bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of binding stoichiometries of the human immunodeficiency virus type 1 reverse transcriptase by capillary electrophoresis and laser‐induced fluorescence polarization using aptamers as probes
Authors: Fu Hao , Guthrie Jeffrey W. , Le X. Chris 
Published: December 2005

AbstractBinding stoichiometries between four DNA aptamers (RT12, RT26, RTlt49, and ODN93) and the reverse transcriptase (RT) of the type 1 human immunodeficiency virus (HIV‐1) were studied using affinity CE (ACE) coupled with LIF polarization and fluorescence polarization (FP). The ACE/LIF study showed evidence of two binding stoichiometries between the HIV‐1 RT protein and aptamers RT12, RT26, and ODN93, suggesting that these aptamers can bind to both the p66 and p51 subunits of the HIV‐1 RT. Only one binding stoichiometry for aptamer RTlt49 was found. The affinity complexes were easily separated from the unbound aptamers; however, the different stoichiometries were not well resolved. A complementary technique, FP, was able to provide additional information about the binding and supporting evidence for the ACE/LIF results. The ACE/LIFP study also revealed that the FP values of the 1:1 complexes of the HIV‐1 RT protein with aptamers RT12, RT26, and ODN93 were always much greater than those of the 1:2 complexes. This was initially surprising because the larger molecular size of the 1:2 complexes was expected to result in higher FP values than the corresponding 1:1 complexes. This phenomenon was probably a result of fluorescence resonance energy transfer between the two fluorescent molecules bound to the HIV‐1 RT protein.
New universal primers facilitate Pyrosequencing™
Authors: Aydin Atakan , Toliat Mohammad R. , Bähring Sylvia , Becker Christian , Nürnberg Peter 
Published: December 2005

AbstractA cost‐driving factor in Pyrosequencing™ is the need for single‐stranded PCR products that are usually obtained by biotin‐labeling of one primer. We designed new universal primers that allow the introduction of biotin during the specific PCR at either the forward or the reverse primer in a single reaction. When converting five human single nucleotide polymorphism assays from the standard format into the universal format, we obtained pyrograms of similar good quality. Although the universal nonhuman sequences are unlikely to form loop structures, we mostly failed to establish assays without using the proprietary software from Biotage AB. Nevertheless, our universal primer pair adds flexibility to the process of assay design due to optional strand selection and contributes to the reduction of genotyping costs.
Forward‐in‐time upwind‐weighted methods in ocean modelling
Authors: Hecht Matthew W. 
Published: December 2005

AbstractThe World Ocean presents a remarkably wide range of spatial and temporal scales within complicated domains. At larger scales, beyond a few tens of meters, the ocean circulation can be seen to separate into quasi‐horizontal and vertical directions, with the magnitude of mixing differing by many orders of magnitude between the two. It is within this context, and with additional constraints of flux‐conservation when used for coupled climate simulation, that transport schemes are placed within ocean general circulation models.Forward‐in‐time upwind‐weighted methods have made gradual, steady inroads into the field. We review this evolution from centred‐in‐time centred‐in‐space schemes, first discussing temporally hybrid models (centred discretization of the momentum equations with forward‐in‐time treatment of the scalar transport equations), then fully forward‐in‐time models, touching on a number of test problems and analyses that have provided guidance to these model development efforts and discussing selected results. Copyright © 2005 John Wiley & Sons, Ltd.
Performance‐based budgeting in the public sector: an illustration from the VA health care system
Authors: Yaisawarng Suthathip , Burgess James F. 
Published: December 2005

AbstractThis paper estimates frontier cost functions for US Department of Veterans Affairs (VA) hospitals in FY2000 that are consistent with economic theory and explicitly account for cost differences across patients' risk, level of access to care, quality of care, and hospital‐specific characteristics. Results indicate that on average VA hospitals in FY2000 operate at efficiency levels of 94%, as compared to previous studies on US private sector hospitals that average closer to 90% efficient. Using these cost frontiers, management systems potentially could be implemented to enhance the equitable allocation of the VA medical care global budget and systematically distribute funds across hospitals and networks. The paper also provides recommendations to improve the efficiency of delivering health care services applicable to public sector organizations. Copyright © 2005 John Wiley & Sons, Ltd.
Ginkgo biloba: no robust effect on cognitive abilities or mood in healthy young or older adults
Authors: Burns Nicholas R. , Bryan Janet , Nettelbeck Ted 
Published: December 2005

AbstractGinkgo biloba extracts are commonly used to prevent or treat memory problems but evidence on the efficacy of ginkgo is equivocal. In any case, the psychological locus of ginkgo's effects is unknown. A 12‐week, double‐blind, placebo‐controlled study assessed effects of ginkgo (120 mg per day) on a wide range of cognitive abilities, executive function, attention and mood in 93 healthy older adults (55–79 years) and in 104 young adults (18–43 years). For the older adult sample, longer‐term memory assessed by associational learning tasks showed improvement with ginkgo (d = 0.52, p = 0.04). There was no statistically significant difference on any other measure. For the young adult group no measure showed statistically significant effects of ginkgo enhancement. There were no side effects unequivocally attributable to treatment with ginkgo and those reported by participants in the ginkgo groups were mild and similar to those reported elsewhere. Copyright © 2005 John Wiley & Sons, Ltd.
Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update
Authors: Gronwald Jacek , Tung Nadine , Foulkes William D. , Offit Kenneth , Gershoni Ruth , Daly Mary , Kim‐Sing Charmaine , Olsson Hakan , Ainsworth Peter , Eisen Andrea , Saal Howard , Friedman Eitan , Olopade Olufunmilayo , Osborne Michael , Weitzel Jeffrey , Lynch Henry , Ghadirian Parviz , Lubinski Jan , Sun Ping , Narod Steven A. ,   The Hereditary Breast Cancer Clinical Study Group
Published: December 2005

AbstractWomen with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of ∼80%, and following the first diagnosis the10‐year risk of contralateral breast cancer is ∼30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case‐control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30–0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17–1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24–2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27–0.65). © 2005 Wiley‐Liss, Inc.
Human tongue carcinoma growth is inhibited by selective antigelatinolytic peptides
Authors: Heikkilä Pia , Suojanen Juho , Pirilä Emma , Väänänen Anu , Koivunen Erkki , Sorsa Timo , Salo Tuula 
Published: December 2005

AbstractMatrix metalloproteinases (MMP‐2 and MMP‐9, or gelatinases) are involved in tongue SCC invasion, metastasis and angiogenesis. We have recently shown that a novel and selective hydrophobic cyclic CTTHWGFTLC (CTT1) peptide is inhibitor for MMP‐2 and MMP‐9 (Koivunen et al., Nat Biotechnol 1999; 17:768–74). In this study, we demonstrate that both the new hydrophilic derivate GRENYHGCTTHWGFTLC (CTT2) peptide and the CTT1 peptide inhibited specifically the human tongue squamous cell carcinoma (HSC‐3) cell‐derived gelatinolytic activity and in vitro invasion and migration of these cells (p ≤ 0.049). In situ zymography revealed that both peptides also inhibited clearly almost all of the gelatinolytic activity present in the human tongue SCC tissue sections, indicating that MMP‐2 and MMP‐9 are the major gelatinases detected in the tongue carcinomas. However, CTT2 did not inhibit the type I collagen degradation by human collagenases (MMP‐1, MMP‐8 and MMP‐13). Furthermore, CTT2 reduced the blood vessel density (p ≤ 0.043) and clearly improved the survival of the mice bearing human tongue carcinoma xenografts (p ≤ 0.012). Overall, we suggest that CTT1 and CTT2 peptides being selective gelatinase inhibitors with significant anti‐tumor properties could be useful to diminish the invasion and angiogenesis of human tongue carcinomas characterized by enhanced gelatinolytic activity in tumors. © 2005 Wiley‐Liss, Inc.
Confirmation of a linkage between H‐Ras and MMP‐13 expression as well as MMP‐9 by chemical genomic approach
Authors: Lee Su‐Kyung , Kim Jung Min , Lee Mi‐Young , Son Kwang‐Hee , Yeom Young Il , Kim Cheol‐Hee , Shin Youseung , Koh Jong Sung , Han Dong Cho , Kwon Byoung‐Mog 
Published: December 2005

AbstractAs farnesylation of the Ras protein by farnesyl transferase is a critical step for the Ras functional activity, the farnesyl transferase inhibitor could affect H‐Ras functions and the inhibitors such as arteminolide, SCH66336 and LB42908 completely inhibited Ras‐farnesylation. However, they did not induce apoptosis of H‐Ras‐transformed cells with concentration for blocking H‐Ras farnesylation. To determine the antitumor effects of the inhibitors, it was analyzed through the expression profile of genes, regulated by activated H‐Ras or FTIs by using cDNA microarray. On the basis of the results, the relationship between H‐Ras and MMPs expression was confirmed by RT‐PCR, Western bolt, zymographic analysis and angiogenesis assay. Our results suggested that activation of MMP‐13 as well as MMP‐9 induced by H‐Ras is involved in angiogenesis and with farnesyl transferase inhibitors, in part, exerts their anticancer effects. We confirmed that MMP‐13 is a critical H‐Ras target gene through chemical genomic approaches with farnesyl transferase inhibitors. © 2005 Wiley‐Liss, Inc.
Telomerase inhibition by stable RNA interference impairs tumor growth and angiogenesis in glioblastoma xenografts
Authors: Pallini Roberto , Sorrentino Antonio , Pierconti Francesco , Maggiano Nicola , Faggi Riccardo , Montano Nicola , Maira Giulio , Larocca Luigi Maria , Levi Andrea , Falchetti Maria Laura 
Published: December 2005

AbstractTelomerase is highly expressed in advanced stages of most cancers where it allows the clonal expansion of transformed cells by counteracting telomere erosion. Telomerase may also contribute to tumor progression through still undefined cell growth‐promoting functions. Here, we inhibited telomerase activity in 2 human glioblastoma (GBM) cell lines, TB10 and U87MG, by targeting the catalytic subunit, hTERT, via stable RNA interference (RNAi). Although the reduction in telomerase activity had no effect on GBM cell growth in vitro, the development of tumors in subcutaneously and intracranially grafted nude mice was significantly inhibited by antitelomerase RNAi. The in vivo effect was observed within a relatively small number of population doublings, suggesting that telomerase inhibition may hinder cancer cell growth in vivo prior to a substantial shortening of telomere length. Tumor xenografts that arose from telomerase‐inhibited GBM cells also showed a less‐malignant phenotype due both to the absence of massive necrosis and to reduced angiogenesis. © 2005 Wiley‐Liss, Inc.
Steroid hormones stimulate human prostate cancer progression and metastasis
Authors: Ricke William A. , Ishii Kenichiro , Ricke Emily A. , Simko Jeff , Wang Yuzhuo , Hayward Simon W. , Cunha Gerald R. 
Published: December 2005

AbstractTissue recombinants (TRs) composed of mouse urogenital mesenchyme (mUGM) plus an immortalized nontumorigenic human prostatic epithelial cell line (BPH‐1) were grown under the kidney capsule of male athymic nude mice under different hormonal conditions. The objectives were to determine temporal plasma concentrations of testosterone (T) and estradiol‐17β (E2) that elicit progression of nontumorigenic human prostatic epithelial cells in vivo. Second, to determine whether mUGM+BPH‐1 TRs in [T+E2]‐treated hosts could progress to metastases. Control mouse hosts received no exogenous hormonal support, whereas treated mice received Silastic implants containing T and E2 for 1–4 months. Plasma from hormonally treated mice contained significantly higher (p < 0.01) concentrations of T at 1 month (11.7 vs. 0.9 ng/ml). Plasma levels of E2 in steroid implanted mice were significantly higher (p <0.05) at 2 months (104.5 vs. 25.6 ng/l) and 4 months (122.8 vs. 19.2 pg/ml). Wet weights of mUGM+BPH‐1 TRs from [T+E2]‐implanted mice were significantly larger (p < 0.001) than those from untreated hosts. Untreated mUGM+BPH‐1 TRs contained a well organized differentiated epithelium surrounded by smooth muscle stroma similar to developing prostate. In [T+E2]‐implanted mice, mUGM+BPH‐1 TRs formed carcinomas that contained a fibrous connective tissue stroma permeating the tumor; smooth muscle when present was associated with vasculature. Renal lymph nodes collected from [T+E2]‐treated mice, but not untreated mice, contained metastatic carcinoma cells. Moreover, metastases could be observed at distant sites including lung and liver. Epithelial cells isolated from untreated mUGM+BPH‐1 TRs exhibited benign histology and formed small nontumorigenic grafts when subsequently transplanted into athymic nude mice. In contrast, epithelial cells isolated from mUGM+BPH‐1 tumors of [T+E2]‐treated hosts formed large tumors that grew independent of stromal and hormonal support and developed lymph node metastases. We conclude that [T+E2]‐treatment promotes prostatic cancer progression in mUGM + BPH‐1 TRs. Use of mUGM in this system will allow future studies to utilize the power of mouse genetics to identify paracrine factors involved in human prostatic carcinogenesis. © 2005 Wiley‐Liss, Inc.
A prostate secretory protein94‐derived synthetic peptide PCK3145 inhibits VEGF signalling in endothelial cells: Implication in tumor angiogenesis
Authors: Lamy Sylvie , Ruiz Marcia T. , Wisniewski Jan , Garde Seema , Rabbani Shafaat A. , Panchal Chandra , Wu Jinzi J. , Annabi Borhane 
Published: December 2005

AbstractWe have previously observed that the synthetic peptide corresponding to amino acids 31–45 (PCK3145) of PSP94 can reduce prostate tumor growth in vivo. Moreover, a recently concluded phase IIa clinical trial with patients with hormone refractory prostate cancer indicated that PCK3145 down‐regulates the levels of plasma matrix metalloproteinase (MMP)‐9, a MMP involved in metastasis and tumor angiogenesis. The purpose of our study was to investigate the molecular mechanisms of action of PCK3145 and whether this peptide could antagonize tumor neovascularization. We show that, in a syngeneic in vivo model of rat prostate cancer, the expression of endothelial cell (EC) specific CD31, a marker of tumor vessel density, was decreased by 43% in PCK3145‐treated animals. In vitro, PCK3145 specifically antagonized in a dose‐dependent manner the VEGF‐induced ERK phosphorylation as well as the phosphorylation of the VEGFR‐2 in cultured EC (HUVEC). These anti‐VEGF effects were partly reproduced by pharmacological inhibitors such as PD98059 and PTK787, suggesting that PCK3145 inhibits the tyrosine kinase activity associated to VEGFR‐2, which in turn prevents intracellular signalling through the MAPK cascade. Moreover, PCK3145 was also found to inhibit the PDGF‐induced phosphorylation of PDGFR in smooth muscle cells. Finally, PCK3145 inhibited in vitro EC tubulogenesis and VEGF‐induced MMP‐2 secretion suggesting its potential implication as an antiangiogenic agent. Our study demonstrates that PCK3145 interferes with the tyrosine kinase activity associated with VEGF signalling axis in EC. The antiangiogenic properties of this peptide could be highly beneficial and exploited in novel antiangiogenic therapies, for patients with various cancers. © 2005 Wiley‐Liss, Inc.
Short‐term dietary administration of celecoxib enhances the efficacy of tumor lysate‐pulsed dendritic cell vaccines in treating murine breast cancer
Authors: Hahn Tobias , Alvarez Irene , Kobie James J. , Ramanathapuram Lalitha , Dial Sharon , Fulton Amy , Besselsen David , Walker Edwin , Akporiaye Emmanuel T. 
Published: December 2005

AbstractCyclooxygenase‐2 (COX‐2) is a rate‐limiting enzyme in the synthesis of prostaglandins. It is over‐expressed in multiple cancers and has been associated with diminished tumor immunity. Dendritic cells (DCs) are considered candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC‐based vaccines have exhibited minimal effectiveness against established tumors. In this study, we evaluated the effect of short‐term administration of the selective COX‐2 inhibitor celecoxib on the efficacy of DC‐based vaccines in preventing and treating established 4T1 murine mammary tumors. We show that dietary celecoxib alone significantly suppresses the growth of primary tumors and the incidence of lung metastases in the prophylactic setting but is less effective against pre‐established tumors. However, we demonstrate that celecoxib administered after primary tumor establishment synergizes with tumor lysate‐pulsed DC and the adjuvant, GM‐CSF, to improve the antitumor immune response by suppressing primary tumor growth and markedly reducing the occurrence of lung metastases. This triple combination therapy elicits a tumor‐specific immune response evidenced by elevated IFN‐γ and IL‐4 secretion by CD4+ T cells and results in increased infiltration of CD4+ and CD8+ T cells to the tumor site. In addition, dietary celecoxib inhibits angiogenesis evidenced by decreased vascular proliferation within the tumor and serum vascular endothelial growth factor levels. These studies suggest that short‐term celecoxib therapy in combination with DC vaccines may be safely used for treating metastatic breast cancer. © 2005 Wiley‐Liss, Inc.
Serological analysis of human renal cell carcinoma
Authors: Devitt Gerard , Meyer Christiane , Wiedemann Nicole , Eichmüller Stefan , Kopp‐Schneider Annette , Haferkamp Axel , Hautmann Richard , Zöller Margot 
Published: December 2005

AbstractSerological analysis of cDNA expression libraries (SEREX) has proven to be a useful technique in the quest to elucidate the repertoire of immunogenic gene products in human cancer. We have applied the SEREX method to human renal cell carcinoma (RCC) in order to identify associated immunogenic gene products. cDNA expression libraries were prepared from a RCC tumor, a RCC cell line and human testis. The 3 libraries were screened with sera from 35 RCC patients and 15 healthy controls. Approximately 4.5 × 106 phage plaques were screened resulting in 234 positive clones, which corresponded to 74 different gene products. The seroreactivity toward 49 of these antigens was assessed. Seroreactivity to 21 (43%) of the antigens was similar in RCC patients and healthy controls, 9 antigens (18%) elicited antibodies more frequently and 19 antigens (39%) solely in RCC patients. In the reverse setting, reactivity of RCC patients' sera was tested against a panel of 44 previously identified “tumor‐associated” antigens via the SADA (serum antibody detection array) method; 6 antigens reacted with RCC patients' and healthy donors' sera, 8 were reactive only with RCC patients' sera. From the 27 antigens identified by SEREX and SADA, which did not react with sera from healthy controls, 10 antigens reacted with a significant proportion of RCC patients' sera and 77% of RCC patients' sera reacted at least with one of these antigens. Sera from patients with non‐malignant renal diseases or an autoimmune disease did not react with these 10 antigens. © 2005 Wiley‐Liss, Inc.
Predominant T helper type 2‐inflammatory responses promote murine colon cancers
Authors: Osawa Emi , Nakajima Atsushi , Fujisawa Toshio , Kawamura Yuki I. , Toyama‐Sorimachi Noriko , Nakagama Hitoshi , Dohi Taeko 
Published: December 2005

AbstractColon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper‐type 2 (Th2) cell‐derived cytokines. In this study, we investigated the influence of a predominant Th2‐type cytokine response in colitis on carcinogen‐induced colon tumors. Wild type (WT), interferon gamma (IFN‐γ) gene deficient (−/−) [Th2 dominant] or interleukin (IL)‐4−/− [Th1‐dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirty‐three weeks after initial treatment, the total colon was examined. When IFN‐γ−/− mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 ± 1.7) than in WT (3.3 ± 2.9) or IL‐4−/− (3.1 ± 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN‐γ−/− mice than in IL‐4−/− mice. Histologically, the tumors were well‐ or moderately‐differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN‐γ−/− mice showed distinct nuclear expression of β‐catenin, in contrast to the strong membrane staining seen in tumors of IL‐4−/− mice. In conclusion, colonic inflammation associated with Th2‐donimant cytokine responses enhanced the formation of malignant neoplasms. © 2005 Wiley‐Liss, Inc.