Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecules play an important role in tumor metastasis. E-selectin can support adhesion of colon cancer cells through the recognition of specific carbohydrate ligands. High levels of soluble E-selectin (sE-selectin) had been reported in melanoma and some epithelial tumors, especially in colorectal carcinoma. The concentrations of the sE-selectin were investigated in serum samples of 64 patients (32 men and 32 women) with colorectal cancer and 16 healthy subjects. Median age was 57 (range 20-75). Nineteen patients were staged as Dukes D, 9 of whom had liver metastasis. Serum levels of sE-selectin were determined by ELISA. In the study group, sE-selectin concentrations (mean+/-SE, ng/ml) were not significantly elevated, compared with the control group (41.09+/-4.57 in the control group and 43.80+/-1.88 in patients, p>0.05). Mean sE-selectin levels were 42.27+/-1.85 in non-metastatic and 47.42+/-4.57 in metastatic patients (p>0.05). Serum concentrations of sE-selectin were significantly elevated in patients with colorectal cancer metastatic to liver (59.07+/-7.52) in comparison to other patients without liver metastasis (p=0.013). There were no significant correlations between sE-selectin levels and other parameters such as age of patients, stage of disease, histopathological differentiation or localization of primary tumor. Elevated sE-selectin levels were confirmed as correlating with poor overall survival. In conclusion, sE-selectin concentrations may not be used as a predictive marker of metastasis in colorectal carcinoma, but high levels of sE-selectin may support diagnosis of liver metastasis.
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PMID:Serum levels of soluble E-selectin in colorectal cancer. 1525 58

Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence. The abundance of PINCH protein in stroma increased from normal mucosa to primary tumor to metastasis (P <.05), and was more intense at the invasive margin than it was in the intratumoral stroma. Strong stromal immunostaining for PINCH was shown to predict a worse outcome (rate ratio 2.1, 95% CI 1.16-3.37, P=.01), independent of Dukes stage, growth pattern, and tumor differentiation. PINCH was detected in fibroblasts, myofibroblasts, and a proportion of endothelial cells of the tumor vasculature, supporting the involvement of PINCH in promoting tumor-stromal interactions that support tumor progression. Interestingly, stromal staining for PINCH was an independent prognostic indicator in colorectal cancer.
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PMID:Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer. 1572 Aug 6

We have completed a multicenter, randomized controlled phase III clinical trial in Stages II and III colon cancer patients with active specific immunotherapy (ASI) using autologous tumor cells with an immunomodulating adjuvant bacillus Callmette-Guerin (BCG) vaccine (OncoVAX) in an adjuvant setting. In this study, patients were randomized to receive either OncoVAX therapy or no therapy after surgical resection of the primary tumor and stratified by stage of disease. Since the biologic essence of the effective tumor immunotherapy is the presence in the vaccine of a minimum number of viable, metabolically active, autologous tumor cells, the processing of the vaccine product, occurred within 48 h after surgery. Analysis of prognostic benefit in the pivotal phase III trial, with a 5.8 year median follow-up, showed that a beneficial effect of OncoVAX is statistically significant for all endpoints including recurrence-free interval, overall survival, and recurrence-free survival in Stage II colon cancer patients. Surgery alone cures approximately 65% of Stage II (Dukes B2, B3) colon cancer patients. In the remaining patients, OncoVAX in an adjuvant setting, significantly prolongs recurrence-free interval (57.1% relative risk reduction) and significantly improves 5-year overall survival and recurrence-free survival. No statistically significant prognostic benefits were achieved in Stage III (Duke's C1-C3) patients. A health economics assessment was performed on these results in Stage II colon cancer patients using disease-free survival and overall survival (for the entire intent-to-treat population). Cost-effectiveness, cost-utility and sensitivity analysis were applied with, cost of life years, recurrence-free life years and quality adjusted life years (QALYs) as the primary endpoints to this analysis. The perspective of the economic analysis was the current direct medical cost established by the health care providers. The introduction of new technologies often leads to additional costs. This report verified that the use of OncoVAX for patients with Stage II colon cancer not only has significant prognostic benefit and positive clinical outcomes, but also showed that OncoVAX therapy yields impressive health economics benefits.
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PMID:Immunotherapy with autologous tumor cell-BCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits. 1575 32

More than 50% of patients with Dukes C colorectal cancer have disease recurrence and die within 5 years after surgical removal of their primary tumor. It is currently not possible to distinguish patients with good and bad prognosis. SMAD4 is an important tumor suppressor gene that mediates transforming growth factor-beta superfamily signaling and is located in chromosome 18q21, a region with frequent genetic losses in these tumors. Allelic imbalance in 18q has been linked to poor prognosis in a subset of colorectal cancer patients. Therefore, we generated a tissue microarray containing triplicate tumor samples from 86 Dukes C patients and used immunohistochemistry to assess the relative expression level of SMAD4 and its value as a prognostic marker. In addition, SMAD4 was screened for mutations and two polymorphic microsatellite markers were used to assess the presence of allelic imbalance in these tumors. Patients with tumors expressing high SMAD4 levels had significantly better overall (P < 0.025) and disease-free (P < 0.013) survival than patients with low levels. This identifies SMAD4 as a prognostic marker for Dukes C colorectal cancer. Although all tumors with absent SMAD4 staining showed allelic imbalance in 18q21, tumors with 18q21 allelic imbalance as a group showed no difference in SMAD4 levels compared with tumors without allelic imbalance, suggesting that additional mechanisms of SMAD4 down-regulation exist. In addition, although SMAD4 mutations were found in five tumors, they were not associated with shorter survival. In conclusion, the level of expression of SMAD4 was found to be a more sensitive marker than 18q21 allelic imbalance and SMAD4 mutations, which were of no prognostic significance for these patients.
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PMID:SMAD4 as a prognostic marker in colorectal cancer. 1581 40

To identify chromosomal aberrations that differentiate among the Dukes' stages of colorectal cancer (CRC) as well as those that are responsible for the progression into liver metastases, we performed a meta-analysis of data obtained from 31 comparative genomic hybridization (CGH) studies comprising a total of 859 CRCs. Individual copy number profiles for 373 primary tumors and 102 liver metastases were recorded and several statistical analyses, such as frequency, multivariate logistic regression, and trend tests, were performed. In addition, time of occurrence analysis was applied for the first time to copy number changes identified by CGH, and each genomic imbalance was thereby classified as an early or late event in colorectal tumorigenesis. By combining data from the different statistical tests, we present a novel genetic pathway for CRC progression that distinguishes the Dukes' stages and identifies early and late events in both primary carcinomas and liver metastases. Results from the combined analyses suggest that losses at 17p and 18 and gains of 8q, 13q, and 20 occur early in the establishment of primary CRCs, whereas loss of 4p is associated with the transition from Dukes' A to B-D. Deletion of 8p and gains of 7p and 17q are correlated with the transition from primary tumor to liver metastasis, whereas losses of 14q and gains of 1q, 11, 12p, and 19 are late events. We supplement these findings with a list of potential target genes for the specific alterations from a publicly available microarray expression dataset of CRC.
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PMID:The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. 1614 79

Reduction/loss of E-cadherin is associated with the development and progression of many epithelial tumors, while in a limited number of neoplasms, E-cadherin is re-expressed in metastases. Dysadherin, recently characterized by members of our research team, has an anti-cell-cell adhesion function and downregulates E-cadherin in a posttranscriptional manner. Colorectal cancer (CRC) is one of the most common tumors in the developed world, and lymph node metastases are harbingers of aggressive behavior. The aim of the present study was to examine the dysadherin and E-cadherin expression patterns in lymph node metastases vs primary CRC. Dysadherin and E-cadherin expression was examined immunohistochemically in 78 patients with CRC, Dukes' stage C in the primary tumor and in one lymph node metastasis. Dysadherin was expressed in 42% while E-cadherin immunoreactivity was reduced in 45% of primary tumors. In lymph nodes, 33 and 81% of metastatic tumors were positive for dysadherin and E-cadherin, respectively. Dysadherin expression was not correlated with E-cadherin expression in the primary tumor with a reverse correlation evident in the lymph node metastases. Our results suggest that different mechanisms govern E-cadherin expression in the primary tumor and the corresponding lymph node metastases.
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PMID:Expression patterns of dysadherin and E-cadherin in lymph node metastases of colorectal carcinoma. 1657 Jan 80

In the period of November 1999 - June 2003 78 patients with colorectal liver metastases (CLM) were operated at Department of Surgery, University Hospital in Pilsen. In multifactorial analysis there were evaluated these clinical parametres: age of patient, sex, localisation of primary tumor, Dukes classification, grading, staging and histology of primary tumor, histologicaly free resection margin, chemotherapy or actinotherapy after colorectal operation, type of liver resection, complications after liver surgery, radicality of liver surgery, lateralisation of liver metastatic process, number of metastases, blood transfusions, repeated liver surgery, volume of metastases. Kaplan-Meier method was used for evaluation of survival rate and disease free interval (DFI). Statistical analysis of studied clinical parametres was performed by Log-rank test and Wilcoxon test. The medium DFI after liver surgery was 16 months for all the patients (range 0-55 months), the medium DFI for patients after radical surgery was 18 months. The medium survival time after liver surgery for all the patients was 30 months (range 1-57 months), for patients after radical surgery it was 32 months, and for patients after palliative surgery the medium disease free interval was 29 months (range 5-30 months). The 4-year survival rate after the liver surgery was for all the patients 37%. The factors statistically significant for a disease free interval after liver surgery were bilaterality of metastatic process, the microscopically free resection line, radical surgical treatment versus RFA and unilaterality of metastatic process. The authors proved followed factors as statistically significant for survival rate: grading of colorectal cancer and age of patients. The prediction of early recurrence enables us to choose adequate surgical therapy or its extension by oncological therapy. More thorough follow up of patients with tendency to early recurrence of CLM helps to early diagnosis of relaps and it increases the posssibility of repeated liver surgery.
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PMID:[A partial relaps of a colorectal carcinoma metastatic process following liver surgery--a multifactorical study]. 1662 18

The aim of this study was to analyze the prognostic value of TP53 mutations in a consecutive series of patients with hepatic metastases (HMs) from colorectal cancer undergoing surgical resection. Ninety-one patients with liver metastases from colorectal carcinoma were included. Mutational analysis of TP53, exons 4-10, was performed by single-strand conformation polymorphism and sequencing. P53 and P21 protein immunostaining was assessed. Multivariate Cox models were adjusted for gender, number of metastasis, resection margin, presence of TP53 mutations and chemotherapy treatment. Forty-six of 91 (50.05%) metastases showed mutations in TP53, observed mainly in exons 5-8, although 14.3% (n = 13) were located in exons 9 and 10. Forty percent (n = 22) were protein-truncating mutations. TP53 status associated with multiple (> or =3) metastases (65.6%, P = 0.033), advanced primary tumor Dukes' stage (P = 0.011) and younger age (<57 years old, P = 0.03). Presence of mutation associated with poor prognosis in univariate (P = 0.017) and multivariate Cox model [hazard ratio (HR) = 1.80, 95% confidence interval (CI) = 1.07-3.06, P = 0.028]. Prognostic value was maintained in patients undergoing radical resection (R0 series, n = 79, P = 0.014). Mutation associated with a worse outcome in chemotherapy-treated patients (HR = 2.54, 95% CI = 1.12-5.75, P = 0.026). The combination of > or =3 metastases and TP53 mutation identified a subset of patients with very poor prognosis (P = 0.009). P53 and P21 protein immunostaining did not show correlation with survival. TP53 mutational status seems to be an important prognostic factor in patients undergoing surgical resection of colorectal cancer HMs.
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PMID:Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection. 1725 58

Formation of cancer stem cells which are both rare and variably therapy-resistant marks the beginning of a new disease without precursors. Based on molecular changes, these cells are derived from normal cells and exhibit pre-programmed malignant behaviour. In vitro studies have shown that hybrid cancers which behave in a similar way to Dukes A, B or C cancers in vivo can be produce by horizontal gene transfer. The level of aggressiveness follows a Galton curve in the probability distribution. In the current paper we analyzed colorectal cancers by PET-CT in follow-up studies which extended over several years. We conclude that the primary tumors behave differently from distant metastases. Radical exstirpation of the primary tumor is able to cure the malignant process if the homing area is resected. The primary tumor acts as the supplier of cancer stem cells for metastases which appear in different organs. When chemotherapy is administered the distribution of metastases in different organs appears dependent of the response or non-response of cancer stem cells to this therapy. Large numbers of colorectal carcinomas existed for the same time duration before death (15 years) independent of the malignancy grade. The tumor metastasizes immediately after formation. The primary tumor and the metastases appear variably quickly depending on the malignancy grade and are autonomic processes.
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PMID:[PET-CT studies of metastasizing cancer of the colon and rectum. Variability of tumor aggressiveness as a micro-evolutionary process of cancer stem cells with predetermined prognosis]. 1956 40

The aim of this study was to evaluate the results of surgery of colorectal liver metastases and assess prognostic factors influencing the outcome. A total of 135 hepatic resections performed in 107 patients was reviewed. The following prognostic factors were analyzed: primary tumor localization, Dukes stage, number and presence of metastases in one or two lobes, synchronous or metachronous occurrence, type of resection, use and modality of chemotherapy. The perioperative morbidity rate was 6.5% and mortality was 1.9%. Overall survival was 41.2% and disease-free survival 31.5% at 5 years. Survival at 5 years was better for patients with metachronous than for those with synchronous lesions (60.9% vs 28.1%; p<0.05). There were no significant differences in terms of long-term survival between patients with synchronous metastases that were excised simultaneously or with a delay of 3-6 months (p=n.s.). Site of the primary tumor, Dukes stage, number of metastases and type of resection did not influence survival. A favorable survival trend was observed in those patients who underwent both neoadjuvant and adjuvant chemotherapy. The overall survival rate at 5 years was 45.3% for patients undergoing a second hepatic resection and 50% for those with a third or a fourth hepatic resection. Liver resection remains the "gold standard" for the treatment of patients with colorectal liver metastases, with metachronous type having a better outcome than synchronous. Simultaneous or delayed surgery for synchronous metastases does not influence prognosis. Iterative resection is very encouraging and justifies an aggressive surgical approach.
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PMID:Prognostic factors in primary and iterative surgery of colorectal liver metastases. 2112 61


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