Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of endothelin (ET)-1 and its receptors, ETAR and ETBR, commonly referred to as the 'ET-axis', has been demonstrated to play a role in cancer progression for various human tumours. Based on these results we propose a similar role of the expression of the ET-axis in vulvar cancer. Expression of the ET-axis was investigated immunohistochemically using tissue microarrays with tumour samples of 68 vulvar cancer patients. Samples were obtained from patients undergoing local excision or radical vulvectomy. ET-1 expression of tumour cells correlated highly significantly with early stages of vulvar cancer (p=0.004), whereas neither ETAR nor ETBR expression showed any association with TNM stages. High staining levels of ETBR in the tumour tissue were significantly related to tumour progression (p=0.01) and early metastases (p=0.09); low ETBR staining intensity correlated with longer relapse-free survival (p=0.019). In patients with ETBR overexpressing low-stage tumours (pT1-2) we observed a significantly reduced overall survival and disease-free survival (p=0.036 and 0.021, respectively). ETAR expression and ETBR expression were significantly correlative (p=0.018). Accordingly, co-expression of both receptors was related to tumour progression (p=0.022) and an increased risk for local recurrence (p=0.005). These results suggest that, in addition to established histological and clinical prognostic factors, analysis of ET-receptor and, in particular, of ETBR expression by means of simple immunohistochemical analysis might improve prediction of the prognosis for patients with vulvar squamous cell carcinoma.
 ...
PMID:Expression and prognostic relevance of endothelin-B receptor in vulvar cancer. 1761 49

The activity of T regulatory cells (Tregs) is known to be closely associated with the expression of forkhead/winged helix transcription factor, FOXP3. To determine, whether accumulation and activation of intratumoral Tregs help in the progression of breast carcinoma, we have analyzed the intratumoral expression of FOXP3 in invasive breast carcinoma and compared it with its level in ductal carcinoma in situ (DCIS) and adjacent normal tissue with the main aim of using this factor as marker of tumor progression. Intratumoral FOXP3 levels were correlated with the levels of transforming growth factor beta1 (TGF-beta1), vascular endothelial growth factor (VEGF, an invasogenic and angiogenic growth factor) and intratumoral microvessel density (IMD, a prognostic marker for angiogenesis). We also analyzed whether FOXP3 gene expression correlated with other clinicopathological variables like age, tumor stage, histological grade and lymph node metastasis. Infiltrating cancers had higher FOXP3 transcription (7.43+/-3.44) than did ductal carcinoma in situ (4.27+/-1.97, p<0.05) and normal tissues (3.51+/-1.22, p<0.001). Intratumoral FOXP3 expression was significantly higher in patients with stage III disease (TNM classification) compared to patients who had stage II disease (p=0.037). In infiltrating carcinoma, a significant positive correlation between FOXP3 expression and TGF-beta1 expression was noted (p<0.001). Furthermore, a positive correlation between FOXP3 expression with VEGF expression and IMD values was also detected, however, statistically that was non-significant. A linear association of intratumoral FOXP3 expression with invasion, size and vascularity suggests a utility of FOXP3, an indicator of Treg activity as a marker of tumor progression and metastasis in breast carcinoma.
 ...
PMID:Intratumoral FOXP3 expression in infiltrating breast carcinoma: Its association with clinicopathologic parameters and angiogenesis. 1765 2

The complex roles of genomic instability, MYC oncogene amplification, activation of telomerase, and p53 function still remain to be fully described in breast tumors. MYC stimulates the telomerase catalytic subunit, TERT, which interacts with p53. Oncogene MYC amplification analysis was performed on 27 paraffin-embedded breast tumor samples by fluorescence in situ hybridization, selected on the basis of chromosomal instability. TERT immunostaining was performed on a larger group of breast tumor sections. All tumor samples were analyzed for TP53 mutation, genomic index, S-phase fraction, and pathological stages. Amplification of MYC was detected in 16 of 27 tumors (59%) and found to be associated with TNM stages I and II (P = 0.018), genomic index > 1.5 (P = 0.033), and S-phase fraction > 5% (P = 0.020). No association was found between MYC amplification and TERT immunostaining or TP53 mutations. Analysis of TERT in 103 primary breast tumors showed > 50% nuclei immunostaining in 58% of cases. High TERT immunostaining associated with genomic index > 1.5 (P = 0.017), high S-phase fraction (P = 0.056), and TP53 mutations (P = 0.030). No association was found between TERT staining and TNM stages. This study supports early involvement of MYC amplification in breast tumor progression. Both MYC amplification and TERT expression appear to be associated with high genomic instability and proliferation. TERT association with TP53 mutations indicates that TERT activity is downregulated by functional p53 protein in breast tumors.
 ...
PMID:MYC amplification and TERT expression in breast tumor progression. 1765 50

By regulating matrix metalloproteinase (MMP) activity and controlling the breakdown of extracellular matrix components, tissue inhibitors of metalloproteinases (TIMPs) play an important role in the process of tumor invasion and metastasis. The present study was designed to clarify the role of TIMP-2 in nasopharyngeal carcinoma (NPC) patients and to evaluate its importance relative to clinicopathologic parameters. It was carried out in 30 patients with NPC and 20 controls. Tissue biopsies were studied and graded pathologically, and Western blot analysis was performed to assess TIMP-2 protein expression. Clinically, in accordance with TNM classification (T: tumor size, N: lymph node involvement, M: distant metastasis), 8 cases were diagnosed as stage II, 12 as stage III, and 10 cases as stage IV; however, pathologic typing with use of the World Health Organization (WHO) classification revealed the presence of 9 specimens of squamous cell carcinoma (WHO type 1), 6 cases of nonkeratinizing carcinoma (WHO type 2), and 15 cases of undifferentiated carcinoma (WHO type 3). The difference in percentage of TIMP-2 positivity between NPC patients (76.6%) and normal controls (30%) was statistically highly significant (P < .01). In addition, there was a significant positive correlation between TIMP-2 protein positivity and either the clinical staging or the histopathologic typing (P < .01) using Chi-square test (x(2)), suggesting that TIMP-2 can be used as a marker of the severity of NPC.Accordingly, we can assume that TIMP-2 may play a role in regional lymph node and/or distant metastasis and in progression of squamous cell carcinoma. Further studies are needed to investigate the role of TIMP-2 as a marker for tumor progression and to evaluate its potential value in the follow-up of patients.
 ...
PMID:Tissue inhibitor of matrix metalloproteinase-2 in nasopharyngeal carcinoma. 1809 10

Liver transplantation (LT) in the presence of hepatocellular carcinoma (HCC) remains a controversial issue because the current staging systems are not sufficiently predictive of outcomes. Paraffin blocks from 183 patients that underwent LT in the presence of HCC were collected. Molecular analysis was carried out blindly on the native liver specimens in all cases with respect to recurrence outcomes. The fractional allelic imbalance (FAI) rate index was determined in each case and was used to compare the acquired mutational load between different tumors. The FAI was determined from the microdissected tissue site displaying the greatest amount of acquired allelic loss. FAI was found to be the strongest predictor of recurrence followed by vascular invasion and then by tumor number or hepatic lobar involvement. Based on these findings, 3 prognostic models were constructed for selection of candidates for LT in patients with concomitant HCC. Molecular markers of tumor progression are the strongest predictors of HCC recurrence currently available, surpassing all components of the tumor-node-metastasis classification system for staging of malignant tumors (TNM), including vascular invasion. Incorporation of these molecular markers of tumor progression could help resolve the ongoing conundrum of organ allocation for patients with HCC.
 ...
PMID:Fractional allelic imbalance could allow for the development of an equitable transplant selection policy for patients with hepatocellular carcinoma. 1826 11

In order to define more effective predictive markers for clinical management and prognosis, we evaluated the expression of cyclin D1 and survivin in large papillary thyroid carcinoma (LPTC) and microcarcinoma (PTM). Sixty-seven patients operated for papillary carcinoma (36 of which with PTM) were considered. Immunochemistry for cyclin D1 and survivin was performed in samples from tumor mass and nodal metastases. There were not significant differences between LPTC and PTM as to patients personal data, TNM or MACIS staging, nodal invasion and multifocality, while capsular invasion was significantly more frequent in LPTC. Cyclin D1 and survivin were expressed at a very high rate and almost to the same extent in LPTC and PTM, both in tumoral mass and in nodal metastases. Survivin showed only cytoplasmic expression. Cyclin D1 and survivin over-expression are probably early events in tumorigenesis of thyroid papillary carcinoma but their full role in the process of tumor progression and their clinical value are still to be investigated.
 ...
PMID:Survivin and cyclin D1 are jointly expressed in thyroid papillary carcinoma and microcarcinoma. 1857 19

Cortactin, fascin-1 and EGFR are recognized as important factors in tumor progression. We tested the hypothesis that cortactin, fascin-1 and EGFR expression correlates with clinicopathological parameters of the four most common ovarian surface epithelial carcinomas--serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma, and clear cell carcinoma. Immunohistochemical analysis of cortactin, fascin-1 and EGFR was performed using tissue microarrays of 172 specimens comprising 69 serous cystadenocarcinomas, 44 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas and 14 clear cell carcinomas. All ovarian carcinomas showed significant expression of cortactin, fascin-1 and EGFR in staining intensity, tumor percentages and immunostaining scores. In addition, higher immunostaining scores of fascin-1 correlated with more advanced cancer stages (TNM), poorer histological differentiation and poorer survival rate of mucinous cystadenocarcinoma. Similarly, higher immunostaining scores of cortactin correlated with T stages and histological differentiation of serous cystadenocarcinoma. The immunostaining scores of EGFR did not correlate with TNM stages, tumor differentiation or prognosis in the four ovarian surface epithelial carcinomas. Our findings suggest that cortactin and fascin-1 may serve as good biomarkers in evaluating aggressiveness of ovarian serous and mucinous cystadenocarcinoma. And the pharmacological inhibitors of fascin-1 activity may slow down tumor progression and prolong survival time in patients with mucinous cystadenocarcinoma.
 ...
PMID:Association of cortactin, fascin-1 and epidermal growth factor receptor (EGFR) expression in ovarian carcinomas: correlation with clinicopathological parameters. 1877 88

Adhesion molecules take part in physiological and pathological processes. They involved in inflammatory reactions and play important role in tumor invasion and the development of metastases. Soluble forms of P-selectin, E-selectin and ICAM-1 have been described in this study in patient with colorectal cancer. Plasma was obtained from 44 patients with colorectal cancer and 34 control subject's prior surgery, by an enzyme-linked immunosorbent assay (ELISA). The patients were divided according to TNM classification. Plasma level of all three molecules was significantly higher in colorectal cancer patients than in the control (p < 0.001). The highest level of sE-selectin and ICAM-1 were observed in patients with liver metastasis. There was no correlation between sP-selectin and sE-selectin, but we found a significant correlation between sE-selectin and ICAM-1 in all patients. These findings suggest that plasma concentration of E-selectin and ICAM-1 may indicate tumor progression and liver metastasis.
 ...
PMID:Does colorectal cancer clinical advancement affect adhesion molecules (sP-selectin, sE-selectin and ICAM-1) concentration? 1913 45

Osteopontin is a tumor-associated protein that promotes tumor development and metastasis. The preoperative blood samples of 94 oral squamous cell carcinoma (OSCC) patients and 28 healthy individuals were analyzed for plasma osteopontin levels, and another 256 paraffin-embedded OSCC specimens were analyzed by osteopontin immunostaining. The patients with advanced tumor (T) stage (T3/T4 vs. T1/T2) and positive nodal (N) status had significantly higher plasma levels of osteopontin (both p<0.001). Positive osteopontin immunostaining also correlated significantly with advanced T stage (p<0.001), positive N status (p<0.001), advanced TNM stage (p<0.001) and male gender (p=0.016). Unfavorable cumulative 5-year overall survival rates correlated significantly with positive osteopontin immunostaining (p<0.001), advanced T stage (p<0.001), positive N status (p<0.001) and advanced TNM stage (p<0.001). However, Cox regression analysis revealed that T stage and N status were independent prognostic factors for survival (both p<0.001) and osteopontin immunostaining was marginally significant for survival (p=0.056). The present study demonstrated that high expression level of osteopontin in either the plasma or the tumor of the patients with OSCC was associated with tumor progression, suggesting that osteopontin expression is an important prognostic factor for OSCC.
 ...
PMID:Comprehensive study on the prognostic role of osteopontin expression in oral squamous cell carcinoma. 1921 94

Colorectal cancers with microsatellite instability are characterized by an important density of tumor-infiltrating lymphocytes and a good prognosis. Microsatellite instability results from the inactivation of the DNA mismatch repair system and induces secondary somatic frameshift mutations within target genes harboring repeat sequences in their coding frame. By disrupting the open reading frame, frameshift mutations can result in the appearance of potentially immunogenic neopeptides. To determine the frameshift mutations inducing a T-cell response during the development of a tumor with microsatellite instability, we studied in 61 colorectal cancer patients with microsatellite instability, using a fluorescent multiplex PCR comparative analysis, the relative frequency of frameshift mutations within 19 target genes and analyzed the correlation of these frameshift mutations with the density of CD3+ tumor-infiltrating lymphocytes. The four most frequently mutated genes were ACVR2 (92%), TAF1B (84%), ASTE1/HT001 (80%) and TGFBR2 (77%). The vast majority (95%) of the tumors exhibited at least three frameshift mutations, and the number of frameshift mutations was associated with tumor progression (TNM stage, wall invasion and tumor diameter). Tumor-infiltrating lymphocyte density was associated with the overall number of frameshift mutations and with the presence of frameshift mutations within two target genes, namely ASTE1/HT001 and PTEN. These results strongly argue for the clinical relevance of immunotherapy of colorectal cancers with microsatellite instability.
 ...
PMID:Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations. 1950 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>