UMLS:C0684249 - FACTA Search

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Query: UMLS:C0684249 (lung carcinoma)
23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific CD44 isoforms are the surface adhesion molecules that have been shown to be associated with metastasis. In the present study, the role of the expression of standard and variant CD44 isoform (CD44s and CD44v6) as prognostic indicators in pathological stage I non-small cell lung carcinoma was investigated immunohistologically using monoclonal antibodies. The results showed that the expression of CD44v6 correlates with adverse prognosis in stage I non-small cell lung carcinoma but not CD44s. The 5-year survival rate of the patients with CD44v6-positive tumors was 50%, which was significantly lower than that of CD44v6-negative patients (88%; P = 0.001). The incidence of recurrent distant metastasis in the CD44v6-positive patients (45%; 9 of 20 patients) was significantly higher than that in the CD44v6-negative patients (20%; 10 of 49 patients; P = 0.038), suggesting the involvement of CD44v6 in hematogeneous metastasis of lung carcinoma. Although the incidence of the expression of CD44v6 in squamous cell carcinoma was significantly higher than that in adenocarcinoma, histological type was not a significant prognostic factor. No significant correlation was found between the expression of CD44v6 and lymphatic or vascular vessel invasion, although lymphatic vessel invasion was found to be an independent prognostic factor in the multivariate analysis. To investigate the relationship between the expression of CD44v6 and proliferative activity of tumor cells, the expression of proliferating cell nuclear antigen (PCNA) was examined. The expression of CD44v6 was more frequently observed in PCNA-positive patients than in PCNA-negative patients (P = 0.019), but the expression of PCNA was not a statistically significant prognostic indicator. The results of multivariate analysis by the Cox proportional hazards model showed that CD44v6 was an independent prognostic indicator. We concluded that the expression of CD44v6 is a useful prognostic factor in stage I non-small cell lung carcinoma.
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PMID:Expression of CD44 variant exon 6 in stage I non-small cell lung carcinoma as a prognostic factor. 951 89

A high level of apoptotic activity and an independence of apoptosis from the expression of p53 and bcl-2 have been observed in non-small-cell lung carcinoma. We examined 44 samples of normal, metaplastic and premalignant (i.e. mild, moderate and severe dysplasias and carcinoma in situ) bronchial epithelia to evaluate whether differences in the apoptotic activity could already be seen in the stages preceding squamous cell carcinoma of the lung (SQCLC). Apoptotic cells and bodies were visualized by 3' end labelling. The expression of p53 and members of the bcl-2 gene family, such as bcl-2, bax and mcl-1, were determined immunohistochemically with specific antibodies. The relative number of apoptotic cells and bodies [apoptotic index (AI%)] was already increased threefold as the normal bronchial epithelium changed to squamous metaplasia, and the AIs of the dysplastic lesions were about four times higher than those of the normal epithelium. Apoptosis was significantly associated with cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry. However, the extent of apoptosis did not correlate with the expression of p53, bcl-2, bax and mcl-1. We conclude that, in the metaplasia-dysplasia-carcinoma sequence in the lung, the elevation of the AI% is an early event associated with cell proliferation activity, but is independent of the expression of p53, bcl-2, mcl-1 and bax.
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PMID:Apoptotic activity is increased in parallel with the metaplasia-dysplasia-carcinoma sequence of the bronchial epithelium. 1007 Sep 3

The retinoblastoma gene family is composed of three members: the retinoblastoma gene, one of the most studied tumor suppressor genes, and two related genes: p107 and pRb2/p130. These proteins are also known as the pocket proteins due to a unique structural and functional domain composed of subdomains A and B separated by a spacer region that is highly conserved among each of the proteins. These proteins exhibit unique growth suppressive properties that are cell type specific, suggesting that although the pocket proteins may complement each other, they are not fully functionally redundant. With the development of antibodies recognizing these three proteins it is now possible to detect expression in formalin-embedded specimens. Recent studies on 235 lung cancers, using immunohistochemical techniques, suggested an independent role for Rb2/p130 in the development and/or progression of human lung carcinoma. We found a statistically significant inverse relationship between the histological grading (degree of malignant potential) and the expression of pRb/p105, p107 and pRb2/p130 in squamous cell carcinomas, meaning that an increase in grading resulted in a significant decrease in protein expression. This phenomenon was particularly evident for pRb2/p130 (p < .0001) which had the highest percentage of undetectable levels in all the specimens examined and the tightest inverse correlation (p value) with both the histological grading and PCNA expression in the most aggressive tumor types, suggesting an important role for pRb2/p130 in the pathogenesis and progression of certain lung cancers. We further explored the expression of pRb2/p130 protein in routine archival FNAB cytological material from 30 Patients with lung cancer using immunocytochemical techniques, comparing protein expression with tumor type. Two pathologists evaluated the staining pattern and scored the percentage of positive cells. Of the 30 neoplasms, 27 displayed a positive staining for pRb2/p130. In particular, we detected pRb2/p130 in 9 (100%) squamous carcinomas, 11 (84%) adenocarcinomas, 5 (100%) BAC, and 2 (66%) SCC. The percentage of positive nuclei varied in different tumors with the highest expression level in adenocarcinomas. Immunocytochemistry represents a sensitive method for detection of pRb2/p130 expression in cytological or archival specimens, and the level of detection seems to be comparable to paraffin sections. Therefore, this methodology could be used in the preoperative evaluation of routine cytological specimens in order to improve the diagnostic and prognostic evaluation of lung cancer patients.
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PMID:The role of pRb2/p130 protein in diagnosing lung carcinoma on fine needle aspiration biopsies. 1009 23

Small cell carcinoma is a rare neoplasm in the esophagus. To evaluate cell proliferation activity and its underlying mechanisms in this tumor, we examined immunohistochemically 5 cases of small cell carcinoma of the esophagus (SCCE) for expressions of tumor suppressor proteins, oncoproteins and cell proliferation markers including p53, p21WAF1/CIP1, retinoblastoma (Rb) protein, bcl-2, Ki-67 and PCNA, and compared the results with those of 5 cases of small cell carcinoma of the lung (SCCL) and 10 cases of squamous cell carcinoma of the esophagus (SQCE). The prevalence and labeling index of p53-immunoreactivity tended to be higher in SCCE (4/5; 56.6%) and SCCL (4/5; 79.9%) than in SQCE (6/10; 48.8%). Expression of p21WAF1/CIP1 was observed in 2 of 10 cases of SQCE. In contrast, its expression could not be detected in any cases of SCCE and SCCL examined. Expression of Rb protein was observed in 9 out of 10 cases of SQCE, but not in any cases of SCCE and SCCL. SCCE and SCCL showed more frequent and intense immunoreactivity for bcl-2 than SQCE. In expression of cell proliferation markers (Ki-67 and PCNA), no remarkable difference was observed among SCCE, SCCL and SQCE. These results suggest that SCCE and SCCL could share some genetic alternations including mutation of p53, loss of Rb gene and overexpression of bcl-2, and these may be related to the similar biological potentials between the two. Furthermore, SCCE was different from SQCE in expression of Rb protein and bcl-2, and these two types of esophageal carcinoma could arise through different molecular mechanisms.
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PMID:Immunohistochemical analysis for cell proliferation-related protein expression in small cell carcinoma of the esophagus; a comparative study with small cell carcinoma of the lung and squamous cell carcinoma of the esophagus. 1021 9

The biologic characteristics of the two human giant-cell lung carcinoma strains with high (strain D) and low metastatic potential (strain C) were studied, including karyotype of chromosome, intracellular free calcium ([Ca2+]i), morphologic changes of cell surface and the expression of nm23-H1, p53, ras, c-myc, c-erbB2, bcl-2 genes and PCNA. The correlation between different biologic features and the metastatic potential of the two strains was analyzed. We found: 1) Both strains had the karyotypic abnormality of -13, -14, -15, +20, +21 with seven same marker chromosomes. Only strain D had the karyotypic abnormality of +7, -17, -18, +X, 7p+; 2) [Ca2+]i of the strain C (984.7 +/- 573.8) and D (517.6 +/- 216.6) was significantly different (p < 0.05). The amplitude of intracellular calcium oscillations of strain C was lower than the one of strain D; 3) strain C had more villous-like protrusions on the cell surface, whereas strain D had more bubble-like protrusions; 4) The expression of nm23-H1 and p53 protein of strain C was all higher than that of strain D. The expression of PCNA of strain C was lower than strain D; 5) nm23-H1 mRNA levels of strain C was lower than that of strain D. We consider that the karyotype of chromosomes, intracellular free calcium, the structure of cell membrane and the expression of nm23-H1 gene, p53 gene, PCNA could be closely related to the metastatic potential of human giant-cell lung carcinoma. They could be used as the sign for judging whether the tumor will metastasize in clinical practice as well as in judging the prognoses of patients.
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PMID:Study on the metastatic mechanisms of human giant-cell lung carcinoma comparison between the strains C and D. 1021 98

We produced a rat IgG2a monoclonal antibody against the carboxyl terminal region of human midkine (MK), a novel growth factor. This monoclonal antibody was used in immunohistochemical studies to compare the expression of MK, proliferating cell nuclear antigen (PCNA) and p53 protein in 133 primary brain tumors and 21 carcinoma metastases to the central nervous system. Approximately half of the glioblastomas multiforme (GBMs) (19/32), medulloblastomas (8/14), primitive neuroectodermal tumors (PNETs) (5/11), breast carcinoma metastases (Br-Mts) (6/10) and lung carcinoma metastases (L-Mts) (5/11) as well as some astrocytomas (2/14) had tumor cells that expressed MK; however, oligodendrogliomas, ependymomas, schwannomas, meningiomas, and pituitary adenomas did not express MK. The values of the PCNA-labeling index were statistically higher in GBMs, medulloblastomas, PNETs, Br-Mts, and L-Mts that expressed MK than in those that did not (Wilcoxon rank-sum test, p < 0.05). There was no correlation between MK and p53 protein in all tumor types. Normal and non-neoplastic brain tissues were negative for MK, PCNA, and p53 protein. We conclude that primary and metastatic tumors of the brain express MK and that the MK expression in brain tumors may depend, in part, on the proliferating potential.
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PMID:Monoclonal antibody to human midkine reveals increased midkine expression in human brain tumors. 1033 31

We investigated the expression of thioredoxin (Trx) and thioredoxin reductase (TrxR) in 89 non-small cell lung carcinomas. Additionally, immortalized human bronchial epithelial cells (BEAS 2B) and four human lung carcinoma cells lines (A549, SK-MES-1, CALU-6, and A427) were studied by Western blot and reverse transcription-PCR for the synthesis of Trx and TrxR protein and mRNA expression in vitro. The histological samples were also studied for immunohistochemical p53 and proliferating cell nuclear antigen expression and apoptosis. In non-neoplastic lung, Trx and TrxR expression was seen in bronchial epithelial cells and alveolar macrophages, metaplastic alveolar epithelial cells, and chondrocytes of the bronchus. In non-small cell lung carcinomas, there was a widespread expression of Trx and TrxR with only three and eight cases negative, respectively. Trx and TrxR expression was located in both cytoplasmic and nuclear compartments of the cells. There was a statistical association between cytoplasmic and nuclear Trx or TrxR expression. Grade I-II tumors showed stronger cytoplasmic and nuclear Trx and TrxR immunoreactivity than grade III tumors. No association was found between p53 and proliferating cell nuclear antigen expression and Trx or TrxR immunoreactivity. However, apoptosis was inversely associated with nuclear Trx and TrxR positivity. In the cell lines studied, both non-neoplastic BEAS 2B cells and all of the carcinoma cell lines expressed Trx and TrxR proteins and mRNA. The results show that these redox-regulating proteins are highly expressed in lung carcinomas taking part in activation of transcriptional factors and regulation of apoptosis in non-small cell lung carcinoma. In high-grade tumors, Trx and TrxR expression is diminished, suggesting loss of redox regulation in tumors with low differentiation.
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PMID:Widespread expression of thioredoxin and thioredoxin reductase in non-small cell lung carcinoma. 1141 May 16

This study analyzed the expression of stress-response (heat-shock) protein 60 (srp 60) in a series of 158 human brain tumours. Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 exposed to hyperosmolar stress served as positive controls. Deposits of reaction products were found in the cytoplasm. Approximately half of the glioblastomas multiforme (17/31), breast carcinoma metastases (6/10), and lung carcinoma metastases (5/11) as well as about one-third of the astrocytomas (5/13) and meningiomas (8/23) had tumour cells that expressed srp 60. A positive reaction for srp 60 was also seen in some medulloblastomas (2/16), primitive neuroectodermal tumours (PNETs) (2/11), schwannomas (2/21), and pituitary adenomas (2/7), but no positive reactions were observed with oligodendrogliomas and ependymomas. Compared with srp 60-negative tumours, srp 60-positive tumours coexpressed one or more stress-related proteins, among which srp 90, srp 72, srp 27, alphaB-crystallin and ubiquitin occurred with higher frequencies; a high correlation between srp 60 and the other five srps (0.88 - 0.97, p<0.01, Pearson correlation coefficient) was observed in srp 60-positive tumours. In contrast, the correlation coefficient in srp 60-negative tumours was not significant (-0.26 - 0.71). There was a tendency for the proliferating cell nuclear antigen (PCNA)-labeling index to be higher in glioblastomas, astrocytomas, medulloblastomas, PNETs, and breast and lung carcinoma metastases that expressed srp 60 than in those that did not. No significant immunohistochemical reactions of srp 60, PCNA and p53 protein were seen with sections of normal brain tissues. We conclude that primary and metastatic tumours of the brain produce srp 60 and that srp 60 in certain brain tumour cells may coexpress the other five srps. In addition, srp 60 expression might depend, in part, on proliferating potential.
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PMID:The immunohistochemical expression of stress-response protein (srp) 60 in human brain tumours: relationship of srp 60 to the other five srps, proliferating cell nuclear antigen and p53 protein. 1151 Sep 71

Y box-binding protein-1 (YB-1), a member of the DNA binding protein family, interacts with inverted CCAAT boxes (Y-boxes). Y-boxes are located on the promoter of numerous genes, such as DNA topoisomerase IIalpha (Topo IIalpha), proliferating cell nuclear antigen (PCNA) and multidrug resistance 1 (MDR1). In this study, we used immunohistochemical (IHC) staining to detect YB-1 expression in 59 lung cancer tissues and to evaluate whether YB-1 expression was associated with the expression of YB-1 target genes such as Topo IIalpha, PCNA and MDR1 in human lung carcinoma. Twenty-eight out of 59 cases (47.5%) were stained positive for YB-1 in the cytoplasm, while 30 out of 59 cases (50.8%) were positive for PCNA in the nuclei. Topo IIalpha-positive cells were detected in 16 out of 59 cases (27.1%). Eight out of 59 cases (13.6%) had greater than 5% P-gp positive cells expression. There was a significant correlation between the YB-1 and Topo IIalpha expression in small cell lung cancer (SCLC) (p=0.0242). YB-1 expression also correlated with PCNA expression in non-small cell lung cancer (NSCLC) (p=0.0001). Higher levels of YB-1 expression were associated with T3-4 and Stage III-IV tumors in adenocarcinomas (p=0.0072; p=0.0168). In contrast, no relationship was found between YB-1 expression and P-gp expression. Our study suggests that YB-1 expression correlates with Topo IIalpha and PCNA expression in lung cancer.
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PMID:Expression of Y box-binding protein-1 correlates with DNA topoisomerase IIalpha and proliferating cell nuclear antigen expression in lung cancer. 1172 93

Prognostic value of p53 and PCNA expression in non-small cell lung cancer (NSCLC) remains controversial. In this study we determined the relevance of these abnormalities in terms of overall survival and disease-free survival in 95 NSCLC patients who underwent curative pulmonary resection. Expression of p53 was found in 44 samples (45%), expression of PCNA-in 79 samples (83%), and expression of both markers-in 35 samples (36%). There was no relationship between expression of either protein and major clinicopathological characteristics. Median survival for patients with and without p53 expression was 36 and 33 months, respectively and 5-year survival probability-29 and 37%, respectively (P=0.73). Median survival for patients with and without PCNA expression was 36 and 27 months, respectively and 5-year survival probability-35 and 25%, respectively (P=0.60). There was no significant difference in overall survival between particular groups of patients with tumors carrying four possible p53/PCNA phenotypes. In multivariate analysis including patient age, sex, tumor stage, tumor type and differentiation, p53 and PCNA expression, the only variable important for survival was stage of disease. These results suggest the lack of prognostic relevance of p53 and PCNA expression in surgically treated NSCLC patients.
Lung Cancer 2002 Jan
PMID:Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer. 1175 Jul 11

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