bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive life goals and plans in parasuicide
Authors: Vincent Paula J. , Boddana Pradeep , MacLeod Andrew K.
Published: March 2004

Parasuicidal individuals lack positive expectations about the future. This study set out to examine two aspects of positive future thinking—the ability to think of goals and the presence of cognitions related to achieving those goals, including plans, perceived control and perceived likelihood. Individuals who had recently engaged in an episode of parasuicide (N = 24) were compared with matched, hospital controls (N = 24) on a range of measures to assess number and type of goals, ability to think of plans to achieve goals, sense of control over goal outcomes, and perceived likelihood of achieving goals, as well as self‐report measures of hope, hopelessness, depression and anxiety. The two groups did not differ in the number of goals they could identify, especially after controlling for unemployment. The groups did differ in the quality of goals with the parasuicide patients' goals being less specific and more self‐focused in important goals, though these effects were confounded by group differences in employment status. Compared to controls, and after controlling for employment, parasuicide patients gave less specific plans, could think of more obstacles to achieving their goals and gave lower ratings of control and likelihood of achieving their goals. Parasuicide patients appear able to think of positive life goals but have clear problems in being able to think of how to achieve those goals. Copyright © 2004 John Wiley & Sons, Ltd.
Dose meta‐cognition or responsibility predict obsessive–compulsive symptoms: a test of the metacognitive model
Authors: Gwilliam Petra , Wells Adrian , Cartwright‐Hatton Samantha
Published: March 2004

Cognitive models of Obsessive–Compulsive disorder (OCD) have emphasized inflated responsibility (Salkovskis, 1985), thought–action fusion (Rachman, 1993), and metacognitive beliefs (Wells, 1997; Wells & Matthews, 1994), as factors contributing to disorder. The metacognitive model views responsibility as a by‐product of metacognitions that make little additional contribution to OCD, and gives rise to the following hypotheses: (1) responsibility and meta‐cognitive beliefs are positively correlated with obsessive–compulsive symptoms, (2) the relationship between responsibility and obsessive–compulsive symptoms is statistically dependent on meta‐cognition, (3) meta‐cognitions positively correlate with obsessive–compulsive symptoms independently of responsibility. The results supported each of these hypotheses and exploratory analyses were conducted to find the best unique set of predictors among a range of metacognitive dimensions. Metacognitive beliefs concerning need to control thoughts, thought–action fusion, and negative beliefs about cognitive competence emerged as reliable predictors. An additional contribution was made by thought–event fusion in one equation. The results provide support for the meta‐cognitive model. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis, Solution‐State and Solid‐State Structural Characterization of Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]+ (M = 99Tc, Re; DTC = Dithiocarbamate; PNP = Heterodiphosphane)
Authors: Bolzati Cristina , Refosco Fiorenzo , Cagnolini Aldo , Tisato Francesco , Boschi Alessandra , Duatti Adriano , Uccelli Licia , Dolmella Alessandro , Marotta Ester , Tubaro Michela
Published: March 2004

Mono‐cationic nitrido heterocomplexes of general formula [M(N)(DTC)(PNP)]+ (where M is 99Tc or Re, DTC is the mono‐anionic form of a dithiocarbamate ligand, and PNP is a diphosphane ligand with a tertiary amine‐containing five‐membered spacer) were prepared by ligand‐exchange reactions with the labile precursors [M(N)Cl2(PPh3)2] in dichloromethane/alcohol mixtures. The molecular structure of the representative rhenium complex [Re(N)(dedc)(pnp2)][PF6] (1) displays a distorted, square‐pyramidal geometry with the dithiocarbamate sulfur and the diphosphane phosphorus atoms spanning the four coordination positions on the equatorial plane. If the additional interactions between the nitrido nitrogen and the weakly bonded trans N‐diphosphane heteroatom, the molecular geometry can be viewed as pseudo‐octahedral. The structure in solution, as established by multinuclear NMR spectroscopy and ESI spectrometry, is monomeric, and identical to that shown in the solid state. Replacement of the phenyl groups on the phosphorous atoms in complexes 1, 2, 5, and 6 with alkyl groups modified neither the course of the reaction nor the composition of the resulting complexes. These results, together with the observation that no symmetrical complexes containing two identical bidentate ligands were produced in these reactions, strongly supports the conclusion that a mixed coordination sphere, composed by a combination of π‐donor and π‐acceptor atoms around the [M≡N]2+ group, constitutes a highly stable system. Compounds containing dangling alkyl‐substituted groups in the outer sphere (3, 4, 7, and 8) were fully characterized by multinuclear NMR spectroscopy and ESI mass spectrometry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Hetero‐Diels−Alder Reactions of Ketones — A Challenge for Chemists
Authors: Jørgensen Karl Anker
Published: April 2004

The recent developments of mainly catalytic and enantioselective hetero‐Diels−Alder reactions of ketones are presented. First, direct reactions of unactivated ketones are presented, focusing on the recent hydrogen bond‐promoted hetero‐Diels−Alder reactions with activated conjugated dienes. Then, direct catalytic enantioselective hetero‐Diels−Alder reactions of activated ketones with conjugated dienes are outlined. The use of different chiral copper(II) and zinc(II) catalysts are shown and the use of the hetero‐Diels−Alder adducts in organic synthesis presented. Finally, the inverse‐electron demand hetero‐Diels−Alder reactions of α,β‐unsaturated ketone functionalities are discussed. The different chiral Lewis‐acid complexes and chiral amines used for catalytic asymmetric hetero‐Diels−Alder reactions are presented and the scope of these reactions in the synthesis of optically active α‐hydroxy lactones, formyl esters and carbohydrates are demonstrated. The mechanistic aspects of the catalytic enantioselective hetero‐Diels−Alder reactions are also discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Shellfish Toxins − Chemical Studies on Northern Adriatic Mussels
Authors: Ciminiello Patrizia , Fattorusso Ernesto
Published: April 2004

During our investigation on toxic mussels from the Northern Adriatic sea, initiated about ten years ago, a number of polyether toxins have been isolated and characterized, some of which represent new additions to the diarrhetic shellfish poisoning (DSP) class of biotoxins and seem to be specific to the Adriatic. In addition, we have also isolated new types of toxins, oxazinins and chlorosulfolipids, whose structures were elucidated by extensive use of 1D and 2D NMR spectroscopic techniques. Some of them could represent a further risk to public health due to their cytotoxic activity. A liquid‐chromatography mass‐spectrometry (LC‐MS) method was proposed for the sensitive, specific and direct detection of yessotoxin and its analogs. In addition, the proposed method allows us highlight the possible presence of new analogs, and enables us to propose an effective structural hypothesis even when full structural elucidation of new toxins by NMR spectroscopy is hampered by the limited amount of material available. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Ein Horchposten ins Universum
Authors: Aufmuth Peter
Published: March 2004

Erst seit wenigen Jahren ist es möglich, Gravitationswellen nachzuweisen. Ein neu entwickelter Gravitationswellendetektor zeichnet sich durch besondere Empfindlichkeit aus. Mit seiner Hilfe lassen sich wichtige Informationen über Schwarze Löcher, dunkle Materie und den Ursprung des Alls gewinnen
Keratin 14 Cre transgenic mice authenticate keratin 14 as an oocyte‐expressed protein
Authors: Hafner Martin , Wenk Jutta , Nenci Arianna , Pasparakis Manolis , Scharffetter‐Kochanek Karin , Smyth Neil , Peters Thorsten , Kess Daniel , Holtkötter Olaf , Shephard Pierre , Kudlow Jeffrey E. , Smola Hans , Haase Ingo , Schippers Angela , Krieg Thomas , Müller Werner
Published: April 2004

Summary: Three mouse lines expressing Cre recombinase under the control of the human K14 promoter induced specific deletion of loxP flanked target sequences in the epidermis, in tongue, and thymic epithelium of the offspring where the Cre allele was inherited from the father. Where the mother carried the Cre allele, loxP flanked sequences were completely deleted in all tissues of the offspring, even in littermates that did not inherit the Cre allele. This maternally inherited phenotype indicates that the human K14 promoter is transcriptionally active in murine oocytes and that the enzyme remains active until after fertilization, even when the Cre allele becomes transmitted to the polar bodies during meiosis. Detection of K14 mRNA by RT‐PCR in murine ovaries and immunohistochemical identification of the K14 protein in oocytes demonstrates that the human K14 promoter behaves like its murine homolog, thus identifying K14 as an authentic oocytic protein. genesis 38:176–181, 2004. © 2004 Wiley‐Liss, Inc.
Generation of Pax2‐Cre mice by modification of a Pax2 bacterial artificial chromosome
Authors: Ohyama Takahiro , Groves Andrew K.
Published: April 2004

Summary: The Pax2 gene is expressed in the developing otocyst, kidney, and midbrain–hindbrain boundary. We generated Pax2‐Cre transgenic lines by modification of a Pax2 bacterial artificial chromosome (BAC). In one Pax2‐Cre line, Cre mRNA starts to be expressed in the otic placode at the late presomite stage. R26R reporter mouse analysis revealed that the Cre expression is sufficient to delete the loxP‐flanked sequences in most of the cells in the inner ear. Reporter‐positive cells are also detected in other Pax2‐expressing tissues such as midbrain, cerebellum, olfactory bulb, and kidney, suggesting that these cells are the descendants of Pax2‐expressing cells in these tissues and that Pax2‐Cre transgenic mice can delete genes efficiently in these tissues. genesis 38:195–199, 2004. © 2004 Wiley‐Liss, Inc.
Impaired associative memory in temporal lobe epilepsy subjects after lesions of hippocampus, parahippocampal gyrus, and amygdala
Authors: Weniger Godehard , Boucsein Katrin , Irle Eva
Published: April 2004

There has been growing interest in the differential role of medial temporal lobe structures in learning and memory. The goal of the present study was to clarify how lesions of hippocampus, parahippocampal gyrus, and amygdala interfere with associative learning and memory. Thirty subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 30 matched healthy control subjects. A set of neuropsychological test measures and an associative learning task requiring the learning and recall of objects and faces were administered. The lesions of hippocampus, parahippocampal gyrus, amygdala, and fusiform gyrus of TLE subjects were determined by three‐dimensional magnetic resonance imaging (3‐D MRI) volumetric assessment. The results indicate that TLE subjects with combined large hippocampal lesions, large parahippocampal gyrus (i.e., perirhinal/entorhinal) lesions, and large amygdala lesions learned and recalled the associative task significantly worse than control subjects or subjects with small lesions of the hippocampus, parahippocampal gyrus, and amygdala. Regression analysis revealed that larger lesions of the parahippocampal gyrus (i.e., perirhinal/entorhinal cortices) were significantly related to increasing deficits on the task, and that hippocampal and amygdala lesion size did not significantly improve the prediction. Our results suggest that perirhinal and entorhinal cortices may contribute predominantly to the associative learning and recall of objects and faces. © 2004 Wiley‐Liss, Inc.
Long‐term hydrological simulation based on the Soil Conservation Service curve number
Authors: Mishra Surendra Kumar , Singh Vijay P.
Published: April 2004

Presenting a critical review of daily flow simulation models based on the Soil Conservation Service curve number (SCS‐CN), this paper introduces a more versatile model based on the modified SCS‐CN method, which specializes into seven cases. The proposed model was applied to the Hemavati watershed (area = 600 km2) in India and was found to yield satisfactory results in both calibration and validation. The model conserved monthly and annual runoff volumes satisfactorily. A sensitivity analysis of the model parameters was performed, including the effect of variation in storm duration. Finally, to investigate the model components, all seven variants of the modified version were tested for their suitability. Copyright © 2004 John Wiley & Sons, Ltd.
Hypoxia‐inducible factor‐1α in non small cell lung cancer: Relation to growth factor, protease and apoptosis pathways
Authors: Swinson Daniel E.B. , Jones J. Louise , Cox Giles , Richardson Donna , Harris Adrian L. , O'Byrne Kenneth J.
Published: March 2004

Hypoxia‐inducible factor (HIF)‐1α is the regulatory subunit of HIF‐1 that is stabilized under hypoxic conditions. Under different circumstances, HIF‐1α may promote both tumorigenesis and apoptosis. There is conflicting data on the importance of HIF‐1α as a prognostic factor. This study evaluated HIF‐1α expression in 172 consecutive patients with stage I–IIIA non small cell lung cancer (NSCLC) using standard immunohistochemical techniques. The extent of HIF‐1α nuclear immunostaining was determined using light microscopy and the results were analyzed using the median (5%) as a low cut‐point and 60% as a high positive cut‐point. Using the low cut‐point, positive associations were found with epidermal growth factor receptor (EGFR; p = 0.01), matrix metalloproteinase (MMP)‐9 (p = 0.003), membranous (p < 0.001) and perinuclear (p = 0.004) carbonic anhydrase (CA) IX, p53 (p = 0.008), T‐stage (p = 0.042), tumor necrosis (TN; p < 0.001) and squamous histology (p < 0.001). No significant association was found with Bcl‐2 or either N‐ or overall TMN stage or prognosis. When the high positive cut‐point was used, HIF‐1α was associated with a poor prognosis (p = 0.034). In conclusion, the associations with EGFR, MMP‐9, p53 and CA IX suggest that these factors may either regulate or be regulated by HIF‐1α. The association with TN and squamous‐type histology, which is relatively more necrotic than other NSCLC types, reflects the role of hypoxia in the regulation of HIF‐1α. The prognostic data may reflect a change in the behavior of HIF‐1α in increasingly hypoxic environments. © 2004 Wiley‐Liss, Inc.
Potential efficacy of p16 gene therapy for EBV‐positive nasopharyngeal carcinoma
Authors: Li Anna Aihua , Ng Emily , Shi Wei , Lee Andrew , Chia Marie , Liu Ta‐Jen , Huang Dolly , O'Sullivan Brian , Gullane Pat , Liu Fei‐Fei
Published: April 2004

The p16 cell cycle inhibitory gene is a potentially critical molecular abnormality in nasopharyngeal carcinoma (NPC). Its expression is silenced through either deletion or promoter methylation in the vast majority of NPC. This in turn is associated with absent or reduced protein expression, which has been previously demonstrated by our group to correlate with inferior clinical outcome. Therefore, we were interested in evaluating the potential of adenoviral mediated p16 gene therapy (adv.p16) in an EBV‐positive NPC model (C666‐1). We confirm that under basal conditions, p16 protein is undetectable in C666‐1 cells, which, in turn, is associated with retention of retinoblastoma protein (pRb) expression. P16 expression was observed as early as 4 hr after infection of C666‐1 cells with adv.p16 (10 pfu/cell) with no discernible perturbation in pRb for up to 24 hr. At 48 hr post‐infection, p16 expression continued to increase, but at this point, pRb expression started to decline significantly. Cell viability decreased in a dose‐dependent manner, down to 20% using 50 pfu/cell of adv.p16. The addition of radiation therapy (RT) administered 24 hr post‐infection achieved only a slightly additive cytotoxicity. Adv.p16 therapy resulted in multiple mechanisms of cytotoxicity, including cell cycle arrest at the G0/G1 phase, induction of senescence, along with apoptosis. Ex vivo infection of C666‐1 cells with adv.p16 (25 pfu/cell) with subsequent implantation into scid mice completely prevented tumor formation, followed for up to 51 days. Our study demonstrates the potential efficacy of adv.p16 gene therapy for NPC, mediated through multimodal mechanisms of cytotoxicity. Future evaluations will examine strategies to increase in vivo tumor transduction with a view towards future clinical applications. © 2004 Wiley‐Liss, Inc.
Frequent epigenetic inactivation of RIZ1 by promoter hypermethylation in human gastric carcinoma
Authors: Oshimo Yasuhiro , Oue Naohide , Mitani Yoshitsugu , Nakayama Hirofumi , Kitadai Yasuhiko , Yoshida Kazuhiro , Chayama Kazuaki , Yasui Wataru
Published: March 2004

The retinoblastoma protein‐interacting zinc finger gene, RIZ1 (GenBank accession number U17838), is involved in chromatin‐mediated gene expression and is also a target for frameshift mutation in microsatellite‐unstable cancers. Methylation of the RIZ1 promoter CpG island has been shown to be a common mechanism in inactivating the RIZ1 gene in human liver and breast cancers. We investigated levels of RIZ1 mRNA in 45 gastric carcinoma tissues by quantitative RT‐PCR and in gastric carcinoma cell lines by RT‐PCR. In addition, we examined CpG island methylator phenotype (CIMP) status, p53 mutation status, and the correlation between promoter methylation status and RIZ1 mRNA expression. CIMP status was investigated by examining the methylation status of MINT1, MINT2, MINT12, MINT25 and MINT31. p53 mutation status was examined by PCR‐single strand conformation polymorphism and promoter methylation status was examined by methylation‐specific PCR. Promoter hypermethylation of the RIZ1 gene was found in 31 (69%) of 45 gastric carcinoma tissues and in 3 (21%) of 14 corresponding non‐neoplastic mucosae, the incidence being significantly different (p = 0.002). None of the 12 normal gastric tissues from young non‐cancer individuals showed hypermethylation. Promoter hypermethylation was associated with reduced RIZ1 expression in gastric carcinoma tissues (p = 0.029). Promoter hypermethylation of the RIZ1 gene was significantly associated with CIMP (p = 0.002). Mutation status of the p53 gene was not associated with methylation status or RIZ1 expression in gastric carcinoma. In gastric carcinoma cell lines MKN‐28 and KATO‐III, the RIZ1 promoter was hypermethylated and RIZ1 transcription was inactive. Treatment of these cells with demethylating agent 5‐aza‐2′‐deoxycytidine restored RIZ1 transcription. Our results suggest that transcriptional inactivation of the RIZ1 gene by promoter hypermethylation may participate in stomach carcinogenesis. © 2004 Wiley‐Liss, Inc.
Cancer mortality in Europe, 1995–1999, and an overview of trends since 1960
Authors: Levi Fabio , Lucchini Franca , Negri Eva , Boyle Peter , La Vecchia Carlo
Published: March 2004

Mortality data, abstracted from the World Health Organization database, are presented in tabular form for 26 cancer sites or groups of sites, plus total cancer mortality, in 36 European countries during the period 1995–1999. Trends in mortality are also given in graphic form for 23 major countries plus the European Union as a whole over the period 1960–1999. In the European Union, total cancer mortality declined by 7% for both sexes over the last 5 years considered. The fall since the late 1980s was 10% in both sexes, corresponding to the avoidance of over 90,000 deaths per year, as compared to the rates of the late 1980s. For the first time, over the last few years, some leveling of mortality was reported also in the Russian Federation, the Czech Republic, Poland, Hungary and other Eastern European countries, although cancer rates in those areas remain exceedingly high. The overall favorable pattern of cancer mortality over recent years is largely driven by the decline of tobacco‐related cancer mortality in men. However, important components of the trends are also the persistence of substantial falls in gastric cancer, mainly in Russia and Eastern Europe, the recent decline in intestinal cancer in both sexes and of breast cancer in women, together with the long‐term falls in uterine (cervical) cancer, leukemias, Hodgkin's disease and other neoplasms amenable to advancements in diagnosis and treatment. Female lung cancer mortality has been declining in the Russian Federation, but is still rising in other areas of the continent. Thus, urgent intervention is needed to bring under control the tobacco‐related lung cancer epidemic in European women before it reaches the high level observed in North America. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html © 2004 Wiley‐Liss, Inc.
Carboplatin selectively induces the VEGF stress response in endothelial cells: Potentiation of antitumor activity by combination treatment with antibody to VEGF
Authors: Wild Robert , Dings Ruud P.M. , Subramanian Indira , Ramakrishnan S.
Published: April 2004

Vascular Endothelial Growth Factor (VEGF) functions as a key regulator in tumor angiogenesis. In addition, VEGF is an important survival factor for endothelial cells under chemical or physical stress. In our report, we show that treatment of endothelial cells with the chemotherapeutic agent carboplatin significantly increased the expression of VEGF. Furthermore, neutralization of secreted VEGF with specific polyclonal anti‐VEGF antibodies or monoclonal antibody sensitized endothelial cells to carboplatin treatment and increased apoptosis several‐fold. Interestingly, carboplatin treatment did not alter VEGF expression in tumor cells. Similarly, antibody to VEGF did not change the chemosensitivity of tumor cells to this drug. Most importantly, tumor‐bearing animals treated with carboplatin showed an increase in VEGF immunoreactivity in the tumor vasculature, confirming the in vitro studies. Based on these observations, we determined whether neutralization of VEGF could enhance the anti‐tumor activity of carboplatin in an in vivo ovarian cancer model system. A combination therapy consisting of a suboptimal dose of carboplatin (32.5 mg/kg/inj., q3d×5; i.p.) and polyclonal anti‐VEGF antibody (2 mg/inj., q3d×10; i.p.) significantly enhanced solid tumor growth inhibition over individual monotherapies and included multiple complete responses. These findings suggest that VEGF is a critical endothelial cell specific survival factor that is induced by carboplatin and contributes to the protection of tumor vasculature during chemotherapy treatment. In addition, these results provide evidence for a potential mechanism that underlies enhanced anti‐tumor activity achieved with chemotherapy and anti‐VEGF antibody combination treatment regimens as recently reported in a number of clinical trials. We conclude that a similar type of combination therapy may be applicable to many types of malignancies since VEGF expression was differentially induced in the tumor host environment (i.e., tumor vasculature) and not in the tumor cells themselves; hence, this phenomenon may be independent of the type and origin of the primary cancer. © 2004 Wiley‐Liss, Inc.
Comparative genomic hybridization analysis of hereditary swine cutaneous melanoma revealed loss of the swine 13q36‐49 chromosomal region in the nodular melanoma subtype
Authors: Apiou Françoise , Vincent‐Naulleau Silvia , Spatz Alain , Vielh Philippe , Geffrotin Claudine , Frelat Geffrotin , Dutrillaux Bernard , Le Chalony Catherine
Published: March 2004

Genetic alterations implicated in malignant melanoma are still poorly understood. Malignant melanomas present highly variable histologic and cytologic patterns. The aim of the present study is to define genomic imbalances associated with the development of 2 histologic types of swine hereditary cutaneous melanoma. We have investigated 11 swine tumors by comparative genomic hybridization (CGH), 4 superficial spreading melanomas (SSMs) and 7 nodular melanomas (NMs). Following laser capture microdissection and degenerate oligonucleotide primed‐polymerase chain reaction, we were able to isolate and then amplify DNA from the 2 histologic subtypes. Consensus regions of chromosome gains were identified on both histologic subtypes, on swine chromosomes 3p13‐p17 (75% of the SSMs and 71% of the NMs), 12q (100% of the SSMs and 57% of the NMs) and 14q11‐q21 (75% of the SSMs and 42% of NMs). Chromosomal loss was restricted to NM lesions and the swine 13q36‐49 region was lost in 100% of the NMs. Interphase fluorescence in situ hybridization with a probe mapping to the 13q41‐q42 region indicates loss of the corresponding region on NM lesions. Taking into account this CGH analysis and the comparative genomic data between swine and human genomes, we suggest that a role for the human chromosomes 3p11‐qter and chromosome 21 losses should be investigated in human nodular melanoma progression. © 2004 Wiley‐Liss, Inc.
Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case‐control study
Authors: Linseisen Jakob , Piller Regina , Hermann Silke , Chang‐Claude Jenny
Published: March 2004

A diet high in isoflavonoids (soy) is associated with lower breast cancer risk in Asian populations. Due to the low soy intake, dietary lignans may be the more important phytoestrogen class in Western populations. We used a population‐based case‐control study of breast cancer by age 50 in southern Germany to evaluate the association between dietary intake of different phytoestrogens and premenopausal breast cancer risk. Dietary information was collected from 278 premenopausal cases and 666 age‐matched controls, using a validated FFQ. Using multivariate logistic regression, the highest vs. lowest intake quartiles of daidzein and genistein yielded significantly reduced ORs (95% CI) for breast cancer risk of 0.62 (0.40–0.95) and 0.47 (0.29–0.74), respectively. The protective effects of daidzein and genistein were found only for hormone receptor‐positive tumors. High intake of other isoflavonoids, e.g., formononetin and biochanin A, as well as the sum of isoflavonoids were not associated with a decrease in risk. Breast cancer risk significantly decreased with a high intake of the plant lignan matairesinol (OR = 0.58, 95% CI 0.37–0.94) but not secoisolariciresinol or the sum of plant lignans. However, both estimated mammalian lignans, enterodiol and enterolactone, were inversely associated with breast cancer risk, with ORs (95% CI) of 0.61 (0.39–0.98) and 0.57 (0.35–0.92), respectively. No effect was found for total phytoestrogen intake. Our results suggest an important role of dietary intake of daidzein and genistein, despite low levels, as well as of matairesinol and mammalian lignans to reduce premenopausal breast cancer risk in this study population. © 2004 Wiley‐Liss, Inc.
Impact of GSTT1, GSTM1, GSTP1 and NAT2 genotypes on KRAS2 and TP53 gene mutations in colorectal cancer
Authors: Ferraz Jean‐Marc , Zinzindohoué Franck , Lecomte Thierry , Cugnenc Paul‐Henri , Loriot Marie‐Anne , Beaune Philippe , Stücker Isabelle , Berger Anne , Laurent‐Puig Pierre
Published: March 2004

Which carcinogens are of influence in the development of human colorectal cancers remains a question; one answer could be the finding that specific polymorphisms in xenobiotic metabolizing enzymes are related to particular mutations in cancer genes. KRAS2 and TP53 gene mutations as well as genotypes for GSTM1, GSTP1, GSTT1 and NAT2 were determined in an exploratory series of 165 stable colorectal cancers. Mutations in KRAS2 and TP53 were found in 34% and 57.5% of cases, respectively. The KRAS2 mutation frequency was significantly lower in patients with a GSTT1 null genotype than in those with a GSTT1 non‐null genotype (18% vs. 38%, p = 0.03). The overall risk of KRAS2 mutation for patients with distal colorectal cancer and GSTT1 null genotype was 0.3 (95% CI 0.1–0.9) compared to patients with distal colorectal cancer and non‐null GSTT1 genotype. The overall risk of KRAS2 mutation was similarly reduced (OR = 0.4, 95% CI 0.2–0.9) for patients with distal colorectal cancer and GSTP1 mutated genotypes compared to patients with distal colorectal cancer and wild‐type genotype. Patients with GSTP1 wild‐type genotype appeared to be at significantly lower risk for TP53 mutation compared to patients with mutated genotypes (p = 0.023). Our results suggest that GSTT1 and GSTP1 could play a role in the occurrence of KRAS2 and TP53 mutations in colorectal cancer and generate a hypothesis on the dietary factors that could be incriminated. © 2004 Wiley‐Liss, Inc.
Natural killer cell depletion confounds the antitumor mechanism of endogenous IL‐12 overexpression
Authors: Miller George , Bleier Joshua I. , Antonescu Cristina , Pillarisetty Venu G. , Shah Alaap B. , Lahrs Svenja , DeMatteo Ronald P.
Published: April 2004

IL‐12 gene transfer to hepatocytes using a recombinant adenovirus vector (AdIL‐12) has been shown to protect against primary and metastatic liver tumors in mice. However, the mechanism of protection has been elusive and studies using depleting monoclonal antibodies or transgenic mice have purported it to be independent of T and NK cells. We postulated that depletion of NK cells may distort the experimental model and misrepresent the antitumor mechanism by altering the magnitude and duration of transgene expression. We show in mice treated with AdIL‐12 that NK depletion increased serum IL‐12 levels by more than 250‐fold and prolonged transgene expression by nearly 2 weeks compared to nondepleted mice. To determine the contribution of NK cells to tumor protection after AdIL‐12 treatment, we analyzed NK cells from treated animals. Isolated NK cells were markedly activated in terms of their lytic activity and IFN‐γ secretion. Adoptive transfer of NK cells from mice that had been treated with AdIL‐12 to naive mice was sufficient to confer protection against colorectal hepatic metastases. This protection was mediated in part by NK‐cell production of IFN‐γ. Our findings indicate that NK‐cell depletion distorts the model of systemic AdIL‐12 administration by markedly altering transgene expression, which then may potentiate other antitumor mechanisms, and that endogenous IL‐12 overexpression activates NK cells, rendering them sufficient to protect against liver metastases. These data have critical implications for investigating the immunologic mechanisms of experimental models that utilize gene transfer. © 2004 Wiley‐Liss, Inc.
Null association between pregnancy termination and breast cancer in a registry‐based study of parous women
Authors: Lash Timothy L. , Fink Aliza K.
Published: April 2004

Studies suggesting a positive association between pregnancy termination and breast cancer risk have often been of retrospective case‐control design, so subject to selection and recall biases. We undertook a registry‐based analysis with minimal selection bias and prospective record‐based ascertainment of terminations. The source population comprised Massachusetts women with a record of giving birth between 1987 and 1999 in the Massachusetts Vital Statistics Registry. Primary breast cancer cases were 25–55 years old at diagnosis between 1988 and 2000 and had a record of the diagnosis in the Massachusetts Cancer Registry. We matched 3 controls to each case on maternal age, year of giving birth and birth facility. Information on terminations (induced and spontaneous) before the birth of record, the matched factors and potential confounders were collected from the birth certificate. After adjustment for the matched factors, age, parity and maternal and paternal education, the odds ratio associating any termination history with breast cancer risk equaled 0.91 (95% CI = 0.79–1.05). The marginally protective adjusted odds ratio largely derived from a protective effect among women with parity equaled to 1 (OR for any termination = 0.68; 95% CI = 0.45–1.03), suggesting a protective effect of terminated pregnancy among women with one live birth. © 2004 Wiley‐Liss, Inc.
Non‐Hodgkin's lymphoma and hepatitis C virus: A case‐control study from northern and southern Italy
Authors: Talamini Renato , Montella Maurizio , Crovatto Marina , Dal Maso Luigino , Crispo Anna , Negri Eva , Spina Michele , Pinto Antonio , Carbone Antonino , Franceschi Silvia
Published: April 2004

HCV has been associated with NHL, but the evidence from case series and case‐control studies is not totally consistent. Between 1999 and 2002, we conducted a hospital case‐control study on the association between HCV, HBV and NHL in 2 areas of Italy where HCV infection is relatively frequent. Cases (n = 225, median age 59 years) were consecutive patients with a new diagnosis of NHL admitted to local specialized and general hospitals. Controls (n = 504, median age 63 years) were patients with a wide spectrum of acute conditions admitted to the same hospitals as cases. HCV prevalence was 19.6% among NHL cases and 8.9% among controls (adjusted OR = 2.6, 95% CI 1.6–4.3). The ORs for HCV were similar for low‐grade and intermediate‐/high‐grade B‐cell NHL (3.2 and 2.4, respectively) as well as for nodal and extranodal NHL (2.7 and 2.6, respectively). Positivity for HBsAg was found in 3.8% of cases and 0.9% of controls (OR = 4.1, 95% CI 1.2–14.4). An elevated OR was also found for history of hepatitis C (OR = 4.7, 95% CI 2.3–9.5). History of blood transfusion before 1990 was associated with HCV positivity among controls but not with NHL risk. In conclusion, HCV infection was associated with an increase in NHL risk, and the fraction of NHL cases attributable to HCV was 12.4% (range 6.3–18.5%). © 2004 Wiley‐Liss, Inc.
Interferon‐γ differentially regulates susceptibility of lung cancer cells to telomerase‐specific cytotoxic T lymphocytes
Authors: Tajima Kouhei , Ito Yoshinori , Demachi Ayako , Nishida Keiko , Akatsuka Yoshiki , Tsujimura Kunio , Hida Toyoaki , Morishima Yasuo , Kuwano Hiroyuki , Mitsudomi Tetsuya , Takahashi Toshitada , Kuzushima Kiyotaka
Published: April 2004

There is accumulating evidence that peptides derived from the catalytic subunit of human telomerase reverse transcriptase (hTERT) are specifically recognized by CD8+ cytotoxic T lymphocytes. We investigated the cytotoxicity of a human leukocyte antigen (HLA)‐A*2402‐restricted hTERT‐derived peptide 461–469 (hTERT461)‐specific CD8+ T‐cell clone, designated as K3‐1, established from a healthy donor by repetitive peptide stimulation. This clone exhibited cytotoxicity against 4 out of 6 HLA‐A24‐positive lung cancer cell lines with positive telomerase activity but not 4 HLA‐A24‐negative examples. When the target cells were pretreated with 100 U/ml of interferon (IFN)‐γ for 48 hr, the susceptibility to K3‐1 increased with PC9 cells but unexpectedly decreased with LU99 cells. However, in both cell lines, the expression of molecules associated with epitope presentation such as HLA‐A24, transporters associated with antigen processing, low molecular weight polypeptide 7 and proteasome activator 28 was similarly increased after IFN‐γ treatment. Results of CTL assays using acid‐extracted peptides indicated that the epitope increased on PC9 cells but not on LU99 cells after IFN‐γ treatment. Semi‐quantitative reverse transcriptase polymerase chain reaction disclosed that the expression of hTERT was attenuated in LU99 but not in PC9 cells, accounting for the decreased cytotoxicity mediated by K3‐1. The attenuation of the hTERT expression and K3‐1‐mediated cell lysis after IFN‐γ treatment was also observed in primary adenocarcinoma cells obtained from pulmonary fluid of a lung cancer patient. Our data underline the utility of peptide hTERT461 in immunotherapy for lung cancer, as with other malignancies reported earlier, and suggest that modulation of hTERT expression by IFN‐γ needs to be taken into account in therapeutic approach. © 2004 Wiley‐Liss, Inc.
B‐cell non‐Hodgkin's lymphoma and hepatitis C virus infection: A systematic review
Authors: Negri Eva , Little D'Anna , Boiocchi Mauro , La Vecchia Carlo , Franceschi Silvia
Published: March 2004

A high prevalence of hepatitis C virus (HCV) infection in patients with B‐cell non‐Hodgkin's lymphoma (B‐NHL) has been reported in some, but not all, studies, and the association showed a strong regional variation. We conducted a systematic review of the prevalence of HCV infection in case series of B‐NHL and, when an appropriate control group was available, of the odds ratio of B‐NHL associated with HCV infection. A high HCV prevalence in B‐NHL was found in southern and eastern Europe, Japan and the southern United States, but not in central and northern Europe, Canada, northern United States, or a few Asian countries. Possible sources of heterogeneity and bias are discussed. The odds ratio of B‐NHL for HCV infection was relatively weak, ranging from 2 to 4 in most studies. Thus, even if the observed association were causal, the percentage of cases of B‐NHL attributable to HCV infection would be relatively low (10%) also in countries with a high prevalence of HCV infection in the general population, and extremely low in other countries. This may explain apparent inconsistencies between studies. Potential mechanisms of action are also discussed. © 2004 Wiley‐Liss, Inc.
Bone metastasis: Osteoblasts affect growth and adhesion regulons in prostate tumor cells and provoke osteomimicry
Authors: Knerr Kerstin , Ackermann Karin , Neidhart Tanja , Pyerin Walter
Published: March 2004

Bone metastasis is the primary cause of death in human prostate cancer. Disseminated from primary tumor and distributed via the bloodstream, a proportion of prostate carcinoma cells eventually reach the skeleton and develop into metastases, requiring adhesion to inner bone surfaces lined by osteoblasts. The crosstalk of tumor cells with osteoblasts is a critical but poorly characterized step in the metastatic process. Using an in vitro metastasis model system, we have been examining effects of osteoblast‐released factors on gene expression of prostate carcinoma cells. Here, we show by large‐scale transcript profiling and quantitative RT‐PCR that osteoblast‐released factors target in particular the proliferation and adhesion regulons of tumor cells. Genes encoding components of the cell‐cycle control machinery and connected pathways are predominantly repressed and cell proliferation is slowed down, resembling in vivo observations assumed to render commonly used chemotherapeutic measures ineffective. Genes encoding anchoring junction components are predominantly elevated, and the adhesion properties of tumor cells are altered. Moreover, prostate carcinoma cells are provoked to undergo osteomimicry, i.e., to express bone cell–related genes. The data indicate that the crosstalk with osteoblasts induces expressional changes in prostate carcinoma cells favoring the bone colonization process. © 2004 Wiley‐Liss, Inc.
Polygenic control of hepatocarcinogenesis in Copenhagen × F344 rats
Authors: De Miglio Maria R. , Pascale Rosa M. , Simile Maria M. , Muroni Maria R. , Virdis Patrizia , Kwong Kelvin M.‐T. , Wong Leslie K.L. , Bosinco Giovanni M. , Pulina Franca R. , Calvisi Diego F. , Frau Maddalena , Wood Geoffrey A. , Archer Michael C. , Feo Francesco
Published: March 2004

Cop and CFF1 rats exhibit resistance to hepatocarcinogenesis, associated with high rates of remodeling of neoplastic lesions. We have mapped hepatocarcinogenesis susceptibility, resistance and remodeling loci affecting the number, volume and volume fraction of neoplastic nodules induced by the “resistant hepatocyte” model in male CFF2 rats. Three loci in significant linkage with the number or volume of nonremodeling lesions were identified on chromosomes 1, 4 and 18. Suggestive linkage with number or volume fraction of total, nonremodeling or remodeling lesions was found for 7 loci on chromosomes 1, 2, 13, 14 and 15. All of these loci showed significant allele‐specific effects on the phenotypic traits. We also detected by analysis of variance 19 2‐way interactions inducing phenotypic effects not predictable on the basis of the sum of separate effects. These novel epistatic loci were in significant linkage with the number and/or volume of total, nonremodeling or remodeling nodules. These data indicate that susceptibility to hepatocarcinogenesis in Cop rats is controlled by a complex array of genes with several gene–gene interactions and that different genetic mechanisms control remodeling and nonremodeling liver nodules. Frequent deregulation in human liver cancer of genes positioned in chromosomal segments syntenic to rat susceptibility/resistance loci suggests some similarities between the genetic mechanisms involved in hepatocarcinogenesis in rats and humans. © 2004 Wiley‐Liss, Inc.
Enhanced efficacy of DNA vaccination against Her‐2/neu tumor antigen by genetic adjuvants
Authors: Chang Sun Young , Lee Kyung‐Chul , Ko Sung‐Youl , Ko Hyun‐Jeong , Kang Chang‐Yuil
Published: March 2004

Certain types of malignant tumors overexpress Her‐2/neu, a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family. To develop an effective Her‐2/neu vaccine for selective immunotherapy of these malignancies, we prepared Her‐2/neu DNA plasmid encoding the transmembrane and extracellular domain (pHM) and tested the ability of this construct to induce antitumor immunity in animal models. In addition, we investigated the effects of cytokine used as a genetic adjuvant. Modulation by factors that affect T‐cell function or hematopoiesis, including interleukin‐12, interleukin‐15, interleukin‐18, interleukin‐23, Eta‐1, Flt3L and GM‐CSF, was studied in the forms of monocistronic and bicistronic plasmid. Our results demonstrated that vaccination of pHM could induce successful antitumor immunity against Her‐2/neu‐expressing murine tumor cells in BALB/c mice. We also showed that the antitumor activity of pHM was augmented by coadministration and coexpression of different cytokines. Despite the similar levels of gene expression, the antitumor effects of bicistronic plasmids coexpressing Her‐2/neu antigen and cytokine were improved in comparison with coadministration of separate monocistronic plasmid. In particular, coexpression of interleukin‐18 or GM‐CSF with Her‐2/neu increased antitumor activity in both preventive and therapeutic experiments. These findings can help in the decision concerning which of the various cytokine adjuvants should be used for the development of a Her‐2/neu DNA vaccine. In addition, our results from a large panel of cytokine adjuvants in the various tumor models may provide an insight into the important immune components of antitumor immunity. © 2004 Wiley‐Liss, Inc.
Association of cigarette smoking with the risk of ovarian cancer
Authors: Pan Sai Yi , Ugnat Anne‐Marie , Mao Yang , Wen Shi Wu , Johnson Kenneth C. ,   The Canadian Cancer Registries Epidemiology Research Group
Published: March 2004

Cigarette smoking may be associated with ovarian cancer risk. This association may differ by histological type. The authors conducted a population‐based case‐control study in Canada of 442 incident cases of ovarian cancer and 2,135 controls 20–76 years of age during 1994–1997 to examine this association, overall and by histological type. Compared to women who never smoked, those who smoked had higher odds (odds ratio [OR] = 1.22; 95% confidence interval [CI] = 0.98–1.53) of having ovarian cancer, and the OR was larger for ex‐smokers (1.30; 95% CI = 1.01–1.67) than for current smokers (1.10; 95% CI = 0.81–1.49). The association with cigarette smoking was stronger for mucinous tumors (OR = 1.77; 95% CI = 1.06–2.96) than for nonmucinous tumors (OR = 1.13; 95% CI = 0.89–1.44). In addition, the odds of smokers having mucinous tumors increased with years of smoking (OR = 1.36, 1.88, 1.19, 4.89 for <20, 21–30, 31–40 and >40 years, respectively; p for trend = 0.002), number of cigarettes smoked per day (OR = 1.55, 1.89, 2.28 for <10, 11–20 and >20 cigarettes/day, respectively; p for trend = 0.014) and smoking pack‐years (OR = 1.13, 2.65, 1.77 and 2.39 for <10, 11–20, 21–30 and >30 pack‐years, respectively; p for trend = 0.004). Our data suggest that cigarette smoking is associated with an increased risk of ovarian cancer, especially for mucinous types. © 2004 Wiley‐Liss, Inc.
Short‐term monitoring of fiscal policy discipline
Authors: Camba‐Mendez Gonzalo , Lamo Ana
Published: April 2004

Under the Maastricht Treaty and the Stability and Growth Pact (SGP), European Union (EU) Member States commit themselves to avoid excessive deficits over 3% of GDP and to pursue the medium‐term objective of budgetary positions close to balance or in surplus. The SGP also provides regulation for the surveillance of budgetary positions. An analysis of tools for the surveillance of budgetary positions is the focus of this paper. In particular, it addresses two open issues in the empirical public finance literature which are crucial for monitoring fiscal policy discipline in the EU. First, the estimation of the structural component of the fiscal balance ratio. Second, the computation, when only annual fiscal data are available, of quarterly budget balance ratios, using relevant information from quarterly measured macroeconomic series. An econometric model that addresses both issues is presented and estimated. Additionally, this modelling framework allows us to answer questions such as: what is the safety margin that will prevent a particular country from reaching, with certain probability, a budget deficit that breaches the 3% upper bound? Copyright © 2004 John Wiley & Sons, Ltd.
Do dropouts suffer from dropping out? Estimation and prediction of outcome gains in generalized selection models
Authors: Li Mingliang , Poirier Dale J. , Tobias Justin L.
Published: April 2004

In this paper we describe methods for predicting distributions of outcome gains in the framework of a latent variable selection model. We describe such procedures for Student‐t selection models and a finite mixture of Gaussian selection models. Importantly, our algorithms for fitting these models are simple to implement in practice, and also permit learning to take place about the non‐identified cross‐regime correlation parameter. Using data from High School and Beyond, we apply our methods to determine the impact of dropping out of high school on a math test score taken at the senior year of high school. Our results show that selection bias is an important feature of this data, that our beliefs about this non‐identified correlation are updated from the data, and that generalized models of selectivity offer an improvement over the ‘textbook’ Gaussian model. Further, our results indicate that on average dropping out of high school has a large negative impact on senior‐year test scores. However, for those individuals who actually drop out of high school, the act of dropping out of high school does not have a significantly negative impact on test scores. This suggests that policies aimed at keeping students in school may not be as beneficial as first thought, since those individuals who must be induced to stay in school are not the ones who benefit significantly (in terms of test scores) from staying in school. Copyright © 2004 John Wiley & Sons, Ltd.