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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent progress of molecular oncology has made it possible for us to begin to understand the molecular mechanism for tumor development. However, from a viewpoint of its diagnostic and therapeutic applications, it seems that we have just left a starting line. Even Ki-ras and p53 genes that have been most extensively analysed, their most important clinical significances are considered to be giving us pathogenetic informations at the present time. Of note, allelic loss of chromosome 18q was shown a significant prognostic factor for colorectal cancer patients in stage II. One of most important clinical applications of molecular oncology in near future in our country is diagnosis of hereditary cancer. Analyses of sporadic cases with mutations in hereditary cancer genes will be of special importance.
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PMID:[Recent progress of molecular oncology and its contribution to clinical gastroenterology]. 892 Jun 48

The development of sensitive polymerase chain reaction (PCR)-based techniques in recent years has enabled us to verify the possible presence of mutated oncogenes and tumor suppressor genes in stages preceding tumor formation. Early detection of mutants serves as a powerful tool for detecting exposure to carcinogens and can assist in diagnosis. In studies performed in the past few years, we have identified mutant ras alleles in preneoplastic samples of patients with and without colorectal cancer. Our studies have shown (i) that mutant ras alleles are present at low incidence in normal appearing tissues of patients with colorectal cancer. Such mutations are also found in colonic effluents of patients at risk for developing this tumor type; and (ii) that the method of sampling is critical to ensure true representation of the entire colonic mucosa. The implications of identifying ras mutations in patients without evidence for neoplasma are discussed.
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PMID:Sampling method as a key factor in identifying K-ras oncogene mutations in preneoplastic colorectal lesions. 892 20

The geographic differences in the incidence of colorectal cancer have been mostly attributed to variations in diet. The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer sets the stage for investigating the possible association between dietary factors and mutations in tumor genes known to play a role in the pathogenesis of these neoplasms. With this purpose, we have studied the Ki-ras gene in 108 colorectal cancers using archival tissue and epidemiological data from our previous case-control study. Mutations in exon 1 of the Ki-ras gene were detected by a PCR-single strand conformation polymorphism approach. A polychotomous logistic regression model was used to assess the significance of observed differences between wild-type and mutated tumors with respect to population controls in the different categories of nutrient consumption. Multivariate density models were used to adjust the correlation between nutrients and total energy. Our studies show that high consumption of monounsaturated fats, mostly derived from olive oil, is associated with a statistically significant decrease in the risk of cancer with wild-type Ki-ras genotype but not of Ki-ras mutated cancers. Conversely, we find that high calcium intake is associated with a decreased risk of Ki-ras mutated tumors but not of wild-type tumors. Tumor genotyping can reveal epidemiological associations that are weak or unapparent when cases-control studies are not stratified by tumor genotype.
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PMID:Ki-ras mutation modifies the protective effect of dietary monounsaturated fat and calcium on sporadic colorectal cancer. 899 98

Liver metastases arise in about a third of patients with colorectal cancer. Although important clinical results have been obtained by surgical treatment in patients with limited liver involvement, other intra-arterial or systemic therapies do not provide important long term clinical benefits in patients with unresectable liver metastases. Better knowledge of the biology of liver metastases could imply a more appropriate use of the available therapeutic approaches and a retrospective definition the biologic subgroups of patients who benefit from them. Phenotypic and molecular aspects of tumor cells have been investigated and have proven to be important determinants of clinical outcome in patients with different human tumor types. Liver metastases from colorectal cancer have been scarcely studied, but cell proliferation has been shown to be a discriminant of freedom from progression and even more of long-term clinical outcome in subsets in patients treated with radical surgery. Moreover, in patients with resectable liver metastases, DNA and entity of DNA abnormalities are significantly associated with patient survival. A few recent reports have indicated a potential prognostic relevance of abnormal activation or expression of the p53 tumor suppressor gene, bel-2 protein and ras oncogene. In conclusion, prognostic biologic factors are acquiring an important role as indicators of clinical outcome in patients with liver metastases. However, all information is derived from retrospective analyses heterogeneous for patient population and biomarkers analyzed. Therefore, the comparison among results from different studies is difficult, and prospective studies are needed to develop a prognostic classification which integrates biologic and pathologic factors.
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PMID:Biological prospectives to define prognosis and treatment strategies in liver metastases from colorectal cancer. 912 89

The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21ras or pp60c-src in human colonic cells is associated with alterations of the activity and expression of nuclear factor kappaB (NF-kappaB), a transcription factor suspected to participate in the development of cancer. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated Val-12 human Ha-ras gene or with the polyoma middle T (PyMT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. Compared with control vector-transfected Caco-2 cells, both oncogene-transfected cell lines exhibited: (i) decreased constitutive NF-kappaB DNA-binding activity and NF-kappaB-mediated reporter gene expression, without alteration of their response to TNF-alpha for activation of these parameters; (ii) reduced NF-kappaB cytosolic stores along with a decreased p65 expression due, at least in part, to destabilization of p65 mRNA; (iii) a decrease in adhesion to extracellular matrix component-coated substrata which was partially corrected when stimulating NF-kappaB transcriptional activity with TNF-alpha. These results indicate that the tumorigenic progression induced by oncogenic p21ras or PyMT/pp60c-src in human colonic Caco-2 cells is associated with a down-regulation of p65 expression and NF-kappaB activity which could be responsible for the reduced adhesive properties of these cells after oncogene transfection.
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PMID:Down-regulation of NF-kappaB activity and NF-kappaB p65 subunit expression by ras and polyoma middle T oncogenes in human colonic Caco-2 cells. 912 50

The protein encoded by ras and src protooncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study, we investigated the effect of oncogenic p21ras and Py-MT/pp60c-src on the synthesis of syndecan-1, a membrane anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells transfected with an activated (Val-12) human Ha-ras gene or the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. As compared to control vector-transfected Caco-2 cells, both oncogene-transfected cells exhibited: (1) a decrease in syndecan-1 specific activity; (2) a decrease in size and sulfation of syndecan-1 ectodomain glycosaminoglycan side chains; and (3) an active heparanase specifically degrading the heparan sulfate chains. In conclusion, the tumorigenic progression induced by oncogenic p21ras or Py-MT/pp60c-src is associated with marked alterations of syndecan-1 at the post-translational level.
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PMID:[Oncogenic activation of p21ras or pp60c-src in human colonic Caco-2 cells induces post-translation alterations of syndecan-1]. 920 67

Human solid tumors develop multiple genetic evolutionary abnormalities as they evolve. Studies that have focused primarily on early colorectal cancer have suggested that genetic instability is a prominent feature of preinvasive disease. At least two separate mechanisms for the generation of genetic instability have been identified. The first, which involves widespread microsatellite instability in near-diploid cells, affects less than one-fifth of colon cancers. The second form of genetic instability is characterized by the development of p53 gene abnormalities that result in gross aneuploidy and multiple structural chromosomal changes. p53/aneuploidy affects most colon cancers, breast cancers, and many other solid tumors. This genetic evolutionary change commonly occurs at the interface between severe dysplasia and invasive disease. Specific post-aneuploid sequences of genetic changes that are relevant to tumor progression often involve the accumulation of multiple gain-of-function abnormalities in individual cells. The co-occurrence of Her-2/neu overexpression and EGF receptor overexpression in the same aneuploid cells defines an adeno/squamous genetic evolutionary sequence that is common to ductal breast cancers, non-small cell lung cancers, and other solid tumors. Later steps in this sequence include ras and c-myc overexpression. The neuroendocrine genetic evolutionary sequence is a separate branch of the p53/aneuploidy sequence with distinctive features that include loss of Rb and raf1 overexpression. Her-2/neu overexpression is not characteristic of this sequence; c-myc amplification/overexpression is common to both p53-associated sequences. The neuroendocrine sequence is found in small cell carcinoma of the lung and in minor proportions of other solid tumors, including breast cancer. Multiparameter cell-based methods are especially well suited for elucidation in human solid tumors of the genetic evolutionary sequences that could provide a rational scientific basis for determining prognosis and for optimizing therapy in individual cancer patients.
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PMID:Common patterns of genetic evolution in human solid tumors. 929 7

Tumor samples from five patients with metastatic colorectal cancer who demonstrated tumor regressions in clinical trials of interleukin (IL)-1 beta, IL-2, and adoptive cellular therapy were analyzed for oncogene and cytokine mRNA expression. Tumors from eight nonresponding patients were also studied. Mutations of the ras protooncogene and overexpression of c-myc protooncogene were observed in both responding and nonresponding tumors. In contrast, none of the responding tumors expressed transforming growth factor (TGF)-beta 1 mRNA, whereas nonresponding tumors did. The expression of IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, granulocyte macrophage-colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, macrophage chemotactic protein, and RANTES was variable between responding and nonresponding patients. Although we cannot conclude that a pattern of oncogene and/or cytokine mRNA expression specifically characterizes sensitive colorectal cancers, these analyses-the assessment of TGF-beta 1 mRNA in particular-merit further evaluation as biomarkers prognostic of immunotherapy response.
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PMID:Oncogene and cytokine expression of human colorectal tumors responding to immunotherapy. 933 44

Increased understanding of the molecular basis of colorectal cancer and recognition that extracellular DNA circulates in the plasma and serum of cancer patients enables new approaches to detection and monitoring. We used a polymerase chain reaction (PCR) assay to demonstrate mutant K-ras DNA in the plasma or serum of patients with colorectal cancer. Plasma or serum was fractionated from the blood of 31 patients with metastatic or unresected colorectal cancer and from 28 normal volunteers. DNA was extracted using either a sodium chloride or a gelatin precipitation method and then amplified in a two-stage PCR assay using selective restriction enzyme digestion to enrich for mutant K-ras DNA. Mutant K-ras DNA was detected in the plasma or serum of 12 (39%) patients, all confirmed by sequencing, but was not detected in any of the normal volunteers. K-ras mutations were detected in plasma or serum regardless of sex, primary tumour location, principal site of metastasis or proximity of chemotherapy and surgery to blood sampling. Tumour specimens available for 19 of the patients were additionally assayed for ras mutations and compared with blood specimens. Our results indicate mutant K-ras DNA is readily detectable by PCR in the plasma or serum of patients with advanced colorectal cancer. Thus, plasma- or serum-based nucleic acid amplification assays may provide a valuable method of monitoring and potentially detecting colorectal cancer.
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PMID:Detection of mutant K-ras DNA in plasma or serum of patients with colorectal cancer. 937 74

Colorectal cancer (CRC) is one of the most frequent cancers in Western countries. The identification of individuals at risk and the early diagnosis of CRC are of critical importance since a large proportion can be prevented or cured by surgical removal before metastasis has occurred. With increasing understanding of the genetic basis of hereditary and sporadic (non-hereditary) CRC, it becomes feasible to detect genetic alterations by molecular techniques. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) as well as early stages of spontaneous CRC can be diagnosed by molecular characterization of the adenomatous polyposis coli (APC) gene, the ras oncogene and other genes, respectively, in DNA from peripheral blood, stool or intestinal biopsies. At present, careful patient and family history, physical examination, testing for occult blood as well as colonoscopy are still the key elements, however, for clinical patient management. Molecular diagnosis will hopefully soon complement these analyses and should result in a reduction of morbidity and mortality from CRC. Further, gene therapy offers some potential to prevent or treat CRC.
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PMID:[Colon carcinoma: molecular diagnosis and therapy]. 941 70


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