-1 receptor in human colon cancer cells. 1605 20

Development of cutaneous metastases from colon cancer is a rare event, usually occurring in the setting of diffusely-disseminated disease and commonly carrying a dismal prognosis. Cutaneous and subcutaneous metastases in surgical scars occur extremely rarely, with only a few cases reported. We describe two cases of cutaneous metastases from colon cancer. A 62-year-old woman developed an 11-cm midline abdominal mass that slowly grew on the skin surface. The mass occurred at the scar site of her previous surgery performed 5 years prior for resection of a colon adenocarcinoma. A 46-year-old male presented with a subcutaneous 4.5-cm nodule in midline-abdominal scar, 3 years after resection of the primary colon cancer. These cases illustrate the pathological features and natural history of cutaneous metastases observed until the tumors have reached a very large size. Particular features of cutaneous scar metastases from colon cancer observed in our cases are a superficial pattern of spread, strong positivity for EGFR, low serum carcinoembrionic antigen, and long survival of the patients, possibly contributed to by the use of chemotherapy.
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PMID:Unusually large colon cancer cutaneous and subcutaneous metastases occurring in resection scars. 1615 Feb 30

Caveolin is a major component of caveolae which is a plasma membrane microdomain. The emerging role of caveolin in tumorigenesis was based mainly on in vitro experiments with cancer cell lines. We performed semi-quantitative RT-PCR for caveolin, Akt and EGFR to understand the role of caveolins in colorectal tumor biology. Cancer tissue samples and the neighboring normal colon mucosa were obtained from 95 colorectal cancer patients who underwent operations at Ewha Womans University Mokdong Hospital. With these fresh tissues, semi-quantitative RT-PCR was performed by coamplification of the gene for caveolin-1, EGFR and Akt-1 with beta-actin. The average age was 60.21+/-13.33 years old, and sex ratio was 1.44:1. Caveolin-1 is more expressed in tumors than normal mucosa (P=0.025). The expression of caveolin-1 and Akt-1 had a definitive positive relationship (P=0.002). But, the expression of caveolin-1 and EGFR was not significantly related. We could not find correlations between caveolin-1 expression and clinical factors. In conclusion, caveolin-1 is more expressed in cancer tissues than normal colon and related with Akt-1, not with EGFR expression in colorectal cancer tissues, which suggests that signaling for caveolin-1 affects Akt-1 activation, but this reaction is not initiated by EGFR stimulation in colon cancer.
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PMID:Expression of caveolin-1 is correlated with Akt-1 in colorectal cancer tissues. 1620 96

The gene that encodes the alpha-isoform of phosphatidylinositol 3-kinase (PIK3Ca) is frequently mutated in human cancers. We profiled the mutation status of the PIK3Ca gene in the National Cancer Institute (NCI)-60 panel of human cancer cell lines maintained by the Developmental Therapeutics Program of the NCI. Mutation hotspots on the gene were PCR amplified and sequenced, and the trace data were analyzed with software designed to detect mutations. Seven of the cell lines tested have PIK3Ca mutations: two lines derived from breast cancer, two from colon cancer, two from ovarian cancer, and one from lung cancer. BRAF and EGFR genes were normal in the PIK3Ca mutant lines. Two of the cell lines with mutant PIK3Ca also have a mutant version of the KRAS gene. The mutation status was correlated with array-based gene expression that is publicly available for the NCI-60 cell lines. We found increased expression levels for estrogen receptor (ER) and ERBB2 in PIK3Ca mutant lines. The PIK3Ca mutation status was also correlated with compound screening data for the cell lines. PIK3Ca-mutant cell lines were relatively more sensitive than PIK3Ca-normal cell lines to the ER inhibitor tamoxifen and the AKT inhibitor triciribine, among other compounds. The results provide insights into the role of mutant PIK3Ca in oncogenic signaling and allow preliminary identification of novel targets for therapeutic intervention in cancers harboring PIK3Ca mutations.
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PMID:Correlation of PIK3Ca mutations with gene expression and drug sensitivity in NCI-60 cell lines. 1637 1

Increased expression of COX-2 appears to play an important role in the development of colorectal cancer. The level of COX-2 expression is regulated by various factors including activation of members of the EGFR family of RTKs. We previously reported that in HT29 human colon cancer cells EGCG, the major biologically active component of green tea, inhibits activation of two members of this family, EGFR and HER2, and multiple downstream signaling pathways. In this study we examined the effects of EGCG on the HER3 RTK and on COX-2 expression in the SW837 human colon cancer cell line that expresses a high level and constitutive activation of HER3 and also expresses a high level of COX-2. Treatment of these cells with 20 microg/ml of EGCG (the IC50 concentration for growth inhibition) caused, within 6 hours, a decrease in the phosphorylated (i.e. activated) forms of not only EGFR and HER2, but also HER3. At 6 to 12 hours there was a decrease in the phosphorylated forms of the downstream signaling proteins ERK and Akt. Within 6 to 12 hours there was a decrease in cellular levels of both COX-2 protein and mRNA, and within 48 hours the cells displayed apoptosis. Reporter assays indicated that EGCG inhibited the transcriptional activities of the COX-2, AP-1, and NF-kappaB promoters. EGCG also caused a decrease in production of PGE2, a major product of COX-2. With a longer incubation time, 96 hours, a very low dose (1.0 microg/ml) of EGCG also caused inhibition of cell growth, inhibition of activation of EGFR, HER2, and HER3, a decrease in the levels of COX-2 and Bcl-xL proteins, and apoptosis. These results provide the first evidence that a low concentration of EGCG can inhibit activation of, at least, three members of the EGFR family of RTKs, and also inhibit COX-2 expression in colon cancer cells. These findings extend our previous evidence that EGCG may be useful in the chemoprevention and/or treatment of colorectal cancer.
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PMID:EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. 1641 3

The epidermal growth factor has long been known to be strictly correlated with the highly proliferating activities of cancer cells and primary tumors. Moreover, in the nucleus, the epidermal growth factor/epidermal growth factor receptor complex (EGF/EGFR) functions as a transcriptional regulator that activates the cyclin D1 gene. 9-hydroxystearic acid (9-HSA) induces cell proliferation arrest and differentiation in HT29 colon cancer cells by inhibiting histone deacetylase 1 (HDAC1). 9-HSA-treated HT29, when stimulated with EGF, are not responsive and surprisingly undergo a further arrest. In order to understand the mechanisms of this effect, we analyzed the degree of internalization of the EGF/EGFR complex and its interactions with HDAC1. It appears that HDAC1, as modified by 9-HSA, is unable to associate with cyclin D1, interfering with the cell proliferation program, and sequesters the EGF/EGFR complex interrupting the transduction of the mitogenic signal.
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PMID:9-Hydroxystearic acid interferes with EGF signalling in a human colon adenocarcinoma. 1648 28


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