bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological and transcriptomic characterization of a fliA mutant of Pseudomonas putida KT2440
Authors: Rodríguez‐Herva José Juan , Duque Estrella , Molina‐Henares María Antonia , Navarro‐Avilés Gloria , Van Dillewijn Pieter , De La Torre Jesús , Molina‐Henares Antonio J. , La Campa Ana Sánchez‐de , Ran F. Ann , Segura Ana , Shingler Victoria , Ramos Juan‐Luis 
Published: October 2009

Summary Pseudomonas putida KT2440 encodes 23 alternative sigma factors. The fliA gene, which encodes σ28, is in a cluster with other genes involved in flagella biosynthesis and chemotaxis. Reverse transcriptase‐PCR revealed that this cluster is comprised of four independent transcriptional units: flhAF, fleNfliA, cheYZA and cheBmotAB. We generated a nonpolar fliA mutant by homologous recombination and tested its motility, adhesion to biotic and abiotic surfaces, and responses to various stress conditions. The mutant strain was nonmotile and exhibited decreased capacity to bind to corn seeds, although its ability to colonize the rhizosphere of plants was unaffected. The mutant was also affected in binding to abiotic surfaces and its ability to form biofilms decreased by almost threefold. In the fliA mutant background expression of 25 genes was affected: two genes were upregulated and 23 genes were downregulated. In addition to a number of motility and chemotaxis genes, the fliA gene product is also necessary for the expression of some genes potentially involved in amino acid utilization or stress responses; however, we were unable to assign specific phenotypes linked to these genes since the fliA mutant used the same range of amino acids as the parental strain, and was as tolerant as the wild type to stress imposed by heat, antibiotics, NaCl, sodium dodecyl sulfate, H2O2 and benzoate. Based on the sequence alignment of promoters recognized by FliA and genome in silico analysis, we propose that P. putidaσ28 recognizes a TCAAG‐t‐N12‐GCCGATA consensus sequence located between −34 and −8 and that this sequence is preferentially associated with an AT‐rich upstream region.
Screening of antenatal depression in Pakistan: risk factors and effects on obstetric and neonatal outcomes
Authors: Imran Nazish , Haider Imran Ijaz 
Published: October 2009

AbstractIntroduction: To determine the frequency of probable antenatal depression (AD) in pregnant women in third trimester, assess the risk factors and its impact on obstetric and neonatal outcomes in a developing country.Methods: A prospective study conducted in a tertiary care hospital in Lahore from March 2007 to July 2007. Two hundred and thirteen pregnant women in the third trimester, attending the Gynecology Outpatient Clinic were recruited. They were assessed by a semistructured questionnaire to gather demographic details and various risk factors for AD. AD was assessed by Edinburgh Postnatal Depression Scale. All women were followed until delivery to determine their obstetric and neonatal outcomes.Results: Out of 213 women, 91 (42.7%) scored above the cut‐off for AD. More women with depression reported problems in their marriage, problems with parents/in laws, history of domestic violence, past history of psychiatric problems and history of postnatal depression. In the obstetric risk factors history of previous miscarriages, stillbirths, and complications in previous pregnancy reached statistical significance. Thirty‐seven (17.3%) women were lost to follow up. Women with AD had more obstetric complications during delivery. Babies of mothers with AD had significantly low birth weight, as well as low mean APGAR scores at 1 and 5 minutes following birth.Discussion: AD is a common problem in Pakistani Society. In view of the risk factors and adverse outcomes associated with depression during pregnancy, there is need for close liaison between Gynaecologists and Psychiatrists in managing these patients.
Turbulence-shear interaction pressure contributions to wind noise.
Authors: Raspet Richard , Yu Jiao , Webster Jeremy 
Published: October 2009

In an earlier paper [Raspet et al., J. Acoust. Soc. Am. 123, 1260–1269 (2008)], the mean shear-turbulence interaction pressure predicted by George et al. [J. Fluid Mech. 148, 155–191 (1984)] was calculated for outdoor wind noise measurements. It was found that the mean shear-turbulence interaction pressure predictions overestimated the spectral levels at low wave numbers and were not consistent with measurements. A new calculation based on Kraichnan’s method [J. Acoust. Soc. Am. 28, 378–390 (1956)] includes two significant improvements: It uses a logarithmic wind velocity profile instead of a linear wind velocity profile, and it models the reduction in the vertical turbulence spectrum as the ground surface is approached. The effects of the change in vertical spectrum with height and the curvature of the wind profile are analyzed by comparing the two calculations. The height dependence of the predicted turbulence-shear interaction pressure spectrum is also calculated. The predictions with the improved method agree with measurements made within large (1.0 m) wind-screens. [Research supported by the U.S. Army TACOM-ARDEC at Picatinny Arsenal, NJ.]
Inhibition of Tumor Cell Growth, Invasion, and Metastasis by EXEL-2880 (XL880, GSK1363089), a Novel Inhibitor of HGF and VEGF Receptor Tyrosine Kinases
Authors: Qian Fawn , Engst Stefan , Yamaguchi Kyoko , Yu Peiwen , Won Kwang-Ai , Mock Lillian , Lou Tracy , Tan Jenny , Li Connie , Tam Danny , Lougheed Julie , Yakes F. Michael , Bentzien Frauke , Xu Wei , Zaks Tal , Wooster Richard , Greshock Joel , Joly Alison H. 
Published: October 2009

Abstract
The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a wide variety of human malignancies. Vascular endothelial growth factor (VEGF) receptors are expressed on the surface of vascular endothelial cells and cooperate with Met to induce tumor invasion and vascularization. EXEL-2880 (XL880, GSK1363089) is a small-molecule kinase inhibitor that targets members of the HGF and VEGF receptor tyrosine kinase families, with additional inhibitory activity toward KIT, Flt-3, platelet-derived growth factor receptor β, and Tie-2. Binding of EXEL-2880 to Met and VEGF receptor 2 (KDR) is characterized by a very slow off-rate, consistent with X-ray crystallographic data showing that the inhibitor is deeply bound in the Met kinase active site cleft. EXEL-2880 inhibits cellular HGF-induced Met phosphorylation and VEGF-induced extracellular signal-regulated kinase phosphorylation and prevents both HGF-induced responses of tumor cells and HGF/VEGF-induced responses of endothelial cells. In addition, EXEL-2880 prevents anchorage-independent proliferation of tumor cells under both normoxic and hypoxic conditions. In vivo, these effects produce significant dose-dependent inhibition of tumor burden in an experimental model of lung metastasis. Collectively, these data indicate that EXEL-2880 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of invasion and angiogenesis mediated by HGF and VEGF receptors. [Cancer Res 2009;69(20):8009–16]
A Novel Experimental Heme Oxygenase-1–Targeted Therapy for Hormone-Refractory Prostate Cancer
Authors: Alaoui-Jamali Moulay A. , Bismar Tarek A. , Gupta Ajay , Szarek Walter A. , Su Jie , Song Wei , Xu Yingjie , Xu Bin , Liu Guoan , Vlahakis Jason Z. , Roman Gheorghe , Jiao Jinsong , Schipper Hyman M. 
Published: October 2009

Abstract
Heme oxygenase-1 (HO-1), a member of the heat shock protein family, plays a key role as a sensor and regulator of oxidative stress. Herein, we identify HO-1 as a biomarker and potential therapeutic target for advanced prostate cancer (PCA). Immunohistochemical analysis of prostate tissue using a progression tissue microarray from patients with localized PCA and across several stages of disease progression revealed a significant elevation of HO-1 expression in cancer epithelial cells, but not in surrounding stromal cells, from hormone-refractory PCA (HRPCA) compared with hormone-responsive PCA and benign tissue. Silencing the ho-1 gene in HRPCA cells decreased the HO-1 activity, oxidative stress, and activation of the mitogen-activated protein kinase–extracellular signal-regulated kinase/p38 kinase. This coincided with reduced cell proliferation, cell survival, and cell invasion in vitro, as well as inhibition of prostate tumor growth and lymph node and lung metastases in vivo. The effect of ho-1 silencing on these oncogenic features was mimicked by exposure of cells to a novel selective small-molecule HO-1 inhibitor referred to as OB-24. OB-24 selectively inhibited HO-1 activity in PCA cells, which correlated with a reduction of protein carbonylation and reactive oxygen species formation. Moreover, OB-24 significantly inhibited cell proliferation in vitro and tumor growth and lymph node/lung metastases in vivo. A potent synergistic activity was observed when OB-24 was combined with Taxol. Together, these results establish HO-1 as a potential therapeutic target for advanced PCA. [Cancer Res 2009;69(20):8017–24]
Height, Body Mass Index, and Physical Activity in Relation to Glioma Risk
Authors: Moore Steven C. , Rajaraman Preetha , Dubrow Robert , Darefsky Amy S. , Koebnick Corinna , Hollenbeck Albert , Schatzkin Arthur , Leitzmann Michael F. 
Published: October 2009

Abstract
Whether energy balance during early life and/or adulthood is related to glioma risk is unknown. We therefore investigated height, body mass index (BMI), and physical activity in relation to glioma risk in the prospective NIH-AARP Diet and Health Study. Participants completed a baseline questionnaire (sent in 1995-1996) inquiring about height, weight, and potential confounders. A second questionnaire (sent in 1996) inquired about physical activity during ages 15 to 18, 19 to 29, and 35 to 39 years and the past 10 years and body weight at ages 18, 35, and 50 years. During follow-up from 1995/1996 to 2003, we documented 480 cases of glioma among 499,437 respondents to the baseline questionnaire and 257 cases among 305,681 respondents to the second questionnaire. Glioma risk among tall persons (≥1.90 m) was twice that of short persons [&lt;1.60 m; multivariate relative risk (RR), 2.12; 95% confidence interval (95% CI), 1.18-3.81; Ptrend = 0.006]. Risk among participants who were obese (BMI 30.0-34.9 kg/m2) at age 18 years was nearly four times that of persons of normal weight (BMI 18.5-24.9 kg/m2) at age 18 years (RR, 3.74; 95% CI, 2.03-6.90; Ptrend = 0.003); 11 cases were obese at age 18 years. Risk among participants who were active during ages 15 to 18 years was 36% lower than that of persons who were inactive during ages 15 to 18 years (RR, 0.64; 95% CI, 0.44-0.93; Ptrend = 0.02). BMI and physical activity after age 18 years were unrelated to glioma risk. Adult height, BMI during adolescence, and physical activity during adolescence were each associated with glioma risk, supporting a role for early-life energy balance in glioma carcinogenesis. [Cancer Res 2009;69(21):8349–55]
Sox11 Prevents Tumorigenesis of Glioma-Initiating Cells by Inducing Neuronal Differentiation
Authors: Hide Takuichiro , Takezaki Tatsuya , Nakatani Yuka , Nakamura Hideo , Kuratsu Jun-ichi , Kondo Toru 
Published: October 2009

Abstract
Recent findings have shown that malignant tumors contain cancer-initiating cells (CIC), which self-renew and are tumorigenic. However, CICs have not been characterized properly due to lack of specific markers. We recently established a mouse glioma cell line, NSCL61, by overexpressing an oncogenic HRasL61 in p53-deficient neural stem cells. Using limiting dilution assays, we show that only 2 of 24 NSCL61 clones retained their tumorigenicity in vivo, although the others also expressed oncogenic HRasL61 and could proliferate in culture. A comparison of the gene expression profiles of tumorigenic and nontumorigenic clones showed that the tumorigenic clones had lost Sox11 expression. We show that overexpression of sox11 prevented tumorigenesis of NSCL61s by inducing their neuronal differentiation accompanied with decreased levels of plagl1. We also show that overexpression of plagl1 abolished neuronal commitment of nontumorigenic cells and induced them to become tumorigenic. Moreover, we show that human glioma-initiating cells lost sox11 expression, and overexpression of sox11 prevented their tumorigenesis in vivo. Together with the clinical evidence showing that downregulation of sox11 mRNA correlates with a significant decrease in survival, these findings suggest that Sox11 prevents gliomagenesis by blocking the expression of oncogenic plagl1. [Cancer Res 2009;69(20):7953–9]
Dose-Ranging Study of Metronomic Oral Vinorelbine in Patients with Advanced Refractory Cancer
Authors: Briasoulis Evangelos , Pappas Periklis , Puozzo Christian , Tolis Christos , Fountzilas George , Dafni Urania , Marselos Marios , Pavlidis Nicholas 
Published: October 2009

Abstract
Aim: To determine the safe dose range and pharmacokinetics of metronomic oral vinorelbine and obtain preliminary data on biomarkers and efficacy in patients with advanced cancer.
Methods: Successive cohorts of patients received escalated doses of oral vinorelbine given thrice a week until disease progression, unacceptable toxicity (UT), or consent withdrawal. UT was any grade 4 toxicity, or grade 2 or 3 toxicity that would result to longer than 2-week break during the first 2 months of treatment. Blood samples were collected for pharmacokinetics and quantification of angiogenesis regulatory proteins.
Results: Sixty-two patients (median age, 60 years) enrolled at six dose levels from 20 to 70 mg and received treatment for median 12.25 weeks (range, 2-216+). Unacceptable toxicity occurred in two of six patients treated at 60 mg (leucopenia grade 4 and epistaxis grade 2) and in one at 70 mg (leucopenia grade 2). The upper metronomic dose was 50 mg. Objective antitumor response documented in eight cases and 32% of patients experienced disease stability for minimum 6 months. Three responders (renal cancer, medullary thyroid carcinoma, and Kaposi sarcoma) received nonstop treatment for over 3 years without overt toxicity. Low pretreatment levels of circulating interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor were found predictors of efficacy. Steady-state concentrations of vinorelbine and its active metabolite ranged from 0.5 to 1.5 ng/mL.
Conclusions: Metronomic administration of oral vinorelbine is feasible at doses up to 50 mg thrice a week and can yield sustainable antitumor activity without overt toxicity, probably through antiangiogenic mechanism. Further clinical investigation is warranted. (Clin Cancer Res 2009;15(20):6454–61)
An Embryonic Stem Cell–Like Signature Identifies Poorly Differentiated Lung Adenocarcinoma but not Squamous Cell Carcinoma
Authors: Hassan Khaled A. , Chen Guoan , Kalemkerian Gregory P. , Wicha Max S. , Beer David G. 
Published: October 2009

Abstract
Purpose: An embryonic stem cell (ESC) profile correlates with poorly differentiated breast, bladder, and glioma cancers. In this article, we assess the correlation between the ESC profile and clinical variables in lung cancer.
Experimental Design: Microarray gene expression analysis was done using Affymetrix Human Genome U133A on 443 samples of human lung adenocarcinoma and 130 samples of squamous cell carcinoma (SCC). To identify gene set enrichment patterns, we used the Genomica software.
Results: Our analysis showed that an increased expression of the ESC gene set and a decreased expression of the Polycomb target gene set identified poorly differentiated lung adenocarcinoma. In addition, this gene expression signature was associated with markers of poor prognosis and worse overall survival in lung adenocarcinoma. However, there was no correlation between this ESC gene signature and any histologic or clinical variable assessed in lung SCC.
Conclusions: This work suggests that not all poorly differentiated non–small cell lung cancers exhibit a gene expression profile similar to that of ESC, and that other characteristics may play a more important role in the determination of differentiation and survival in SCC of the lung. (Clin Cancer Res 2009;15(20):6386–90)
Identification of Novel Kinase Targets for the Treatment of Estrogen Receptor–Negative Breast Cancer
Authors: Speers Corey , Tsimelzon Anna , Sexton Krystal , Herrick Ashley M. , Gutierrez Carolina , Culhane Aedin , Quackenbush John , Hilsenbeck Susan , Chang Jenny , Brown Powel 
Published: October 2009

Abstract
Purpose: Previous gene expression profiling studies of breast cancer have focused on the entire genome to identify genes differentially expressed between estrogen receptor (ER) α–positive and ER-α–negative cancers.
Experimental Design: Here, we used gene expression microarray profiling to identify a distinct kinase gene expression profile that identifies ER-negative breast tumors and subsets ER-negative breast tumors into four distinct subtypes.
Results: Based on the types of kinases expressed in these clusters, we identify a cell cycle regulatory subset, a S6 kinase pathway cluster, an immunomodulatory kinase–expressing cluster, and a mitogen-activated protein kinase pathway cluster. Furthermore, we show that this specific kinase profile is validated using independent sets of human tumors and is also seen in a panel of breast cancer cell lines. Kinase expression knockdown studies show that many of these kinases are essential for the growth of ER-negative, but not ER-positive, breast cancer cell lines. Finally, survival analysis of patients with breast cancer shows that the S6 kinase pathway signature subtype of ER-negative cancers confers an extremely poor prognosis, whereas patients whose tumors express high levels of immunomodulatory kinases have a significantly better prognosis.
Conclusions: This study identifies a list of kinases that are prognostic and may serve as druggable targets for the treatment of ER-negative breast cancer. (Clin Cancer Res 2009;15(20):6327–40)
Phase I Study of Ipilimumab, an Anti–CTLA-4 Monoclonal Antibody, in Patients with Relapsed and Refractory B-Cell Non–Hodgkin Lymphoma
Authors: Ansell Stephen M. , Hurvitz Sara A. , Koenig Patricia A. , LaPlant Betsy R. , Kabat Brian F. , Fernando Donna , Habermann Thomas M. , Inwards David J. , Verma Meena , Yamada Reiko , Erlichman Charles , Lowy Israel , Timmerman John M. 
Published: October 2009

Abstract
Purpose: The growth of non–Hodgkin lymphomas can be influenced by tumor–immune system interactions. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative regulator of T-cell activation that serves to dampen antitumor immune responses. Blocking anti–CTLA-4 monoclonal antibodies improves host resistance to immunogenic tumors, and the anti–CTLA-4 antibody ipilimumab (MDX-010) has clinical activity against melanoma, prostate, and ovarian cancers.
Experimental Design: We did a phase I trial of ipilimumab in patients with relapsed/refractory B-cell lymphoma to evaluate safety, immunologic activity, and potential clinical efficacy. Treatment consisted of ipilimumab at 3 mg/kg and then monthly at 1 mg/kg × 3 months (dose level 1), with subsequent escalation to 3 mg/kg monthly × 4 months (dose level 2).
Results: Eighteen patients were treated, 12 at the lower dose level and 6 at the higher dose level. Ipilimumab was generally well tolerated, with common adverse events attributed to it, including diarrhea, headache, abdominal pain, anorexia, fatigue, neutropenia, and thrombocytopenia. Two patients had clinical responses; one patient with diffuse large B-cell lymphoma had an ongoing complete response (&gt;31 months), and one with follicular lymphoma had a partial response lasting 19 months. In 5 of 16 cases tested (31%), T-cell proliferation to recall antigens was significantly increased (&gt;2-fold) after ipilimumab therapy.
Conclusions: Blockade of CTLA-4 signaling with the use of ipilimumab is well tolerated at the doses used and has antitumor activity in patients with B-cell lymphoma. Further evaluation of ipilimumab alone or in combination with other agents in B-cell lymphoma patients is therefore warranted. (Clin Cancer Res 2009;15(20):6446–53)
In vivoeffects of targeting CD79b with antibodies and antibody-drug conjugates
Authors: Zheng Bing , Fuji Reina N. , Elkins Kristi , Yu Shang-Fan , Fuh Franklin K. , Chuh Josefa , Tan Christine , Hongo Jo-Anne , Raab Helga , Kozak Katherine R. , Williams Marna , McDorman Elena , Eaton Dan , Ebens Allen , Polson Andrew G. 
Published: October 2009

AbstractAntibodies directed against B cells are in use for the treatment of non-Hodgkin's lymphoma and autoimmune disorders. The B-cell–restricted surface antigen CD79b, a signaling component of the B-cell receptor, has been shown as a promising antibody target in mouse efficacy models of systemic lupus erythematosus. Anti-CD79b antibody-drug conjugates (ADC), cytotoxic drugs linked through specialized chemical linkers to antibodies, are effective in mouse xenograft models of non-Hodgkin's lymphoma. We were interested in evaluating the systemic effects of anti-CD79b antibodies and ADCs in normal animals as a step toward the development of these molecules as therapeutics. As we were unable to identify any cell surface binding anti-human CD79b antibodies that were cross-reactive to other species, we developed an antibody to cynomolgus monkey (Macaca fascicularis) CD79b (anti-cyCD79b). The anti-cynomolgus antibody, anti-cyCD79b (10D10), and the maytansine (tubulin inhibitor)–conjugated ADC, anti-cyCD79b (10D10)-MCC-DM1, were administered to cynomolgus monkeys at ∼30 mg/kg (6,000 μg DM1/m2) for two doses 3 weeks apart. Anti-cyCD79b and anti-cyCD79b-MCC-DM1 resulted in peripheral blood B-cell depletion of ∼65% and ∼94%, respectively. In addition, anti-cyCD79b-MCC-DM1 resulted in near-complete absence of splenic germinal centers, an observation supporting an effect on dividing B cells. Both molecules were well tolerated, with minimal findings for the antibody and findings for the ADC limited to the lymphoid and hematopoietic systems, liver, and peripheral nerves. These preclinical data suggest that targeting CD79b with antibodies or ADCs may provide safe and effective therapies for B-cell malignancies and autoimmune diseases. [Mol Cancer Ther 2009;8(10):2937–46]