bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced antitumor efficacy of telomerase‐selective oncolytic adenoviral agent OBP‐401 with docetaxel: Preclinical evaluation of chemovirotherapy
Authors: Fujiwara Toshiya , Kagawa Shunsuke , Kishimoto Hiroyuki , Endo Yoshikatsu , Hioki Masayoshi , Ikeda Yoshihiro , Sakai Ryo , Urata Yasuo , Tanaka Noriaki , Fujiwara Toshiyoshi 
Published: February 2006

AbstractOncolytic adenoviruses are being developed as novel anticancer therapeutics and currently undergoing clinical trials. We previously demonstrated that telomerase‐specific replication‐competent adenovirus (Telomelysin: OBP‐301), in which the human telomerase reverse transcriptase (hTERT) promoter regulates viral replication, efficiently killed human tumor cells. We further constructed OBP‐401 (Telomelysin‐GFP) that expresses the green fluorescent protein (GFP) reporter gene under the control of the cytomegalovirus promoter in the E3 region to monitor viral distribution. Here, we examined the feasibility of a single‐agent therapy with OBP‐401 as well as of combining OBP‐401 with chemotherapeutic agents. Infection of OBP‐401 alone or followed by the treatment of a chemotherapeutic drug, docetaxel (Taxotere), resulted in a profound in vitro cytotoxicity and GFP expression in various human cancer cell lines originating from different organs (lung, colon, esophagus, stomach, liver and prostate), although the magnitude of antitumor effect varied among the cell types. Other chemotherapeutic drugs such as vinorelbine (Navelbine) and SN38 (the potent active metabolite of irinotecan) combined with OBP‐401 also inhibited the growth of human cancer cells. Quantitative real‐time PCR analysis demonstrated that docetaxel did not affect viral replication. For in vivo evaluation, nu/nu mice xenografted with H1299 human lung tumor received intratumoral injection of OBP‐401 and intraperitoneal administration of docetaxel. Analysis of growth of implanted tumors showed a significant, therapeutic synergism, although OBP‐401 alone and docetaxel alone showed modest inhibition of tumor growth. Thus, OBP‐401 in combination with docetaxel efficiently enhances the antitumor efficacy both in vitro and in vivo, and the outcome has important implications for tumor‐specific oncolytic chemovirotherapies for human cancers. © 2006 Wiley‐Liss, Inc.
Estrogen and progesterone receptor gene polymorphisms and sporadic breast cancer risk: A Spanish case‐control study
Authors: Fernández L.P. , Milne R.L. , Barroso E. , Cuadros M. , Arias J.I. , Ruibal A. , Benítez J. , Ribas G. 
Published: February 2006

AbstractEstrogens, and to a lesser extent progesterones, influence the proliferation, differentiation and physiology of breast tissue as well as the development and progression of breast cancer. Genetic variants in the steroid hormone receptor genes ESR1 and PGR (belonging to the nuclear receptor superfamily) could therefore modify sporadic breast cancer susceptibility. Two studies have shown a protective effect associated with variants in ESR1 in 2 distinct populations. We studied 4 single nucleotide polymorphisms (SNPs) in ESR1 and 4 in PGR in 550 consecutive and unrelated sporadic Spanish breast cancer patients and 564 healthy Spanish controls. We observed a dominant protective effect for the S10S variant in ESR1, with an estimated odds ratio (OR) of 0.75 (95% CI = 0.58–0.97; p = 0.03) although functional studies did not show changes in the RNA stability. A small subset of individuals carried a haplotype combination that corroborates this protection. No other SNP considered in either gene was found to be associated with sporadic breast cancer. Our results obtained in a European population confirm the protective role of the S10S variant in ESR1, previously reported in an Asian and a European–American population. © 2006 Wiley‐Liss, Inc.
The prognostic impact of O6‐Methylguanine‐DNA Methyltransferase (MGMT) promotor hypermethylation in esophageal adenocarcinoma
Authors: Baumann S. , Keller G. , Pühringer F. , Napieralski R. , Feith M. , Langer R. , Höfler H. , Stein H. J. , Sarbia M. 
Published: February 2006

AbstractPromotor hypermethylation is a common event in human cancer. O6‐Methylguanine‐DNA Methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancer types. In colorectal cancer and lung cancer, hypermethylation of MGMT has been correlated with p53 mutation. In the present study, 132 samples of esophageal adenocarcinoma and 58 samples of normal esophageal tissue were investigated for MGMT hypermethylation status by methylation‐specific real‐time PCR and results were correlated to clinicopathological parameters, patient's survival, p53 mutation and expression of p53 protein and MGMT protein. In the carcinomas, hypermethylation of MGMT was found in 63.6% of cases and loss of MGMT protein expression in 48.5% of cases. Furthermore, MGMT hypermethylation was found in 5.7% of normal esophageal smooth muscle tissue, in 20.0% of esophageal squamous epithelium and in 61.5% of nonneoplastic Barrett's mucosa. In the carcinomas, hypermethylation of the MGMT gene was correlated with loss MGMT protein expression (p < 0.0001) and with high tumor differentiation (p = 0.0079). In contrast, no correlation between MGMT hypermethylation, Lauren's classification, WHO classification, tumor size, gender, age, pT category and pN category, and p53 status was found. Neither MGMT hypermethylation nor loss of MGMT protein expression was correlated with patient's survival. In conclusion, MGMT hypermethylation in esophageal adenocarcinoma is a frequent event that is associated with loss of MGMT protein expression but not with patient's outcome. © 2006 Wiley‐Liss, Inc.
Enhanced antiangiogenic therapy with antibody‐collagen XVIII NC1 domain fusion proteins engineered to exploit matrix remodeling events
Authors: Sánchez‐Arévalo Lobo Víctor J. , Cuesta Ángel M. , Sanz Laura , Compte Marta , García Pascal , Prieto Jesús , Blanco Francisco J. , Álvarez‐Vallina Luis 
Published: February 2006

AbstractAntiangiogenic therapy is nowadays one of the most active fields in cancer research. The first strategies, aimed at inhibiting tumor vascularization, included upregulation of endogenous inhibitors and blocking of the signals delivered by angiogenic factors. But interaction between endothelial cells and their surrounding extracellular matrix also plays a critical role in the modulation of the angiogenic process. This study introduces a new concept to enhance the efficacy of antibody‐based antiangiogenic cancer therapy strategies, taking advantage of a key molecular event occurring in the tumor context: the proteolysis of collagen XVIII, which releases the endogenous angiogenesis inhibitor endostatin. By fusing the collagen XVIII NC1 domain to an antiangiogenic single‐chain antibody, a multispecific agent was generated, which was efficiently processed by tumor‐associated proteinases to produce monomeric endostatin and fully functional trimeric antibody fragments. It was demonstrated that the combined production in the tumor area of complementary antiangiogenic agents from a single molecular entity secreted by gene‐modified cells resulted in enhanced antitumor effects. These results indicate that tailoring recombinant antibodies with extracellular matrix‐derived scaffolds is an effective approach to convert tumor progression associated processes into molecular clues for improving antibody‐based therapies. © 2006 Wiley‐Liss, Inc.
Biomarker analysis on breast ductal lavage cells in women with and without breast cancer
Authors: Zhang Wei , Yang Yu‐Ching , Zhang Bao‐Ning , Pan Qin‐Jing , Hart Steven D , Duvall Karen , Zhang Zuo‐Feng , Rao Jian‐Yu 
Published: February 2006

AbstractRecent studies show that morphology based analysis of ductal lavage specimens failed to detect many cancers in women with breast cancer. Such an observation raises doubts about the potential role of ductal lavage in an individual's risk assessment and early detection of breast cancer. We hypothesize that biomarker‐based analysis using markers of malignancy field defects including DNA 5c exceeding rate (DNA 5cER) and G‐actin might provide a more reliable test for breast cancer risk. The study was performed in 2 phases, the training and validation phase. For the training phase, 36 Chinese women were recruited (13 with breast cancer, 8 with intraductal papilloma and 15 with benign breast diseases). The validation phase included 10 women with cancer and 7 women without cancer. Ductal lavage samples were processed by the ThinPrep technique and evaluated by morphology followed by biomarker analysis using laser scan cytometry (LSC) for G‐actin and DNA5cER. In the training phase, biomarker analysis was performed on the 67% (24 of 36) of samples that had over 100 epithelial cells. The sensitivity of DNA5cER was 90% with a specificity of 100%, and G‐actin was 100% and 93%, respectively. By contrast, the sensitivity and specificity obtained by cytology alone were 67% and 93%, respectively. Similar results were obtained from the small validation study. Quantitative analysis of biomarkers for G‐actin and DNA5cER is feasible and useful in distinguishing benign from malignant breast disease on archived ductal lavage slides. Further studies are warranted to determine the value of these biomarkers in prospective trials. © 2006 Wiley‐Liss, Inc.
Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers
Authors: Wu Chan‐Hang , Lin Shiu‐Ru , Yu Fang‐Jung , Wu Deng‐Chyang , Pan Yong‐Sang , Hsieh Jan‐Sing , Huang Sung‐Yu , Wang Jaw‐Yuan 
Published: February 2006

AbstractRecently several noninvasive methods have been employed to detect circulating tumor cells (CTCs) in cancer patients. In this study, we have developed a highly sensitive, high‐throughput colorimetric membrane‐array method that was designed to detect a panel of mRNA markers including human telomerase reverse transcriptase (hTERT), cytrokeratin‐19 (CK‐19), carcinoembryonic antigen (CEA) and mucin 1 (MUC1) mRNA for the presence of CTCs in the peripheral blood of patients with gastric cancer (GC). Digoxigenin‐labeled cDNA targets synthesized following total RNA isolation from peripheral blood samples of 64 GC patients and 80 healthy individuals were subjected to membrane‐array hybridization. The results showed that membrane array could positively detect 5 cancer cells/ml of peripheral blood in GC cell‐dilution experiments. The sensitivity, specificity and diagnostic accuracy for hTERT, CK‐19, CEA and MUC1 mRNA ranged from 78.1% to 82.8%, 76.3% to 85% and 81.3% to 83.3%, respectively. Both CEA and MUC1 mRNA expression was correlated significantly with all malignant biological properties of GC, such as macroscopic type, depth of tumor invasion, lymph‐node metastasis, TNM stage and coexisting distant metastasis (all p < 0.05). Using these 4 markers in combination, the sensitivity, specificity and diagnostic accuracy of membrane array were raised to 89.1%, 91.3% and 90.3%, respectively. The expression of all 4 mRNA markers was an independent predictor for postoperative recurrence/metastasis. GC patients with the expression of all the 4 mRNA markers showed a poorer survival rate than those without the expression of any 1 mRNA marker (p = 0.0223). These findings demonstrated that our membrane‐array method could detect CTCs in the circulation of GC patients with considerably high sensitivity and specificity. The identification of CTCs in the peripheral blood may be useful in the auxiliary cancer diagnostics or postoperative surveillance of GC patients for recurrence/metastasis. © 2006 Wiley‐Liss, Inc.
Revive energy audits with today's cost management
Authors: Roth Harold P. 
Published: February 2006

AbstractRemember the 1970s? We had petroleum shortages and price increases back then, too. But many companies also had conducted energy audits—to see where they could reduce energy usage. Accountants contributed their skills in auditing and cost management to make the process even more successful.In many ways, we're in a similar situation today. But energy audits aren't as popular—even though recent advances in cost management could make energy audits even more useful.The author thinks it's time to revive energy audits—using today's cost management techniques. And he shows how to do it. © 2006 Wiley Periodicals, Inc..
Taming SOX costs with six sigma
Authors: Martin Dale R. , Juras Paul E. , Aldhizer III George R. 
Published: February 2006

AbstractThe Sarbanes‐Oxley Act (SOX) was passed to fight fraud. But SOX has imposed a lot of additional work and expense on public companies and their independent auditors. Large public companies have been shocked at the multibillion‐dollar costs of first‐year SOX compliance. And year two's costs do not look much better.Is there a way to get SOX costs under control? The authors say the answer is yes, and it can be done by using a powerful quality improvement tool: Six Sigma. They show how to use it and how to avoid common pitfalls. © 2006 Wiley Periodicals, Inc.
Managing M&A costs
Authors: Venema William H. 
Published: February 2006

AbstractMerger and acquisition (M&A) activity increased in 2005, but vocal critics are decrying the huge transaction costs usually involved. Shareholders of the buying firms mostly lost out.But it doesn't have to be that way, says the author, who has assisted scores of M&A clients over two decades. And he explains how to control M&A costs. © 2006 Wiley Periodicals, Inc..
How the nanotechnology revolution will affect cost management
Authors: Dutta Saurav , Lawson Raef , Marcinko David 
Published: February 2006

AbstractNanotechnology—the application of research about objects at the molecular level—holds the promise of transforming the processes used to produce goods, revolutionizing whole industries, and transforming society as a whole. This article explores the cost management and corporate financial implications of this coming revolution. © 2006 Wiley Periodicals, Inc.
Zippo lights up with ABC/M
Authors: Miller John , Muras Andrew , Vecchio Robert 
Published: February 2006

AbstractZippo Manufacturing wanted a product‐ and customer‐profitability reporting system, but it was leery of the potential costs and complexities. By using a few simple principles to get results quickly and inexpensively, Zippo soon had a working and effective system. Partly as a result, Zippo was recognized in 2005 as a best practice organization for Calculating and Reporting Customer Profitability by the APQC, a member‐based nonprofit for process and performance improvement. © 2006 Wiley Periodicals, Inc.
Involvement of somatolactin in background adaptation of the cichlid fish Cichlasoma dimerus
Authors: Cánepa Maximiliano Martín , Pandolfi Matías , Maggese María Cristina , Vissio Paula Gabriela 
Published: February 2006

AbstractSomatolactin (SL) is a pituitary hormone present exclusively in fish that is involved in different physiological processes. The role of SL was evaluated in Cichlasoma dimerus (Teleostei, Perciformes) exposed for 10 days to a black and white background (BB and WB). Changes in α‐melanophore stimulating hormone (αMSH) and melanin concentrating hormone (MCH) cells were also analyzed for comparison with SL. A melanin dispersing effect was observed in fish exposed to a BB, while a concentrating one was observed in those exposed to a WB. By Western blot, three SL‐immunoreactive (ir) bands (32, 28 and 23.5 kD) were evidenced. Pituitary SL‐ir levels were 2.66‐ and 2.67‐fold greater in the 32 Kd and 28 kD bands, respectively, in BB fish compared with those of WB fish. The SL‐ir 23.5 Kd band was not included in the analysis because of its unknown identity. In addition, SL‐ir cell number and area were significantly higher in the BB condition (BB 22.73±1.46, WB 7.37±0.54 and BB 27.39±1.00 μm2; WB: 16.61±0.65 μm2). No significant differences were observed in the number of the hypothalamic MCH‐ir neurons. However, a significant difference was observed in their nuclear area (BB 11.61±0.42 μm2, WB 17.80±0.84 μm2). αMSH‐ir cells showed a marked increased in number (BB 35.96±1.22, WB 24.36±1.04), but no significant differences were observed in the cell area. In conclusion, this study presented clear evidence towards a possible involvement of SL in the adaptation to background colors in teleost together with αMSH and MCH. J. Exp. Zool. 305A, 2006. © 2006 Wiley‐Liss, Inc.
Influence of local and systemic CTLA4Ig gene transfer on corneal allograft survival
Authors: Gong Nianqiao , Pleyer Uwe , Yang Jun , Vogt Katrin , Hill Marcelo , Anegon Ignacio , Volk Hans‐Dieter , Ritter Thomas 
Published: February 2006

AbstractBackgroundTo analyse the effects of local (ex vivo) or systemic (in vivo) administration of adenovirus type 5 encoding CTLA4Ig (AdCTLA4Ig) on its influence to prolong corneal allograft survival and to study the underlying mechanisms.MethodsA MHC class I/II mismatched rat corneal transplant model was used. Recipients were randomly assigned to receive ex vivo gene‐modified corneas expressing either CTLA4Ig, CTLA4Ig/IL‐10 or a single intraperitoneal (i.p.) injection (1.0 × 109 or 1.0 × 1010 infectious particles) of AdCTLA4Ig 1 day before transplantation and graft survival was analysed. The immunoregulatory effect of this treatment was examined by analysing intra‐graft cytokine mRNA expression pattern at day 12 post‐transplant. The anti‐adenovirus immunity also was investigated.ResultsEx vivo gene transfer resulted in a modest but significant prolongation of graft survival (p = 0.0036 compared to no treatment). In contrast, systemic gene therapy (1.0 × 109 or 1.0 × 1010 infectious particles) significantly prolonged graft survival (p = 0.0007 and 0.0001, respectively, compared to no treatment). Systemic (1.0 × 1010 infectious particles) therapy resulted in frequent indefinite survival of allogeneic grafts which was not observed in the other therapeutic regimens. Moreover, systemic therapy prevented the intra‐graft accumulation and activation of T cells and resulted in a reduced mRNA expression of both TH1 and TH2 cytokines. The generation of anti‐adenovirus antibodies was also efficiently inhibited.ConclusionsCTLA4Ig gene therapy is a successful strategy for the prevention of allogeneic graft rejection in corneal transplantation. Our work has further elucidated the mechanisms of corneal allograft rejection which may lead to novel therapeutic strategies. Copyright © 2006 John Wiley & Sons, Ltd.
Imaging and therapy of malignant pleural mesothelioma using replication‐competent herpes simplex viruses
Authors: Adusumilli Prasad S. , Stiles Brendon M. , Chan Mei‐Ki , Mullerad Michael , Eisenberg David P. , Ben‐Porat Leah , Huq Rumana , Rusch Valerie W. , Fong Yuman 
Published: February 2006

AbstractBackgroundMalignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication‐competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy.MethodsThe infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: G207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model.ResultsAll three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. Furthermore, NV1066 was able to reduce the tumor burden and prolong survival even when treatment was at an advanced stage of the disease.ConclusionThese findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy‐resistant MPM. Copyright © 2006 John Wiley & Sons, Ltd.
Efficient in toto targeted recombination in mouse liver by meganuclease‐induced double‐strand break
Authors: Gouble Agnès , Smith Julianne , Bruneau Sylvia , Perez Christophe , Guyot Valérie , Cabaniols Jean‐Pierre , Leduc Sophie , Fiette Laurence , Avé Patrick , Micheau Béatrice , Duchateau Philippe , Pâques Frédéric 
Published: February 2006

AbstractBackgroundSequence‐specific endonucleases with large recognition sites can cleave DNA in living cells, and, as a consequence, stimulate homologous recombination (HR) up to 10 000‐fold. The recent development of artificial meganucleases with chosen specificities has provided the potential to target any chromosomal locus. Thus, they may represent a universal genome engineering tool and seem to be very promising for acute gene therapy. However, in toto applications depend on the ability to target somatic tissues as well as the proficiency of somatic cells to perform double‐strand break (DSB)‐induced HR.MethodsIn order to investigate DSB‐induced HR in toto, we have designed transgenic mouse lines carrying a LagoZ gene interrupted by one I‐SceI cleavage site surrounded by two direct repeats. The LagoZ gene can be rescued upon cleavage by I‐SceI and HR between the two repeats in a process called single‐strand annealing. β‐Galactosidase activity is monitored in liver after tail vein injection of adenovirus expressing the meganuclease I‐SceI.ResultsIn toto staining revealed a strong dotted pattern in all animals injected with adenovirus expressing I‐SceI. In contrast, no staining could be detected in the control. β‐Galactosidase activity in liver extract, tissue section staining, and PCR analysis confirmed the presence of the recombined LagoZ gene.ConclusionsWe demonstrate for the first time that meganucleases can be successfully delivered in animal and induce targeted genomic recombination in mice liver in toto. These results are an essential step towards the use of designed meganucleases and show the high potential of this technology in the field of gene therapy. Copyright © 2006 John Wiley & Sons, Ltd.
Comparison of wing morphology in three birds of prey: Correlations with differences in flight behavior
Authors: Corvidae Elaine L. , Bierregaard Richard O. , Peters Susan E. 
Published: February 2006

AbstractFlight is the overriding characteristic of birds that has influenced most of their morphological, physiological, and behavioral features. Flight adaptations are essential for survival in the wide variety of environments that birds occupy. Therefore, locomotor structure, including skeletal and muscular characteristics, is adapted to reflect the flight style necessitated by different ecological niches. Red‐tailed hawks (Buteo jamaicensis) soar to locate their prey, Cooper's hawks (Accipiter cooperii) actively chase down avian prey, and ospreys (Pandion haliaetus) soar and hover to locate fish. In this study, wing ratios, proportions of skeletal elements, and relative sizes of selected flight muscles were compared among these species. Oxidative and glycolytic enzyme activities of several muscles were also analyzed via assays for citrate synthase (CS) and for lactate dehydrogenase (LDH). It was found that structural characteristics of these three raptors differ in ways consistent with prevailing aerodynamic models. The similarity of enzymatic activities among different muscles of the three species shows low physiological differentiation and suggests that wing architecture may play a greater role in determining flight styles for these birds. J. Morphol. © 2006 Wiley‐Liss, Inc.