bluuebunny/crossref_metadata_2025_split huggingface dataset:
Δ9-Tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells through Cdc2 Regulation
Authors: Caffarel María M. , Sarrió David , Palacios José , Guzmán Manuel , Sánchez Cristina 
Published: July 2006

Abstract
It has been proposed that cannabinoids are involved in the control of cell fate. Thus, these compounds can modulate proliferation, differentiation, and survival in different manners depending on the cell type and its physiopathologic context. However, little is known about the effect of cannabinoids on the cell cycle, the main process controlling cell fate. Here, we show that Δ9-tetrahydrocannabinol (THC), through activation of CB2 cannabinoid receptors, reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis. In particular, THC arrests cells in G2-M via down-regulation of Cdc2, as suggested by the decreased sensitivity to THC acquired by Cdc2-overexpressing cells. Of interest, the proliferation pattern of normal human mammary epithelial cells was much less affected by THC. We also analyzed by real-time quantitative PCR the expression of CB1 and CB2 cannabinoid receptors in a series of human breast tumor and nontumor samples. We found a correlation between CB2 expression and histologic grade of the tumors. There was also an association between CB2 expression and other markers of prognostic and predictive value, such as estrogen receptor, progesterone receptor, and ERBB2/HER-2 oncogene. Importantly, no significant CB2 expression was detected in nontumor breast tissue. Taken together, these data might set the bases for a cannabinoid therapy for the management of breast cancer.(Cancer Res 2006; 66(13): 6615-21)
Role of B-Cell–Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment
Authors: Tai Yu-Tzu , Li Xian-Feng , Breitkreutz Iris , Song Weihua , Neri Paola , Catley Laurence , Podar Klaus , Hideshima Teru , Chauhan Dharminder , Raje Noopur , Schlossman Robert , Richardson Paul , Munshi Nikhil C. , Anderson Kenneth C. 
Published: July 2006

Abstract
Recent studies have underscored the role of B-cell-activating factor (BAFF), a member of the tumor necrosis factor superfamily, in promoting the survival of malignant B cells, including human multiple myeloma. We here characterized the functional significance of BAFF in the interaction between multiple myeloma and bone marrow stromal cells (BMSC) and further defined the molecular mechanisms regulating these processes. BAFF is detected on BMSCs derived from multiple myeloma patients as evidenced by flow cytometry. BAFF secretion is 3- to 10-fold higher in BMSCs than in multiple myeloma cells, and tumor cell adhesion to BMSCs augments BAFF secretion by 2- to 5-fold, confirmed by both ELISA and immunoblotting. Adhesion of MM1S and MCCAR multiple myeloma cell lines to KM104 BMSC line transfected with a luciferase reporter vector carrying the BAFF gene promoter (BAFF-LUC) significantly enhanced luciferase activity, suggesting that nuclear factor-κB (NF-κB) activation induced by multiple myeloma adhesion to BMSCs mediates BAFF up-regulation. Moreover, BAFF (0-100 ng/mL) increases adhesion of multiple myeloma lines to BMSCs in a dose-dependent manner; conversely, transmembrane activator and calcium modulator and cyclophylin ligand interactor-Ig or B-cell maturation antigen/Fc blocked BAFF stimulation. Using adenoviruses expressing dominant-negative and constitutively expressed AKT as well as NF-κB inhibitors, we further showed that BAFF-induced multiple myeloma cell adhesion is primarily mediated via activation of AKT and NF-κB signaling. Importantly, BAFF similarly increased adhesion of CD138-expressing patient multiple myeloma cells to BMSCs. These studies establish a role for BAFF in localization and survival of multiple myeloma cells in the bone marrow microenvironment and strongly support novel therapeutics, targeting the interaction between BAFF and its receptors in human multiple myeloma. (Cancer Res 2006; 66(13): 6675-82)
Arming Tumor-Reactive T Cells with Costimulator B7-1 Enhances Therapeutic Efficacy of the T Cells
Authors: Zheng Guoxing , Liu Shanrong , Wang Peijie , Xu Ying , Chen Aoshuang 
Published: July 2006

Abstract
T cells ectopically expressing costimulators are pathogenic and contribute to autoimmunity against self-antigens. Given that tumor antigens are often self-antigen or mutated self-antigens, we hypothesize that neoexpressing a costimulator on tumor-reactive T cells may likewise enhance their reactivity to tumor. To test this hypothesis, we have expressed B7-1 on OT-1 CD8+ T-cell receptor transgenic T cells via protein transfer (or protein “painting”). Naïve OT-1 T cells, after being painted with B7-1, can self-costimulate themselves, elicit enhanced proliferative and CTL responses to E.G7-ovalbumin tumor cells (expressing a cognate antigen), and become resistant to CD4+CD25+ regulatory T-cell-mediated suppression. Importantly, these T cells, when coimplanted with E.G7-ovalbumin tumor cells into a syngeneic host, are three to nine times more potent than are control T cells (mock painted with human IgG) in inhibiting tumor growth. Further, on transfer into mice bearing established E.G7-ovalbumin tumors, B7-1-painted ex vivo–amplified OT-1 T cells induced complete tumor regression in 65% of treated mice, whereas the control T cells did so in only 28% of treated mice. Finally, on transfer into mice bearing less immunogenic 4T1 breast tumors, B7-1-painted tumor-reactive CD8+ T cells improved the survival of treated mice to a greater extent than did the control T cells. Hence, this study establishes that arming tumor-reactive T cells with a costimulator can enhance their antitumor efficacy. (Cancer Res 2006; 66(13): 6793-9)
A Novel Role for Human Sulfiredoxin in the Reversal of Glutathionylation
Authors: Findlay Victoria J. , Townsend Danyelle M. , Morris Taylor E. , Fraser Jacob P. , He Lin , Tew Kenneth D. 
Published: July 2006

Abstract
Modification of protein cysteine residues by disulfide formation with glutathione (glutathionylation) is a reversible posttranslational modification of critical importance in controlling cell signaling events following oxidative and/or nitrosative stress. Here, we show that human sulfiredoxin, a small redox protein conserved in eukaryotes, can act as a novel regulator of the redox-activated thiol switch in cells by catalyzing deglutathionylation of a number of distinct proteins in response to oxidative and/or nitrosative stress. Actin and protein tyrosine phosphatase 1B were identified in vitro as targets of sulfiredoxin 1 (Srx1)–dependent deglutathionylation and confirmed in vivo by two-dimensional gel electrophoresis analysis. In addition, we show that Srx1-dependent deglutathionylation is functionally relevant through restoration of phosphatase activity. Human sulfiredoxin contains one cysteine residue (Cys99) that is conserved in all family members. Mutation of the cysteine residue inhibits deglutathionylation but did not affect its capacity to bind intracellular proteins. Furthermore, sulfiredoxin is not an acceptor molecule for the GS− moiety during the reaction process. Using two-dimensional gel electrophoresis, we identified multiple protein targets in vivo that are deglutathionylated by sulfiredoxin following oxidative and/or nitrosative stress. This novel deglutathionylation function of sulfiredoxin suggests it has a central role in redox control with potential implications in cell signaling. (Cancer Res 2006; 66(13): 6800-6)
Inhibition of Tumor Growth and Progression of LNCaP Prostate Cancer Cells in Athymic Mice by Androgen and Liver X Receptor Agonist
Authors: Chuu Chih-pin , Hiipakka Richard A. , Kokontis John M. , Fukuchi Junichi , Chen Rou-Yu , Liao Shutsung 
Published: July 2006

Abstract
Androgen-dependent human LNCaP 104-S tumor xenografts progressed to androgen-independent relapsed tumors (104-Rrel) in athymic mice after castration. The growth of 104-Rrel tumors was suppressed by testosterone. However, 104-Rrel tumors adapted to androgen and regrew as androgen-stimulated 104-Radp tumors. Androgen receptor expression in tumors and serum prostate-specific antigen increased during progression from 104-S to 104-Rrel but decreased during transition from 104-Rrel to 104-Radp. Expression of genes related to liver X receptor (LXR) signaling changed during progression. LXRα, LXRβ, ATP-binding cassette transporter A1 (ABCA1), and sterol 27-hydroxylase decreased during progression from 104-S to 104-Rrel. These coordinated changes in LXR signaling in mice during progression are consistent with our previous findings that reduction of ABCA1 gene expression stimulates proliferation of LNCaP cells. To test if attenuation of LXR signaling may enhance prostate cancer progression from an androgen-dependent state to an androgen-independent state, castrated mice carrying 104-S tumors were given the synthetic LXR agonist T0901317 by gavage. T0901317 delayed progression from 104-S to 104-Rrel tumors. Based on our in vivo model, androgen is beneficial for the treatment of androgen-independent androgen receptor–rich prostate cancer and modulation of LXR signaling may be a potentially useful therapy for prostate cancer. (Cancer Res 2006; 66(13): 6482-6)
CD1d-Restricted T Cells License B Cells to Generate Long-Lasting Cytotoxic Antitumor ImmunityIn vivo
Authors: Chung Yeonseok , Kim Byung-Seok , Kim Yeon-Jeong , Ko Hyun-Jeong , Ko Sung-Youl , Kim Dong-Hyeon , Kang Chang-Yuil 
Published: July 2006

AbstractAlthough resting B cells are known for being poorly immunogenic and for inducing T-cell tolerance, we have here attempted to test whether their immunogenicity could be enhanced by CD1d-restricted invariant T cells (iNKT) to a point where they could be used in cellular vaccines. We found that the addition of the iNKT ligand α-galactosylceramide (αGalCer) to peptide-loaded B cells overcame peptide-specific T-cell unresponsiveness and allowed for the generation of peptide-specific memory CTL immunity. This CTL was induced independently of CD4 T and natural killer cells but required iNKT and CD8 T cells. B cells directly primed CTL, and the αGalCer and the peptide must be presented on the same cell. Importantly, our B-cell–based vaccine is comparable in efficiency with dendritic cell–based vaccines, inducing similar CTL responses as well as providing an effective regimen for preventing and suppressing s.c. and metastatic tumors. Therefore, with the help of iNKT, peptide-pulsed B cells can establish long-lasting antitumor immunity and so show promise as the basis for an alternative cell-based vaccine. (Cancer Res 2006; 66(13): 6843-50)
Raimon Panikkar's Cosmotheandrism — Theologizing at the Meeting Point of Hinduism and Christianity
Authors: Komulainen Jyri 
Published: July 2006

AbstractRaimon Panikkar (b. 1918), a Catalan-born Hindu-Christian, is a prominent theorist of interreligious dialogue. This article provides an analysis of his theology of religions. On the basis of the most recent sources available, it appears that even his 'radical pluralism' cannot eschew the inherent problems characteristic of pluralistic theologies of religions.Unlike other pluralists, Panikkar does not subscribe to the Enlightenment tradition. Instead, his plea for the transformation of religions is based on an idiosyncratic 'Cosmotheandrism', which draws on both primordial religious traditions and existentialist philosophy. The prerequisites of interreligious dialogue, as outlined in his work, thus entail commitment to a particular cosmology and mode of consciousness.
Satellite Measurement of Stratospheric Winds and Ozone Using Doppler Michelson Interferometry. Part II: Retrieval Method and Expected Performance
Authors: Rochon Yves J. , Rahnama Peyman , McDade Ian C. 
Published: July 2006

Abstract
This paper is about the retrieval of horizontal wind and ozone number density from measurement simulations for the Stratospheric Wind Interferometer for Transport Studies (SWIFT). This instrument relies on the concept of imaging Doppler Michelson interferometry applied to thermal infrared emission originating from the stratosphere. The instrument and measurement simulations are described in detail in the first of this series of two papers. In this second paper, a summary of the measurement simulations and a data retrieval method suited to these measurements are first presented. The inversion method consists of the maximum a posteriori solution approach with added differential regularization and, when required, iterations performed with the Gauss–Newton method. Inversion characterization and an error analysis have been performed. Retrieval noise estimates have been obtained both from derived covariance matrices and sample inversions. Retrieval noise levels for wind and ozone number density of ∼1–3 m s−1 and &lt;1% have been obtained over the altitude range of 20–45 km with Backus–Gilbert resolving lengths of ∼1.5 km. Retrieval noise levels over the extended altitude range of 15–55 km are less than 10 m s−1 and 2%. The sensitivity to other error sources has been examined through a few sample realizations. The contributions from these other errors can be as important as or more so than retrieval noise. An error budget identifying contributing wind and ozone error levels to total errors of 5 m s−1 and 5% for altitudes of 20–45 km has been prepared relying on the retrieval errors and knowledge of the instrument design.
Clay mineralogy of the Tertiary onshore and offshore strata of the British Isles
Authors: Huggett J. M. , Knox R. W. O'B. 
Published: July 2006

AbstractTertiary sediments are of restricted occurrence in the onshore British Isles but occur extensively offshore, attaining thicknesses of ~4 km in the Faroe—Shetland Basin and ~3 km in the North Sea Basin. Clay mineral stratigraphic studies of the North Sea Paleocene to Lower Miocene successions show a dominance of smectite (and smectite-rich illite-smectite) with minor illite, kaolin and chlorite. Abundant smectite in the Paleocene and Eocene reflects alteration of volcanic ash derived from pyroclastic activity associated with the opening of the North Atlantic between Greenland and Europe. However, the persistence of high smectite into the Oligocene and Middle Miocene indicates that smectite-rich soils on adjacent land areas may also have been an important source of detrital clays. An upwards change to illite-dominated assemblages in the Middle Miocene reflects higher rates of erosion and detrital clay supply, with a subsequent increase in chlorite reflecting climatic cooling. The persistence of smectite-rich assemblages to depths of >3000 m in the offshore indicates little burial-related diagenesis within the mudstone succession, possibly as a consequence of over-pressuring. Despite the importance of Paleocene and Eocene sandstones as hydrocarbon reservoirs in the North Sea and Faroe-Shetland basins, there are few published details of the authigenic clays. The principal clay cements in these sandstones are kaolin and chlorite, with only minor illite reported.The offshore successions provide a valuable background to the interpretation of the more intensively studied, but stratigraphically less complete, onshore Tertiary successions. The most extensive onshore successions occur in the London and Hampshire basins where sediments of Paleocene to earliest Oligocene age are preserved. Here clay assemblages are dominated by illite and smectite with subordinate kaolin and chlorite. The relatively large smectite content of these successions is also attributed primarily to the alteration of volcanic ash. Associated non-smectitic clays are largely detrital in origin and sourced from areas to the west, with reworking of laterites and “china clay” deposits developed over Cornish granites. Authigenic clays include glauconite (sensu lato), early diagenetic kaolin that has replaced muscovite (principally in the London Clay Formation of the London Basin) and smectite that has replaced ash. Pedogenesis has extensively modified the assemblages in the Reading Formation and Solent Group. Tertiary sediments are largely missing from onshore northern and western Britain, but clays and sands of Eocene and Oligocene age are locally preserved in small fault-bounded basins. Here, clay assemblages are dominated by kaolin with minor illite.
Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a
Authors: Nie Huan , Yang Fan , Zhang Xiaobing , Yang Jian , Chen Lihong , Wang Jing , Xiong Zhaohui , Peng Junping , Sun Lilian , Dong Jie , Xue Ying , Xu Xingye , Chen Shuxia , Yao Zhijian , Shen Yan , Jin Qi 
Published: July 2006

Abstract

Background

Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301).

Results
The Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes.

Conclusion
Our data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.
Relationship between resident workload and self-perceived learning on inpatient medicine wards: a longitudinal study
Authors: Haney Elizabeth M , Nicolaidis Christina , Hunter Alan , Chan Benjamin KS , Cooney Thomas G , Bowen Judith L 
Published: July 2006

Abstract

Background
Despite recent residency workload and hour limitations, little research on the relationship between workload and learning has been done. We sought to define residents' perceptions of the optimal patient workload for learning, and to determine how certain variables contribute to those perceptions. Our hypothesis was that the relationship between perceived workload and learning has a maximum point (forming a parabolic curve): that either too many or too few patients results in sub-optimal learning.

Methods
Residents on inpatient services at two academic teaching hospitals reported their team and individual patient censuses, and rated their perception of their learning; the patient acuity; case variety; and how challenged they felt. To estimate maximum learning scores, linear regression models with quadratic terms were fit on learning score.

Results
Resident self-perceived learning correlated with higher acuity and greater heterogeneity of case variety. The equation of census versus learning score, adjusted for perception of acuity and case mix scores, showed a parabolic curve in some cases but not in others.

Conclusion
These data suggest that perceived resident workload is complex, and impacted by additional variables including patient acuity and heterogeneity of case variety. Parabolic curves exist for interns with regard to overall census and for senior residents with regard to new admissions on long call days.
Effect of Letrozole Versus Placebo on Bone Mineral Density in Women With Primary Breast Cancer Completing 5 or More Years of Adjuvant Tamoxifen: A Companion Study to NCIC CTG MA.17
Authors: Perez Edith A. , Josse Robert G. , Pritchard Kathleen I. , Ingle James N. , Martino Silvana , Findlay Brian P. , Shenkier Tamara N. , Tozer Richard G. , Palmer Michael J. , Shepherd Lois E. , Liu Shifang , Tu Dongsheng , Goss Paul E. 
Published: July 2006

Purpose Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. Patients and Methods Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. Results Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81% < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (−3.6% v −0.71%; P = .044) and lumbar spine BMD (−5.35% v −0.70%; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1% v 0%; P = .064). Conclusion After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference.