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Lung Cancers (lung + cancers)
Kinds of Lung Cancers Selected AbstractsBirth Cohort Effects on Incidence of Lung Cancers: A Population-based Study in Nagasaki, JapanCANCER SCIENCE, Issue 10 2000Hiroshi Soda Smoking prevalence remains high (around 60%) among Japanese males, but smoking initiation among males born in the 1930s decreased by approximately 10% due to economic difficulties following World War II. The present study was designed to examine whether this temporary decline in smoking initiation influenced the subsequent incidence of lung cancers, especially adenocarcinoma. Trends of lung cancer incidence by histological type in both sexes were investigated using data from the population-based cancer registry in Nagasaki, Japan, from 1986 through 1995. During this period, 5668 males and 2309 females were diagnosed as having lung cancer, and the overall incidence of lung cancers among both sexes remained stable. However, males aged 55,59 years showed a decrease in the age-specific incidence of adenocarcinoma and squamous-cell carcinoma (P < 0.05 and P < 0.01, respectively). In birth cohort analyses, the incidence of adenocarcinoma and squamous-cell carcinoma was lower in the 1935,1939 birth male cohort than in the successive cohorts. The incidence of lung cancers among females with low smoking prevalence did not change with birth cohort. The low smoking initiation among the 1935,1939 birth male cohort appeared to have resulted in a decreased incidence of adenocarcinoma and squamous cell carcinoma among middle-aged Japanese males. The present study suggests that smoking prevention has an effect in reducing the incidence of lung adenocarcinoma, as well as squamous-cell carcinoma, among smokers. [source] Gastroesophageal reflux disease and non-small cell lung cancer.DISEASES OF THE ESOPHAGUS, Issue 5 2008Results of a pilot study SUMMARY., The sharp rise in the frequency of adenocarcinoma and relative decrease of squamous cell carcinoma of the respiratory and digestive systems, raises suspicion of a common element in their carcinogenetic cascade, which could result in similar trends in cell,type distribution changes of esophageal and lung cancers. The possible role of chemical irritation caused by gastroesophageal reflux disease (GERD) in non-small cell lung cancer (NSCLC) patients was investigated. There was no significant difference between the adenocarcinoma and the squamous cell carcinoma groups, neither in the composite DeMeester scores nor in any of the separate parameters of the complex score investigated. However, the ratio of detected gastroesophageal reflux cases was considerably higher than in the average population. This factor may be one element of a multifactorial cancer promotion. [source] 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteinsELECTROPHORESIS, Issue 23 2007Paul Dowling Dr. Abstract Most lung cancers are diagnosed too late for curative treatment to be possible, therefore early detection is crucial. Serum proteins are a rich source of biomarkers and have the potential to be used as diagnostic and prognostic indicators for lung cancer. In order to examine differences in serum levels of specific proteins associated with human lung squamous carcinoma, immunodepletion of albumin and five other high-abundant serum proteins followed by 2-D difference gel electrophoresis (DIGE) analysis and subsequent MS was used to generate a panel of proteins found to be differentially expressed between the cancer and normal samples. Proteins found to have increased abundance levels in squamous cell carcinoma sera compared to normal sera included apolipoprotein A-IV precursor, chain F; human complement component C3c, haptoglobin, serum amyloid A protein precursor and Ras-related protein Rab-7b. Proteins found to have lower abundance levels in squamous cell carcinoma sera compared to normal sera included alpha-2-HS glycoprotein, hemopexin precursor, proapolipoprotein, antithrombin III and SP40; 40. The data presented here demonstrate that high-abundant protein removal combined with 2-D DIGE is a powerful strategy for the discovery of potential biomarkers. The identification of lung cancer-specific biomarkers is crucial to early detection, which in turn could lead to a dramatic increase in survival rates. [source] Alternative splicing of MDM2 mRNA in lung carcinomas and lung cell linesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Mao-Wen Weng Abstract The MDM2 gene is overexpressed in several human tumors and its product may be processed into various isoforms. Recently, alternative splicing forms of MDM2 mRNA have been detected in various types of tumors. In this study, lung tissue from human non small cell lung cancers was examined for MDM2 mRNA splicing variants by nested RT-PCR. Of the 117 lung cancer tissue samples analyzed, a total of 31 (26.5%) had splice variants for the MDM2 gene, while 59 (50.4%) had undetectable levels of MDM2 transcript. Further analysis indicated that the predominant variant for 26 of the 31 samples with alternative MDM2 splicing products was MDM2-657, a splice variant lacking exons 3,11. Significant associations were found between the frequency of alternative splicing and the gender and smoking habits of the patients. Approximately 36% of male patients had alternative splicing of MDM2 compared with only 9.5% of female patients (P = 0.008); 44.2% of the smoker patients had alternative MDM2 splice forms versus 16.2% of nonsmokers (P = 0.003). Furthermore, most normal lung cell lines examined possessed only full-length MDM2 mRNA, while among several lung cancer cell lines, only H1355 and CaLu-1 cells lacked alternatively spliced MDM2 transcripts. When H1355 cells were treated in vitro with the cigarette smoke carcinogen benzo[a]pyrene (B[a]P) or the B[a]P metabolite benzo[a]pyrene diolepoxide (BPDE), three MDM2 splicing products were detected by nested RT-PCR. Finally, with the use of several specific inhibitors, we found that BPDE-induced MDM2 mRNA alternative splicing in H1355 cells may occur through the PI3K or MAPK pathway. Overall, our results suggest that carcinogens present in cigarette smoke increase the risk of alternative MDM2 splicing, which is highly associated with lung cancer. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] Cutaneous T-cell lymphoma-associated lung cancers show chromosomal aberrations differing from primary lung cancerGENES, CHROMOSOMES AND CANCER, Issue 2 2008Sonja Hahtola Cutaneous T-cell lymphoma (CTCL) patients have an increased risk of certain secondary cancers, the most common of which are lung cancers, especially small cell lung cancer. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, we analyzed genomic aberrations in CTCL-associated and reference lung cancer samples. DNA derived from microdissected lung cancer cells of five CTCL-associated lung cancers and five reference lung cancers without CTCL association was analyzed by comparative genomic hybridization (CGH). Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and loss of heterozygosity (LOH) analysis were performed for selected genes. In CTCL-associated lung cancer, CGH revealed chromosomal aberrations characterizing both lung cancer and CTCL, but also losses of 1p, and 19, and gains of 4q and 7, hallmarks of CTCL. LOH for the CTCL-associated NAV3 gene was detected in two of the four informative primary lung cancers. FISH revealed increased copy number of the KIT gene in 3/4 of CTCL-associated lung cancers and 1/5 of primary lung cancers. PDGFRA and VEGFR2 copy numbers were also increased. IHC showed moderate KIT expression when the gene copy number was increased. CTCL-associated lung cancer shows chromosomal aberrations different from primary lung cancer, especially amplifications of 4q, a chromosome arm frequently deleted in the latter tumor type. Copy numbers and expression of selected genes in chromosome 4 differed between CTCL-associated and reference lung cancers. These preliminary observations warrant further prospective studies to identify the common underlying factors between CTCL and CTCL-associated lung cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2007 Wiley-Liss, Inc. [source] ERG rearrangement in small cell prostatic and lung cancerHISTOPATHOLOGY, Issue 7 2010Veit J Scheble Scheble V J, Braun M, Wilbertz T, Stiedl A-C, Petersen K, Schilling D, Reischl M, Seitz G, Fend F, Kristiansen G & Perner S (2010) Histopathology,56, 937,943 ERG rearrangement in small cell prostatic and lung cancer Aims:, Small cell prostatic cancer is a rare but aggressive disease. Currently, its histogenetic origin is unclear and its distinction from metastatic small cell lung cancer is challenging. The aim of our study was to determine whether the ERG rearrangement commonly observed in acinar prostatic cancer can distinguish small cell prostatic cancer from small cell lung cancer samples. Methods and results:, We assessed 15 small cell prostatic cancers and 22 small cell lung cancers for ERG rearrangement using fluorescence in situ hybridization. Commonly used and novel immunohistochemical markers (i.e. androgen receptor, calcium activated nucleotidase 1, Golgi phosphoprotein 2, prostate-specific antigen, prostate-specific membrane antigen, CD56, epithelial membrane antigen, thyroid transcription factor 1, chromogranin A, synaptophysin and Ki67) were further studied. ERG rearrangement occured in 86% of small cell prostatic cancers but in none of the small cell lung cancers and was the best marker to differentiate between both tumours (P < 0.0001). Conclusions:, The ERG rearrangement is commonly observed in small cell prostatic cancer, supporting the hypothesis that ERG rearrangement occurs in aggressive prostatic cancers. Furthermore, the ERG rearrangement is the most significant marker to differentiate between small cell prostatic cancer and small cell lung cancer. Moreover, our data suggest that small cell prostatic cancer is not a tumour entity on its own, but a dedifferentiated variant of common acinar prostatic cancer. [source] A critical appraisal of prognostic and predictive factors for common lung cancersHISTOPATHOLOGY, Issue 7 2006F B J M Thunnissen The outlook for patients with lung cancer remains poor despite advances in the understanding of the pathology and biology of this disease. To optimize treatment protocols prognostic data are essential. The current era with molecular research on mRNA expression analysis and proteomics will lead to a plethora of new molecular markers, which are likely to be correlated, at least in part, with each other and with disease activity, progression and survival. However, although the number of prognostic factors analysed in published systematic reviews on lung cancer is large, the scope of these factors in individual studies is often narrow. In daily practice prognostic factors other than general TNM staging are not implemented. To assess the efficacy of new prognostic factors for the management of individual patients with non-small cell lung cancer, studies with clinically relevant modelling are required. In this review arguments are provided to use a model combining radiological and histopathological growth rate, histopathological diagnosis and molecular characteristics as markers for metastatic capacity, tumour volume doubling time and expected response to targeted therapy. This may reveal time-related predictive information useful for treatment guidance of the individual patient. [source] The current status of targeted therapy for non-small cell lung cancerINTERNAL MEDICINE JOURNAL, Issue 9 2010H. Francis Abstract Lung cancer accounts for more cancer-related deaths than any other malignancy in Australia and worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers and is associated with a 5-year survival of only 15%. Treatment with platinum-based doublets in the first-line setting and single agent chemotherapy in the second-line setting has improved survival and quality of life in patients with NSCLC. However, the benefits associated with chemotherapy are modest and serve to stress the need for novel therapeutic approaches. In the last decade a range of targeted therapies has been evaluated in NSCLC. Dramatic and often durable responses were seen in patients treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib particularly in females, non-smokers, patients of East Asian ethnicity and those with adenocarcinomas , a group subsequently found to be enriched for tumours with activating EGFR mutations. Large randomized phase III trials have since established a role for EGFR TKI in the second- and third-line setting as well as a potential role for the monoclonal antibodies bevacizumab and cetuximab, directed at vascular endothelial growth factor and EGFR, respectively, in the combination with chemotherapy in the first-line setting. Recently it has been shown that patients with EGFR mutations may benefit from gefitinib in the first-line setting. Other promising agents under evaluation are inhibitors of the insulin-like growth factor-1 receptor and inhibitors of recently described ALK gene rearrangements. [source] MicroRNA-34a is an important component of PRIMA-1-induced apoptotic network in human lung cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Wenrui Duan Abstract Restoration of p53 function in tumor cells would be an attractive strategy for lung cancer therapy because p53 mutations are found in more than 50% of lung cancers. The small molecule PRIMA-1 has been shown to restore the tumor suppression function of p53 and to induce apoptosis in human tumor cells. The mechanism of apoptosis induced by PRIMA-1 remains unclear. We investigated the effects of PRIMA-1 in apoptosis with Western immunoblot analysis, TaqMan microRNA real-time PCR, cell viability analysis and flow cytometry using human lung cancer cell lines containing mutant (H211 and H1155), wild-type (A549) or null (H1299) p53. PRIMA-1 induced massive apoptosis in the H211 and H1155 cells, but was less toxic to the A549 and H1299 cells. Western immunoblot analysis showed cleavage of PARP in H211 and H1155 cells but not in A549 and H1299 cells following treatment with PRIMA-1. In addition, p53 protein was also phosphorylated in H211 and H1155 cells. TaqMan microRNA assay showed that the expression of microRNA-34a was increased in the H211 and H1155 cells posttreatment. Knockdown microRNA-34a decreased the rate of apoptosis caused by PRIMA-1. The above results suggest that microRNA-34a is one of the important components of PRIMA-1-induced apoptotic network in the cancer cells harboring mutant p53. [source] Frequency of and variables associated with the EGFR mutation and its subtypesINTERNATIONAL JOURNAL OF CANCER, Issue 3 2010Tomoaki Tanaka Mutation in the epidermal growth factor receptor (EGFR) is frequently seen in non-small cell lung cancers (NSCLCs), especially in Asian females with adenocarcinoma. The frequency of mutation and the factors associated requires to be elucidated by analyzing a large number of consecutive clinical samples. We summarized the result of the EGFR mutation analysis for 1,176 patients performed at the time of diagnosis or relapse. The PNA-LNA PCR clamp, a highly sensitive detection method for the EGFR mutation, was employed. For fresh cases a portion of samples isolated to establish the diagnosis of lung cancer was used. For cases with a relapsed disease archival tissue were tested. The variables associated with the EGFR mutation after removing the confound factors were investigated by the logistic analysis using the samples collected in our university (n = 308) where detailed information on patients were available. The frequency of the EGFR mutation and its subtypes were investigated using all samples (n = 1,176). The EGFR mutation was significantly associated with adenocarcinoma (p = 0.006) and light-smoking (p < 0.0001), but not gender. The deletions in exon 19 were more frequently associated with male gender while exon 21 deletions were with female gender (p = 0.0011). The overall frequency of the EGFR mutation was 31%. Our result suggests that the female predominance in the EGFR mutation rate is a reflection of a higher frequency of adenocarcinoma in females. The gender difference in the mutation subtypes may provide a clue for the mechanism of the occurrence of the EGFR mutation. [source] Reduced expression of MYO18B, a candidate tumor-suppressor gene on chromosome arm 22q, in ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Nozomu Yanaihara Abstract Allelic imbalance on chromosome arm 22q has been detected in 50,70% of ovarian cancers, suggesting the presence of a tumor-suppressor gene on this chromosome arm that is involved in ovarian carcinogenesis. Recently, we isolated a candidate tumor-suppressor gene, MYO18B, at 22q12.1, which is deleted, mutated and hypermethylated in approximately 50% of lung cancers. In our study, we analyzed genetic and epigenetic alterations of the MYO18B gene in ovarian cancers. Missense MYO18B mutations were detected in 1 of 4 (25%) ovarian cancer cell lines and in 1 of 17 (5.9%) primary ovarian cancers. MYO18B expression was reduced in all 4 ovarian cancer cell lines and in 12 of 17 (71%) of primary ovarian cancers. MYO18B expression was restored by treatment with 5-aza-2,-deoxycytidine and/or trichostatin A in 3 of 4 cell lines with reduced MYO18B expression, and hypermethylation of the promoter CpG island for MYO18B was observed in 2 of these 3 cell lines. Its hypermethylation was also observed in 2 of 15 (13%) primary ovarian cancers. Thus, it was indicated that MYO18B expression is reduced in a considerable fraction of ovarian cancers by several mechanisms, including hypermethylation, while the MYO18B gene is mutated in a small subset of ovarian cancers. The present results suggest that MYO18B alterations, including both epigenetic and genetic alterations, play an important role in ovarian carcinogenesis. © 2004 Wiley-Liss, Inc. [source] Diagnosis of recurrent lung cancer in the mediastinum using endosonographically guided fine-needle aspiration biopsyJOURNAL OF CLINICAL ULTRASOUND, Issue 4 2009Sandeep Singh MD Abstract Endoscopic sonography is a well-established tool for the diagnosis and staging of gastrointestinal malignancies. It has been found to be of increasing utility in the diagnosis and management of lung cancers. We report a case of recurrent lung cancer presenting 4 years after initial diagnosis and treatment, in which endoscopic sonography was used to guide the fine-needle aspiration biopsy. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2009 [source] The influence of cytosine methylation on the chemoselectivity of benzo[a]pyrene diol epoxide-oligonucleotide adducts determined using nanoLC/MS/MSJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2009James Glick Abstract Benzo[a]pyrene is a major carcinogen implicated in human lung cancer. Almost 60% of human lung cancers have a mutation in the p53 tumor suppressor gene at several specific codons. An on-line nanoLC/MS/MS method using a monolithic nanocolumn was applied to investigate the chemoselectivity of the carcinogenic diol epoxide metabolite, ( ± )-(7R,8S,9S,10R)-benzo[a]pyrene 7,8-diol 9,10-epoxide [( ± )- anti -benzo[a]pyrene diol epoxide (BPDE)], which was reacted in vitro with a synthesized 14-mer double stranded oligonucleotide (5,-ACCCG5CG7TCCG11CG13C-3,/5,-GCGCGGGCGCGGGT-3,) derived from the p53 gene. This sequence contained codons 157 and 158, which are considered mutational ,hot spots' and have also been reported as chemical ,hot spots' for the formation of BPDE-DNA adducts. In evaluating the effect of cytosine methylation on BPDE-DNA adduct binding, it was found that codon 156, containing the nucleobase G5 instead of the mutational hot spot codons 157 (G7) and 158 (G11), was the preferential chemoselective binding site for BPDE. In all permethylated cases studied, the relative ratio for adduction was found to be G5, G11 > G13 > G7. Permethylation of CpG dinucleotide sites on either the nontranscribed or complementary strand did not change the order of sequence preference but did enhance the relative adduction level of the G11 CpG site (codon 158) approximately two-fold versus the unmethylated oligomer. Permethylation of all CpG dinucleotide sites on the duplex changed the order of relative adduction to G5, G7 > G11 > G13. The three- to four-fold increase in adduction at the mutational hot spot codon 157 (G7) relative to the unmethylated or single-stranded permethylated cases suggests a possible relationship between the state of methylation and adduct formation for a particular mutation site in the p53 gene. Using this method, only 125 ng (30 pmol) of adducted oligonucleotide was analyzed with minimal sample cleanup and high chromatographic resolution of positional isomers in a single chromatographic run. Copyright © 2009 John Wiley & Sons, Ltd. [source] Bone resorption activity of osteolytic metastatic lung and breast cancersJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2004Lih-Yuann Shih Abstract Production of bone resorption mediators and bone resorption activity were compared among osteolytic metastatic cancers, normal bone tissues, and soft tissue metastatic cancers to search for the possible factors leading to cancer-induced bone resorption. Twenty-five patients with untreated osteolytic metastatic breast or non-small cell lung cancers consisted of the study group. Normal bone tissues obtained from the same patient were used as internal controls; and tumor tissues from patients with soft tissue metastasis were used as external controls. Serum and urinary bone turnover markers were measured. Tissues harvested during surgery were subjected to tissue culture. The levels of prostaglandin E2 (PGE2), tumor necrosis factor-, (TNF-,), and interleukin-6 (IL-6) in the supernatant after 72 h of culture were measured. Bone resorption activity was measured by calcium release from cultured calvarias, and bone volume as well as osteoclast number in bone sections. Patients with osteolytic metastatic cancers showed significantly decreased serum osteocalcin, increased serum alkaline phosphatase, and urinary deoxypyridinoline levels. Osteolytic metastatic cancers produced significantly more PGE2 than both controls. Conditioned medium from osteolytic metastatic tumors showed significantly enhanced bone resorption activity, and indomethacin significantly reduced this activity. Levels of PGE2, and bone resorption activity increased in osteolytic tumor tissues than soft tissue metastatic tissues in the same patient indicated that the same tumor cells might respond differently to different microenvironments. Our observation showed that PGE2 was produced by osteolytic metastatic cancers and stimulated bone resorption in mice calvarias. PGE2 inhibitor may be applicable in reducing bone resorption by osteolytic metastatic cancers. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Risk factors and incidence of de novo malignancy in liver transplant recipients: a systematic reviewLIVER INTERNATIONAL, Issue 9 2010Eric Chak Abstract Orthotopic liver transplant (OLT) is an established life saving procedure for both acute and chronic liver failure, but incidences and risk factors for development of these malignancies are yet to be established. To determine the incidences and risk factors associated with de novo malignancy after OLT. We performed a systematic review of relevant epidemiological studies available on MEDLINE, which provided information on the incidences and risk factors for the development malignancies in adult OLT recipients published from 1983 to 2009. All data was compiled from retrospective studies. Independent risk factors for the development of de novo malignancy in adult OLT recipients were identified to be statistically significant including immunosuppression, hepatitis C virus infection, smoking, alcoholic cirrhosis and sun exposure. OLT recipients with smoking and alcohol history are of particular risk for head and neck and lung cancers. Primary sclerosing cholangitis and inflammatory bowel disease were found to be independent risk factors for colon cancer. Adult OLT recipients are at increased risk for the development of post-transplant malignancies and obviates the need for surveillance protocols that are safe and cost-effective. OLT recipients should be advised on taking proper precautions in the sun, smoking cessation, and eliminating alcohol consumption. Given the emergence of alcoholic cirrhosis as a leading indication for liver transplantation, the early detection of lung and head and neck cancers is of particular importance. [source] HMGA2 overexpression in non-small cell lung cancerMOLECULAR CARCINOGENESIS, Issue 7 2007Britta Meyer Abstract Lung cancer is still the leading cause of death from cancer worldwide primarily because of the fact that most lung cancers are diagnosed at advanced stages. Overexpression of the high mobility group protein HMGA2 has been observed in a variety of malignant tumors and often correlates with poor prognosis. Herein, HMGA2 expression levels were analyzed in matching cancerous and non-cancerous lung samples of 17 patients with adenocarcinoma (AC) and 17 patients with squamous cell carcinoma (SCC) with real-time quantitative RT-PCR (qRT-PCR). Transcript levels were compared to results obtained by immunohistochemistry (IHC). HMGA2 expression was detectable by qRT-PCR in all samples tested and varied from 5422 to 16,991,545 copies per 250 ng total RNA in the carcinoma samples and from 289 to 525,947 copies in the non-cancerous tissue samples. In 33/34 non-small cell lung cancer (NSCLC) samples tested, an overexpression of HMGA2 was revealed with statistically highly significant differences between non-neoplastic and tumor samples for both AC (P,<,0.0001) as well as for SCC (P,<,0.0001). Expression varies strongly and is increased up to 911-fold for AC and up to 2504-fold for SCC, respectively, with statistically significant higher increase in SCC (P,<,0.05). The results presented herein indicate that HMGA2 overexpression is a common event in NSCLC and could serve as molecular marker for lung cancer. © 2007 Wiley-Liss, Inc. [source] Loss of Betaig-h3 protein is frequent in primary lung carcinoma and related to tumorigenic phenotype in lung cancer cellsMOLECULAR CARCINOGENESIS, Issue 2 2006Yongliang Zhao Abstract Betaig-h3 as a secreted protein induced by transforming growth factor-, has been suggested to modulate cell adhesion and tumor formation. Although we have previously shown that downregulation of Betaig-h3 gene is involved in the cellular transformation of human bronchial epithelial cells induced by radiation, its regulation in primary human lung cancers is not clearly understood. In this study, Betaig-h3 expression was studied in 130 primary human lung carcinomas by immunohistochemistry. Betaig-h3 protein was absent or reduced by more than two-fold in 45 of 130 primary lung carcinomas relative to normal lung tissues examined. Recovery of Betaig-h3 expression in H522 lung cancer cells lacking endogenous Betaig-h3 protein significantly suppressed their in vitro cellular growth and in vivo tumorigenicity. In addition, parental H522 cancer cells are resistant to the etoposide induced apoptosis compared with normal human bronchial epithelial cells. However, recovery of Betaig-h3 expression in H522 cancer cells results in significantly higher sensitivity to apoptotic induction than parental tumor cells. IGFBP3 is upregulated in Betaigh3-transfected H522 cells that may mediate the apoptotic sensitivity and antitumor function of Betaig-h3 gene. These observations demonstrate that downregulation of Betaig-h3 gene is a frequent event and related to the tumor progression in human lung cancer. © 2005 Wiley-Liss, Inc. [source] Inorganic arsenic as a developmental toxicant: In utero exposure and alterations in the developing rat lungsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2009Jay S. Petrick Abstract In the present study, we characterize the toxic effects of in utero arsenic exposure on the developing lung. We hypothesize that in utero exposure to inorganic arsenic through maternal drinking water causes altered gene and protein expression in the developing lung, indicative of downstream molecular and functional changes. From conception to embryonic day 18, we exposed pregnant Sprague-Dawley rats to 500 ppb arsenic (as arsenite) via the drinking water. Subtracted cDNA libraries comparing control to arsenic exposed embryonic lungs were generated. In addition, a broad Western blot analysis was performed to identify altered protein expression. A total of 59 genes and 34 proteins were identified as being altered. Pathway mapping and analysis showed that cell motility was the process most affected. The most likely affected pathway was alteration in integrin signaling through the ,-catenin pathway, altering c-myc. The present study shows that arsenic induces alterations in the developing lung. These data may be useful in the elucidation of molecular targets and biomarkers of arsenic exposure during lung development and may aid in understanding the etiology of arsenic induced adult respiratory disease and lung cancers. [source] Sodium/iodide symporter expression in primary lung cancer and comparison with glucose transporter 1 expressionPATHOLOGY INTERNATIONAL, Issue 2 2009Do Y. Kang The aim of the present study was to evaluate the expression of sodium/iodide symporter (NIS) and glucose transporter 1 (Glut1) in 139 primary lung cancers on immunohistochemistry, and to determine the diagnostic utility of NIS as an imaging reporter. Immunoreactivity for NIS and Glut1 was noted in 75 (54.0%) and 72 (51.8%) of the 139 cases, respectively. Analysis of NIS expression on Western blot confirmed the immunohistochemistry. NIS expression was significantly higher in the adenocarcinomas than in the other carcinomas, and Glut1 expression was significantly higher in the squamous cell carcinomas than in the other carcinomas (each P < 0.0001). The frequency of NIS expression in those carcinomas lacking Glut1 expression was significantly higher than in those with Glut1 expression (P = 0.012). Among 64 adenocarcinomas, the frequency of the NIS(+)/Glut1(,) phenotype was 61.0%, which was the most frequent expression pattern. By studying the expression pattern of NIS in lung cancer, the present paper provides a helpful foundation for examining the potential utility of NIS-mediated radioiodide as an alternative diagnostic modality, especially for the management of patients with lung adenocarcinoma lacking Glut1 expression. [source] Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastasesPATHOLOGY INTERNATIONAL, Issue 4 2007Yoshin Adachi In lung cancers, lymph node metastasis of cancer cells is one of the most important prognostic factors, and lymphatic vessel invasion (LVI) is very important in the stage preceding lymph node metastases. Recently, it has been reported that lymphatic vessel density (LVD) is associated with lymph node metastasis. The aim of the present study was to evaluate the relationship between LVD and LVI based on the immunohistochemical expression of podoplanin or D2-40, which are new specific markers for lymphatic endothelium. Using 76 cases of pulmonary adenocarcinoma, the relationship between LVD and LVI, lymph node metastases, vascular endothelial growth factor C (VEGF-C), VEGF-D or hepatocyte growth factor (HGF) expression was investigated. LVD was significantly associated with LVI, lymph node metastases and VEGF-D expression. LVI was also associated with lymph node metastases, histological subtype, VEGF-C or VEGF-D expression. High LVD, induced by VEGF-C or VEGF-D expression of cancer cells, is a good indicator of lymphatic metastases and LVI in pulmonary adenocarcinoma. [source] Immunohistochemical expression of aminopeptidase N (CD13) in human lung squamous cell carcinomas, with special reference to Bestatin adjuvant therapyPATHOLOGY INTERNATIONAL, Issue 6 2006Eiji Ichimura Bestatin, a specific inhibitor of aminopeptidase N (CD13), has been reported to prolong survival time in patients with completely resected stage I lung squamous cell carcinoma. Considering the antitumor mechanism of Bestatin, it is interesting to know whether CD13 is expressed in human lung squamous cell carcinoma. The immunohistochemical expression of CD13 was examined in human lung carcinoma and the question of whether CD13 was immunohistochemically expressed in the interstitial tissue was investigated, mainly in the fibroblasts and blood vessels, surrounding the tumor nests of various kinds of non-small cell lung cancers, especially of squamous cell carcinomas. In Japanese squamous cell carcinoma of the lung, 38 (61.3%) out of 62 cancers were positively stained in the same manner on immunohistochemistry for CD13. The area of interstitial tissue positively stained for CD13 varied depending on the case. To confirm the cell nature of the interstitial tissue with CD13 positivity, double immunohistochemistry using CD34 and ,-smooth muscle actin was performed. Double immunohistochemistry showed that the majority of CD13-positive cells were slender fibroblastic cells around the blood vessels and some endothelial cells. [source] Lung adenocarcinoma associated with atypical adenomatous hyperplasia.PATHOLOGY INTERNATIONAL, Issue 12 2003A clinicopathological study with special reference to smoking, cancer multiplicity Atypical adenomatous hyperplasia (AAH) of the lung has been proposed as a possible precursor lesion of adenocarcinoma of the lung. In the present study, we sought to clarify the clinicopathological characteristics of lung adenocarcinoma cases associated with AAH, with special reference to tobacco smoking and the presence of multiple primary carcinomas of pulmonary and extrapulmonary organs. We examined 123 surgically resected lung adenocarcinomas and conducted histopathological diagnoses for AAH and multiple primary pulmonary carcinomas. Clinicopathological characteristics such as age, sex, smoking index, survival, and the presence of extrapulmonary primary carcinomas were obtained from clinical records, and the associations among these factors were examined statistically. Sixteen lung adenocarcinoma patients had accompanying AAH (the AAH group) and 107 cases did not (the NAAH group). The incidence of primary carcinomas in extrapulmonary organs was higher in the AAH group (37.5%; 6/16) than in the NAAH group (12.5%; 13/107) (P = 0.01). Multiple primary lung cancers tended to be more frequent in the AAH group, but the difference was not statistically significant (P = 0.07). Although there was no difference in tobacco smoking between the two groups, all eight cases with multiple primary lung carcinomas were smokers. Furthermore, multiple primary lung carcinomas were found more frequently in smokers of the AAH group (37.5%; 3/8) than in the smokers of the NAAH group (7.2%; 5/69) (P = 0.04). The results suggested that constitutional or genetic factors might predispose patients to the development of AAH together with extrapulmonary primary carcinomas, and that smoking might contribute to the development of multiple primary lung adenocarcinomas, especially in patients with pre-existing AAH. [source] Identification of occupational cancer risk in British Columbia: A population-based case,control study of 2,998 lung cancers by histopathological subtypeAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 3 2009Amy C. MacArthur MHSc Abstract Background Few studies have investigated occupational lung cancer risk in relation to specific histopathological subtypes. Methods A case,control study was conducted to evaluate the relationship between lung cancer and occupation/industry of employment by histopathological subtype. A total of 2,998 male cases and 10,223 cancer controls, diagnosed between 1983 and 1990, were identified through the British Columbia Cancer Registry. Matched on age and year of diagnosis, conditional logistic regression analyses were performed for two different estimates of exposure with adjustment for potentially important confounding variables, including tobacco smoking, alcohol consumption, marital status, educational attainment, and questionnaire respondent. Results For all lung cancers, an excess risk was observed for workers in the primary metal (OR,=,1.31, 95% CI, 1.01,1.71), mining (OR,=,1.53, 95% CI, 1.20,1.96), machining (OR,=,1.33, 95% CI, 1.09,1.63), transport (OR,=,1.50, 95% CI, 1.08,2.07), utility (OR,=,1.60, 95% CI, 1.22,2.09), and protective services (OR,=,1.27, 95% CI, 1.05,1.55) industries. Associations with histopathological subtypes included an increased risk of squamous cell carcinoma in construction trades (OR,=,1.25, 95% CI, 1.06,1.48), adenocarcinoma for professional workers in medicine and health (OR,=,1.73, 95% CI, 1.18,2.53), small cell carcinoma in railway (OR,=,1.62, 95% CI, 1.06,2.49), and truck transport industries (OR,=,1.51, 95% CI, 1.00,2.28), and large cell carcinoma for employment in the primary metal industry (OR,=,2.35, 95% CI, 1.11,4.96). Conclusions Our results point to excess lung cancer risk for occupations involving exposure to metals, polyaromatic hydrocarbons and asbestos, as well as several new histopathologic-specific associations that merit further investigation. Am. J. Ind. Med. 52:221,232, 2009. © 2008 Wiley-Liss, Inc. [source] Gene amplification of the transcription factor DP1 and CTNND1 in human lung cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2010Sandra D. Castillo Abstract The search for novel oncogenes is important because they could be the target of future specific anticancer therapies. In the present paper we report the identification of novel amplified genes in lung cancer by means of global gene expression analysis. To screen for amplicons, we aligned the gene expression data according to the position of transcripts in the human genome and searched for clusters of over-expressed genes. We found several clusters with gene over-expression, suggesting an underlying genomic amplification. FISH and microarray analysis for DNA copy number in two clusters, at chromosomes 11q12 and 13q34, confirmed the presence of amplifications spanning about 0.4 and 1 Mb for 11q12 and 13q34, respectively. Amplification at these regions each occurred at a frequency of 3%. Moreover, quantitative RT,PCR of each individual transcript within the amplicons allowed us to verify the increased in gene expression of several genes. The p120ctn and DP1 proteins, encoded by two candidate oncogenes, CTNND1 and TFDP1, at 11q12 and 13q amplicons, respectively, showed very strong immunostaining in lung tumours with gene amplification. We then focused on the 13q34 amplicon and in the TFDP1 candidate oncogene. To further determine the oncogenic properties of DP1, we searched for lung cancer cell lines carrying TFDP1 amplification. Depletion of TFDP1 expression by small interference RNA in a lung cancer cell line (HCC33) with TFDP1 amplification and protein over-expression reduced cell viability by 50%. In conclusion, we report the identification of two novel amplicons, at 13q34 and 11q12, each occurring at a frequency of 3% of non-small cell lung cancers. TFDP1, which encodes the E2F-associated transcription factor DP1 is a candidate oncogene at 13q34. The data discussed in this publication have been deposited in NCBIs Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO Series Accession No. GSE21168. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell lineTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006William J. Brackenbury We have shown previously that voltage-gated Na+ channels (VGSCs) are up-regulated in human metastatic disease (prostate, breast and small-cell lung cancers), and that VGSC activity potentiates metastatic cell behaviours. However, the mechanism(s) regulating functional VGSC expression in cancer cells remains unknown. We investigated the possibility of activity-dependent (auto)regulation of VGSC functional expression in the strongly metastatic Mat-LyLu model of rat prostate cancer. Pretreatment with tetrodotoxin (TTX) for 24,72 h subsequently suppressed peak VGSC current density without affecting voltage dependence. The hypothesis was tested that the VGSC auto-regulation occurred via VGSC-mediated Na+ influx and subsequent activation of protein kinase A (PKA). Indeed, TTX pretreatment reduced the level of phosphorylated PKA, and the PKA inhibitor KT5720 decreased, whilst the adenylate cyclase activator forskolin and the Na+ ionophore monensin both increased the peak VGSC current density. TTX reduced the mRNA level of Nav1.7, predominant in these cells, and VGSC protein expression at the plasma membrane, although the total VGSC protein level remained unchanged. TTX pretreatment eliminated the VGSC-dependent component of the cells' migration in Transwell assays. We concluded that the VGSC activity in Mat-LyLu rat prostate cancer cells was up-regulated in steady-state via a positive feedback mechanism involving PKA, and this enhanced the cells' migratory potential. [source] Somatic mutations of EGFR, ERBB2, ERBB3 and ERBB4 in juxtamembrane activating domains are rare in non-small cell lung cancersAPMIS, Issue 1 2010SANG WOOK PARK No abstract is available for this article. [source] Patients with bladder and lung cancer: a long-term outcome analysisBJU INTERNATIONAL, Issue 9 2004A. El-Hakim OBJECTIVES To report on patient characteristics, stage of disease and long-term outcome and prognosis of patients with dual bladder and lung cancers, as there is an established increased risk of smoking-related second primary cancers, especially lung cancer, developing in patients with bladder cancer. PATIENTS AND METHODS We reviewed our hospital tumour registry database from 1990 to 2002, and identified 27 patients who had both bladder and lung cancers among 1038 with bladder cancer and 2427 with lung cancer. Seventeen patients had bladder cancer detected before lung cancer (group 1), and the remaining 10 had lung cancer diagnosed first (group 2). RESULTS Group 1 and 2 were comparable in terms of patients' characteristics, mean interval between cancer detection and their use of tobacco. Group 1 patients had a tendency towards more invasive lung cancer at diagnosis than had group 2 patients (11/17 vs 2/10 stage ,,IIB, respectively; P = 0.082). The mean follow-up was 49.8 and 64.5 months for groups 1 and 2, respectively (not significant). The mean (sd) interval to death from the date of diagnosis of lung cancer was 18 (17) months for group 1 and 65 (42) months for group 2 (P < 0.05). CONCLUSIONS Patients with bladder and lung cancer who have lung cancer detected first have a lower lung cancer stage and higher overall survival rate than patients diagnosed with bladder cancer first. [source] Immunohistochemical analysis of CYP2A13 in various types of human lung cancersCANCER SCIENCE, Issue 4 2010Tatsuki Fukami Human CYP2A13, which is expressed in the respiratory tract, is the most efficient enzyme for the metabolic activation of tobacco-specific nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The relevance of CYP2A13 in carcinogenicity and toxicity in the respiratory tract has been suggested, but the expression of CYP2A13 protein in lung cancer tissues remains to be determined. We first prepared a mouse monoclonal antibody against human CYP2A13. The antibody showed no cross reactivity with the other CYP isoforms including CYP2A6. Using the specific antibody, we performed immunohistochemical analysis for human lung carcinomas. In adenocarcinomas (n = 15), all specimens were positive for the staining and five samples showed strong staining. In squamous cell carcinomas (n = 15) and large cell carcinomas (n = 15), each 14 samples were positive for the staining and two and three samples showed strong staining, respectively. In small cell carcinoma samples (n = 15), eight samples were negative for the staining and five samples showed weak or moderate staining. In conclusion, we first found that the expression of CYP2A13 was markedly increased in non-small cell lung carcinomas. The high expression might be associated with the tumor development and progression in non-small cell lung carcinomas. (Cancer Sci 2010; 101: 1024,1028) [source] Soy consumption reduces the risk of non-small-cell lung cancers with epidermal growth factor receptor mutations among JapaneseCANCER SCIENCE, Issue 6 2008Keitaro Matsuo Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs). We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case-control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild-type) and 1765 age-sex matched non-cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild-type NSCLCs, with multivariate-adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50,1.27) and 0.56 (0.34,0.93) relative to those in the lowest tertile (trend P = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis. (Cancer Sci 2008; 99: 1202,1208) [source] Characterization of SEZ6L2 cell-surface protein as a novel prognostic marker for lung cancerCANCER SCIENCE, Issue 8 2006Nobuhisa Ishikawa To identify molecules that might serve as biomarkers or targets for development of novel molecular therapies, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using cDNA microarrays coupled with purification of tumor cells by laser microdissection. A gene encoding seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) protein, was chosen as a candidate for such molecule. Semi-quantitative RT-PCR and western-blot analyses documented increased expression of SEZ6L2 in the majority of primary lung cancers and lung-cancer cell lines examined. SEZ6L2 protein was proven to be present on the surface of lung-cancer cells by flow cytometrical analysis using anti-SEZ6L2 antibody. Immunohistochemical staining for tumor tissue microarray consisting of 440 archived lung-cancer specimens detected positive SEZ6L2 staining in 327 (78%) of 420 non-small cell lung cancers (NSCLCs) and 13 (65%) of 20 small-cell lung cancers (SCLCs) examined. Moreover, NSCLC patients whose tumors revealed a higher level of SEZ6L2 expression suffered shorter tumor-specific survival compared to those with no SEZ6L2 expression. These results indicate that SEZ6L2 should be a useful prognostic marker of lung cancers. (Cancer Sci 2006; 97: 737,745) [source] | ||||||||||||||||||||||||||||