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

Regarding HER-2/neu expression (gene or protein level) in lung cancer, several studies with inconsistent results have been recently reported, partially due to variable techniques used and/or heterogeneous populations examined. The objective of this study was to examine HER-2/neu expression in a well-defined cohort of non-small-cell lung cancers (NSCLC) and in nonneoplastic lung tissue utilizing a combination of high-density tissue microarray, immunohistochemistry (IHC), and fluorescent in situ hybridization (FISH) under uniform test conditions. One hundred forty stage I-IIIA primary NSCLCs and 38 non-neoplastic lung samples were examined. IHC, using an FDA-approved Hercept monoclonal antibody kit, was performed and HER-2/neu gene alteration was assessed by FISH. The association of expression of HER-2/neu with clinicopathologic parameters was analyzed. Ninety-four percent of tumor samples (131/140) were fully interpretable after tissue processing. Twenty-five of them (19%) overexpressed (2+, 3+) HER-2/neu, while 106 (81%) had no or weak expression. All thirty-four interpretable non-neoplastic lung samples were negative for HER-2/neu alteration at protein and gene level. HER-2/neu protein overexpression correlated well with HER-2/neu gene amplification (r =.83, P < 0.001). HER-2/neu overexpression was significantly associated with histologic subtype: 19 adenocarcinomas (19/82, 23%) versus 4 squamous cell carcinomas (4/44, 9%) overexpressed Her-2/neu (P = 0.04). Statistical significance was observed between HER-2/neu expression and tumor differentiation, with strong positive (3+) expression observed more frequently in poorly differentiated tumors (P = 0.01). Patients with HER-2/neu abnormalities, particularly HER-2/neu gene amplification, exhibited a shorter survival (P = 0.043). The statistically significant difference (P < 0.005) between HER-2/neu alteration in tumor samples(25/131, 19%) and in the nonneoplastic tissue (0/34, 0%) implies that HER-2/neu may have a role in the carcinogenesis of NSCLC. The findings provide evidence supporting the hypothesis that the HER-2/neu receptor may represent a useful molecular target in the treatment of NSCLC. The significant association of HER-2/neu expression and gene amplification with poorly differentiated carcinoma compared with well differentiated carcinoma suggests that HER-2/neu may be involved in NSCLC tumor evolution. Patients with HER-2/neu gene amplification and strong positive expression of HER-2/neu protein showed a strong tendency toward shorter survival.
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PMID:HER-2/neu protein expression and gene alteration in stage I-IIIA non-small-cell lung cancer: a study of 140 cases using a combination of high throughput tissue microarray, immunohistochemistry, and fluorescent in situ hybridization. 1463 6

Endostatin is an angiogenesis inhibitor that is an endogenously produced proteolytic fragment of type XVIII collagen. Although serum levels of endostatin have extensively been studied in patients with malignant diseases, endostatin in pleural effusion has not been fully evaluated. In order to determine whether endostatin is present in pleural effusion, and to determine whether endostatin levels vary in pleural effusion of different etiology, we measured levels of endostatin in 38 malignant pleural effusion due to lung cancer patients and 29 patients with non-malignant disease using an ELISA kit. Free form of endostatin was measurable (> 11.2 pg/ml) in 26 of 38 malignant and 13 of 29 non-malignant pleural effusion. Endostatin levels in the 38 malignant pleural effusion were significantly higher than those in patients with the 29 patients with non-malignant diseases ( p = 0.0131). However, there was not statistically significant difference between the patients with pleuropneumonia and those with tuberculous pleurisy ( p = 0.2194). In malignant pleural effusion due to lung cancer, the pleural effusion endostatin levels did not differ when the histological types of lung cancer were considered ( p = 0.0674). Endostatin was present in both malignant and non-malignant pleural effusion, and elevated levels of endostatin were observed in malignant pleural effusion. Although the mechanisms are unclear, elevated levels of endostatin in pleural effusion may represent the local productions of endostatin in pleural space.
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PMID:Endostatin levels in exudative pleural effusions. 1474 37

ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) as genes have been known to be belonged to the nucleotide excision repair pathway and therefore related to DNA repair. Polymorphisms in these genes have been rarely evaluated in terms of predicting cancer patient survival. We investigated whether these polymorphisms have an effect on response to chemotherapy and survival in 109 patients with non-small-cell lung cancer treated with cisplatin combination chemotherapy. Polymorphisms of ERCC1 Asn118Asn (C --> T), XPD Lys751Gln (A --> C) and Asp312Asn (G --> A) were evaluated using a SNaPshot kit. As for chemotherapy response, treatment response did not show statistically significant differences between the wild genotypes and the variant genotypes for the ERCC1 and XPD gene. The median survival time of all patients was 376 days (95% CI, 291-488). As for survival rate according to the polymorphism of codon 118 in ERCC1, median survival time in patients showing C/C genotype was 486 days (95% CI, 333-x), which was significantly different from the 281 days (95% CI, 214-376) of patients with the variant genotype (T/T or C/T) (P = 0.0058). Using the Cox-proportional hazards model, the polymorphism of codon 118 in ERCC1, response to chemotherapy, weight loss and performance status effected overall survival significantly (P = 0.0001, 0.0001, 0.0028 and 0.0184, respectively). However, polymorphisms of codons 751 and 312 in the XPD gene did not affect patient survival (P = 0.4711 and 0.4542, respectively). Therefore, we suggest that the C/C genotype in codon 118 of ERCC1 is a surrogate marker for predicting better survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.
Lung Cancer 2004 Jun
PMID:Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. 1514 May 44

Between February and July 2001, 15 patients were diagnosed as Clostridium difficile-associated diarrhea in a ward of hematological neoplasm and lung cancer in a cancer center hospital. Of these 15 patients, 10 had malignant lymphoma, and 12 and 11 had exposure to antimicrobial agents and cancer chemotherapy, respectively, before the onset of diarrhea. Toxin A-positive, toxin B-positive (A+ B+) C. difficile was recovered from five patients and the remaining 10 patients suffered from diarrhea caused by toxin A-negative, toxin B-positive (A- B+) strains. All of the 10A- B+ isolates represented an identical banding pattern by PCR ribotyping and classified into one type (two subtypes) by pulsed field gel electrophoresis typing, indicating that a nosocomial outbreak of diarrhea caused by A- B+ C. difficile occurred among the patients hospitalized on this ward. Detection of toxin A in stool specimens by a toxin A detection kit was performed on 14 patients. Although two patients who carried A+ B+ strains were positive for toxin A assay, toxin A detection test was negative in 12 patients including 10 patients with A- B+ C. difficile infection. Diagnosis of C. difficile-associated diarrhea by combination of toxin A assay in feces and culture of C. difficile could successfully lead to recognition of an outbreak caused by A- B+ C. difficile in a cancer center hospital.
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PMID:[A nosocomial outbreak of diarrhea caused by toxin A-negative, toxin B-positive Clostridium difficile in a cancer center hospital]. 1517 35

Smoking is a major cause of human lung cancer. Past studies suggest that apoptosis might influence the malignant phenotype, but little is known about the association between apoptosis and cigarette smoke (CS)-induced lung pathogenesis. Using an in situ cell death detection kit (TA300), the association of CS with apoptosis was determined in a concentration-dependent manner. Furthermore, the expression of related proteins were investigated in the terminal bronchiole areas of the lung tissue from rats exposed to CS. Results showed that the expression of phosphotyrosine proteins was increased significantly in lung tissue of rats exposed to CS from 5 to 15 cigarettes. Using Western blotting and immunoprecipitation assay, Fas, a death receptor, was proved just be one of these phosphotyrosine proteins. CS triggered activation of MAP kinase (p38/JNK or ERK2) pathway, which led to Jun or p53 phosphorylation and FasL induction links Fas phosphorylation. Further, smoke treatment produced an increase in the level of proapoptotic proteins (Bax, t-Bid, cytochrome c and caspase-3), but a decline in Bcl-2, procaspase-8 and procaspase-9 proteins. Thus, CS-induced apoptosis may result from two main mechanisms, one is the activation of p38/JNK-Jun-FasL signaling, and the other is stimulated by the stabilization of p53, increase in the ratio of Bax/Bcl-2, release of cytochrome c; thus, leading to activation of caspase cascade.
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PMID:Induction of apoptosis in the lung tissue from rats exposed to cigarette smoke involves p38/JNK MAPK pathway. 1597 Feb 77

The pathologic distinction of small cell from non-small cell-lung carcinoma is of considerable therapeutic significance. In particular, the ability to distinguish poorly differentiated non-small-cell lung cancer from small-cell lung carcinoma (SCLC) is at times difficult based upon morphology alone; available immunohistochemical markers such as neuroendocrine markers are of limited utility. We have demonstrated the role of p63 and thyroid transcription factor-1 (TTF-1) in the differential diagnosis of poorly differentiated squamous-cell carcinoma (PDSCC) versus SCLC, mostly in biopsy samples (Wu et al., American Journal of Clinical Pathology 2003;119:696-702). Here, we examine further the utility of this panel in cytologic cell-block samples of lung cancers including both primary and metastatic cancers of pulmonary origin, and cases of nonpulmonary cancers metastatic to lung in which differential diagnoses included a lung primary.Four-micron thick sections of 30 alcohol-fixed paraffin-embedded cell blocks from 14 lung FNAs, 6 liver FNAs, 3 bronchial washings, 1 subcarinal lymph node FNA, 1 iliac lymph node FNA, 1 pelvic mass FNA, 1 neck lymph node FNA, 1 adrenal FNA, and 1 pleural effusion were deparaffinized and stained with monoclonal antibodies reactive to p63 (1:800, Santa Cruz Biotechnology) and TTF-1 (1:50, Dako). Slides were stained for p63 using a streptavidin-biotin kit (BioGenex) and diaminobenzidine as chromagen, and counterstained with hematoxylin. Slides were stained for TTF-1 using a Dako Autostainer. Thirty cases were examined, including 8 primary SCLCs, 8 extra-pulmonary metastases of lung SCLCs, 4 PDSCCs and 4 primary pulmonary adenocarcinomas, and 6 nonpulmonary adenocarcinomas metastatic to lung or other sites. Fifteen out of 16 (94%) SCLC cases were p63-/TTF-1+, ranging in intensity from focal-weak to diffuse-strong; 1/16 SCLCs from a bronchial washing was p63-/TTF-1- but synaptophysin was positive. All 4 primary lung adenocarcinoma cases were p63-/TTF-1+; contrasting with nonpulmonary adenocarcinomas that were all p63-/TTF-1-. All 4 PDSCC cases were p63+/TTF-1-. The panel of p63 and TTF-1 appears to be useful in the diagnostic evaluation of cytologic cell-block samples of pulmonary malignancy.
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PMID:Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers. 1613 74

Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer. However, the health effects of arsenic, chromium, and nickel exposures are equivocal for children. Therefore, we performed a cross-sectional study to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress to DNA in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking children using atomic absorption spectrometry. As a biomarker for oxidative stress, urinary 8-hydroxy-2 -deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine. No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean +/- SE, 16.0 +/- 1.3; vs. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 +/- 1.6; vs. low arsenic/low chromium, p = 0.25), high arsenic/low chromium (12.9 +/- 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 +/- 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children.
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PMID:Increased levels of 8-hydroxy-2 -deoxyguanosine attributable to carcinogenic metal exposure among schoolchildren. 1620 52

Protein markers are commonly used in forensic medicine to establish the origin of human fluids detected in crime scenes. Semenogelins, the major protein constituents of semen coagulum, are the most effective markers for semen detection. Recently, it has been demonstrated that semenogelins are also ectopically expressed in small cell lung carcinomas (SCLC) and in a minority of non-small cell lung carcinomas (NSCLC). This finding prompted us to look for semenogelin expression in the serum of lung cancer patients. A set of 13 serum samples (3 from SCLC and 10 from NSCLC patients) was screened by enzyme-linked immunosorbent assay (ELISA), using a commercially available kit. Four of the NSCLC cases showed positive results. Ectopic expression of marker proteins in individuals affected by cancer could represent a potential source of forensic pitfalls.
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PMID:Expression of seminal vesicle-specific antigen in serum of lung tumor patients. 1622 16

Our previous study demonstrated that bone marrow microinvolvement (BMM) is an epiphenomenon of tumor progression rather than a prognostic factor in non-small cell lung cancer. We hypothesize that an increase in mesenchymal transition power in epithelial tumor cells by up-regulation of the matrix metalloproteinases (MMPs) may contribute to the existence of BMM and poorer prognosis. Hereby we conducted a prospective study of BMM and MMPs expression in a cohort of 57 non-small cell lung cancer patients. Bone aspirates were examined by immunohistochemical stains. Expressions of MMPs were checked by Human MMP primer set kit (Maxim Biotech, USA). Correlations between the MMPs expression and BMM, nodal metastasis, and prognosis were examined. Cox model analysis was used to identify independent prognostic factors. Though positive BMM was identified in 38 (66.7%) of the patients, none of the clinicopathological factors, including sex, age, cell types, tumor differentiation, nodal metastasis and TNM status of the tumor, was related to BMM by the tumor cells. Up-regulation was observed in a broad spectrum of MMPs with the exception of MMP-3. However, only MMP-13 expression correlated with the existence of BMM (p=0.006). Univariate analysis revealed MMP-3, MMP-7 and MMP-13 as negative prognostic factors. Cox model analysis revealed T-status, cell differentiation, and MMP-13 expression of the tumor as independent prognostic factors. The overall 5-year survival rate of the patients was 36.8%. The existence of BMM itself did not influence the prognosis (p=0.109), however, patients with positive MMP-13 expression (N=34) had a poorer 5-year survival rate of 26.5% (p=0.025). In summary, non-small cell lung cancer cells with MMP-13 expression, despite of BMM status, tend to shed and aggregate in the bone marrow, which is subsequently reflected in a poorer survival rate.
Lung Cancer 2006 Jun
PMID:Matrix metalloproteinase-13 expression is associated with bone marrow microinvolvement and prognosis in non-small cell lung cancer. 1656 61

In non-small-cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2 genes which are important in apoptosis and c-kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC) methods. IHC evaluation was done by the semichantitative method according to the distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%) stage IIIB and three cases (4.4%) were stage IV patients. Their histological subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma, 28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma (two patients) and large-cell carcinoma (three patients). The positive immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%, respectively. The positive immune staining rates for c-kit in whole group, squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%, respectively. We didn't find any correlation with Bax, bcl-2 and c-kit expressions and clinicopathological parameters such as age, tumour size, lymph node involvement, smoking, stage of the disease, response to radiotherapy and chemotherapy. Results are interpreted according to survival; bax and bcl-2 expressions were not so effective both in whole group and histologically subgrouped patients. C-kit expression was also found not related with survival in whole group whereas found as a bad prognostic factor in patients with squamous cell carcinoma. These findings could indicate that the expression of apoptotic pathway markers and c-kit may have a role in the prognosis of early stage NSCLC, especially with squamous cell carcinoma subtype.
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PMID:Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis. 1680 52


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