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

We report a rare case of basaloid squamous cell carcinoma of the lung in a young Japanese woman. An 18-year-old woman presented with productive cough. Chest radiogram and computed tomography (CT) revealed a tumor in the left hilum accompanied by partial atelectasis of the left upper lobe and pleural effusion. Transbronchial fine-needle aspiration cytology supported a tentative diagnosis of primary squamous-cell carcinoma of the lung. The clinical stage was T4N2M1, with multiple bone metastases. Despite a transient response to chemotherapy consisting of carboplatin and paclitaxel, the patient died because of tumor progression 2 months after the start of the chemotherapy. Necropsy established the diagnosis of basaloid squamous-cell carcinoma of the lung. Immunohistochemical studies of the necropsy specimen indicated that the tumor was positive for keratin, vimentin, and S100, and negative for chromogranin A, cytokeratin CAM5.2, and bcl-2. Besides the rarity of the disease itself, the present case seemed to have additional uniqueness in that the patient was 18 years old and female. This is the youngest patient with a case of basaloid squamous cell carcinoma of the lung ever reported.
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PMID:Basaloid squamous-cell carcinoma of the lung in a young woman. 1650 33

Our aim was to retrospectively evaluate the influence of gemistocytic astrocytes, cellular proliferation indices, immunoexpression of proteins p53 and bcl-2 in the clinical outcome of 39 patients with WHO grade II and III astrocytomas with the presence of gemistocytes. The mean proportion of gemistocytes was 18.7% and the mean proliferative index was 3.3%. Immunoexpression of p53 was detected in 29 cases (74.4%) and all cases (100%) were positive for bcl-2. The median overall survival was 97.2 months and the progression-free survival was 43.1 months. Estimated 1-, 5- and 10-year overall survival rates were 94.3%, 69.5% and 46.4%; 1-, 5- and 10-year progression-free survival rates were 91.1%, 26.1% and 13.1%. Out of 24 who presented clinical and neuroimaging worsening, characterized as tumor progression or recurrence, 16 had histological confirmation and were also analyzed. We could not detect significant differences when comparing all the indices between WHO grade II and III and also between the first and second biopsies. We also could not detect significant differences in progression-free and overall survival when analyzing the gemistocyte index and the immunohistochemical labeling indices p53, bcl-2 and MIB-1, as well as patientsa9 age (median value, up to 34 vs. over 34 years) and histological grade (II or III). Our finding confirms recent reports that question the role of gemistocytes as a prognostic factor in diffuse astrocytomas. The significance and role of gemistocytes in astrocytomas has yet to be defined and warrants further study.
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PMID:Gemistocytes in astrocytomas: are they a significant prognostic factor? 1664 16

To analyze the possibility that immunological alteration in asbestos-related diseases (ARDs) such as asbestosis (ASB) and malignant mesothelioma (MM) may affect the progression of cancers, a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) was continuously exposed to 10 mug/ml of chrysotile-B (CB), an asbestos. After at least 8 months of exposure, the rate of apoptosis in the cells became very low and the resultant subline was designated MT-2Rst. The MT-2Rst cells were characterized by (i) enhanced expression of bcl-2, with regain of apoptosis-sensitivity by reduction of bcl-2 by siRNA, (ii) excess IL-10 secretion and expression, and (iii) activation of STAT3 that was inhibited by PP2, a specific inhibitor of Src family kinases. These results suggested that the contact between cells and asbestos may affect the human immune system and trigger a cascade of biological events such as activation of Src family kinases, enhancement of IL-10 expression, STAT3 activation and Bcl-2 overexpression. This speculation was partially confirmed by the detection of elevated bcl-2 expression levels in CD4 + peripheral blood T cells from patients with MM compared with those from patients with ASB or healthy donors. Further studies will be required to verify the role of T cells with enhanced bcl-2 expression in tumor progression induced by asbestos exposure.
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PMID:Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells. 1685 Jan 64

Cell cycle and apoptosis regulatory proteins are markers of tumor progression in colorectal cancer. In a series of 1,274 mismatch repair-proficient colorectal cancers, immunohistochemical analysis of p21, p27, p53, and bcl-2 expression was performed using the tissue microarray technique. In univariate analysis, p21 expression was associated with tumor location and pN0; p27 expression with tumor location, lower tumor grade, early pT, and pN; p53 expression with tumor location; and bcl-2 with early pT and pN. Expression of p27 identified subgroups with worse prognosis in pT3 N0 and pT3 N+ patients. None of the 4 tumor markers were independent prognostic indicators of survival. The multimarker phenotypes p21/p27/p53 and p21/p27/bcl-2 were associated with survival. In mismatch repair-proficient colorectal cancer, p27 expression is associated with a better prognosis, and pT, pN, and vascular invasion are independent prognostic factors. In addition, multimarker phenotypes are useful to identify colorectal cancer subgroups with different prognoses.
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PMID:Prognostic value of cell cycle and apoptosis regulatory proteins in mismatch repair-proficient colorectal cancer: a tissue microarray-based approach. 1714 38

The hypothesis tested in the study suggests that mechanisms of the earlier described delayed or accelerated tumor progression may be regulated by the antiapoptotic and proapoptotic cellular programs activated in stress reactions of transformed cells to the host normal cellular environment. Therefore, spontaneously transformed hamster cell line STHE, its bcl-2-transduced line STHE-Bcl-2, and 64 of their descendant tumor cell variants naturally selected in two in vivo regimes (local tumor growth versus dissemination) were examined. The role of Bcl-2 and the possible activation of endogenous death-signaling Bax, Ras, and HSP90/HSP70 stress proteins in STHE (Bcl-2+/-) tumor cell variants were studied in dynamics of in vivo tumor progression. The data demonstrate: (1) Immediate in vivo activation of Bax and of HSP90/HSP70 stress proteins in disseminated STHE cells on the background of accelerated tumor progression; (2) No immediate activation of Bax and the gradual downregulation of Bcl-2 in STHE-Bcl-2 cells on the background of delayed tumor progression; (3) Alternative and mutually suppressive character of Bcl-2 and Bax expression in both regimes of tumor progression; (4) In the later stages of tumor progression, the regular transit of the initial Bcl-2 antiapoptotic, Bax-suppressing program, and the delayed tumor progression towards Bcl-2 loss, activation of Bax, and acceleration of tumor progression. Thus, the delay of tumor progression is apparently determined by the ability of Bcl-2-expressing tumor cells to extinguish the cell-damaging environmental stress signals and Bax activation, while its acceleration correlates with Bcl-2 loss, activation of proapoptotic Bax, and tumor cells damage.
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PMID:Alternative production of Bcl-2 and Bax by tumor cells determines the rates of in vivo tumor progression: suggested mechanisms. 1729 4

Experimental animal model of tumor progression based on mice lymphosarcoma (LS) and resistant lymphosarcoma (RLS) has been developed. LS tumor displays high sensitivity to cyclophosphamide, which is widely used in anticancer therapy. RLS tumor was derived from LS by passaging in mice receiving low concentration of cyclophosphamide (20 mg/kg) and display resistance to cyclophosphamide (up to dose 150 mg/kg). The primary cultures of LS and RLS tumors display different expression levels of the genes related to apoptosis and multiple drug-resistant phenotype: in RLS tumor high levels of mdr1b and bcl-2 genes and low level of p53 gene expression were found. A total of 10% of cells in RLS primary culture display multiple drug-resistant phenotype and survive even at high dose of cytostatics. Cultivation of RLS primary culture in the presence of increasing vinblastine concentrations gives RLS(40) cell culture, which exhibits high levels of mdr1a/1b genes expression as compared to RLS and 20-fold increase of resistance to cytostatics. Drug-resistant RLS(40) cells were transplanted into CBA mice and sensitivity of the tumors to anticancer drugs was tested. RLS(40) tumors were resistant to a number of cytostatics used in anticancer therapy (cyclophosphamide, cysplatin, vinblastine, rubomycinum). Thus, RLS(40) tumor can be used as model, which corresponds to tumor status observed in patients after one or several courses of chemotherapy and can be useful for testing conventional therapy alone or together with newly developed gene-targeted therapeutics.
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PMID:Animal model of drug-resistant tumor progression. 1734 38

The role of survivin that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367), and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis, TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.
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PMID:Survivin expression in non-small-cell lung carcinomas: correlation with apoptosis and other apoptosis-related proteins, clinicopathologic prognostic factors and prognosis. 1753 4

Plexiform neurofibroma (PNF) has a low potential to undergo malignant transformation. Identification of markers associated with tumor progression is important since it may serve as prognostic indicators or adjuncts to standard pathological examination. In the present study, the authors immunostained 20 neurofibromatosis type I-associated PNFs with cyclinD1, p27kip-1, and bcl-2. Six of the cases had progressed into malignant peripheral nerve sheath tumor (MPNST), and the transitional area of each sample was also stained separately in order to identify protein(s) associated with tumor progression. Cyclin D1 was found to be significantly increased in the transitional zone, compared to the ordinary PNF (p = 0.007). The protein is, thus, likely to play a role in the malignant transformation. There was no significant difference in the expression of p27kip-1 and bcl-2 during the malignant progression of PNF.
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PMID:Expression of CyclinD1, p27kp-1, and bcl-2 in plexiform neurofibroma with and without malignant transformation in neurofibromatosis type 1. 1771 69

The Ets family of transcription factors is implicated in malignant transformation and tumor progression, including invasion, metastasis and neo-angiogenesis. In the present study, we found that the Fli-1 gene, a member of the Ets family, was highly expressed in several breast cancer cell lines (MDA-MB231, MDA-MB436, BT-549 and HCC1395). To investigate the functional roles of Fli-1 in breast cancer malignancy, we introduced an expression plasmid containing full-length Fli-1 cDNA into MCF7 breast cancer cells in which endogenous expression of Fli-1 was barely detectable.Overexpression of Fli-1 in MCF7 cells led to inhibition of apoptosis induced by serum depletion or ultraviolet irradiation, although it did not affect cell growth rate in liquid media, colony formation in soft agar or the in vitro invasion capacity of the cells. Expression of Fli-1 and antiapoptotic bcl-2 was coordinately upregulated by serum depletion in MCF7 cells, and the upregulation was inhibited by treatment of the cells with a c-Jun-NH(2)-terminal kinase-specific inhibitor. Furthermore, expression of the bcl-2 gene and protein was enhanced in Fli-1-overexpressing MCF7 cells compared with mock-transfected cells. In addition, human bcl-2 promoter activity was transactivated by Fli-1. These results suggest that Fli-1 contributes to the malignancy of human breast cancer by inhibiting apoptosis through upregulated expression of the bcl-2 gene.
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PMID:Functional roles of Fli-1, a member of the Ets family of transcription factors, in human breast malignancy. 1772 80


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