bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis
Authors: Chen Yuan , Knösel Thomas , Kristiansen Glen , Pietas Agnieszka , Garber Mitchell E , Matsuhashi Sachiko , Ozaki Iwata , Petersen Iver 
Published: July 2003

AbstractThe programmed cell death 4 gene (PDCD4), a newly identified transformation suppressor, was analysed in lung tumour cell lines and primary lung carcinomas. Reduced PDCD4 mRNA expression was observed in two immortalized lung cell lines and 18 cancer cell lines by northern blot analysis. In the survey of primary lung tumours, PDCD4 cDNA was poorly represented in 47 lung tumours compared with normal lung tissue by cDNA microarray analysis and this poor representation was significantly associated with high‐grade (G3) adenocarcinomas (p = 0.012). Immunohistochemical analysis of 124 primary carcinomas comprising all subtypes demonstrated that PDCD4 protein expression was widely lost in tumour samples (83%) and was negatively related to poor prognosis (p = 0.013). The loss of PDCD4 expression correlated with higher grade and disease stage (p = 0.045 and 0.034, respectively), but not tumour size and nodal status. Similarly to the cDNA data, lack of PDCD4 expression was significantly linked to tumour grade in adenocarcinoma (n = 59, p = 0.048), while in squamous cell carcinoma (n = 58), no relationship between PDCD4 expression and clinicopathological parameters was established. These data suggest that the loss of PDCD4 expression is a prognostic factor in lung cancer and may correlate with tumour progression. Copyright © 2003 John Wiley & Sons, Ltd.
High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease
Authors: Ros Jenny E , Libbrecht Louis , Geuken Mariska , Jansen Peter LM , Roskams Tania AD 
Published: July 2003

AbstractAn increase in bile ductular structures is observed in diverse human liver diseases. These structures harbour the progenitor cell compartment of the liver. Since ATP‐binding cassette (ABC) transporters may have a cytoprotective role in liver disease, an immunohistochemical study was performed on human liver specimens from patients with primary biliary cirrhosis (PBC), chronic hepatitis C virus (HCV) infection, submassive cell necrosis, and normal liver. The expression of MDR1, MDR3, BSEP, MRP1, MRP2, and MRP3 was determined using specific antibodies. Dilution series were constructed to determine the critical staining level in order to estimate the factor of up‐regulation. In normal liver, hepatocytes showed canalicular staining for MDR3, BSEP, and MRP2. MDR1 stained the canalicular membrane of hepatocytes as well as that of cholangiocytes. MRP3 showed low immunoreactivity of bile duct epithelial cells and centrilobular hepatocytes only. Normal liver showed no immunoreactivity for MRP1. In diseased liver, the expression of MDR3, BSEP, and MRP2 was relatively stable. In PBC, HCV, and submassive necrosis, the expression levels of MDR1, MRP1, and MRP3 were increased. The strongest immunoreactivity was seen after submassive necrosis, where remaining islands of hepatocytes showed strong canalicular staining for MDR1 and MRP3. Regenerating bile ductules at the interface of portal tracts and necrotic areas stained intensely for MDR1, MRP1, and MRP3. In conclusion, MDR1, MRP1, and MRP3 are up‐regulated in hepatocytes in severe human liver disease. Strong MDR1, MRP1, and MRP3 reactivity is seen in regenerating human bile ductules. Copyright © 2003 John Wiley & Sons, Ltd.
Ets 1 is expressed in capillary blood vessels but not in lymphatics
Authors: Wernert Nicolas , Okuducu Ali‐Fuat , Pepper Michael S 
Published: July 2003

AbstractLittle is known about the mechanisms that regulate lymphangiogenesis and, in particular, about regulation at the transcriptional level. To determine whether parallels exist in the mechanisms of angiogenesis and lymphangiogenesis, the expression of the Ets 1 transcription factor (which has previously been shown to be involved in angiogenesis) was examined in two transgenic mouse lines, namely RipVEGF‐C mice (which develop lymphatic capillaries ectopically around islets of Langerhans) and Rip1Tag2 mice (which develop insulinomas that are not lymphangiogenic). Crossing the two lines results in double transgenic mice that develop lymphatics around insulinomas, which in turn promotes metastasis to regional lymph nodes. By immunohistochemistry, it was found that, in contrast to blood vessels, lymphatic vessels in wild‐type and transgenic mice did not express Ets 1. Immunohistochemical staining for matrix metalloproteinase (MMP)‐2 and MMP‐9 as well as membrane type 1‐MMP (MT1‐MMP/MMP‐14), all of which are encoded by known or potential Ets 1 target genes, showed the same cellular distribution as Ets 1. These findings suggest that the transcriptional regulatory mechanisms of lymphangiogenesis differ from those involved in angiogenesis. Furthermore, if proteases are involved in lymphangiogenesis, these observations suggest that they are different from those considered to be important for blood vessel formation. Copyright © 2003 John Wiley & Sons, Ltd.
Nuclear localization of the metastasis‐related protein S100A4 correlates with tumour stage in colorectal cancer
Authors: Flatmark Kjersti , Pedersen Kjetil Boye , Nesland Jahn M , Rasmussen Heidi , Aamodt Geir , Mikalsen Svein‐Ole , Bjørnland Kristin , Fodstad Øystein , Mælandsmo Gunhild M 
Published: July 2003

AbstractA large number of experimental studies have linked the S100A4 gene product to the metastatic phenotype of cancer cells and clinical evidence indicates a correlation between S100A4 expression and poor prognosis in several cancer types. The aim of the present study was to analyse the expression of the S100A4 protein in colorectal cancer. Paraffin‐embedded samples from 277 colorectal cancer patients were immunostained with anti‐S100A4 antibody. Cytoplasmic staining was observed in 178 of 277 samples (64%), whereas, unexpectedly, nuclear expression of S100A4 was found in 88 of 277 of the samples (32%). This novel finding was confirmed by western blot analysis of nuclear fractions isolated from frozen tumour tissue. Statistical analysis revealed a significant correlation between nuclear expression of S100A4 and tumour stage at diagnosis, while there was no such correlation between cytoplasmic staining and tumour stage. The nuclear localization of S100A4 in colorectal cancer and its relationship to tumour stage suggest that this protein may be involved in gene regulatory pathways of relevance to the metastatic phenotype of cancer cells. Copyright © 2003 John Wiley & Sons, Ltd.
Immunoreactivity for cyclin D3 is frequently detectable in high‐grade primary gastric lymphomas in the absence of the t(6;14)(p21.1;q32.3) chromosomal translocation
Authors: Pruneri Giancarlo , Fabris Sonia , Fasani Roberta , Del Curto Barbara , Capella Carlo , Pozzi Barbara , Motta Teresio , Andreola Salvatore , Ferreri Andres JM , Ponzoni Maurilio , Viale Giuseppe , Neri Antonino 
Published: July 2003

AbstractCyclin D3 plays a pivotal role in controlling the physiological progression from the G1 to the S phase of the cell cycle. Recent data suggest that cyclin D3 may be deregulated in extranodal non‐Hodgkin's lymphomas (NHLs) as a consequence of the t(6;14)(p21.1;q32.3) translocation. The present study investigated for the first time by dual‐colour fluorescence in situ hybridization (FISH) on interphase nuclei and immunohistochemistry the prevalence of the t(6;14) translocation and cyclin D3 immunoreactivity (IR) in a series of 29 stage I–IIE primary gastric NHLs (PGLs). No case showed the t(6;14) translocation. However, in five (17.2%) cases (two extranodal marginal zone lymphomas of MALT type, LGM; one diffuse large‐cell lymphoma with a MALT component, DLCLM; and two diffuse large‐cell lymphomas without a MALT component, DLCL), three to four cyclin D3 signals were detected by FISH. Co‐hybridization with probes specific for the centromeric region and long arm of chromosome 6 indicated trisomy in one case (DLCL), whereas in the remaining four cases the pattern was highly suggestive of the presence of an isochromosome 6p. One (12.5%) case of LGM, six (75%) cases of DLCLM, and seven (53.8%) cases of DLCL (p = 0.0378) were immunoreactive for cyclin D3. Cyclin D3 IR was detected in two (40%) of the five cases with extra cyclin D3 signals and in 12 of the remaining 24 cases (50%, p = 1.000). These results suggest that the t(6;14) may represent a rare event in the pathogenesis of PGL and that cyclin D3 deregulation is most likely the result of epigenetic mechanisms. Copyright © 2003 John Wiley & Sons, Ltd.
Typical genomic imbalances in primary MALT lymphoma of the orbit
Authors: Matteucci Caterina , Galieni Piero , Leoncini Lorenzo , Lazzi Stefano , Lauria Francesco , Polito Ennio , Martelli Massimo F , Mecucci Cristina 
Published: July 2003

AbstractPrimary orbital non‐Hodgkin lymphoma is a mucosa‐associated lymphoid tissue (MALT)‐type extranodal marginal zone lymphoma. Little information is available on its genome as conventional cytogenetics is limited by scarce biopsy material, while fluorescence in situ hybridization (FISH) explores only selected regions. Comparative genomic hybridization (CGH) performs full genomic analysis and is applicable to different sources of DNA, such as fresh and frozen cells, as well as paraffin‐embedded tissues. In this study, CGH was used to analyse primary MALT lymphoma of the orbit. Aneuploidy was identified in six of the ten cases studied. Gains (19) were more frequent than losses (5). The most frequent duplications involved chromosome 3 (common region at 3q24‐qter), as expected in marginal zone lymphoma, and chromosome 6 (common region at 6p21.1–21.3), which is typical of an orbital location. Other chromosome gains were found at 1p, 7, 8q, 9q, 12, 13, 17, 18, 19, 22, and X. Losses were located at 1q, 6q, 9q, 11q, and 13q. Two cases showed isolated duplications of chromosome 6p or 9q. Isolated imbalances were found only in tumours affecting the conjunctiva. Complex aneuploidies were observed in lymphoma of the retro‐orbital tissue. In summary, CGH in orbital MALT lymphoma provided new insights into typical genomic imbalances and underlying pathogenetic mechanisms. Copyright © 2003 John Wiley & Sons, Ltd.
Association of ets‐related transcriptional factor E1AF expression with tumour progression and overexpression of MMP‐1 and matrilysin in human colorectal cancer
Authors: Horiuchi Shina , Yamamoto Hiroyuki , Min Yongfen , Adachi Yasushi , Itoh Fumio , Imai Kohzoh 
Published: July 2003

AbstractExpression of E1AF/PEA3 (ETV4), an ets family transcription factor, has been implicated in the invasive potential of several cancer cell lines through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human colorectal cancer. Using the semi‐quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR), 100 colorectal cancer tissues were analysed for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets‐1 and Ets‐2 was also analysed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 62% of the 100 colorectal cancer tissues, but was undetectable or only faintly detected in adjacent non‐tumour tissues. E1AF mRNA was detected in all of the ten liver metastases from colorectal cancers. E1AF expression correlated significantly with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumour–node–metastasis stage, and recurrence. Patients with E1AF‐positive tumours had significantly shorter overall and disease‐free survival periods than did those with E1AF‐negative tumours (p < 0.0001 and p < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease‐free survival in multivariate analysis that included conventional clinicopathological factors (p = 0.0066 and p = 0.0109, respectively). Among the MMPs analysed, expression of MMP‐1 and matrilysin correlated significantly with E1AF expression. In contrast, expression of ER81 and ERM did not correlate with clinicopathological characteristics or the expression of these MMPs. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of MMP‐1 and matrilysin and nuclear β‐catenin expression were often co‐localized. Antisense E1AF‐transfected HT‐29 colon cancer cells expressed reduced levels of MMP‐1 and matrilysin and were less invasive in vitro than neo‐transfected HT‐29 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of MMP‐1 and matrilysin, plays a key role in the progression of colorectal cancer. Copyright © 2003 John Wiley & Sons, Ltd.
Survivin gene expression in early‐stage non‐small cell lung cancer
Authors: Falleni Monica , Pellegrini Caterina , Marchetti Antonio , Oprandi Barbara , Buttitta Fiamma , Barassi Fabio , Santambrogio Luigi , Coggi Guido , Bosari Silvano 
Published: July 2003

AbstractSurvivin is an inhibitor of apoptosis protein, overexpressed in most human malignancies and implicated in mitosis regulation and preservation of cell viability. In order to investigate the prevalence and clinical significance of survivin in early‐stage non‐small cell lung carcinoma (NSCLC), survivin mRNA levels and protein expression were evaluated, using quantitative real‐time RT‐PCR and immunohistochemistry, respectively, in a series of 83 patients with stage I (IA and IB) surgically resected NSCLC. Detectable survivin mRNA levels could be demonstrated in all non‐neoplastic lung tissue samples and in the tumours analysed. Survivin mRNA levels were elevated in 80 carcinomas (96%) compared to normal lung (p = 0.008). Among all tumours, survivin transcripts were present at a higher level in squamous cell carcinomas (p = 0.0022). Cytoplasmic and nuclear immunoreactivity was found in 70% and 80% of tumours, respectively and both were present in 54%. Cytoplasmic immunoreactivity correlated with tumour stage (p = 0.019). Survivin expression levels did not correlate with patient survival. In one specimen, cytoplasmic and focal nuclear immunostaining was observed in dysplastic bronchial squamous metaplasia. These results document that survivin overexpression is almost always present in early‐stage NSCLC, suggesting that this protein may play a role in lung tumourigenesis. This ubiquitous expression makes survivin an appealing new target for novel therapies in lung cancer. In addition, this study also documents that survivin overexpression could be exploited for diagnostic purposes and that quantitative real‐time RT‐PCR can be a useful tool for evaluating survivin activation in NSCLC. Copyright © 2003 John Wiley & Sons, Ltd.
The wt1‐heterozygous mouse; a model to study the development of glomerular sclerosis
Authors: Menke Aswin L , IJpenberg Annemieke , Fleming Stewart , Ross Allyson , Medine Claire N , Patek Charles E , Spraggon Lee , Hughes Jeremy , Clarke Alan R , Hastie Nicholas D 
Published: July 2003

AbstractIn the present study, it is shown that mice heterozygous for wt1 develop glomerular sclerosis and the nature and time course of events leading to the glomerular scarring are determined. Wt1‐heterozygous (wt1het) mice and their wild‐type littermates were closely monitored from birth and plasma levels of urea, creatinine, and albumin were compared with histological data and clinical features. One of the first indications of nephropathy in the wt1het mouse was the development of proteinuria, accompanied by progressive elevation of the plasma levels of urea and creatinine. Subsequently, the mice developed albuminuria, which correlated with thickening of the glomerular basement membrane and fusion of the podocyte foot processes. Glomerulosclerosis was a relatively late event, accompanied by severe albuminuria and loss of WT1, nephrin, CD2AP, and α‐actinin‐4. Copyright © 2003 John Wiley & Sons, Ltd.
β‐catenin abnormalities and associated insulin‐like growth factor overexpression are important in phyllodes tumours and fibroadenomas of the breast
Authors: Sawyer Elinor J , Hanby Andrew M , Poulsom Richard , Jeffery Rosemary , Gillett Cheryl E , Ellis Ian O , Ellis Paul , Tomlinson Ian PM 
Published: July 2003

AbstractThe aim of this study was to assess the expression of IGF‐I and IGF‐II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear β‐catenin expression and IGF‐I and IGF‐II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of β‐catenin in the stromal cells of these tumours. However, not all tumours with β‐catenin accumulation showed Wnt overexpression. One other possible cause of β‐catenin accumulation is overexpression of insulin‐like growth factors (IGFs), as both IGF‐I and IGF‐II have been shown to stabilize β‐catenin. In this study, 30 fibroadenomas of the breast were assessed for β‐catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF‐I and IGF‐II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF‐II and 5/23 (22%) showed widespread overexpression of IGF‐I. IGF‐I expression correlated with nuclear β‐catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF‐I expression. There was a degree of nuclear β‐catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear β‐catenin staining correlated with IGF‐I overexpression. Extensive IGF‐II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF‐I and IGF‐II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF‐I overexpression is likely to be contributing to the nuclear β‐catenin localization observed in the tumours. Copyright © 2003 John Wiley & Sons, Ltd.
Measurement of telomere length on tissue sections using quantitative fluorescence in situ hybridization (Q‐FISH)
Authors: Ferlicot Sophie , Youssef Nelly , Feneux Danielle , Delhommeau François , Paradis Valérie , Bedossa Pierre 
Published: July 2003

AbstractLoss of telomere repeat sequences occurs after each cell division and telomere shortening has been implicated in cellular senescence. The measurement of telomere length might therefore assess the lifespan of a cell. The aim of this study was to set up and validate a technique enabling the assessment of telomere length on tissue sections. Quantitative fluorescence in situ hybridization (Q‐FISH) with telomeric probes was performed on smears and sections from cell preparations or human tissues. The mean fluorescence intensity of telomere spots (FI/spot) was automatically quantified by image analysis. Telomeric restriction fragment (TRF) length was assessed by Southern blotting. There was a positive significant correlation between telomere length, as assessed by Q‐FISH, and TRF length determined by Southern blotting in corresponding samples (p < 0.01, r = 0.6 for tissue and p < 0.01, r = 0.79 for cells). FI/spot was higher on smears than on sections, but pairwise comparison showed a significant correlation both for cells and for tissues (r = 0.77, p < 0.001 for cells and p ≤ 0.01, r = 0.64 for tissue). Finally, since telomere length is expected to shorten with age, FI/spot was assessed in liver samples according to the age of patients: a negative correlation was demonstrated (r = 0.76, p < 0.01). Inter‐assay variation was 7% for Q‐FISH performed on tissue sections and 12% on touch preparations. This study shows that Q‐FISH can be performed with confidence on fixed frozen tissue sections in order to assess telomere length. It is an easy, accurate, and reproducible in situ method for assessing telomeres in the context of cell type and tissue architecture. Copyright © 2003 John Wiley & Sons, Ltd.
Lymphatics and vascular channels; the differences behind similarity
Authors: Jones Pamela F 
Published: July 2003

AbstractAlthough sharing many features and functions, there is a mounting body of evidence to suggest that there are subtle differences between lymphatics and vascular channels. New data suggest that Ets‐1 and Ets‐1‐target MMP genes are differentially expressed in lymphatic and vascular channels. Since it is generally accepted that the Ets family of transcription factors play a significant role in the regulation of the expression of angiogenic factors, the finding that Ets‐1 is apparently not involved in lymphangiogenesis may highlight one aspect where angiogenesis and lymphangiogenesis are differently regulated. Copyright © 2003 John Wiley & Sons, Ltd.
Tissue‐based stem cells: ABC transporter proteins take centre stage
Authors: Alison Malcolm R 
Published: July 2003

AbstractIn adult tissues, with the notable exception of the haematopoietic system, the identity of somatic stem cells has often been inferred based on no more evidence than their location. Functional data (clonogenicity) to confirm such an appellation has been absent due to the inability to find appropriate cellular markers with which to isolate live stem cells. Flow cytometry has isolated haematopoietic stem cells based on their ability to exclude Hoechst dye. Named the side population (SP), this phenotype may be a universal marker of stem cells in adult tissues. Copyright © 2003 John Wiley & Sons, Ltd.
Digital Holography for Instantaneous Spray Diagnostics on a Plane
Authors: Burke Jan , Hess Cecil F. , Kebbel Volker 
Published: July 2003

AbstractWe present a measurement technique that is capable of simultaneously determining sizes and positions of multiple transparent droplets in a plane from scattered light features. The technique is largely independent of particle intensity and mutual obscuration. Reflected and refracted light from the droplets in a pulsed laser sheet is recorded holographically to yield the smallest possible probe volume and the largest possible number density. Larger droplets are best analyzed at the image plane; in this case, the droplets appear as two spots (glare points), whose separation is proportional to the droplet diameter. Smaller droplets are easier to analyze at an out‐of‐focus plane, where their images appear as fringe patterns whose spatial frequency is related to droplet size. Photographic techniques allow only one of these planes to be chosen and are therefore not suitable for multidisperse sprays. Optical holography allows to analyze arbitrary depths, but often suffers from low sensitivity and long analysis times. With digital holography, the spray images are captured digitally by a CCD camera and reconstructed numerically; as in optical holography, the particle reconstruction plane can be freely chosen a posteriori to optimize the measurement. We discuss the issues raised by the transition from holographic film to a CCD sensor as the recording medium, and demonstrate the capabilities of the digital technique.