bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activator Protein 2α Status Determines the Chemosensitivity of Cancer Cells: Implications in Cancer Chemotherapy
Authors: Wajapeyee Narendra , Raut Chandrashekhar Ganpat , Somasundaram Kumaravel 
Published: October 2005

AbstractCancer chemotherapeutic drugs induce apoptosis by several pathways. Inactivation of proapoptotic genes, or activation of survival signaling, leads to chemoresistance. Activator protein 2α (AP-2α), a developmentally regulated sequence-specific DNA-binding transcription factor, has been shown to function like a tumor suppressor. Here, we show that controlled expression of AP-2α, using tetracycline-inducible system, increased the chemosensitivity of cancer cells by severalfold by sensitizing cells to undergo apoptosis upon chemotherapy. Under these conditions, neither AP-2α expression nor drug treatment resulted in apoptosis induction, whereas in combination the cancer cells underwent massive apoptosis. We found that endogenous AP-2α protein is induced posttranscriptionally by various chemotherapeutic drugs. Blocking the endogenous AP-2α by small interfering RNA in human cancer cells lead to decreased apoptosis, increased colony formation, and chemoresistance irrespective of their p53 status upon chemotherapy. We further show that 5-aza-2′-deoxycytidine induced reexpression of AP-2α in MDA-MB-231 breast cancer cells (wherein AP-2α expression is silenced by hypermethylation), resulted in massive apoptosis induction, increased chemosensitivity, decreased colony formation, and loss of tumorigenesis upon chemotherapy. However, in MDA-MB-231 cells transfected with AP-2α small interfering RNA, 5-aza-2′-deoxycytidine treatment failed to increase apoptosis and chemosensitivity. The treatment also resulted in increased colony formation and efficient tumor formation upon chemotherapy. These results establish an important role for AP-2α in cancer cell chemosensitivity and provide new insights for modifying the chemosensitivity of cancer cells by activating apoptotic pathways.
Destruction Box–Dependent Degradation of Aurora B Is Mediated by the Anaphase-Promoting Complex/Cyclosome and Cdh1
Authors: Stewart Scott , Fang Guowei 
Published: October 2005

Abstract
Aurora B kinase, a subunit of the chromosomal passenger protein complex, plays essential roles in spindle assembly, chromosome bi-orientation, and cytokinesis. The kinase activity of Aurora B, which peaks in mitosis, is tightly controlled in the cell cycle. Modulation of Aurora B protein levels could partly account for the regulation of its kinase activity in the cell cycle. However, little is known on the molecular mechanism of regulation of Aurora B levels. Here, we examined Aurora B protein levels and confirmed that they fluctuate during the cell cycle, peaking in mitosis and dropping drastically in G1. This profile for Aurora B in the cell cycle is reminiscent of those for substrates of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase essential for mitotic progression. Indeed, Aurora B is a substrate of APC/C both in vitro and in vivo. Aurora B is efficiently ubiquitinated in an in vitro reconstituted system by APC/C that had been activated by Cdh1. The recognition of Aurora B by APC/C-Cdh1 is specific as it requires the presence of a conserved D-box at the COOH terminus of Aurora B. Furthermore, endogenous Aurora B and Cdh1 form a complex exclusively in mitotic cells. Degradation of Aurora B at the end of mitosis requires Cdh1 in vivo as a reduction of the Cdh1 level by RNA interference stabilizes the Aurora B protein. We conclude that, as a key mitotic regulator, Aurora B is regulated both by its activation during early mitosis and by its destruction by APC/C-Cdh1 in late mitosis and in G1.
Atm Heterozygosity Cooperates with Loss of Brca1 to Increase the Severity of Mammary Gland Cancer and Reduce Ductal Branching
Authors: Bowen T.J. , Yakushiji Hiroyuki , Montagna Cristina , Jain Sonia , Ried Thomas , Wynshaw-Boris Anthony 
Published: October 2005

Abstract
The role of homozygous ataxia telangiectasia mutated (ATM) mutations in familial and sporadic forms of cancer is well established, but the contribution of ATM heterozygosity to mammary gland and other cancers has been controversial. To test the effect of Atm heterozygosity on mammary gland cancer, mice with complete loss of exon 11 of Brca1 specifically in mammary epithelium (Brca1-MG-Δex11) were studied in either Atm heterozygous or Atm wild-type backgrounds. Targeted deletion of Brca1 in mammary epithelium resulted in carcinomas and adenocarcinomas of varying histology with long (&gt;9 months) latency. Latency to tumorigenesis was found to be unchanged in the Brca1-MG-Δex11;Atm heterozygous mice compared with Brca1-MG-Δex11;Atm wild-type mice. However, the mice displayed variable tumor severity and differences in mammary tissue development. Mammary tumors from Brca1-MG-Δex11;Atm heterozygous mice were anaplastic and undifferentiated in all 20 tumors tested, whereas tumors from mice that were Brca1-MG-Δex11 but wild-type for Atm displayed variable histologic profiles, with some anaplastic tumors and other differentiated and less invasive tumor types. Previously reported developmental defects for Brca1-deficient mice were also observed in our model with and without Atm heterozygosity, but Brca1-MG-Δex11;Atm heterozygous mice displayed decreased ductal branching during puberty, a phenotype that was not observed in Brca1-MG-Δex11;Atm wild-type mice. Our results provide evidence that Atm heterozygosity influences severity of mammary gland tumors in the Brca1-MG-Δex11 tumor-prone mouse and suggest that this mutation leads to a newly characterized developmental defect during glandular maturation.
Expression of the EWS/FLI-1 Oncogene in Murine Primary Bone-Derived Cells Results in EWS/FLI-1–Dependent, Ewing Sarcoma–Like Tumors
Authors: Castillero-Trejo Yeny , Eliazer Susan , Xiang Lilin , Richardson James A. , Ilaria Robert L. 
Published: October 2005

Abstract
Ewing sarcoma is the second most common malignant pediatric bone tumor. Over 80% of Ewing sarcoma contain the oncogene EWS/FLI-1, which encodes the EWS/FLI-1 oncoprotein, a hybrid transcription factor comprised of NH2-terminal sequences from the RNA-binding protein EWS and the DNA-binding and COOH-terminal regions of the Ets transcription factor FLI-1. Although numerous genes are dysregulated by EWS/FLI-1, advances in Ewing sarcoma cancer biology have been hindered by the lack of an animal model because of EWS/FLI-1–mediated cytotoxicity. In this study, we have developed conditions for the isolation and propagation of murine primary bone-derived cells (mPBDC) that stably express EWS/FLI-1. Early-passage EWS/FLI-1 mPBDCs were immortalized in culture but inefficient at tumor induction, whereas later-passage cells formed sarcomatous tumors in immunocompetent syngeneic mice. Murine EWS/FLI-1 tumors contained morphologically primitive cells that lacked definitive lineage markers. Molecular characterization of murine EWS/FLI-1 tumors revealed that some but not all had acquired a novel, clonal in-frame p53 mutation associated with a constitutive loss of p21 expression. Despite indications that secondary events facilitated EWS/FLI-1 mPBDC tumorigenesis, cells remained highly dependent on EWS/FLI-1 for efficient transformation in clonogenic assays. This Ewing sarcoma animal model will be a useful tool for dissecting the molecular pathogenesis of Ewing sarcoma and provides rationale for the broader use of organ-specific progenitor cell populations for the study of human sarcoma.
Breast Cancer Cells Stimulate Neutrophils to Produce Oncostatin M: Potential Implications for Tumor Progression
Authors: Queen Marisa M. , Ryan Randall E. , Holzer Ryan G. , Keller-Peck Cynthia R. , Jorcyk Cheryl L. 
Published: October 2005

AbstractTumor-associated and tumor-infiltrating neutrophils (TAN) and macrophages (TAM) can account for as much as 50% of the total tumor mass in invasive breast carcinomas. It is thought that tumors secrete factors that elicit a wound-repair response from TAMs and TANs and that this response inadvertently stimulates tumor progression. Oncostatin M is a pleiotropic cytokine belonging to the interleukin-6 family that is expressed by several cell types including activated human T lymphocytes, macrophages, and neutrophils. Whereas oncostatin M can inhibit the proliferation of breast cancer cells in vitro, recent studies suggest that oncostatin M may promote tumor progression by enhancing angiogenesis and metastasis. In addition, neutrophils can be stimulated to synthesize and rapidly release large quantities of oncostatin M. In this article, we show that human neutrophils secrete oncostatin M when cocultured with MDA-MB-231 and T47D human breast cancer cells. Neutrophils isolated from whole blood or breast cancer cells alone express little oncostatin M by immunocytochemistry and ELISA, but neutrophils express and release high levels of oncostatin M when they are cocultured with breast cancer cells. In addition, we show that granulocyte-macrophage colony-stimulating factor produced by breast cancer cells and cell-cell contact are both necessary for the release of oncostatin M from neutrophils. Importantly, neutrophil-derived oncostatin M induces vascular endothelial growth factor from breast cancer cells in coculture and increases breast cancer cell detachment and invasive capacity, suggesting that neutrophils and oncostatin M may promote tumor progression in vivo.
Epidermal Growth Factor–Independent Transformation of Ba/F3 Cells with Cancer-Derived Epidermal Growth Factor Receptor Mutants Induces Gefitinib-Sensitive Cell Cycle Progression
Authors: Jiang Jingrui , Greulich Heidi , Jänne Pasi A. , Sellers William R. , Meyerson Matthew , Griffin James D. 
Published: October 2005

AbstractEpidermal growth factor receptor (EGFR) plays critical roles in many biological processes and in tumorigenesis. Here, we show that two mutated EGFRs found in lung and other malignancies, EGFR-G719S and EGFR-L858R, could transform Ba/F3 cells to interleukin-3 (IL-3)–independent growth, in a ligand-independent manner, an activity associated with the transforming function of other mutated tyrosine kinases. The mutated receptors are autophosphorylated in the absence of IL-3 without EGF stimulation, and their expression led to the constitutive activation of signal transducers and activators of transcription 5, extracellular signal-regulated kinase 1/2 (ERK1/2), ERK5, and AKT. In wild-type EGFR-expressing Ba/F3 cells, the major EGF-mediated signaling pathways were still intact. Gefitinib inhibited the growth of mutant EGFR-transformed Ba/F3 cells. Strikingly, the gefitinib sensitivity of cells expressing the L858R mutant was significantly greater than that of cells expressing the G719S mutant form, suggesting that distinct EGFR mutations may be differentially sensitive to small-molecule inhibitors. Furthermore, our data showed an antiproliferative effect of gefitinib on the EGFR-transformed Ba/F3 cells. Our results provide a model system to study the function of mutated EGFR and the differential effects of pharmacologic EGFR inhibition on the distinct mutant forms of this tyrosine kinase.
A Functional Role for Hemostasis in Early Cancer Development
Authors: Boccaccio Carla , Comoglio Paolo M. 
Published: October 2005

Abstract
Blood coagulation disorders have been known to be associated with cancer for many years. However, the mechanisms responsible for their relationship have not been understood. Recent work indicates that activation of the MET oncogene, which drives invasion and metastasis in cancer, can promote a cancer-associated thrombohemorrhagic syndrome that is mediated by transcriptional up-regulation of the procoagulation factors plasminogen activator inhibitor type-1 and cyclooxygenase-2. These findings reveal a long-sought mechanistic link between coagulation and cancer, highlighting a clinically important perspective on malignant invasion and metastasis.
Atypical Protein Kinase Cι Is an Oncogene in Human Non–Small Cell Lung Cancer
Authors: Regala Roderick P. , Weems Capella , Jamieson Lee , Khoor Andras , Edell Eric S. , Lohse Christine M. , Fields Alan P. 
Published: October 2005

Abstract
Protein kinase C (PKC) isozymes have long been implicated in carcinogenesis. However, little is known about the functional significance of these enzymes in human cancer. We recently showed that the atypical PKC (aPKC) isozyme PKCι is overexpressed in human non–small cell lung cancer (NSCLC) cells and that PKCι plays a critical role in the transformed growth of the human lung adenocarcinoma A549 cell line in vitro and tumorigenicity in vivo. Here we provide compelling evidence that PKCι is an oncogene in NSCLC based on the following criteria: (a) aPKCι is overexpressed in the vast majority of primary NSCLC tumors; (b) tumor PKCι expression levels predict poor survival in patients with NSCLC; (c) the PKCι gene is frequently amplified in established NSCLC cell lines and primary NSCLC tumors; (d) gene amplification drives PKCι expression in NSCLC cell lines and primary NSCLC tumors; and (e) disruption of PKCι signaling with a dominant negative PKCι allele blocks the transformed growth of human NSCLC cells harboring PKCι gene amplification. Taken together, our data provide conclusive evidence that PKCι is required for the transformed growth of NSCLC cells and that the PKCι gene is a target for tumor-specific genetic alteration by amplification. Interestingly, PKCι expression predicts poor survival in NSCLC patients independent of tumor stage. Therefore, PKCι expression profiling may be useful in identifying early-stage NSCLC patients at elevated risk of relapse. Our functional data indicate that PKCι is an attractive target for development of novel, mechanism-based therapeutics to treat NSCLC.
Barriers to Medical Nutrition Therapy in Black Women With Type 2 Diabetes Mellitus
Authors: Galasso Pamela , Amend Allison , Melkus Gail D. , Nelson Genice T. 
Published: October 2005

Purpose The purpose of this study was to explore food purchasing, preparation, and consumption among black women with type 2 diabetes mellitus (T2DM) in an urban setting to assess barriers to medical nutrition therapy recommendations. Methods A telephone survey was developed to assess shopping habits, the use of community resources for food supplementation, use of restaurant/fast-food establishments, dining habits, food purchasing and consumption, and food preparation methods. This 38-item questionnaire provided both frequencies and trends regarding participants’ dietary habits. Results Black women identified ways in which their participation in a culturally competent intervention of diabetes care and education helped them to change dietary behaviors. The most common areas of change included purchasing, preparation, and portion size. Barriers to medical nutrition therapy identified included low income, time constraints, competing demands, and knowledge deficits. Conclusions Culturally sensitive diabetes interventions are an effective way to overcome some of the barriers to medical nutrition therapy. Feedback provided by this survey suggests that identification of more affordable healthy food resources in the community is necessary. In addition, access issues such as transportation to grocery stores should be on the agenda for public policy issues. Finally, alternate sites for nutrition education, such as a supermarket forum, warrant further investigation.
Synthesis of N-Aryl Pyridin-2-ones via Ligand Coupling Reactions Using Pentavalent Organobismuth Reagents
Authors: Ikegai Kazuhiro , Mukaiyama Teruaki 
Published: October 2005

Abstract
An efficient method for the synthesis of N-aryl pyridin-2-ones was established by way of ligand coupling reactions using pentavalent organobismuth reagents such as triarylbismuth dichlorides.
Adsorption-induced Self-fusion of Cationic Gold Nanoparticles on Tobacco Mosaic Virus (TMV)
Authors: Yonezawa Tetsu , Onoue Shin-ya , Kimizuka Nobuo 
Published: October 2005

Abstract
The surface of tobacco mosaic virus (TMV) is densely coated by quaternary ammonium-modified gold nanoparticles. By dropping gold nanoparticle dispersions onto TMV pre-cast substrates (“after-staining method”), nanoparticles are spontaneously adsorbed on TMVs. The adsorbed nanoparticles were fused to form semi-continuous structures. This observation indicates the possibility of preparing 1-D arrays from wide variety of nanosized materials, by using TMV tubules as templates.
Fifteen years of dancing with vanadium
Authors: Crans Debbie C. 
Published: October 2005

Abstract
The advances in vanadium chemistry over the past 15 years are discussed in the areas of solution chemistry, coordination chemistry, and bioinorganic chemistry and will be presented using the perspectives of "What exists in solution?", "What is its structure?", "How does it react?", and "What are its biological effects?". Current and future challenges will be described briefly.
Sustainable vanadium(V)-catalyzed oxybromination of styrene: Two-phase system versus ionic liquids
Authors: Conte Valeria , Floris Barbara , Galloni Pierluca , Silvagni Adriano 
Published: October 2005

Abstract
Oxybromination reaction of styrene was performed in a two-phase system of water/ionic liquids (ILs). The aim of the work was to make the mild and efficient two-phase system previously developed for the vanadium(V)-catalyzed oxybromination of alkenes, inspired by the activity of haloperoxidase enzymes, even more interesting from a sustainable point of view. As in that case, a brominating intermediate was formed from the metal catalyst, H2O2, and bromide ion in the acid aqueous phase, but chlorinated solvents were replaced with ILs.
[bmim+][PF6
-], [bm2im+][PF6
-], [bmim+][BF4
-], [bmim+][CF3SO3
-], and [bmim+][(CF3SO2)2N-] were tested. We report on interesting results in terms of reaction rates and selectivities.
Neutron physics in the early 1930s
Authors: DE GREGORIO ALBERTO G. 
Published: October 2005

ABSTRACT:
Dawning neutron physics was more complex than one might expect. The chance that the neutron comprised a proton and an electron was diffusely taken into account after the discovery of the neutron. Moreover, uncertainties persisted about the composition of beryllium radiation until it was realized that the latter comprised both neutrons and γ-rays. The interaction of neutrons with matter and nuclei was soon investigated. Both a spatial symmetry, a symmetry of charge, and a symmetry in the nuclear reactions soon emerged. The relation of negative β-decay to the neutron abundance in nuclei was moreover reviewed. Positive β-radioactivity induced by α-particles was eventually announced, having been foreseen some weeks before. Accelerated deutons and protons shortly afterwards revealed to be efficient in inducing radioactivity. The physics institute in Rome got ready to start research on neutrons, but apparently it only planned to go through α-induced radioactivity, at first. If so, it is then plausible that some new results achieved by foreign laboratories eventually bent Fermi to neutrons. Fermi's discovery of neutron-induced radioactivity is reviewed with regard to investigations then current, once more showing simplicity as a distinctive trait of Fermi's way of doing physics.
After the famine: Plant pathology, Phytophthora infestans, and the late blight of potatoes, 1845–1960
Authors: TURNER R. STEVEN 
Published: October 2005

ABSTRACT:
The late blight disease of potatoes, which triggered the great Irish famine of 1845-1849, remains one of the most feared and intractable plant diseases today. Decades of dispute about the cause of the disease followed the outbreak of 1845, and the scientifi c controversy illustrates the uneasy historical relationship among farmers, scientifi c agronomists, and plant pathologists. Consensus fi nally emerged that the fungus Phytophthora infestans was the true cause of the disease, but that organism's full life cycle remained obscure. Its sexual oospores could not be readily obtained by mycologists, despite sporadic reports that had been observed. The 20th century opened with great optimism that resistant varieties could be developed using dominant R-genes obtainable from some wild species, and this optimism led to a proliferation of public breeding programs between 1925 and 1935. But these hopes had foundered by the early 1950s with the inexplicable appearance of new fungal races that could overwhelm the most blight-resistant germplasm. The Rockefeller Foundation's postwar agricultural initiative in Mexico led during the 1950s to dramatic and unexpected solutions to some of the late blight puzzles. But even then the fungus remained obscure, and effective, non-chemical control methods have never been forthcoming. This article examines the historical frustrations of late-blight science and advances that history as a case study illustrating the rise and fall of an “heroic age” of resistance breeding and plant pathology in the first half of the 20th century.
Del déficit a la insolvencia. Finanzas y real hacienda en Yucatán, 1760 –1816
Authors: Quezada Sergio , Acevedo Elda Moreno 
Published: October 2005

A lo largo de la segunda mitad del siglo XVIII la provincia de Yucatán enfrentó un permanente déficit hacendario como resultado de su creciente gasto militar. La sangría de recursos por parte de la Metrópoli y la desarticulación del sistema fiscal colonial, resultado de la guerra de Independencia, llevaron a Yucatán en 1814 a una crisis financiera. Este artículo analiza, desde la perspectiva de las finanzas coloniales, el déficit fiscal y los mecanismos para solventarlo. El estudio se sustenta en la organización de los ramos hacendarios bajo los principios fiscales coloniales.
During the second half of the eighteenth-century the province of Yucatan faced a permanent fiscal deficit as a result of the increasing military expenses. The continuos draining from Spain and the disarticulation of the colonial fiscal system as well as the effects of the independence war lead Yucatan into a financial crisis. This article analizes the fiscal deficit and the strategies to solve it from the colonial finances perspective. In order to accomplish this, the organization of the fields of the royal treasury, under the colonial fiscal principles was necessary.
Sistema financiero, banca privada y crédito agrícola en México, 1897–1913: ¿Un desencuentro anunciado?
Authors: Riguzzi Paolo 
Published: October 2005

El artículo abordalas relaciones entre el sistema financiero y la agricultura, desde la ley bancaria de 1897 hasta 1913, último año en que los bancos mantuvieron operaciones regulares. Se pretende medir el acceso de las unidades productivas al crédito de largo plazo y reconstruir los canales de financiamiento. La pregunta central es si y en qué condiciones los bancos u otros intermediarios financieros encauzaban una oferta de crédito hacia el sector agrícola y en qué términos. O si, por otro lado, la banca privada manifestaba una incapacidad estructural para acomodar en sus actividades el crédito agrícola; en este caso se pretende conocer qué caminos alternativos estaban disponibles y qué consecuencias derivaron de ello.
The article deals with the relationships between the financial system and agriculture, from the first Banking Law in 1897 until the last year of bank operations before the Revolution, 1913. It aims at reconstructing the credit channels and measuring the access of rural estates to long-term credit. The central question is whether banks or other financial intermediaries supplied funds to Mexican agriculture, and in what terms. Was private banking structurally incapable of providing agricultural credit? And if so, were alternative means available? What consequences this situation had on the rural economy?