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)

Oncogenes, the abnormal forms of proto-oncogenes, were shown to be involved in malignant transformation and in tumor progression. c-erbB2/HER2/neu is member of EGFR family and encodes the p185 protein, which functions as a tyrosine-kinase. Gene amplification and/or p185 overexpression were reported to be associated with poor prognostic in cancer. Our purpose was to investigate p185 immunohistochemical expression in breast carcinomas and in the corresponding axillary lymph nodes metastases and to identify possible correlation between p185 and other factors of poor prognostic, such as loss of hormonal receptors expression. In our study, 40.91% of cases were erbB-2 positive, p185 expression being maintained from the primary tumors to axillary metastases and associated with positive nodal status and with the absence of hormonal receptors expression (p < 0.05). These findings support the hypothesis the c-erbB2 is an advantageous acquisition for the aggressive behavior of the tumor cell and for its ability to invade and metastasize.
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PMID:[Overexpression of c-erbB-2 gene product is associated with poor prognosis factors in breast carcinoma]. 1475 39

90K/Mac-2 Binding Protein (M2BP) plays a role in regulation of immune responses and cell adhesive ability in patients with cancer and infectious diseases. We previously reported that M2BP was highly expressed in lung cancer and that immune responses to M2BP were increased in many patients with lung cancer. To determine the involvement of M2BP in metastatic processes of cancer progression, we examined the ability of M2BP DNA-transduced lung carcinoma cell lines to adhere to extracellular matrices. Although expressions of cell-surface integrins were not modulated in the M2BP transfectants, they showed increased adhesiveness to fibronectin and collagen IV. We next analyzed the serum levels of M2BP in patients with lung cancer and normal donors and the relationships between M2BP expression and clinicopathological factors in the patients. The M2BP level was markedly elevated in the patients and was strongly correlated with nodal involvement and clinical staging. To determine whether expression of M2BP by cancer cells is modulated in the environment of tumor-bearing hosts, M2BP expression in M2BP-positive QG56 cells following exposure of the cells to pro-inflammatory cytokines was examined. The M2BP expression in QG56 cells was up-regulated by many of the cytokines that activate host protective immunity. The findings in this study suggest that M2BP plays a role in cancer metastasis by increased adhesiveness of cancer cells and that M2BP is increasingly produced even in a state of exposure to the host immune system. This molecule may be useful as a predictive factor of disease progression in lung cancer.
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PMID:Involvement of 90K/Mac-2 binding protein in cancer metastases by increased cellular adhesiveness in lung cancer. 1549 95

The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival.
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PMID:K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma. 1549 79

Cytokines produced by T lymphocytes are critical to the efficacy of a given immune response and dysregulation of immune responses may play a role in cancer progression. We assessed the intracellular cytokine profiles of T cells in the peripheral blood of women with breast cancer and explored the relationship of these responses with the presence of cancer in lymph nodes and bone marrow. Peripheral blood lymphocytes from 84 patients and 26 healthy volunteers were analyzed by 4-color flow cytometry for surface markers and for intracellular cytokines. Bone marrow samples from some of these patients were also collected and analyzed for the presence of epithelial cells (micrometastases) by flow cytometry. The percentages of both CD4(+) and CD8(+) cells producing type1 (IL-2, IFN-gamma or TNF-alpha) and type 2 (IL-4) were significantly lower in patients with breast cancer compared to healthy controls. These results indicate a general immune dysfunction in these patients as opposed to a shift in the balance of type1 and type2 cells. These dysregulated T cell responses did not correlate with age, stage of disease, or nodal status. However, we did observe a correlation between number of micrometastases in the bone marrow and T cell responsiveness.
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PMID:Immune dysfunction and micrometastases in women with breast cancer. 1586 44

In breast cancer, vascular endothelial growth factor (VEGF) is a prognostic factor, but the relationship of VEGF mRNA levels with various parameters or tumor progression is unclear. VEGF mRNA levels were measured in 48 cases of invasive ductal carcinoma by using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean VEGF mRNA levels were compared among different histological types and grades in 41 and 29 samples of invasive and intraductal components, respectively. VEGF mRNA levels were always higher in cancerous cells than in non-cancerous cells, but mean VEGF mRNA levels were not significantly different between invasive component (3.24 +/- 3.18-fold the value of non-cancerous tissue) and intraductal component (4.14 +/- 4.43-fold). They were higher in papillotubular type than in other types, and higher in grade 2 carcinomas than in grade 3 carcinomas of invasive component, and higher in comedo type than in other types of intraductal component. Mean VEGF mRNA levels were higher in the VEGF-immunopositive group than in the VEGF-immunonegative group. There was no correlation between VEGF mRNA levels and tumor size, nodal status, or hormone receptor status. VEGF expression may play an important role in the development of both invasive and intraductal carcinoma components, especially those carcinoma components of less aggressive histological features.
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PMID:Vascular endothelial growth factor mRNA levels quantified by reverse transcription-polymerase chain reaction in microdissected breast carcinoma tissues are correlated with histological type and grade of both invasive and intraductal components. 1587 23

ID4 gene is a member of the inhibitor of DNA-binding (ID) family, which inhibits DNA binding of basic helix-loop-helix transcription factors. Certain human primary breast cancers reportedly have low or no expression of ID4 protein, but its role in carcinogenesis and cancer progression is unknown. To determine its possible role, we examined epigenetic inactivation of ID4 gene by promoter hypermethylation in human breast cell lines and T1 breast cancer tissues. Methylation status of ID4 promoter CpG island was assessed by methylation-specific PCR (MSP); ID4 mRNA level was assessed by quantitative real-time RT-PCR. Of eight cell lines, two were fully methylated, four were partially methylated, and two were not methylated. ID4 mRNA level was suppressed in fully methylated cell lines. ID4 hypermethylation was observed in 16 of 24 (67%) node-positive and seven of 36 (19%) node-negative T1 primary breast cancers matched by patient age and tumor diameter. It was a significant risk factor for nodal metastasis (OR 13.1, P=0.0004). ID4 mRNA level was suppressed in hypermethylated cancer specimens (P=0.014). ID4 may play an important suppressive role in tumor progression, and its silencing by hypermethylation may increase the risk of regional lymph node metastasis.
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PMID:Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer. 1589 10

p53, cyclin D1 and epidermal growth factor receptor (EGFR) are molecular markers that regulate the cell cycle or cell growth and play important roles in tumor development and progression. In this study, we examined the impact of immunohistochemical expression of these markers on tumor progression in 140 oral cancers. p53, cyclin D1 and EGFR were expressed in 64 cases (46%), 54 cases (39%) and 54 cases (39%), respectively, but there was no inter-relationship between any two of these markers. In the association of these markers with clinicopathological features, EGFR expression alone was significantly associated with poor differentiation (P=0.0008) and invasive growth pattern (P=0.0003). Any of these markers, including EGFR, had no significant impact on survival. Coexpression of all these markers, however, was significantly associated with invasive growth pattern (P=0.0149) and shortened survival (P=0.0181), and was a significant and independent unfavorable prognostic factor (P=0.0002), along with tumor size (P=0.0040), nodal metastasis (P=0.0137) and growth pattern (P=0.0017) in a multivariate analysis. Simultaneous coexpression of these markers in oral cancers might prove to be a useful indicator for identification of low- or high-risk patients.
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PMID:Combined expression of p53, cyclin D1 and epidermal growth factor receptor improves estimation of prognosis in curatively resected oral cancer. 1600 67

Chemokine receptor 7 (CCR7) upregulation, which mediates immune cell survival and migration to lymph nodes, has recently been associated with nodal metastasis of squamous cell carcinoma of the head and neck (SCCHN). However, the mechanism of CCR7 in tumor progression, its downstream signaling mediators, and interactions with other pathways contributing to metastasis of SCCHN have not been determined. We hypothesized that inflammatory chemokine-mediated signals could also promote tumor proliferation and mitogenic effects. Functional assays showed that chemotaxis and invasion of metastatic SCCHN cells were dependent on phosphoinositide-3 kinase (PI3K) and its substrate, activated phospholipase Cgamma-1. In addition, treatment of CCR7(+) metastatic SCCHN cells with CCL19 (MIP-3beta) showed rapid activation of the prosurvival, PI3K/Akt pathway. Transactivation of EGFR-mediated and mitogen-activated protein kinase signaling pathways, which can promote migration and survival in parallel, did not appear to contribute to the functional or biochemical effects of CCR7 stimulation. Thus, proinflammatory chemokine signals that mediate activation, trafficking and survival of tumor-infiltrating immune cells in the tumor microenvironment actually appear to induce signals for progression of cancer cells. The CCR7-mediated pathway in metastatic SCCHN cells functions independently of EGFR signal transduction and therefore may represent an additional target for therapeutic intervention to prevent tumor progression and metastasis.
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PMID:Chemokine receptor 7 activates phosphoinositide-3 kinase-mediated invasive and prosurvival pathways in head and neck cancer cells independent of EGFR. 1600 9

Extrahepatic bile duct carcinomas (EHBDCs) consist of primary tumors, tumors in vessels, and tumors in lymph nodes. The purpose of this study was to prospectively investigate whether the histological characteristics of tumor cells and tumor stromal cells in vessels and lymph nodes were significantly associated with the outcomes of 60 EHBDC patients as compared with the histological characteristics of tumor cells and tumor stromal cells in primary tumors. Multivariate analyses, using the Cox proportional hazard regression model, showed that in EHBDCs without nodal metastasis, blood vessel tumor emboli with an angiomatous stroma significantly increased the hazard ratios (HRs) of tumor recurrence and death ( P < .05). In EHBDCs with nodal metastasis, the presence of tumor necrosis in the nodal tumors significantly increased the HRs of tumor recurrence and initial distant organ metastasis ( P < .05). In EHBDCs located in the distal to middle portion of the extrahepatic bile duct, blood vessel tumor emboli with an angiomatous stroma significantly increased the HRs of tumor recurrence, initial distant organ metastasis, and death ( P < .05). Severe nuclear atypia of the tumor cells in lymph vessels significantly increased the HRs of tumor recurrence and initial distant organ metastasis ( P < .05). In EHBDCs located in the hilar portion of the extrahepatic bile duct, the presence of nodal tumors with more than 4 mitotic figures significantly increased the HRs of tumor recurrence and initial distant organ metastasis ( P < .05). Several histological characteristics of tumor cells and tumor stromal cells in vessels and lymph nodes have significant effects on tumor progression of EHBDCs.
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PMID:Histological characteristics of tumor cells and stromal cells in vessels and lymph nodes are important prognostic parameters of extrahepatic bile duct carcinoma: a prospective study. 1602 72

Carbonyl reductase (CBR) is a cytosolic NADPH-dependent oxidoreductase metabolizing prostaglandins, steroids, quinines, and anthracycline antibiotics. Many experimental studies have shown that CBR plays important roles in the regulation of tumor progression, but clinical significance of CBR status remains unclear. Thus, we conducted a retrospective study on CBR mRNA expression in lung cancer. Tumor tissues obtained from 59 non-small-cell lung cancer patients were analyzed by quantitative real-time reverse transcription-PCR assay to reveal clinical significance of CBR expression. Angiogenesis was measured immunohistochemically as intratumoral microvessel density (IMVD) using anti-CD34 monoclonal antibody CD34-IMVD) and anti-CD105 monoclonal antibody (CD105-IMVD). CBR mRNA expression was significantly reduced along with progression of primary tumors (the mean CBR mRNA/GAPDH mRNA, 3.288x10(-2) for pT1, 1.628x10(-2) for pT2, and 1.175x10(-2) for pT3-4 disease, respectively; P=0.02). Moreover, CBR mRNA expression in tumor with nodal involvement seemed to be reduced as compared with that in tumor without nodal involvement (the mean CBR mRNA/GAPDH mRNA, 1.446x10(-2) and 2.531x10(-2), respectively), whereas the difference did not reach a statistical significance (P=0.09). The mean CD105-IMVD for CBR-high tumor was 59.2, which was significantly lower than that for CBR-low tumor (130.6, P=0.02), whereas no significant difference between the mean CD34-IMVDs for CBR-high tumor and CBR-low tumor was found. The 5-year survival rate of CBR-high patients was 68.3%, significantly higher than that of CBR-low patients (36.5%; P=0.03). A multivariate analysis confirmed that CBR-high expression was a significant factor to predict a favorable prognosis (P=0.04; relative risk, 0.39; 95% confidence interval, 0.16-0.98). Expression of CBR mRNA was a significant prognostic factor in non-small-cell lung cancer and was inversely associated with tumor progression and angiogenesis.
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PMID:Carbonyl reductase expression and its clinical significance in non-small-cell lung cancer. 1610 46


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