bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas
Authors: Senkal Can E. , Ponnusamy Suriyan , Rossi Michael J. , Bialewski Jacek , Sinha Debijyati , Jiang James C. , Jazwinski S. Michal , Hannun Yusuf A. , Ogretmen Besim 
Published: February 2007

Abstract
In this study, quantitative isobologram studies showed that treatment with gemcitabine and doxorubicin, known inducers of ceramide generation, in combination, supra-additively inhibited the growth of human UM-SCC-22A cells in situ. Then, possible involvement of the human homologue of yeast longevity assurance gene 1 (LASS1)/C18-ceramide in chemotherapy-induced cell death in these cells was examined. Gemcitabine/doxorubicin combination treatment resulted in the elevation of mRNA and protein levels of LASS1 and not LASS2-6, which was consistent with a 3.5-fold increase in the endogenous (dihydro)ceramide synthase activity of LASS1 for the generation of C18-ceramide. Importantly, the overexpression of LASS1 (both human and mouse homologues) enhanced the growth-inhibitory effects of gemcitabine/doxorubicin with a concomitant induction of caspase-3 activation. In reciprocal experiments, partial inhibition of human LASS1 expression using small interfering RNA (siRNA) prevented cell death by about 50% in response to gemcitabine/doxorubicin. In addition, LASS1, and not LASS5, siRNA modulated the activation of caspase-3 and caspase-9, but not caspase-8, in response to this combination. Treatment with gemcitabine/doxorubicin in combination also resulted in a significant suppression of the head and neck squamous cell carcinoma (HNSCC) tumor growth in severe combined immunodeficiency mice bearing the UM-SCC-22A xenografts. More interestingly, analysis of endogenous ceramide levels in these tumors by liquid chromatography/mass spectroscopy showed that only the levels of C18-ceramide, the main product of LASS1, were elevated significantly (about 7-fold) in response to gemcitabine/doxorubicin when compared with controls. In conclusion, these data suggest an important role for LASS1/C18-ceramide in gemcitabine/doxorubicin-induced cell death via the activation of caspase-9/3 in HNSCC. [Mol Cancer Ther 2007;6(2):712–22]
R16, a novel amonafide analogue, induces apoptosis and G2-M arrest via poisoning topoisomerase II
Authors: Zhu Hong , Huang Min , Yang Fan , Chen Yi , Miao Ze-Hong , Qian Xu-Hong , Xu Yu-Fang , Qin Yu-Xin , Luo Hai-Bin , Shen Xu , Geng Mei-Yu , Cai Yu-Jun , Ding Jian 
Published: February 2007

Abstract
Amonafide, a naphthalimide derivative, although selected for exploratory clinical trials for its potent anticancer activity, has long been challenged by its unpredictable side effects. In the present study, a novel amonafide analogue, 2-(2-dimethylamino)-6-thia-2-aza-benzo-[def]-chrysene-1,3-diones (R16) was synthesized by substituting 5′-NH2 of the naphthyl with a heterocyclic group to amonafide, with additional introduction of a thiol group. In a panel of various human tumor cell lines, R16 was more cytotoxic than its parent compound amonafide. It was also effective against multidrug-resistant cells. Importantly, the i.p. administration of R16 inhibited tumor growth in mice implanted with S-180 sarcoma and H22 hepatoma. The molecular and cellular machinery studies showed that the R16 functions as a topoisomerase II (topo II) poison via binding to the ATPase domain of human topo IIα. The superior cytotoxicity of R16 to amonafide was ascribed to its potent effects on trapping topo II–DNA cleavage complexes. Moreover, using a topo II catalytic inhibitor aclarubicin, ataxia-telangiectasia-mutated (ATM)/ATM- and Rad3-related (ATR) kinase inhibitor caffeine and topo II–deficient HL-60/MX2 cells, we further showed that R16-triggered DNA double-strand breaks, tumor cell cycle arrest, and apoptosis were in a topo II–dependent manner. Taken together, R16 stood out by its improved anticancer activity, appreciable anti–multidrug resistance activities, and well-defined topo II poisoning mechanisms, as comparable with the parent compound amonafide. All these collectively promise the potential value of R16 as an anticancer drug candidate, which deserves further development. [Mol Cancer Ther 2007;6(2):484–95]
Waldenström macroglobulinemia
Authors: Vijay Arun , Gertz Morie A. 
Published: February 2007

AbstractIn the past 36 months, new developments have occurred both in the understanding of the biology of Waldenström macroglobulinemia (WM) and in therapeutic options for WM. Here, we review the classification, clinical features, and diagnostic criteria of the disease. WM is a B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and a monoclonal immunoglobulin M (IgM) protein. The symptoms of WM are attributable to the extent of tumor infiltration and to elevated IgM levels. The most common symptom is fatigue attributable to anemia. The prognostic factors predictive of survival include the patient's age, β2-microglobulin level, monoclonal protein level, hemoglobin concentration, and platelet count. Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. No specific agent or regimen has been shown to be superior to another for treatment of WM. Novel agents such as bortezomib, perifosine, atacicept, oblimersen sodium, and tositumomab show promise as rational targeted therapy for WM.
Novel gene expression patterns along the proximo-distal axis of the mouse embryo before gastrulation
Authors: Frankenberg Stephen , Smith Lee , Greenfield Andy , Zernicka-Goetz Magdalena 
Published: February 2007

Abstract

Background
To date, the earliest stage at which the orientation of the anterior-posterior axis in the mouse embryo is distinguishable by asymmetric gene expression is shortly after E5.5. At E5.5, prospective anterior markers are expressed at the distal tip of the embryo, whereas prospective posterior markers are expressed more proximally, close to the boundary with the extraembryonic region.

Results
To contribute to elucidating the mechanisms underlying the events involved in early patterning of the mouse embryo, we have carried out a microarray screen to identify novel genes that are differentially expressed between the distal and proximal parts of the E5.5 embryo. Secondary screening of resulting candidates by in situ hybridisation at E5.5 and E6.5 revealed novel expression patterns for known and previously uncharacterised genes, including Peg10, Ctsz1, Cubilin, Jarid1b, Ndrg1, Sfmbt2, Gjb5, Talia and Plet1. The previously undescribed gene Talia and recently identified Plet1 are expressed specifically in the distal-most part of the extraembryonic ectoderm, adjacent to the epiblast, and are therefore potential candidates for regulating early patterning events. Talia and the previously described gene XE7 define a gene family highly conserved among metazoans and with a predicted protein structure suggestive of a post-transcriptional regulative function, whilst Plet1 appears to be mammal-specific and of unknown function.

Conclusion
Our approach has allowed us to compare expression between dissected parts of the egg cylinder and has identified multiple genes with novel expression patterns at this developmental stage. These genes are potential candidates for regulating tissue interactions following implantation.
A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains
Authors: Hutchinson John N , Ensminger Alexander W , Clemson Christine M , Lynch Christopher R , Lawrence Jeanne B , Chess Andrew 
Published: February 2007

AbstractBackgroundNoncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment.ResultsThis screen identified no more than three transcripts;XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11:NEAT1, a noncoding RNA from the locus encoding forTncRNA, andNEAT2(also known asMALAT-1). While the twoNEATtranscripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs.NEAT2is extraordinarily well conserved for a noncoding RNA, more so than evenXIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts,NEAT1localizes to the periphery of such domains, whereas the neighboring transcript,NEAT2, is part of the long-sought polyadenylated component of nuclear speckles.ConclusionOur genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNAXISTandNEAT1andNEAT2. The function of these noncoding RNAs in mRNA metabolism is suggested by their high levels of conservation and their intimate association with SC35 splicing domains in multiple mammalian species.
Blockade of catecholamine-induced growth by adrenergic and dopaminergic receptor antagonists in Escherichia coli O157:H7, Salmonella enterica and Yersinia enterocolitica
Authors: Freestone Primrose PE , Haigh Richard D , Lyte Mark 
Published: February 2007

Abstract

Background
The ability of catecholamines to stimulate bacterial growth was first demonstrated just over a decade ago. Little is still known however, concerning the nature of the putative bacterial adrenergic and/or dopaminergic receptor(s) to which catecholamines (norepinephrine, epinephrine and dopamine) may bind and exert their effects, or even whether the binding properties of such a receptor are similar between different species.

Results
Use of specific catecholamine receptor antagonists revealed that only α, and not β, adrenergic antagonists were capable of blocking norepinephrine and epinephrine-induced growth, while antagonism of dopamine-mediated growth was achieved with the use of a dopaminergic antagonist. Both adrenergic and dopaminergic antagonists were highly specific in their mechanism of action, which did not involve blockade of catecholamine-facilitated iron-acquisition. Use of radiolabeled norepinephrine suggested that the adrenergic antagonists could be acting by inhibiting catecholamine uptake.

Conclusion
The present data demonstrates that the ability of a specific pathogen to respond to a particular hormone is dependent upon the host anatomical region in which the pathogen causes disease as well as the neuroanatomical specificity to which production of the particular hormone is restricted; and that both are anatomically coincidental to each other. As such, the present report suggests that pathogens with a high degree of exclusivity to the gastrointestinal tract have evolved response systems to neuroendocrine hormones such as norepinephrine and dopamine, but not epinephrine, which are found with the enteric nervous system.
Androgen responsive intronic non-coding RNAs
Authors: Louro Rodrigo , Nakaya Helder I , Amaral Paulo P , Festa Fernanda , Sogayar Mari C , da Silva Aline M , Verjovski-Almeida Sergio , Reis Eduardo M 
Published: February 2007

AbstractBackgroundTranscription of large numbers of non-coding RNAs originating from intronic regions of human genes has been recently reported, but mechanisms governing their biosynthesis and biological functions are largely unknown. In this work, we evaluated the existence of a common mechanism of transcription regulation shared by protein-coding mRNAs and intronic RNAs by measuring the effect of androgen on the transcriptional profile of a prostate cancer cell line.ResultsUsing a custom-built cDNA microarray enriched in intronic transcribed sequences, we found 39 intronic non-coding RNAs for which levels were significantly regulated by androgen exposure. Orientation-specific reverse transcription-PCR indicated that 10 of the 13 were transcribed in the antisense direction. These transcripts are long (0.5–5 kb), unspliced and apparently do not code for proteins. Interestingly, we found that the relative levels of androgen-regulated intronic transcripts could be correlated with the levels of the corresponding protein-coding gene (asGAS6andasDNAJC3) or with the alternative usage of exons (asKDELR2andasITGA6) in the corresponding protein-coding transcripts. Binding of the androgen receptor to a putative regulatory region upstream fromasMYO5A, an androgen-regulated antisense intronic transcript, was confirmed by chromatin immunoprecipitation.ConclusionAltogether, these results indicate that at least a fraction of naturally transcribed intronic non-coding RNAs may be regulated by common physiological signals such as hormones, and further corroborate the notion that the intronic complement of the transcriptome play functional roles in the human gene-expression program.
The HBZ-SP1 isoform of human T-cell leukemia virus type I represses JunB activity by sequestration into nuclear bodies
Authors: Hivin Patrick , Basbous Jihane , Raymond Frédéric , Henaff Daniel , Arpin-André Charlotte , Robert-Hebmann Véronique , Barbeau Benoit , Mesnard Jean-Michel 
Published: February 2007

Abstract

Background
The human T-cell leukemia virus type I (HTLV-I) basic leucine-zipper factor (HBZ) has previously been shown to modulate transcriptional activity of Jun family members. The presence of a novel isoform of HBZ, termed HBZ-SP1, has recently been characterized in adult T-cell leukemia (ATL) cells and has been found to be associated with intense nuclear spots. In this study, we investigated the role of these nuclear bodies in the regulation of the transcriptional activity of JunB.

Results
Using fluorescence microscopy, we found that the HBZ-SP1 protein localizes to intense dots corresponding to HBZ-NBs and to nucleoli. We analyzed the relative mobility of the EGFP-HBZ-SP1 fusion protein using fluorescence recovery after photobleaching (FRAP) analysis and found that the deletion of the ZIP domain perturbs the association of the HBZ-SP1 protein to the HBZ-NBs. These data suggested that HBZ needs cellular partners, including bZIP factors, to form HBZ-NBs. Indeed, by cotransfection experiments in COS cells, we have found that the bZIP factor JunB is able to target delocalized form of HBZ (deleted in its nuclear localization subdomains) into the HBZ-NBs. We also show that the viral protein is able to entail a redistribution of JunB into the HBZ-NBs. Moreover, by transfecting HeLa cells (known to express high level of JunB) with a vector expressing HBZ-SP1, the sequestration of JunB to the HBZ-NBs inhibited its transcriptional activity. Lastly, we analyzed the nuclear distribution of HBZ-SP1 in the presence of JunD, a Jun family member known to be activated by HBZ. In this case, no NBs were detected and the HBZ-SP1 protein was diffusely distributed throughout the nucleoplasm.

Conclusion
Our results suggest that HBZ-mediated sequestration of JunB to the HBZ-NBs may be causing the repression of JunB activity in vivo.
Isolated right atrial appendage (RAA) rupture in blunt trauma – a case report and an anatomic study comparing RAA and right atrium (RA) wall thickness
Authors: Figueiredo Adoniram M , Poggetti Renato S , Quintavalle Fabio G , Fontes Belchor , Dalva Moise , Younes Riad N , Jatene Fabio B , Birolini Dario 
Published: February 2007

Abstract

Background
Heart chambers rupture in blunt trauma is uncommon and is associated with a high mortality. The determinant factors, and the incidence of isolated heart chambers rupture remains undetermined. Isolated rupture of the right atrium appendage (RAA) is very rare, with 8 cases reported in the reviewed literature. The thin wall of the RAA has been presumed to render this chamber more prone to rupture in blunt trauma.

Objective
To report a case of isolated RAA rupture in blunt trauma, and to compare right atrium (RA) and RAA wall thickness in a necropsy study.

Methods
The thickness of RA and RAA wall of hearts from cadavers of fatal penetrating head trauma victims was measured. Our case of isolated RAA rupture is presented. The main findings of the 8 cases reported in the literature, and the findings of our case, were organized in a table.

Result
The comparison of the data showed that wall thickness of the RAA (0.53 ± 0.33 mm) was significantly thinner than that of RA (1.11 ± 0.42 mm) (p < 0.05).

Comments
In all these 9 cases of isolated RAA rupture, cardiac tamponade occurred, RAA rupture was diagnosed intraoperatively and sutured, and the patients survived. Main mechanisms hypothesized for heart chamber rupture include mechanical compression coincident with phases of cardiac cycle, leading to high hydrostatic pressure inside the chamber. Published series include numerous cases of RA rupture, and only a few cases of RAA rupture.

Conclusion
Thus, our data suggests that wall thickness is not a determinant factor for RA or RAA rupture in blunt trauma.
Effect of the medical emergency team on long-term mortality following major surgery
Authors: Jones Daryl , Egi Moritoki , Bellomo Rinaldo , Goldsmith Donna 
Published: February 2007

Abstract
Introduction
Introducing an intensive care unit (ICU)-based medical emergency team (MET) into our hospital was associated with decreased postoperative in-hospital mortality after major surgery. The purpose of the present study was to assess the effect of the MET and other variables on long-term mortality in this patient population.

Methods
We conducted a prospective, controlled, before-and-after trial in a University-affiliated hospital. Participants included consecutive patients admitted for major surgery (surgery requiring hospital stay > 48 hours) during a four month control phase and a four month MET phase. The intervention involved the introduction of a hospital-wide ICU-based MET service to evaluate and treat ward patients with acutely deranged vital signs. Information on long-term mortality was obtained from the Australian death registry. The main outcome measure was patient mortality at 1500 days. Data on patient demographics, surgery undertaken and whether the surgery was scheduled or unscheduled was obtained from the hospital electronic database. Multivariable analysis was conducted to determine independent predictors of 1500-day mortality.

Results
There were 1,369 major operations in 1,116 patients during the control period and 1,313 operations in 1,067 patients during the MET (intervention) period. Overall survival at 1500 days was 65.8% in the control period and 71.6% during the MET period (P = 0.001). Patients in the control phase were statistically less likely to be admitted under orthopaedic surgery, urology and faciomaxillary surgery units, but more likely to be admitted under cardiac surgery or neurosurgery units. Patients in the MET period were less likely to undergo unscheduled surgery. Multivariable analysis revealed that age, unscheduled surgery and admission under thoracic surgery, neurosurgery, oncology and general medicine were independent predictors of increased 1500-day mortality. Admission during the MET period was also an independent predictor of decreased 1500-day mortality (odds ratio 0.74; P = 0.005).

Conclusion
Introduction of a MET service in a teaching hospital was associated with increased long-term survival even after adjusting for other factors that contribute to long-term surgical mortality.
The Use of Simulation in Emergency Medicine: A Research Agenda
Authors: Bond William F. , Lammers Richard L. , Spillane Linda L. , Smith‐Coggins Rebecca , Fernandez Rosemarie , Reznek Martin A. , Vozenilek John A. , Gordon James A. 
Published: February 2007

AbstractMedical simulation is a rapidly expanding area within medical education. In 2005, the Society for Academic Emergency Medicine Simulation Task Force was created to ensure that the Society and its members had adequate access to information and resources regarding this new and important topic. One of the objectives of the task force was to create a research agenda for the use of simulation in emergency medical education. The authors present here the consensus document from the task force regarding suggested areas for research. These include opportunities to study reflective experiential learning, behavioral and team training, procedural simulation, computer screen–based simulation, the use of simulation for evaluation and testing, and special topics in emergency medicine. The challenges of research in the field of simulation are discussed, including the impact of simulation on patient safety. Outcomes‐based research and multicenter efforts will serve to advance simulation techniques and encourage their adoption.
What Is the Most Cost-Effective Population-Based Cancer Screening Program for Chinese Women?
Authors: Woo Pauline P.S. , Kim Jane J. , Leung Gabriel M. 
Published: February 2007

Purpose To develop a policy-relevant generalized cost-effectiveness (CE) model of population-based cancer screening for Chinese women. Methods Disability-adjusted life-years (DALYs) averted and associated screening and treatment costs under population-based screening using cervical cytology (cervical cancer), mammography (breast cancer), and fecal occult blood testing (FOBT), sigmoidoscopy, FOBT plus sigmoidoscopy, or colonoscopy (colorectal cancer) were estimated, from which average and incremental CE ratios were generated. Probabilistic sensitivity analysis was undertaken to assess stochasticity, parameter uncertainty, and model assumptions. Results Cervical, breast, and colorectal cancers were together responsible for 13,556 DALYs (in a 1:4:3 ratio, respectively) in Hong Kong's 3.4 million female population annually. All status quo strategies were dominated, thus confirming the suboptimal efficiency of opportunistic screening. Current patterns of screening averted 471 DALYs every year, which could potentially be more than doubled to 1,161 DALYs under the same screening and treatment budgetary threshold of US $50 million with 100% Pap coverage every 4 years and 30% coverage of colonoscopy every 10 years. With higher budgetary caps, biennial mammographic screening starting at age 50 years can be introduced. Conclusion Our findings have informed how best to achieve allocative efficiency in deploying scarce cancer care dollars but must be coupled with better integrated care planning, improved intersectoral coordination, increased resources, and stronger political will to realize the potential health and economic gains as demonstrated.