bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clustering of deletions on chromosome 13 in benign and low‐malignant lipomatous tumors
Authors: Dahlén Anna , Debiec‐Rychter Maria , Pedeutour Florence , Domanski Henryk A. , Höglund Mattias , Bauer Henrik C. F. , Rydholm Anders , Sciot Raf , Mandahl Nils , Mertens Fredrik 
Published: December 2002

AbstractDeletions and structural rearrangements of the long arm of chromosome 13 are frequently observed in benign and low‐malignant lipomatous tumors, but nothing is known about their molecular genetic consequences. We assessed the karyotypes of 40 new and 22 previously published cases (35 ordinary lipomas, 15 spindle cell/pleomorphic lipomas, 2 myxolipomas, 1 angiomyxolipoma and 9 atypical lipomatous tumors) with chromosome 13‐abnormalities, and found bands 13q12–22 to be frequently affected. Twenty‐seven cases with structural abnormalities within this region were selected for breakpoint and deletion mapping by metaphase fluorescencein situhybridization (FISH), using a set of 20 probes. Deletions were found in 23 of 27 cases. The remaining 4 cases had seemingly balanced rearrangements. The breakpoints were scattered but clustered to band 13q14, and in all cases with unbalanced abnormalities, a limited region within band 13q14 was partially or completely deleted. A deletion within band 13q14 was found together with a breakpoint on the other homologue in 5 cases, 4 of which could be tested further with regard to the status of the retinoblastoma (RB1)‐gene. In all 4 cases, only 1 copy of the gene was deleted. In addition to the breaks and deletions in the vicinity of theRB1‐locus, several other regions of 13q were recurrently affected,e.g., in the vicinity of the hereditary breast cancer (BRCA2; 13q12)‐ and lipoma HMGIC fusion partner (LHFP; 13q13)‐ genes. Our findings strongly indicate that deletion of a limited region (∼2.5 Mbp) within 13q14, distal to theRB1‐locus, is of importance in the development of a subset of lipomatous tumors. © 2002 Wiley‐Liss, Inc.
Hereditary nonpolyposis colorectal cancer: Frequent occurrence of large genomic deletions in MSH2 and MLH1 genes
Authors: Wang Yaping , Friedl Waltraut , Lamberti Christof , Jungck Matthias , Mathiak Micaela , Pagenstecher Constanze , Propping Peter , Mangold Elisabeth 
Published: December 2002

AbstractHereditary nonpolyposis colorectal cancer (HNPCC) is often caused by a deficiency in DNA mismatch repair. By using conventional methods of mutation analysis, point mutations in the DNA mismatch repair genes MSH2 and MLH1 have been detected in up to 64% of patients suspected of HNPCC. However, large genomic deletions cannot be detected by these methods. In our study, we applied a semiquantitative multiplex PCR to detect the proportion of large deletions in patients meeting the Bethesda criteria whose tumours exhibited microsatellite instability (MSI). Of 368 unrelated patients, 180 exhibited MSI. In these patients, 68 disease‐causing point mutations (38%) had previously been detected in the MSH2 and MLH1 genes by SSCP, heteroduplex analysis or DHPLC followed by direct sequencing. The remaining 112 patients (including 24 patients with rare missense or other unclarified variants) were examined for large deletions. We identified deletions in 19 patients (10.6%); 11/19 (58%) deletions were located in MSH2 and 8/19 (42%) in MLH1, respectively. The size of deletions ranged from 1 exon to a deletion of a whole gene. Five breakpoints of deletions were sequenced; Alu‐repetitive elements were involved in all of them. In patients meeting the Amsterdam criteria the proportion of large deletions was 12.6%. A similar proportion of deletions was found in the group of patients with a positive family history for colorectal cancer and MSI tumours, not meeting the Amsterdam criteria. The results of our study suggest that large genomic deletions in both MSH2 and MLH1 genes play a considerable role in the pathogenesis of HNPCC and should be part of the routine HNPCC mutation detection protocols. © 2002 Wiley‐Liss, Inc.
Single nucleotide polymorphisms in the XPG gene: Determination of role in DNA repair and breast cancer risk
Authors: Kumar Rajiv , Höglund Lotta , Zhao Chunyan , Försti Asta , Snellman Erna , Hemminki Kari 
Published: December 2002

AbstractIn this study we determined the effect of single nucleotide polymorphisms in the XPG gene on DNA repair and breast cancer susceptibility. Ninety individuals, with previously studied DNA repair rate at 24 hr of 2 types of UV‐specific cyclobutane pyrimidines dimers (CPDs) in skin were genotyped for XPG polymorphism at codon 1104 (exon 15 G>C; Asp > His). The repair rate of TT=C dimer was similar in both wild‐type GG homozygotes and GC heterozygotes, whereas, for TT=T, dimer repair was non‐significantly (Student's t‐test, p = 0.34) lower in GC heterozygotes than wild‐type GG homozygotes. Genotyping of 220 breast cancer cases and 308 controls for the same single nucleotide polymorphism in exon 15 of the XPG gene exhibited marginally significant increased frequency of the variant allele (χ2 3.84, p = 0.05; OR 1.33, 95% CI 1.0–1.8) in cases (C‐allele 0.29) compared to controls (C‐allele 0.24). Combined heterozygote and variant homozygote genotype frequency was also higher in cases than controls (χ2 4.79, p = 0.03; OR 1.50, 95%CI 1.04–2.16). © 2002 Wiley‐Liss, Inc.
Insulin‐like growth factor binding protein‐3 is overexpressed in endothelial cells of mouse breast tumor vessels
Authors: Schmid Michael C. , Bisoffi Marco , Wetterwald Antoinette , Gautschi Elsbeth , Thalmann George N. , Mitola Stefania , Bussolino Federico , Cecchini Marco G. 
Published: December 2002

AbstractAngiogenesis is a key process in a variety of human diseases, including cancer. The ability to target selectively the tumor vasculature is potentially useful for the diagnosis and treatment of cancer. Still, little information is available regarding markers that are restricted to the ECs of tumor vessels. cDNA array technology allows simultaneous analysis of relative expression levels of a broad spectrum of genes in 2 related cell populations. We used this technology with the aim of identifying markers specific for TECs. TECs were isolated by CD31‐mediated immunomagnetic separation from tumors induced by s.c. injection of NF9006 breast carcinoma cells into syngeneic mice. NECs were isolated from lactating mammary glands. The endothelial nature of isolated cells was confirmed by RT‐PCR using CD31‐specific primers and by uptake of DiI‐Ac‐LDL. Macrophage contamination in the EC isolations could be reasonably ruled out by assessing the expression of the macrophage marker c‐fms. 32P‐labeled cDNA probes generated by reverse transcription from total RNA were hybridized to mouse‐specific gene arrays. Several genes consistently showed differential expression between TECs and NECs. However, expression of only 1 of these genes, IGFBP‐3, was restricted exclusively to ECs. Semiquantitative RT‐PCR revealed 22‐ to 33‐fold differential expression of IGFBP‐3 in the TEC fraction. IGFBP‐3 was overexpressed by a factor of 5 in an additional mouse model of breast carcinoma induced by 4T1.2 tumor cells. These results indicate that IGFBP‐3 is a potential novel marker of angiogenesis. Elucidation of its role in tumor neovascularization may open the possibility of IGFBP‐3 as a therapeutic target for antiangiogenesis. © 2002 Wiley‐Liss, Inc.
Abortions and breast cancer: Record‐based case‐control study
Authors: Erlandsson Gunnar , Montgomery Scott M. , Cnattingius Sven , Ekbom Anders 
Published: December 2002

AbstractIt has been suggested that abortions leave the breast epithelium in a proliferative state with an increased susceptibility to carcinogenesis. Results from previous studies of induced or spontaneous abortions and risk of subsequent breast cancer are contradictory, probably due to methodological considerations. We investigated the relationship between abortions and subsequent breast cancer risk in a case‐control study using prospectively recorded exposure information. The study population comprised women recorded in the population‐based Swedish Medical Birth Register between 1973–91. Cases were defined by linkage of the birth register to the Swedish Cancer Register and controls were randomly selected from the birth register. From the subjects' antenatal care records we abstracted prospectively collected information on induced and spontaneous abortions, as well as a number of potential confounding factors. Relative risk of breast cancer was estimated by odds ratios (OR) with 95% confidence intervals (95% CI). A reduced risk of breast cancer was observed for women with a history of at least 1 compared to no abortions (adjusted OR = 0.84, 95% CI = 0.72–0.99). The adjusted OR decreases step‐wise with number of abortions to 0.59 (95% CI = 0.34–1.03) for 3 or more compared to no abortions. The patterns are similar for induced and spontaneous abortions. In conclusion, neither a history of induced nor spontaneous abortions is associated with an increased risk of breast cancer. Our data suggest a protective effect of pregnancies regardless of outcome. © 2002 Wiley‐Liss, Inc.
Direct interaction with and activation of p53 by SMAR1 retards cell‐cycle progression at G2/M phase and delays tumor growth in mice
Authors: Kaul Ruchika , Mukherjee Sujoy , Ahmed Farid , Bhat Manoj Kumar , Chhipa Rishiraj , Galande Sanjeev , Chattopadhyay Samit 
Published: December 2002

AbstractThe tumor‐suppressor p53 is a multifunctional protein mainly responsible for maintaining genomic integrity. p53 induces its tumor‐suppressor activity by either causing cell‐cycle arrest (G1/S or G2/M) or inducing cells to undergo apoptosis. This function of wild‐type p53 as “guardian of the genome” is presumably achieved by forming molecular complexes with different DNA targets as well as by interacting with a number of cellular proteins, e.g., Mdm2, Gadd45, p21, 14‐3‐3σ, Bax and Apaf‐1. Upon activation, p53 activates p21, which in turn controls the cell cycle by regulating G1 or G2 checkpoints. Here, we report SMAR1 as one such p53‐interacting protein that is involved in delaying tumor progression in vivo as well as in regulating the cell cycle. SMAR1 is a newly identified MARBP involved in chromatin‐mediated gene regulation. The SMAR1 gene encodes at least 2 alternatively spliced variants: SMAR1L (the full‐length form) and SMAR1S (the shorter form). We report that expression of SMAR1S, but not of SMAR1L, mRNA was decreased in most of the human cell lines examined, suggesting selective silencing of SMAR1S. Overexpression of SMAR1S in mouse melanoma cells (B16F1) and their subsequent injection in C57BL/6 mice delays tumor growth. Exogenous SMAR1S causes significant retardation of B16F1 cells in the G2/M phase of the cell cycle compared to SMAR1L. SMAR1S activates p53‐mediated reporter gene expression in mouse melanoma cells, breast cancer cells (MCF‐7) and p53 null cells (K562), followed by activation of its downstream effector, p21. We further demonstrate that SMAR1 physically interacts and colocalizes with p53. These data together suggest that SMAR1 is the only known MARBP that delays tumor progression via direct activation and interaction with tumor‐suppressor p53. © 2002 Wiley‐Liss, Inc.
Analysis of the human APC mutation spectrum in a saccharomyces cerevisiae strain with a mismatch repair defect
Authors: Otsuka Kazunori , Suzuki Takao , Shibata Hiroyuki , Kato Satoshi , Sakayori Masato , Shimodaira Hideki , Kanamaru Ryunosuke , Ishioka Chikashi 
Published: December 2002

AbstractSomatic APC mutations in colorectal tumors with an RER phenotype reflect excessive frameshift mutations, especially in simple repetition tracts within the coding sequence. Because this type of mutation is characteristic of cells with a deficient DNA MMR system, the APC mutation signature of RER tumors may be attributable to a defect in the MMR system. However, there is little experimental evidence to prove that the spectrum of mutations and the APC gene distribution are directly influenced by MMR system defects. We therefore examined the mutation spectrum of the MCR of the APC gene after transfection into both MMR‐proficient and MMR‐deficient yeast strains and compared it with a previously reported human APC mutation database. Small insertions or deletions in mono‐ or dinucleotide repeats were more common in the MMR‐deficient than in the MMR‐proficient strain (91.2% vs. 38.1%, Fisher's exact test p < 0.0001). Furthermore, the 2 mutation hot spots, 4385–4394(AG)5 and 4661–4666(A)6, found in the yeast system corresponded with those in human tumors. Combining our data with those from human tumors, there appears to be hypermutable mutations in specific simple repetitive sequences within the MCR, which are more prevalent in MMR‐deficient cells and RER tumors than in MMR‐proficient cells and non‐RER tumors. We therefore consider that the differences in the spectra of RER and non‐RER tumors are attributable at least in part to the MMR system of the host cells. © 2002 Wiley‐Liss, Inc.
Tissue microarray‐based analysis shows phospho‐β‐catenin expression in malignant melanoma is associated with poor outcome
Authors: Kielhorn Eric , Provost Elayne , Olsen Drew , D'Aquila Thomas G. , Smith Bradley L. , Camp Robert L. , Rimm David L. 
Published: December 2002

AbstractBeyond depth of invasion, there are very few prognostic markers to predict outcome in melanoma. It has been shown recently that the β‐catenin oncogene is mutated or shows altered subcellular localization suggesting that activation of β‐catenin mediated signaling plays a role in oncogenesis. We hypothesize that assessment of activated β‐catenin, as detected by a phospho‐specific antibody, may be useful to predict outcome in melanoma. We use immuno‐histochemical analysis of β‐catenin and phospho‐β‐catenin, first to verify the specificity of the phospho‐β‐catenin antibody and then to assay expression in a tissue microarray‐based study. The subcellular localization of β‐catenin is membranous in some cases and cytoplasmic and nuclear in others. We validate the specificity of a ser33/37/thr41 phospho‐β‐catenin antibody in transfected cells and show that the expression is almost exclusively localized to the nucleus in both cultured cells and human tissue. Evaluation of both total and phospho‐β‐catenin antibodies showed that cytoplasmic/nuclear staining was more common in primary lesions, whereas nuclear phospho‐β‐catenin was more common in metastatic lesions. High levels of nuclear phospho‐β‐catenin are associated with significantly worse overall survival (51% vs. 25% overall survival at 5 years, p = 0.046). These results suggest that phospho‐specific antibodies to β‐catenin define a unique subset of cases and that monitoring of phospho‐β‐catenin expression may be useful for assessing prognosis in malignant melanoma. © 2002 Wiley‐Liss, Inc.
Changing epidemiology of nasopharyngeal carcinoma in Hong Kong over a 20‐year period (1980–99): An encouraging reduction in both incidence and mortality
Authors: Lee Anne W.M. , Foo William , Mang Oscar , Sze W.M. , Chappell Rick , Lau W.H. , Ko W.M. 
Published: December 2002

AbstractEpidemiological data from the Hong Kong Cancer Registry for the period 1980–99 were analyzed. Altogether 21,768 new cases of nasopharyngeal carcinoma (NPC) and 8,664 related deaths were registered. In both genders, the peak incidence occurred in the 50–59 years age group, and this age distribution pattern remained similar throughout. The age‐standardized incidence rate steadily decreased from 28.5 in 1980–84 to 20.2 in 1995–99 per 100,000 males, and from 11.2–7.8 per 100,000 females, resulting in a total decrease of 29% for males and 30% for females over this 20‐year period. The magnitude of total decrease in NPC mortality amounted to 43% and 50%, respectively, as the age‐standardized mortality rate steadily decreased from 13.7 in 1980–84 to 7.8 in 1995–99 per 100,000 males, and from 4.5–2.2 per 100,000 females. The age‐standardized mortality/incidence ratio also decreased from the peak of 0.48 in 1980–84 to 0.39 in 1995–99 for males, and from 0.40–0.29 for females. Females had significantly lower age‐standardized incidence (male/female ratio 2.5–2.6, p < 0.01) and mortality (male/female ratio 3.0–3.5, p< 0.01) throughout the whole period. Furthermore, females had consistently lower mortality/incidence ratio: 0.29 vs. 0.39 in 1995–99. These data are highly suggestive of significant improvement in prevention and control of NPC in Hong Kong. Closer scrutiny of the differences in intrinsic and extrinsic factors between the genders might help to show important factors affecting oncogenesis and prognosis. Possible ways for further reduction of incidence and mortality are discussed. © 2002 Wiley‐Liss, Inc.
Development of an in vitro miniature model to simulate immunoadsorption in patients with systemic lupus erythematosus
Authors: Avenhaus Birgit , Avenhaus Wolfgang , Schneider Matthias , Domschke Wolfram , Gaubitz Markus 
Published: December 2002

AbstractIn SLE, immunoadsorption is used as an adjuvant therapy; however, adsorption profiles and binding mechanisms have not yet been completely investigated. Using a minicolumn filled with the sorbent IMPH with or without the ligand phenylalanine, we developed a model simulating clinical conditions in a reduced scale with a constant ratio of plasma to column volume and a constant plasma flow at room temperature. By desorbing the column, the adsorption efficacy for different antibodies could be measured directly. We demonstrate that the adsorption rate can be increased by a low plasma flow and by covering the column surface. Double perfusion of the same column did not increase the amount of adsorbed antibodies. We further demonstrate that the carrier material without a ligand is unable to bind antibodies or protein. In the IMPH sorbent anti‐dsDNA antibodies were significantly better adsorbed than total IgG or total protein. After a single perfusion of 21 samples, we estimated a mean anti‐dsDNA antibody adsorption rate of 22.5% (±13.6). A group of ten responders with a medium adsorption rate of 35.4% (±6.5) clearly differed from a second group of eleven nonresponders (10.9% ± 4.2). Anti‐cardiolipin antibodies (ACA) were adsorbed in a wide range (IgG type, 2.5–52.7%, IgM type, 1.1–37.8%) while anti‐Ro (SSA) antibody adsorption was negligible. This in vitro minimodel provides a precise simulation of therapeutic immunoadsorption and helps to analyze the binding characteristics of the sorbent IMPH and shows its effectiveness in several antibody subsets of different patients. J. Clin. Apheresis 17:183–189, 2002. © 2002 Wiley‐Liss, Inc.
Direct adsorption of low‐density lipoprotein and lipoprotein(a) from whole blood: Results of the first clinical long‐term multicenter study using DALI apheresis
Authors: Bosch T. , Lennertz A. , Schenzle D. , Dräger J. ,   for the DALI Study Group
Published: December 2002

AbstractDirect adsorption of lipoproteins (DALI) is the first low‐density lipoprotein (LDL)‐apheresis technique by which atherogenic LDL and lipoprotein(a) (Lp(a)) can be selectively removed from whole blood without plasma separation. The present study was performed to evaluate the efficacy, selectivity and safety of long‐term DALI apheresis. Sixty‐three hypercholesterolemic coronary patients were treated by weekly DALI sessions. Initial LDL‐cholesterol (C) plasma levels averaged 238 ± 87 mg/dl (range 130–681 mg/dl). On average, 34 sessions (1–45) were performed processing 1.5 patient blood volumes. The primary aim was to acutely reduce LDL‐C by ≥60% per session. To this end, three different adsorber sizes could be employed, i.e., DALI 500, 750, and 1,000, which were used in 4, 73, and 23% of the 2,156 sessions, respectively. On average, 7,387 ml of blood were processed in 116 min per session. This resulted in the following mean acute changes: LDL‐C 198 → 63 mg/dl (−69%), Lp(a) 86 → 32 mg/dl (−64%), triglycerides 185 → 136 mg/dl (−27%). HDL‐C (−11%) and fibrinogen (−15%) were not significantly influenced. The mean long‐term reduction of LDL‐C was 42% compared to baseline while HDL‐C slightly increased in the long run (+4%). The selectivity of LDL removal was good as recoveries of albumin, immunoglobulins, and other proteins exceeded 85%. Ninety‐five percent of 2,156 sessions were completely uneventful. The most frequent adverse effects were hypotension (1.2% of sessions) and paresthesia (1.1%), which were probably due to citrate anticoagulation. Access problems had to be overcome in 1.5%, adsorber and hardware problems in 0.5% of the sessions. In this multicenter long‐term study, DALI apheresis proved to be an efficient, safe, and easy procedure for extracorporeal LDL and Lp(a) elimination. J. Clin. Apheresis 17:161–169, 2002. © 2002 Wiley‐Liss, Inc.
Fuji surge technique and continuous in‐line filtration to improve the quality of single donor platelet concentrates
Authors: Moog R. 
Published: December 2002

AbstractWhite blood cell (WBC)‐reduced single donor platelet concentrates (SDPs) can be collected by most cell separators. WBC reduction can be achieved directly during plateletpheresis or by filtration. Continuous filtration with low filtration rates provides SDPs of good purity. To compensate the platelet (PLT) loss due to filtration, the PLT yield in the unfiltered primary product should be optimal. Fifty donors underwent plateletpheresis with the MCS+ blood cell separator (Haemonetics) with the new Fuji surge technique and continuous WBC filtration. Twelve SDPs were analysed for PLT yield, red blood cells (RBC), WBC, and pH after collection (Day 0) and at the end of storage (Day 5). Thereafter, further 38 SDPs were measured for PLT and WBC content in routine production at Day 0. PLT were determined electronically, RBC and WBC were counted manually (Neubauer and Nageotte chamber, respectively). For pH measurement, a pH‐meter was used. Mean blood volume processed was 2,621 ± 112 ml in a donation time of 76 ± 10 min. An average PLT yield of 3.45 ± 0.88 × 1011 was collected in a product volume of 325 ± 77 ml. The collection efficiency was 60.0 ± 5.5%. WBC contamination of all units tested was 0.046 ± 0.059 × 106 and the RBC content of the SDPs analysed at Day 0 was 0.014 ± 0.003 × 109. The pH was well maintained over the storage period of 5 days. The data indicate that Fuji surge technique and continuous in‐line leukocyte filtration allow for the collection of SDPs with high platelet yield and low leukocyte contamination, meeting the Council of Europe quality standards. J. Clin. Apheresis 17:199–203. © 2002 Wiley‐Liss, Inc.
Molecular cloning of Drosophila HCF reveals proteolytic processing and self‐association of the encoded protein
Authors: Mahajan Shahana S. , Johnson Kristina M. , Wilson Angus C. 
Published: December 2002

AbstractHCF‐1 functions as a coactivator for herpes simplex virus VP16 and a number of mammalian transcription factors. Mature HCF‐1 is composed of two subunits generated by proteolytic cleavage of a larger precursor at six centrally‐located HCFPRO repeats. The resulting N‐ and C‐terminal subunits remain tightly associated via two complementary pairs of self‐association domains: termed SAS1N‐SAS1C and SAS2N‐SAS2C. Additional HCF proteins have been identified in mammals (HCF‐2) and Caenorhabditis elegans (CeHCF). Both contain well‐conserved SAS1 domains but do not undergo proteolytic processing. Thus, the significance of the cleavage and self‐association of HCF‐1 remains enigmatic. Here, we describe the isolation of the Drosophila HCF homologue (dHCF) using a genetic screen based on conservation of the SAS1 interaction. The N‐terminal β‐propeller domain of dHCF supports VP16‐induced complex formation and is more similar to mammalian HCF‐1 than other homologues. We show that full‐length dHCF expressed in Drosophila cells undergoes proteolytic cleavage giving rise to tightly associated N‐ and C‐terminal subunits. As with HCF‐1, the SAS1N and SAS1C elements of dHCF are separated by a large central region, however, this sequence lacks obvious homology to the HCFPRO repeats required for HCF‐1 cleavage. The conservation of HCF processing in insect cells argues that formation of separate N‐ and C‐terminal subunits is important for HCF function. © 2002 Wiley‐Liss, Inc.