Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.
 ...
PMID:Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. 773 90

Bcl-2 oncoprotein, a member of a new category of oncogenes associated with the regulation of programmed cell death (apoptosis), has been considered to be involved in biological processes such as tumorigenesis and tumor development. To determine the role of bcl-2 oncoprotein in lung cancer, we preliminarily examined the expression of this protein in various histological types. Immunohistochemical staining using monoclonal bcl-2 oncoprotein antibody was performed in surgically resected frozen specimens. Bcl-2 staining was seen in nine of 13 small cell lung cancers (69%), while only 18 out of 69 non-small cell lung cancers (26%) expressed bcl-2 oncoprotein, showing a significantly increased incidence of bcl-2 oncoprotein expression in the former histological type. Considering the greater aggressiveness of small cell lung cancer compared to non-small cell lung cancer, the possibility exists that the high prevalence of bcl-2 oncoprotein expression in small cell lung cancer is closely associated with tumorigenesis and tumor development.
 ...
PMID:High prevalence of bcl-2 oncoprotein expression in small cell lung cancer. 776 30

The expression of Bcl-2 protein in 29 small cell carcinomas (SCCs; 6 surgical and 15 biopsy specimens obtained from various organs, 7 metastatic lymph nodes, and 1 metastatic liver tissue) was investigated by immunohistochemical technique. Negative staining was observed in only two cases (7%). The majority of Bcl-2-positive tumors had > 95% positive cells, with a moderate staining intensity. A combined small-cell lung cancer showed discordant staining results between two different histology types. No correlations of Bcl-2 immunoreactivity with p53 expression and clinical staging were found. Our findings suggest that Bcl-2 expression may play a certain role in the early phases of SCC tumorigenesis, or that it may solely be a succeeding property directly derived from the tumor progenitor cells. As the Bcl-2 protein was present in most cases, it is not a useful prognostic or treatment marker for the cancer.
 ...
PMID:Immunohistochemical detection of Bcl-2 protein in small cell carcinomas. 857 Jan 34

As a first step towards elucidating the potential role(s) of bcl-2 and bcl-2-related genes in lung tumorigenesis and therapeutic responsiveness, the expression of these genes has been examined in a panel of lung cancer cell lines derived from untreated and treated patients, and in cell lines selected in vitro for multidrug resistance. Bcl-2 was hyperexpressed in 15 of 16 small-cell lung cancer (SCLC) cell lines and two of five non-small-cell lung cancer (NSCLC) lines compared with normal lung and brain, and hyperexpression was not chemotherapy related. Bcl-x was hyperexpressed in the majority of SCLC and NSCLC cell lines as compared with normal tissues, and all lung tumour lines preferentially expressed bcl-x1-mRNA, the splice variant form that inhibits apoptosis. Bax gene transcripts were hyperexpressed in most SCLC and NSCLC cell lines examined compared with normal adult tissues. Mutant p53 gene expression was detected in the majority of the cell lines and no relationship between p53 gene expression and the expression of either bcl-2, bcl-x or bax was observed. No changes in bcl-2, bcl-x and bax gene expression were observed in multidrug-resistant cell lines compared with their drug-sensitive counterparts.
 ...
PMID:Expression of apoptosis-regulatory genes in lung tumour cell lines: relationship to p53 expression and relevance to acquired drug resistance. 863 Feb 78

We investigated expression of Bcl-2, mutations in p53, and K-ras oncogene in 51 resected human non-small cell lung cancers. The studies were designed to test for the possibility of cooperativity between these oncogenes and p53 in the pathogenesis of lung cancer. An inverse relationship was found between expression of Bcl-2 and mutant p53 by immunohistochemistry (P < 0.01; Fisher exact test), suggesting that either Bcl-2 overexpression or mutations in p53 may fulfill a critical function in the pathogenesis of human non-small cell lung cancers. Tumors that harbored K-ras codon 12 mutations seldom had p53 mutations or overexpressed Bcl-2. Statistical analysis of these data showed that mutations in p53 and K-ras or overexpression of Bcl-2 and mutations in K-ras occurred at a frequency that could be explained only by chance [P > 0.1 in each case (Fisher exact tests)]. This suggests that cooperativity between mutant K-ras and mutant p53 or mutant K-ras and overexpressed Bcl-2 is not a common mechanism in the pathogenesis of human non-small cell lung cancers.
 ...
PMID:Overexpression of Bcl-2 and mutations in p53 and K-ras in resected human non-small cell lung cancers. 867 21

Recent advances in molecular biology have revealed various genetic lesions in lung cancer. Mutations of the K-ras gene, amplification or overexpression of myc family genes, erbB2 gene, or bcl2 gene are frequent genetic changes of oncogenes in lung cancer. Inactivation of tumor suppressor genes such as Rb gene, p53 gene, or p16 gene are also seen rather frequently. Furthermore, loss of heterozygosity at certain chromosomal arms such as 3p, 5q, 18q and 22q suggesting inactivation of yet unidentified tumor suppressor genes, also occurs in a significant proportion of lung cancers. Most of these genetic lesions have been reported to be associated with a poor prognostic outcome of the patients. However, great controversy exists as to whether a certain genetic lesion is really a prognostic marker. For example, although about 20 studies have been published, the prognostic implications of the p53 gene for patients with lung cancer still remain unclear. Little is known about the mechanism through which a certain genetic change affects the patient's prognosis. To ultimately improve the prognosis of patients with this deadly disease, definitive studies on which subsequent clinical trials can rely are much awaited.
 ...
PMID:[Genetic abnormalities in lung cancer and their prognostic implications]. 868 34

For determination of the cellular distribution of bcl-2 expression in lung cancer and clarification of its correlation with cell neuroendocrine differentiation, Bcl-2 immunostaining was carried out on a large series of formalin-fixed, paraffin-embedded lung cancer samples, and four general neuroendocrine marker and seven peptide hormone stainings were carried out on all Bcl-2-positive squamous cell carcinomas and adenocarcinomas of the lung as well as on 8 pulmonary neuroendocrine carcinomas histologically diagnosed. In addition, 3 small cell lung cancer cell lines were studied by Western blotting. Neuroendocrine differentiation in Bcl-2-negative squamous cell carcinomas and adenocarcinomas was examined with chromogranin A and alpha-subunit of Go protein stainings. Bcl-2 protein was detected in 104/111 small cell carcinomas, 8/8 neuroendocrine carcinomas, 0/6 typical (well differentiated) carcinoids, 23/64 squamous cell carcinomas, 4/65 adenocarcinomas, and all 3 small cell lung cancer cell lines. All 8 neuroendocrine carcinomas, 11 of the Bcl-2-positive squamous cell carcinomas, and all 4 Bcl-2 positive adenocarcinomas expressed multiple neuroendocrine markers. The distributions of Bcl-2 and neuroendocrine marker immunoreactivity closely paralleled each other on consecutive sections. In squamous cell carcinomas, Bcl-2-positive cells could be roughly subdivided into those with neuroendocrine differentiation features, usually demonstrating intense Bcl-2 staining, with basaloid tumor cells usually expressing weak to moderate Bcl-2 staining. The present study clearly shows Bcl-2 protein expression to be remarkably differentially regulated according to histological types of lung cancers and to appear to quite likely be closely associated with neuroendocrine differentiation of tumor cells, indicating that bcl-2 is importantly involved in cell development and differentiation, in addition to protecting cells from apoptosis. Bcl-2 might be usable as a neuroendocrine marker in lung cancers and possibly also in neural-crest-derived tumors.
 ...
PMID:Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation. 877 38

The expression of the proto-oncogene bcl-2, whose main function appears to be an inhibition of apoptosis, was investigated in 164 cases of primary small cell lung cancer by means of immunohistochemistry in a retrospective analysis. One-hundred twenty-five cases (76%) demonstrated expression of bcl-2. There was no difference in serum LDH levels and proliferative activity between the two groups. An analysis revealed a median survival time of 12 months for patients with bcl-2 positive tumors compared to 9.5 months for patients with bcl-2 negative tumors. Although statistical significance is not achieved, there is a trend towards longer survival in patients whose tumors express bcl-2. This tendency is also reflected by a higher rate of complete remission after chemotherapy: 40% in patients with bcl-2+ tumors versus 27% in patients with bcl-2- tumors. In multivariate analysis, tumor stage followed by Karnofsky index were the most valuable predictors for complete remission. LDH and tumor stage were most predictive for 1-year survival. Bcl-2 expression is frequent in SCLC and may reflect a less aggressive mechanism of transformation and a higher susceptibility to cytostatic treatment.
Lung Cancer 1996 Aug
PMID:Expression of bcl-2--protein in small cell lung cancer. 886 21

Immunohistochemical analysis of Bcl-2 oncoprotein, one of the oncogenes associated with the regulation of programmed cell death, was performed on 12 surgically resected tumors of the combined type of small-cell lung cancer. Ten cases (83%) expressed Bcl-2 oncoprotein within the tumor tissues. Two of them showed its expression in both the small cell carcinoma and non-small cell carcinoma types, and 7 cases exhibited Bcl-2 expression only in the portion of the small cell carcinoma. Considering previous reports indicating a high prevalence of Bcl-2 oncoprotein expression in small cell lung cancer, it is suggested that Bcl-2 oncoprotein even in the combined type of lung cancer may play an important role in tumorigenesis and tumor development and ensuing histological alterations between small cell carcinoma and non-small cell carcinoma types.
 ...
PMID:Bcl-2 oncoprotein expression is increased especially in the portion of small cell carcinoma within the combined type of small cell lung cancer. 893 49

To explore the mechanism by which lung cancers excessively arise from pneumoconiosis, we determined the altered expression of p53 and Bcl-2 by immunohistochemistry (IHC) in lung cancers, dysplasias and non-cancerous pulmonary epithelia in pneumoconiotics in comparison with those from non-pneumoconiotic patients. We examined p53 expression in squamous cell carcinomas (SCCs) and dysplasias separately in the central and peripheral zones of bronchial trees, based on observations that SCCs from pneumoconiotic patients occurr more frequently in peripheral epithelia than those from non-pneumoconiotic patients (55 of 72 SCCs with pneumoconiosis vs. 33 of 72 SCCs without pneumoconiosis). Forty-one of 72 patients with pneumoconiosis-related lung cancers had altered p53 expression, which was comparable to the positivity of p53 expression in lung cancers without pneumoconiosis. p53 expression was observed significantly more frequently in bronchiolar dysplasias with pneumoconiosis than in those from non-pneumoconiotic patients (13 of 23 vs. 4 of 22), while p53 expression was found in bronchial dysplasias with pneumoconiosis as frequently as those without pneumoconiosis. Moreover, in patients with pneumoconiosis, bronchiolar dysplasias exhibited p53 expression more frequently than bronchial dysplasias (13 of 23 vs. 4 of 19). When comparison was restricted to bronchiolar dysplasias from patients without lung cancer, p53 expression had a strikingly higher frequency in the dysplasias with pneumoconiosis than in those from non-pneumoconiotic patients (8 of 15 vs. 0 of 14). Bcl-2 occasionally was expressed in squamous metaplasias and basal cell hyperplasias, in contrast to p53, for which immunostaining was negative in these lesions. Altogether, our results show that pre-cancerous and/or cancerous targets in pneumoconiosis may be distributed over a more peripheral zone than those in patients without pneumoconiosis.
 ...
PMID:p53 and Bcl-2 expression in pneumoconiosis-related pre-cancerous lesions and lung cancers: frequent and preferential p53 expression in pneumoconiotic bronchiolar dysplasias. 946 48


1 2 3 4 5 6 7 8 9 10 Next >>