bluuebunny/crossref_metadata_2025_split huggingface dataset:
c‐Kit is preferentially expressed in MYCN‐amplified neuroblastoma and its effect on cell proliferation is inhibited in vitro by STI‐571
Authors: Vitali Roberta , Cesi Vincenzo , Nicotra Maria Rita , McDowell Heather P. , Donfrancesco Alberto , Mannarino Olga , Natali Pier Giorgio , Raschellà Giuseppe , Dominici Carlo 
Published: June 2003

AbstractCoexpression for c‐Kit receptor and its ligand stem cell factor (SCF) has been described in neuroblastoma (NB) cell lines and tumors, suggesting the existence of an autocrine loop modulating tumor growth. We evaluated c‐Kit and SCF expression by immunohistochemistry in a series of 75 primary newly diagnosed neuroblastic tumors. Immunostaining for c‐Kit was found in 10/75 and for SCF in 17/75, with 5/10 c‐Kit–positive tumors also expressing SCF. For both, c‐Kit and SCF staining were predominantly found in the most aggressive subset of tumors, i.e., those amplified for MYCN: c‐Kit was detected in 8/14 amplified vs. 2/61 single copy (p<0.001), and SCF in 9/14 amplified vs. 8/61 single copy tumors (p<0.001). Furthermore, the association of c‐Kit expression with advanced stage (3 or 4) (p=0.001) and of SCF expression with adrenal primary (p=0.03) was substantiated. The in vitro activity of the tyrosine kinase inhibitor STI‐571 (imatinib mesylate, Gleevec, Glivec) on NB cell lines positive or negative for c‐Kit was also assessed. When cells were grown in 10% fetal calf serum, the 4 c‐Kit‐positive cell lines tested were sensitive to STI‐571 growth inhibition to a different extent (ranging from 30 to 80%); also the c‐Kit‐negative cell line GI‐CA‐N was slightly affected, suggesting that other STI‐571 targets operate in regulating NB proliferation. In addition, c‐Kit‐positive cell lines SK‐N‐BE2(c) and HTLA230, grown in SCF only, remained sensitive (40 and 70% of growth inhibition, respectively), while, in the same conditions, proliferation of the c‐Kit‐negative cell line GI‐CA‐N was not affected. Immunoprecipitation of c‐Kit from cell lysates of SK‐N‐BE2(c) and HTLA230 cells grown in SCF and subsequent western blot analysis of the immunoprecipitates revealed a sharp decrease of c‐Kit phosphorylation after STI‐571 treatment. These data demonstrate that both c‐Kit and SCF are preferentially expressed in vivo in the most aggressive neuroblastic tumors and that their signaling is active in promoting in vitro NB cell proliferation that can be selectively inhibited by treatment with STI‐571. © 2003 Wiley‐Liss, Inc.
Capsaicin consumption, Helicobacter pylori positivity and gastric cancer in Mexico
Authors: López‐Carrillo Lizbeth , López‐Cervantes Malaquías , Robles‐Díaz Guillermo , Ramírez‐Espitia Armando , Mohar‐Betancourt Alejandro , Meneses‐García Abelardo , López‐Vidal Yolanda , Blair Aaron 
Published: June 2003

AbstractGastric cancer (GC) incidence has not declined in Mexico. We assessed whether the intake of capsaicin (CAP), the pungent compound of chili peppers, increases the risk of GC independently of H. pylori positivity (Hp). From 1994 to 1996, a hospital‐based case‐control study was performed in 3 areas of Mexico; 234 cases of GC and 468 matched controls were enrolled and their diet and other characteristics were inquired. Chili pepper intake was queried by interview and CAP content of chilies was determined in a separate analysis by gas chromatography to estimate CAP intake; IGg Hp serum antibodies were determined by ELISA. The risk of GC was increased (OR = 1.71; 95% CI = 0.76–3.88) among high‐level consumers of CAP (90–250 mg of capsaicin per day, approximately 9–25 jalapeño peppers per day) as compared to low‐level consumers (0–29.9 mg of capsaicin per day, approximately 0 to less than 3 jalapeño peppers per day; p for trend p = 0.026); this effect was independent of Hp status and other potential GC determinants and was higher among diffuse GC cases (OR = 3.64; 95% CI = 1.09–12.2; p for trend = 0.002) compared to intestinal GC cases (OR = 1.36; 95% CI = 0.31–5.89; p for trend = 0.493). No significant interaction was found between CAP intake and Hp on GC risk. Chili pepper consumption might be an independent determinant of GC in Mexico. © 2003 Wiley‐Liss, Inc.
Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: Relationships with abnormal E‐cadherin and catenin expression and microsatellite instability
Authors: Sarrió David , Moreno‐Bueno Gema , Hardisson David , Sánchez‐Estévez Carolina , Guo Mingzhou , Herman James G. , Gamallo Carlos , Esteller Manel , Palacios José 
Published: June 2003

AbstractThe causes and functional consequences of E‐cadherin (E‐CD) loss in breast cancer are poorly understood. E‐CD loss might act in concert with alterations in the APC/β‐catenin pathway to permit oncogenic β‐catenin signaling. To test this hypothesis, we have analyzed the presence of genetic and epigenetic alterations affecting E‐CD (CDH1), APC and β‐catenin (CTNNB1) genes and the immunohistochemical expression of E‐CD, β‐ and γ‐catenin in a series of 46 infiltrating lobular breast carcinomas (ILCs). Since 80% of ILCs featured complete loss of E‐CD expression, we analyzed the molecular alterations responsible for E‐CD inactivation in these tumors. We found that 10 of 46 (22%) cases harbored mutations in CDH1, including 1 case with 2 different mutations (1 of which was germline). CDH1 was also inactivated by loss of heterozygosity (LOH; 30/41, 73%) and promoter hypermethylation (19/46, 41%). Interestingly, LOH and mutations were also detected in the corresponding in situ lesions of the ILCs, implying that these alterations are early events in lobular cancer tumorogenesis. Additionally, the presence of a polymorphism in the CDH1 promoter was found to be inversely correlated with CDH1 mutations, but not with E‐CD levels. We next examined whether alterations in the APC/β‐catenin pathway also occurred in the same series of ILCs. Although no CTNNB1 or APC mutations were detected, promoter methylation (25/46, 52%) and LOH (7/30, 23%) of APC were found. Moreover, methylation of APC and CDH1 occurred concordantly. However, β‐ and γ‐catenin were severely reduced or absent in 90% of these tumors, implying that alterations in CDH1 and APC genes do not promote β‐catenin accumulation in ILC. These molecular alterations were not associated with microsatellite instability. In summary, several different mechanisms (mutations, LOH, methylation) are involved in the frequent CDH1 inactivation in invasive and in situ lobular breast cancer. The same tumors also show genetic and epigenetic alterations of APC gene. However, altered CDH1 and APC genes do not promote β‐catenin accumulation in this tumor type. © 2003 Wiley‐Liss, Inc.
Characterization of several leukemia‐associated antigens inducing humoral immune responses in acute and chronic myeloid leukemia
Authors: Greiner Jochen , Ringhoffer Mark , Taniguchi Masanori , Hauser Thomas , Schmitt Anita , Döhner Hartmut , Schmitt Michael 
Published: June 2003

AbstractTo design a specific immunotherapy for leukemia patients, the identification of leukemia‐associated antigens (LAAs) is a pivotal step. Antileukemic effects after hematopoetic stem cell transplantation for myeloid leukemias are observed and might be related to the recognition of LAAs. Using the serological screening of an expression library (SEREX) of K562 cells, we identified 16 different clones encoding LAAs eliciting a humoral immune response, among them the heat shock proteins HSJ2 and HSP70, the M‐phase phosphoprotein 11 (MPP11), the BRCA1‐associated protein (BRAP), the Jκ recombination binding protein (RBPJκ) and the receptor for hyaluronic acid mediated motility (RHAMM). Serological responses to MPP11 were observed in 7/19 (37%) of patients with acute myeloid leukemia (AML) and 6/16 (38%) of patients with chronic myeloid leukemia (CML), but not in healthy volunteers (0/20). IgG antibodies directed against MPP11 were also detected in 25–50% of the sera of patients with solid tumors such as melanoma, renal cell, ovarian and breast carcinoma. mRNA expression of MPP11 was detected in 20/20 AML patients and 7/10 patients with CML. In normal tissues, strong mRNA expression of MPP11 was only detected in testis. By real‐time PCR, we detected upregulation of MPP11 in leukemic blasts. Simultaneous humoral immune responses to 2 or more of the 16 LAAs identified here was observed, suggesting the feasibility of a polyvalent vaccination as an option for immunotherapies in leukemia patients. © 2003 Wiley‐Liss, Inc.
Induced and spontaneous abortion and breast cancer risk: Results from the E3N cohort study
Authors: Paoletti Xavier , Clavel‐Chapelon Françoise 
Published: June 2003

AbstractRecent reviews reach conflicting conclusions on breast cancer risk after spontaneous or induced abortion. E3N is a large‐scale cohort study collecting detailed information on environmental and reproductive factors. We investigated the relation between breast cancer and a history of induced and/or spontaneous abortion, using the data from the 100,000 women aged 40–65 at entrance in 1990. Among them, over 2,600 new invasive breast cancers had been diagnosed by June 2000. Multivariate analysis, adjusted for known potential confounders, showed no association between a history of induced abortion and breast cancer risk either in the whole population (relative risk [RR] = 0.91, 95% confidence interval [CI] 0.82–0.99) or in subgroups defined by parity or by menopausal status. Overall, the association between spontaneous abortion and breast cancer was not significant (RR = 1.05, 95% CI 0.95–1.15). However, there is a suggestion of increased risk with increased number of miscarriages (RR = 1.20, 95% CI 0.92–1.56 after 3 or more). Moreover, an interaction with menopausal status was observed. In premenopause, the risk decreased with increasing number of spontaneous abortions, whereas it increased in postmenopause. Among nulliparous and parous women, the relative risk estimates were respectively equal to 1.16 (95% CI 1.04–1.30, p trend < 0.0008) and 1.14 (95% CI 1.01–1.28, p trend = 0.005). Premenopausal breast cancer, on the other hand, appeared to be less frequent in women who had had repeated miscarriages. We conclude that there is no relationship between breast cancer and induced abortion but that an association with spontaneous abortion is possible and may depend on menopausal status. © 2003 Wiley‐Liss, Inc.
Dietary influences on survival after ovarian cancer
Authors: Nagle Christina M. , Purdie David M. , Webb Penelope M. , Green Adèle , Harvey Philip W. , Bain Christopher J. 
Published: June 2003

AbstractWe evaluated the effects of various food groups and micronutrients in the diet on survival among women who originally participated in a population‐based case‐control study of ovarian cancer conducted across 3 Australian states between 1990 and 1993. This analysis included 609 women with invasive epithelial ovarian cancer, primarily because there was negligible mortality in women with borderline tumors. The women's usual diet was assessed using a validated food frequency questionnaire. Deaths in the cohort were identified using state‐based cancer registries and the Australian National Death Index (NDI). Crude 5‐year survival probabilities were estimated using the Kaplan‐Meier technique, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression models. After adjusting for important confounding factors, a survival advantage was observed for those who reported higher intake of vegetables in general (HR = 0.75, 95% CI = 0.57–0.99, p‐value trend 0.01 for the highest third, compared to the lowest third), and cruciferous vegetables in particular (HR = 0.75, 95% CI = 0.57–0.98, p‐value trend 0.03), and among women in the upper third of intake of vitamin E (HR = 0.76, 95% CI = 0.58–1.01, p‐value trend 0.04). Inverse associations were also seen with protein (p‐value trend 0.09), red meat (p‐value trend 0.06) and white meat (p‐value trend 0.07), and modest positive trends (maximum 30% excess) with lactose (p‐value trend 0.04), calcium and dairy products. Although much remains to be learned about the influence of nutritional factors after a diagnosis of ovarian cancer, our study suggests the possibility that a diet high in vegetable intake may help improve survival. © 2003 Wiley‐Liss, Inc.
Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer
Authors: Virmani Arvind , Rathi Asha , Sugio Kenji , Sathyanarayana Ubaradka G. , Toyooka Shinichi , Kischel Frank C. , Tonk Vijay , Padar Asha , Takahashi Takashi , Roth Jack A. , Euhus David M. , Minna John D. , Gazdar Adi F. 
Published: June 2003

AbstractTMS1 (target of methylation‐induced silencing) is a CpG island‐associated gene that functions in the regulation of apoptosis and encodes a caspase recruitment domain, a recently described motif found in apoptotic signaling molecules. Recent evidence suggests that silencing of genes in the apoptotic pathway contribute to human carcinogenesis. We examined the DNA methylation status of the TMS1 promoter in lung and breast tumor tissues, tumor cell lines and nonmalignant tissues by methylation‐specific polymerase chain reaction (MSP) and its mRNA expression by reverse transcription PCR. Aberrant methylation of TMS1 was present in 70% (40 of 57) of small cell lung cancer (SCLC) cell lines and 41% (13 of 32) of SCLC tumor tissues, 48% (29 of 61) of non small cell lung cancer (NSCLC) cell lines and 40% (28 of 70) of NSCLC tumor tissues and 46% (12 of 26) of breast cancer cell lines and 32% (20 of 63) of breast tumor tissues. Methylation was absent in the peripheral blood lymphocytes and buccal epithelium from healthy volunteers, as well as in nonmalignant lung tissues and was rare in nonmalignant breast tissues 7% (2 of 30). DNA methylation was confirmed by sequence analysis and the methylation status correlated inversely with TMS1 RNA expression in 18 cell lines tested. RNA expression was restored by treatment with the demethylating agent 5‐aza‐2′‐deoxycytidine, in 4 of 4 methylated cell lines that lacked the TMS1 transcript. Our results suggest that methylation of TMS1 may play a role in the pathogenesis of small cell and non small lung and breast cancers. © 2003 Wiley‐Liss, Inc.
Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries
Authors: Behrends Uta , Schneider Inken , Rössler Sabine , Frauenknecht Heinrich , Golbeck Anja , Lechner Brigitte , Eigenstetter Gerhard , Zobywalski Colette , Müller‐Weihrich Stephan , Graubner Ulrike , Schmid Irene , Sackerer Dieter , Späth Manfred , Goetz Claudia , Prantl Franz , Asmuss Hans‐Peter , Bise Karl , Mautner Josef 
Published: June 2003

AbstractMedulloblastoma is an embryonal childhood malignancy with poor prognosis. By screening 4 medulloblastoma cDNA expression libraries (SEREX) with autologous sera, 15 different antigens were identified. These antigens were encoded by 3 novel genes, genes of unknown function (KIAA0445, KIAA1853, KIAA0665, FLJ13942, HSPC213), a proto‐oncogene (rab18), candidate tumor suppressor genes (BAP1, PRDM13) and genes encoding a motor protein (kinesin‐2), a histone (H2A1.2), the ankyrin residue‐rich nasopharyngeal cancer susceptibility protein (NZ16) and the transcription factor TZP, which is homologous to the tumor‐associated antigens HCA58 and GLEA2. In a consecutive analysis of serum antibody titers and tumor load, a more than 10‐fold increase in serum antibodies against PRDM13 preceded the clinical diagnosis of recurrent tumor growth in a patient with aggressive large cell medulloblastoma. When sera of pediatric patients with cancer (n = 40) and healthy controls (n = 40) were tested for humoral responses against the SEREX‐defined antigens, 5 antigens were exclusively recognized by sera from cancer patients. These antigens included a novel rab18 gene product translated from mRNA sequences formerly described as 3′ untranslated region. Humoral responses against 2 of the remaining 10 antigens were found preferentially in cancer patients. Antibodies against these antigens were detected in 8/40 and 12/40 cancer patients, respectively, but in only 1 healthy control. The 2 antigens were characterized by a tumor‐specific deletion and a tumor‐specific mutation, respectively. These findings indicate that the humoral immune response against medulloblastoma is directed against diverse antigens that may be useful as diagnostic markers or targets for immunotherapy. © 2003 Wiley‐Liss, Inc.
Spontaneously formed tumorigenic hybrids of Meth A sarcoma cells and macrophages in vivo
Authors: Busund Lill‐Tove R. , Killie Mette K. , Bartnes Kristian , Seljelid Rolf 
Published: June 2003

AbstractWe have recently demonstrated that malignant cells can hybridize with tissue macrophages in vitro, giving rise to tumorigenic hybrids. We now demonstrate that this can occur spontaneously in vivo as a result of fusion between inoculated Meth A sarcoma cells and host cells, presumably macrophages. Thus, from tumor cell suspensions prepared by collagenase perfusion and density centrifugation, hybrid cells could be isolated that were neoplastic but in contrast to Meth A expressed macrophage markers and had phagocytic capacity. Their morphologic features were intermediate between Meth A and macrophages. By taking advantage of a semiallogeneic experimental system by inoculation of Meth A cells from BALB/c (H‐2 Kd) into (BALB.K × BALB/c) F1 (H‐2k/d), hybrid cells from these tumors could be shown to express MHC antigens of both the Meth A and the host haplotypes. Hybrid cells grew faster than Meth A cells in vivo, indicating acquisition of growth‐promoting properties through heterotypic cell fusion. © 2003 Wiley‐Liss, Inc.
Homozygous deletions scanning in tumor cell lines detects previously unsuspected loci
Authors: Pineau Pascal , Marchio Agnès , Cordina Emilie , Tiollais Pierre , Dejean Anne 
Published: June 2003

AbstractHigh rates of loss of heterozygosity commonly affect multiple chromosomes in individual tumor types, yet the number of known tumor suppressor genes (TSGs) systematically mutated in the corresponding tumors is usually low. The search for homozygously deleted genome segments in tumor samples or cell lines has become a method of choice to identify major TSGs or to reveal their influence on the development of a given tumor type. Here, we report a detailed homozygous deletion (HD) profiling for 246 critical loci on a panel of 89 tumor cell lines containing significant subsets of lung, ovarian and head and neck squamous cell carcinomas. We found a total of 53 HDs affecting 17 loci. The major target for HDs was p16‐INK4A/p14‐ARF (23/89, 26% of cases). Among the remaining alterations, HDs affecting TP73 or telomeric markers have never been previously described, whereas other HDs represent the first examples associating lesions of certain TSGs with a given tumor type (NF2 in lung and ovarian cells, STK11 in HELA cells). Overall, tumor cell lines established from ovarian or lung carcinomas displayed a surprising diversity of loci targeted by HDs with 7 and 6 loci involved, respectively. Our data suggest that, beside allelotyping or transcriptome/proteome studies, extensive HD profiling represents a promising approach for the detection of hitherto not implicated signalling pathways of tumorigenesis. © 2003 Wiley‐Liss, Inc.
Expression profiling of CC531 colon carcinoma cells reveals similar regulation of β‐catenin target genes by both butyrate and aspirin
Authors: Germann Anja , Dihlmann Susanne , Hergenhahn Manfred , von Knebel Doeberitz Magnus , Koesters Robert 
Published: June 2003

AbstractThe CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal‐transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki‐ras signaling pathways. We found both a prototypic β‐catenin (Ctnnb1) mutation (Thr41Ile) and a ki‐ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c‐myc, Fosl1, c‐fos, Cd44 and follistatin, which are known targets of the β‐catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). © 2003 Wiley‐Liss, Inc.
Visual speech, a trajectory in viseme space
Authors: Kalberer Gregor A. , Müller Pascal , Gool Luc Van 
Published: June 2003

AbstractEfficient, realistic face animation is still a challenge. A system is proposed that yields realistic animations for speech. It starts from real 3D face dynamics, observed at frame rate for thousands of points on the faces of speaking actors. When asked to animate a face it replicates the visemes that it has learned, and adds the necessary coarticulation effects. The speech animation could be based on as few as 16 modes, extracted through independent component analysis from the observed face dynamics. Rather than animating via verbatim copying the deformation fields that come with the different visemes are adapted to the shape of the given face. By localizing the face to be animated in a face space, where also the locations of the example faces are known, visemes are adapted automatically according to the relative distance with respect to these examples. © 2003 Wiley Periodicals, Inc. Int J Imaging Syst Technol 13: 74–84, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10044