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Abstract: Small cell lung cancer (SCLC) appears to arise from neuroendocrine cells with the potential to differentiate into a variety of lung epithelial cell lineages. In order to investigate molecular events underlying the cell type transition in SCLC, we treated a SCLC cell line H526 with a differentiation inducing agent 5-bromodeoxyuridine (BrdU). The treatment led to a dramatic conversion from suspension cells to adherent cells exhibiting an epithelioid phenotype, which remarkably reduced the ability of colony formation in soft agar and suppressed the tumor growth rate in nude mice. The phenotypic transition was consistent with upregulation of surfactant protein C (SFTPC), thyroid transcription factor 1 (TTF-1), Connexin 26 (Cx26), insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1), as well as homeobox genes LAGY, PITX1, and HOXB2. Our data suggest that BrdU induced cell differentiation could be linked to the development of a less aggressively phenotype in small cell lung cancer. [Copyright &y& Elsevier]

Studies the effect of copper status on specific immune responses of cattle and to determine whether molybdenum and iron-induced copper deficiencies have differential effects on the specific immune function of cattle. Formulation of feed diet; Tabulation on the diet composition; Collection of blood and colostrum samples; Analysis using the greater linear method.

Investigates the effect of copper (Cu) deficiency and copper deficiency combined with high dietary iron (Fe) or molybdenum (Mo) on phagocytic cell function and response of calves to a respiratory disease challenge. Higher leukocyte numbers of calves fed the Mo-supplemented diet as compared to the Cu and Fe-supplemented ones; Neutrophil function.

Aims: Archived tissue blocks preserve the antigenicity of samples for a long time under normal storage conditions, whereas tissue sections may show a diminished immunoreactivity over time. Little is known about the processes responsible for antigenicity loss and how tissue sections should be conserved for extended storage. Oxidation and drying are presumed mechanisms of antigenicity loss. To prove this, degradation of immunoreactivity was provoked by chemical oxidation, photo-oxidation and artificial drying. Methods: First, paraffin sections of an oestrogen receptor (ER) positive breast carcinoma were subjected for variable time periods to H202, ultraviolet A (UVA) irradiation and dry heat (56°C) prior to ER immunohistochemistry. Second, using heat and UVA irradiation several other antigens (ER, PR, HER-2neu, p53, p63, p16, PSA, CK5/6, CK7, CK20, SMA, Fli-1, c-kit, CD20 and EGFR) were tested, using internal control tissue microarray sections. Results: While H202 had no effect on the ER-staining intensity, extended drying showed a detectable decrease in staining after 10 days, and UVA irradiation induced a decrease after 3 days. Entire antigenicity loss was not observed. Except for HER-2neu, PSA and Fli-1, all antigens showed some diminution in antigenicity, but no entire antigenicity loss, after heating and UVA irradiation. Conclusions: This study confirms that photo-oxidation and drying have an influence on immunohistochemistry outcome, and protocols for testing the stability of specific antigens are provided. [ABSTRACT FROM AUTHOR]

We have isolated a novel gene, lung cancer-associated gene Y (LAGY), by suppression subtractive hybridization. The nucleotide sequence of LAGY predicts a small protein of 73 amino acids containing a putative homeobox domain with a molecular mass of 8.1 kD. Multiple-tissue Northern blot analysis revealed that LAGY is present in human placenta, lung, brain, heart and skeletal muscle. Gene mapping locates LAGY on chromosome 4q11–13.1. The expression of LAGY mRNA was widely lost in 18 lung tumor cell lines comprising all major histological types, as shown by Northern blot analysis and semiquantitative reverse transcription-polymerase chain reaction. In an investigation of 72 primary lung tumors, this gene was significantly downregulated in tumors compared to 9 normal lung tissue samples. There was a significant reduction of LAGY expression in squamous cell carcinoma (SCC; n = 27) with increasing grade and stage. No expression was detectable in two high-grade SCCs or two small cell and large cell lung carcinomas (n = 4 for each). In adenocarcinoma (n = 37), expression was reduced; however, this did not reach statistical significance. Since homeodomain-containing genes are known to transcriptionally regulate key cellular processes and are associated with carcinogenesis, we suggest that LAGY might be linked to lung cancer development and progression.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Conventional photoelectron and time-of-flight photoelectron-photoelectron coincidence (TOF-PEPECO) spectra have been measured for the outer valence region of the 1,4-bromofluorobenzene molecule. The photoelectron spectra were recorded using HeIα radiation from a resonance source, and the TOF-PEPECO spectra were recorded using HeIIα radiation from a pulsed resonance source. The former provide energies of the cationic states and the latter of the dicationic states. The spectra are adequately interpreted with the aid of accurate Green’s function calculations, showing very significant correlation effects. The lowest double ionization energy is found at 23.45 eV associated with the (4b1)-2X 1A1 dicationic state. [ABSTRACT FROM AUTHOR]

The study of nuclei in the region around the N = Z doubly-magic nucleus 100Sn has been of long standing interest for the nuclear structure and nuclear astrophysics. Recently, Park et al. have reported on properties of -decaying isomers and isomeric ratios in the vicinity of 100Sn. That experiment was performed at the Radioactive Ion Beam Factory (RIBF) of the RIKEN Nishina Center in Japan as a part of the EURICA campaign. Neutron-deficient nuclei were produced in a fragmentation reaction of a 124Xe primary beam on a 9Be target at an energy of 345 MeV/A. Secondary ions were separated and identified in the BigRIPS fragment separator and implanted in the silicon detector array WAS3ABi. The data presented here were obtained in another experiment performed at the RIBF using the same reaction but slightly different separator settings. New results of ratios of isomeric population and half-lives of -decaying isomers populated in the experiment are presented. [ABSTRACT FROM AUTHOR]

The first evidence for β -delayed proton emission from the 16 + spin gap isomer in 96 Cd is presented. The data were obtained from the Rare Isotope Beam Factory, at the RIKEN Nishina Center, using the BigRIPS spectrometer and the EURICA decay station. βp branching ratios for the ground state and 16 + isomer have been extracted along with more precise lifetimes for these states and the lifetime for the ground state decay of 95 Cd. Large scale shell model (LSSM) calculations have been performed and WKB estimates made for ℓ = 0 , 2 , 4 proton emission from three resonance-like states in 96 Ag, that are populated by the β decay of the isomer, and the results compared to the new data. The calculations suggest that ℓ = 2 proton emission from the resonance states, which reside ∼ 5 MeV above the proton separation energy, dominates the proton decay. The results highlight the importance of core-excited wavefunction components for the 16 + state. [ABSTRACT FROM AUTHOR]

Background: Nuclear structure information for the neutron-rich actinide nuclei is important since it is the benchmark for theoretical models that provide predictions for the heaviest nuclei. Purpose: γ - ray spectroscopy of neutron-rich heavy nuclei in the actinide region. Method: Multinucleon-transfer reactions in 70Zn + 238U and 136Xe + 238U have been measured in two experiments performed at the INFN Legnaro, Italy. In the 70Zn experiment the high-resolution HPGe Clover Array (CLARA) coupled to the magnetic spectrometer PRISMA was employed. In the 136Xe experiment the high-resolution Advanced Gamma Tracking Array (AGATA) was used in combination with PRISMA and the Detector Array for Multinucleon Transfer Ejectiles (DANTE). Results: The ground-state band (g.s. band) of _40U was measured up to the 20+ level and a tentative assignment was made up to the (24+) level. Results from γ γ coincidence and from particle coincidence analyses are shown. Moments of inertia (Mol) show a clear upbend. Evidence for an extended first negative-parity band of 240U is found. Conclusions: A detailed comparison with latest calculations shows best agreement with cranked relativistic Hartree-Bogoliubov (CRHB) calculations for the g.s. band properties. The negative-parity band shows the characteristics of a Kπ n = 0- band based on an octupole vibration. [ABSTRACT FROM AUTHOR]

Background: Multinucleon transfer reactions (MNT) are a competitive tool to populate exotic neutron-rich nuclei in a wide region of nuclei, where other production methods have severe limitations or cannot be used at all. Purpose: Experimental information on the yields of MNT reactions in comparison with theoretical calculations are necessary to make predictions for the production of neutron-rich heavy nuclei. It is crucial to determine the fraction of MNT reaction products which are surviving neutron emission or fission at the high excitation energy after the nucleon exchange. Method: Multinucleon transfer reactions in 136Xe + 238U have been measured in a high-resolution γ-ray/particle coincidence experiment. The large solid-angle magnetic spectrometer PRISMA coupled to the high-resolution Advanced Gamma Tracking Array (AGATA) has been employed. Beamlike reaction products after multinucleon transfer in the Xe region were identified and selected with the PRISMA spectrometer. Coincident particles were tagged by multichannel plate detectors placed at the grazing angle of the targetlike recoils inside the scattering chamber. Results: Mass yields have been extracted and compared with calculations based on the grazing model for MNT reactions. Kinematic coincidences between the binary reaction products, i.e., beamlike and targetlike nuclei, were exploited to obtain population yields for nuclei in the actinide region and compared to x-ray yields measured by AGATA. Conclusions: No sizable yield of actinide nuclei beyond Z=93 is found to perform nuclear structure investigations. In-beam γ-ray spectroscopy is feasible for few-neutron transfer channels in U and the -2p channel populating Th isotopes. [ABSTRACT FROM AUTHOR]

Wild tree resins generate billions of dollars in revenue annually but many species face extinction. The lansan tree Protium attenuatum has disappeared across most of its range as a result of overexploitation for its valuable oleoresin, which is used as incense. This study in Saint Lucia aimed to determine whether lansan resin could be harvested sustainably. Over 34 months, 298 trees were tapped using 10 experimental methods, and compared with 74 controls. Significantly more resin was produced by tapping the same trees repeatedly, tapping trees with a wider girth, cutting the same part of the trunk repeatedly, and, in particular, spraying diluted sulphuric acid on the cut. Applying 5 and 30% sulphuric acid boosted yields by 58 and 134%, respectively, without negative impacts on tree growth, condition or mortality. In contrast, traditional methods used by local tappers were destructive, causing greater decay and infection, slower growth rates and increased mortality. Results show tappers can obtain more resin and maintain healthy populations by tapping mature trees of ≥ 20 cm diameter at breast height, using only one shallow cut per tree (refreshed every 2 weeks) and applying weak sulphuric acid solution. A blind survey found consumers could not distinguish between incense produced with or without this stimulant. A national management plan has been devised whereby tappers will be licensed and trained in the optimal method and granted their own forest coupes to manage under Forestry Department supervision. The methods and findings may guide the sustainable use and conservation of other resin-producing trees. [ABSTRACT FROM PUBLISHER]

The neutron-deficient semimagic (neutron number N = 50) 95Rh nucleus has been produced at high spins using the projectile-target system 40Ca +58Ni at 125 MeV beam energy. The y-decays of levels populated by the 3p fusion evaporation reaction channel were studied using y-y coincidences, and 20 new y-ray transitions involving 15 new positive- and negative-parity states were observed. Spin and parity for many of the excited states were firmly deduced for the first time using the combined directional angular correlation and direction-polarization techniques. The observed structures are discussed within the framework of large-scale shell model calculations. E1 transition strengths were deduced and used together with the results of the shell model calculations to study the contribution of different partic'e-hole configurations, in particular for analyzing contributions from core-excited configurations. [ABSTRACT FROM AUTHOR]

Linear polarization and angular correlations of γ-rays depopulating excited states in the neutron-deficient nucleus 9444Ru50 have been measured, enabling firm spin-parity assignments for several excited states in this nucleus. The deduced multipolarities of strong transitions in the yrast structure were found to be mostly of stretched M1, E1, and E2 types and, in most cases, in agreement with previous tentative assignments. The deduced multipolarity of the 1869 keV and the connecting 257 and 1641 keV transitions indicates that the state at 6358 keV excitation energy has spin parity 12-1 rather than 12+3 as proposed in previous works. The presence of a 12-1 state is interpreted within the framework of large-scale shell-model calculations as a pure proton-hole state dominated by the π(p-11/2⊗g-59/2) and π(p-13/2⊗g-59/2) configurations. A new positive-parity state is observed at 6103 keV and is tentatively assigned as 12+2. The 14-1 state proposed earlier is reassigned as 13-4 and is interpreted as being dominated by neutron particle-hole core excitations. The strengths of several E1 transitions have been measured and are found to provide a signature of core-excited configurations. [ABSTRACT FROM AUTHOR]

Desmosomes are intercellular junctions that confer strong cell–cell adhesion. Altered expression of desmocollin 3 (DSC3), a member of the desmosomal cadherin family, was found in various cancers; however, its functional involvement in carcinogenesis has not yet been elucidated. Expression/localization of DSC3 was analyzed by real-time reverse transcription–PCR, western blotting, immunofluorescence and immunohistochemistry. Methylation status of DSC3 was examined by demethylation tests, methylation-specific PCR and bisulfite sequencing. It turned out that downregulation of DSC3 in lung cancer cells was associated with DNA hypermethylation. In primary lung tumors, DSC3 was a potential diagnostic marker for lung squamous cell carcinoma, and DSC3 DNA hypermethylation was correlated with poor clinical outcome. To investigate the effect of the tumor suppressor gene p53 on DSC3, transient transfection with a wild-type p53-expression vector was performed. Overexpression of p53 resulted in an increased expression of DSC3 in a DSC3-unmethylated lung cancer cell line H2170, but not in H1299, a DSC3-methylated cell line. However, combination of p53 transfection with demethylation agent 5-aza-2ʹ-deoxycytidine treatment led to increased expression of DSC3 in H1299 cells. Furthermore, functional studies after stable transfection of a DSC3 expression vector showed that ectopic expression of DSC3 inhibited cell proliferation, anchorage-independent growth, migration, as well as invasion, and most interestingly led to reduced phosphorylation levels of extracellular signal-regulated kinase1/2. Taken together, our data suggested that DSC3 acts as a novel tumor suppressor gene through inhibition of epidermal growth factor receptor/extracellular signal-regulated kinase signaling in lung cancer cells. [ABSTRACT FROM PUBLISHER]

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor whose pathological diagnosis can be difficult. In the literature two cases of EHE were found to harbor a balanced t(1;3)(p36.3;q25) translocation, suggesting a characteristic chromosomal rearrangement as cause for the development of EHE. In this study, 14 cases of EHE were investigated by interphase fluorescence in situ hybridization (FISH) directed against the translocation breakpoint 1p36.3. A subset of cases was also analyzed by comparative genomic hybridization (CGH) and image cytometry. Five out of eight cases that could be successfully analyzed by FISH harbored a chromosomal break in the 1p36.3 region. The break-apart signals were present in diploid nuclei, and less frequently also in tetraploid nuclei. In the latter, the chromosomal break was present twice, suggesting that polyploidy occurred after the chromosomal alteration. DNA cytometry confirmed that tetraploid cells were present in most examined cases with one case indicating almost equal amounts of diploid and tetraploid tumor cells. CGH revealed single chromosomal imbalances of unclear significance. We could confirm that EHE may harbor a recurrent mutation involving the 1p36.3 chromosomal region thus supporting the notion that the t(1;3)(p36.3;q25) translocation is a relevant genetic finding in this tumor entity. [ABSTRACT FROM AUTHOR]

Objectives: The expression patterns of cytokeratin (CK) filaments in human epithelial neoplasms are complex and distinctive. The aims of this study were to analyze CK expression and to evaluate the diagnostic application of CKs in human non-small cell lung cancer (NSCLC). Methods: mRNA expression of CK5, CK6, CK14, CK15, CK17, and CK19 was analyzed by Northern blotting. Protein expression of CK5/6, CK7, CK14, CK17, and CK18 was evaluated by immunohistochemistry on tissue microarrays. Results: Northern blotting showed that CKs were highly expressed in human bronchial epithelial cells and/or small airway epithelial cells. In NSCLC cell lines, the expression pattern of CKs was heterogeneous. Regarding protein expression of CKs in 95 primary lung tumors, expression of CK5/6, CK14, and CK17 proteins was increased in squamous cell carcinomas compared to adenocarcinomas (ADC; p = 0.001, p = 0.030, and p = 0.001, respectively), and higher expression was significantly associated with lower grading (p = 0.006, p = 0.002, and p = 0.001, respectively), while increased expression of CK7 and CK18 was observed in ADC (p = 0.001, respectively). Conclusions: Our data suggest that CK5/6, CK7, CK14, CK17, and CK18 have diagnostic value in the subclassification of NSCLC. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Aims: The study intended to reveal whether HPV infection is reflected by nuclear morphology and DNA cytometry parameters in head and neck squamous cell carcinomas (HNSCC). Methods: In total, 39 HNSCC were selected for reanalysis by histomorphology applying the core classification, DNA cytometry and HPV detection. For the core classification, HE sections were assessed by a score system to evaluate the nuclear size, the mitosis size, their variabilities and the presence of tripolar or tetrapolar mitoses. HPV was analyzed by consensus PCR followed by a hybridization method for virus typing. Static DNA cytometry was applied on single cell suspension focusing particularly on the parameters DNA modal value, DNA index peak, DNA index mean, 2c deviation index and 5c exceeding rate. Statistical analysis was done by T-test or Fisher''s exact test. Results: The analysis revealed that HPV positive HNSCC had significantly smaller nuclei than HPV negative cases. Increasing values of the nuclear size and mitosis size were significantly associated with higher indices of the DNA cytometry analysis. Conclusions: The study confirms that the core classification can provide information on the ploidy of HNSCC and that HPV positive tumors represent a distinct morphological and genetic carcinoma subtype. [Copyright &y& Elsevier]

DNA amplifications, leading to the overexpression of oncogenes, are a cardinal feature of lung cancer and directly contribute to its pathogenesis. To uncover such novel alterations, we performed an array-based comparative genomic hybridization survey of 128 non-small-cell lung cancer cell lines and tumors. Prominent among our findings, we identified recurrent high-level amplification at cytoband 22q11.21 in 3% of lung cancer specimens, with another 11% of specimens exhibiting low-level gain spanning that locus. The 22q11.21 amplicon core contained eight named genes, only four of which were overexpressed (by transcript profiling) when amplified. Among these, CRKL encodes an adapter protein functioning in signal transduction, best known as a substrate of the BCR-ABL kinase in chronic myelogenous leukemia. RNA-interference-mediated knockdown of CRKL in lung cancer cell lines with (but not without) amplification led to significantly decreased cell proliferation, cell-cycle progression, cell survival, and cell motility and invasion. In addition, overexpression of CRKL in immortalized human bronchial epithelial cells led to enhanced growth factor-independent cell growth. Our findings indicate that amplification and resultant overexpression of CRKL contribute to diverse oncogenic phenotypes in lung cancer, with implications for targeted therapy, and highlight a role of adapter proteins as primary genetic drivers of tumorigenesis. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types. The smallest region of recurrent amplification spanned the homeobox transcription factor TITF1 (thyroid transcription factor 1; also called NKX2-1), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein levels. Small interfering RNA (siRNA)-mediated knockdown of TITF1 in lung cancer cell lines with amplification led to reduced cell proliferation, manifested by both decreased cell-cycle progression and increased apoptosis. Our findings indicate that TITF1 amplification and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer.Oncogene (2008) 27, 3635–3640; doi:10.1038/sj.onc.1211012; published online 21 January 2008 [ABSTRACT FROM AUTHOR]

Insulin-like growth factor binding protein 7 (IGFBP-7) is considered a tumor suppressor in various cancers, but its role in colorectal cancer (CRC) is still uncertain. The aims of this study were to analyze the IGFBP-7 expression, and explore the mechanism responsible for the inactivation of IGFBP-7 in CRC. mRNA expression was studied by RT-PCR and Northern blot analysis of cultured cells. Methylation status was analyzed by treatment with 5-aza-2′-deoxycytidine followed by sequencing of PCR products of sodium bisulfite-treated genomic DNA. IGFBP-7 protein expression was evaluated by immunohistochemistry (IHC) on tissue microarrays. mRNA expression was lost in six out of eight CRC cell lines as compared to normal colon cells. DNA methylation was found in the region of exon 1 and intron 1 of IGFBP-7. In tumor tissue, 107 out of 279 samples showed a negative expression of IGFBP-7 by IHC, which was significantly associated with poor prognosis. The analysis of 37 paired cancerous and normal mucosa samples confirmed the downregulation in the tumors, but revealed variable basal expression levels of IGFBP-7 in normal mucosal samples. DNA methylation is a mechanism responsible for IGFBP-7 gene silencing providing a target for therapeutic intervention of this tumor suppressor gene. [ABSTRACT FROM AUTHOR]

Summary: The PITX1 (pituitary homeobox 1) gene has essential roles in human development and has been considered a tumor suppressor in various cancers. However, in lung cancer the role of PITX1 remains to be elucidated. In this study, we analyzed the expression of PITX1 at both mRNA and protein levels in human lung cancer. The reduced PITX1 expression was found in cancer cell lines test compared to normal human bronchial epithelia cells (HEBC) and small airway epithelia cells (SAEC) by Northern blot analysis and RT-PCR as well as Western blot analysis. In primary lung tissues, PITX1 mRNA was found to be downregulated in the majority of tumors compared with normal lung tissues. An association between the lack of PITX1 mRNA expression and higher tumor grade was observed. A tissue microarray containing 135 primary lung carcinomas was analyzed by immunohistochemistry. Eighty-four cases (62%) exhibited no expression of PITX1 and the lower expression of PITX1 was significantly linked to higher tumor stages. Additionally, PITX1 was found to be upregulated in lung cancer cell lines H2228 and H526 after they were exposed to a differentiation modifying agent 5-bromodeoxyuridine (BrdU). Since homeobox genes are known to transcriptionally regulate key cellular processes and associated with differentiation and carcinogenesis, we suggest that PITX1 might be linked to lung cancer development and progression. [Copyright &y& Elsevier]

Suppression subtractive hybridisation (SSH) was performed comparing normal bronchial epithelial cells with a lung squamous cell carcinoma (SCC) and a metastatic small-cell lung carcinoma (SCLC). The sequence analysis of four cDNA libraries revealed 869 individual sequences. Of these, 342 were tested using northern blots of lung cancer cell lines representing the three major subtypes (SCC, adenocarcinoma, SCLC) which confirmed the differential expression of 236 cDNAs. The extended analysis of 31 randomly chosen fragments confirmed the validity of the approach to identify genes associated with lung cancer development. Additionally, five novel full-length cDNA were isolated encoding the microtubule-associated proteins 1A/1B light chain 3, the epithelial V-like antigen 1 (EVA1), the GTP-binding protein SAR1, a new member of the S100-type calcium binding protein family and a new homeobox-containing gene. [Copyright &y& Elsevier]

Studies the diversity of gene expression in adenocarcinoma of the lung. Morphological classification of the tumors into squamous, large cell, small cell, and adenocarcinoma; Discussion of gene expression analysis.