bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth of lesions of Phytophthoracinnamomi in stems and roots of jarrah (Eucalyptusmarginata) in relation to rainfall and stand density in mediterranean forest of Western Australia
Authors: Bunny F.J. , Crombie D.S. , Williams M.R.
Published: January 2008

The effects of reduced stand density on (i) water status of jarrah (Eucalyptusmarginata Donn ex Sm.) and (ii) growth rate of artificially induced lesions of Phytophthoracinnamomi Rands in phloem of E. marginata were examined. Plots in the high ( > 1100 mm•year−1), intermediate (900–1100 mm•year−1), and low ( < 900 mm•year−1) rainfall zones of the jarrah forest were thinned to controlled fractions of original stand density. Phytophthoracinnamomi lesions in the phloem of stems and roots were established by wound inoculation. Lesions of P. cinnamomi were longer in stems of trees with small water deficits than in trees with larger water deficits. For example, in 1991 at the intermediate rainfall site, water potentials and lesion lengths of trees on unthinned and thinned plots were −1.1 and −0.9 MPa and 23 and 45 cm, respectively. Lesions grew more slowly in roots than in stems (average 10.0 and 26.2 cm, respectively, after 55 days at unthinned high rainfall site in 1991); however, the relative difference between lesions in trees with the highest and lowest water potentials was greater in roots (up to 2.7 times) than in stems. Lesion extension was also affected by summer rainfall, with longer lesions occurring in summers of highest rainfall. Viability of P. cinnamomi in 10-week-old and 1-year-old lesions decreased as tree water deficits increased. Differences in lesion extension between jarrah in different amounts of summer rainfall were largely explained by differences in dawn water potential.
Effects of osmotic potential on virulent and hypovirulent strains of the chestnut blight fungus
Authors: Gao S. , Shain L.
Published: January 2008

Mycelial growth and conidial germination of two virulent and four isogenic hypovirulent strains of Cryphonectriaparasitica (Murr.) Barr were monitored on cornmeal agar media osmotically adjusted with NaCl, KCl, sucrose, or a salt mixture of NaCl–KCl–Na2SO4 of 5:3:2. Mycelial growth generally was not inhibited on KCl or sucrose adjusted media with an osmotic potential above −2.0 MPa. Mycelial growth generally was inhibited at this osmotic potential, however, on those media that contained sodium in the osmoticum. While conidial germination was more sensitive than mycelial growth to sodium, conidia were more tolerant than mycelia to osmotic potentials less than −2.0 MPa when media were adjusted with KCl or sucrose. Conidia of all strains germinated on media adjusted to −6.0 MPa with these two osmotica after incubation for 48 h but not 24 h at 25 °C. Hypovirulent strains generally reacted similarly to their isogenic virulent strains with regard to reduced osmotic potential. Because the lowest osmotic potential of chestnut (Castaneadentata (Marsh.) Borkh.) bark observed in monthly samples was −2.0 MPa (see companion paper), it appears that water stress has little direct impact on the pathogen during pathogenesis.
Sequestration of 137Cs and 90Sr from soil by seedlings of Eucalyptustereticotnis
Authors: Entry James A. , Emmingham William H.
Published: January 2008

The ability of seedlings of Eucalyptustereticornis Smith to accumulate 137Cs and 90Sr, characteristic radioisotopes of nuclear fallout, from contaminated growth medium was tested. All seedlings were grown for 3 months in 165 cm3 of sphagnum peat moss–perlite (1:1 v/v) in a growth chamber before treatment with an isotope. After 1 month of exposure, seedlings had accumulated 31.0% of the 137Cs and 11.3% of the 90Sr originally present in the growth medium, with bioconcentration ratios of 54:1 for 137Cs and 13:1 for 90Sr. Accumulation of 137Cs and 90Sr in plant tissue was correlated curvilinearly with increasing time of exposure and with increasing concentration of radioisotope in the growth medium. Because seedlings of E. tereticornis accumulate these radioisotopes rapidly, they may be valuable in remediation of contaminated soils.
A SUPERSYMMETRIC 3-4-1 MODEL
Authors: RODRIGUEZ M. C.
Published: January 2008

We build the complete supersymmetric version of a 3-4-1 gauge model using the superfield formalism. We point out that a discrete symmetry, similar to the R-symmetry in the minimal supersymmetric standard model, is possible to be defined in this model. Hence we have both R-conserving and R-violating possibilities. We also discuss some phenomenological results coming from this model.
GAUGE-INVARIANT REFORMULATION OF THE VECTOR SCHWINGER MODEL WITH A PHOTON MASS TERM AND ITS HAMILTONIAN, PATH INTEGRAL AND BRST FORMULATIONS
Authors: KULSHRESHTHA USHA , KULSHRESHTHA D. S.
Published: January 2008

Using the Stueckelberg formalism, we construct a gauge-invariant version of the vector Schwinger model (VSM) with a photon mass term studied by one of us recently. This model describes two-dimensional massive electrodynamics with massless fermions, where the left-handed and right-handed fermions are coupled to the electromagnetic field with equal couplings. This model describing the 2D massive electrodynamics becomes gauge-noninvariant (GNI). This is in contrast to the case of the massless VSM which is a gauge-invariant (GI) theory (as a consequence of demanding the regularization for the theory to be GI). In this work we first construct a GI theory corresponding to this model describing the 2D massive electrodynamics, using the Stueckelberg formalism and then we recover the physical contents of the original GNI theory studied earlier, under some special gauge choice. We then study the Hamiltonian, path integral and BRST formulations of this GI theory under appropriate gauge-fixing. The theory presents a new class of models in the 2D quantum electrodynamics with massless fermions but with a photon mass term.
QUANTUM INFORMATION ENTROPY FOR A MULTILEVEL SYSTEM
Authors: ABDEL-ATY M. , HASSAN S. S. , SEBAWE ABDALLA M. , OBADA A.-S. F.
Published: January 2008

We study the uncertainty relations between photon number and canonical phase of a multilevel system. All the relevant quantities can be sampled directly from the measured phase-dependent quadrature distribution. Some comments are made on the extension of these relations to the case where the Hilbert space is of infinite dimension. We describe its theoretical basis and discuss its practical relevance, especially in comparison with already known results. Numerical calculations under specified initial conditions are presented.
GROUND-STATE ENERGY DENSITY OF A DILUTE BOSE GAS IN THE CANONICAL TRANSFORMATION
Authors: KIM SANG-HOON , KIM CHUL KU , DAS MUKUNDA P.
Published: January 2008

The ground-state energy density of an interacting dilute Bose gas system is studied in the canonical transformation scheme. It is shown that the transformation scheme enables us to calculate a higher order correction of order na3 in the particle depletion and ground-state energy density of a dilute Bose gas system, which corresponds to the density fluctuation resulting from the excited states. Considering a two-body interaction only, the coefficient of the na3 term is shown to be 2(π-8/3) for the particle depletion, and 16(π-8/3) for the ground-state energy density.
CHARACTERISTIC OF SURFACE WAVES IN NONLINEAR LEFT HANDED — PHOTOSENSITIVE SEMICONDUCTOR WAVEGUIDE STRUCTURE
Authors: HAMADA M. S. , EL-ASTAL A. H. , SHABAT M. M.
Published: January 2008

The nonlinear electromagnetic surface waves in waveguide structure which contains photosensitive semiconductor layer and left-handed material (LHM) layer have been studied. The effects of light intensity and the LHM on the dispersion of electromagnetic surface waves have been investigated. It has been noticed that, as a result of the foundation of LHM layer in the structure, both forward and backward electromagnetic surface waves exist in the waveguide. It has also been shown that the photosensitive semiconductor layer controls the propagation characteristics of the electromagnetic surface waves.

The power flow of the nonlinear surface waves has also been examined. It has been found that the majority of the electromagnetic surface waves propagate in the forward direction.
Revealing Targeted Therapy for Human Cancer by Gene Module Maps
Authors: Wong David J. , Nuyten Dimitry S.A. , Regev Aviv , Lin Meihong , Adler Adam S. , Segal Eran , van de Vijver Marc J. , Chang Howard Y.
Published: January 2008

A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new genetic subtypes of cancers should be treated is unknown. Here, we show that a gene module map can guide the prospective identification of targeted therapies for genetic subtypes of cancer. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. We show that in human breast cancers, activation of a poor-prognosis “wound signature” is strongly associated with induction of both a mitochondria gene module and a proteasome gene module. We found that 3-bromopyruvic acid, which inhibits glycolysis, selectively killed breast cells expressing the mitochondria and wound signatures. In addition, inhibition of proteasome activity by bortezomib, a drug approved for human use in multiple myeloma, abrogated wound signature expression and selectively killed breast cells expressing the wound signature. Thus, gene module maps may enable rapid translation of complex genomic signatures in human disease to targeted therapeutic strategies. [Cancer Res 2008;68(2):369–78]
Acquired Lymphedema: An Urgent Need for Adequate Animal Models
Authors: Hadamitzky Catarina , Pabst Reinhard
Published: January 2008

In cancer patients, the removal of tumor-draining lymph nodes during tumor resection can lead to acquired lymphedema. This disease, which is characterized by tissue swelling and increased risk of infection due to restricted lymph flow, lacks an effective treatment. Limitations to the design and conduct of randomized trials to date have limited the evaluation of proposed surgical techniques. As a result, animal models have provided an important research base. This review summarizes work in canine, rabbit, and rodent models of acquired lymphedema, focusing on arising limitations and potential applications. [Cancer Res 2008;68(2):343–5]
Cannabinoids for Cancer Treatment: Progress and Promise
Authors: Sarfaraz Sami , Adhami Vaqar M. , Syed Deeba N. , Afaq Farrukh , Mukhtar Hasan
Published: January 2008

Cannabinoids are a class of pharmacologic compounds that offer potential applications as antitumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival. In particular, emerging evidence suggests that agonists of cannabinoid receptors expressed by tumor cells may offer a novel strategy to treat cancer. Here, we review recent work that raises interest in the development and exploration of potent, nontoxic, and nonhabit forming cannabinoids for cancer therapy. [Cancer Res 2008;68(2):339–42]
Phosphatidylinositol Ether Lipid Analogues Induce AMP-Activated Protein Kinase–Dependent Death in LKB1-Mutant Non–Small Cell Lung Cancer Cells
Authors: Memmott Regan M. , Gills Joell J. , Hollingshead Melinda , Powers Margaret C. , Chen Zhiping , Kemp Bruce , Kozikowski Alan , Dennis Phillip A.
Published: January 2008

Loss of function of the tumor suppressor LKB1 occurs in 30% to 50% of lung adenocarcinomas. Because LKB1 activates AMP-activated protein kinase (AMPK), which can negatively regulate mTOR, AMPK activation might be desirable for cancer therapy. However, no known compounds activate AMPK independently of LKB1 in vivo, and the usefulness of activating AMPK in LKB1-mutant cancers is unknown. Here, we show that lipid-based Akt inhibitors, phosphatidylinositol ether lipid analogues (PIA), activate AMPK independently of LKB1. PIAs activated AMPK in LKB1-mutant non–small cell lung cancer (NSCLC) cell lines with similar concentration dependence as that required to inhibit Akt. However, AMPK activation was independent of Akt inhibition. AMPK activation was a major mechanism of mTOR inhibition. To assess whether another kinase capable of activating AMPK, CaMKKβ, contributed to PIA-induced AMPK activation, we used an inhibitor of CaMKK, STO-609. STO-609 inhibited PIA-induced AMPK activation in LKB1-mutant NSCLC cells, and delayed AMPK activation in wild-type LKB1 NSCLC cells. In addition, AMPK activation was not observed in NSCLC cells with mutant CaMKKβ, suggesting that CaMKKβ contributes to PIA-induced AMPK activation in cells. AMPK activation promoted PIA-induced cytotoxicity because PIAs were less cytotoxic in AMPKα−/− murine embryonic fibroblasts or LKB1-mutant NSCLC cells transfected with mutant AMPK. This mechanism was also relevant in vivo. Treatment of LKB1-mutant NSCLC xenografts with PIA decreased tumor volume by ∼50% and activated AMPK. These studies show that PIAs recapitulate the activity of two tumor suppressors (PTEN and LKB1) that converge on mTOR. Moreover, they suggest that PIAs might have utility in the treatment of LKB1-mutant lung adenocarcinomas. [Cancer Res 2008;68(2):580–8]
Regulation of Vascular Endothelial Growth Factor D by Orphan Receptors Hepatocyte Nuclear Factor-4α and Chicken Ovalbumin Upstream Promoter Transcription Factors 1 and 2
Authors: Schäfer Georgia , Wißmann Christoph , Hertel Johannes , Lunyak Victoria , Höcker Michael
Published: January 2008

Vascular endothelial growth factor D has recently been linked to the control of lymphangiogenesis and lymphatic metastasis. The molecular determinants regulating vegf-D gene transcription, however, have not yet been identified. After isolation of 2 kb of 5′-flanking DNA of the human vegf-D gene, we identified a novel, atypical direct repeat (DR) element consisting of a consensus half-site (AGGTCA) at −125/−119 and a degenerated DR half-site (ATGTTA) at −99/−94 as sufficient and necessary for vegf-D transcription. The vegf-D DR element is bound and activated by the orphan receptors hepatocyte nuclear factor 4α (HNF-4α) and chicken ovalbumin upstream promoter transcription factor (COUP-TF)-1/COUP-TF2. Additionally, chromatin immunoprecipitation assays identified transcriptional coactivators cyclic AMP–responsive element binding protein–binding protein and glucocorticoid receptor interacting protein 1 at the vegf-D DR element and functional assays confirmed their stimulatory effect on the vegf-D promoter. Histone deacetylase inhibition by trichostatin A led to accumulation of acetylated histones H3/H4 at the vegf-D promoter, up-regulation of vegf-D mRNA levels, and transactivation of vegf-D promoter reporter gene constructs in cancer cell lines. This study for the first time describes the molecular determinants in cis and trans controlling vegf-D gene transcription and identifies interaction of HNF-4α and COUP-TF1/COUP-TF2 with a proximal, atypical DR element as indispensable for vegf-D transcription. Moreover, our findings suggest that epigenetic control of histone acetylation represents an important determinant of vegf-D gene expression in cancer cells. These results provide novel insights into the molecular machinery controlling vegf-D gene expression and may add to a better understanding of the regulation of lymphangiogenesis in vascular development and cancer. [Cancer Res 2008;68(2):457–66]
Superior Activity of Fusion Protein scFvRit:sFasL over Cotreatment with Rituximab and Fas Agonists
Authors: Bremer Edwin , ten Cate Bram , Samplonius Douwe F. , Mueller Nicole , Wajant Harald , Stel Alja J. , Chamuleau Martine , van de Loosdrecht Arjan A. , Stieglmaier Julia , Fey Georg H. , Helfrich Wijnand
Published: January 2008

The clinical efficacy of the CD20-specific chimeric monoclonal antibody rituximab is significantly hampered by intrinsic or acquired resistance to therapy. Rituximab activates antibody-dependent cellular cytotoxicity/complement-dependent cytotoxicity–dependent lysis but also induces apoptosis by cross-linking of its target antigen CD20. Recent reports indicate that this apoptotic activity of rituximab can be synergized by cotreatment with Fas agonists. Here, we report on a strategy designed to exploit and optimize the synergy between rituximab and Fas signaling by genetically fusing a rituximab-derived antibody fragment to soluble Fas ligand (sFasL). The resultant fusion protein, designated scFvRit:sFasL, potently induced CD20-restricted apoptosis in a panel of malignant B-cell lines (10 of 11) and primary patient-derived malignant B cells (two of two non–Hodgkin lymphoma and five of six B cell chronic lymphocytic leukemia). ScFvRit:sFasL efficiently activated CD20 and Fas apoptotic signaling, resulting in a far superior proapoptotic activity compared with cotreatment with rituximab and Fas agonists. ScFvRit:sFasL lacked activity toward normal human B cells and also lacked systemic toxicity in nude mice with no elevation of aspartate aminotransferase and alanine aminotransferase levels or liver caspase-3 activity. In conclusion, scFvRit:sFasL efficiently activates CD20 and Fas-apoptotic signaling and may be useful for the elimination of malignant B cells. [Cancer Res 2008;68(2):597–604]
Protective Role of Toll-like Receptor 4 during the Initiation Stage of Cutaneous Chemical Carcinogenesis
Authors: Yusuf Nabiha , Nasti Tahseen H. , Long J. Alan , Naseemuddin Mohammed , Lucas Alan P. , Xu Hui , Elmets Craig A.
Published: January 2008

Toll-like receptors (TLR) activate multiple steps in inflammatory reactions in innate immune responses. They also activate signals that are critically involved in the initiation of adaptive immune responses. Many tumorigenic chemicals have been associated with endotoxin hypersensitivity mediated through TLR4. To determine the role of TLR4 in cutaneous skin carcinogenesis, we treated TLR4-deficient C3H/HeJ mice and the TLR4-normal C3H/HeN mice with the carcinogenic polyaromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA). TLR4-deficient C3H/HeJ mice developed more tumors relative to the TLR4-normal C3H/HeN mice. Both C3H/HeN and C3H/HeJ mice developed a T-cell–mediated immune response to topically applied DMBA. Interestingly, the cell-mediated immune response was mediated by IFN-γ in C3H/HeN mice and by interleukin (IL)-17 in C3H/HeJ mice. Moreover, C3H/HeN mice had elevated circulating levels of IFN-γ following topical application of DMBA, whereas IL-17 was elevated in C3H/HeJ mice. The results of this study indicate that TLR4 plays an important role in the prevention of DMBA skin tumorigenesis and that this is associated with differences in the T-cell subtype activated. Efforts to divert the cell-mediated immune response from one that is IL-17 mediated to one that is IFN-γ mediated may prove to be beneficial in the prevention of DMBA-induced cutaneous tumors. [Cancer Res 2008;68(2):615–22]
Exercise Effect on Oxidative Stress Is Independent of Change in Estrogen Metabolism
Authors: Schmitz Kathryn H. , Warren Meghan , Rundle Andrew G. , Williams Nancy I. , Gross Myron D. , Kurzer Mindy S.
Published: January 2008

Purpose: The effect of exercise training on lipid peroxidation and endogenous estrogens is not well understood in premenopausal women. Exercise effects on these variables could mediate observed associations of exercise with hormonally related cancers, including breast cancer. The purpose of the study is to determine the effect of 15 weeks of aerobic exercise on lipid peroxidation, endogenous estrogens, and body composition in young, healthy eumenorrheic women.

Methods: Fifteen sedentary premenopausal women (18-25 years) participated. Pre- and post-exercise training urine collection (three 24-h samples) started 48 h after most recent exercise session for analysis of a marker of lipid peroxidation (F2-isoprostane) and endogenous estrogens, including 2-hydroxyestrogens, 4-hydroxyestrogens, 16-α-hydroxyestrone, and ratios of these metabolites (2:16, 2:4). Body composition was measured by dual-energy X-ray absorptiometry, and F2-isoprostanes and estrogens were measured by gas chromatography-mass spectrometry.

Results: Aerobic exercise resulted in a 34% decrease in F2-isoprostane (P = 0.02), a 10% increase in fitness (P = 0.004), a 1.2 kg decrease in body mass (P = 0.007), and a 1.8 kg decrease in fat mass (P = 0.04). No significant changes were noted in estrogens.

Conclusions: The effect of exercise training on oxidative stress may be relevant to risk for hormonally related cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(1):220–3)
Increased Human Buccal Cell Autofluorescence Is a Candidate Biomarker of Tobacco Smoking
Authors: Paszkiewicz Geraldine M. , Timm Earl A. , Mahoney Martin C. , Wallace Paul K. , Sullivan Nasca Maureen A. , Tammela Tracey L. , Hutson Alan , Pauly John L.
Published: January 2008

Human buccal cells display diverse changes that are associated with smoked and smokeless tobacco, and clinicopathologic studies have correlated human buccal cell changes with oral cancer. Reported herein are the results of studies that were undertaken to identify a high-throughput technology that would advance efforts to use human buccal cells. We report that (a) a relatively large (mean ± SD, 2.1 ± 1.4 × 105 cells) population of human buccal cells can be collected in a noninvasive manner with a toothbrush and purified (>98% human buccal cells; n = 138 samples of the oral mucosa; n = 69 donors); (b) despite their large size (diameter, ∼65 μm), the human buccal cells were analyzed successfully with a single laser cytometer (FACScan) and an advanced multispectral cytometer (FACSAria) having three lasers (excitation = 488, 633, and 407 nm wavelengths) and nine distinct emission channels; (c) cytometry revealed that the buccal cells expressed a high level of autofluorescence that was displayed over a broad spectrum (450-780 nm wavelength); (d) autofluorescence of human buccal cells collected from the left and right cheek was consistent, illustrating the reproducibility of the sample collection and assay procedure; (e) human buccal cell autofluorescence differed significantly among 69 adult subjects; and (f) a statistical difference (P = 0.018) between current, former, and never smokers. Summarily, this report is thought to be the first to show the application of flow cytometry for assaying human buccal cells and identifies buccal cell autofluorescence as a candidate biomarker of tobacco smoking. (Cancer Epidemiol Biomarkers Prev 2008;17(1):239–44)
Seroreactivity to Cutaneous Human Papillomaviruses among Patients with Nonmelanoma Skin Cancer or Benign Skin Lesions
Authors: Andersson Kristin , Waterboer Tim , Kirnbauer Reinhard , Slupetzky Katharina , Iftner Thomas , de Villiers Ethel-Michele , Forslund Ola , Pawlita Michael , Dillner Joakim
Published: January 2008

Cutaneous human papillomaviruses (HPV) are common in nonmelanoma skin cancers, benign skin lesions, and healthy skin. Increased seroprevalences for cutaneous HPV among nonmelanoma skin cancer patients have been described. To determine whether antibodies to cutaneous HPV are related to presence of the virus and/or to skin disease, we collected serum and biopsies from both lesions and healthy skin from 434 nonimmunosuppressed patients (72 squamous cell carcinomas, 160 basal cell carcinomas, 81 actinic keratoses, and 121 benign lesions). Biopsies were analyzed for HPV DNA by PCR, cloning, and sequencing. Serum antibodies to the major capsid protein L1 of HPV 1, 5, 6, 8, 9, 10, 15, 16, 20, 24, 32, 36, 38, and 57 as well as to the oncoproteins E6 and E7 of HPV 8 and 38 were detected using a multiplexed fluorescent bead-based assay. Type-specific seroprevalence among patients with the same type of HPV DNA (sensitivity of serology) varied from 0% to at most 28%. Presence of HPV DNA and antibodies to the same HPV type was not significantly correlated. However, seropositivity to any HPV type was significantly more common among patients positive for HPV DNA of any HPV type (odds ratio, 1.90; 95% confidence interval, 1.55-2.34). Seroprevalences were similar among the different patient groups but was, for most HPV types, somewhat higher among squamous cell carcinoma patients than among basal cell carcinoma patients (P < 0.01). In conclusion, additional studies are required to clarify the biological meaning of seropositivity as a marker of cutaneous HPV infection and skin disease. (Cancer Epidemiol Biomarkers Prev 2008;17(1):189–95)
Statin Induces Apoptosis and Cell Growth Arrest in Prostate Cancer Cells
Authors: Hoque Ashraful , Chen Hongli , Xu Xiao-chun
Published: January 2008

Statins are a class of low molecular weight drugs that inhibit the rate-limiting enzyme of the mevalonate pathway 3-hydroxy-3-methylglutaryl-CoA reductase. Statins have been approved and effectively used to control hypercholesterolemia in clinical setting. Recent study showed statin's antitumor activity and suggested a potential role for prevention of human cancers. In this study, we did cell viability, DNA fragmentation, and terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling assays to evaluate the action of statins on prostate cancer cells and used Western blotting and RhoA activation assay to investigate the underlying molecular mechanism of action. Our data showed that lovastatin and simvastatin effectively decreased cell viability in three prostate cancer cell lines (PC3, DU145, and LnCap) by inducing apoptosis and cell growth arrest at G1 phase. Both lovastatin and simvastatin induced activation of caspase-8, caspase-3, and, to a lesser extent, caspase-9. Both statins suppressed expression of Rb, phosphorylated Rb, cyclin D1, cyclin D3, CDK4, and CDK6, but induced p21 and p27 expression in prostate cancer cells. Furthermore, lovastatin and simvastatin suppressed RhoA activation and c-JUN expression, but not cyclooxygenase-2 expression. Our data showed that the antitumor activity of statins is due to induction of apoptosis and cell growth arrest. The underlying molecular mechanism of statin's action is mediated through inactivation of RhoA, which in turn induces caspase enzymatic activity and/or G1 cell cycle. Future studies should focus on examining statins and other apoptosis-inducing drugs (e.g., cyclooxygenase-2 inhibitors or curcumin) together to assess their efficacy in prevention of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(1):88–94)
Cord Serum Estrogens, Androgens, Insulin-Like Growth Factor-I, and Insulin-Like Growth Factor Binding Protein-3 in Chinese and U.S. Caucasian Neonates
Authors: Troisi Rebecca , Lagiou Pagona , Trichopoulos Dimitrios , Xu Biao , Chie Lucy , Stanczyk Frank Z. , Potischman Nancy , Adami Hans-Olov , Hoover Robert N. , Hsieh Chung-Cheng
Published: January 2008

Markedly lower breast cancer incidence rates in Asians than Caucasians are not explained by established adult risk factors. Migration studies suggest the importance of early-life exposures, including perhaps the in utero period. Concentrations of steroid hormones and insulin-like growth factors (IGF) were measured in umbilical cord sera from pregnancies in Shanghai, China (n = 121) and Boston, MA (n = 111). Pregnancy characteristics were ascertained by interview and medical records. Means and percent differences in hormone concentrations comparing Chinese with Caucasians and 95% confidence intervals were estimated from linear regression models. Cord concentrations of androstenedione (91.9%), testosterone (257%), estriol (48.6%), and IGF binding protein-3 (21.1%) were significantly higher in the Chinese than U.S. samples, and cord prolactin was lower (−14.9%). Cord estradiol and IGF-I concentrations did not differ by race/ethnicity. With adjustment for gestational length, maternal age, pre-pregnancy weight, and weight gain, androstenedione (60.5%), testosterone (185%), and IGF binding protein-3 (40.4%) remained significantly higher in the Chinese, whereas the higher estriol and lower prolactin concentrations were attenuated. In addition, estradiol levels became lower in the Chinese (−29.8%) but did not reach statistical significance. Results were generally similar when restricted to first full-term pregnancies, with reduced estradiol concentrations in the Chinese reaching statistical significance after adjustment. These data are consistent with the hypothesis that elevated prenatal androgen exposure could mediate reductions in breast cancer risk. The meaning of the change in findings for estrogens after controlling for factors related to the pregnancy is unclear with regard to explaining international breast cancer differences. (Cancer Epidemiol Biomarkers Prev 2008;17(1):224–31)
Sequence Variants of NAT1 and NAT2 and Other Xenometabolic Genes and Risk of Lung and Aerodigestive Tract Cancers in Central Europe
Authors: McKay James D. , Hashibe Mia , Hung Rayjean J. , Wakefield Jon , Gaborieau Valerie , Szeszenia-Dabrowska Neonila , Zaridze David , Lissowska Jolanta , Rudnai Peter , Fabianova Eleonora , Mates Dana , Foretova Lenka , Janout Vladimir , Bencko Vladimir , Chabrier Amelie , Hall Janet , Boffetta Paolo , Canzian Federico , Brennan Paul
Published: January 2008

Tobacco smoke contains an extensive cocktail of highly carcinogenic chemicals. Individuals with a slower elimination rate of the chemicals in tobacco smoke may have increased exposure to their carcinogenic properties compared with those with a faster rate. Polymorphisms that alter the function of the genes involved in the activation or the detoxification of the chemical carcinogens in tobacco smoke can potentially influence an individual's risk of developing a tobacco-related cancer. To test this hypothesis, we have genotyped polymorphisms in 16 genes involved in metabolism of chemical carcinogens in a Central and Eastern European case-control study comprising 2,250 lung cases, 811 upper aerodigestive cancer (UADT) cases, and 2,704 controls. The N-acetyltransferase (NAT) genes were the most implicated in risk, with the NAT1*10 haplotype showing an inverse association in lung cancer, in both heterozygote carriers [odds ratio (OR), 0.81; 95% confidence interval (95% CI), 0.70-0.93] and homozygote carriers (OR, 0.70; 95% CI, 0.48-1.01), suggesting a genotype dose response (P < 0.001). In UADT cancer, a similar inverse association was noted in NAT1*10 although only in heterozygotes (OR, 0.78; 95%CI, 0.65-0.95). In NAT2, when considering the individuals inferred acetylator phenotypes based on their NAT2 diplotype, “slow” acetylators compared with intermediate or fast acetylators showed no association with risk. None of the other 14 genes provided robust evidence of an association for either lung or UADT cancer. We therefore conclude that, of the genetic variation studied, NAT1 gene was the most likely candidate to influence the risk of developing a tobacco-related cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(1):141–7)
Dietary Vitamin B6 Intake and the Risk of Colorectal Cancer
Authors: Theodoratou Evropi , Farrington Susan M. , Tenesa Albert , McNeill Geraldine , Cetnarskyj Roseanne , Barnetson Rebecca A. , Porteous Mary E. , Dunlop Malcolm G. , Campbell Harry
Published: January 2008

Vitamin B6, a coenzyme in the folate metabolism pathway, may have anticarcinogenic effects. Laboratory and epidemiologic studies support the hypothesis of its protective effect against colorectal cancer (CRC). The aim of this large Scottish case-control study, including 2,028 hospital-based cases and 2,722 population-based controls, was to investigate the associations between dietary and supplementary intake of vitamin B6 and CRC. Three logistic regression models adjusted for several confounding factors, including energy, folate, and fiber intake, were applied in the whole sample and after age, sex, cancer site, folate, MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), MTR A2756G (rs1805087), and MTRR A66G (rs1801394) stratification (analysis on genotypes on 1,001 cases and 1,010 controls ≤55 years old). Moderately strong inverse and dose-dependent associations in the whole sample were found between CRC risk and the intake of dietary and total vitamin B6 in all three models [model III: odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.61-0.98; P for trend = 0.03; OR, 0.86; 95% CI, 0.69-1.07; P for trend = 0.12]. In addition, meta-analyses of published studies showed inverse associations between vitamin B6 and CRC (combined relative risk, 0.81; 95% CI, 0.68-0.96; test for overall effect P = 0.01; combined odds ratio, 0.67; 95% CI, 0.60-0.75; test for overall effect P < 0.00001). Analysis within the stratified subgroups showed similar associations apart from a stronger effect among ≤55-year-old individuals. Evidence from larger cohort and experimental studies is now required to confirm and define the anticarcinogenic actions of vitamin B6 and to explore the mechanisms by which this effect is mediated. (Cancer Epidemiol Biomarkers Prev 2008;17(1):171–82)
Haplotype Analyses of CYP19A1 Gene Variants and Breast Cancer Risk: Results from the Shanghai Breast Cancer Study
Authors: Cai Qiuyin , Kataoka Nobuhiko , Li Chun , Wen Wanqing , Smith Jeffrey R. , Gao Yu-Tang , Shu Xiao Ou , Zheng Wei
Published: January 2008

Estrogens play a central role in the etiology of breast cancer. The CYP19A1 gene encodes aromatase, a key enzyme in the biosynthesis of estrogens. Several single nucleotide polymorphisms (SNP) or haplotypes in the CYP19A1 gene have been evaluated in relation to breast cancer risk. However, the results have been inconsistent. In this study, we constructed haplotypes of the CYP19A1 gene using 19 haplotype-tagging SNPs in Chinese women and evaluated the variation of this gene in relation to breast cancer risk in a population-based case-control study involving 1,140 cases and 1,244 community controls of the Shanghai Breast Cancer Study. Five common haplotypes in block 1, three common haplotypes in block 2, five common haplotypes in block 3, and four common haplotypes in block 4 were identified. No apparent association was observed between common haplotypes and breast cancer risk in analyses including all subjects nor in analyses stratified by menopausal status. Similarly, no statistically significant differences were found between cases and controls in the genotype distributions of the 19 individual SNPs and the (TTTA)n repeat polymorphism evaluated in the study. No overall association of breast cancer risk with common CYP19A1 gene variants among Chinese women was observed in this large-scale, comprehensive study. Further studies are needed to explore CYP19A1 gene-environment interactions in relation to breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(1):27–32)
Measurement and Meaning of Oxidatively Modified DNA Lesions in Urine
Authors: Cooke Marcus S. , Olinski Ryszard , Loft Steffen ,   members of the European Standards Committee on Urinary (DNA) Lesion Analysis (ESCULA)
Published: January 2008

Background: Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. The noninvasive assessment of such damage, i.e., in urine, and application to large-scale human studies are vital to understanding this role and devising intervention strategies.

Methods: We have reviewed the literature to establish the status quo with regard to the methods and meaning of measuring DNA oxidation products in urine.

Results: Most of the literature focus upon 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and whereas a large number of these reports concern clinical conditions, there remains (a) lack of consensus between methods, (b) possible contribution from diet and/or cell death, (c) no definitive DNA repair source of urinary 2′-deoxyribonucleoside lesions, and (d) no reference ranges for healthy or diseased individuals.

Conclusions: The origin of 8-oxodG is not identified; however, recent cell culture studies suggest that the action of Nudix hydrolase(s) on oxidative modification of the nucleotide pool is a likely candidate for the 8-oxodG found in urine and, potentially, of other oxidized 2′-deoxyribonucleoside lesions. Literature reports suggest that diet and cell death have minimal, if any, influence upon urinary levels of 8-oxodG and 8-oxo-7,8-dihydroguanine, although this should be assessed on a lesion-by-lesion basis. Broadly speaking, there is consensus between chromatographic techniques; however, ELISA approaches continue to overestimate 8-oxodG levels and is not sufficiently specific for accurate quantification. With increasing numbers of lesions being studied, it is vital that these fundamental issues are addressed. We report the formation of the European Standards Committee on Urinary (DNA) Lesion Analysis whose primary goal is to achieve consensus between methods and establish reference ranges in health and disease. (Cancer Epidemiol Biomarkers Prev 2008;17(1):3–14)
Predictors of Ductal Closure and Intestinal Complications in Very Low Birth Weight Infants Treated with Indomethacin
Authors: Madan Juliette , Fiascone John , Balasubramanian Vidhya , Griffith John , Hagadorn James I.
Published: January 2008

Objective: To describe factors associated with failure of patent ductus arteriosus closure and development of gastrointestinal complications in subjects treated with indomethacin. Study Design: Infants ≤30 weeks and <1,500 g delivered between 1997–2003 with patent ductus arteriosus treated with indomethacin were included in this single-center retrospective study. Risk factors for failed ductal closure rates and gastrointestinal complications were identified with uni- and multivariable analyses. Results: Among 210 subjects treated with indomethacin, ductal closure increased from 43% at 23 weeks to 87% at 27 weeks (OR 1.51 per week gestation, 95% CI 1.14–2.01, p = 0.004) and was unchanged thereafter. Gastrointestinal complications decreased with increasing gestational age (OR 0.67/week, 95% CI 0.52–0.84) but increased with male gender (OR 2.41, 95% CI 1.07–5.45). SNAP-II (Score for Neonatal Acute Physiology-II) scores at birth and at the time of first indomethacin therapy were not associated with likelihood of closure or with gastrointestinal complications. Duration of ductal patency was not associated with risk of necrotizing enterocolitis or intestinal perforation after adjusting for gestational age and gender. Conclusions: Ductal closure with indomethacin is linearly associated with gestational age in infants ≤27 weeks. Illness severity at the time of treatment is not predictive of treatment outcome or gastrointestinal complications. The duration of ductal patency is not associated with an increase in adjusted risk of necrotizing enterocolitis or intestinal perforation in patients treated with indomethacin.
Influence of Age and Gender on Cytokine Expression in a Murine Model of Parkinson’s Disease
Authors: Ciesielska Agnieszka , Joniec Ilona , Kurkowska-Jastrzębska Iwona , Przybyłkowski Adam , Gromadzka Grażyna , Członkowska Anna , Członkowski Andrzej
Published: January 2008

Objective: The neuroinflammatory reaction has been linked with Parkinson’s disease. One of the hypotheses to explain the significance of age and gender (male predominance) effects on neurodegeneration in Parkinson’s disease may result from a link between these risk factors and the inflammatory processes. Here, we investigated the expression of inflammatory mediators in relation to 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP)-induced neurodegenerative processes in nigrostriatal pathway in young and aged male and female mice.Methods and Results: We simultaneously assessed striatal tyrosine hydroxylase (TH) protein concentrations (Western blotting) and cytokine (TNFα, IFNγ, IL-1β, IL-6 and TGFβ1) mRNA levels (RT-PCR) in young and aged (2- and 12-month-old) C57BL/6 male and female mice after 6 h, 1, 3, 7, 14, 21 days after MPTP intoxication.Western blotting analysis showed that at the early time points, males showed a greater reduction in striatal TH versus females. Additionally, in contrast to the aged mice, in young males and females the TH concentration gradually increased between the 7th and the 21st day after intoxication. The increases in TNFα, IL-1β and IFNγ after intoxication were faster in both young and aged males than females. In males (both ages), we observed an increase in TGFβ1 at the early time points. In contrast, in females (both ages) TGFβ1 was elevated at later time points. MPTP caused an increase in IL-6 in males and females, but this increase was significantly higher in females. Conclusions: A gender and age skewing of the cytokine gene expression in the striatum after intoxication may be related to the greater susceptibility in males as well as older animals to the detrimental effects of MPTP.
Tenascin-C Expression and Its Prognostic Significance in Colorectal Cancer
Authors: Lundin M. , Nordling S. , Lundin J. , Haglund C.
Published: January 2008

Objective: The extracellular matrix glycoprotein tenascin-C has been proposed as a tumor marker with prognostic significance in many cancer forms, but in colorectal cancer, reported results have been controversial. The aim of this study was to evaluate the prognostic value of immunohistochemical tenascin-C expression in a series of 231 patients with colorectal cancer. Methods: Paraffin-embedded formalin-fixed specimens were stained with a tenascin-C-specific monoclonal antibody, and the stromal staining intensity and pattern were analyzed. Results: Tenascin-C immunoreactivity was observed in all 231 specimens, with a pattern of staining that was diffuse and interstitial. The staining was occasional in 39 (17%), moderate in 106 (46%) and strong in 86 specimens (37%). There was no statistically significant association between tenascin-C immunoreactivity and any of the other clinicopathological variables. The cumulative 5-year survival rates of patients with occasional and weak staining were similar (56.8 and 54.9%, respectively), while the patients with strong tenascin-C staining had a lower survival rate (46.1%). This difference in survival was not significant (p = 0.23). The staining pattern and distribution can be viewed from digitized representative microscope slides (virtual slides) at http://www.webmicroscope.net/supplements/tenascin. Conclusions: Our results indicate that immunohistochemical expression of tenascin-C is not of prognostic significance in colorectal cancer.
Transcriptional Profiling of Chromosome 17 Quantitative Trait Loci for Carbohydrate and Total Calorie Intake in a Mouse Congenic Strain Reveals Candidate Genes and Pathways
Authors: Kumar K. Ganesh , Smith Richards Brenda K.
Published: January 2008

Background/Aims: The genetic basis for ingestive behaviors is virtually unknown. Quantitative trait loci (QTLs) for carbohydrate and energy intake map to mouse chromosome 17 and were previously confirmed by a congenic strain bearing CAST/Ei (CAST) donor segment on the C57BL/6J (B6) background. Methods: We used microarray technology to facilitate gene identification. Gene expression was compared between the B6.CAST-17 (BC-17) congenic and B6 strains in two diets: (1) chow, and (2) carbohydrate/protein vs. fat/protein. Results: Within the QTL and unique to macronutrient selection, Agpat1 (acylglycerol-3-phosphate O-acyltransferase 1) was differentially expressed in hypothalamus. Irrespective of diet, the gene with the highest fold difference in congenic mice was trefoil factor 3 (Tff3) in liver. Several genes involved in fat metabolism were decreased in carbohydrate-preferring congenic mice, while genes associated with carbohydrate metabolism were increased. In particular, the glyoxalase pathway was enhanced including Glo1, Glo2, and dLDH. Higher expression of Glo1 mRNA in BC-17 congenic mice corresponded to increased protein expression revealed by Western blot, and to higher GLO1 activity in blood. Conclusion: These genes represent new candidates for nutrient intake phenotypes. We propose that increased GLO1 in the BC-17 strain supports its need to protect against dietary oxidants resulting from high carbohydrate intake.
Modeling Turbulent Flow in an Urban Central Business District
Authors: Burrows Donald A. , Hendricks Eric A. , Diehl Steve R. , Keith Robert
Published: January 2008

The Realistic Urban Spread and Transport of Intrusive Contaminants (RUSTIC) model has been developed as a simplified computational fluid dynamics model with a k–ω turbulence model to be used to provide moderately fast simulations of turbulent airflow in an urban environment. RUSTIC simulations were compared with wind tunnel measurements to refine and “calibrate” the parameters for the k–ω model. RUSTIC simulations were then run and compared with data from five different periods during the Joint Urban 2003 experiment. Predictions from RUSTIC were compared with data from 33 near-surface sonic anemometers as well as 8 sonic anemometers on a 90-m tower and a sodar wind profiler located in the Oklahoma City, Oklahoma, central business district. The data were subdivided into daytime and nighttime datasets and then the daytime data were further subdivided into exposed and sheltered sonic anemometers. While there was little difference between day and night for wind speed and direction comparisons, there was considerable difference for the turbulence kinetic energy (TKE) comparisons. In the nighttime cases, RUSTIC overpredicted the TKE but without any correlation between model and observations. On the other hand, for the daytime cases, RUSTIC underpredicted the TKE values and correlated well with the observations. RUSTIC predicted both winds and TKE much better for the exposed sonic anemometers than for the sheltered ones. For the 90-m tower location downwind of the central business district, RUSTIC predicted the vertical profile of wind speed and direction very closely but underestimated the TKE.
Properties of the Wind Field within the Oklahoma City Park Avenue Street Canyon. Part II: Spectra, Cospectra, and Quadrant Analyses
Authors: Nelson M. A. , Pardyjak E. R. , Brown M. J. , Klewicki J. C.
Published: January 2008

Velocity data were obtained within Park Avenue in Oklahoma City, Oklahoma, using three-dimensional sonic anemometers under unstable atmospheric conditions. These data are used to produce velocity spectra, cospectra, and weighted joint probability density functions at various heights and horizontal locations in the street canyon. This analysis has helped to describe a number of physically interesting urban flow phenomena. Previous research has shown that the ratio of Reynolds shear stresses to normal stresses is typically much smaller deep within the canopy than those ratios found at the top of canopy and in the roughness sublayer. The turbulence in this region exhibits significant contributions to all four quadrants of a weighted joint-probability density function of horizontal and vertical velocity fluctuations, yielding the characteristic small Reynolds shear stresses in the flow. The velocity cospectra measured at the base of the canopy show evidence of discrete frequency bands of both positive and negative correlation that yield a small correlation, as indicated by the Reynolds shear stresses. Two major peaks were often observed in the spectra and cospectra: a low-frequency peak that appears to be associated with vortex shedding off the buildings and a midfrequency peak generally associated with canyon geometry. The low-frequency peak was found to produce a countergradient contribution to the along-wind vertical velocity covariance. Standard spectral tests for local isotropy indicate that isotropic conditions occur at different frequencies depending on spatial location, demonstrating the need to be thorough when testing for local isotropy with the urban canopy.