bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor‐targeted immune complex formation: Effects on myeloid cell activation and tumor‐directed immune cell migration
Authors: Kroesen Bart‐Jan , McLaughlin Pamela M.J. , Schuilenga‐Hut Petra H.L. , Jacobs Susan C. , Molema Grietje , Helfrich Wijnand , De Leij Lou F.M.H. 
Published: August 2002

AbstractThe effectiveness of cellular immunotherapy of solid tumors is often hampered by the lack of specific infiltration of immune effector cells into the tumor mass. Therefore, we studied the potential of tumor antigen‐specific antibodies to elicit tumor‐specific myeloid cell activation, to induce or enhance tumor infiltration by immune cells. To this end, we developed an in vitro model system using the human myeloid cell line MonoMac‐6. Incubation of IFN‐γ–primed MonoMac‐6 cells with serum‐opsonized zymosan or EGP‐2–directed, mouse IgG2a‐opsonized, EGP‐2‐positive tumor cells resulted in the production of ROS and TNF‐α and induced E‐selectin and ICAM‐1 expression on HUVECs. FcR‐mediated MonoMac‐6 cell activation was strictly dependent on the activation of MonoMac‐6 cells with IFN‐γ. In addition, no myeloid cell activation was observed in the presence of human serum or using tumor antigen‐specific mouse antibody subclasses other than IgG2a, suggesting the crucial involvement of CD64 (FcγR1) in the effects observed. However, serum‐inhibited myeloid cell activation was completely restored employing a 2‐step targeting approach in which tumor cell opsonization with mouse anti‐EGP‐2 antibodies was followed by incubation with human antimouse Ig antibodies. Moreover, using this 2‐step approach, not only anti‐EGP‐2–directed mouse IgG2a but also mouse IgG1 antibodies effectively induced tumor‐specific myeloid cell activation. In conclusion, we describe a method to induce efficient and tumor‐specific activation of myeloid cells based on the sequential use of mouse tumor antigen‐specific and human antimouse Ig antibodies. Targeted myeloid cell activation may provide a means to aid in the induction of a tumor‐directed immune response and as such, the method described here could be of clinical significance. © 2002 Wiley‐Liss, Inc.
Prognostic significance of Ep‐CAM AND Her‐2/neu overexpression in invasive breast cancer
Authors: Spizzo Gilbert , Obrist Peter , Ensinger Christian , Theurl Igor , Dünser Martina , Ramoni Angela , Gunsilius Eberhard , Eibl Günther , Mikuz Gregor , Gastl Günther 
Published: August 2002

AbstractTo assess the frequency and prognostic impact of Ep‐CAM and Her‐2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow‐up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep‐CAM and Her‐2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her‐2/neu 2+ staining were additionally analyzed by FISH to exclude false positive results. Ep‐CAM and Her‐2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep‐CAM and Her‐2/neu overexpression were predictive for poor disease‐free (DFS) and disease‐related overall survival (DROS). Concurrent Ep‐CAM and Her‐2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her‐2/neu and Ep‐CAM overexpression. By multivariate analysis Ep‐CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her‐2/neu overexpression. In conclusion, overexpression of Ep‐CAM and Her‐2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories. © 2002 Wiley‐Liss, Inc.
Identification of cancer/testis genes by database mining and mRNA expression analysis
Authors: Scanlan Matthew J. , Gordon Claudia M. , Williamson Barbara , Lee Sang‐Yull , Chen Yao‐Tseng , Stockert Elisabeth , Jungbluth Achim , Ritter Gerd , Jäger Dirk , Jäger Elke , Knuth Alexander , Old Lloyd J. 
Published: August 2002

AbstractCancer/testis (CT) antigens are immunogenic proteins expressed predominantly in gametogenic tissue and cancer; they are considered promising target molecules for cancer vaccines. The identification of new CT genes is essential to the development of polyvalent cancer vaccines designed to overcome tumor heterogeneity and antigen loss. In the current study, a search for new CT genes was conducted by mining the Unigene database for gene clusters that contain expressed sequence tags derived solely from both normal testis and tumor‐derived cDNA libraries. This search identified 1,325 different cancer/testis‐associated Unigene clusters. The mRNA expression pattern of 73 cancer/testis‐associated Unigene clusters was assessed by reverse transcriptase polymerase chain reaction. Three gene products, CT15/Hs.177959, CT16/Hs.245431 and CT17/Hs.178062, were detected only in testis and in tumor tissue. CT15 is equivalent to ADAM2/fertilin‐β. CT16, an uncharacterized gene product, has homology (30–50%) to members of the GAGE gene family and is 89% identical to CT16.2/Hs.293317, indicating that CT16 and CT16.2 are members of a new GAGE gene family. The uncharacterized gene product, CT17, has homology (30%) to phospholipase A1. RT‐PCR analysis showed that CT15 is expressed exclusively in renal cancer, whereas CT16 and CT17 are expressed in a range of human cancers. Real‐time RT‐PCR analysis of newly defined CT genes and the prototype CT antigens, MAGE‐3 and NY‐ESO‐1, revealed low levels (less than 3% of the level detected in testis) of CT15, CT16 and NY‐ESO‐1 in a limited range of normal, non‐gametogenic tissues. This study demonstrates the merits of database mining with respect to the identification of tissue‐restricted gene products expressed in cancer. © 2002 Wiley‐Liss, Inc.
Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy
Authors: Siemann Dietmar W. , Mercer Emma , Lepler Sharon , Rojiani Amyn M. 
Published: August 2002

AbstractThe utility of combining the vascular targeting agents 5,6‐dimethyl‐xanthenone‐4 acetic acid (DMXAA) and combretastatin A‐4 disodium phosphate (CA4DP) with the anticancer drugs cisplatin and cyclophosphamide (CP) was evaluated in experimental rodent (KHT sarcoma), human breast (SKBR3) and ovarian (OW‐1) tumor models. Doses of the vascular targeting agents that led to rapid vascular shutdown and subsequent extensive central tumor necrosis were identified. Histologic evaluation showed morphologic damage of tumor cells within a few hours after treatment, followed by extensive hemorrhagic necrosis and dose‐dependent neoplastic cell death as a result of prolonged ischemia. Whereas these effects were induced by a range of CA4DP doses (10–150 mg/kg), the dose response to DMXAA was extremely steep; doses ≤ 15 mg/kg were ineffective and doses ≥ 20 mg/kg were toxic. DMXAA also enhanced the tumor cell killing of cisplatin, but doses > 15 mg/kg were required. In contrast, CA4DP increased cisplatin‐induced tumor cell killing at all doses studied. This enhancement of cisplatin efficacy was dependent on the sequence and interval between the agents. The greatest effects were achieved when the vascular targeting agents were administered 1–3 hr after cisplatin. When CA4DP (100 mg/kg) or DMXAA (17.5 mg/kg) were administered 1 hr after a range of doses of cisplatin or CP, the tumor cell kill was 10–500‐fold greater than that seen with chemotherapy alone. In addition, the inclusion of the antivascular agents did not increase bone marrow stem cell toxicity associated with these anticancer drugs, thus giving rise to a therapeutic gain. © 2002 Wiley‐Liss, Inc.
Intragenic amplification and formation of extrachromosomal small circular DNA molecules from the PIP gene on chromosome 7 in primary breast carcinomas
Authors: Autiero Monica , Camarca Alessandra , Ciullo Marina , Debily Marie‐Anne , El Marhomy Sandrine , Pasquinelli Rosa , Capasso Immacolata , D'Aiuto Giuseppe , Anzisi Anna Maria , Piatier‐Tonneau Dominique , Guardiola John 
Published: August 2002

AbstractThe PIP gene is expressed in exocrine glands and, in pathologic conditions, in breast cysts and breast cancers exhibiting apocrine features. It is localized on the long arm of chromosome 7, a region frequently alterated in mammary tumors. We previously described an abnormal restriction pattern of the PIP gene in 33% of prostate carcinomas analyzed. Here, we analyze the structure of the PIP gene in primary breast carcinomas. We report that part of the 3′ end, including exon 3, intron C, two‐thirds of exon 4 and a small portion of intron B, is amplified and involved in the formation of extrachromosomal spcDNA molecules in 3/14 (21.4%) breast cancers analyzed. The involvement of a well‐defined intragenic region of a gene in the formation of spcDNA appears to be unprecedented. Since spcDNA has been suggested to serve as an enhancer of genetic instability, the PIP gene may be the target of genomic variability processes in breast cancer. © 2002 Wiley‐Liss, Inc.
A model for stock return distribution
Authors: Linden Mikael 
Published: August 2002

AbstractThe Laplace mixture distribution for stock share returns is derived from conditional N(0, σ2) distribution. The conditioning variable, σ2, is assumed to be an exponentially distributed random variable. This offers a natural stochastic interpretation of the risk involved with the stock share. Maximum likelihood (ML) estimates for returns of the 20 most traded shares and the aggregate index of the Helsinki stock market in late 1980s do not reject the Laplace distribution model. The results extend to returns over longer periods than 1 day. Copyright © 2001 John Wiley & Sons, Ltd.
The non‐linear dynamics of output and unemployment in the U.S.
Authors: Altissimo Filippo , Violante Giovanni L. 
Published: August 2002

AbstractThis paper studies the joint dynamics of U.S. output and unemployment rate in a non‐linear VAR model. The non‐linearity is introduced through a feedback variable that endogenously augments the output lags of the VAR in recessionary phases. Sufficient conditions for the ergodicity of the model, potentially applying to a larger class of threshold models, are provided. The linear specification is rejected in favour of our threshold VAR. However, in the estimation the feedback is found to be statistically significant only on unemployment, while it transmits to output through its cross‐correlation. This feedback effect from recessions generates important asymmetries in the propagation of shocks, a possible key to interpret the divergence in the measures of persistence in the literature. The regime‐dependent persistence also explains the finding that the feedback from recession exerts a positive effect on the long‐run growth rate of the economy, an empirical validation of the Schumpeterian macroeconomic theories. Copyright © 2001 John Wiley & Sons, Ltd.
Engineering protein and cell adhesivity using PEO‐terminated triblock polymers
Authors: Liu Valerie A. , Jastromb William E. , Bhatia Sangeeta N. 
Published: August 2002

AbstractPrevious studies on customizing cell culture environments have utilized a variety of microfabrication‐based tools to control the spatial localization of adhesive proteins and subsequently mammalian cells. Others have used various methods to immobilize nonadhesive PEO‐based polymers on surfaces to inhibit protein absorption and cell adhesion. In this study, we report the application of a well‐characterized, commercially available, PEO‐terminated triblock polymer (Pluronic™ F108) to create micropatterned nonadhesive domains on a variety of biomaterials that deter cell adhesion for up to 4 weeks in culture. The Pluronic can be applied using microfluidic tools or photolithographic techniques, and can be adsorbed to a variety of common surfaces including tissue culture polystyrene, methylated glass, silicone, and polylactic‐co‐glycolic acid. The effectiveness of the Pluronic in inhibiting cell adhesion in the presence of collagen I is also quantified. Finally, these patterning techniques are generalized to control tissue organization on a variety of common biomaterials. This simple method for micropatterning PEO and, therefore, proteins and cells should prove useful as a tool for biomolecular surface engineering. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 126–134, 2002
Retention and activity of BMP‐2 in hyaluronic acid‐based scaffolds in vitro
Authors: Kim Hyun D. , Valentini Robert F. 
Published: August 2002

AbstractBone morphogenetic protein‐2 (BMP‐2) delivered in a suitable implantable matrix has the potential to repair local skeletal defects by inducing new bone formation from undifferentiated plurpotent stem cells resident in host tissue. In this study, we examined in vitro the potential of a derivatized hyaluronic acid (Hyaff‐11) scaffold as a delivery vehicle for recombinant human BMP‐2 (rhBMP‐2) in bone and cartilage repair therapies. Hyaff‐11 scaffolds were fabricated using a phase inversion/particulate leaching method and soak‐loaded with rhBMP‐2. In vitro release kinetics of rhBMP‐2, demonstrated using enzyme‐linked immunosorbant assay and alkaline phosphatase (ALP) assay revealed a slow, sustained rhBMP‐2 release during 28 days, with a cumulative release of 31.82% of the initial rhBMP‐2 loaded. rhBMP‐2 was released in bioactive form as demonstrated by ALP induction of pluripotent cell line, C3H10T1/2 (T1/2), down the osteoblast lineage when incubated with the release supernatants. rhBMP‐2 retention in Hyaff‐11 scaffolds was greater than that from collagen gels, which released most of the initially loaded rhBMP‐2 by 14 days. rhBMP‐2‐loaded Hyaff‐11 scaffolds were also seeded with T1/2 cells and evaluated at 3, 7, 14, and 28 days for viability and expression of osteoblast phenotype. Cells remained viable throughout the study and expressed a time‐ and dose‐dependent ALP and osteocalcin expression in the rhBMP‐2 groups. Based on these observations, Hyaff‐11 scaffolds may be suitable delivery systems for rhBMP‐2 in bone/cartilage repair because of their ability to retain rhBMP‐2, release low levels of bioactive rhBMP‐2 to the local environment in a sustained manner, and stimulate differentiation of pluripotent stem cells. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 573–584, 2002
Effect of elastin on the calcification rate of collagen‐elastin matrix systems
Authors: Singla Anuj , Lee Chi H. 
Published: August 2002

AbstractThe role of elastin in the aortic wall calcification and involved mechanisms were investigated. The major hypothesis of this work is that elastin is one of the major components to regulate calcification of bioprosthetic heart valve (BHV). The relationship between the elastin content and the calcification rate of the aortic wall was established using collagen‐elastin matrices (CEM) made of varying ratios of collagen and elastin (90 and 10, 50 and 50, and 20 and 80). Biophysical characterization of CEM was performed by water content measurement and the tensile strength test. The conformational changes of the calcifiable matrix were evaluated as a function of elastin content using Fourier transform infrared (FTIR) spectroscopy. The calcium contents in CEM implanted in the rat subcutaneous model for 7 days were measured using atomic absorption (AA) spectroscopy. As the concentration of elastin in CEM increased from 10 to 80%, the total amount of calcium accumulated in CEM also increased. The calcium level in CEM containing the collagen and an elastin ratio of 20:80 was 20.16 ± 0.70 μg/mg compared with 1.96 ± 0.04 μg/mg in CEM containing the collagen and an elastin ratio of 90:10. The calcification rate of CEM pretreated with ethanol increased, as the elastin concentration in the CEM. However, the calcification rate of CEM pretreated with ethanol is significantly lower than that of the untreated control. The permeation rate of ethanol through CEM with the collagen and an elastin ratio of 20:80 (0.37 ± 0.13 mmol/cm2/h) is significantly smaller than that through CEM with 90:10 (0.94 ± 0.27 mmol/cm2/h). These results indicate that elastin has a significant role in tissue calcification and that elastin's resistance to ethanol penetration partially contributes less effectiveness of ethanol on aortic wall calcification. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 368–374, 2002; DOI 10.1002/jbm.10077
Leukodepletion for acute lymphocytic leukemia in a three‐week‐old infant
Authors: Woloskie Sheryl , Armelagos Heidi , Meade J. Michael , Haas Debra 
Published: August 2002

AbstractWe report the smallest infant (4.5 kg) to receive leukapheresis as an immediate treatment for Infantile Acute Lymphocytic Leukemia. Leukodepletion helps prevent the risks of hyperviscosity and cerebrovascular and pulmonary leukostasis. In addition, it is a desirable precursor to chemotherapy to potentially reduce metabolic and renal complications associated with rapid cell lysis. Because of this infant's small size, she presented us with multiple concerns, including hypocalcemia from citrate anticoagulation, extracorporeal volume and fluid balance, inlet flow rates. and establishment of adequate interface. Our positive experience in performing this procedure suggests that cytapheresis is a feasible treatment even for very young infants. J. Clin. Apheresis. 16:31‐32, 2001. © 2001 Wiley‐Liss, Inc.
Cactus‐independent nuclear translocation of Drosophila RELISH
Authors: Cornwell William D. , Kirkpatrick Robert B. 
Published: August 2002

AbstractInsects can effectively and rapidly clear microbial infections by a variety of innate immune responses including the production of antimicrobial peptides. Induction of these antimicrobial peptides in Drosophila has been well established to involve NF‐κB elements. We present evidence here for a molecular mechanism of Lipopolysaccharide (LPS)‐induced signaling involving Drosophila NF‐κB, RELISH, in Drosophila S2 cells. We demonstrate that LPS induces a rapid processing event within the RELISH protein releasing the C‐terminal ankyrin‐repeats from the N‐terminal Rel homology domain (RHD). Examination of the cellular localization of RELISH reveals that the timing of this processing coincides with the nuclear translocation of the RHD and the retention of the ankyrin‐repeats within the cytoplasm. Both the processing and the nuclear translocation immediately precede the expression of antibacterial peptide genes cecropin A1, attacin, and diptericin. Over‐expression of the RHD but not full‐length RELISH results in an increase in the promoter activity of the cecropin A1 gene in the absence of LPS. Furthermore, the LPS‐induced expression of these antibacterial peptides is greatly reduced when RELISH expression is depleted via RNA‐mediated interference. In addition, loss of cactus expression via RNAi revealed that RELISH activation and nuclear translocation is not dependent on the presence of cactus. Taken together, these results suggest that this signaling mechanism involving the processing of RELISH followed by nuclear translocation of the RHD is central to the induction of at least part of the antimicrobial response in Drosophila, and is largely independent of cactus regulation. J. Cell. Biochem. 82: 22–37, 2001. © 2001 Wiley‐Liss, Inc.
Green tea extracts decrease carcinogen‐induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture
Authors: Kavanagh Kathryn T. , Hafer Laurie J. , Kim Dong W. , Mann Koren K. , Sherr David H. , Rogers Adrianne E. , Sonenshein Gail E. 
Published: August 2002

AbstractEpidemiological evidence suggests tea (Camellia sinensis L.) has chemopreventive effects against various tumors. Green tea contains many polyphenols, including epigallocatechin‐3 gallate (EGCG), which possess anti‐oxidant qualities. Reduction of chemically induced mammary gland carcinogenesis by green tea in a carcinogen‐induced rat model has been suggested previously, but the results reported were not statistically significant. Here we have tested the effects of green tea on mammary tumorigenesis using the 7,12‐dimethylbenz(a)anthracene (DMBA) Sprague‐Dawley (S‐D) rat model. We report that green tea significantly increased mean latency to first tumor, and reduced tumor burden and number of invasive tumors per tumor‐bearing animal; although, it did not affect tumor number in the female rats. Furthermore, we show that proliferation and/or viability of cultured Hs578T and MDA‐MB‐231 estrogen receptor‐negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA‐transformed D3‐1 cell line. Growth inhibition of Hs578T cells correlated with induction of p27Kip1 cyclin‐dependent kinase inhibitor (CKI) expression. Hs578T cells expressing elevated levels of p27Kip1 protein due to stable ectopic expression displayed increased G1 arrest. Thus, green tea had significant chemopreventive effects on carcinogen‐induced mammary tumorigenesis in female S‐D rats. In culture, inhibition of human breast cancer cell proliferation by EGCG was mediated in part via induction of the p27Kip1 CKI. J. Cell. Biochem. 82:387–398, 2001. © 2001 Wiley‐Liss, Inc.
Relation between the flexibility of the WPD loop and the activity of the catalytic domain of protein tyrosine phosphatase SHP‐1
Authors: Yang Jian , Niu Tianqi , Zhang Aihua , Mishra Ashwini K. , Zhao Zhizhuang Joe , Zhou G. Wayne 
Published: August 2002

AbstractThe conserved WPD loop of protein tyrosine phosphatases play an important role in the catalytic activity and the invariant aspartate residue acts as a general acid/base catalyst in the dephosphorylation reaction. In our previous report, we have demonstrated that the catalytic activities of the PTPs are influenced by the flexibility and stability of the WPD loop in its active “open” conformation [Yang et al., 1998]. Phosphatases with a more flexible WPD loop generally have higher specific activity. In this report, we modify the WPD loop of SHP‐1 by alanine‐scan mutation of the residues flanking the loop and measure their effects on the catalytic activity of the phosphatase. We show that the S418A, V424A, S426A, E427A, and P428A mutants increase the phosphatase activity, possibly due to the increased flexibility of the WPD loop, whereas the L417A, L417G and P425A mutants decrease its phosphatase activity. In addition, we propose that the two‐proline residues in the WPD loop (Pro420 and Pro425 in SHP‐1) work as pivotal points through a conserved hydrophobic network and allows residues between the pivotal points to have maximum flexibility in enhancing the phosphatase activity. Furthermore, our data suggest that the hydrolysis of the phosphoryl‐cysteine intermediate, not its formation, is the rate‐limiting step with p‐nitrophenyl phosphate as the substrate while both the steps are rate‐limiting with phosphotyrosine as the substrate. J. Cell. Biochem. 84: 47–55, 2002. © 2001 Wiley‐Liss, Inc.