bluuebunny/crossref_metadata_2025 huggingface dataset:
The Shiga toxin B‐subunit targets antigen in vivo to dendritic cells and elicits anti‐tumor immunity
Authors: Vingert Benoit , Adotevi Olivier , Patin Delphine , Jung Steffen , Shrikant Protul , Freyburger Ludovic , Eppolito Cheryl , Sapoznikov Anita , Amessou Mohamed , Quintin‐Colonna Françoise , Fridman Wolf Herman , Johannes Ludger , Tartour Eric
Published: March 2006

The non‐toxic B‐subunit of Shiga toxin (STxB) interacts with the glycolipid Gb3, which is preferentially expressed on dendritic cells (DC) and B cells. After administration of STxB chemically coupled to OVA (STxB‐OVA) in mice, we showed that the immunodominant OVA257–264 peptide restricted by Kb molecules is specifically presented by CD11c+CD8α– DC, some of them displaying a mature phenotype. Using mice carrying a transgene encoding a diphtheria toxin receptor (DTR) under the control of the murine CD11c promoter, which allows inducible ablation of DC, we showed that DC are required for efficient priming of CTL after STxB‐OVA vaccination. Immunization of mice with STxB‐OVA induced OVA‐specific CD8+ T cells detected ex vivo; these cells were long lasting, since they could be detected even 91 days after the last immunization and were composed of both central and memory T cells. Vaccination of mice with STxB‐OVA and STxB coupled to E7, a protein derived from HPV16, inhibited tumor growth in prophylactic and therapeutic experiments. This effect was mainly mediated by CD8+ T cells. STxB therefore appears to be a powerful carrier directly targeting DC in vivo, resulting in a strong and durable CTL response associated with tumor protection.
IL‐18 stimulates IL‐13‐mediated IFN‐γ‐sensitive host resistance in vivo
Authors: Liu Qian , Liu Zhugong , Whitmire Jeannette , Alem Farhang , Hamed Hossein , Pesce John , Urban Joseph F. , Gause William C.
Published: March 2006

IL‐4 and IL‐13 are up‐regulated during in vivo responses to many nematode parasites, but increasing evidence suggests that increases in IL‐13 can also occur independently of the IL‐4‐dominant Th2 response. Blocking B7 after Trichuris muris inoculation inhibits resistance and IL‐4 elevations, instead resulting in an IFN‐γ‐dominant response associated with susceptibility. However, blocking IFN‐γ under these conditions restores IL‐13‐dependent resistance. In this study, we examined the mechanism of IL‐13 up‐regulation and associated protection during this in vivo immune response. CD4+ T cells and DX5+TCR– cells were identified as the major producers of IL‐13, and the DX5+TCR– cells were phenotyped as NK cells, since they expressed CD11b, IL‐2Rβ and Ly49C but not c‐kit or FcϵRI. NK cell‐derived IL‐13 elevations were T cell‐dependent, as CD4+ T cell depletion blocked IL‐13 production by mesenteric lymph node cells and induced susceptibility. IL‐13 expression was increased independently of IL‐12; however, blocking IL‐18 function inhibited IL‐13 production and increased susceptibility. These results indicate that CD4+ T cells and NK cells are the major sources of IL‐13 during the in vivo Th1 response induced by B7 blockade and that under these conditions, IL‐18 is specifically required for the in vivo up‐regulation of IL‐13 production and associated host protection.
Cover Picture: Beyond TPPTS: New Approaches to the Development of Efficient Palladium‐Catalyzed Aqueous‐Phase Cross‐Coupling Reactions (Eur. J. Org. Chem. 8/2006)
Authors: Shaughnessy Kevin H.
Published: March 2006

The cover picture shows Little River Falls in the Little River Canyon National Preserve in Northeastern Alabama. Water is the solvent of life, and increasingly, water is being applied as a solvent in organic synthesis. Shown going over the falls are typical substrates for palladium‐catalyzed cross‐coupling reactions and their products collected in the pool below the falls. New hydrophilic phosphane architectures, such as those shown, are discussed in the Microreview by K. H. Shaughnessy on p. 1827 ff. These new classes of hydrophilic ligands provide palladium catalysts that can activate a wide variety of organohalide substrates under very mild conditions.
A theoretical study of the possible use of electroosmotic flow to extend the read length of DNA sequencing by end‐labeled free solution electrophoresis
Authors: McCormick Laurette C. , Slater Gary W.
Published: March 2006

End‐labeled free solution electrophoresis (ELFSE) provides a means of separating DNA with free‐solution CE, eliminating the need for gels and polymer solutions which increase the run time and can be difficult to load into a capillary. In free‐solution electrophoresis, DNA is normally free‐draining and all fragments reach the detector at the same time, whereas ELFSE uses an uncharged label molecule attached to each DNA fragment in order to render the electrophoretic mobility size‐dependent. With ELFSE, however, the larger molecules are not separated enough (limiting the read length in the case of ssDNA sequencing) while the smaller ones are overseparated; the larger ones are too fast while the shorter ones are too slow, which is the opposite of traditional gel‐based methods. In this article, we show how an EOF could be used to overcome these problems and extend the DNA sequencing read length of ELFSE. This counterflow would allow the larger, previously unresolved molecules more time to separate and thereby increase the read length. Through our theoretical investigation, we predict that an EOF mobility of approximately the same magnitude as that of unlabeled DNA would provide the best results for the regime where all molecules move in the same direction. Even better resolution would be possible for smaller values of EOF which allow different directions of migration; however, the migration times then would become too large. The flow would need to be well controlled since the gain in read length decreases as the magnitude of the counterflow increases; an EOF mobility double that of unlabeled DNA would no longer increase the read length, although ELFSE would still benefit from a reduction in migration time.
Silver staining method for DNA in polyacrylamide gels using eriochrome black T as a silver‐ion sensitizer
Authors: Hwang Sun‐young , Jin Li‐tai , Yoo Gyurng‐soo , Choi Jung‐Kap
Published: March 2006

A sensitive silver staining method using eriochrome black T as a silver‐ion sensitizer for DNA detection in polyacrylamide gels was developed. The sensitivity of this staining method was significantly improved by the new silver‐ion sensitizer containing a diazo group, which has reducing power. The staining method lasted a total of approximately 15 min following a fixing step for 2×20 min. The detection limit of this staining method was 1–4 pg for ΦX174 DNA/HaeIII in both nondenaturing and denaturing polyacrylamide gels. This staining method was especially effective in low‐base pair DNA, with a sensitivity that was approximately ten‐fold higher than previously published silver staining methods.
Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients
Authors: Zhang Yu‐Jing , Rossner Pavel , Chen Yu , Agrawal Meenakshi , Wang Qiao , Wang Lillian , Ahsan Habibul , Yu Ming‐Whei , Lee Po‐Huang , Santella Regina M.
Published: March 2006

Elevated aflatoxin B1‐albumin adducts (AFB1‐Alb) have been associated with an increased risk for HCC development. However, there are no studies in humans, correlating albumin adducts in blood with liver DNA adducts. Forty frozen tumor tissues and 39 paired plasma samples from HCC patients were collected in Taiwan, to determine the relationship between albumin adducts in blood and DNA adducts in liver tissue as well as mutations in p53 and methylation of p16. AFB1‐ and polycyclic aromatic hydrocarbon (PAH)‐DNA adducts in tissue and albumin adducts in plasma were determined by immunohistochemistry and competitive ELISA, respectively. Plasma AFB1‐Alb adducts in subjects with low, medium and high levels of AFB1‐DNA adducts in tumor tissues were 51.0 ± 36.5, 70.5 ± 48.1 and 84.9 ± 48.2 fmol/mg, respectively (ptrend = 0.05). No significant correlation was found for PAH. Fourteen of 40 (36%) tissues were positive for mutant p53 protein by immunohistochemistry; 11 of 40 tissue DNA samples (28%) were positive for p53 mutations, but not their corresponding plasma DNAs. p16 was methylated in 24 of 40 (62%) tissues and 12 of 39 (32%) plasma DNAs. Significant correlations were observed between AFB1‐Alb adducts and p53 mutations and p16 methylation. These data suggest that genetic, epigenetic and environmental exposure biomarkers in plasma may help in estimating the risk for the development of HCC. © 2006 Wiley‐Liss, Inc.
iNOS‐dependent DNA damage via NF‐κB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel
Authors: Pinlaor Somchai , Hiraku Yusuke , Yongvanit Puangrat , Tada‐Oikawa Saeko , Ma Ning , Pinlaor Porntip , Sithithaworn Paiboon , Sripa Banchob , Murata Mariko , Oikawa Shinji , Kawanishi Shosuke
Published: March 2006

Inflammation‐mediated DNA damage triggered by Opisthorchis viverrini (OV) infection is a major risk factor of cholangiocarcinoma (CCA). We have recently reported that nitrative and oxidative DNA damage participates in CCA development caused by repeated infection with OV [Pinlaor et al., Carcinogenesis 2004; 25:1535–42]. Therefore, to clarify the preventive effect of the antihelminthic drug praziquantel against cholangiocarcinogenesis, we assessed the effect of this drug on nitrative and oxidative DNA damage, including the formation of 8‐nitroguanine and 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG), and the expression of inducible nitric oxide synthase (iNOS) by immunohistochemistry in OV‐infected hamsters. We also examined the expression of nuclear factor‐κB (NF‐κB), which functions as a tumor promoter in inflammation‐associated cancer. Our results showed that although 1‐week treatment with praziquantel did not kill parasites completely in hamsters on days 14 and 30, this drug dramatically reduced inflammatory cell infiltration. Double immunofluorescence staining showed that drug treatment almost completely diminished OV‐induced 8‐nitroguanine and 8‐oxodG formation in bile duct epithelial cells. Quantitative analysis using an electrochemical detector coupled to HPLC revealed that 8‐oxodG level in the liver of OV‐infected hamsters was significantly decreased by drug treatment (p<0.05). Western blotting and immunohistochemistry revealed that the expression of NF‐κB and iNOS in bile duct epithelium was reduced by drug treatment. The amount of nitrate plus nitrite in the liver and plasma was significantly decreased after drug treatment. It is concluded that praziquantel can exhibit a preventive effect against OV‐induced cholangiocarcinoma by inhibiting iNOS‐dependent DNA damage through not only elimination of parasites but also a potential antiinflammatory effect. © 2006 Wiley‐Liss, Inc.
Small molecule drug activity in melanoma models may be dramatically enhanced with an antibody effector
Authors: Popkov Mikhail , Rader Christoph , Gonzalez Beatriz , Sinha Subhash C. , Barbas Carlos F.
Published: March 2006

Monoclonal antibody (mAb) 38C2 belongs to a group of catalytic antibodies that were generated by reactive immunization and contains a reactive lysine. 38C2 catalyzes aldol and retro‐aldol reactions, using an enamine mechanism, and mechanistically mimics natural aldolase enzymes. In addition, mAb 38C2 can be redirected to target integrins αvβ3 and αvβ5 through the formation of a covalent bond between a β‐diketone derivative of an arginine–glycine–aspartic acid (RGD) peptidomimetic and the reactive lysine residue in the antibody combining site to provide the chemically programmed mAb cp38C2. In this study, we investigated the potential of enhancing the activity of receptor‐binding small molecule drug (SCS‐873) through antibody conjugation. Using a M21 human melanoma xenograft model in nude mice, cp38C2 inhibited the growth of the tumor by ˜81%. The chemically programmed antibody was shown to be highly active at a low concentration while SCS‐873 alone was ineffective even at dosages ˜1,000‐fold higher than those used for the chemically programmed antibody. In vitro programming of the catalytic antibody was shown to be as effective as in vivo programming. In an experimental metastasis assay, treatment with mAb cp38C2 significantly prolonged overall survival of tumor‐bearing severe combined immuno‐deficient (SCID) mice when compared to treatment with unprogrammed mAb 38C2, SCS‐873 alone or the integrin‐specific monoclonal antibody LM609. In vitro, cp38C2 inhibited human and mouse endothelial and human melanoma cell adhesion, migration and invasion. Additionally, cp38C2 inhibited human and mouse endothelial cell proliferation and was active in complement‐dependent cytotoxicity assays. These studies establish the potential of chemically programmed monoclonal antibodies as a novel and effective class of immunotherapeutics that combine the merits of traditional small molecule drug design with immunotherapy. © 2006 Wiley‐Liss, Inc.
Insulin‐like growth factor binding protein 3 as an anticancer molecule in Ewing's sarcoma
Authors: Benini Stefania , Zuntini Monia , Manara Maria Cristina , Cohen Pinchas , Nicoletti Giordano , Nanni Patrizia , Oh Youngman , Picci Piero , Scotlandi Katia
Published: March 2006

The IGF/IGF‐IR system plays a major role in the pathogenesis and progression of Ewing's sarcoma. In this article, the authors evaluated whether the insulin‐like growth factor binding protein‐3 (IGFBP‐3), a molecule with growth‐inhibitory and proapoptotic activities, may be exploited for therapeutic applications in the treatment of Ewing's sarcoma (EWS). Expression of IGFBP‐3 was analyzed in a panel of EWS cell lines and clinical samples. Parameters related to malignancy (growth in anchorage‐independent conditions, migration, invasion and angiogenesis properties) were studied to establish the potential in vitro anticancer effects of exogenous IGFBP‐3. The activity of the molecule against metastasis was analyzed by taking advantage of selected clones in which IGFBP‐3 endogenous production was induced by gene transfection. The authors observed a generally low expression of IGFBP‐3 either in a panel of EWS cell lines or clinical samples. Exogenous IGFBP‐3 remarkably inhibits EWS growth, both in monolayer and anchorage‐independent conditions, and significantly reduces cell motility. Forced expression of IGFBP‐3 in TC‐71 EWS cells confirms the growth and migratory effects observed with the exogenous protein, decreases the production or activity of the matrixmetalloprotease MMP‐9 and vascular endothelial factor (VEGF)‐A and abrogates EWS metastasis ability. IGFBP‐3 acts mainly through IGF‐dependent mechanisms and the protein may therefore represent an alternative strategy to inhibit IGF‐IR functions. The data indicate IGFBP‐3 as a molecule of therapeutic potential in EWS. © 2006 Wiley‐Liss, Inc.
Chromosome 5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutation carriers and sporadic breast tumors
Authors: Johannsdottir Hrefna K. , Jonsson Goran , Johannesdottir Gudrun , Agnarsson Bjarni A. , Eerola Hannaleena , Arason Adalgeir , Heikkila Paivi , Egilsson Valgardur , Olsson Hakan , Johannsson Oskar Th. , Nevanlinna Heli , Borg Ake , Barkardottir Rosa B.
Published: March 2006

Comparative genomic hybridization (CGH) analysis has shown that chromosome 5q deletions are the most frequent aberration in breast tumors from BRCA1 mutation carriers. To map the location of putative 5q tumor suppressor gene(s), 26 microsatellite markers covering chromosome 5 were used in loss of heterozygosity (LOH) analysis of breast tumors from BRCA1 (n = 42) and BRCA2 mutation carriers (n = 67), as well as in sporadic cases (n = 65). High‐density array CGH was also used to map chromosome 5 imbalance in 10 BRCA1 tumors. A high LOH frequency was found in BRCA1 tumors (range 19–82%), as compared to BRCA2 and sporadic tumors (ranges 11–44% and 7–43%, respectively). In all, 11 distinct chromosome 5 regions with LOH were observed, the most frequent being 5q35.3 (82%), 5q14.2 (71%) and 5q33.1 (69%) in BRCA1 tumors; 5q35.3 (44%), 5q31.3 (43%) and 5q13.3 (43%) in BRCA2 tumors and 5q31.3 (43%) in sporadic tumors. Array CGH analysis confirmed the very high frequency of 5q deletions, including candidate tumor suppressor genes such as XRCC4, RAD50, RASA1, APC and PPP2R2B. In addition, 2 distinct homozygous deletions were identified, spanning regions of 0.7–1.5 Mbp on 5q12.1 and 5q12.3‐q13.1, respectively. These regions include only a few genes, most notably BRCC3/DEPDC1B (pleckstrin/G protein interacting and RhoGAP domains) and PIK3R1 (PI3 kinase P85 regulatory subunit). Significant association (p ≤ 0.05) was found between LOH at certain 5q regions and factors of poor prognosis, including negative estrogen and progesterone receptor status, high grade, large tumor size and high portion of cells in S‐phase. In conclusion, our results confirm a very high prevalence of chromosome 5q alterations in BRCA1 tumors, pinpointing new regions and genes that should be further investigated. © 2006 Wiley‐Liss, Inc.
Methodological issues in international comparison of interval breast cancers
Authors: Bulliard Jean‐Luc , Sasieni Peter , Klabunde Carrie , De Landtsheer Jean‐Pierre , Yankaskas Bonnie C. , Fracheboud Jacques
Published: March 2006

International comparisons of interval cancers (IC) are important to better understand the relationship between programmes' performance and screening practices. In this respect, differences in (i) definition, (ii) identification and (iii) quantification of IC have received little attention. To examine these 3 comparability issues and activities involving IC, an assessment was conducted among member countries of the International Breast Cancer Screening Network, and the impact of accuracy of identification and quantification practices was estimated using 1996–98 data from the Dutch breast cancer screening programme. Information was obtained from 19 screening programmes in 18 countries, 16 of which acknowledged the coexistence of opportunistic screening. IC data were collected to evaluate performance of the screening programme (100% of programmes) and the radiologists (89%); 53% of programmes had a designated review process for IC. Most programmes (84%) agreed with the European Guidelines definition of IC, but a case situation exercise evidenced substantial discrepancy in classification of cancers that occurred after a positive screen. Completeness of identification of IC appears to contribute most to international variation, and cannot be easily controlled for in methodologically rigorous comparisons. Statistically significant differences of about 4% were measured between quantification methods for IC. An operational definition of IC is proposed to enhance international comparability. Valid comparisons of IC are possible with careful attention to the definition but true differences in IC frequency across screening programmes should exceed 10% to be possibly indicative of real differences between programmes. © 2006 Wiley‐Liss, Inc.
Overexpression of RB1 transcript is significantly correlated with 13q14 allelic imbalance in colorectal carcinomas
Authors: Lai Poh‐San , Cheah Peh Yean , Kadam Priya , Chua Constance Li‐Ming , Lie Daniel Khun Hong , Li Hui‐Hua , Eu Kong‐Weng , Seow‐Choen Francis , Lee Ann Siew‐Gek
Published: March 2006

RB1 gene expression has been reported to be upregulated in colorectal carcinomas (CRC) at both the mRNA and protein levels when compared to normal colonic mucosa. However, allelic loss at the genomic level has been detected in CRC with widely differing frequencies ranging from 11.5% to 50%. To determine whether there is indeed a correlation between RB1 allelic imbalance (AI) and expression, a consecutive series of 55 CRC from Singapore patients were analysed by microsatellite analysis, real‐time RT‐PCR and immunohistochemistry. Microsatellite analysis using 3 RB1 intragenic microsatellite markers and 2 markers flanking RB1 detected AI in 32.7% (18/55) of the cases, in at least 1 locus. The highest AI frequency (22.9%) was observed at the microsatellite marker D13S137 (Cu13), which maps 5 cM distal to RB1. AI was present in both early and late Dukes stages. Real‐time RT‐PCR revealed that all 40 cases analysed expressed RB1 mRNA, with mRNA overexpression in 37.5% (15/40) and pRB protein expression in 88.2% (30/34) of cases. Notably, a statistically significant correlation was found between AI of RB1 and mRNA overexpression of RB1 (p < 0.001, Fishers exact test). These findings provide evidence that despite AI, RB1 expression is not abrogated. Thus, our data suggests that RB1 may play a role in colorectal tumorigenesis through functional regulation of the transcript and protein rather than through its tumour suppressor role by gene inactivation. © 2006 Wiley‐Liss, Inc.
Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: A systematic review
Authors: Gallicchio Lisa , Matanoski Genevieve , Tao Xuguang (Grant) , Chen Liwei , Lam Tram K. , Boyd Kristina , Robinson Karen A. , Balick Lyssa , Mickelson Stephanie , Caulfield Laura E. , Herman James G. , Guallar Eliseo , Alberg Anthony J.
Published: March 2006

The incidence rates of nasopharyngeal carcinoma (NPC) are dramatically higher in certain regions of Asia compared to the rest of the world. Few risk factors for NPC are known; however, in contrast to the hypothesized health benefits of nonpreserved vegetables, it is thought that preserved vegetable intake may play a role in contributing to the higher incidence of NPC in high‐risk regions. Therefore, the purpose of this study was to systematically review the epidemiologic evidence on the associations between adulthood intake of preserved and nonpreserved vegetables and NPC risk. A search of the epidemiological literature from 1966 to 2004 was performed using several bibliographic databases, including PubMed and the Chinese Biomedical Literature Database System. There were no language restrictions. Meta‐analysis was conducted to obtain pooled odds ratios (ORs) for the highest‐versus‐lowest categories of preserved and nonpreserved vegetable intake. A total of 16 case‐control studies were identified in the search. Results showed that highest‐versus‐lowest preserved vegetable intake was associated with a 2‐fold increase in the risk of NPC (Random Effects Odds Ratio (RE OR) 2.04; 95% Confidence Limits (CL) 1.43, 2.92). Conversely, high nonpreserved vegetable intake was associated with 36% decrease in the risk of NPC (RE OR 0.64; 95% CL 0.48, 0.85). Findings for both preserved and nonpreserved vegetables were consistent across vegetable type and by country of study. Further research in high‐risk areas to gain insight into the risk associated with preserved vegetables and protection associated with nonpreserved vegetables may advance understanding of NPC and yield clues for prevention. © 2006 Wiley‐Liss, Inc.
Brain cancer mortality and potential occupational exposure to lead: Findings from the National Longitudinal Mortality Study, 1979–1989
Authors: van Wijngaarden Edwin , Dosemeci Mustafa
Published: March 2006

We evaluated the association between potential occupational lead exposure and the risk of brain cancer mortality in the National Longitudinal Mortality Study (NLMS), which is a prospective census‐based cohort study of mortality among the noninstitutionalized United States population (1979–1989). The present study was limited to individuals for whom occupation and industry were available (n = 317,968). Estimates of probability and intensity of lead exposure were assigned using a job‐exposure matrix (JEM). Risk estimates for the impact of lead on brain cancer mortality were computed using standardized mortality ratio (SMR) and proportional hazards and Poisson regression techniques, adjusting for the effects of age, gender and several other covariates. Brain cancer mortality rates were greater among individuals in jobs potentially involving lead exposure as compared to those unexposed (age‐ and gender‐adjusted hazard ratio (HR) = 1.5; 95% confidence interval (CI) = 0.9–2.3) with indications of an exposure–response trend (probability: low HR = 0.7 (95% CI = 0.2–2.2), medium HR = 1.4 (95% CI = 0.8–2.5), high HR = 2.2 (95% CI = 1.2–4.0); intensity: low HR = 1.2 (95% CI = 0.7–2.1), medium/high HR = 1.9 (95% CI = 1.0–3.4)). Brain cancer risk was greatest among individuals with the highest levels of probability and intensity (HR = 2.3; 95% CI = 1.3–4.2). These findings provide further support for an association between occupational lead exposure and brain cancer mortality, but need to be interpreted cautiously due to the consideration of brain cancer as one disease entity and the absence of biological measures of lead exposure. © 2006 Wiley‐Liss, Inc.
Nicotine induces the fragile histidine triad methylation in human esophageal squamous epithelial cells
Authors: Soma Toshiya , Kaganoi Junichi , Kawabe Atsushi , Kondo Kan , Imamura Masayuki , Shimada Yutaka
Published: March 2006

The fragile histidine triad (FHIT) gene has been proposed to have an important role in very early carcinogenesis. Methylation of the FHIT gene is associated with transcriptional inactivation in esophageal squamous cell carcinoma, and FHIT inactivation has been linked to smoking‐related carcinogenesis. In this study, we confirmed methylation of the FHIT gene in human esophageal squamous epithelial cells (HEECs) and examined whether nicotine induced alteration of FHIT. Methylation status in the promoter region of the FHIT gene and p16INK4A gene was determined by methylation‐specific PCR in HEECs exposed to nicotine under various conditions. Methylation status of the FHIT gene was confirmed by DNA‐sequencing analysis. Protein expression of Fhit and the DNA methyltransferases (DNMTs) DNMT1 and DNMT3a were assessed by immunoblot analysis. In the absence of nicotine, methylation of the FHIT gene and attenuation of Fhit protein were not detected in HEECs. Nicotine induced the methylation of FHIT gene and attenuated Fhit protein in association with increased expression of DNMT3a. Reexpression of Fhit protein in HEECs was found after cessation of moderate‐ to long‐term exposure to nicotine. Our results show that nicotine induces methylation of the FHIT gene followed by loss of Fhit protein expression in HEECs. Continuous smoking may thus increase the risk of esophageal cancer. © 2006 Wiley‐Liss, Inc.
Association of meningioma with reproductive factors
Authors: Lee Eunsuk , Grutsch James , Persky Victoria , Glick Roberta , Mendes Juliana , Davis Faith
Published: March 2006

Meningiomas occur more commonly in females. The coincidence between meningioma and breast cancer and case reports of tumor growth during pregnancy support a hormonal hypothesis. A case control study was conducted to investigate this. Female subjects treated between 1987 and 1992 were identified from 3 hospitals in the Chicago area. Female spouses of male back pain patients were recruited as controls. A self‐administered mail questionnaire focused on exogenous, endogenous and other hormonal factors, personal and family medical history as well as radiation exposures. Odds ratios and 95% confidence intervals were estimated using crude, stratified and multivariable logistic models including 219 cases and 260 controls. Participation rates were 86% among cases and 75% among controls. An increased odds ratio (OR) was observed comparing African Americans to Caucasians [OR = 2.4, 95% confidence interval (CI) = 1.0–6.1]. A protective effect was observed for pregnancy, which increased with number and age at first pregnancy. The odds ratio for 3 or more pregnancies compared to none was 0.3 (95% CI = 0.2–0.6). Age at menarche or total period of hormonal activity was not protective. Ever smokers showed a decreased odds ratio for meningioma (OR = 0.6, 95% CI = 0.4–0.9). The increased odds ratios with African Americans was retained in post‐menopausal women, while the protective odds ratios for pregnancy, smoking and oral contraceptives (OCs) became stronger in pre‐menopausal women. The pattern by duration and timing of use does not suggest an etiologic role for OCs or hormone replacement therapy. These data add to the evidence that factors known to influence endogenous hormones (pregnancy and indirectly smoking) may have protective effects for meningiomas primarily in premenopausal women. © 2006 Wiley‐Liss, Inc.
Zoledronic acid slows down rat primary chondrosarcoma development, recurrent tumor progression after intralesional curretage and increases overall survival
Authors: Gouin François , Ory Benjamin , Rédini François , Heymann Dominique
Published: March 2006

Chondrosarcoma is a difficult musculoskeletal tumor to treat. Surgical treatment leads to severe disability, with high rates of local recurrence and life threat. No adjuvant therapy is effective in differentiated chondrosarcomas. Bisphosphonates (BPs) are a class of molecules which is effective in malignant bone diseases. The aim of the present study was to determine the effects of zoledronic acid (ZOL) on chondrosarcoma tumor progression. ZOL was tested in vivo (s.c. 100 μg/kg, twice a week) in a rat chondrosarcoma model and in vitro (10−7–10−4 M) on cells derived from this model. Two types of animal models were assessed, the first simulated development after intralesional curettage, the second nonoperative development of the tumor. Cell proliferation, caspase‐1, ‐3 activities and cell cycle analysis were studied. The results revealed that ZOL slows down primary tumor development, tumor progression after intralesional curretage and increases overall survival. ZOL inhibits cell proliferation and increases cell death, with no significant variation of caspase‐1 and ‐3 activities and cell cycle profiles. The present study demonstrates for the first time that in addition to surgery, the therapy of chondrosarcoma with BPs might be beneficial. Because of these first results, new therapeutic approaches of chondrosarcoma must be considered, mainly for low grade chondrosarcoma when disabling operation is planned and when only intralesional resection can be undertaken. © 2006 Wiley‐Liss, Inc.
Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies
Authors:   International Collaboration of Epidemiological Studies of Cervical Cancer
Published: March 2006

The International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full‐term pregnancies, and age at first full‐term pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full‐term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first full‐term pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53–2.02) for ≥≥7 full‐term pregnancies compared with 1–2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full‐term pregnancy among parous women. Early age at first full‐term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full‐term pregnancies, the RR for first full‐term pregnancy at age <17 years compared with ≥≥25 years was 1.77 (95% CI: 1.42–2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26–2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high‐risk human papilloma virus (HPV)‐positive cases and controls. No relationship was found between cervical HPV positivity and number of full‐term pregnancies, or age at first full‐term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries. © 2006 Wiley‐Liss, Inc.
KIF14 mRNA expression is a predictor of grade and outcome in breast cancer
Authors: Corson Timothy W. , Gallie Brenda L.
Published: March 2006

Gain of chromosome 1q is a hallmark of breast cancer, and likely reflects oncogene amplification. We previously identified mitotic kinesin KIF14 (kinesin family member 14) as an overexpressed candidate oncogene in the 1q31.3–1q32.1 minimal region of genomic gain in breast cancer cell lines. KIF14 also showed high expression in other cancers, notably an association with survival in lung tumors. We now report KIF14 expression in 99 primary breast tumors and 10 normal breast controls. Measured by real‐time RT‐PCR, KIF14 was overexpressed 10‐fold on average in tumors relative to normals (t test p = 0.000054); expression increased with grade (ANOVA p = 0.000006). Infiltrating ductal carcinomas had higher KIF14 levels than lobular (p = 0.017), and estrogen receptor (ER) negative tumors had higher KIF14 levels than ER positive tumors (t test p = 0.030). KIF14 expression correlated positively with Ki‐67 mRNA level (Spearman r = 0.692, p = 0.000001), fraction of positive nodes (r = 0.227, p = 0.024) and percent invasive cells (r = 0.360, p = 0.0002), and negatively with percent fatty stroma (r = −0.258, p = 0.010) and percent normal epithelium (r = −0.291, p = 0.003). KIF14 expression is thus tumor‐specific and increased in more aggressive tumors. Indeed, KIF14 expression predicted overall survival (univariate Cox p = 0.010), with an odds ratio of 3.60 (1.37–9.48), in 50 tumors with available outcome data. KIF14 overexpression also predicted decreased disease‐free survival (log‐rank p = 0.049). These findings are the first evidence of association between expression of a mitotic kinesin and prognostic variables in breast cancer. © 2006 Wiley‐Liss, Inc.
Effects of single nucleotide polymorphisms in human N‐acetyltransferase 2 on metabolic activation (O‐acetylation) of heterocyclic amine carcinogens
Authors: Hein David W. , Fretland Adrian J. , Doll Mark A.
Published: March 2006

N‐Acetyltransferase 2 (NAT2) catalyzes the O‐acetylation of N‐hydroxy heterocyclic amines such as N‐hydroxy‐2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (NOHMeIQx) and N‐hydroxy‐2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b] pyridine (NOH PhIP) to DNA binding metabolites that initiate mutagenesis and carcinogenesis. NAT2 acetylator phenotype is associated with increased cancer risk. Single nucleotide polymorphisms (SNPs) have been identified in the NAT2 coding region. Although the effects of these SNPs on N‐acetyltransferase activity have been reported, very little is known regarding their effects on O‐acetylation activity. To investigate the functional consequences of SNPs in the NAT2 coding region on the O‐acetylation of N‐hydroxy heterocyclic amines, reference NAT2*4 and NAT2 variant alleles possessing one were cloned and expressed in yeast (Schizosaccaromyces pombe). T111C, C282T, C481T, C759T, and A803G (K268R) SNPs did not significantly (p > 0.05) modify O‐acetylation catalysis with NOHPhIP or NOHMeIQx. C190T (R64W), G191A (R64Q), T341C (I114T), A434C (E145P), G590A (R197Q) and A845C (K282T) significantly (p < 0.01) reduced the O‐acetylation of both NOHPhIP and NOHMeIQx, whereas G857A (G286E) significantly (p < 0.05) decreased catalytic activity towards the O‐acetylation of NOHMeIQx but not NOHPhIP. These results have important implications towards the interpretation of molecular epidemiological studies of NAT2 genotype and cancer risk. © 2006 Wiley‐Liss, Inc.
Presence of high‐risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival
Authors: Lont Anne P. , Kroon Bin K. , Horenblas Simon , Gallee Maarten P.W. , Berkhof Johannes , Meijer Chris J.L.M. , Snijders Peter J.F.
Published: March 2006

There is evidence that a subset of penile carcinomas is caused by infection with high‐risk human papillomavirus (HPV). However, extensive studies on the possible influence of HPV infection on clinical outcome of penile cancer are lacking. This investigation is aimed to examine the prevalence of high‐risk HPV in a large series of penile squamous‐cell carcinomas (SCCs) and to determine the relationship between HPV and survival. Formalin‐fixed, paraffin‐embedded tumor specimens of 171 patients with penile carcinoma were tested for high‐risk HPV DNA presence by GP5+/6+‐PCR. The clinical course of the patients and the histopathological characteristics of the primary tumors were reviewed. High‐risk HPV DNA was detected in 29% of the tumors, with HPV 16 being the predominant type, accounting for 76% of high‐risk HPV containing SCCs. Disease‐specific 5‐year survival in the high‐risk HPV‐negative group and high‐risk HPV‐positive group was 78% and 93%, respectively (log rank test p = 0.03). In multivariate analysis, the HPV status was an independent predictor for disease‐specific mortality (p = 0.01) with a hazard ratio of 0.14 (95% CI: 0.03–0.63). Our results indicate that the presence of high‐risk HPV (29%) confers a survival advantage in patients with penile carcinoma. © 2006 Wiley‐Liss, Inc.
Pharmacologic transgene control systems for gene therapy
Authors: Weber Wilfried , Fussenegger Martin
Published: March 2006

Pharmacologic transgene‐expression dosing is considered essential for future gene therapy scenarios. Genetic interventions require precise transcription or translation fine‐tuning of therapeutic transgenes to enable their titration into the therapeutic window, to adapt them to daily changing dosing regimes of the patient, to integrate them seamlessly into the patient's transcriptome orchestra, and to terminate their expression after successful therapy. In recent years, decisive progress has been achieved in designing high‐precision trigger‐inducible mammalian transgene control modalities responsive to clinically licensed and inert heterologous molecules or to endogenous physiologic signals. Availability of a portfolio of compatible transcription control systems has enabled assembly of higher‐order control circuitries providing simultaneous or independent control of several transgenes and the design of (semi‐)synthetic gene networks, which emulate digital expression switches, regulatory transcription cascades, epigenetic expression imprinting, and cellular transcription memories. This review provides an overview of cutting‐edge developments in transgene control systems, of the design of synthetic gene networks, and of the delivery of such systems for the prototype treatment of prominent human disease phenotypes. Copyright © 2006 John Wiley & Sons, Ltd.
Accelerating MR elastography: A multiecho phase‐contrast gradient‐echo sequence
Authors: Maderwald Stefan , Uffmann Kai , Galbán Craig. J. , de Greiff Armin , Ladd Mark E.
Published: March 2006

Purpose

To demonstrate the feasibility of using a multiecho phase‐contrast (PC) gradient‐echo sequence with motion‐sensitizing gradient (MSG) to accelerate MR elastography (MRE) acquisitions in comparison to single‐echo PC sequences.

Materials and Methods

The sequence was implemented and compared with a conventional single‐echo sequence as the standard of reference in both agarose phantoms and in vivo in the biceps of three healthy volunteers. For reconstruction of the elasticity modulus, a local frequency estimation (LFE) algorithm was used. ETL factors of 1–16 were evaluated.

Results

Phantom experiments demonstrated excellent consistency between single‐echo and multiecho measurements in terms of wave equivalency, SNR, and reconstructed shear modulus. Additionally, the in vivo MRE examinations showed an excellent correspondence to the single‐echo results. Minor loss of wave amplitude was observed at higher ETL factors.

Conclusion

The results demonstrate that a multiecho sequence is suitable for accelerating MRE in nearly homogeneous tissue, such as muscle. It provides equivalent elasticity values in a significantly reduced scan time compared to a single‐echo sequence. The maximum achievable ETL factor must be individually determined for the target tissue. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Extended harmonic phase tracking of myocardial motion: Improved coverage of myocardium and its effect on strain results
Authors: Tecelão Sandra R.R. , Zwanenburg Jaco J.M. , Kuijer Joost P.A. , Marcus J. Tim
Published: March 2006

Purpose

To extend the harmonic phase (HARP) tracking method in order to track the myocardial tissue that appears near the epicardial contour during systole and reappears near the endocardial contour during diastole, due to the longitudinal motion and conical shape of the heart.

Materials and Methods

A mathematical model of myocardial deformation was used to quantify the accuracy of the extended HARP tracking and of the strain computation. For six healthy volunteers, the number of tracked points and the two‐dimensional strain components were computed with the extended and with the original HARP tracking version.

Results

High accuracy was obtained for the circumferential strain (maximum error is 0.5% relative to analytical strain). The extended version tracked 22 ± 7%, 51 ± 19%, and 67 ± 20% more points than the original version on the basal, mid, and apical slices, respectively (P ≤ 0.001 for each slice), and yielded a decreased circumferential shortening (relative decrease: 2 ± 4%, 9 ± 4%, and 12 ± 5% for the three slices; P < 0.005 for mid and apex), at end systole. These differences in circumferential strain were related to the more complete coverage of the myocardial wall with tracked points.

Conclusion

The extended HARP tracking also provides strain values from myocardial regions that were not covered by the original HARP tracking. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Organic fertilizers derived from plant materials Part I: Turnover in soil at low and moderate temperatures
Authors: Müller Torsten , von Fragstein und Niemsdorff Peter
Published: March 2006

The aim was to investigate different organic fertilizers derived from plant materials with respect to their nitrogen and carbon turnover in soil in comparison with organic fertilizers derived from animal‐waste products. In a 64‐day incubation study at 5°C and 15°C, the following fertilizers were used: coarse faba bean–seed meal (Vicia faba L.), coarse meals of yellow and white lupin seeds (Lupinus albus L. and Lupinus luteus L.), Phytoperls® (waste products of maize [Zea mays L.] processing), coarse meal of castor cake (Ricinus communis L.) as a widely used organic fertilizer, and horn meal as a reference fertilizer‐derived from animal waste products. At 15°C, horn meal showed the highest apparent net N mineralization of fertilizer‐derived N, followed by castor cake and the two lupin meals. At 5°C, apparent net N mineralization of fertilizer‐derived N from horn meal and coarse meal of yellow lupin seeds was nearly identical, followed by castor‐cake meal. Net N mineralization from legume‐seed meals showed no or even a negative temperature response, at least temporarily. In contrast, the other fertilizers showed a positive temperature response of net N mineralization. The content in recalcitrant structural components and the decoupling of decomposition of N‐rich and C‐rich tissue components in time are discussed as controlling factors of fertilizer‐N turnover at low temperature. Microbial residues seem to be an important temporary sink of fertilizer‐derived C and N. Legume‐seed meals induced considerable N‐priming effects. Temperature induced differences in the decomposition of total fertilizer C, indicated by changes in the sum of cumulative CO2‐C evolution, total K2SO4‐soluble organic C and microbial‐biomass C were much smaller than indicated by cumulative CO2‐C evolution alone. Our results indicate that legume‐seed meals have the potential to replace horn meal and castor‐cake meal in organic vegetable production, especially when soil temperatures in early spring are still low.
Organic fertilizers derived from plant materials Part II: Turnover in field trials
Authors: Müller Torsten , von Fragstein und Niemsdorff Peter
Published: March 2006

Our aim was to investigate two different organic fertilizers derived from plant materials (OFDP) with respect to their nitrogen (N) and carbon (C) turnover in field trials planted with small radish (Raphanus sativus L. var. sativus) and white cabbage (Brassica oleracea L. convar. capitata var. alba) or fallow. The two fertilizers investigated were coarse seed meal of yellow lupin (Lupinus luteus L.) and coarse meal of castor cake (Ricinus communis L.). Under cool spring conditions, the soil turnover of yellow lupin–seed meal was slightly enhanced compared to castor‐cake meal. During the vegetation period of the vegetables, N added with both fertilizers was metabolized more or less completely by soil microorganisms. Due to similar efficiencies of the fertilizers tested, no significant difference could be found in the N uptake of plants. From this point of view, yellow lupin–seed meal, which can be produced by farmers themselves, has the potential to replace the widely used castor‐cake meal. Considerable amounts of N may remain in the field after fertilization with OFDPs either as mineral N or as easily mineralizable organic N. This N should be utilized immediately by a succeeding crop to avoid leaching losses.
Phosphate‐solubilizing potential of the nematophagous fungus Arthrobotrys oligospora
Authors: Duponnois Robin , Kisa Marija , Plenchette Christian
Published: March 2006

The nematophagous fungus Arthrobotrys oligospora was tested in vitro and in vivo for its ability to solubilize rock phosphate. Three types of rock phosphate (RP) from Burkina Faso (KRP), Senegal (TRP), and Mali (TIRP) were used at four concentrations for the in‐vitro experiment. All three types of RP were solubilized by the fungus. The maximum quantity of P recovered in solution was obtained with TRP, 12.5% for an application of 1 g L–1. The effect of TRP and A. oligospora applied separately or in combination was tested in vivo on the growth of A. holosericea. In a P‐deficient soil without addition of RP, P solubilization was increased by addition of A. oligospora. The P uptake by plants growing in soil amended with TRP and inoculated with A. oligospora was significantly higher compared to noninoculated controls, thus demonstrating the ability of the fungus to solubilize additional phosphate from RP in vivo.
Effects of phosphate supply and elevated CO2 on root acid phosphatase activity in Pinus densiflora seedlings
Authors: Norisada Mariko , Motoshige Tetsuya , Kojima Katsumi , Tange Takeshi
Published: March 2006

The exudation of root acid phosphatase (APase) is a plant response mechanism to phosphorus (P) deficiency. Under conditions of elevated CO2, P demand increases and possibly further enhances APase activity. We examined the activity of APase in 1‐year‐old ectomycorrhizal Pinus densiflora Sieb. et Zucc. seedlings grown in potted sand in the greenhouse under ambient (400 μmol mol–1) and elevated (700 μmol mol–1) CO2 with three modes of P supply: inorganic (NaH2PO4; Pin), organic (inositol hexaphosphate dodecasodium salt; Porg), and no phosphate (P0) for 78 d. Phosphorus limitations decreased P content in leaves and roots with lowest P content in P0 treatments, irrespective of CO2 conditions. However, P limitations decreased plant biomass at elevated CO2 levels, but not at ambient CO2 levels. The content in leaves of nutrients other than P was mostly unaffected by P supply, but decreased under elevated CO2. This observation was attributed to starch accumulation in leaves at elevated CO2, especially in the P0 treatment. The photosynthetic activity (expressed per unit of chlorophyll) was unaffected by P supply, but tended to be less at elevated CO2. There was no increase in root APase activity of Pinus densifolia in response to the P shortage caused by elevated CO2.