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

Lack of surface Fas expression is a main route for apoptotic resistance which is considered an important mechanism of tumorigenesis and tumor progression. Fas and FasL expressions in 110 non-small cell lung carcinomas (NSCLCs) were investigated to evaluate their roles in pulmonary carcinogenesis and to examine the clinicopathologic significance of Fas expression with its relationship with p53 and bcl-2 overexpressions. Immunohistochemical analysis using tissue microarray demonstrated that a large proportion of NSCLC patients (60%) showed lack of membranous Fas expression. The Fas-negative cases revealed the significantly lower survival rate than Fas-positive ones. Also, the loss of Fas receptor expression was found more frequently in advanced stage and higher nodal status. FasL protein was increased in most NSCLCs (89%) compared to normal lungs. p53 and bcl-2 overexpressions showed no association with Fas expression. Conclusively, reduced membranous Fas expression as a mechanism of apoptotic resistance is considered to play an important part of the pulmonary carcinogenesis, which may predict poor survival and have a bad prognostic influence. Increased FasL expression is thought to be a basis for the immune evasion in NSCLCs. The rare bcl-2 overexpression suggests that this anti-apoptotic protein is unlikely to play a role in the apoptotic resistance of NSCLCs.
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PMID:Tissue microarray analysis of Fas and FasL expressions in human non-small cell lung carcinomas; with reference to the p53 and bcl-2 overexpressions. 1622 50

Cyclin D1 (CCND1) is a set of periodic regulatory proteins that is believed to govern cell cycle transit from G1 into S phase. Overexpression of CCND1 leads to abnormal cellular proliferation which underlies processes of tumorigenesis; CCND1 can thus function as a cooperative oncogene in cell transformation. In the present study we investigate the immunohistochemical expression of CCND1 in a well-documented series of 58 laryngeal squamous cell carcinomas (LSCC) and search for statistical associations between CCND1 index and various clinicopathological parameters including several immunomarkers' expression as well as patients' disease-free survival. Tissue sections from archival paraffin blocks were stained using the avidin-biotin-peroxidase complex method; the H-295 rabbit polyclonal antibody was applied at dilution of 1:150. The percentage of CCND1 immunoreactive tumor cells for each tumor was counted by an image analysis system. CCND1 staining was confined to cell nuclei and, in the examined samples, ranged from undetectable (i.e. 0% of tumor cells, n = 6) to the majority of tumor cells (i.e. 89% of tumor cells) with mean value: 15.73%. In tumor adjacent, non invasive lesions, strong CCND1 staining was noticed in areas with cellular atypia. In cases with nodal metastases, no change in CCND1 expression in the nodal metastases compared with the primary tumors was observed. p53 protein accumulation in malignant cells was positively linked with CCND1 index (Mann-Whitney U: 205.5, p = 0.034). CCND1 expression appears to be an early event in processes of tumorigenesis and tumor progression in some LSCC. Apart from p53 protein accumulation, CCND1 immunohistochemical expression does not seem to correlate with nodal metastasis, disease recurrence or any other clinicopathological prognostic indicator.
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PMID:Cyclin D1 protein tissue detection in laryngeal cancer. 1632 70

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.
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PMID:A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer. 1635 94

Primary cutaneous T cell lymphomas (CTCL) represent the most frequently occurring group of extra-nodal T cell lymphomas, originating from skin-homing memory T cells. Sezary syndrome (SS) is a leukemic variant of CTCL that presents with erythroderma, lymphadenopathies and presence of malignant T cells in peripheral blood. SS has an unfavourable prognosis, and is refractory to current treatments. Progress in understanding the pathogenesis and tumor progression of SS is limited. In the past few years, we have identified and reported several CTCL-associated antigens, CD158k/KIR3DL2, CD85j/ILT2, and SC5/vimentin. KIR3DL2 is the first phenotypic marker of Sezary cells that can be used for the diagnostic and follow-up of Sezary syndrome. The SC5 antibody is the only monoclonal antibody reacting with vimentin on the surface of viable Sezary cells. CTCL are characterized by a predominance of Th2 cytokines. The recent suggestion that CTCL cells could be regulatory T (Tr) cells remains controversial. Gene expression studies suggest that in the future we may develop new diagnostic and prognostic tools, and identify subsets of patients who would benefit from more appropriate treatment protocols. Future challenges are to render tumor cells sensitive to apoptosis by inhibiting specific signalling pathways such as the constitutively activated NF-KB pathway, to identify specific surface kinase receptors and to develop specific inhibitors, to develop humanized monoclonal antibodies directed against tumor specific antigens, able to kill tumor cells via complement-dependent and antibody-dependent cytotoxicity, and to stimulate innate immunity.
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PMID:[Epidermotropic T cell lymphomas as models for tumor progression]. 1645 62

Our previous study demonstrated that bone marrow microinvolvement (BMM) is an epiphenomenon of tumor progression rather than a prognostic factor in non-small cell lung cancer. We hypothesize that an increase in mesenchymal transition power in epithelial tumor cells by up-regulation of the matrix metalloproteinases (MMPs) may contribute to the existence of BMM and poorer prognosis. Hereby we conducted a prospective study of BMM and MMPs expression in a cohort of 57 non-small cell lung cancer patients. Bone aspirates were examined by immunohistochemical stains. Expressions of MMPs were checked by Human MMP primer set kit (Maxim Biotech, USA). Correlations between the MMPs expression and BMM, nodal metastasis, and prognosis were examined. Cox model analysis was used to identify independent prognostic factors. Though positive BMM was identified in 38 (66.7%) of the patients, none of the clinicopathological factors, including sex, age, cell types, tumor differentiation, nodal metastasis and TNM status of the tumor, was related to BMM by the tumor cells. Up-regulation was observed in a broad spectrum of MMPs with the exception of MMP-3. However, only MMP-13 expression correlated with the existence of BMM (p=0.006). Univariate analysis revealed MMP-3, MMP-7 and MMP-13 as negative prognostic factors. Cox model analysis revealed T-status, cell differentiation, and MMP-13 expression of the tumor as independent prognostic factors. The overall 5-year survival rate of the patients was 36.8%. The existence of BMM itself did not influence the prognosis (p=0.109), however, patients with positive MMP-13 expression (N=34) had a poorer 5-year survival rate of 26.5% (p=0.025). In summary, non-small cell lung cancer cells with MMP-13 expression, despite of BMM status, tend to shed and aggregate in the bone marrow, which is subsequently reflected in a poorer survival rate.
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PMID:Matrix metalloproteinase-13 expression is associated with bone marrow microinvolvement and prognosis in non-small cell lung cancer. 1656 61

The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore, the authors investigated the protein expression of Glutathione S-transferase (GST) isoforms and cytochrome P450 (CYP) known to be involved in the metabolism of steroid hormones and endogenous as well as exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. Expression of GST pi, mu, alpha and CYP1A1/2, 1A2, 3A4/5, 1B1, 2E1 was assessed by immunohistochemistry for primary breast carcinomas of 393 patients from the German GENICA breast cancer collection. The percentages of positive tumors were 50.1 and 44.5% for GST mu and CYP2E1, and ranged from 13 to 24.7% for CYP1A2, GST pi, CYP1A1/2, CYP3A4/5, CYP1B1. GST alpha was expressed in 1.8% of tumors. The authors observed the following associations between strong protein expression and histopathological characteristics: GST expression was associated with a better tumor differentiation (GST mu, p = 0.018) and with reduced lymph node metastasis (GST pi, p = 0.02). In addition, GST mu expression was associated with a positive estrogen receptor and progesterone receptor status (p < 0.001). CYP3A4/5 expression was associated with a positive nodal status (p = 0.018). Expression of CYP1B1 was associated with poor tumor differentiation (p = 0.049). Our results demonstrate that the majority of breast carcinomas expressed xenobiotic and drug metabolizing enzymes. They particularly suggest that GST mu and pi expression may indicate a better prognosis and that strong CYP3A4/5 and CYP1B1 expression may be key features of nonfavourable prognosis.
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PMID:Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas. 1672 11

Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease that is only cured 50% of the time. A better understanding of the molecular mechanisms involved in HNSCC progression may lead to earlier detection and improved cure rates. CD44 is a ubiquitous transmembrane glycoprotein comprising a family of alternatively spliced isoforms involved in cell migration and cell proliferation. CD44 isoforms containing the variant 3 (v3) exon include a growth factor binding site and may be involved in tumor progression. To characterize CD44v3-containing isoforms expression in HNSCC we purified RNA from four HNSCC cell lines and performed RT-PCR using junction primer strategies followed by gel elecrophoresis. Cloning and sequencing of HNSCC cell line PCR products revealed two isoforms. One of these, CD44v3-10, has been previously described. The other isoform, CD44v3, has not been characterized in HNSCC tissues. To further study this isoform, we purified RNA from 19 HNSCC tissues, 7 normal margin tissues and 5 true normal tissues. Following reverse-transcription, we performed quantitative PCR using junction primers specific for CD44v3. Results show that HNSCC tumor tissues expressed mean CD44v3 levels that were elevated 4.5 times more than true normal tissues (p < 0.01). Mean CD44v3 values for HNSCC tumors were 0.43 +/- 0.44 while mean levels for true normal tissues were 0.10 +/- 0.11. Levels in tumor tissue did not vary significantly with tumor characteristics such as site, stage, prior treatment, or nodal status. In addition, to characterize the role of this molecule plays in tumor progression, we overexpressed CD44v3 in a HNSCC cell line. Our results indicate that although higher levels of CD44v3 did not affect the rate of proliferation, a significant increase in migration was observed. CD44v3 may provide a target for future diagnostic and therapeutic interventions for HNSCC.
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PMID:Characterization of CD44v3-containing isoforms in head and neck cancer. 1729 3

The calcium-binding protein, S100A4, with an inverse association of E-cadherin, is known to correlate with prognosis in various cancers. In this study, we investigated the expression of the S100A4 and E-cadherin status in relation to the clinicopathological parameters of pancreatic cancer. The expression status of these two proteins was examined in 72 specimens of primary pancreatic carcinoma with immunohistochemistry. Fifty-six of 72 (78%) surgical specimens of primary pancreatic cancer were positive for S100A4 according to immunohistochemistry. Thirty-one (43%) specimens of pancreatic cancer showed positive expression of E-cadherin. The inverse association of S100A4 and E-cadherin expression was significant in the cancers (p < 0.0001). The S100A4 expression correlated significantly with the pathological T stage and poorer prognosis (p = 0.024). The 41 E-cadherin-negative cases showed poorer prognoses and a higher incidence of liver metastasis (p = 0.0344, p = 0.027). The 10 cases with S100A4-negative/E-cadherin-positive cancers showed a significantly better prognosis than the others (p < 0.05). The histological grade (p = 0.004), nodal status (p < 0.0001) and S100A4-positive status (p = 0.048) were highly significant independent prognostic predictors (p < 0.05). These results suggest that S100A4 overexpression combined with reduced E-cadherin expression play important roles in tumor progression and metastasis in pancreatic cancer. The combined examination of these two molecules is useful in evaluating the outcome of pancreatic cancer patient.
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PMID:Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer. 1686 43

Alkylation of DNA at the O(6) position of guanine is a critical step in the induction of mutations by carcinogenic and chemotherapeutic alkylating agents. O(6)-methylguanine-DNA methyltransferase (MGMT) is an enzyme that removes mutagenic adducts from the O(6) position of guanine, thereby protecting the genome against guanine to adenine transitions. We hypothesized that alteration in MGMT expression might occur in early stages of development of oral cancer and be associated with disease progression. Immunohistochemical analysis of MGMT expression was carried out in 107 oral squamous cell carcinomas (OSCCs), 78 oral precancerous lesions (OPLs) (58 hyperplasias and 20 dysplasias) and 30 histologically normal oral tissues and correlated with clinicopathological parameters as well as major risk factors. Decreased MGMT expression was observed as early as in hyperplasia (p=0.003; Odd's Ratio (OR)=5.0). Significant loss of MGMT expression was observed from hyperplasia to dysplasia (p=0.034; OR=4.0). Loss of MGMT expression was associated with late clinical stage of OSCCs (p=0.027, OR=2.0) and nodal metastasis (p=0.031, OR=2.5). Decreased MGMT expression was associated with smokeless tobacco (ST) consumption in patients with OPLs (p=0.017, OR=3.6) and OSCCs (p=0.031, OR=2.8). Significant association was also observed between loss of MGMT expression and poor prognosis of OSCC patients (p=0.02; OR=5.2). The decreased MGMT expression in OPLs suggested that deregulation of MGMT expression is an early event in the development of oral cancer. In OSCCs, its correlation with late clinical stage, and nodal metastasis suggests association with aggressive tumor behavior and cancer progression, underscoring its potential as a candidate predictive marker for nodal metastasis and disease prognosis. Correlation of loss of MGMT expression with ST consumption underscored its significance in ST-associated oral carcinogenesis.
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PMID:MGMT expression in oral precancerous and cancerous lesions: correlation with progression, nodal metastasis and poor prognosis. 1699 81

C-erbB-2 oncogene protein (ErbB-2/HER-2) overexpression is a prognostic marker of breast carcinoma. The purpose of this study was to evaluate serum ErbB-2 for monitoring tumor recurrence of operable breast carcinoma patients. The subjects were 86 breast carcinoma patients with stage I-IIIB. Sera were collected at preoperative and postoperative periods from 1996 to 2000. The cutoff value was set at 5.4 ng/ml for preoperative patients and at 6.5 ng/ml for postoperative patients. Twenty-nine patients (34%) had higher preoperative serum ErbB-2 levels (>or=5.4 ng/ml). A higher preoperative serum ErbB-2 was associated with higher clinical stage, larger tumor size, nodal metastasis, higher histologic grade and lymphatic invasion, but not with vascular invasion, hormonal receptor status or other tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3). As of April 2005, 27 patients (31%) had recurrence and 18 (62%) of them had a higher preoperative serum ErbB-2. Seventeen patients died of tumor progression. The recurrence-free survival rates at 7 years after breast surgery were 84% in 57 patients with a normal preoperative serum ErbB-2 and 41% in 29 patients with a higher preoperative serum ErbB-2 (p < 0.0001). The overall survival rates at 7 years were 93% and 55% (p < 0.0001), respectively. A multivariate analysis revealed that preoperative serum ErbB-2 was an independent prognostic factor for recurrence-free survival and overall survival in breast carcinoma patients. The specificities and sensitivities of postoperative tumor markers (CEA, CA15-3 and ErbB-2) were 91%, 100% and 85%, and 40%, 30% and 70%, respectively. Serum ErbB-2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast.
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PMID:Serum c-erbB-2 protein is a useful marker for monitoring tumor recurrence of the breast. 1704 19


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