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)

Overexpression of aspartyl (asparaginyl) beta-hydroxylase (AAH) has been demonstrated in hepatocellular carcinoma, cholangiocarcinoma, and pancreatic carcinoma. AAH has an important role in regulating cell motility and invasiveness. Humbug is a truncated homolog of AAH, with a role in calcium regulation. The present study examines the prognostic use of AAH and humbug gene expression in stage II colon cancer. One hundred thirty cases of TNM stage II colon carcinoma were retrieved from the Rhode Island Hospital pathology archives. Tissue microarrays were immunostained with the FB50 and 15C7 monoclonal antibodies generated to recombinant AAH. However, FB50 also recognizes humbug. In addition, AAH and humbug expression was analyzed in samples of colon cancer and adjacent normal mucosa by real-time quantitative reverse transcriptase-polymerase chain reaction. Humbug (FB50) expression was localized to the tumor cytoplasm, whereas normal colonic epithelium did not exhibit significant immunoreactivity. Humbug staining was detected in 85% of the neoplasms, 23% of which stained strongly. Strong humbug immunoreactivity positively correlated with nuclear grade (P = .006) and inversely with survival (P = .027). In contrast to humbug, AAH (15C7) immunoreactivity was seen in normal and neoplastic epithelium. There was no correlation between AAH immunoreactivity and tumor grade, or survival. Correspondingly, reverse transcriptase-polymerase chain reaction studies demonstrated up-regulation of humbug but not AAH in 95% of colon carcinomas relative to adjacent colon cancer-free mucosa (P < .0001). This study demonstrates that high levels of humbug immunoreactivity in colon carcinomas correlate with histologic grade and tumor behavior, suggesting that humbug can serve as a prognostic biomarker of TNM stage II colon cancers. In addition, molecular studies demonstrated that the increased levels of FB50 detected were due to humbug, as opposed to AAH overexpression.
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PMID:Prognostic value of humbug gene overexpression in stage II colon cancer. 1702 Jul 79

Colon cancer patients routinely undergo preoperative computed tomography (CT) scanning, but local staging is thought to be inaccurate. We aimed to determine if clinical outcome could be predicted from radiological features of the primary tumour. Consecutive patients at one hospital undergoing primary resection for colon cancer during 2000-2004 were included. Patients with visible metastases were excluded. Preoperative CT scans were reviewed independently by two radiologists blinded to histological stage and outcome. Images of the primary tumour were evaluated according to conventional TNM criteria and patients were stratified into 'good' or 'poor' prognosis groups. Comparison was made between prognostic group and actual clinical outcome. Hundred and twenty-six preoperative CT scans were reviewed. T-stage and nodal status was correctly predicted in only 60 and 62%, respectively. However, inter-observer agreement for prognostic group was 79% (kappa=0.59) and 3-year relapse-free survival was 71 and 43% for the CT-predicted 'good' and 'poor' groups, respectively (P<0.0066). This compared favourably with 75 vs 43% for histology-predicted prognostic groups. Computed tomography is a robust method for stratifying patients preoperatively, with similar accuracy to histopathology for predicting outcome. Recognition of poor prognosis tumours preoperatively may permit investigation into the future use of neo-adjuvant therapy in colon cancer.
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PMID:Preoperative computed tomography staging of nonmetastatic colon cancer predicts outcome: implications for clinical trials. 1735 25

The current TNM classification considers a tumor nodule in the pericolic/perirectal adipose tissue as venous invasion if the nodule has an irregular contour and as regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node. However, detailed studies on the clinico-pathological implications of pericolonic tumor deposits and of extranodal extension are still lacking. We investigated the impact of these metastatic deposits in the pericolic fat in a series of 228 patients with advanced colon cancer. The pericolonic tumor deposits were characterized by their appearance, size, distance from the primary tumor and by their relation with the lymphatic tissue not organized in lymph nodes. These features were then compared with the clinico-pathological characteristics of the tumors and with the patients' survival. All these lesions were associated with reduced disease-free and overall survivals in a univariate analysis, but only pericolonic tumor deposits retained an independent prognostic role in the multivariate analysis. Our findings suggest that pericolonic tumor deposits are a destructive type of venous invasion different from other types of vessel involvement, and that these lesions may rather be included in the M category for staging purposes.
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PMID:Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging. 1749 97

Hedgehog-interacting protein (HHIP) was identified as a putative antagonist of the Hh pathway and as a target of Hh signalling. Our aim was to clarify the expression profiles and epigenetic alterations of the HHIP gene in gastrointestinal cancer. The expression and promoter epigenetic status of HHIP in cancer cell lines and freshly resected gastrointestinal cancer tissues were examined using RT-PCR, tissue microarray analysis, methylation-specific PCR, and chromatin immunoprecipitation assay. Cells were treated with the demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor trichostatin A. WST-8 assays and in vitro invasion assays after treatment with HHIP-specific siRNA were performed. HHIP expression levels were reduced in most of the gastrointestinal cancer cell lines and in a certain subset of cancer tissues, and these were correlated with promoter hypermethylation. A heterochromatic structure characterized by neither acetylated H3 nor acetylated H4, and histone H3 lysine 9 hypermethylation and histone H3 lysine 4 hypomethylation was observed in cancer cells in which the HHIP gene was aberrantly silenced. On the other hand, overexpression of the HHIP gene was also found in some cancer tissues and there were significant correlations between protein expression levels of HHIP and those of Sonic hedgehog (Shh), Indian hedgehog, Patched, and glioma-associated oncogene homologue-1. An association was found between lymph node metastasis and HHIP silencing in colorectal cancer tissues with strong Shh expression and between advanced TNM stage and HHIP silencing in diffuse-type gastric cancer tissues with strong Shh expression. Down-regulation of HHIP expression by siRNA resulted in a significant increase in colon cancer cell growth and invasion in vitro. Silencing of the HHIP gene due to hypermethylation and chromatin remodelling appears to be frequently involved in gastrointestinal tumourigenesis.
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PMID:Transcriptional silencing of hedgehog-interacting protein by CpG hypermethylation and chromatic structure in human gastrointestinal cancer. 1772 92

Hazard regression models and cure rate models can be advantageously used in cancer relative survival analysis. We explored the advantages and limits of these two models in colon cancer and focused on the prognostic impact of the year of diagnosis on survival according to the TNM stage at diagnosis. The analysis concerned 9,998 patients from three French registries. In the hazard regression model, the baseline excess death hazard and the time-dependent effects of covariates were modelled using regression splines. The cure rate model estimated the proportion of 'cured' patients and the excess death hazard in 'non-cured' patients. The effects of year of diagnosis on these parameters were estimated for each TNM cancer stage. With the hazard regression model, the excess death hazard decreased significantly with more recent years of diagnoses (hazard ratio, HR 0.97 in stage III and 0.98 in stage IV, P < 0.001). In these advanced stages, this favourable effect was limited to the first years of follow-up. With the cure rate model, recent years of diagnoses were significantly associated with longer survivals in 'non-cured' patients with advanced stages (HR 0.95 in stage III and 0.97 in stage IV, P < 0.001) but had no significant effect on cure (odds ratio, OR 0.99 in stages III and IV, P > 0.5). The two models were complementary and concordant in estimating colon cancer survival and the effects of covariates. They provided two different points of view of the same phenomenon: recent years of diagnosis had a favourable effect on survival, but not on cure.
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PMID:Hazard regression model and cure rate model in colon cancer relative survival trends: are they telling the same story? 1826 81

The efficacy of adenovirus vector-based cancer gene therapy is controversial. Its uptake by cells in many cases requires the major receptor for adenoviruses, the coxsackievirus and adenovirus receptor (CAR). Low transduction is believed to be one of the main barriers as the expression of CAR on tumor cells is frequently reduced. Increasing CAR expression on tumor cells thus offers a promising opportunity for more effective adenovirus based treatment. Expression of CAR in 62 cases of colon tumor specimens were examined with immunohistochemistry. To modify the CAR expression, the effects of proteasome inhibitor MG132 on CAR expression of colon cancer cell lines were determined by flow cytometry, RT-PCR, and western blot. To evaluate adenovirus transfer, we further used rAd.EGFP, rAd.p53, and oncolytic adenovirus to infect target cells. The CAR expression was significantly decreased in colon carcinomas, both in primary tumors and lymphonode metastasis. Though the deregulation of CAR occurred in early disease and showed no relationship with TNM stage, when primary tumors are more than 5 cm in diameter, this deregulation becomes more frequent. More importantly, proteasome inhibitor MG-132 could enhance CAR expression in colon carcinoma cell line lovo, accompanied with enhanced adenovirus transfer, target gene expression, and oncolysis. These data provide a rational basis for evaluation of CAR expression in tumors and pretreatment with CAR conditioner prior to adenovirus vector-based gene therapy.
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PMID:Proteasome inhibitor MG-132 modifies coxsackie and adenovirus receptor expression in colon cancer cell line lovo. 1841 65

The authors analyzed a group of 1281 subjects with colorectal cancer operated and followed up in a single institution from I/1992 to VIII/2007. Colon carcinoma patients were assessed separately (C18). Patients with rectal and rectosigmoid tumors are not included in the presentation. A total of 846 patients were operated for colon carcinomas. In 546 subjects, radical R0 resections were achieved. In the R0 group, the male/female ratio is 315/231, age 29-94 years, the mean age of 69 years. The R0 group stratification by TNM classification was: I 17.8%, II 49.6%, III 24.0%, IV 8.1%, TNMx 0.5%. Irrespective of the TNM staging, three-year, five-year and ten-year survival rates were 80%, 71%, and 51%, resp. The median survival time was 9.85 years. Postoperative morality was 5.5%, morbidity 29.8%, anastomic leak occured in 5.7%. Systematic lymph node dissection up to the apical level, had been gradually introduced as an integral part of the R0 surgery. The aim of the study is to analyze outcomes of the colon carcinoma surgical management, combined with radical lymphadenectomy. Furthermore, effects of the extensive procedure on the postoperative morbidity and moratility rates are analyzed as well.
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PMID:[Treatment outcomes of colon cancer surgery combined with radical lymphadenectomy]. 1859 40

A rare case of breast cancer associated with von Recklinghausen's neurofibromatosis is reported. This case and review of the literature illustrate the problems of clinical diagnosis.A 66-year-old woman who had undergone sigmoidectomy for sigmoid colon cancer two years previously, was admitted to the hospital because of a left breast skin retraction in October, 1998. The patient had von Recklinghausen's disease (neurofibromatosis type 1). The TNM clinical staging was TlcNOMO. Modified radical mastectomy was performed. The histopathological diagnosis of the breast tumor was invasive ductal carcinoma and the skin tumor was neurofibroma. The pTNM pathological staging was pTlcNlaMO.Among patients similar to our case, almost all were staged higher than T2. This may be because multiple neurofibromas obscure breast mass at palpation, leading to delayed detection of the cancer. Systemic and careful exploration is essential for patients with von Recklinghausen's neurofibromatosis to detect breast cancer at an early stage.
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PMID:Ti breast cancer associated with Von Recklinghausen's neurofibromatosis. 1884 52

We are just beginning to understand how microRNAs (miRNAs) are involved in tumor-related processes in humans. Applying real-time RT-PCR, we investigated the miR-31, miR-143 and miR-145 expression in 98 primary CRC specimens, along with the corresponding normal mucosa specimens, and analyze the relationship of their expression with clinicopathological features. Our results showed the miR-31 expression was up-regulated in CRC compared to normal mucosa (p = 0.001). Furthermore, miR-31 expression was positively related to advanced TNM stage (p = 0.026) and deeper invasion of tumors (p = 0.024). MiR-145 was down-regulated in both colon (p = 0.001) and rectal (p = 0.012) cancer. MiR-143 was only down-regulated in colon cancer (p = 0.023) but not in rectal cancer (p = 0.351). There was no relationship of miR-143 and miR-145 expression with other clinicopathological features (p > 0.05), except that the miR-145 expression was related to cancer site (p = 0.03). In conclusion, the miR-31 overexpression may be involved in the development and progression of CRC. The miR-143 and miR-145 may play a certain role in the development of colon and/or rectal cancers but not in progression of the disease.
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PMID:Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. 1924 66

In colorectal cancer, the relation between duration of symptoms and stage at presentation and prognosis is not yet settled. All 1263 patients treated for colorectal cancer at Levanger Hospital, 1980-2004, and 2892 patients treated in Norway during 2004 were included. The association between symptom duration as an explanatory variable and tumour stage as a dependent variable was analysed using a proportional odds logistic regression model. Known duration of symptoms was divided into four categories: <1 week, 1-8 weeks, 2-6 months and >6 months. There was an inverse relationship between symptom duration and colon cancer TNM-stage, OR=0.73 (95% CI 0.63-0.84), p<0.001 (Levanger Hospital) and 0.84 (0.75-0.95), p=0.004 (Norway 2004), where the OR is per category of symptom duration. Duration of symptoms were also inversely associated with T-stage, N-stage and M-stage in colon cancer. These relationships were not found for rectal cancer. In colon cancer the relative five-year survival for the four intervals of symptom duration was 44%, 39%, 54% and 66%, p<0.001, in Levanger, 1980-2004, and four-year survival was 46%, 62%, 75% and 74%, p<0.001, in Norway 2004, respectively. For rectal cancer survival was not dependent on symptom duration. In a multivariate analysis of relative survival of patients with colon cancer, duration of symptoms was associated with survival independent of tumour differentiation and TNM-stage. Increasing duration of symptoms was positively associated with less advanced disease and better survival in colon cancer, but not in rectal cancer.
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PMID:Duration of symptoms, stage at diagnosis and relative survival in colon and rectal cancer. 1935 23


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