bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ablation of Sphingosine Kinase-2 Inhibits Tumor Cell Proliferation and Migration
Authors: Gao Peng , Smith Charles D. 
Published: September 2011

Abstract
Sphingosine kinases (SK) regulate the balance between proapoptotic ceramides and mitogenic sphingosine-1-phosphate (S1P); however, the functions of the two isoenzymes (SK1 and SK2) in tumor cells are not well defined. Therefore, RNA interference was used to assess the individual roles of SK1 and SK2 in tumor cell sphingolipid metabolism, proliferation, and migration/invasion. Treatment of A498, Caki-1, or MDA-MB-231 cells with siRNAs specific for SK1 or SK2 effectively suppressed the expression of the target mRNA and protein. Ablation of SK1 did not affect mRNA or protein levels of SK2 and reduced intracellular levels of S1P while elevating ceramide levels. In contrast, ablation of SK2 elevated mRNA, protein, and activity levels of SK1 and increased cellular S1P levels. Interestingly, cell proliferation and migration/invasion were suppressed more by SK2-selective ablation than by SK1-selective ablation, showing that the increased S1P does not rescue these phenotypes. Similarly, exogenous S1P did not rescue the cells from the antiproliferative or antimigratory effects of the siRNAs. Consistent with these results, differential effects of SK1- and SK2-selective siRNAs on signaling proteins, including p53, p21, ERK1, ERK2, FAK, and VCAM1, indicate that SK1 and SK2 have only partially overlapping functions in tumor cells. Overall, these data indicate that loss of SK2 has stronger anticancer effects than does suppression of SK1. Consequently, selective inhibitors of SK2 may provide optimal targeting of this pathway in cancer chemotherapy. Mol Cancer Res; 9(11); 1509–19. ©2011 AACR.
Phase III Trial of Selenium to Prevent Prostate Cancer in Men with High-grade Prostatic Intraepithelial Neoplasia: SWOG S9917
Authors: Marshall James R. , Tangen Catherine M. , Sakr Wael A. , Wood David P. , Berry Donna L. , Klein Eric A. , Lippman Scott M. , Parnes Howard L. , Alberts David S. , Jarrard David F. , Lee W. Robert , Gaziano J. Michael , Crawford E. David , Ely Benjamin , Ray Michael , Davis Warren , Minasian Lori M. , Thompson Ian M. 
Published: September 2011

Abstract
The threat of prostate cancer and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of prostate cancer and substantial evidence suggests that men with HGPIN are in need of prostate cancer prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against prostate cancer motivated the study we report here: a double-blind, randomized, placebo-controlled trial of selenium 200 (μg/d) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to prostate cancer over a 3-year period. This National Cancer Institute Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212 selenium and 211 placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium and 75.5%, placebo) had a Gleason score of 6 or less than 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced prostate cancer risk (relative risk = 0.82; 95% CI: 0.40–1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (&lt;106 ng/mL). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on prostate cancer risk. The 36% prostate cancer rate in men with HGPIN indicates the association of this lesion with an elevated prostate cancer risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics. Cancer Prev Res; 4(11); 1761–9. ©2011 AACR.
Boxing Bladder Cancer with COX-2–specific Inhibition
Authors: Kelly John D. , Hall Emma 
Published: September 2011

Abstract
Preventing recurrence of non–muscle-invasive bladder cancer (NMIBC) is important for improving patient well-being and reducing the health economic burden of this disease. To date, no oral agent has shown sufficient benefit to be adopted in clinical practice, where current strategies rely on topical (intravesical) administration of chemotherapy and immunotherapy. In this issue of the journal (beginning on page 1580), Sabichi and colleagues report the first phase II randomized controlled trial of the COX-2 inhibitor celecoxib in bladder cancer. The trial set out to measure an overly ambitious effect size but nevertheless showed encouraging signs of celecoxib activity. It lends support to COX-2 inhibition in NMIBC, which is being tested in several subsequent trials, and to the need for conclusive evidence. Cancer Prev Res; 4(10); 1534–5. ©2011 AACR.
Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease
Authors: Reynolds Harmony R. , Srichai Monvadi B. , Iqbal Sohah N. , Slater James N. , Mancini G.B. John , Feit Frederick , Pena-Sing Ivan , Axel Leon , Attubato Michael J. , Yatskar Leonid , Kalhorn Rebecca T. , Wood David A. , Lobach Iryna V. , Hochman Judith S. 
Published: September 2011

Background—
There is no angiographically demonstrable obstructive coronary artery disease (CAD) in a significant minority of patients with myocardial infarction, particularly women. We sought to determine the mechanism(s) of myocardial infarction in this setting using multiple imaging techniques.

Methods and Results—
Women with myocardial infarction were enrolled prospectively, before angiography, if possible. Women with ≥50% angiographic stenosis or use of vasospastic agents were excluded. Intravascular ultrasound was performed during angiography; cardiac magnetic resonance imaging was performed within 1 week. Fifty women (age, 57±13 years) had median peak troponin of 1.60 ng/mL; 11 had ST-segment elevation. Median diameter stenosis of the worst lesion was 20% by angiography; 15 patients (30%) had normal angiograms. Plaque disruption was observed in 16 of 42 patients (38%) undergoing intravascular ultrasound. There were abnormal myocardial cardiac magnetic resonance imaging findings in 26 of 44 patients (59%) undergoing cardiac magnetic resonance imaging, late gadolinium enhancement (LGE) in 17 patients, and T2 signal hyperintensity indicating edema in 9 additional patients. The most common LGE pattern was ischemic (transmural/subendocardial). Nonischemic LGE patterns (midmyocardial/subepicardial) were also observed. Although LGE was infrequent with plaque disruption, T2 signal hyperintensity was common with plaque disruption.

Conclusions—
Plaque rupture and ulceration are common in women with myocardial infarction without angiographically demonstrable obstructive coronary artery disease. In addition, LGE is common in this cohort of women, with an ischemic pattern of injury most evident. Vasospasm and embolism are possible mechanisms of ischemic LGE without plaque disruption. Intravascular ultrasound and cardiac magnetic resonance imaging provide complementary mechanistic insights into female myocardial infarction patients without obstructive coronary artery disease and may be useful in identifying potential causes and therapies.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00798122.
Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure
Authors: Montgomery Rusty L. , Hullinger Thomas G. , Semus Hillary M. , Dickinson Brent A. , Seto Anita G. , Lynch Joshua M. , Stack Christianna , Latimer Paul A. , Olson Eric N. , van Rooij Eva 
Published: September 2011

Background—
Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown.

Methods and Results—
Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment.

Conclusions—
These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression.
Marte Meo Counselling: a promising tool to support positive interactions between residents with dementia and nurses in nursing homes
Authors: Alnes Rigmor Einang , Kirkevold Marit , Skovdahl Kirsti 
Published: September 2011

Marte Meo Counselling (MMC) is an educational video-based counselling method developed to improve interactions between persons. This study aimed at investigating whether changes could be identified in the interactions between people with dementia and their nurses during morning care, following MMC. An intervention study based on video recordings before and after a MMC intervention was used. Thirteen nurses and 10 residents from six dementia-specific care units at six different institutions in Norway participated. Data were collected through video recording of six pairs (nurse and resident) in interaction before and after the staff received MMC. Four pairs participated as controls. The findings suggest that nurses who received MMC succeeded, to a greater degree than did the comparison nurses, in providing care consistent with promoting positive interactions. We found clearer indications of increased positive interactions and a reduction in inappropriate interactions in the intervention group. In the control group, the variation was greater, with both good and poor interactions present in the same cases. This study indicates that MMC can serve as a facilitator for positive interactions and can also lead to a reduction in inappropriate interactions. Further research is needed to evaluate the effect of MMC.
Post-registration interprofessional learning: a literature review and consideration of research methods
Authors: Norrie Peter , Thorpe Lucy N. , Karagic Lazar , Dyson Susan 
Published: September 2011

This review explores the literature with regards to interprofessional learning (IPL) for qualified nurses and other health care workers. Three research studies were found. These showed that IPL can promote interprofessional trust, knowledge and skills. There is as yet no evidence that patient outcomes are changed, and taken as a whole, the evidence is not strong. There is also evidence that the providers of IPL for post-registration health care workers also tend to be the researchers. This is not ideal; it raises the possibility of the inclusion of bias and, using the values of evidence based practice, weakens the evidence. It is suggested that workers who comment on their own IPL initiatives should make explicit the measures they have taken to minimise bias. Comparison of findings from the literature is made with pre-registration IPL and a tabulated summary of much of the published evidence is included, which may be a useful source for future authors in this field.
Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance
Authors: Mateos María-Victoria , Gutiérrez Norma C. , Martín-Ramos María-Luisa , Paiva Bruno , Montalbán María-Angeles , Oriol Albert , Martínez-López Joaquín , Teruel Ana-Isabel , Bengoechea Enrique , Martín Alejandro , Díaz-Mediavilla Joaquín , de Arriba Felipe , Palomera Luis , Hernández José-Mariano , Sureda Anna , Bargay Joan , Peñalver Francisco-Javier , Ribera Josep-Maria , Martín-Mateos María-Luisa , Fernández Manuela , García-Sanz Ramón , Vidriales María-Belén , Bladé Joan , Lahuerta Juan-José , San Miguel Jesús F. 
Published: September 2011

AbstractCytogenetic abnormalities (CAs) such as t(4;14), t(14;16) or del(17p), and nonhyperdiploidy are associated with poor prognosis in multiple myeloma. We evaluated the influence of CAs by FISH and DNA ploidy by flow cytometry on response and survival in 232 elderly, newly diagnosed multiple myeloma patients receiving an induction with weekly bortezomib followed by maintenance therapy with bortezomib-based combinations. Response was similar in the high-risk and standard-risk CA groups, both after induction (21% vs 27% complete responses [CRs]) and maintenance (39% vs 45% CR). However, high-risk patients showed shorter progression-free survival (PFS) than standard-risk patients, both from the first (24 vs 33 months; P = .04) and second randomization (17 vs 27 months; P = .01). This also translated into shorter overall survival (OS) for high-risk patients (3-year OS: 55% vs 77%; P = .001). This adverse prognosis applied to either t(4;14) or del(17p). Concerning DNA ploidy, hyperdiploid patients showed longer OS than nonhyperdiploid patients (77% vs 63% at 3 years; P = .04), and this was more evident in patients treated with bortezomib, thalidomide, and prednisone (77% vs 53% at 3 years; P = .02). The present schema does not overcome the negative prognosis of high-risk CAs and nonhyperdiploidy. This trial was registered with www.ClinicalTrials.gov as NCT00443235.
Transdifferentiation from cornea to lens in Xenopus laevis depends on BMP signalling and involves upregulation of Wnt signalling
Authors: Day Robert C , Beck Caroline W 
Published: September 2011

Abstract
Background
Surgical removal of the lens from larval Xenopus laevis results in a rapid transdifferention of central corneal cells to form a new lens. The trigger for this process is understood to be an induction event arising from the unprecedented exposure of the cornea to the vitreous humour that occurs following lens removal. The molecular identity of this trigger is unknown.

Results
Here, we have used a functional transgenic approach to show that BMP signalling is required for lens regeneration and a microarray approach to identify genes that are upregulated specifically during this process. Analysis of the array data strongly implicates Wnt signalling and the Pitx family of transcription factors in the process of cornea to lens transdifferentiation. Our analysis also captured several genes associated with congenital cataract in humans. Pluripotency genes, in contrast, were not upregulated, supporting the idea that corneal cells transdifferentiate without returning to a stem cell state. Several genes from the array were expressed in the forming lens during embryogenesis. One of these, Nipsnap1, is a known direct target of BMP signalling.

Conclusions
Our results strongly implicate the developmental Wnt and BMP signalling pathways in the process of cornea to lens transdifferentiation (CLT) in Xenopus, and suggest direct transdifferentiation between these two anterior eye tissues.
Comprehensive SNP array study of frequently used neuroblastoma cell lines; copy neutral loss of heterozygosity is common in the cell lines but uncommon in primary tumors
Authors: Kryh Hanna , Carén Helena , Erichsen Jennie , Sjöberg Rose-Marie , Abrahamsson Jonas , Kogner Per , Martinsson Tommy 
Published: September 2011

Abstract

Background
Copy neutral loss of heterozygosity (CN-LOH) refers to a special case of LOH occurring without any resulting loss in copy number. These alterations is sometimes seen in tumors as a way to inactivate a tumor suppressor gene and have been found to be important in several types of cancer.

Results
We have used high density single nucleotide polymorphism arrays in order to investigate the frequency and distribution of CN-LOH and other allelic imbalances in neuroblastoma (NB) tumors and cell lines. Our results show that the frequency of these near-CN-LOH events is significantly higher in the cell lines compared to the primary tumors and that the types of CN-LOH differ between the groups. We also show that the low-risk neuroblastomas that are generally considered to have a "triploid karyotype" often present with a complex numerical karyotype (no segmental changes) with 2-5 copies of each chromosome. Furthermore a comparison has been made between the three related cell lines SK-N-SH, SH-EP and SH-SY5Y with respect to overall genetic aberrations, and several aberrations unique to each of the cell lines has been found.

Conclusions
We have shown that the NB tumors analyzed contain several interesting allelic imbalances that would either go unnoticed or be misinterpreted using other genome-wide techniques. These findings indicate that the genetics underlying NB might be even more complex than previously known and that SNP arrays are important analysis tools. We have also showed that these near-CN-LOH events are more frequently seen in NB cell lines compared to NB tumors and that a set of highly related cell lines have continued to evolve secondary to the subcloning event. Taken together our analysis highlights that cell lines in many cases differ substantially from the primary tumors they are thought to represent, and that caution should be taken when drawing conclusions from cell line-based studies.
Peer-based behavioral health program for drug users in China: a pilot study
Authors: Shen Song-Ying , Zhang Zhou-Bin , Tucker Joseph D , Chang Helena , Zhang Guan-Rong , Lin Ai-Hua 
Published: September 2011

Abstract

Background
Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.

Methods
A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).

Results
Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.

Conclusions
This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.
Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast
Authors: Markey Oonagh , McClean Conor M , Medlow Paul , Davison Gareth W , Trinick Tom R , Duly Ellie , Shafat Amir 
Published: September 2011

Abstract

Background
Cinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal.

Methods
A single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined.

Results
Cinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal.

Conclusions
3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies.

Trial registration
Trial registration number: at http://www.clinicaltrial.gov: NCT01350284