bluuebunny/crossref_metadata_2025_split huggingface dataset:
The stable traits of melanoma genetics: an alternate approach to target discovery
Authors: Spivey Tara L , De Giorgi Valeria , Zhao Yingdong , Bedognetti Davide , Pos Zoltan , Liu Qiuzhen , Tomei Sara , Ascierto Maria Libera , Uccellini Lorenzo , Reinboth Jennifer , Chouchane Lotfi , Stroncek David F , Wang Ena , Marincola Francesco M 
Published: April 2012

Abstract

Background
The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number.

Results
Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis.

Conclusions
This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.
Role of CD40 ligation in dendritic cell semimaturation
Authors: Gerlach Anna-Maria , Steimle Alexander , Krampen Lea , Wittmann Alexandra , Gronbach Kerstin , Geisel Julia , Autenrieth Ingo B , Frick Julia-Stefanie 
Published: April 2012

AbstractBackgroundDC are among the first antigen presenting cells encountering bacteria at mucosal surfaces, and play an important role in maintenance of regular homeostasis in the intestine. Upon stimulation DC undergo activation and maturation and as initiators of T cell responses they have the capacity to stimulate naïve T cells. However, stimulation of naïve murine DC withB. vulgatusor LPS at low concentration drives DC to a semimature (sm) state with low surface expression of activation-markers and a reduced capacity to activate T-cells. Additionally, semimature DC are nonresponsive to subsequent TLR stimulation in terms of maturation, TNF-α but not IL-6 production. Ligation of CD40 is an important mechanism in enhancing DC maturation, function and capacity to activate T-cells. We investigated whether the DC semimaturation can be overcome by CD40 ligation.ResultsUpon CD40 ligation smDC secreted IL-12p40 but not the bioactive heterodimer IL-12p70. Additionally, CD40 ligation of smDC resulted in an increased production of IL-6 but not in an increased expression of CD40. Analysis of the phosphorylation pattern of MAP kinases showed that in smDC the p38 phosphorylation induced by CD40 ligation is inhibited. In contrast, phosphorylation of ERK upon CD40 ligation was independent of the DC maturation state.ConclusionOur data show that the semimature differentiation state of DC can not be overcome by CD40 ligation. We suggest that the inability of CD40 ligation in overcoming DC semimaturation might contribute to the tolerogenic phenotype of semimature DC and at least partially account for maintenance of intestinal immune homeostasis.
Inhibitory effect of Bifidobacterium infantis-mediated sKDR prokaryotic expression system on angiogenesis and growth of Lewis lung cancer in mice
Authors: Li Zhao-Jun , Zhu Hong , Ma Bu-Yun , Zhao Fen , Mao Shu-Hua , Liu Tai-Guo , He Jian-Ping , Deng Li-Cong , Yi Cheng , Huang Ying 
Published: April 2012

Abstract

Background
To construct the Bifidobacterium infantis-mediated soluble kinase insert domain receptor (sKDR) prokaryotic expression system and to observe its inhibitory effect on growth of human umbilicus vessel endothelial cells (HUVECs) in vitro and Lewis lung cancer (LLC) on mice in vivo.

Methods
The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed through electroporation and subsequently identified through PCR and Western blot analysis. HUVECs were added to the products of this system to evaluate the anti-angiogenesis effect through MTT assay in vitro. The LLC mice models were divided into three groups: one group treated with saline (group a); one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT plasmid group (group b); and one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid group (group c). The quality of life and survival of mice were recorded. Tumor volume, tumor weight, inhibitive rate, and necrosis rate of tumor were also evaluated. Necrosis of tumor and signals of blood flow in tumors were detected through color Doppler ultrasound. In addition, microvessel density (MVD) of the tumor tissues was assessed through CD31 immunohistochemical analysis.

Results
The positively transformed Bifidobacterium infantis with recombinant pTRKH2-PsT/sKDR plasmid was established, and was able to express sKDR at gene and protein levels. The proliferation of HUVECs cultivated with the extract of positively transformed bacteria was inhibited significantly compared with other groups (P < 0. 05). The quality of life of mice in group c was better than in group a and b. The recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid enhanced the efficacy of tumor growth suppression and prolongation of survival, increased the necrosis rate of tumor significantly, and could obviously decrease MVD and the signals of blood flow in tumors.

Conclusion
The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed successfully. This system could express sKDR at gene and protein levels and significantly inhibit the growth of HUVECs induced by VEGF in vitro. Moreover, it could inhibit tumor growth and safely prolong the survival time of LLC C57BL/6 mice.
The use of complementary and alternative medicine by people with cardiovascular disease: a systematic review
Authors: Grant Suzanne J , Bin Yu Sun , Kiat Hosen , Chang Dennis Hsu-Tung 
Published: April 2012

Abstract

Background
Complementary and alternative medicine (CAM) may offer benefits as well as risks to people with cardiovascular disease. Understanding the prevalence and the nature of CAM use will encourage beneficial CAM therapies, prevent potential herb-drug interactions and foster communication between patients and physicians.

Methods
A systematic search of eight bibliographic databases was conducted for studies that investigated CAM use in patients with cardiovascular diseases. Two independent reviewers selected relevant abstracts and evaluated the quality of included studies.

Results
Twenty-seven studies were included. Prevalence of CAM use in cardiac patients ranged from 4% - 61%. Biologically-based therapies usage ranged from 22% to 68%. Herbal medicines were used by between 2% and 46%. A large proportion of patients did not inform medical practitioners about their CAM use and up to 90% of treating physicians did not discuss CAM use with their patients.

Conclusions
CAM use in patients with cardiovascular disease appears common. The findings suggest that the effects of CAM on medical management of cardiovascular disease may be overlooked and that patient-physician communication need to be strengthened.
Reliability and validity of the Korean standard pattern identification for stroke (K-SPI-Stroke) questionnaire
Authors: Kang Byoung-Kab , Park Tae-Yong , Lee Ju Ah , Moon Tae-Woong , Ko Mi Mi , Choi Jiae , Lee Myeong Soo 
Published: April 2012

Abstract

Background
The present study was conducted to examine the reliability and validity of the ‘Korean Standard Pattern Identification for Stroke (K-SPI-Stroke)’, which was developed and evaluated within the context of traditional Korean medicine (TKM).

Methods
Between September 2006 and December 2010, 2,905 patients from 11 Korean medical hospitals were asked to complete the K-SPI-Stroke questionnaire as a part of project ' Fundamental study for the standardization and objectification of pattern identification in traditional Korean medicine for stroke (SOPI-Stroke). Each patient was independently diagnosed by two TKM physicians from the same site according to one of four patterns, as suggested by the Korea Institute of Oriental Medicine: 1) a Qi deficiency pattern, 2) a Dampness-phlegm pattern, 3) a Yin deficiency pattern, or 4) a Fire-heat pattern. We estimated the internal consistency using Cronbach’s α coefficient, the discriminant validity using the means score of patterns, and the predictive validity using the classification accuracy of the K-SPI-Stroke questionnaire.

Results
The K-SPI-Stroke questionnaire had satisfactory internal consistency (α = 0.700) and validity, with significant differences in the mean of scores among the four patterns. The overall classification accuracy of this questionnaire was 65.2 %.

Conclusion
These results suggest that the K-SPI-Stroke questionnaire is a reliable and valid instrument for estimating the severity of the four patterns.
Using routine data to monitor inequalities in an acute trust: a retrospective study
Authors: Langford Katharine M , Bottle Alex , Aylin Paul P , Ward Helen 
Published: April 2012

AbstractBackgroundReducing inequalities is one of the priorities of the National Health Service. However, there is no standard system for monitoring inequalities in the care provided by acute trusts. We explore the feasibility of monitoring inequalities within an acute trust using routine data.MethodsA retrospective study of hospital episode statistics from one acute trust in London over three years (2007 to 2010). Waiting times, length of stay and readmission rates were described for seven common surgical procedures. Inequalities by age, sex, ethnicity and social deprivation were examined using multiple logistic regression, adjusting for the other socio-demographic variables and comorbidities. Sample size calculations were computed to estimate how many years of data would be ideal for this analysis.ResultsThis study found that even in a large acute trust, there was not enough power to detect differences between subgroups. There was little evidence of inequalities for the outcome and process measures examined, statistically significant differences by age, sex, ethnicity or deprivation were only found in 11 out of 80 analyses. Bariatric surgery patients who were black African or Caribbean were more likely than white patients to experience a prolonged wait (longer than 64 days, aOR = 2.47, 95% CI: 1.36-4.49). Following a coronary angioplasty, patients from more deprived areas were more likely to have had a prolonged length of stay (aOR = 1.66, 95% CI: 1.25-2.20).ConclusionsThis study found difficulties in using routine data to identify inequalities on a trust level. Little evidence of inequalities in waiting time, length of stay or readmission rates by sex, ethnicity or social deprivation were identified although some differences were identified which warrant further investigation. Even with three years of data from a large trust there was little power to detect inequalities by procedure. Data will therefore need to be pooled from multiple trusts to detect inequalities.
Central obesity is important but not essential component of the metabolic syndrome for predicting diabetes mellitus in a hypertensive family-based cohort. Results from the Stanford Asia-pacific program for hypertension and insulin resistance (SAPPHIRe) Taiwan follow-up study
Authors: Lee I-Te , Chiu Yen-Feng , Hwu Chii-Min , He Chih-Tsueng , Chiang Fu-Tien , Lin Yu-Chun , Assimes Themistocles , Curb J David , Sheu Wayne H-H 
Published: April 2012

Abstract

Background
Metabolic abnormalities have a cumulative effect on development of diabetes, but only central obesity has been defined as the essential criterion of metabolic syndrome (MetS) by the International Diabetes Federation. We hypothesized that central obesity contributes to a higher risk of new-onset diabetes than other metabolic abnormalities in the hypertensive families.

Methods
Non-diabetic Chinese were enrolled and MetS components were assessed to establish baseline data in a hypertensive family-based cohort study. Based on medical records and glucose tolerance test (OGTT), the cumulative incidence of diabetes was analyzed in this five-year study by Cox regression models. Contribution of central obesity to development of new-onset diabetes was assessed in subjects with the same number of positive MetS components.

Results
Among the total of 595 subjects who completed the assessment, 125 (21.0%) developed diabetes. Incidence of diabetes increased in direct proportion to the number of positive MetS components (P ≪ 0.001). Although subjects with central obesity had a higher incidence of diabetes than those without (55.7 vs. 30.0 events/1000 person-years, P ≪ 0.001), the difference became non-significant after adjusting of the number of positive MetS components (hazard ratio = 0.72, 95%CI: 0.45-1.13). Furthermore, in all participants with three positive MetS components, there was no difference in the incidence of diabetes between subjects with and without central obesity (hazard ratio = 1.04, 95%CI: 0.50-2.16).

Conclusion
In Chinese hypertensive families, the incidence of diabetes in subjects without central obesity was similar to that in subjects with central obesity when they also had the same number of positive MetS components. We suggest that central obesity is very important, but not the essential component of the metabolic syndrome for predicting of new-onset diabetes. (Trial registration: NCT00260910, ClinicalTrials.gov).
Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells
Authors: Buqué Aitziber , Muhialdin Jangi Sh , Muñoz Alberto , Calvo Begoña , Carrera Sergio , Aresti Unai , Sancho Aintzane , Rubio Itziar , López-Vivanco Guillermo 
Published: April 2012

Abstract

Background
Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA) is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC), and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet.

Results
In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and –independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS) and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC) to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis.

Conclusions
We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and –independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.
Runx2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B/GDF10) in lung cancer cells
Authors: Tandon Manish , Gokul Karthiga , Ali Syed A , Chen Zujian , Lian Jane , Stein Gary S , Pratap Jitesh 
Published: April 2012

Abstract

Background
The Runt-related transcription factor Runx2 is essential for bone development but is also implicated in progression of several cancers of breast, prostate and bone, where it activates cancer-related genes and promotes invasive properties. The transforming growth factor β (TGF-β) family member bone morphogenetic protein-3B (BMP-3B/GDF10) is regarded as a tumor growth inhibitor and a gene silenced in lung cancers; however the regulatory mechanisms leading to its silencing have not been identified.

Results
Here we show that Runx2 is highly expressed in lung cancer cells and downregulates BMP-3B. This inverse relationship between Runx2 and BMP-3B expression is further supported by increased expression of BMP-3B in mesenchymal cells from Runx2 deficient mice. The ectopic expression of Runx2, but not DNA binding mutant Runx2, in normal lung fibroblast cells and lung cancer cells resulted in suppression of BMP-3B levels. The chromatin immunoprecipitation studies identified that the mechanism of Runx2-mediated suppression of BMP-3B is due to the recruitment of Runx2 and histone H3K9-specific methyltransferase Suv39h1 to BMP-3B proximal promoter and a concomitant increase in histone methylation (H3K9) status. The knockdown of Runx2 in H1299 cells resulted in decreased histone H3K9 methylation on BMP-3B promoter and increased BMP-3B expression levels. Furthermore, co-immunoprecipitation studies showed a direct interaction of Runx2 and Suv39h1 proteins. Phenotypically, Runx2 overexpression in H1299 cells increased wound healing response to TGFβ treatment.

Conclusions
Our studies identified BMP-3B as a new Runx2 target gene and revealed a novel function of Runx2 in silencing of BMP-3B in lung cancers. Our results suggest that Runx2 is a potential therapeutic target to block tumor suppressor gene silencing in lung cancer cells.
Nuclear overexpression of metastasis-associated protein 1 correlates significantly with poor survival in nasopharyngeal carcinoma
Authors: Li Wen-Fei , Liu Na , Cui Rui-Xue , He Qing-Mei , Chen Mo , Jiang Ning , Sun Ying , Zeng Jing , Liu Li-Zhi , Ma Jun 
Published: April 2012

AbstractBackgroundMetastasis-associated protein 1 (MTA1) has been associated with poor prognosis in several malignant carcinomas. The purpose of this study was to investigate the expression and prognostic value of MTA1 in nasopharyngeal carcinoma (NPC).MethodsMTA1 expression was assessed using immunohistochemistry in paraffin-embedded tumor specimens from 208 untreated NPC patients. Cox regression analysis was used to calculate the hazard ratio (HR), 95% confidence interval (CI) and identify independent prognostic factors, and recursive partitioning analysis was used to create a decision tree.ResultsNuclear overexpression of MTA1 was observed in 48.6% (101/208) of the NPC tissues. Nuclear overexpression of MTA1 correlated positively with N classification (P= 0.02), clinical stage (P= 0.04), distant metastasis (P< 0.01) and death (P= 0.01). Additionally, nuclear overexpression of MTA1 correlated significantly with poorer distant metastasis-free survival (DMFS;P<0.01) and poorer overall survival (OS;P< 0.01). MTA1 had prognostic significance in NPC patients with stage II disease, but not stage III or IV disease. Multivariate analysis demonstrated that nuclear overexpression of MTA1 was independently associated with poorer DMFS (HR, 2.05; 95% CI, 1.13–3.72;P= 0.02) and poorer OS (HR, 1.98; 95% CI, 1.09–3.59;P= 0.03). Using recursive partitioning analysis, the NPC patients could be classified with a low, intermediate or high risk of distant metastasis and death, on the basis of clinical stage, age and MTA1 expression.ConclusionThe results of this study suggest that nuclear overexpression of MTA1 correlates significantly with poorer DMFS and poorer OS in NPC. MTA1 has potential as a novel prognostic biomarker in NPC.
Carbon-modified TiO2 for photocatalysis
Authors: Wojtoniszak Malgorzata , Dolat Diana , Morawski Antoni , Mijowska Ewa 
Published: April 2012

Abstract
Here we present a method to produce TiO2 nanocrystals coated by thin layer of graphitic carbon. The coating process was prepared via chemical vapor deposition (CVD) with acetylene used as a carbon feedstock with TiO2 used as a substrate. Different temperatures (400°C and 500°C) and times (10, 20, and 60 s) of reaction were explored. The prepared nanocomposites were investigated by means of transmission electron microscopy, Raman spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy/diffuse reflectance spectroscopy and ultraviolet-vis (UV-vis)/diffuse reflectance spectroscopy. Furthermore, photocatalytic activity of the materials was investigated under visible and UV-vis light irradiation in the process of phenol decomposition. It was found that TiO2 modification with carbon resulted in a significant increase of photoactivity under visible irradiation and decrease under UV-vis light irradiation. Interestingly, a shorter CVD time and higher process temperature resulted in the preparation of the samples exhibiting higher activity in the photocatalytic process under visible light irradiation.
Face recognition using nonparametric-weighted Fisherfaces
Authors: Li Dong-Lin , Prasad Mukesh , Hsu Sheng-Chih , Hong Chao-Ting , Lin Chin-Teng 
Published: April 2012

Abstract
This study presents an appearance-based face recognition scheme called the nonparametric-weighted Fisherfaces (NW-Fisherfaces). Pixels in a facial image are considered as coordinates in a high-dimensional space and are transformed into a face subspace for analysis by using nonparametric-weighted feature extraction (NWFE). According to previous studies of hyperspectral image classification, NWFE is a powerful tool for extracting hyperspectral image features. The Fisherfaces method maximizes the ratio of between-class scatter to that of within-class scatter. In this study, the proposed NW-Fisherfaces weighted the between-class scatter to emphasize the boundary structure of the transformed face subspace and, therefore, enhances the separability for different persons' face. The proposed NW-Fisherfaces was compared with Orthogonal Laplacianfaces, Eigenfaces, Fisherfaces, direct linear discriminant analysis, and null space linear discriminant analysis methods for tests on five facial databases. Experimental results showed that the proposed approach outperforms other feature extraction methods for most databases.