bluuebunny/crossref_metadata_2025_split huggingface dataset:
More extensive genetic alterations in unmutated than in hypermutated cases of chronic lymphocytic leukemia
Authors: Karhu Ritva , Tobin Gerard , Thunberg Ulf , Vilpo Leena , Sundström Christer , Knuutila Sakari , Rosenquist Richard , Vilpo Juhani 
Published: June 2003

AbstractB‐cell chronic lymphocytic leukemia (CLL) is not a uniform disease entity; approximately half of the CLL cases have undergone immunoglobulin VH gene hypermutation, whereas the other half display unmutated VH genes. We investigated genome changes in 12 hypermutated cases (M‐CLL) and 22 unmutated cases (UM‐CLL) by use of comparative genomic hybridization, G‐banding, and multicolor fluorescence in situ hybridization (m‐FISH) after optimal mitogen stimulation and FISH analysis of typical CLL aberrations: 11q deletion, 13q deletion, and trisomy 12. Very high frequencies of aberrations were found in both groups: 82% in UM‐CLL and 83% in M‐CLL. Deletions of 11q and 13q were equally distributed in M‐CLL and UM‐CLL. However, larger aberrations detectable by CGH, trisomy 12, and complex aberrations were less frequent in M‐CLL than in UM‐CLL. These observations led to a hypothesis that unmutated and mutated CLL have different biological Backgrounds, given that large and/or complex chromosomal aberrations and hypermutation of the CLL progenitor cells tend to be mutually exclusive. © 2003 Wiley‐Liss, Inc.
Monochromosome transfer provides functional evidence for growth‐suppressive genes on chromosome 14 in nasopharyngeal carcinoma
Authors: Cheng Yue , Ko Josephine M. Y. , Lung Hong L. , Lo Paulisally H. Y. , Stanbridge Eric J. , Lung Maria L. 
Published: June 2003

AbstractIn many cancers, including nasopharyngeal carcinoma (NPC), extensive and multiple regions of allelic loss occur on chromosome 14. However, to date no functionally conclusive tumor suppressor genes have yet been identified on this chromosome. Through use of the monochromosome transfer technique, this study provides functional evidence for the importance of two discrete regions of chromosome 14. A newly established A9 mouse donor cell line containing an intact copy of chromosome 14 was used for transfer of this intact chromosome into the NPC HONE1 cell line. Twelve independently established microcell hybrids demonstrated uniform loss of specific chromosome 14 loci from both endogenous and exogenous alleles. By microsatellite typing and fluorescence in situ hybridization with BAC probes, the two critical regions were localized to 14q11.2–13.1 and 14q32.1. Selective elimination of these regions during hybrid selection was strongly associated with both hybrid survival and tumor growth in vivo. This functional evidence now narrows down the candidate areas for further studies and suggests that at least two hitherto unidentified growth‐related genes localized on two critical regions of chromosome arm 14q play an important role in tumorigenesis. © 2003 Wiley‐Liss, Inc.
A new chromosome banding technique, spectral color banding (SCAN), for full characterization of chromosomal abnormalities
Authors: Kakazu Naoki , Bar‐Am Irit , Hada Satoshi , Ago Hiroatsu , Abe Tatsuo 
Published: June 2003

AbstractWe have developed spectral color banding (SCAN) as a new chromosome banding technique based on spectral analysis of differentially labeled chromosome band‐specific painting probes. In this study, we succeeded in displaying a multicolor banding pattern for chromosome 3, which was almost identical to the pattern obtained with the corresponding G‐banding. We applied this method to metaphase cells from different normal male donors with various levels of G‐banding resolution, ranging from 250 to 850 bands per haploid set. The same multicolor banding pattern was observed in all samples regardless of the length of the chromosomes or the quality of the G‐banding. We then used SCAN in a diffuse large B‐cell lymphoma case for a complete analysis of the intrachromosomal change for chromosome 3, which could not be fully characterized by G‐banding or even by spectral karyotyping (SKY). SCAN could detect the duplicated segment and identify the origin of the chromosome band on the basis of the specific spectral color of each band. This study demonstrates that SCAN is a useful tool for full characterization of chromosomal abnormalities not identified by SKY. © 2003 Wiley‐Liss, Inc.
Globalization, global health, and access to healthcare
Authors: Collins Téa 
Published: June 2003

AbstractIt is now commonly realized that the globalization of the world economy is shaping the patterns of global health, and that associated morbidity and mortality is affecting countries' ability to achieve economic growth. The globalization of public health has important implications for access to essential healthcare. The rise of inequalities among and within countries negatively affects access to healthcare. Poor people use healthcare services less frequently when sick than do the rich. The negative impact of globalization on access to healthcare is particularly well demonstrated in countries of transitional economies. No longer protected by a centralized health sector that provided free universal access to services for everyone, large segments of the populations in the transition period found themselves denied even the most basic medical services. Only countries where regulatory institutions are strong, domestic markets are competitive and social safety nets are in place, have a good chance to enjoy the health benefits of globalization. Copyright © 2003 John Wiley & Sons, Ltd.
Prioritization of prevention activities to combat the spread of HIV/AIDS in resource constrained settings: a cost‐effectiveness analysis from Chad, Central Africa
Authors: Hutton Guy , Wyss Kaspar , N'Diékhor Yemadji 
Published: June 2003

AbstractIn Chad, as in most sub‐Saharan Africa countries, HIV/AIDS poses a massive public health threat as well as an economic burden, with prevalence rates estimated at 9% of the adult population. In defining and readjusting the scope and content of the national HIV/AIDS control activities, policy makers sought to identify the most cost‐effective options for HIV/AIDS control. The cost‐effectiveness analysis reported in this paper uses a mixture of local and international information sources combined with appropriate assumptions to model the cost‐effectiveness of feasible HIV prevention options in Chad, with estimates of the budget impact. The most cost‐effective options at under US$100 per infection prevented were peer group education of sex workers and screening of blood donors to identify infected blood before transfusion. These options were followed by mass media and peer group education of high risk men and young people, at around US$500 per infection prevented. Anti‐retroviral therapy for HIV infected pregnant women and voluntary counselling and testing were in the order of US$1000 per infection prevented. The paper concludes with recommendations for which activities should be given priority in the next phase of the national HIV/AIDS control programme in Chad. Copyright © 2003 John Wiley & Sons, Ltd.
Alterations of BLU, a candidate tumor suppressor gene on chromosome 3p21.3, in human nasopharyngeal carcinoma
Authors: Liu Xiao‐Qiong , Chen Han‐Kui , Zhang Xiao‐Shi , Pan Zhi‐Gang , Li Ang , Feng Qi‐Sheng , Long Qing‐Xin , Wang Xun‐Zhang , Zeng Yi‐Xin 
Published: June 2003

AbstractNonrandom allelic loss on chromosome 3p is a common event in nasopharyngeal carcinoma (NPC) with the implication that certain tumor suppressor gene(s) in this region are involved in the pathogenesis of these tumors. The BLU gene, located at 3p21.3, has recently been identified as a candidate tumor suppressor gene due to the occurrence of missense mutations and loss of its expression in lung cancer. To investigate the involvement of BLU gene in NPC, we examined both genetic and epigenetic changes of BLU in NPC primary tumors and cell lines. No pathogenic mutations were detected in the entire coding region of this gene in 45 primary NPC tumors and 5 NPC cell lines. While BLU was expressed in 100% (15 of 15) of noncancerous nasopharyngeal epithelia, its transcripts were missing in all 5 NPC cell lines, and absent or reduced mRNA levels were observed in 78% (28 of 36) of the primary tumors. In the NPC cell lines, loss of BLU expression correlated with hypermethylation of the CpG island promoter sequence, and expression was restored after treatment with 5′‐aza‐2′‐deoxycytidine. Methylation specific PCR analysis revealed that the BLU promoter was highly methylated in 74% (17 of 23) of primary tumors in which BLU was downregulated, whereas only 2 of 9 non‐neoplastic nasopharyngeal epithelia exhibited hypermethylation in the BLU promoter region. The high incidence of BLU alterations suggests that it may be one of the critical tumor suppressor genes on chromosome 3p21.3 involved in the development of NPC. © 2003 Wiley‐Liss, Inc.
Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas ligand in human pancreatic adenocarcinoma
Authors: Tsuji Shoichiro , Hosotani Ryo , Yonehara Shin , Masui Toshihiko , Tulachan Sidhartha S. , Nakajima Sanae , Kobayashi Hiroyuki , Koizumi Masayuki , Toyoda Eiji , Ito Daisuke , Kami Kazuhiro , Mori Tomohiko , Fujimoto Koji , Doi Ryuichiro , Imamura Masayuki 
Published: June 2003

AbstractMany cancers are resistant to Fas‐mediated apoptosis despite the expression of Fas. To investigate the mechanisms by which Fas signals are attenuated, we focused on decoy receptor 3 (DcR3). DcR3 is a soluble receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily and overexpresses in some forms of cancers. Exogenous DcR3 inhibits Fas‐mediated apoptosis in Fas‐sensitive Jurkat cells. In our study, we examined the expression and function of DcR3 in pancreatic cancers. TaqMan RT‐PCR showed that DcR3 mRNA was highly expressed in pancreatic cancer cell lines (71%) and tissues (67%). Its expression significantly correlated with cancer invasion to veins. Western blotting showed that the DcR3 protein was produced and secreted in 4 of 6 cell lines. The protein expressions were compatible with the mRNA expression. Five of 7 pancreatic cancer cell lines became sensitive to agonistic anti‐Fas antibody (CH‐11) to various extents, without Fas upregulation, when exposed to CH‐11 for 48 hr after pretreatment with IFNγ. Four of 7 pancreatic cancer cell lines were inhibited from growing, compared to control cells, when cocultured with membrane‐bounded Fas ligand (mFasL) transfected lymphomas for 48 hr after pretreatment with IFNγ. DcR3 reduced this growth inhibition when added exogenously. Regression analysis showed that the DcR3 expression significantly correlated with the sensitivity to mFasL, and not to CH‐11. These results suggest that DcR3 is highly expressed in many pancreatic cancers and endogenous DcR3 blocks the growth inhibition signals mediated by mFasL. DcR3 can be a candidate target molecule for the therapeutic intervention. © 2003 Wiley‐Liss, Inc.
Synergistic antiproliferative and apoptotic effects induced by epidermal growth factor receptor and protein kinase a inhibitors in human prostatic cancer cell lines
Authors: Mimeault Murielle , Pommery Nicole , Hénichart Jean‐Pierre 
Published: June 2003

AbstractOur results revealed that the blockade of epidermal growth factor receptor (EGFR) tyrosine kinase and protein kinase A (PKA) signaling pathways by specific inhibitors (PD153035 and Rp‐cAMPs) leads to a synergistic inhibition of EGF‐ and serum‐stimulated growth of human prostatic cancer cells (LNCaP, DU145 and PC3) concomitant with an arrest in the G1 phase of cellular cycle. Of particular interest, the combination of PD153035 and Rp‐cAMPs also caused a more substantial apoptotic/necrotic death of these prostatic cancer cells as compared to drugs alone. Moreover, we observed that the inhibition of acidic sphingomyelinase and caspase cascades results in a marked reduction of DNA fragmentation and apoptotic death induced by PD153035, alone or in combination with Rp‐cAMPs, in EGF stimulated PC3 cells. This suggests that these agents might mediate their cytotoxic effects at least in part via the ceramide generation and activation of caspase signaling pathways. N‐oleoylethanolamine (OE), an inhibitor of acidic ceramidase, consistently potentiated the apoptotic effects of PD153035 in all the prostatic cancer cell lines tested. Additionally, the cellular ceramide content estimated for PC3 cells was increased after treatment with PD153035, alone or in combination, at a lower dose with OE and Rp‐cAMPs.The synergistic apoptotic effect of PD153035 plus Rp‐cAMPs induced in PC3 was also accompanied by a significant rate of mitochondrial membrane depolarization and release of cytochrome c into cytosol as compared to drugs alone. Combined, the results indicated that the simultaneous inhibition of EGFR and PKA signaling cascades might lead to a more massive apoptotic death of metastatic prostatic cancer cells by increasing ceramide accumulation and activating of caspase cascade of a mitochondrial dependent manner. © 2003 Wiley‐Liss, Inc.
Breast cell invasive potential relates to the myoepithelial phenotype
Authors: Gordon Linda A. , Mulligan Kellie T. , Maxwell‐Jones Helen , Adams Matthew , Walker Rosemary A. , Jones J. Louise 
Published: June 2003

AbstractOn the basis of marker profile, the majority of breast carcinomas are thought to be derived from luminal epithelial cells; however, a subgroup of tumours with more mesenchymal characteristics are associated with a worse prognosis. The hypothesis of our study is that some breast carcinomas exhibit myoepithelial rather than pure mesenchymal differentiation and that acquisition of myoepithelial characteristics confers an aggressive phenotype. Pure luminal epithelial cells and fibroblasts are readily distinguished by many markers but distinguishing between myoepithelial and fibroblast cell lineages is more problematic. The markers found to be most discriminating in our study were CK14, α6β4 integrin and the myoepithelial‐associated desmosomal cadherin DSg3. These markers were applied to a series of breast cell lines and purified normal breast cell populations and the expression profile related to in vitro invasive behaviour. This demonstrated that expression of one or more myoepithelial markers by tumour cells (MDA MB 231, MDA MB 468, MDA MB 436) was associated with a high invasive capacity compared with cells with a pure luminal phenotype (MCF‐7, T47D, ZR75). To address why myoepithelial characteristics are associated with higher invasion, the in vitro behaviour of normal myoepithelial cells and two other nontumourigenic breast cell lines (MCF‐10A, HBL100) was also analysed. Primary myoepithelial cells from normal human breast exhibit a high invasive capacity when grown at low density, suggesting that invasive capacity is part of the myoepithelial phenotype. In keeping with this, both nontumourigenic cell lines exhibited features of the myoepithelial phenotype and a high invasive capacity. These results suggest that tumours that exhibit a myoepithelial phenotype may be clinically more aggressive because a high invasive capacity is intrinsic to the myoepithelial phenotype. © 2003 Wiley‐Liss, Inc.
Distinct methylation profiles of glioma subtypes
Authors: Uhlmann Karen , Rohde Klaus , Zeller Constanze , Szymas Janusz , Vogel Siegfried , Marczinek Karola , Thiel Gundula , Nürnberg Peter , Laird Peter W. 
Published: June 2003

AbstractGliomas are tumors of the central nervous system with a wide spectrum of different tumor types. They range from pilocytic astrocytoma, with a generally good prognosis, to the extremely aggressive malignant glioblastoma. In addition to these 2 types of contrasting neoplasms, several other subtypes can be distinguished, each characterized by specific phenotypic, as well as genotypic features. Recently, the epigenotype, as evident from differentially methylated DNA loci, has been proposed to be useful as a further criterion to distinguish between tumor types. In our study, we screened 139 tissue samples, including 33 pilocytic astrocytomas, 46 astrocytomas of different grades, 7 oligoastrocytomas, 10 oligodendrogliomas, 10 glioblastoma multiforme samples and 33 control tissues, for methylation at CpG islands of 15 different gene loci. We used the semiquantitative high throughput method MethyLight to analyze a gene panel comprising ARF, CDKN2B, RB1, APC, CDH1, ESR1, GSTP1, TGFBR2, THBS1, TIMP3, PTGS2, CTNNB1, CALCA, MYOD1 and HIC1. Seven of these loci showed tumor specific methylation changes. We found tissue as well as grade specific methylation profiles. Interestingly, pilocytic astrocytomas showed no evidence of CpG island hypermethylation, but were significantly hypomethylated, relative to control tissues, at MYOD1. Our results show that glioma subtypes have characteristic methylation profiles and, with the exception of pilocytic astrocytomas, show both locus specific hyper‐ as well as hypomethylation. © 2003 Wiley‐Liss, Inc.
Mammary tumor latency is increased in mice lacking the inducible nitric oxide synthase
Authors: Ellies Lesley G. , Fishman Michael , Hardison Joy , Kleeman Jeanine , Maglione Jeannie E. , Manner Cathyryne K. , Cardiff Robert D. , MacLeod Carol L. 
Published: June 2003

AbstractNitric oxide (NO) and its metabolites are implicated in carcinogenesis and metastasis. Both stimulatory and inhibitory effects of NO have been reported in relation to breast cancer and its role in the development of malignancies and metastasis remains uncertain. We have used the polyomavirus middle T antigen (PyV‐mT) targeted to the mouse mammary gland and bred into an inducible NO synthase (iNOS)‐deficient C57Bl/6 strain to examine a role for nitric oxide in modulating tumors that develop in the complex environment of the whole animal. The development of hyperplasias was delayed to the extent that the earliest palpable tumors arose 2–4 weeks later in PyV‐mT/iNOS−/− mice compared with PyV‐mT/iNOS+/+ mice, identifying a role for iNOS in early events in mammary tumor formation. Tumors that did develop in PyV‐mT/iNOS−/− mice were characteristically well differentiated and had a cribriform pattern. Other tumors were myoepithelial adenocarcinomas with uniform nuclear size. In contrast, mice capable of iNOS activity typically developed solid nodular adenocarcinomas with a high mitotic index and pleomorphic nuclei. No significant effect of iNOS deficiency was found on vascular density in hyperplasias or tumors by examining CD31‐positive vessels. The infiltration of lesions by macrophages, cells capable of significant NO production, remained unchanged in PyV‐mT/iNOS−/− mice. Metastatic potential was retained by PyV‐mT‐transformed epithelium in the absence of iNOS, indicating that NO production by iNOS is not essential for this process. These results indicate a role for iNOS in tumorigenesis, particularly in the regulation of early events. © 2003 Wiley‐Liss, Inc.
Prognostic value of bcl‐6, CD10 and CD38 immunoreactivity in stage I–II gastric lymphomas: Identification of a subset of CD10+ large B‐cell lymphomas with a favorable outcome
Authors: Ponzoni Maurilio , Ferreri Andrés J.M. , Pruneri Giancarlo , Pozzi Barbara , Dell'Oro Stefania , Pigni Alessandra , Pinotti Graziella , Villa Eugenio , Freschi Massimo , Viale Giuseppe , Capella Carlo 
Published: June 2003

Abstractbcl‐6, CD10 and CD38 are useful markers for identifying 2 molecularly and prognostically distinct profiles of diffuse large B‐cell lymphomas (LCLs), defined as germinal‐center B‐like and activated B‐like. We investigated the prognostic role of bcl‐6, CD10 and CD38 immunoreactivity in 102 gastrectomized patients with primary gastric lymphomas (PGLs). There were 41 low‐grade marginal zone lymphomas of MALT‐type (LGML) and 61 diffuse large B‐cell lymphomas with (DLCLMLs; n = 31) or without (DLCLs; n = 30) an LGML component. bcl‐6, CD10 and CD38 were significantly more commonly expressed in DLCL or DLCML as compared with LGML (50% vs. 48% vs. 17%, p = 0.0002 for bcl‐6; 27% vs. 26% vs. 0%, p = 0.0004 for CD10; 45% vs. 48% vs. 13%, p = 0.0005 for CD38, respectively). CD10 immunoreactivity was independently associated with a better survival in diffuse LCL patients (5‐year overall survival: 88% ± 8% vs. 66% ± 7%; p = 0.04); bcl‐6 or CD38 immunoreactivities did not disclose any prognostic implication. Age, presence of LGML component, lactic dehydrogenase serum levels and use of chemotherapy were additional independent prognostic factors. We conclude that CD10 immunoreactivity assessment could be a clear, easy‐to‐interpret and reliable prognostic factor in PGL. Accordingly, patients with CD10+ gastric large B‐cell lymphomas may be at reduced risk and eligible for clinical trials evaluating more conservative therapeutic options. © 2003 Wiley‐Liss, Inc.
Myeloperoxidase promotor polymorphism and risk of hepatoblastoma
Authors: Pakakasama Samart , Chen Tina T.‐L. , Frawley William , Muller Carolyn , Douglass Edwin C. , Tomlinson Gail E. 
Published: June 2003

AbstractMyeloperoxidase (MPO) is a major enzyme found in neutrophils. Oxidation by MPO produces free radicals that demonstrate genotoxic properties. A polymorphism (G to A) within the promotor region of the MPO gene reduces transcription and expression. This polymorphism is associated with a protective effect against some cancers in adults including lung cancer. The objective of our study was to investigate the effect of this MPO polymorphism on the risk of hepatoblastoma, the most common cancer of the liver in childhood. By using PCR‐SSCP, we determined the genotype at this polymorphism in 48 cases of Caucasian children with hepatoblastoma and 180 normal controls. Genotypes were confirmed by a second method using Aci I restriction enzyme restriction. We found that A allele was associated with reduced risk of hepatoblastoma of 50% (OR, 0.51; 95%CI, 0.27–0.93) and G/A or A/A genotype reduced the risk by 56% (OR, 0.44; 95%CI, 0.21–0.90). Our data suggest that A allele is a protective factor with regard to the risk of hepatoblastoma, perhaps by altering genotoxic properties of xenobiotic substances which may act as carcinogens. © 2003 Wiley‐Liss, Inc.