bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody-Mediated Inhibition of Cathepsin S Blocks Colorectal Tumor Invasion and Angiogenesis
Authors: Burden Roberta E. , Gormley Julie A. , Jaquin Thomas J. , Small Donna M. , Quinn Derek J. , Hegarty Shauna M. , Ward Claire , Walker Brian , Johnston James A. , Olwill Shane A. , Scott Christopher J. 
Published: September 2009

Abstract
Purpose: Cathepsin S is a cysteine protease that promotes the invasion of tumor and endothelial cells during cancer progression. Here we investigated the potential to target cathepsin S using an antagonistic antibody, Fsn0503, to block these tumorigenic effects.
Experimental Design: A panel of monoclonal antibodies was raised to human cathepsin S. The effects of a selected antibody were subsequently determined using invasion and proteolysis assays. Endothelial cell tube formation and aorta sprouting assays were done to examine antiangiogenic effects. In vivo effects were also evaluated using HCT116 xenograft studies.
Results: A selected cathepsin S antibody, Fsn0503, significantly blocked invasion of a range of tumor cell lines, most significantly HCT116 colorectal carcinoma cells, through inhibition of extracellular cathepsin S–mediated proteolysis. We subsequently found enhanced expression of cathepsin S in colorectal adenocarcinoma biopsies when compared with normal colon tissue. Moreover, Fsn0503 blocked endothelial cell capillary tube formation and aortic microvascular sprouting. We further showed that administration of Fsn0503 resulted in inhibition of tumor growth and neovascularization of HCT116 xenograft tumors.
Conclusions: These results show that blocking the invasive and proangiogenic effects of cathepsin S with antibody inhibitors may have therapeutic utility upon further preclinical and clinical evaluation. (Clin Cancer Res 2009;15(19):6042–51)
Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone
Authors: Ottewell Penelope D. , Woodward Julia K. , Lefley Diane V. , Evans C. Alyson , Coleman Robert E. , Holen Ingunn 
Published: September 2009

AbstractPatients with advanced breast cancer frequently develop bone metastases, and at this stage, the disease is considered incurable. Here, we show that a 6-week course of weekly administration of doxorubicin (2 mg/kg), followed 24 hours later by the bisphosphonate zoledronic acid (100μg/kg), causes substantial inhibition of MDA-MB-436 breast tumor burden in bone of immunocompromised mice, compared with administration of the single agents. Molecular analysis of tumors from animals treated sequentially with doxorubicin followed by zoledronic acid showed reduced numbers of proliferating tumor cells and decreased expression of cyclins E1, B, D1, and D3 as well as cdk2 and cdk4. Tumors from the sequential treatment group also displayed increased levels of apoptosis, increased expression of bcl2-associated X protein, decreased expression of B-cell chronic lymphocytic leukemia/lymphoma 2, and activation of caspase 3, 8, and 9. Zoledronic acid caused a small reduction in tumor volume, reduced tumor cell proliferation, and decreased expression of cyclins D1 and D3, compared with tumors from animals treated with saline or doxorubicin. Doxorubicin had no effect on tumor growth, cell cycle, or apoptosis in vivo, but did cause increased accumulation of a bisphosphonate in MDA-MB-436 cells in vitro, suggesting that doxorubicin may affect subsequent uptake of zoledronic acid. In support of this, accumulation of unprenylated Rap1A, a surrogate marker of zoledronic acid, was only detected in tumors following sequential treatment, and not following treatment with zoledronic acid alone. Our data are the first to show the specific molecular pathways by which sequential treatment with doxorubicin and zoledronic acid induce tumor cell apoptosis and inhibit proliferation in an in vivo model of breast tumor growth in bone. [Mol Cancer Ther 2009;8(10):2821–32]
Urinary Phytoestrogen Excretion and Postmenopausal Breast Cancer Risk: The Multiethnic Cohort Study
Authors: Goodman Marc T. , Shvetsov Yurii B. , Wilkens Lynne R. , Franke Adrian A. , Le Marchand Loic , Kakazu Kerry K. , Nomura Abraham M.Y. , Henderson Brian E. , Kolonel Laurence N. 
Published: September 2009

AbstractThe objective of this study was to examine the association of urinary phytoestrogens with the risk of postmenopausal breast cancer. Participants in the Multiethnic Cohort Study included 36,458 postmenopausal women who provided blood or urine specimens. A nested case-control study of breast cancer with biospecimens was created in which cases diagnosed after specimen collection were matched to two controls. Two hundred fifty-one women with breast cancer and 462 controls had urine available for analysis of urinary phytoestrogens. Odds ratios (OR) and 95% confidence intervals (CI) were obtained using conditional logistic regression. A nonmonotonic inverse trend (P = 0.04) in breast cancer risk was associated with increasing urinary excretion of genistein (OR 25th-75th percentile, 0.88; 95% CI, 0.78-0.99) and total isoflavones (OR 25th-75th percentile, 0.80; 95% CI, 0.65-0.99). A significant reduction in breast cancer risk in Japanese-American women was associated with the highest compared with the lowest quartile excretion of urinary daidzein (OR, 0.41; 95% CI, 0.19-0.89; Ptrend, 0.005). The risk of breast cancer was reduced among White women with the highest compared with the lowest quartile excretion of equol (OR, 0.27; 95% CI, 0.08-0.95), although the trend in risk was not significant (P = 0.07). Our results provide some support to the hypothesis that a diet rich in isoflavones from soy products reduces the risk of postmenopausal breast cancer, particularly in populations with comparatively high excretion of phytoestrogens.
All-Trans Retinoic Acid Suppresses Stat3 Signaling during Skin Carcinogenesis
Authors: Syed Zanobia , Cheepala Satish B. , Gill Jennifer N. , Stein Jennica , Nathan Cherie Ann , DiGiovanni John , Batra Vinita , Adegboyega Patrick , Kleiner Heather E. , Clifford John L. 
Published: September 2009

Abstract
Squamous cell carcinoma (SCC) of the skin is the most clinically aggressive form of nonmelanoma skin cancer. We have determined the effects of all-trans retinoic acid (ATRA), a naturally occurring chemopreventive retinoid, on signal transducer and activator of transcription 3 (Stat3) signaling during the development of skin SCC. Stat3 is a transcription factor that plays a critical role in cell proliferation and survival, and it is constitutively active in several malignant cell types. We have previously shown that Stat3 is required for the initiation, promotion, and progression of skin SCC. ATRA is a highly efficient suppressor of tumor formation in the two-stage mouse skin carcinogenesis model and we have shown that this effect correlates with the suppression of the B-Raf/Mek/Erk signaling pathway. In this study, we have determined the pattern of Stat3 phosphorylation throughout the course of the two-stage protocol, both in the presence and absence of ATRA. We have used both SENCAR mice and K5.Stat3C transgenic mice, which express the Stat3C protein, a constitutively active form of Stat3, in the skin. Using Western blotting and immunohistochemical staining with phosphospecific antibodies, we show that coadministration of ATRA suppressed the 12-O-tetradecanoylphorbol-13-acetate–induced phosphorylation of Stat3 in both models, but was only able to suppress tumor formation in the SENCAR mice. Surprisingly, ATRA actually enhanced tumor formation in 12-O-tetradecanoylphorbol-13-acetate–treated K5.Stat3C mice. We hypothesize that ATRA blocks tumor formation, at least in part, by targeting events upstream of Stat3, such as the B-Raf/Mek/Erk pathway, and that in the K5.Stat3C mice, in which Stat3 activity is constitutive, it cannot suppress tumor formation.
Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism
Authors: Grossmann Michael E. , Mizuno Nancy K. , Dammen Michelle L. , Schuster Todd , Ray Amitabha , Cleary Margot P. 
Published: September 2009

Abstract
Eleostearic acid (α-ESA) is a conjugated linolenic acid that makes up ∼60% of Momordica charantia (bitter melon) seed oil. Prior work found that water extract from bitter melon was able to inhibit breast cancer. Here, we investigated effects of α-ESA on both estrogen receptor (ER)–negative MDA-MB-231 (MDA-wt) and ER-positive MDA-ERα7 human breast cancer cells. We found that α-ESA inhibited proliferation of both MDA-wt and MDA-ERα7 cells, whereas conjugated linoleic acid had comparatively weak antiproliferative activity at 20 to 80 μmol/L concentrations. We also found that α-ESA (40 μmol/L) treatment led to apoptosis in the range of 70% to 90% for both cell lines, whereas conjugated linoleic acid (40 μmol/L) resulted in only 5% to 10% apoptosis, similar to results for control untreated cells. Addition of α-ESA also caused loss of mitochondrial membrane potential and translocation of apoptosis-inducing factor as well as endonuclease G from the mitochondria to the nucleus. Additionally, α-ESA caused a G2-M block in the cell cycle. We also investigated the potential for lipid peroxidation to play a role in the inhibitory action of α-ESA. We found that when the breast cancer cells were treated with α-ESA in the presence of the antioxidant α-tocotrienol (20 μmol/L), the growth inhibition and apoptosis effects of α-ESA were lost. An AMP-activated protein kinase inhibitor (Dorsomorphin) was also able to partially abrogate the effects of α-ESA, whereas a caspase inhibitor (BOC-D-FMK) did not. These results illustrate that α-ESA can block breast cancer cell proliferation and induce apoptosis through a mechanism that may be oxidation dependent.
UVR Exposure Sensitizes Keratinocytes to DNA Adduct Formation
Authors: Nair Sudhir , Kekatpure Vikram D. , Judson Benjamin L. , Rifkind Arleen B. , Granstein Richard D. , Boyle Jay O. , Subbaramaiah Kotha , Guttenplan Joseph B. , Dannenberg Andrew J. 
Published: September 2009

AbstractUV radiation (UVR) and exposure to tobacco smoke, a source of polycyclic aromatic hydrocarbons (PAH), have been linked to skin carcinogenesis. UVR-mediated activation of the aryl hydrocarbon receptor (AhR) stimulates the transcription of CYP1A1 and CYP1B1, which encode proteins that convert PAH to genotoxic metabolites. We determined whether UVR exposure sensitized human keratinocytes to PAH-induced DNA adduct formation. UVR exposure induced CYP1A1 and CYP1B1 in HaCaT cells, an effect that was mimicked by photooxidized tryptophan (aTRP) and FICZ, a component of aTRP. UVR exposure or pretreatment with aTRP or FICZ also sensitized cells to benzo(a)pyrene (B[a]P)-induced DNA adduct formation. αNF, an AhR antagonist, suppressed UVR-, aTRP-, and FICZ-mediated induction of CYP1A1 and CYP1B1 and inhibited B[a]P-induced DNA adduct formation. Treatment with 17-AAG, an Hsp90 inhibitor, caused a marked decrease in levels of AhR; inhibited UVR-, aTRP-, and FICZ-mediated induction of CYP1A1 and CYP1B1; and blocked the sensitization of HaCaT cells to B[a]P-induced DNA adduct formation. FICZ has been suggested to be a physiologic ligand of the AhR that may have systemic effects. Hence, studies of FICZ were also carried out in MSK-Leuk1 cells, a model of oral leukoplakia. Pretreatment with α-naphthoflavone or 17-AAG blocked FICZ-mediated induction of CYP1A1 and CYP1B1, and suppressed the increased B[a]P-induced DNA adduct formation. Collectively, these results suggest that sunlight may activate AhR signaling and thereby sensitize cells to PAH-mediated DNA adduct formation. Antagonists of AhR signaling may have a role in the chemoprevention of photocarcinogenesis.
Isolating the Effects of Social Interactions on Cancer Biology
Authors: Trainor Brian C. , Sweeney Colleen , Cardiff Robert 
Published: September 2009

Abstract
This perspective on Williams et al. (beginning on p. 850 in this issue of the journal) examines the connections between biological responses activated during psychosocial stress and mammary tumorigenesis. Experiments in mouse models of cancer are identifying aspects of tumor biology that may be regulated by hormones such as glucocorticoids released during psychosocial stress. Our growing understanding of the actions of glucocorticoids on breast tumors could lead to important changes in cancer treatment.
Favoritism in DNA Methylation
Authors: Hitchins Megan P. , Ward Robyn L. 
Published: September 2009

Abstract
This perspective on Candiloro and Dobrovic (beginning on p. 862 in this issue of the journal) highlights the interplay between epigenetic aberrations and underlying DNA sequence changes and illustrates how these alterations may predispose individuals to cancer. Candiloro and Dobrovic clearly show that particular genotypes of the MGMT gene are associated with its methylation in healthy individuals. Aberrant MGMT methylation may identify individuals who could be targeted for cancer screening and chemoprevention strategies.
'Cognitive Capitalism' and the Rat-Race: How Capital Measures Immaterial Labour in British Universities
Authors: Harvie David , De Angelis Massimo 
Published: September 2009

AbstractOne hundred years ago, Frederick Taylor and the pioneers of scientific management went into battle on US factory-floors. Armed with stopwatches and clipboards, they were fighting a war over measure. A century on and capitalist production has spread far beyond the factory walls and the confines of 'national economies'. Although capitalism increasingly seems to rely on 'cognitive' and 'immaterial' forms of labour and social cooperation, the war over measure continues. Armies of economists, statisticians, management-scientists, information-specialists, accountants and others are engaged in a struggle to connect heterogeneous concrete human activities on the basis of equal quantities of human labour in the abstract – that is, to link work and capitalist value. In this paper, we discuss contemporary capital's attempt to (re)impose the 'law of value' through its measuring of immaterial labour. Using the example of higher education in the UK – a 'frontline' of capitalist development – as our case-study, we explain how measuring takes places on various 'self-similar' levels of social organisation. We suggest that such processes are both diachronic and synchronic: socially-necessary labour-times of 'immaterial doings' are emerging and being driven down at the same time as heterogeneous concrete activities are being made commensurable. Alongside more overt attacks on academic freedom, it is in this way that neoliberalism appears on campus.
The Logical Construction of Value-Theory: More on Fine and Saad-Filho
Authors: Kincaid Jim 
Published: September 2009

AbstractFine and Saad-Filho are wrong to insist that an abstract category of production should be the starting point of Marxist value-theory in logical, temporal and causal terms. Marx, in Capital, begins with a repertoire of simpler categories and slowly constructs the complex category of capitalist production. It is vital that exploitation should be seen as one phase (however crucial) of a process of capital-in-motion, and due weight given to money, competition and realisation.
Althusser and Monod: A 'New Alliance'?
Authors: Turchetto Maria 
Published: September 2009

AbstractAlthusser dedicated the fourth lesson of his 'course of philosophy for scientists' at the Ecole Normale Supériere in the autumn of the 1967 to the inaugural lecture held by Jacques Monod at the Collège de France on 3 November in the same year. Althusser defined the concepts of 'living system' and of 'emergence' that Monod uses in his interpretation of evolution as 'materialist'; whereas he judged his conception of human history as the evolution of ideas in the 'noosphere' as 'idealistic'. Against the latter, Althusser counterposed a reading of Marx's work centred on the notion of 'structure' – which is very close to that of 'system' used within biology – and on the refusal of teleology and finalism. This last position, which Althusser takes up particularly in the writings of the 1980s on the 'materialism of the encounter', represent a particularly significant break with orthodox Marxism.
Expression of active human sialyltransferase ST6GalNAcI in Escherichia coli
Authors: Skretas Georgios , Carroll Sean , DeFrees Shawn , Schwartz Marc F , Johnson Karl F , Georgiou George 
Published: September 2009

Abstract

Background
The presence of terminal, surface-exposed sialic acid moieties can greatly enhance the in vivo half-life of glycosylated biopharmaceuticals and improve their therapeutic efficacy. Complete and homogeneous sialylation of glycoproteins can be efficiently performed enzymically in vitro but this process requires large amounts of catalytically active sialyltransferases. Furthermore, standard microbial hosts used for large-scale production of recombinant enzymes can only produce small quantities of glycosyltransferases of animal origin, which lack catalytic activity.

Results and conclusion
In this work, we have expressed the human sialyltransferase ST6GalNAc I (ST6), an enzyme that sialylates O-linked glycoproteins, in Escherichia coli cells. We observed that wild-type bacterial cells are able to produce only very small amounts of soluble ST6 enzyme. We have found, however, that engineered bacterial strains which possess certain types of oxidative cytoplasm or which co-express the molecular chaperones/co-chaperones trigger factor, DnaK/DnaJ, GroEL/GroES, and Skp, can produce greatly enhanced amounts of soluble ST6. Furthermore, we have developed a novel high-throughput assay for the detection of sialyltransferase activity and used it to demonstrate that the bacterially expressed ST6 enzyme is active and able to transfer sialic acid onto a desialylated O-glycoprotein, bovine submaxillary mucin. To the best of our knowledge, this is the first example of expression of active human sialyltransferase in bacteria. This system may be used as a starting point for the evolution of sialyltransferases with better expression characteristics or altered donor/acceptor specificities.
Anti-inflammatory and arthritic effects of thiacremonone, a novel sulfurcompound isolated from garlic via inhibition of NF-κB
Authors: Ban Jung Ok , Oh Ju Hoon , Kim Tae Myoung , Kim Dae Joong , Jeong Heon-Sang , Han Sang Bae , Hong Jin Tae 
Published: September 2009

Abstract
Introduction
Sulfur compounds isolated from garlic exert anti-inflammatory properties. We recently isolated thiacremonone, a novel sulfur compound from garlic. Here, we investigated the anti-inflammatory and arthritis properties of thiacremonone through inhibition of NF-κB since NF-κB is known to be a target molecule of sulfur compounds and an implicated transcription factor regulating inflammatory response genes.

Methods
The anti-inflammatory and arthritis effects of thiacremone in in vivo were investigated in 12-O-tetradecanoylphorbol-13-acetate-induced ear edema, carrageenan and mycobacterium butyricum-induced inflammatory and arthritis models. Lipopolysaccharide-induced nitric oxide (NO) production was determined by Griess method. The DNA binding activity of NF-κB was investigated by electrophoretic mobility shift assay. NF-κB and inducible nitric oxide synthetase (iNOS) transcriptional activity was determined by luciferase assay. Expression of iNOS and cyclooxygenase-2 (COX-2) was determined by western blot.

Results
The results showed that topical application of thiacremonone (1 or 2 μg/ear) suppressed the 12-O-tetradecanoylphorbol-13-acetate-induced (1 μg/ear) ear edema. Thiacremonone (1-10 mg/kg) administered directly into the plantar surface of hind paw also suppressed the carrageenan (1.5 mg/paw) and mycobacterium butyricum (2 mg/paw)-induced inflammatory and arthritic responses as well as expression of iNOS and COX-2, in addition to NF-κB DNA-binding activity. In further in vitro study, thiacremonone (2.5-10 μg/ml) inhibited lipopolysaccharide (LPS, 1 μg/ml)-induced nitric oxide (NO) production, and NF-κB transcriptional and DNA binding activity in a dose dependent manner. The inhibition of NO by thiacremonone was consistent with the inhibitory effect on LPS-induced inducible nitric oxide synthase (iNOS) and COX-2 expression, as well as iNOS transcriptional activity. Moreover, thiacremonone inhibited LPS-induced p50 and p65 nuclear translocation, resulting in an inhibition of the DNA binding activity of the NF-κB. These inhibitory effects on NF-κB activity and NO generation were suppressed by reducing agents dithiothreitol (DTT) and glutathione, and were abrogated in p50 (C62S)-mutant cells, suggesting that the sulfhydryl group of NF-κB molecules may be a target of thiacremonone.

Conclusions
The present results suggested that thiacremonone exerted its anti-inflammatory and anti-arthritic properties through the inhibition of NF-κB activation via interaction with the sulfhydryl group of NF-κB molecules, and thus could be a useful agent for the treatment of inflammatory and arthritic diseases.
How mothers with borderline personality disorder relate to their year-old infants
Authors: Hobson R. Peter , Patrick Matthew P. H. , Hobson Jessica A. , Crandell Lisa , Bronfman Elisa , Lyons-Ruth Karlen 
Published: September 2009

BackgroundWomen with borderline personality disorder have conflictual interpersonal relations that may extend to disrupted patterns of interaction with their infants.AimsTo assess how women with borderline personality disorder engage with their 12 to 18-month-old infants in separation–reunion episodes.MethodWe videotaped mother–infant interactions in separation–reunion episodes of the Strange Situation test. The mothers were women with borderline personality disorder, with depression, or without psychopathological disorder. Masked ratings of maternal behaviour were made with the Atypical Maternal Behavior Instrument for Assessment and Classification.ResultsAs predicted, a higher proportion (85%) of women with borderline personality disorder than women in the comparison groups showed disrupted affective communication with their infants. They were also distinguished by the prevalence of frightened/disoriented behaviour.ConclusionsMaternal borderline personality disorder is associated with dysregulated mother–infant communication.
Age at onset and cognition in schizophrenia: meta-analysis
Authors: Rajji T. K. , Ismail Z. , Mulsant B. H. 
Published: September 2009

BackgroundThe relationship between cognition and age at onset of schizophrenia is largely unknown.AimsTo compare cognitive deficits in individuals with youth-onset and late-onset schizophrenia with those in adults with first-episode schizophrenia.MethodTwenty-nine databases (including EMBASE, MEDLINE and PsycINFO) were searched from 1980 to 2008. Selected publications had to include healthy controls and analyse separately individuals diagnosed with schizophrenia or a related disorder and individuals with first-episode, youth-onset or late-onset schizophrenia. Descriptive and cognitive data were extracted and the latter aggregated into 22 cognitive measures. Cohen's effect size raw and weighted means of cognitive deficits were generated and compared in the three groups.ResultsIndividuals with youth-onset and first-episode schizophrenia demonstrate large deficits (mean effect size ⩾0.8) on almost all cognitive measures. Individuals with youth-onset schizophrenia demonstrate larger deficits than those with first-episode schizophrenia on arithmetic, executive function, IQ, psychomotor speed of processing and verbal memory. In contrast, those with late-onset schizophrenia demonstrate minimal deficits on arithmetic, digit symbol coding and vocabulary, but larger ones on attention, fluency, global cognition, IQ and visuospatial construction.ConclusionsIndividuals with youth-onset schizophrenia have severe cognitive deficits, whereas those with late-onset schizophrenia have some relatively preserved cognitive functions. This finding supports the view that severity of the disease process is associated with different ages at onset. In addition, the cognitive pattern of people with late-onset schizophrenia suggests that their deficits are specific rather than solely as a result of ageing and related factors.