bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carcinogenicity of dimethylarsinic acid in Ogg1‐deficient mice
Authors: Kinoshita Anna , Wanibuchi Hideki , Morimura Keiichirou , Wei Min , Nakae Dai , Arai Tsuyoshi , Minowa Osamu , Noda Tetsuo , Nishimura Susumu , Fukushima Shoji 
Published: May 2007

Oxidative stress to DNA is recognized as a mechanism underlying carcinogenic effects of some environmental agents. Here, we hypothesized that dimethylarsinic acid (DMAV), an organic metabolite of inorganic arsenic in humans, might exert carcinogenic potential in a mouse line carrying a mutant Mmh allele of the Mmh/OGG1 gene encoding the enzyme 8‐hydroxyguanine DNA glycosylase 1 (OGG1). Ogg1 mutant and wild type mice were treated with DMAV in their drinking water at a dose of 200 p.p.m. for up to 72 weeks. All DMAV‐treated Ogg1−/–animals developed tumors, with a tendency for lower total incidences in the Ogg1+/+ cases. Lung tumors in particular were induced as compared to the lack in non‐carcinogen controls and were significantly more frequent in the homozygotes. At week 4, the levels of DNA 8‐OH‐dG and cell proliferation were significantly elevated in the lungs of non‐treated Ogg1−/– as compared to Ogg1+/+ mice and were strongly enhanced by DMAV treatment. Marked induction of Pola1, Cyp7b1, Ndfua3, Mmp13 and other genes specific to cell proliferation, cell signaling and xenobiotic metabolism in the lungs of DMAV‐treated Ogg1−/– mice was found. Electron microscopic examination revealed the growth of microvilli, with increased numbers of mitochondria only in lungs and lung tumors of DMAV‐exposed Ogg1−/– mice. Therefore, we strongly suggest that DMAV exerts carcinogenicity in the lungs of Ogg1−/– mutant mice, with a possible role for persistent accumulation of DNA oxidative adducts. (Cancer Sci 2007; 98: 803–814)
DNA topoisomerase inhibitor, etoposide, enhances GC‐box‐dependent promoter activity via Sp1 phosphorylation
Authors: Niina Ichiro , Uchiumi Takeshi , Izumi Hiroto , Torigoe Takayuki , Wakasugi Tetsuro , Igarashi Tomonori , Miyamoto Naoya , Onitsuka Takamitsu , Shiota Masaki , Okayasu Ryuichi , Chijiiwa Kazuo , Kohno Kimitoshi 
Published: May 2007

Modification of transcription factors by anticancer agents plays an important role in both apoptotic and survival signaling. Here we report that both DNA topoisomerase I and II inhibitors such as SN‐38 and etoposide, but not cisplatin, 5‐fluorouracil or actinomycin D, can induce phosphorylation of the transcription factor Sp1. Furthermore, DNA topoisomerase inhibitors were shown to transactivate GC‐box‐dependent promoters such as the SV40 and vascular endothelial growth factor promoters. The phosphorylated form of Sp1 was detectable within 30 min of etoposide treatment and was greatly diminished by the presence of the PI3K inhibitor wortmannin and by DNA‐dependent protein kinase (DNA‐PK) knockdown. We also confirmed that the phosphorylated form of DNA‐PK was increased by treatment with both etoposide and SN‐38. Taken together, these findings demonstrate a novel genomic response to anticancer agents that induce Sp1 phosphorylation, and might contribute to tumor progression and drug resistance. (Cancer Sci 2007; 98: 858–863)
Helicobacter pylori infection‐negative gastric cancer in Japanese hospital patients: Incidence and pathological characteristics
Authors: Kato Shunji , Matsukura Norio , Tsukada Katsuya , Matsuda Noriko , Mizoshita Tsutomu , Tsukamoto Tetsuya , Tatematsu Masae , Sugisaki Yuichi , Naito Zenya , Tajiri Takashi 
Published: May 2007

We used Helicobacter pylori sero‐positivity and mucosal atrophy as detected by the serum pepsinogen method to identify H. pylori infection‐negative gastric cancer patients with or without atrophy. One hundred and six of 748 (14.2%) primary gastric cancer patients were infection‐negative by a serum antibody detection system. Further, 121 (16.2%) of the 748 were negative for gastric mucosal atrophy by the pepsinogen method, of whom 15/748 (2.0%) were H. pylori‐negative by pepsinogen I level (>70 ng/mL) and pepsinogen I/II ratio (>3.0). Twenty‐seven of 782 (3.6%) gastric cancer patients were H. pylori‐negative by antibodies and severe atrophy as determined by pepsinogen I level (<30 ng/mL) and pepsinogen I/II ratio (<2.0). H. pylori‐negative gastric cancer patients with severe atrophy likely had a previous infection. These results indicate that the actual number of H. pylori‐negative patients is 2.0% at minimum and 10.6% (14.2% minus 3.6%) at maximum in the general Japanese population. Five of 15 (33%) cases displaying neither anti‐H. pylori antibodies nor atrophy were intestinal‐type and 10 (67%) were diffuse‐type adenocarcinomas. Thirteen surgical patients with primary gastric cancer displaying neither antibodies nor mucosal atrophy were further analyzed for pathological and phenotypic characteristics. The mucin phenotype was divided into four gastric, five gastric and intestinal, two intestinal and two null types, independent of histological classification. Intestinal phenotype elements were detected by Cdx2 immunohistochemical methods in nine of 13 (70%) cases examined. We conclude that a small fraction of gastric cancer patients displayed multifactorial carcinogenesis without H. pylori infection, indicating that gastric cancer risk still exists in the absence of H. pylori infection, at an incidence of 2.0% at minimum and 10.6% at maximum in the general Japanese population. (Cancer Sci 2007; 98: 790–794)
Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2
Authors: Ishikawa Makoto , Kitayama Joji , Yamauchi Toshimasa , Kadowaki Takashi , Maki Toshiyuki , Miyato Hideyo , Yamashita Hiroharu , Nagawa Hirokazu 
Published: May 2007

Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity‐related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 µg/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down‐regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells. (Cancer Sci 2007; 98: 1120–1127)
c‐Met activation in lung adenocarcinoma tissues: An immunohistochemical analysis
Authors: Nakamura Yu , Niki Toshiro , Goto Akiteru , Morikawa Teppei , Miyazawa Keiji , Nakajima Jun , Fukayama Masashi 
Published: May 2007

c‐Met is often overexpressed in non‐small cell lung cancer, but it remains unsolved whether its overexpression leads to its activation. We used an antibody specific to phospho‐c‐Met (Tyr1235) to investigate c‐Met activation immunohistochemically in 130 surgically resected lung adenocarcinomas. The expression of c‐Met and hepatocyte growth factor (HGF) was also investigated. Phospho‐c‐Met was positive in 21.5% (28/130) of cases. c‐Met was positive in 74.6% of cases (97/130) and was expressed at high levels in 36.1% of cases (47/130). HGF was expressed at high levels in 31.5% of cases (41/130). Phospho‐c‐Met was correlated with high levels of HGF (P =0.0010) and high levels c‐Met expression (P = 0.0303), but it was also found to be positive in 12 cases with little to no HGF expression. Phospho‐c‐Met expression was significantly associated with tumor differentiation (P = 0.0023) and papillary histology (P = 0.0011), but not with pathological stage, lymph node metastasis or survival. High levels of c‐Met and HGF were also associated with papillary histology (P = 0.0056 and P = 0.0396, respectively), but not with tumor differentiation. Phospho‐c‐Met was correlated with phospho‐Akt (P = 0.0381), but not with phospho‐Erk or phospho‐Stat3. Phospho‐Akt expression was marginally correlated with the expression of phospho‐epidermal growth factor receptor (EGFR) (P = 0.0533) and, importantly, it was strongly correlated with the expression of either phospho‐c‐Met or phospho‐EGFR (P = 0.0013). The data suggest that in lung adenocarcinoma tissue, c‐Met activation may take place either ligand‐dependently or ligand‐independently via c‐Met overexpression. c‐Met activation may play special roles in the papillary subtype and in well differentiated lung adenocarcinomas. (Cancer Sci 2007; 98: 1006–1013)
Association of KLK5 overexpression with invasiveness of urinary bladder carcinoma cells
Authors: Shinoda Yasuo , Kozaki Ken‐ichi , Imoto Issei , Obara Wataru , Tsuda Hitoshi , Mizutani Yoichi , Shuin Taro , Fujioka Tomoaki , Miki Tsuneharu , Inazawa Johji 
Published: May 2007

Array‐based comparative genomic hybridization (array‐CGH) has powerful potential for high‐throughput identification of genetic aberrations in cell genomes. We identified high‐level amplification of kallikrein (KLK) genes, which are mapped to 19q13.3 and belong to the serine protease family, in the course of a program to screen a panel of urinary bladder carcinoma cell lines for genomic copy number aberrations using our in‐house CGH‐array. Expression levels of KLK5, ‐6, ‐8 and ‐9 were significantly increased in three cell lines with copy number gains of these KLK genes. Knockdown of these KLK transcripts by specific small interfering RNA significantly inhibited the invasion of a bladder carcinoma cell line through Matrigel in vitro. Reverse transcription–polymerase chain reaction analysis of 42 primary bladder tumor samples showed that increased expression of KLK5 was frequently observed in invasive tumors (pT2–pT4) (14.3%, 6/42) compared with superficial tumors (pTa, pT1) (0%, 0/42; P = 0.0052), and expression levels of KLK5, ‐6, ‐8 and ‐9 mRNA were higher in invasive tumors than in superficial tumors (P < 0.0001, P = 0.0043, P = 0.0790 and P = 0.0037, respectively). These observations indicate that KLK5, ‐6, ‐8 and ‐9 may be the most likely targets of the 19q13.3 amplification, and may play a crucial role in promoting cancer‐cell invasion in bladder tumor. (Cancer Sci 2007; 98: 1078–1086)
Immunological evaluation of personalized peptide vaccination in combination with a 5‐fluorouracil derivative (TS‐1) for advanced gastric or colorectal carcinoma patients
Authors: Sato Yuji , Fujiwara Toshiyoshi , Mine Takashi , Shomura Hiroki , Homma Shigenori , Maeda Yoshiaki , Tokunaga Naoyuki , Ikeda Yoshihiro , Ishihara Yuki , Yamada Akira , Tanaka Noriaki , Itoh Kyogo , Harada Mamoru , Todo Satoru 
Published: May 2007

The aim of the present study was to investigate the safety and immunological responses of personalized peptide vaccination in combination with oral administration of a 5‐fluorouracil derivative (TS‐1) in advanced gastric or colorectal carcinoma patients. Eleven patients (four with gastric cancer and seven with colorectal cancer) who failed to improve by prior TS‐1‐based chemotherapies were enrolled in this study. Peptides to be administered to patients were determined based on the presence of peptide‐specific cytotoxic T lymphocyte (CTL) precursors in peripheral blood mononuclear cells and peptide‐specific IgG in the plasma of cancer patients. Patients were vaccinated with peptides (a maximum of four) biweekly in combination with or without three different doses of TS‐1 (20, 40 and 80 mg/m2/day). Although grade 3 toxicity, including anemia (one patient) and neutropenia (one patient) were observed, the combination therapy was generally well tolerated. An increase in peptide‐specific IgG after the sixth vaccination was observed in the vast majority of patients irrespective of the dose of TS‐1 used. In contrast, an increase in peptide‐specific interferon‐γ production by CTL was most evident in patients who were administered the highest dose of TS‐1. Furthermore, in the patients who received 80 mg/m2/day TS‐1, CTL‐mediated cytotoxicity against cancer cells was maintained at the prevaccination level. These results indicate that administration of the standard dose (80 mg/m2/day) of TS‐1 in combination with a personalized peptide vaccination does not necessarily impede immunological responses in cancer patients, and could actually maintain or augment them. (Cancer Sci 2007; 98: 1113–1119)
Genetic relationships between feral cattle from Chirikof Island, Alaska and other breeds
Authors: MacNeil M. D. , Cronin M. A. , Blackburn H. D. , Richards C. M. , Lockwood D. R. , Alexander L. J. 
Published: May 2007

SummaryThe origin of cattle on Chirikof Island, off the coast of Alaska, is not well documented. We assessed genetic differentiation of cattle isolated on Chirikof Island from several breeds commonly used for commercial production in North America including breeds popularly believed to have contributed to the Chirikof Island population. A set of 34 microsatellite loci was used to genotype Angus, Charolais, Hereford, Highland, Limousin, Red Angus, Salers, Shorthorn, Simmental, Tarentaise and Texas Longhorn cattle sampled from North America and the Chirikof Island population. Resulting FST statistics for these loci ranged from 0.06 to 0.22 and on average, 14% of total genetic variation was between breeds. Whether population structure was modelled as a bifurcating tree or genetic network, Chirikof Island cattle appeared to be unique and strongly differentiated relative to the other breeds that were sampled. Bayesian clustering for multiple‐locus assignment to genetic groups indicated low levels of admixture in the Chirikof Island population. Thus, the Chirikof Island population may be a novel genetic resource of some importance for conservation and industry.
QTL modulating ear size and erectness in pigs
Authors: Wei W. H. , De Koning D. J. , Penman J. C. , Finlayson H. A. , Archibald A. L. , Haley C. S. 
Published: May 2007

SummaryEar size and erectness are important conformation measurements in pigs. An F2 population established by crossing European Large White (small, erect ears) with Chinese Meishan (large, flop ears) was used to study the genetic influence of the two ear traits for the first time. A linkage map incorporating 152 markers on 18 autosomal chromosomes was utilised in a genome scan for QTL. Significant QTL were found on SSC1, 5, 7, 9 and 12 for the two traits. The QTL on SSC5 and SSC7 had major effects and were significant at the genome‐wide level (P < 0.01). The QTL on SSC1 for ear erectness also had a major effect and was genome‐wide significant (P < 0.01). The 95% confidence interval (CI) of the ear size QTL on SSC5 spanned only 4 cM. The QTL on SSC7 for the two ear traits each had a CI of <20 cM, and their positions overlapped with those of the major QTL affecting subcutaneous fat depths on the same chromosome. This study provides insights on the complex genetic influences underlying pig ear traits and will facilitate positional candidate gene analysis to identify causative DNA variants.
A genome scan reveals QTL for growth, fatness, leanness and meat quality in a Duroc‐Pietrain resource population
Authors: Liu G. , Jennen D. G. J. , Tholen E. , Juengst H. , Kleinwächter T. , Hölker M. , Tesfaye D. , Ün G. , Schreinemachers H.‐J. , Murani E. , Ponsuksili S. , Kim J.‐J. , Schellander K. , Wimmers K. 
Published: May 2007

SummaryWe performed a genome‐wide QTL scan for production traits in a line cross between Duroc and Pietrain breeds of pigs, which included 585 F2 progeny produced from 31 full‐sib families genotyped with 106 informative microsatellites. A linkage map covering all 18 autosomes and spanning 1987 Kosambi cM was constructed. Thirty‐five phenotypic traits including body weight, growth, carcass composition and meat quality traits were analysed using least square regression interval mapping. Twenty‐four QTL exceeded the genome‐wide significance threshold, while 47 QTL reached the suggestive threshold. These QTL were located at 28 genomic regions on 16 autosomal chromosomes and QTL in 11 regions were significant at the genome‐wide level. A QTL affecting pH value in loin was detected on SSC1 between marker‐interval S0312‐S0113 with strong statistical support (P < 3.0 × 10−14); this QTL was also associated with meat colour and conductivity. QTL for carcass composition and average daily gain was also found on SSC1, suggesting multiple QTL. Seventeen genomic segments had only a single QTL that reached at least suggestive significance. Forty QTL exhibited additive inheritance whereas 31 QTL showed (over‐) dominance effects. Two QTL for trait backfat thickness were detected on SSC2; a significant paternal effect was found for a QTL in the IGF2 region while another QTL in the middle of SSC2 showed Mendelian expression.
The extent of linkage disequilibrium in a large cattle population of western Africa and its consequences for association studies
Authors: Thévenon S. , Dayo G. K. , Sylla S. , Sidibe I. , Berthier D. , Legros H. , Boichard D. , Eggen A. , Gautier M. 
Published: May 2007

SummarySeveral previous studies concluded that linkage disequilibrium (LD) in livestock populations from developed countries originated from the impact of strong selection. Here, we assessed the extent of LD in a cattle population from western Africa that was bred in an extensive farming system. The analyses were performed on 363 individuals in a Bos indicus × Bos taurus population using 42 microsatellite markers on BTA04, BTA07 and BTA13. A high level of expected heterozygosity (0.71), a high mean number of alleles per locus (9.7) and a mild shift in Hardy–Weinberg equilibrium were found. Linkage disequilibrium extended over shorter distances than what has been observed in cattle from developed countries. Effective population size was assessed using two methods; both methods produced large values: 1388 when considering heterozygosity (assuming a mutation rate of 10−3) and 2344 when considering LD on whole linkage groups (assuming a constant population size over generations). However, analysing the decay of LD as a function of marker spacing indicated a decreasing trend in effective population size over generations. This decrease could be explained by increasing selective pressure and/or by an admixture process. Finally, LD extended over small distances, which suggested that whole‐genome scans will require a large number of markers. However, association studies using such populations will be effective.
Mitochondrial DNA analyses of Indian water buffalo support a distinct genetic origin of river and swamp buffalo
Authors: Kumar S. , Nagarajan M. , Sandhu J. S. , Kumar N. , Behl V. , Nishanth G. 
Published: May 2007

SummaryWater buffalo (Bubalus bubalis) is broadly classified into river and swamp categories, but it remains disputed whether these two types were independently domesticated, or if they are the result of a single domestication event. In this study, we sequenced the mitochondrial D‐loop region and cytochrome b gene of 217 and 80 buffalo respectively from eight breeds/locations in northern, north‐western, central and southern India and compared our results with published Mediterranean and swamp buffalo sequences. Using these data, river and swamp buffalo were distinguished into two distinct clades. Based upon the existing knowledge of cytogenetic, ecological and phenotypic parameters, molecular data and present‐day distribution of the river and swamp buffalo, we suggest that these two types were domesticated independently, and that classification of the river and swamp buffalo as two related subspecies is more appropriate.
Matched‐related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research
Authors: Panepinto Julie A. , Walters Mark C. , Carreras Jeanette , Marsh Judith , Bredeson Christopher N. , Gale Robert Peter , Hale Gregory A. , Horan John , Hows Jill M. , Klein John P. , Pasquini Ricardo , Roberts Irene , Sullivan Keith , Eapen Mary , Ferster Alina ,   On behalf of the Non‐Malignant Marrow Disorders Working Committee, Center for International Blood and Marrow Transplant Research
Published: May 2007

SummaryWe report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)‐matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso‐occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty‐seven percent of patients had a poor performance score at transplantation. Ninety‐four percent received busulfan and cyclophosphamide‐containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post‐transplant period. Rates of acute and chronic graft‐versus‐host disease were 10% and 22% respectively. Sixty‐four of 67 patients are alive with 5‐year probabilities of disease‐free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle‐related events. This report confirms and extends earlier reports that HCT from HLA‐matched related donors offers a very high survival rate, with few transplant‐related complications and the elimination of sickle‐related complications in the majority of patients who undergo this therapy.