bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Antitumor Activity of Anti-CD25 Recombinant Immunotoxin LMB-2 with Chemotherapy
Authors: Singh Rajat , Zhang Yujian , Pastan Ira , Kreitman Robert J. 
Published: November 2011

AbstractPurpose: Although anti-CD25 recombinant immunotoxin LMB-2 is effective against CD25+ hairy cell leukemia, activity against more aggressive diseases such as adult T-cell leukemia (ATL) is limited by rapid disease progression between treatment cycles. Our goal was to determine in vivo whether rapid growth of CD25+ tumor is associated with high levels of tumor interstitial soluble CD25 (sCD25) and whether chemotherapy can reduce tumor sCD25 and synergize with LMB-2.Experimental Design: Tumor xenografts expressing human CD25 were grown in mice, which were then treated with LMB-2 and chemotherapy either alone or in combination, and sCD25 level and antitumor activity were measured.Results: CD25+ human xenografts growing rapidly in nude mice had intratumoral sCD25 at levels that were between 21- and 2,200 (median 118)-fold higher than in serum, indicating that interstitial sCD25 interacts with LMB-2 in tumors. Intratumoral sCD25 levels were in the range 21 to 157 (median 54) ng/mL without treatment and 0.95 to 6.1 (median 2.6) ng/mL (P &lt; 0.0001) 1 day after gemcitabine administration. CD25+ xenografts that were too large to regress with LMB-2 alone were minimally responsive to gemcitabine alone but completely regressed with the combination. Ex vivo, different ratios of gemcitabine and LMB-2 were cytotoxic to the CD25+ tumor cells in an additive, but not synergistic, manner.Conclusions: Gemcitabine is synergistic with LMB-2 in vivo unrelated to improved cytotoxicity. Synergism, therefore, appears to be related to improved distribution of LMB-2 to CD25+ tumors, and is preceded by decreased sCD25 within the tumor because of chemotherapy. To test the concept of combined treatment clinically, patients with relapsed/refractory ATL are being treated with fludarabine plus cyclophosphamide before LMB-2. Clin Cancer Res; 18(1); 152–60. ©2011 AACR.
Two Distinct Routes to Oral Cancer Differing in Genome Instability and Risk for Cervical Node Metastasis
Authors: Bhattacharya Aditi , Roy Ritu , Snijders Antoine M. , Hamilton Gregory , Paquette Jesse , Tokuyasu Taku , Bengtsson Henrik , Jordan Richard C. K. , Olshen Adam B. , Pinkel Daniel , Schmidt Brian L. , Albertson Donna G. 
Published: November 2011

Abstract
Purpose: Problems in management of oral cancers or precancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors or risk for progression of precancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis.
Experimental Design: The spectrum of copy number alterations in oral dysplasia and squamous cell carcinomas (SCC) was determined by array comparative genomic hybridization. Associations with clinical characteristics were studied and results confirmed in an independent cohort.
Results: The presence of one or more of the chromosomal aberrations +3q24-qter, -8pter-p23.1, +8q12-q24.2, and +20 distinguishes a major subgroup (70%–80% of lesions, termed 3q8pq20 subtype) from the remainder (20%–30% of lesions, non-3q8pq20). The 3q8pq20 subtype is associated with chromosomal instability and differential methylation in the most chromosomally unstable tumors. The two subtypes differ significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts.
Conclusions: Two subtypes of oral lesions indicative of at least two pathways for oral cancer development were distinguished that differ in chromosomal instability and risk for metastasis, suggesting that +3q,–8p, +8q, and +20 constitute a biomarker with clinical utility for identifying patients at risk for metastasis. Moreover, although increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 locally invasive, yet not metastatic oral SCC. Clin Cancer Res; 17(22); 7024–34. ©2011 AACR.
The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms
Authors: Arcaini Luca , Zibellini Silvia , Boveri Emanuela , Riboni Roberta , Rattotti Sara , Varettoni Marzia , Guerrera Maria Luisa , Lucioni Marco , Tenore Annamaria , Merli Michele , Rizzi Silvia , Morello Lucia , Cavalloni Chiara , Da Vià Matteo C. , Paulli Marco , Cazzola Mario 
Published: November 2011

Abstract
The somatically acquired V600E mutation of the BRAF gene has been recently described as a molecular marker of hairy cell leukemia (HCL). We developed an allele-specific PCR for this mutation and studied 62 patients with HCL, 1 with HCL variant, 91 with splenic marginal zone lymphoma, 29 with Waldenström macroglobulinemia, and 57 with B-cell chronic lymphoproliferative disorders. The BRAF V600E mutation was detected in all HCL cases and in only 2 of the remaining 178 patients. These 2 subjects had B-cell chronic lymphoproliferative disorders that did not fulfill the diagnostic criteria for HCL. Despite the positive PCR finding, the mutation could not be detected by Sanger sequencing in these 2 cases, suggesting that it was associated with a small subclone. We conclude that the BRAF V600E mutation is present in all patients with HCL and that, in combination with clinical and morphologic features, represents a reliable molecular marker for this condition.
Transfer of in vivo primed transgenic T cells supports allergic lung inflammation and FIZZ1 and Ym1 production in an IL-4Rα and STAT6 dependent manner
Authors: Dasgupta Preeta , Chapoval Svetlana P , Smith Elizabeth P , Keegan Achsah D 
Published: November 2011

AbstractBackgroundCD4+ T helper type 2 (TH2) cells, their cytokines IL-4, IL-5 and IL-13 and the transcription factor STAT6 are known to regulate various features of asthma including lung inflammation, mucus production and airway hyperreactivity and also drive alternative activation of macrophages (AAM). However, the precise roles played by the IL-4/IL-13 receptors and STAT6 in inducing AAM protein expression and modulating specific features of airway inflammation are still unclear. Since TH2 differentiation and activation plays a pivotal role in this disease, we explored the possibility of developing an asthma model in mice using T cells that were differentiatedin vivo.ResultsIn this study, we monitored the activation and proliferation status of adoptively transferred allergen-specific naïve orin vivoprimed CD4+ T cells. We found that both the naïve andin vivoprimed T cells expressed similar levels of CD44 and IL-4. However,in vivoprimed T cells underwent reduced proliferation in a lymphopenic environment when compared to naïve T cells. We then used thesein vivogenerated effector T cells in an asthma model. Although there was reduced inflammation in mice lacking IL-4Rα or STAT6, significant amounts of eosinophils were still present in the BAL and lung tissue. Moreover, specific AAM proteins YM1 and FIZZ1 were expressed by epithelial cells, while macrophages expressed only YM1 in RAG2-/-mice. We further show that FIZZ1 and YM1 protein expression in the lung was completely dependent on signaling through the IL-4Rα and STAT6. Consistent with the enhanced inflammation and AAM protein expression, there was a significant increase in collagen deposition and smooth muscle thickening in RAG2-/-mice compared to mice deficient in IL-4Rα or STAT6.ConclusionsThese results establish that transfer ofin vivoprimed CD4+ T cells can induce allergic lung inflammation. Furthermore, while IL-4/IL-13 signaling through IL-4Rα and STAT6 is essential for AAM protein expression, lung inflammation and eosinophilia are only partially dependent on this pathway. Further studies are required to identify other proteins and signaling pathways involved in airway inflammation.
BRAD, the genetics and genomics database for Brassica plants
Authors: Cheng Feng , Liu Shengyi , Wu Jian , Fang Lu , Sun Silong , Liu Bo , Li Pingxia , Hua Wei , Wang Xiaowu 
Published: November 2011

Abstract

Background
Brassica species include both vegetable and oilseed crops, which are very important to the daily life of common human beings. Meanwhile, the Brassica species represent an excellent system for studying numerous aspects of plant biology, specifically for the analysis of genome evolution following polyploidy, so it is also very important for scientific research. Now, the genome of Brassica rapa has already been assembled, it is the time to do deep mining of the genome data.

Description
BRAD, the Brassica database, is a web-based resource focusing on genome scale genetic and genomic data for important Brassica crops. BRAD was built based on the first whole genome sequence and on further data analysis of the Brassica A genome species, Brassica rapa (Chiifu-401-42). It provides datasets, such as the complete genome sequence of B. rapa, which was de novo assembled from Illumina GA II short reads and from BAC clone sequences, predicted genes and associated annotations, non coding RNAs, transposable elements (TE), B. rapa genes' orthologous to those in A. thaliana, as well as genetic markers and linkage maps. BRAD offers useful searching and data mining tools, including search across annotation datasets, search for syntenic or non-syntenic orthologs, and to search the flanking regions of a certain target, as well as the tools of BLAST and Gbrowse. BRAD allows users to enter almost any kind of information, such as a B. rapa or A. thaliana gene ID, physical position or genetic marker.

Conclusion
BRAD, a new database which focuses on the genetics and genomics of the Brassica plants has been developed, it aims at helping scientists and breeders to fully and efficiently use the information of genome data of Brassica plants. BRAD will be continuously updated and can be accessed through http://brassicadb.org.
An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects
Authors: Phillips J Theodore , Fox Edward , Grainger William , Tuccillo Dianne , Liu Shifang , Deykin Aaron 
Published: November 2011

Abstract

Background
The ability to self-inject in patients with multiple sclerosis (MS) has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patients' independence. However, injection anxiety, needle phobia and disease-related disability are major barriers to a patient's ability to self-administer treatment. Use of an autoinjector may improve patients' ability to self-inject. This study evaluated the safe and effective use of Avonex Pen™ (prefilled pen), a single use autoinjector, for intramuscular delivery of interferon beta-1a (IM IFNβ-1a, Avonex) in MS patients.

Methods
This was a Phase IIIb, open-label, single-country, multicenter trial in MS patients currently using IM IFNβ-1a prefilled syringes. Patients received weekly 30 mcg IM IFNβ-1a treatment over 4 weeks. On Day 1, patients self-administered IM IFNβ-1a using a prefilled syringe at the clinic. On Day 8, patients received training on the prefilled pen and self-administered IM IFNβ-1a using the device. On Day 15, patients self-administered IM IFNβ-1a at home using the prefilled pen. A final injection occurred at the clinic on Day 22 when patients self-administered IM IFNβ-1a using the prefilled pen while clinic staff observed and completed a detailed questionnaire documenting patients' ability to self-inject with the device. Serum neopterin levels were evaluated pre and post-injection on Days 1 and 8. Adverse events were monitored throughout.

Results
Seventy-one (96%) patients completed the study. The overall success rate in safely and effectively using the prefilled pen was 89%. No device malfunctions occurred. One unsuccessful administration occurred at Day 22 due to patient error; no patient injury resulted. Patients gave the prefilled pen high ratings (8.7-9.3) on a 10-point scale for ease of use (0 = extremely difficult, 10 = extremely easy). Ninety-four percent of patients preferred the prefilled pen over the prefilled syringe. Induction of serum neopterin levels, serving as a biomarker for type 1 interferon action, was similar to that of the prefilled syringe. The prefilled pen demonstrated a safety profile comparable to the prefilled syringe.

Conclusions
The prefilled pen is a safe and effective device for administration of IM IFNβ-1a and represents an alternative method for self-injection for MS patients using this therapy.

Trial registration
This study is registered at clinicaltrials.gov, identifier: NCT00828204
Predicting insulin resistance using the triglyceride-to-high-density lipoprotein cholesterol ratio in Taiwanese adults
Authors: Chiang Jui-Kun , Lai Ning-Sheng , Chang Jiunn-Kae , Koo Malcolm 
Published: November 2011

Abstract

Background
The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) has been advocated as a simple clinical indicator of insulin resistance. Thresholds of TG/HDL-C appeared to depend on ethnicity. However, no studies have specifically compared the accuracy of TG/HDL-C with and without other clinical and demographic factors in predicting insulin resistance in Taiwanese adults. The aim of the present investigation was to use TG/HDL-C and other clinical available factors to predict insulin resistance in Taiwanese adults.

Methods
A total of 812 subjects were recruited from at the time of their general health examination at the Buddhist Dalin Tzu Chi General Hospital, Taiwan. Demographic information and clinical characteristics were obtained. Insulin resistance was defined by the homeostasis model assessment for insulin resistance (HOMA-IR). Simple and multiple logistic regression analyses were used to obtain probabilities of insulin resistance (HOMA-IR > 2) using TG/HDL-C with (Model 2) and without (Model 1) other clinical variables. A receiver operating characteristic (ROC) analysis was conducted to evaluate the ability of the two models to correctly discriminate between subjects of low and elevated HOMA-IR.

Results
Female sex, greater waist circumferences, and higher ALT levels were significantly associated with the risk of elevated HOMA-IR in addition to TG/HDL-C in the multiple logistic regression (Model 2). The area under the ROC curve (AUC) of Model 2 was 0.71 [95% CI = 0.67-0.75] and was significantly higher (P = 0.007) than the AUC 0.66 [95% CI = 0.62-0.71] of Model 1.

Conclusions
The diagnostic accuracy of insulin resistance, defined by HOMA-IR, using TG/HDL-C can be significantly enhanced by including three additional clinically available factors - sex, waist circumferences, and ALT levels.
Polyphenolic extract of lotus root (edible rhizome of Nelumbo nucifera) alleviates hepatic steatosis in obese diabetic db/db mice
Authors: Tsuruta Yumi , Nagao Koji , Kai Shunichi , Tsuge Keisuke , Yoshimura Takashi , Koganemaru Kazuyoshi , Yanagita Teruyoshi 
Published: November 2011

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease of industrialized countries. Thus, discovering food components that can ameliorate NAFLD is of interest. Lotus root, the edible rhizome of Nelumbo nucifera, contains high levels of polyphenolic compounds, and several health-promoting properties of lotus root have been reported. In this study, we tested whether feeding a polyphenolic extract of lotus root to db/db mice protects them from hepatic steatosis.

Results
After 3 weeks of feeding, the hepatomegaly and hepatic triglyceride accumulation were markedly alleviated in the lotus polyphenol-diet-fed db/db mice relative to the control mice. Although the lipolytic enzyme activity was not changed, the activities of lipogenic enzymes, such as fatty acid synthase and malic enzyme, were significantly lower in the lotus polyphenol diet-fed db/db mice. Additionally, the ESI-IT/MS and MALDI-TOF MS spectra revealed the presence of B-type proanthocyanidin polymers with polymerization degree up to 9 in the polyphenolic lotus root extract.

Conclusion
We speculate that the condensed tannins contained in lotus root can alleviate hepatic steatosis by suppressing the lipogenic enzyme activity in the livers of db/db mice.
Cytolytic replication of echoviruses in colon cancer cell lines
Authors: Israelsson Stina , Jonsson Nina , Gullberg Maria , Lindberg A Michael 
Published: November 2011

AbstractBackgroundColorectal cancer is one of the most common cancers in the world, killing nearly 50% of patients afflicted. Though progress is being made within surgery and other complementary treatments, there is still need for new and more effective treatments. Oncolytic virotherapy, meaning that a cancer is cured by viral infection, is a promising field for finding new and improved treatments. We have investigated the oncolytic potential of several low-pathogenic echoviruses with rare clinical occurrence. Echoviruses are members of the enterovirus genus within the familyPicornaviridae.MethodsSix colon cancer cell lines (CaCo-2, HT29, LoVo, SW480, SW620 and T84) were infected by the human enterovirus B species echovirus 12, 15, 17, 26 and 29, and cytopathic effects as well as viral replication efficacy were investigated. Infectivity was also tested in spheroids grown from HT29 cells.ResultsEchovirus 12, 17, 26 and 29 replicated efficiently in almost all cell lines and were considered highly cytolytic. The infectivity of these four viruses was further evaluated in artificial tumors (spheroids), where it was found that echovirus 12, 17 and 26 easily infected the spheroids.ConclusionsWe have found that echovirus 12, 17 and 26 have potential as oncolytic agents against colon cancer, by comparing the cytolytic capacity of five low-pathogenic echoviruses in six colon cancer cell lines and in artificial tumors.
Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study
Authors: Tartibian Bakhtyar , Hajizadeh Maleki Behzad , Kanaley Jill , Sadeghi Karim 
Published: November 2011

AbstractBackgroundEvidence indicates that dietary fats and physical activity influence bone health. The purpose of this study was to examine the effects of long-term aerobic exercise and omega-3 (N-3) supplementation on serum inflammatory markers, bone mineral density (BMD), and bone biomarkers in post-menopausal women.MethodsSeventy-nine healthy sedentary post-menopausal women aged 58-78 years participated in this study. Subjects were randomized to one of 4 groups: exercise + supplement (E+S, n = 21), exercise (E, n = 20), supplement (S, n = 20), and control (Con, n = 18) groups. The subjects in the E+S and E groups performed aerobic exercise training (walking and jogging) up to 65% of HRmax, three times a week for 24 weeks. Subjects in the E+S and S groups consumed 1000 mg/d N-3 for 24 weeks. The lumbar spine (L2-L4) and femoral neck BMD, serum tumor necrosis factor (TNF) α, interleukin (IL) 6, prostaglandin (PG) E2, estrogen, osteocalcin, 1, 25-dihydroxyvitamin D3(1, 25 Vit D), C-telopeptide (CTX), parathyroid hormone (PTH) and calcitonin (CT) were measured at baseline, the end of week 12 and 24.ResultsSerum estrogen, osteocalcin, 1, 25 Vit D, CT, L2-L4and femoral neck BMD measures increased (P< 0.05) and the serum CTX, PTH, TNF-α, IL-6, and PGE2decreased (P< 0.05) in E + S group after the 24 wk intervention but not in the E or S intervention groups. L2-L4and femoral neck BMD, estrogen, osteocalcin, and CT were negatively (P< 0.05) correlated with TNF-α and PGE2. PTH and CT were correlated positively and negatively with IL-6, respectively (P< 0.05).ConclusionsThe present study demonstrates that long-term aerobic exercise training plus N-3 supplementation have a synergistic effect in attenuating inflammation and augmenting BMD in post-menopausal osteoporosis.
The treatment of scaphoid nonunion using the Ilizarov fixator without bone graft, a study of 18 cases
Authors: Bumbaširević Marko , Tomić Slavko , Lešić Aleksandar , Bumbaširević Vesna , Rakočević Zoran , Atkinson Henry D 
Published: November 2011

AbstractObjectivesEvaluating the safety and efficacy of the Ilizarov fine-wire compression/distraction technique in the treatment of scaphoid nonunion (SNU), without the use of bone graft.DesignA retrospective review of 18 consecutive patients in one centre.Patients and Methods18 patients; 17 males; 1 female, with a mean SNU duration of 13.9 months. Patients with carpal instability, humpback deformity, carpal collapse, avascular necrosis or marked degenerative change, were excluded. Following frame application the treatment consisted of three stages: the frame was distracted 1 mm per day until radiographs showed a 2-3 mm opening at the SNU site (mean 10 days); the SNU site was then compressed for 5 days, at a rate of 1 mm per day, with the wrist in 15 degrees of flexion and 15 degrees of radial deviation; the third stage involved immobilization with the Ilizarov fixator for 6 weeks. The technique is detailed herein.ResultsRadiographic (CT) and clinical bony union was achieved in all 18 patients after a mean of 89 days (70-130 days). Mean modified Mayo wrist scores improved from 21 to 86 at a mean follow-up of 37 months (24-72 months), with good/excellent results in 14 patients. All patients returned to their pre-injury occupations and levels of activity at a mean of 117 days. Three patients suffered superficial K-wire infections, which resolved with oral antibiotics.ConclusionsIn these selected patients this technique safely achieved bony union without the need to open the SNU site and without the use of bone graft.
The ATP-binding cassette transporters ABCB1 and ABCC1 are not regulated by hypoxia in immortalised human brain microvascular endothelial cells
Authors: Patak Pauline , Jin Fengyan , Schäfer Simon T , Metzen Eric , Hermann Dirk M 
Published: November 2011

Abstract

Background
ATP-binding cassette transporters at the blood-brain barrier are actively regulated upon ischemic stroke in a way that impedes the access of pharmacological compounds to the brain tissue. The luminal endothelial transporter ABCB1 was recently shown to be increased, whereas the abluminal transporter ABCC1 was decreased on ischemic brain capillaries. In vitro studies using epithelial cells suggested that ABCB1 is regulated during hypoxia in a hypoxia-inducible factor (HIF)-1α-dependent way.

Methods
In order to investigate whether hypoxia might be responsible for the expression changes of ABCB1 and ABCC1 in the ischemic brain, the immortalised human brain microvascular endothelial cell line hCMEC/D3 was exposed to hypoxia (1%) or anoxia (0%). Cell lysates were analysed by Western blot to detect the protein expression of ABCB1, ABCC1, HIF-1α and HIF-2α.

Results
During hypoxia, an accumulation of HIF-1α and HIF-2α was noticed in hCMEC/D3 cells that followed different time kinetics. Both HIF-1α and HIF-2α abundance increased within 4 h of hypoxia. HIF-1α levels decreased to below detection levels within 16 h of hypoxia, whereas HIF-2α remained elevated even after 48 h. No changes of ABCB1 and ABCC1 expression were detected, neither on the mRNA nor protein level.

Conclusion
Our data suggests that other factors than hypoxia may be responsible for the expression changes of ATP-binding cassette transporters in the ischemic brain.