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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibody reactivity against survivin, a recently identified tumor-associated protein, was determined in sera from patients with lung (n = 51) or colorectal cancer (n = 49). The same collection of sera was tested for the presence of antibodies against p53. Eleven sera from lung cancer patients and four sera from colorectal cancer patients reacted with purified recombinant survivin in an ELISA (21.6% and 8.2%, respectively), whereas four sera from lung cancer patients and nine sera from colorectal cancer patients contained anti-p53 antibodies (7.8% and 18.4%, respectively). The increase in prevalence when anti-survivin and anti-p53 antibodies were determined in parallel was statistically significant (29.4% versus 7.8%, P = 0.005 in lung cancer population; 26.6% versus 8.2%, P = 0.015 in colorectal cancer population). The high prevalence of anti-survivin antibodies makes these antibodies an attractive novel marker for the diagnosis of lung and colorectal cancer, particularly in patients lacking anti-p53 antibodies.
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PMID:Antibody response to the tumor-associated inhibitor of apoptosis protein survivin in cancer patients. 1076 64

The purpose of this study was to investigate the possible association between expression of survivin, pathological findings in the tumor and survival in patients with small adenocarcinoma of the lung. Seventy-nine patients with resected tumors <2 cm in diameter were entered into the study. There were 33 males and 46 females, with a median age of 64 years (range 26-83 years). The pathological stage of the tumors was recorded as stage I, II, III and IV in 72, one, five and one case, respectively. Each patient underwent curative surgical resection for lung cancer between July 1992 and November 1999. The resected tumors were subjected to immunostaining for survivin. Thirty-eight patients had tumors with < or = 10% survivin-positive cells and 41 patients had tumors with >10% survivin-positive cells. When survivin expression and pathological findings in the resected tumors were analyzed, the frequency of venous invasion was significantly higher in the survivin-positive group (36.6% vs. 13.2%; p=0.0167). In contrast, the overall survival of survivin-positive patients (n=41) was significantly worse than that of individuals whose tumors were negative for survivin expression (n=38; log-rank test, p=0.014; Wilcoxon test, p=0.021). It can be concluded that the expression of survivin in tumor cells is a factor of poor prognosis in patients with small adenocarcinoma of the lung.
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PMID:Expression of survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung. 1206 18

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer especially in India and displays resistance to anticancer treatment. In our earlier study we had isolated a cDNA clone from rat thymocytes induced to undergo apoptosis, which was found to encode S29 ribosomal protein [Biochem. Biophys. Res. Commun. 277 (2000) 476]. In the present study an attempt has been made to find out whether enhanced expression of S29 cDNA can kill NSCLC H520 cells. We found that S29 induced apoptosis and augmented the effect of anticancer drugs. Expressions of several molecular determinants of apoptosis were analyzed in order to understand the mechanism of apoptosis induced by S29. We observed downregulation of the expression of inhibitors of apoptosis proteins (IAPs) Bcl-2, Bcl-X(L), and survivin and upregulation of pro-apoptotic p53 and Bax as assessed by Western blotting. Mitochondrial release of cytochrome c and activation of initiator caspase-8 and -9 and effector caspase-3, followed by cleavage of nuclear substrate poly(ADP-ribose) polymerase, were also observed. Permeability transition as determined by changes in DeltaPsi(m) was not a requirement for cytochrome c release. There was a marginal increase in the release of apoptosis inducing factor (AIF) and reduction of NF-kappaB dependent transcriptional activity. There was non-involvement of calcium and the telomerase activity, a proliferation marker.
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PMID:S29 ribosomal protein induces apoptosis in H520 cells and sensitizes them to chemotherapy. 1270 79

Survivin is an inhibitor of apoptosis protein, overexpressed in most human malignancies and implicated in mitosis regulation and preservation of cell viability. In order to investigate the prevalence and clinical significance of survivin in early-stage non-small cell lung carcinoma (NSCLC), survivin mRNA levels and protein expression were evaluated, using quantitative real-time RT-PCR and immunohistochemistry, respectively, in a series of 83 patients with stage I (IA and IB) surgically resected NSCLC. Detectable survivin mRNA levels could be demonstrated in all non-neoplastic lung tissue samples and in the tumours analysed. Survivin mRNA levels were elevated in 80 carcinomas (96%) compared to normal lung (p = 0.008). Among all tumours, survivin transcripts were present at a higher level in squamous cell carcinomas (p = 0.0022). Cytoplasmic and nuclear immunoreactivity was found in 70% and 80% of tumours, respectively and both were present in 54%. Cytoplasmic immunoreactivity correlated with tumour stage (p = 0.019). Survivin expression levels did not correlate with patient survival. In one specimen, cytoplasmic and focal nuclear immunostaining was observed in dysplastic bronchial squamous metaplasia. These results document that survivin overexpression is almost always present in early-stage NSCLC, suggesting that this protein may play a role in lung tumourigenesis. This ubiquitous expression makes survivin an appealing new target for novel therapies in lung cancer. In addition, this study also documents that survivin overexpression could be exploited for diagnostic purposes and that quantitative real-time RT-PCR can be a useful tool for evaluating survivin activation in NSCLC.
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PMID:Survivin gene expression in early-stage non-small cell lung cancer. 1289 98

We assessed a nonradioactive approach to induce apoptosis in non-small cell lung cancer by a novel iodide uptake and retention mechanism. To enhance tumor apoptosis, we transduced non-small cell lung cancer cells with retroviral vectors containing the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes. Expression of NIS and TPO facilitated concentration of iodide in tumors. As a consequence of the marked increase in intracellular levels of iodide, apoptosis was seen in >95% of NIS/TPO-modified lung cancer cells. Intraperitoneal injection of potassium iodide resulted in significant tumor volume reduction in NIS/TPO-modified tumor xenografts without apparent adverse effects in SCID mice. Iodide induced an increase in the level of reactive oxygen species. Iodide-induced apoptosis is sensitive to N-acetylcysteine inhibition, suggesting an important role by reactive oxygen species in this apoptotic process. In addition, iodide-induced apoptosis is associated with overexpression of CDKN1A (p21/Waf1)and down-regulation of survivin at both mRNA and protein levels. This is the first report demonstrating that a therapeutic dose of nonradioactive iodide has potent efficacy and high selectivity against lung cancer when used in combination with genetic modification of cancer cells to express the NIS/TPO genes.
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PMID:Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells. 1294 36

Malignant transformation of cells is accompanied by multiple genetic abnormalities with aberrant expression of genes. By using the reverse transcriptase polymerase chain reaction (RT-PCR) assay, we have assessed the regulation of survivin gene expression in a prospectively collected series of 83 human non small-cell lung cancers. Survivin gene transcripts were identified in 71 (85.5%) of the tumor samples, while they were detected in only 10 (12%) of the paired histopathologically normal lung samples. Furthermore, a diminished overall survival was associated with survivin expression (Log-rank, P=0.01). This review discusses the structure, expression, and function of the survivin gene. It presents updated pooled data on survivin, analyzed by either immunochemistry or by RT-PCR, and the clinical correlates of aberrant expression in several tumors. We conclude that estimation of survivin gene transcripts by RNA techniques may have relevant applications in the prognostic and therapeutic assessment of lung cancer.
Clin Lung Cancer 1999 Nov
PMID:The anti-apoptosis survivin gene and its role in human cancer: an overview. 1473 65

Expression of survivin is elevated in most malignancies, especially in radiation-resistant cell lines. In this study, we investigated how radiation affects survivin expression in primary endothelial cells as well as in malignant cell lines. We found that 3 Gy significantly reduced survivin protein level in human umbilical vein endothelial cells (HUVECs) but not in tumor cell lines. Flow cytometry studies suggest that the down-regulation of survivin is independent of cell cycle. In addition, survivin mRNA level was also down-regulatable by irradiation. However, it was abrogated by actinomycin D-mediated inhibition of gene transcription. Luciferase reporter gene assays suggest that irradiation suppressed the survivin promoter. p53 overexpression reduced survivin expression, but overexpression of a p53 mutant failed to abolish the radiation-induced down-regulation in HUVECs. Alteration of p53 status in Val138 lung cancer cell line also failed to restore the radiation-inducible down-regulation. Overexpression of survivin in 293 cells prevented apoptosis induced by irradiation and increased cell viability after irradiation. The inhibition of survivin using antisense oligonucleotides caused a significant decrease in cell viability of irradiated H460 lung cancer cells. These data suggest that radiation transcriptionally down-regulates survivin in HUVECs. This regulatory mechanism is defective in malignancies and is not mediated by p53. Survivin overexpression may lead to resistance to radiotherapy by inhibiting apoptosis and enhancing cell viability. The inhibition of survivin results in sensitization of H460 lung cancer cells to radiation. These studies suggest that survivin may be a target for cancer therapy.
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PMID:Survivin as a therapeutic target for radiation sensitization in lung cancer. 1508 1

Inhibitors of apoptosis, including bcl-2 and survivin (a novel gene encoding a unique apoptosis inhibitor), regulate cell proliferation by promoting cell survival. Although survivin has been detected in several human cancers, its prognostic significance and relationship to bcl-2 are not well characterized in lung cancer. Tissue sections from 102 non-small cell lung carcinomas (NSCLC) were immunostained using antibodies against survivin and bcl-2. Staining results were correlated with prognostic variables. Immunoreactivity for survivin and bcl-2 was observed in 53% and 21% of NSCLCs, respectively. Fifty-two percent of the 50 squamous cell carcinomas and 54% of the 52 adenocarcinomas expressed survivin. Survivin positivity correlated with tumor stage in squamous cell carcinoma. On univariate analysis, survivin expression correlated with decreased patient survival in NSCLC and in the subset of squamous cell carcinomas, but not in adenocarcinomas. On multivariate analysis, survivin was an independent predictor, along with distant metastasis and large tumor size. Eighteen percent of squamous cell carcinomas and 24% of adenocarcinomas expressed bcl-2. On univariate analysis, bcl-2 expression correlated with increased patient survival in NSCLC and in the subset of squamous cell carcinomas. An inverse correlation between the expression of survivin and bcl-2 was noted. Survivin immunoreactivity is an independent predictor of shortened survival in NSCLC, while bcl-2 protein expression correlated with prolonged patient survival. These findings indicate an inverse relationship between survivin and bcl-2 expression and suggest that these two inhibitors of apoptosis function through different pathways in the regulation of tumorigenesis in NSCLC.
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PMID:Prognostic significance of anti-apoptosis proteins survivin and bcl-2 in non-small cell lung carcinomas: a clinicopathologic study of 102 cases. 1516 19

Survivin and XIAP are members of inhibitors of apoptosis (IAPs) family. They are upregulated in various malignancies. Inactivation of these molecules has resulted in chemosensitization. The purpose of this study was to determine whether inhibition of survivin, XIAP, or both enhances radiotherapy in a lung cancer model. Transient transfection of H460 cells with antisense oligonucleotides (ASOs) against either molecule has specifically reduced their expression, by Western analysis. Results from 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and clonogenic assays suggest that inhibition of survivin or XIAP greatly decreased cell survival following irradiation. A significantly increased number of apoptotic cells were detected when H460 cells were treated with either antisurvivin, anti-XIAP or both ASOs (P=0.03, 0.0003 and 0.01, respectively) plus irradiation. H460 xenografts that were treated with ASOs plus radiotherapy demonstrated growth delay beyond 15 days. Growth delay in the groups of combined treatment was greater than that in other groups. However, treatment with ASOs alone did not affect tumor growth delay in mice, but decreased the survival of H460 cells in culture. Antisense treatment did not cause any mortality or weight loss during the 32 days of study. These data suggest that inhibition of survivin or XIAP radiosensitizes H460 lung cancer cells by upregulating apoptosis and downregulating cell survival. Combination of radiotherapy and inhibition of survivin and XIAP through the antisense approach results in improved tumor control by radiotherapy in a mouse model of lung cancer.
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PMID:XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. 1525 65

Survivin inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localisation of survivin predicts survival of 48 patients with resected non-small-cell lung cancer (NSCLC). Patients with nuclear staining of survivin had significantly worse survival (relative risk: 3.9, P=0.02). Therefore, survivin may be a biomarker for NSCLC.
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PMID:Nuclear survivin as a biomarker for non-small-cell lung cancer. 1526 13


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