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)

There are few reports on the p53 status of small cell lung cancer (SCLC) and advanced non-SCLC (NSCLC) because surgically resected specimens are generally not available. Therefore, we evaluated p53 immunostaining in 175 transbronchial biopsy (TBB) specimens obtained from patients with all stages of lung cancer and retrospectively evaluated the relationship between p53 status and clinical parameters. All of the specimens were obtained prior to therapy. Formalin-fixed, paraffin-embedded TBB specimens were immunostained using an anti-p53 antibody (DO-1). p53 protein was detected in 55% (61 of 111) of NSCLCs and 58% (37 of 64) of SCLCs. The rate of positivity increased significantly with increasing stage (stages I and II, 45%; stage III, 54%; stage IV, 66%), but not with other clinical parameters. Ninety-five patients were evaluated for their response to chemotherapy. Positive staining for p53 correlated significantly with unresponsiveness to chemotherapy in NSCLC (response rate of 13 versus 60%; P = 0.006), but not in SCLC (80 versus 57%; P = 0.22). p53 positivity was a statistically significant negative prognostic factor for stage III and stage IV NSCLC (P = 0.02), but not for stage I and stage II NSCLC (P = 0.79). There was no survival difference relative to p53 status in SCLC (P = 0.35). These results indicate that p53 overexpression in TBB specimens predicts poor prognosis and chemoresistance in advanced stage NSCLC.
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PMID:The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer. 981 99

While resistance to chemotherapy is a major problem in lung cancer treatment, there is no useful predictor of treatment response. We thus designed this study to determine the utility of p53 and P-glycoprotein expression in predicting the response to chemotherapy in patients with primary lung cancer, retrospectively. We evaluated transbronchial biopsy (TBB) specimens from 60 patients with lung cancer, who were previously untreated. Formalin-fixed, paraffin-embedded TBB specimens were immunostained using anti-p53 antibody (DO-1) and anti-P-glycoprotein antibody (JSB-1). The positivity of p53 was 63%, and that of P-glycoprotein was 17%. No correlation was observed between p53 and P-glycoprotein immunostaining. Positivity of p53 correlated significantly (P = 0.004) with a lack of response to chemotherapy in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC). In contrast, positivity of P-glycoprotein was correlated with chemotherapy resistance in SCLC (P = 0.003), but not in NSCLC. Multiple logistic regression analysis revealed that positive immunostaining for p53 was a significant risk factor for chemotherapy resistance in NSCLC. These results suggest that immunostaining of p53 and P-glycoprotein for TBB specimens may help to predict response to chemotherapy in NSCLC and SCLC, although the results should be confirmed in a larger, more homogeneous series.
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PMID:Immunohistochemically detected p53 and P-glycoprotein predict the response to chemotherapy in lung cancer. 984 16

The knowledge of specific problems of occupational cancer in Spain is scarce. The environment of the workplace has improved over the last few years after a long period distinguished by bad working conditions, incomplete legislation, and insufficient safety measures and control. It has been estimated that 3,083,479 workers (25.4% of employees) were exposed to carcinogens. The most common occupational exposures to carcinogenic agents were solar radiation, environmental tobacco smoke, silica, and wood dust. The highest number of employees were exposed to silica crystalline (404,729), diesel engine exhaust (274,321), rubber products (99,804), benzene (89,932), ethylene dibromide (81,336), agents used in furniture and cabinet making (72,068), and formaldehyde (71,189). The percentage of total cancer deaths attributed to occupational exposure was 4% (6% in men, 0.9% in women). Compared with other European countries, the incidence of lung cancer and leukemia in Spain are one of the lowest, but it is rapidly increasing. The incidence of urinary bladder and larynx cancer, on the contrary, are one of the highest. Few studies on occupational cancer have been conducted in Spain. The main problems are the availability of death certificates and the quality of the information on occupation in mortality of statistics. It is necessary to improve methods of assessment of exposures using expert hygienists and biologic markers of exposure and diseases. Reduction of cancer by limiting or avoiding exposure to known occupational carcinogens is still necessary.
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PMID:Occupational cancer in Spain. 1035 May 10

Single-strand conformational polymorphism (SSCP) analysis and direct sequencing methods were used to examine lung tumors derived from a cohort of beagle dogs with inhalational exposures to 239PuO2. These exposures were done at Pacific Northwest Laboratories where 18-month-old beagle dogs were given 239PuO2 by single-dose inhalation and allowed to live out their life-spans. Formalin-fixed paraffin-embedded blocks of tissues from 25 dogs exposed to 239PuO2 by aerosol inhalation which later developed lung tumors were available for this study. Two of 25 tumors had mutations within exon 1 of K-ras detected by SSCP analysis. Both mutations were GGT to GAT transitions at codon 12 confirmed by direct sequencing experiments. One was an adenocarcinoma from the medium-high exposure group and the other was a broncheolo-alveolar carcinoma from the medium-low exposure group. The rate of K-ras mutations in plutonium-induced lung tumors described herein (8%) was greater than previously described in canine plutonium-induced lung tumors (0%), but was less than that which we have described in spontaneous canine lung cancer (16%), less than that reported for human spontaneous non-small cell lung cancer (13-36%) and less than that described in rats with spontaneous lung cancer (40%) or lung tumors following 239Pu inhalation exposure (46%).
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PMID:K-ras mutations in 239PuO2 canine lung neoplasms. 1039 46

Cyclin D1 is one of the G1 cyclins that control cell cycle progression by allowing G1 to S transition. Overexpression of cyclin D1 has been postulated to play an important role in the development of human cancers. We have investigated the correlation between cyclin D1 overexpression and known clinicopathological factors and also its prognostic implication on resected non-small-cell lung cancer (NSCLC) patients. Formalin-fixed and paraffin-embedded tumour tissues resected from 69 NSCLC patients between stages I and IIIa were immunohistochemically examined to detect altered cyclin D1 expression. Twenty-four cases (34.8%) revealed positive immunoreactivity for cyclin D1. Cyclin D1 overexpression is significantly higher in patients with lymph node metastasis (50.0% vs 14.4%, P = 0.002) and with advanced pathological stages (I, 10%; II, 53.8%; IIIa, 41.7%, P = 0.048; stage I vs II, IIIa, P = 0.006). Twenty-four patients with cyclin D1-positive immunoreactivity revealed a significantly shorter overall survival than the patients with negativity (24.0 +/- 3.9 months vs 50.1 +/- 6.4 months, P = 0.0299). Among 33 patients between stages I and II, nine patients with cyclin D1-positive immunoreactivity had a much shorter overall survival (29.7 +/- 6.1 months vs 74.6 +/- 8.6 months, P = 0.0066). These results suggest that cyclin D1 overexpression is involved in tumorigenesis of NSCLCs from early stage and could be a predictive molecular marker for poor prognosis in resectable NSCLC patients, which may help us to choose proper therapeutic modalities after resection of the tumor.
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PMID:Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer. 1048 23

Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.
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PMID:Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature. 1152 Dec 32

We reported the technique of pathological diagnosis for minute lung cancer lesion of early stage during operation. Target lesion for our technique may be less than 1 cm in size and not be detected by palpation. Our technique may superior to usual method of frozen section of tissue specimen without fixation. At first, resected lung specimen was fixed by injection of 20% formalin solution subsequent warming by microwave oven for 40 seconds. Almost all lesions may be detected in proper thickness of specimen. Specimen was washed out and steeped in the 20% of sucrose solution for 30 to 60 seconds in order to avoid crystallization of water that was contained within lung specimen. Then thin sliced section of specimen was made by Cryostat in usual method. The minute cancer lesion was able to detect more easy than usual method of making frozen section of specimen. Formalin fixed and sucrose steeped frozen section may be able to evaluate the surgical margin from cancer exactly than the section made by non-fixed specimen.
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PMID:[Contrivance for frozen section diagnosis of early minute lung cancer during operation]. 1159 26

Formaldehyde (HCHO), which has been shown to be a nasal carcinogen in rats and mice, is used widely and extensively in various manufacturing processes. Studies in rhesus monkeys suggest that the lower respiratory tract may be at risk and some epidemiologic studies have reported an increase in lung cancer associated with HCHO; other studies have not. Thus, an assessment of possible human risk to HCHO exposure based on dosimetry information throughout the respiratory tract (RT) is desirable. To obtain dosimetry estimates for a risk assessment, two types of models were used. The first model (which is the subject of another investigation) used computational fluid dynamics (CFD) to estimate local fluxes in a 3-dimensional model of the nasal region. The subject of the present investigation (the second model) applied a 1-dimensional equation of mass transport to each generation of an adult human symmetric, bifurcating Weibel-type RT anatomical model, augmented by an upper respiratory tract. The two types of modeling approaches were made consistent by requiring that the 1-dimensional version of the nasal passages have the same inspiratory air-flow rate and uptake during inspiration as the CFD simulations for 4 daily human activity levels. Results obtained include the following: (1) More than 95% of the inhaled HCHO is predicted to be retained by the RT. (2) The CFD predictions for inspiration, modified to account for the difference in inspiration and complete breath times, are a good approximation to uptake in the nasal airways during a single breath. (3) In the lower respiratory tract, flux is predicted to increase for several generations and then decrease rapidly. (4) Compared to first pulmonary region generation fluxes, the first few tracheobronchial generations fluxes are over 1000 times larger. Further, there is essentially no flux in the alveolar sacs. (5) Predicted fluxes based on the 1-dimensional model are presented that can be used in a biologically based dose-response model for human carcinogenesis. Use of these fluxes will reduce uncertainty in a risk assessment for formaldehyde carcinogenicity.
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PMID:Dosimetry modeling of inhaled formaldehyde: the human respiratory tract. 1160 8

Recently, therapies targeting signaling pathways involved in the pathogenesis of different tumors have been developed. Studies have shown that the tyrosine kinase inhibitor STI-571 (Gleevec) is used successfully against tumors expressing the c-kit oncogene, such as gastrointestinal stromal tumors (GISTs). A recent in vitro study also demonstrated an antiproliferative effect of STI-571 on small-cell lung cancer (SCLC) cell lines. To determine the expression of c-kit in SCLC, we retrospectively analyzed presence of c-kit by immunohistochemistry in biopsy samples from patients with SCLCs. Formalin-fixed, paraffin-embedded archival tissue samples from 30 SCLCs were stained with an antibody directed against c-kit (CD117) by immunohistochemistry. Thirty cases of SCLCs, including 17 males (age 44 to 89) and 13 females (age 21 to 85), were examined. Sixteen of 30 (53.3%) SCLCs showed c-kit expression. Kaplan-Meier survival analysis with a log-rank test revealed that patients with c-kit expression had a tendency toward lower survival than c-kit-negative patients (median survival, 6 months versus 31 months, P =.062). Based on previously established anti-c-kit effects of STI-571 on SCLC cell lines and our findings, clinical trials may be considered for selected SCLC patients with c-kit expression. Furthermore, determination of c-kit in SCLC may have a prognostic value in SCLC patients.
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PMID:Analysis of c-kit protein expression in small-cell lung carcinoma and its implication for prognosis. 1450 52

Attempts to cause temporary pore formation of cancer cell membrane and to introduce intracellulary attenuated diphtheria toxin (fDT) following treatment with formaldehyde were performed utilizing high-voltage electric pulses. Human pancreatic cancer cell line (ASPC-1) and lung cancer cell line (PC9) were electroporated in the presence or the absence of fDT. Almost complete inhibition of target cell proliferation was observed when the cells were electroporated (90 V, 10 ms, n = 8) in the presence of fDT, even after washing. Similar marked inhibition of PC9 cell proliferation was obtained when anti-DT antibodies were added after electroporation (EP) instead of washing. These results indicate that the presence of fDT is needed only during the time of EP treatment and the side-effects of the agents can be avoided by specific antibodies.
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PMID:Proliferation inhibition of human cancer cells in combined use of electroporation with attenuated diphtheria toxin. 1462 28


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