bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focal Adhesion Kinase Targeting UsingIn vivoShort Interfering RNA Delivery in Neutral Liposomes for Ovarian Carcinoma Therapy
Authors: Halder Jyotsnabaran , Kamat Aparna A. , Landen Charles N. , Han Liz Y. , Lutgendorf Susan K. , Lin Yvonne G. , Merritt William M. , Jennings Nicholas B. , Chavez-Reyes Arturo , Coleman Robert L. , Gershenson David M. , Schmandt Rosemarie , Cole Steven W. , Lopez-Berestein Gabriel , Sood Anil K. 
Published: August 2006

AbstractPurpose: Focal adhesion kinase (FAK) plays a critical role in ovarian cancer cell survival and in various steps in the metastatic cascade. Based on encouraging in vitro results with FAK silencing, we examined the in vivo therapeutic potential of this approach using short interfering RNA (siRNA) in the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).Experimental Design: Therapy experiments of FAK siRNA with or without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8MDR in nude mice. Additional experiments with a cisplatin-resistant cell line (A2780-CP20) were also done. Assessments of angiogenesis (CD31), cell proliferation (proliferating cell nuclear antigen), and apoptosis (terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling) were done using immunohistochemical analysis.Results: A single dose of FAK siRNA-DOPC was highly effective in reducing in vivo FAK expression for up to 4 days as assayed by Western blot and immunohistochemical analysis. Therapy experiments were started 1 week after injection of the ovarian cancer cells. Treatment with FAK siRNA-DOPC (150 μg/kg twice weekly) reduced mean tumor weight by 44% to 72% in the three cell lines compared with the control group (Ps &lt; 0.05 for HeyA8, A2780-CP20, and SKOV3ip1). When FAK siRNA-DOPC was combined with docetaxel, there was even greater reduction in mean tumor weight in all models (all Ps &lt; 0.05). Similar results were observed in combination with cisplatin. Treatment with FAK siRNA-DOPC plus docetaxel resulted in decreased microvessel density, decreased expression of vascular endothelial growth factor and matrix metalloproteinase-9, and increased apoptosis of tumor-associated endothelial cells and tumor cells.Conclusions: Taken together, these findings suggest that FAK siRNA-DOPC plus docetaxel or platinum might be a novel therapeutic approach against ovarian cancer.
Copper Binding by Tetrathiomolybdate Attenuates Angiogenesis and Tumor Cell Proliferation through the Inhibition of Superoxide Dismutase 1
Authors: Juarez Jose C. , Betancourt Oscar , Pirie-Shepherd Steven R. , Guan Xiaojun , Price Melissa L. , Shaw David E. , Mazar Andrew P. , Doñate Fernando 
Published: August 2006

Abstract
Purpose: A second-generation tetrathiomolybdate analogue (ATN-224; choline tetrathiomolybdate), which selectively binds copper with high affinity, is currently completing two phase I clinical trials in patients with advanced solid and advanced hematologic malignancies. However, there is very little information about the mechanism of action of ATN-224 at the molecular level.
Experimental Design: The effects of ATN-224 on endothelial and tumor cell growth were evaluated in cell culture experiments in vitro. The antiangiogenic activity of ATN-224 was investigated using the Matrigel plug model of angiogenesis.
Results: ATN-224 inhibits superoxide dismutase 1 (SOD1) in tumor and endothelial cells. The inhibition of SOD1 leads to inhibition of endothelial cell proliferation in vitro and attenuation of angiogenesis in vivo. The inhibition of SOD1 activity in endothelial cells is dose and time dependent and leads to an increase in the steady-state levels of superoxide anions, resulting in the inhibition of extracellular signal-regulated kinase phosphorylation without apparent induction of apoptosis. In contrast, the inhibition of SOD1 in tumor cells leads to the induction of apoptosis. The effects of ATN-224 on endothelial and tumor cells could be substantially reversed using Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, a catalytic small-molecule SOD mimetic.
Conclusions: These data provide a distinct molecular target for the activity of ATN-224 and provide validation for SOD1 as a target for the inhibition of angiogenesis and tumor growth.
Up-Regulation of Endothelial Delta-like 4 Expression Correlates with Vessel Maturation in Bladder Cancer
Authors: Patel Nilay S. , Dobbie Michael S. , Rochester Mark , Steers Graham , Poulsom Richard , Le Monnier Karena , Cranston David W. , Li Ji-Liang , Harris Adrian L. 
Published: August 2006

Abstract
Purpose: Angiogenesis and vascular endothelial growth factor (VEGF) expression are associated with a poor outcome in bladder cancer. To understand more about the mechanisms, we studied the role of delta-like 4 (DLL4), an endothelial-specific ligand of the Notch signaling pathway, in bladder cancer angiogenesis.
Experimental Design: The expression of DLL4, CD34, and VEGF were studied in a cohort of 60 bladder tumors and 10 normal samples using quantitative PCR. In situ hybridization was used to study the pattern of DLL4 expression in 22 tumor and 9 normal samples. Serial sections were also stained for CD34 and α-smooth muscle actin (α-SMA) using conventional immunohistochemistry.
Results: The expression of DLL4 was significantly up-regulated in superficial (P &lt; 0.01) and invasive (P &lt; 0.05) bladder cancers. DLL4 expression significantly correlated with CD34 (P &lt; 0.001) and VEGF (P &lt; 0.001) expression. The in situ hybridization studies showed that DLL4 was highly expressed within bladder tumor vasculature. Additionally, DLL4 expression significantly correlated with vessel maturation as judged by periendothelial cell expression of α-SMA, 98.7% of DLL4-positive tumor vessels coexpressed α-SMA, compared with 64.5% of DLL4-negative tumor vessels (P &lt; 0.001). High DLL4 expression may have prognostic value in superficial and invasive bladder.
Conclusion: DLL4 expression is associated with vascular differentiation in bladder cancer; thus, targeting DLL4 may be a novel antiangiogenic therapy.
Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma
Authors: Hahtola Sonja , Tuomela Soile , Elo Laura , Häkkinen Tiina , Karenko Leena , Nedoszytko Boguslaw , Heikkilä Hannele , Saarialho-Kere Ulpu , Roszkiewicz Jadwiga , Aittokallio Tero , Lahesmaa Riitta , Ranki Annamari 
Published: August 2006

Abstract
Purpose: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes.
Experimental Design: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4+ cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression.
Results: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations.
Conclusions: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.
A Phase 1 Study of ABT-751, an Orally Bioavailable Tubulin Inhibitor, Administered Daily for 7 Days Every 21 Days in Pediatric Patients with Solid Tumors
Authors: Fox Elizabeth , Maris John M. , Widemann Brigitte C. , Meek Kysa , Goodwin Anne , Goodspeed Wendy , Kromplewski Marie , Fouts Molly E. , Medina Diane , Cho Steve Y. , Cohn Susan L. , Krivoshik Andrew , Hagey Anne E. , Adamson Peter C. , Balis Frank M. 
Published: August 2006

Abstract
Purpose: To determine the toxicity profile, dose-limiting toxicities, and maximum tolerated dose of ABT-751 administered orally once daily for 7 days, repeated every 21 days.
Experimental Design: Patients who were ≤18 years of age, with relapsed or refractory solid tumors, and who were able to swallow capsules were eligible. The starting dose was 100 mg/m2/d (n = 3) and was escalated to 130 mg/m2/d (n = 6), 165 mg/m2/d (n = 6), 200 mg/m2/d (n = 6), and 250 mg/m2/d (n = 2) in cohorts of three to six patients. The maximum tolerated dose was determined from dose-limiting toxicities occurring during the first treatment cycle.
Results: Twenty-four children (median age, 13 years; range, 4-18 years) were enrolled; 23 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 8), sarcomas (n = 8), primary brain tumors (n = 2), Wilms' tumor (n = 2), and other solid tumors (n = 3). Dose-limiting toxicities (grade 3 sensory and motor neuropathy, grade 3 hypertension, and grade 3 fatigue) were observed in patients enrolled at the 250 mg/m2/d dose level. The maximum tolerated dose of ABT-751 administered daily for 7 days every 21 days was 200 mg/m2/d. Non-dose-limiting toxicities at the maximum tolerated dose included anemia, fatigue, peripheral sensory neuropathy, abdominal pain, nausea, constipation, anorexia, fever, and weight loss. Myelosuppression was minimal at the maximum tolerated dose. The median number of cycles administered is 2 (range, 1-50). No significant ABT-751-related cumulative toxicities were observed.
Conclusion: ABT-751 is well tolerated in children. The recommended dose for phase 2 trials in solid tumors is 200 mg/m2/d administered orally, daily for 7 days every 21 days. This dose is &gt;40% higher than the maximum tolerated dose in adults receiving the same dosing schedule.
Molecular mimicry in the chronic myeloproliferative disorders: reciprocity between quantitative JAK2 V617F and Mpl expression
Authors: Moliterno Alison R. , Williams Donna M. , Rogers Ophelia , Spivak Jerry L. 
Published: August 2006

AbstractAn activating JAK2 mutation (JAK2 V617F) is present in the chronic myeloproliferative disorders (MPDs), polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocytosis (ET). JAK2 is also a chaperone for Mpl and responsible for its cell-surface expression. We observed a reciprocal relationship between neutrophil JAK2 V617F allele percentage and platelet Mpl expression in JAK2 V617F–positive PV, IMF, and ET patients. However, severely impaired platelet Mpl expression was present in JAK2 V617F–negative MPD patients. While JAK2 V617F allele status did not necessarily correlate with the clinical MPD phenotype, the degree of impaired platelet Mpl expression did. We conclude that multiple molecular abnormalities are involved in the pathogenesis of the MPDs and that aberrant Mpl expression may be a common denominator of aberrant signaling in both the JAK2 V617F–positive and JAK2 V617F–negative MPDs.
High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics
Authors: Heuser Michael , Beutel Gernot , Krauter Juergen , Döhner Konstanze , von Neuhoff Nils , Schlegelberger Brigitte , Ganser Arnold 
Published: August 2006

AbstractThe translocation t(12;22) involves MN1 and TEL and is rarely found in acute myeloid leukemia (AML). Recently, it has been shown in a mouse model that the fusion protein MN1-TEL can promote growth of primitive hematopoietic progenitor cells (HPCs) and, in cooperation with HOXA9, induce AML. We quantified MN1 expression by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) in 142 adult patients with AML with normal cytogenetics treated uniformly in trial AML-SHG 01/99. AML samples were dichotomized at the median MN1 expression. High MN1 expression was significantly correlated with unmutated NPM1 (P < .001), poor response to the first course of induction treatment (P = .02), a higher relapse rate (P = .03), and shorter relapse-free (P = .002) and overall survivals (P = .03). In multivariate analysis, MN1 expression was an independent prognostic marker (P = .02) in addition to age and Eastern Cooperative Oncology Group (ECOG) performance status. Excluding patients with NPM1mutated/FLT3ITDnegative, high MN1 expression was associated with shorter relapse-free survival (P = .057). MN1 was highly expressed in some patients with acute lymphoblastic but not chronic lymphocytic or myeloid leukemia. MN1 was highly expressed in HPCs compared with differentiated cells and was down-regulated during in vitro differentiation of CD34+ cells, suggesting a functional role in HPCs. In conclusion, our data suggest MN1 overexpression as a new prognostic marker in AML with normal cytogenetics.
Characterization of stem cell–like cancer cells in immune-competent mice
Authors: Kruger Jorg A. , Kaplan Charles D. , Luo Yunping , Zhou He , Markowitz Dorothy , Xiang Rong , Reisfeld Ralph A. 
Published: August 2006

AbstractRecently, the cancer stem cell hypothesis has gained significant recognition as the descriptor of tumorigenesis. Although previous studies relied on transplanting human or rat tumor cells into immunecompromised mice, our study used the Hoechst 33342 dye–based side population (SP) technique to isolate and transplant stem cell–like cancer cells (SCLCCs) from the 4T1 and NXS2 murine carcinoma cell lines into the immune-competent microenvironment of syngeneic mice. 4T1 cells displayed an SP of 2% with a Sca-1highc-Kit–CD45– phenotype, whereas NXS2 cells contained an SP of 0.2% with a Sca-1highCD24highc-Kit–CD45–GD high2 phenotype. Reverse transcription–polymerase chain reaction (RT-PCR) further revealed up-regulation in SP cells of ABCG2, Sca-1, Wnt-1, and TGF-β2. Additionally, 4T1 and NXS2 SP cells exhibited increased resistance to chemotherapy, and 4T1 SP cells also showed an increased ability to efflux doxorubicin, which correlated with a selective increase in the percentage of SP cells found in the tumors of doxorubicin-treated mice. Most importantly, SP cells showed a markedly higher repopulation and tumorigenic potential in vivo, which correlated with an increased number of cells in the SP compartment of SP-derived tumors. Taken together, these results show that we successfully characterized SCLCCs from 2 murine carcinoma cell lines in the immune-competent microenvironment of syngeneic mice.
Retrotranspositions in orthologous regions of closely related grass species
Authors: Du Chunguang , Swigoňová Zuzana , Messing Joachim 
Published: August 2006

Abstract

Background
Retrotransposons are commonly occurring eukaryotic transposable elements (TEs). Among these, long terminal repeat (LTR) retrotransposons are the most abundant TEs and can comprise 50–90% of the genome in higher plants. By comparing the orthologous chromosomal regions of closely related species, the effects of TEs on the evolution of plant genomes can be studied in detail.

Results
Here, we compared the composition and organization of TEs within five orthologous chromosomal regions among three grass species: maize, sorghum, and rice. We identified a total of 132 full or fragmented LTR retrotransposons in these regions. As a percentage of the total cumulative sequence in each species, LTR retrotransposons occupy 45.1% of the maize, 21.1% of the rice, and 3.7% of the sorghum regions. The most common elements in the maize retrotransposon-rich regions are the copia-like retrotransposons with 39% and the gypsy-like retrotransposons with 37%. Using the contiguous sequence of the orthologous regions, we detected 108 retrotransposons with intact target duplication sites and both LTR termini. Here, we show that 74% of these elements inserted into their host genome less than 1 million years ago and that many retroelements expanded in size by the insertion of other sequences. These inserts were predominantly other retroelements, however, several of them were also fragmented genes. Unforeseen was the finding of intact genes embedded within LTR retrotransposons.

Conclusion
Although the abundance of retroelements between maize and rice is consistent with their different genome sizes of 2,364 and 389 Mb respectively, the content of retrotransposons in sorghum (790 Mb) is surprisingly low. In all three species, retrotransposition is a very recent activity relative to their speciation. While it was known that genes re-insert into non-orthologous positions of plant genomes, they appear to re-insert also within retrotransposons, potentially providing an important role for retrotransposons in the evolution of gene function.
Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses
Authors: Jayapal Manikandan , Tay Hwee Kee , Reghunathan Renji , Zhi Liang , Chow Kah Kiong , Rauff Mary , Melendez Alirio J 
Published: August 2006

AbstractBackgroundMast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcεRI aggregation.ResultsOur data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation.ConclusionThis report represents a substantial advance in our understanding of the genome wide effects triggered by "passive sensitization" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses.
Infection by and protective immune responses against Plasmodium berghei ANKA are not affected in macrophage scavenger receptors A deficient mice
Authors: Cunha-Rodrigues Margarida , Portugal Sílvia , Febbraio Maria , Mota Maria M 
Published: August 2006

Abstract

Background
Scavenger receptors (SRs) recognize endogenous molecules modified by pathological processes as well as components of diverse microorganisms. Mice deficient for both SR-AI and II are more susceptible to infections by a variety of bacterial and viral pathogens.

Results
Here we show that SR-A deficient mice and wild type mice are equally susceptible to malaria infection both during liver and blood stages. Moreover, like wild type mice, SR-A deficient mice are able to mount a protective immune response against radiation attenuated sporozoites.

Conclusion
Our results do not reveal a function of SR-A I and II receptors in the Plasmodium berghei ANKA infection, both in the development of CM and parasitemia control. Moreover, these receptors appear not to be required for the establishment of a protective immune response against the malaria liver stages.
Water incident related hospital activity across England between 1997/8 and 2003/4: a retrospective descriptive study
Authors: Henderson Holly , Wilson Richard C 
Published: August 2006

Abstract

Background
No one has ever reported or investigated the number of people who have been admitted to hospital for a water related incident. The purpose of this paper is to examine, the hospital activity resulting from such incidents including to length of stay, gender, age and cause.

Methods
The data was extracted from the Hospital Episode Statistics (HES) for episodes with a mention of ICD 10 (V90–94, W15–16, W65–74, X38, X92, Y21) for the years 1997/8 to 2003/4. Population based rates and relative risk were calculated using the most recent Census data for England (2001).

Results
The 6,793 episodes resulted in a total of 32,520 bed days with an average of length of stay of 5.0 days. Males made up 73.7% (n = 5,006) of episodes and females 26.1% (n = 1,787). Annual trends peaked in 1999–2000 at a rate of 2.4 per 100,000 and have fluctuated on alternate years there after. In terms of relative risk males are at a 2.3 to 3.0 increased annual risk of being admitted compared to females, relating to a water event. The highest annual rates were observed within the 0 – 14 age group, ranging from 3.1 to 4.2 episodes per 100,000.

Conclusion
Based on these findings, for every one drowning that occurs per year there are three hospital episodes. Each of the age groups identified within the study reported an increase in hospital episodes between 2002 – 2003 and 2003 – 2004, when considering the fatality information available it would appear that although fatalities are decreasing in the similar time period, hospital episodes are increasing.
For the 0–14 age group, the cause of the injury had changed over the years, moving away from bath tub and swimming pool, to watercraft incidents (V91 – 93). For the 15 – 59 age group there had been a decline in the frequency of watercraft and water transport episodes, however, an increase in diving and jumping injury and incidents. In the over 60 age group water transport episodes remained the most frequent, with swimming pool related episodes declining and other specified drowning and submersion increasing.
More work needs to be undertaken in regard to who is admitted to hospital, when where, and how to fill gaps in knowledge and highlight information that is critical to prevention strategies.
Anticancer activity of extracts derived from the mature roots of Scutellaria baicalensis on human malignant brain tumor cells
Authors: Scheck Adrienne C , Perry Krya , Hank Nicole C , Clark W Dennis 
Published: August 2006

Abstract

Background
Flavonoid-rich extracts from the mature roots of Scutellaria baicalensis have been shown to exhibit antiproliferative effects on various cancer cell lines. We assessed the ability of an ethanolic extract of S. baicalensis root to inhibit the proliferation of malignant glioma cells.

Methods
Cell lines derived from primary and recurrent brain tumors from the same patient and cells selected for resistance to the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were used to identify antiproliferative effects of this extract when used alone and in conjunction with BCNU.

Results and discussion
Results indicated that Scutellaria baicalensis not only inhibits cellular growth in recurrent and drug resistant brain tumor cell lines, but also demonstrates an increased inhibitory effect when used in conjunction with BCNU.

Conclusion
The results of this study support the efficacy of S. baicalensis as an anticancer agent for glioblastomas multiforme and a potential adjuvant treatment to current chemotherapeutic agents used in the treatment of both primary and recurrent GBMs. Further studies of the effects of individual flavonoids alone and in combination with each other and with currently used therapies are needed.