bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline mutations in E‐cadherin do not explain association of hereditary prostate cancer, gastric cancer and breast cancer
Authors: Jonsson Björn‐Anders , Bergh Anders , Stattin Pär , Emmanuelsson Monika , Grönberg Henrik 
Published: August 2002

AbstractSomatic mutations in the E‐cadherin (CDH1) gene have frequently been reported in cases with diffuse gastric and lobular breast cancers. Recently, germline mutations have been identified in families with diffuse gastric cancers. In families with hereditary prostate cancer (HPC), a significant association of prostate cancer, gastric and/or breast cancer has been observed in epidemiological studies. The aim of this study was to investigate if germline mutations in CDH1 could explain the risk for cancer in HPC families with an excess of gastric and breast cancer. In total, 17 members from 13 HPC families and 3 members from 3 families with hereditary gastric cancer (HGC) were screened for germline CDH1 sequence alterations using PCR/Denaturing HPLC for initial screening of nucleotide variants followed by confirmatory direct sequencing analysis. The frequency of identified novel germline mutations were tested for in 136 cases with hereditary prostate cancer and 215 cases of sporadic prostate cancer with 422 age matched controls in an allelic discrimination assay. In total, 8 sequence variants were detected in 20 samples tested. In the HPC families, we found 2 missense mutations, A592T in exon 12 and a novel D777N in exon 15 and a mutation in intron 5, 687+92T>A. A previously known polymorphism in exon 13 and 3 sequence variations in introns and untranslated regions were also found, of which the significance is unknown. In HGC‐023 with early onset diffuse gastric cancer a truncating mutation, R335X, was identified in exon 7. None of the missense mutations or 687+92T>A were found in the extended HPC material or in the sporadic prostate cancer cases with age‐matched controls in the allelic discrimination assay. We found several germline mutations of unknown clinical significance in the CDH1 gene that probably do not explain the association of prostate, gastric and/or breast cancers in the HPC‐families. Two missense mutations and a mutation in intron 5 were identified that do not influence the risk of hereditary or sporadic prostate cancer in general and are considered to be pedigree specific. In a family with hereditary gastric cancer of the diffuse type, we identified the first truncating germline mutation in a Scandinavian family. © 2002 Wiley‐Liss, Inc.
VEGF‐C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF‐7 tumors
Authors: Mattila Mirjami M‐T. , Ruohola Johanna K. , Karpanen Terhi , Jackson David G. , Alitalo Kari , Härkönen Pirkko L. 
Published: August 2002

AbstractThe spread of cancer cells to regional lymph nodes through the lymphatic system is the first step in the dissemination of breast cancer. In several human cancers including those of the breast and prostate, the expression of vascular endothelial growth factor C (VEGF‐C) is associated with lymph node metastasis. Our study was undertaken to evaluate the effect of VEGF‐C on metastasis of poorly invasive, estrogen dependent human MCF‐7 breast cancer cells. MCF‐7 breast cancer cells transfected with VEGF‐C (MCF‐7‐VEGF‐C) were grown as tumors in the mammary fat pads of nude mice implanted with subcutaneous estrogen pellets. Tumor lymphangiogenesis and lymph node metastasis were studied immunohistochemically using antibodies against lymphatic vessel hyaluronan receptor ‐1 (LYVE‐1), VEGF receptor‐3 (VEGFR‐3), PECAM‐1, pan‐cytokeratin and estrogen dependent pS2 protein. Overexpression of VEGF‐C in transfected MCF‐7 cells stimulated in vivo tumor growth in xenotransplanted mice without affecting estrogen responsiveness. The resulting tumors metastasized to the regional lymph nodes in 75% (in 6 mice out of 8, Experiment I) and in 62% (in 5 mice out of 8, Experiment II) of mice bearing orthotopic tumors formed by MCF‐7‐VEGF‐C cells whereas no metastases were observed in mice bearing tumors of control vector‐transfected MCF‐7 cells (MCF‐7‐Mock). The density of intratumoral and peritumoral lymphatic vessels was increased in tumors derived from MCF‐7‐VEGF‐C cells but not MCF‐7‐Mock cells. Taken together, our results show that VEGF‐C overexpression stimulates tumor lymphangiogenesis and induces normally poorly metastatic estrogen‐dependent MCF‐7 tumors to disseminate to local lymph nodes. These data suggest that VEGF‐C has an important role in lymph node metastasis of breast cancer even at its hormone‐dependent early stage. © 2002 Wiley‐Liss, Inc.
Downregulation of estrogen‐metabolizing 17β‐hydroxysteroid dehydrogenase Type 2 expression correlates inversely with Ki67 proliferation marker in colon‐cancer development
Authors: Oduwole Olayiwola O. , Isomaa Veli V. , Nokelainen Pasi A. , Stenbäck Frej , Vihko Pirkko T. 
Published: August 2002

AbstractThe 17HSDs are a group of isozymes that catalyze the interconversion between high‐activity 17β‐hydroxysteroids and low‐activity 17‐ketosteroids. In the present study, we characterized the expression of 17HSD types 1 and 2 in normal and malignant gastrointestinal tissues and cells. Using the colon as a model for cancer of the gastrointestinal tract, expression of the 17HSD enzymes in cancer development was studied and correlated with proliferation and differentiation markers as assessed by Ki67 and mucin staining, respectively. In normal colon and small intestine, 17HSD type 2 mRNA was expressed in the surface epithelial cells and, to a lesser extent, in the cryptal epithelial cells. In colon‐cancer specimens, 17HSD type 2 expression was downregulated both in the tissues and in the cell lines and correlated inversely with the proliferation marker. No expression for the 17HSD type 1 enzyme was observed in normal or cancerous gastrointestinal tract tissues. In line with the expression studies, 17HSD activity measurements with colon cells showed that only the oxidative conversion of E2 to E1 was present, and Northern blot analysis showed the signal only for 17HSD type 2. Localization of the ERs α and β, assessed by immunohistochemistry and in situ hybridization, showed the presence of ERβ in the lamina propria of the colon. Our study shows that 17HSD type 2 expression is associated with the functional integrity of the gastrointestinal tract. The decrease in expression of the type 2 enzyme may increase estrogen influence in colon cancer. © 2002 Wiley‐Liss, Inc.
Improved detection of melanoma antigen‐specific T cells expressing low or high levels of CD8 by HLA‐A2 tetramers presenting a Melan‐A/Mart‐1 peptide analogue
Authors: Maeurer Markus J. , Necker Antje , Salter Russell D. , Castelli Chiara , Höhn Hanni , Karbach Julia , Freitag Kirsten , Neukirch Claudia , Knuth Alexander , Jäger Elke 
Published: August 2002

AbstractMHC class I tetramers containing peptide epitopes are sensitive tools for detecting antigen‐specific CD8+ T‐cell responses. We demonstrate here that binding of HLA‐A2 tetramers to CD8+ T cells specific for the melanoma‐associated antigen Melan‐A/MART‐1 can be fine‐tuned by altering either the bound peptide epitope or residues in the α3 domain of HLA‐A2, which is important for CD8 binding. Antigen‐specific T cells expressing high levels of CD8 could be detected using HLA‐A2 tetramers containing the peptide AAGIGILTV, an epitope which is naturally processed and presented from Melan‐A/MART‐1. In contrast, low CD8‐expressing, antigen‐specific T cells could be detected efficiently only by using a mutated HLA‐A2 tetramer with an altered CD8 binding site or, less efficiently, using the wild‐type HLA‐A2 tetramer loaded with the peptide analogue ELAGIGILTV, which is superior in stimulating antigen‐specific T‐cell responses. Our results suggest ways to optimize the identification and expansion of antigen‐specific T cells with different requirements for the costimulatory CD8 molecule in facilitating T‐cell receptor binding to peptide variants. © 2002 Wiley‐Liss, Inc.
High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer
Authors: Nordengren Johanna , Lidebring Margareta Fredstorp , Bendahl Pär‐Ola , Brünner Nils , Fernö Mårten , Högberg Thomas , Stephens Ross W. , Willén Roger , Casslén Bertil 
Published: August 2002

AbstractPrevious studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI‐2) and patient survival. High tumor tissue concentrations of PAI‐2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI‐1 have more consistently been associated with poor histologic differentiation and poor prognosis. Our study quantified PAI‐2 and uPAR using specific enzyme‐linked immunosorbent assays in homogenates of 274 samples of endometrial cancer tissue. The prognostic power of each factor was analyzed in the subgroup of patients with early stage disease, i.e., International Federation of Gynecology and Oncology (FIGO) surgical stage I–II (n = 188). This group had a median follow‐up time of 6.8 years (range 0.7–9.9), and 23 progressions were observed. The 80th percentile for PAI‐2 and uPAR was used to dichotomize the material, and the results were analyzed for associations with clinical data including progression‐free survival. The results were also compared with DNA ploidy status, S‐phase fraction, uPA and PAI‐1, which we reported in a previous study (Fredstorp Lidebring et al., Eur J Cancer 2001; in press). A high PAI‐2 level was associated with shorter progression‐free survival in univariate analysis and was an independent prognostic factor in bivariate analyses, which included PAI‐1, uPA and DNA ploidy status. In contrast, a high level of uPAR had no association with prognosis in early stage endometrial cancer. The combination of high PAI‐2 and PAI‐1 levels in tumors revealed a small group of stage I–II patients with an accumulative progression rate of 50%. © 2001 Wiley‐Liss, Inc.
Expression of collagenase‐3 (MMP‐13) enhances invasion of human fibrosarcoma HT‐1080 cells
Authors: Ala‐aho Risto , Johansson Nina , Baker Andrew H. , Kähäri Veli‐Matti 
Published: August 2002

AbstractCollagenase‐3 (MMP‐13) is characterized by an exceptionally wide substrate specificity and restricted expression. MMP‐13 is 1 of the few MMPs primarily expressed by tumor cells in malignant tumors, e.g., squamous cell carcinomas and its expression correlates with their invasion capacity. In this work, we have constructed an expression vector and a recombinant adenovirus harboring human MMP‐13 cDNA to investigate the role of MMP‐13 in cancer cell invasion. Our results show that constitutive expression of MMP‐13 by HT‐1080 cells stably transfected with MMP‐13 expression vector or transduced with MMP‐13 adenovirus markedly increased their invasion both through type I collagen and reconstituted basement membrane (Matrigel) with no alterations in expression or activation of collagenase‐1 (MMP‐1), gelatinase‐A (MMP‐2), or gelatinase‐B (MMP‐9). The enhanced invasion capacity of MMP‐13 expressing HT‐1080 cells was dependent on MMP activity, as it was blocked by MMP inhibitor Batimastat (BB‐94) and tissue inhibitor of metalloproteinases‐3 (TIMP‐3). Our data provide direct evidence for the role of MMP‐13 as a potent invasion proteinase, which alone can enhance the ability of malignant cells to penetrate through both basement membrane and fibrillar collagen. © 2001 Wiley‐Liss, Inc.
Prognostic value of thymidine phosphorylase expression in breast carcinoma
Authors: Yang Qifeng , Barbareschi Mattia , Mori Ichiro , Mauri Francesco , Muscarà Maurizio , Nakamura Misa , Nakamura Yasushi , Yoshimura Goro , Sakurai Takeo , Caffo Orazio , Galligioni Enzo , Dalla Palma Paolo , Kakudo Kennichi 
Published: August 2002

AbstractThymidine phosphorylase (TP), also known as platelet‐derived endothelial cell growth factor (PD‐ECGF), is an enzyme that catalyzes the reversible dephosphorylation of thymidine, deoxyuridine and their analogs. TP has also angiogenic properties, although the precise mechanism by which it promotes angiogenesis is not known. We examined TP expression using immunohistochemistry (654‐1 Mab) in 182 invasive breast carcinomas (67 N0 and 115 N1/2; median follow‐up 78 months [range, 3–177]; 51 patients treated with adjuvant systemic cyclophosphamide, methotrexate and 5‐fluorouracil [CMF] chemotherapy and 82 with tamoxifen). High TP expression was found in 142 cases (78%) and correlated with lower histologic grade and low p53 expression. No correlation was found between TP expression and vascular density. TP‐positive tumors had a significant increase in both disease‐free survival (DFS; p = 0.0025) and overall survival (OS; p = 0.0070) in the total cohort of patients and in the subgroups of node‐positive patients and patients treated with CMF adjuvant therapy; no significant difference in either DFS or OS was observed in patients without CMF treatment. Our findings suggest that TP has little effect on tumor angiogenesis of breast carcinoma, whereas it could represent an interesting marker that could predict response to CMF chemotherapy. © 2001 Wiley‐Liss, Inc.
High expression levels of collagenase‐1 and stromelysin‐1 correlate with shorter disease‐free survival in human metastatic melanoma
Authors: Nikkola Johanna , Vihinen Pia , Vlaykova Tatyana , Hahka‐Kemppinen Marjo , Kähäri Veli‐Matti , Pyrhönen Seppo 
Published: August 2002

AbstractMatrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor‐induced angiogenesis. We studied the expression of collagenase‐1 (MMP‐1), stromelysin‐1 (MMP‐3) and collagenase‐3 (MMP‐13) in 70 melanoma metastases obtained from 56 patients treated with combined chemoimmunotherapy. The patients were divided into 2 groups using a cut‐off point of 0% for MMP‐1 expression and 20% for MMP‐3 expression. We found that patients with MMP‐1 positive metastases (n = 38) had significantly shorter disease‐free survival compared to patients with MMP‐1 negative metastases (n = 18) (median 11.2 vs. 17.0 months, p = 0.0383). The disease‐free survival of patients with high levels of MMP‐3 expression in their metastases (≥20% positive tumor cells, n = 14) was also significantly shorter compared to patients with lower levels of expression (n = 42) (median 5.1 vs. 14.0 months, p = 0.0294). The expression of MMP‐13 did not correlate to survival parameters. We also found that the presence of melanin, a pigment produced by melanocytes, correlated with high expression levels of MMP‐1 (p = 0.0002), MMP‐3 (p < 0.0001) and MMP‐13 (p = 0.0009). The high expression levels of MMP‐13 were also associated with the presence of visceral metastases (p = 0.0284). Our findings suggest that MMP‐1 and ‐3 may have a special role in melanoma metastasis formation and thus they could be used to measure the biological activity of the disease. © 2001 Wiley‐Liss, Inc.
Inactivation of the INK4a/ARF locus and p53 in sporadic extrahepatic bile duct cancers and bile tract cancer cell lines
Authors: Caca Karel , Feisthammel Jürgen , Klee Karen , Tannapfel Andrea , Witzigmann Helmut , Wittekind Christian , Mössner Joachim , Berr Frieder 
Published: August 2002

AbstractThe tumor‐suppressor genes p14(ARF), p16(INK4a) and Tp53 are commonly inactivated in many tumors. We investigated their role in the pathogenesis of 9 bile tract cancer cell lines and 21 primary sporadic extrahepatic bile duct carcinomas. p53 and p16 protein expression was examined by Western blot analysis and immunohistochemistry. Mutation screening of p53 was done by SSCP and direct sequencing. Inactivating mechanisms of p14 and p16 were addressed by screening for mutations, homozygous deletions, chromosomal loss of 9p21 (loss of heterozygosity [LOH] analysis) and promoter hypermethylation of the p14/p16 genes. p53 overexpression could be detected in 7 of 9 cell lines and 7 of 21 primary tumors, but mutations were found in 3 cell lines only. p16 expression was absent in all cell lines, due to homozygous deletion of the gene in 8 of 9 cell lines and hypermethylation of the p16 promoter in one cell line (CC‐LP‐1). p14 exon 1β was homozygously deleted in 6 of 9 cell lines, while retained in CC‐LP‐1 and 2 additional lines. No p14 promoter hypermethylation could be detected. p16 expression was lost in 11 of 21 primary tumors. p16 promoter hypermethylation was present in 9 of 21 primary tumors, all with lost p16 expression. Allelic loss at 9p21 was detected in 13 of 21 primary tumors, 10 of 11 with lost p16 expression and 8 of 9 with methylated p16 promoter. No p14 promoter hypermethylation or p14/p16 mutations could be detected. Neither Tp53 nor p16 alterations showed obvious association with histopathologic or clinical characteristics. In conclusion, inactivation of the p16 gene is a frequent event in primary sporadic extrahepatic bile duct cancers, 9p21 LOH and promoter hypermethylation being the principal inactivating mechanisms. Therefore, p16, but not p14, seems to be the primary target of inactivation at the INK4a locus in bile duct cancers. Other mechanisms than Tp53 mutations seems to be predominantly responsible for stabilization of nuclear p53 protein in bile duct cancers. © 2002 Wiley‐Liss, Inc.
New international monetary arrangements and the exchange rate
Authors: Monacelli Tommaso 
Published: August 2002

AbstractI show how to implement in a simple manner the comparison of alternative monetary policy rules in a two‐country model of the new generation. These rules are: Full Price Stability, Taylor, Fixed and Managed Exchange Rates. I find, first, that the exchange rate dynamic is non‐stationary unless some form of management is undertaken by the respective monetary authorities of the two countries. However, eliminating the excess volatility of the exchange rate does not significantly alter the overall macroeconomic volatility. Second, a floating exchange rate regime based on a Taylor‐type rule seems to better approximate the full price stability benchmark, but at the cost of boosting interest rate volatility. In this respect limiting exchange rate flexibility is desirable. Finally, in all cases the model delivers positive cross‐country correlation of interest rates but negative cross‐country correlation of output. Copyright © 2001 John Wiley & Sons, Ltd.
On holographic transform compression of images
Authors: Bruckstein Alfred M. , Robert J. Holt  , Netravali Arun N. 
Published: August 2002

AbstractLossy transform compression of images is successful and widespread. The JPEG standard uses the discrete cosine transform on blocks of the image and a bit allocation process that takes advantage of the uneven energy distribution in the transform domain. For most images, 10:1 compression ratios can be achieved with no visible degradations. However, suppose that multiple versions of the compressed image exist in a distributed environment such as the internet, and several of them could be made available upon request. The classical approach would provide no improvement in the image quality if more than one version of the compressed image became available. In this paper, we propose a method, based on multiple description scalar quantization, that yields decompressed image quality that improves with the number of compressed versions available. © 2001 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 11, 292–314, 2000
A comparative study of primary and immortalized cell adhesion characteristics to modified polymer surfaces: Toward the goal of effective re‐epithelialization
Authors: Sigurdson Lynn , Carney Denise E. , Hou Yuanxue , Hall Leon , Hard Robert , Hicks Wesley , Bright Frank V. , Gardella Joseph A. 
Published: August 2002

AbstractFacilitating tissue regeneration or replacement requires development of synthetic surfaces that promote cell adhesion, migration, and proliferation. Two successful approaches have been to incorporate minimal cell adhesion recognition sequences at the biomaterial surface and to integrate the entire adhesion molecule into a compatible synthetic matrix. While adhesion assays using immortalized cell lines are important in evaluating synthetic materials, cell type and source play a significant role in the ability of such models to mimic real tissues. Models that utilize multiple cell types or primary cells are more representative of native tissues than models that use single cell types or primary cells. In this study we investigated primary respiratory epithelial cell (REC) adhesion to modified fluoropolymers incorporating simple functional groups and minimal peptide recognition sequences, and we evaluated the potential of hybrid biopolymer materials to support adhesion and proliferation. X‐ray photoelectron spectroscopy (XPS) was used to verify substrate surface composition. Significant differences were found in the adhesion characteristics of primary REC and in the A549 lung carcinoma cell line. Model systems composed of multiple cell types and/or primary cells necessarily represent increased levels of complexity for an investigation of cellular responses to synthetic surfaces. When evaluating biomaterials, adhesion studies using immortalized cell lines cannot necessarily be extrapolated to normal cell behavior. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 357–365, 2002
Sterically blocking adhesion of cells to biological surfaces with a surface‐active copolymer containing poly(ethylene glycol) and phenylboronic acid
Authors: Winblade Natalie D. , Schmökel Hugo , Baumann Marion , Hoffman Allan S. , Hubbell Jeffrey A. 
Published: August 2002

AbstractGraft copolymers were designed that could spontaneously bind to biological surfaces and block subsequent recognition and adhesion at those surfaces. Phenylboronic acid (PBA) moieties in the polymer backbone provided binding to surfaces, forming reversible covalent complexes with cis‐diols found in many biological molecules. Pendant poly(ethylene glycol) (PEG) side chains sterically protected those surfaces from subsequent interactions with other proteins and cells. The PEG and PBA grafting ratios on these poly‐L‐lysine‐graft‐(PEG;PBA) copolymers [PLL‐g‐(PEG;PBA)] were varied, and the polymers were tested in models relevant to undesirable wound‐healing responses such as peritoneal adhesion formation and posterior capsule opacification. PLL‐g‐(PEG;PBA) polymers spontaneously coated tissue culture polystyrene and completely blocked rabbit lens epithelial cell adhesion to the surface over a wide range of PEG grafting ratios. PLL‐g‐(PEG;PBA)s with optimal grafting ratios were able to coat adsorbed serum proteins or extracellular matrices and block cell spreading on the surfaces at 4 h, although the effect was lost within 24 h. The polymer also enhanced the efficacy of surgical lysis of peritoneal adhesions in rats. The reversible covalent complexes formed by the PBA moieties on the copolymer backbone were more effective at binding biological surfaces than electrostatic interactions formed via a copolymer lacking the PBA moieties, that is, PLL‐g‐PEG. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 618–631, 2002