bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination against the Forkhead Family Transcription Factor Foxp3 Enhances Tumor Immunity
Authors: Nair Smita , Boczkowski David , Fassnacht Martin , Pisetsky David , Gilboa Eli 
Published: January 2007

AbstractDepletion of CD4+CD25+ regulatory T cells (Treg) by treatment with αCD25 antibody synergizes with vaccination protocols to engender protective immunity in mice. The effectiveness of targeting CD25 to eliminate Treg is limited by the fact that CD25, the low-affinity interleukin-2 receptor, is up-regulated on conventional T cells. At present, foxp3 is the only product known to be exclusively expressed in Treg of mice. However, foxp3 is not expressed on the cell surface and hence cannot be targeted with antibodies. In this study, we tested the hypothesis that vaccination of mice against foxp3, a self-antigen expressed also in the thymus, is capable of stimulating foxp3-specific CTL that will cause the depletion of Treg and enhanced antitumor immunity. Vaccination of mice with foxp3 mRNA-transfected dendritic cells elicited a robust foxp3-specific CTL response and potentiated vaccine-induced protective immunity comparably with that of αCD25 antibody administration. In contrast to αCD25 antibody treatment, repeated foxp3 vaccination did not interfere with vaccine-induced protective immunity. Importantly, foxp3 vaccination led to the preferential depletion of foxp3-expressing Treg in the tumor but not in the periphery, whereas αCD25 antibody treatment led to depletion of Treg in both the tumor and the periphery. Targeting foxp3 by vaccination offers a specific and simpler protocol for the prolonged control of Treg that may be associated with reduced risk of autoimmunity, introducing an approach whereby specific depletion of cells is not limited to targeting products expressed on the cell surface. [Cancer Res 2006;67(1):371–80]
A Glycolytic Mechanism Regulating an Angiogenic Switch in Prostate Cancer
Authors: Wang Jianhua , Wang Jincheng , Dai Jinlu , Jung Younghun , Wei Chuen-Long , Wang Yu , Havens Aaron M. , Hogg Phillip J. , Keller Evan T. , Pienta Kenneth J. , Nor Jacques E. , Wang Cun-Yu , Taichman Russell S. 
Published: January 2007

Abstract
The generation of an ‘angiogenic switch’ is essential for tumor growth, yet its regulation is poorly understood. In this investigation, we explored the linkage between metastasis and angiogenesis through CXCL12/CXCR4 signaling. We found that CXCR4 regulates the expression and secretion of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 reduced the secretion of vascular endothelial growth factor and interleukin-8 and increased the generation of angiostatin. At metastatic sites, however, high levels of CXCL12 signaling through CXCR4 reduced PGK1 expression, releasing the angiogenic response for metastastic growth. These data suggest that PGK1 is a critical downstream target of the chemokine axis and an important regulator of an ‘angiogenic switch’ that is essential for tumor and metastatic growth. [Cancer Res 2007;67(1):149–59]
Regulation of mTOR by Phosphatidic Acid?
Authors: Foster David A. 
Published: January 2007

Abstract
Interest in the regulation of the mammalian target of rapamycin (mTOR) has increased substantially in recent years largely because of an apparent link between mTOR and survival signals in human cancer cells. Much has been learned about the regulation of mTOR in response to survival signals generated by phosphatidylinositol 3-kinase (PI3K). However, another mechanism for regulating mTOR has been proposed involving the generation of phosphatidic acid (PA). PA is the metabolic product of phospholipase D (PLD), whose activity is elevated in a large number of human cancers, and, like PI3K, has been implicated in the survival of human cancer cells. Although the regulation of mTOR by the PI3K signaling pathway is well established, a role for PLD and PA in regulating mTOR has been controversial. In this review, the evidence implicating PLD and PA in the regulation of mTOR is summarized, and the implications of this novel and potentially important mechanism for regulating mTOR are discussed. [Cancer Res 2007;67(1):1–4]
Perspectives of γδ T Cells in Tumor Immunology
Authors: Kabelitz Dieter , Wesch Daniela , He Wei 
Published: January 2007

Abstract
Subsets of human γδ T cells recognize tumor cell–expressed ligands that are not seen by the T-cell receptor of conventional αβ T cells. Vδ1 T cells recognize MHC class I chain–related molecules A and B and UL-16–binding proteins expressed at variable levels on epithelial tumor cells and some leukemias and lymphomas. In addition, therapeutically used aminobisphosphonates and synthetic phosphoantigens activate Vδ2 T cells, the dominant subset of γδ T cells in human peripheral blood that display strong cytotoxicity towards various epithelial tumors. Intentional activation of γδ T cells in vivo and/or adoptive cell therapy with in vitro expanded γδ T cells holds considerable promise as a novel immunotherapy in certain types of cancer. [Cancer Res 2007;67(1):5–8]
Ribonucleotide Reductase Small Subunit p53R2 Facilitates p21 Induction of G1 Arrest under UV Irradiation
Authors: Xue Lijun , Zhou Bingsen , Liu Xiyong , Heung Yvonne , Chau Jennifer , Chu Emilie , Li Shan , Jiang Chunglin , Un Frank , Yen Yun 
Published: January 2007

Abstract
p53R2, which is one of the two known ribonucleotide reductase small subunits (the other being M2), is suggested to play an important role in supplying deoxynucleotide triphosphates (dNTP) for DNA repair during the G1 or G2 phase of the cell cycle. The ability of p53R2 to supply dNTPs for repairing DNA damages requires the presence of a functional p53 tumor suppressor. Here, we report in vivo physical interaction and colocalization of p53R2 and p21 before DNA damage. Mammalian two-hybrid assay further indicates that the amino acids 1 to 113 of p53R2 are critical for interacting with the NH2-terminal region (amino acids 1–93) of p21. The binding between p21 and p53R2 decreases inside the nucleus in response to UV, the time point of which corresponds to the increased binding of p21 with cyclin-dependent kinase-2 (Cdk2), and the decreased Cdk2 activity in the nucleus at G1. Interestingly, p53R2 dissociates from p21 but facilitates the accumulation of p21 in the nucleus in response to UV. On the other hand, the ribonucleotide reductase activity increases at the corresponding time in response to UV. These data suggest a new function of p53R2 of cooperating with p21 during DNA repair at G1 arrest. [Cancer Res 2007;67(1):16–21]
Metronomic Chemotherapy Enhances the Efficacy of Antivascular Therapy in Ovarian Cancer
Authors: Kamat Aparna A. , Kim Tae Jin , Landen Charles N. , Lu Chunhua , Han Liz Y. , Lin Yvonne G. , Merritt William M. , Thaker Premal H. , Gershenson David M. , Bischoff Farideh Z. , Heymach John V. , Jaffe Robert B. , Coleman Robert L. , Sood Anil K. 
Published: January 2007

AbstractMetronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic taxanes alone and in combination with AEE788—a dual epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) inhibitor—in an orthotopic mouse model of ovarian cancer. Growth-modulating effects of metronomic and maximum tolerated dose (MTD) regimens on overall survival were tested in vivo using both chemotherapy-sensitive (HeyA8 and SKOV3ip1) and chemotherapy-resistant (HeyA8-MDR) models. Treated tumors were stained for microvessel density (CD31), proliferation index (proliferating cell nuclear antigen), and apoptosis (terminal deoxyribonucleotide transferase–mediated nick-end labeling). The cytotoxic effects of MTD and metronomic dosing were tested with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of metronomic regimens on circulating endothelial precursors (CEP) and tumor-specific cell-free DNA levels were assessed. In vivo, metronomic docetaxel resulted in significant reduction of tumor growth in the taxane-sensitive cell lines, whereas metronomic docetaxel plus AEE788 had an additive effect resulting in significant prolongation in survival. Combination therapy was effective even in the taxane-resistant model. Metronomic chemotherapy alone and combined with AEE788 resulted in a decrease in the proliferative index and microvessel density of treated tumors, whereas combination therapy increased the apoptotic index (P &lt; 0.001). In vitro, metronomic taxanes caused endothelial cell toxicity at 10- to 100-fold lower concentrations compared with MTD dosing. Metronomic regimens inhibited mobilization of CEPs (P &lt; 0.05) and led to a decrease in cell-free DNA levels (P &lt; 0.05). Our results suggest that metronomic taxane chemotherapy with dual EGFR and VEGFR inhibition is highly efficacious and should be considered for future clinical trials. [Cancer Res 2007;67(1):281–8]
Understanding Equatorial Atlantic Interannual Variability
Authors: Keenlyside Noel S. , Latif Mojib 
Published: January 2007

Abstract
An observational-based analysis of coupled variability in the equatorial Atlantic and its seasonality is presented. Regression analysis shows that the three elements of the Bjerknes positive feedback exist in the Atlantic and are spatially similar to those of the Pacific. The cross-correlation functions of the elements of the Bjerknes feedback are also similar and consistent with an ocean–atmosphere coupled mode. However, the growth rate in the Atlantic is up to 50% weaker, and explained variance is significantly lower. The Bjerknes feedback in the Atlantic is strong in boreal spring and summer, and weak in other seasons, which explains why the largest sea surface temperature anomalies (SSTAs) occur in boreal summer. Its seasonality is determined by seasonal variations in both atmospheric sensitivity to SSTA and SSTA sensitivity to subsurface temperature anomalies.
Mouse preimplantation embryo responses to culture medium osmolarity include increased expression of CCM2 and p38 MAPK activation
Authors: Fong Barry , Watson Patricia H , Watson Andrew J 
Published: January 2007

AbstractBackgroundMechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK) occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM) was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2). The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments.ResultsOur results indicate thatCcm2along with upstream p38 MAPK pathway constituents (Map3k3,Map2k3,Map2k6,and Map2k4) are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels.ConclusionThese results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.
Molecular analysis of hepatitis B virus "a" determinant in asymptomatic and symptomatic Mexican carriers
Authors: Ruiz-Tachiquín Martha-Eugenia , Valdez-Salazar Hilda-Alicia , Juárez-Barreto Vicencio , Dehesa-Violante Margarita , Torres Javier , Muñoz-Hernández Onofre , Alvarez-Muñoz Ma-Teresa 
Published: January 2007

Abstract

Background
Hepatitis B virus (HBV) is a small DNA-containing virus with 4 genes, C, S, X and P. The S gene codes for the surface antigen (HBsAg), which contains the "a" determinant, the main region for induction of a protective humoral immune response. To compare the genotype and sequence of the "a" determinant between strains isolated from asymptomatic and symptomatic Mexican HBV carriers.

Results
21 asymptomatic (blood donors) and 12 symptomatic (with clinical signs and with >1 year lamivudine treatment) HBV carriers were studied; all patients were positive for the HBsAg in serum. Viral load, genotypes, and subtypes were determined in plasma. A fragment of the S gene including the "a" determinant was PCR amplified and sequenced to determine genotype, subtype and to identify mutations. Mean viral load was 0.7965 × 104 copies/ml in asymptomatic carriers and 2.73 × 106 copies/ml in symptomatic patients. Genotypes H, C, and F were identified in asymptomatic individuals; whereas H was dominant in symptomatic patients. A fragment of 279 bp containing the "a" determinant was amplified from all 33 carriers and sequences aligned with S gene sequences in the GenBank. Mutations identified were Y100N, T126I, Q129H and N146K in the asymptomatic group, and F93I and A128V in the symptomatic group.

Conclusion
Differences in genotype and in mutations in the "a" determinant were found between strains from asymptomatic and symptomatic HBV Mexican carriers.
Pivotal Advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection
Authors: Raué Hans-Peter , Slifka Mark K 
Published: January 2007

AbstractPrevious studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4– T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antivral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.
Medical Oncologists' Views on Communicating With Patients About Chemotherapy Costs: A Pilot Survey
Authors: Schrag Deborah , Hanger Morgan 
Published: January 2007

Purpose As chemotherapy costs escalate, financial concerns have become relevant for more cancer patients. Yet, little is known about how oncologists communicate with patients about coping with chemotherapy treatment costs. Methods To understand how medical oncologists view these issues, we developed a survey eliciting their attitudes and behaviors surrounding discussing costs of therapy in the context of treatment decision making. The survey was piloted at a national meeting and then mailed to a random sample of actively practicing 2005 American Society of Clinical Oncology members in the 50 United States. Survey items used a 5-point Likert scale designed to elicit oncologists' practices and attitudes regarding discussion of chemotherapy costs with patients. The first survey wave also included two clinical vignettes about hypothetical patients contemplating treatment with high-cost regimens. Results Of 530 mailed surveys, 167 were returned for an overall response rate of 31.5%. Most oncologists reported knowledge of their patients' financial well-being: 15% all of the time, 39% most of the time, 33% some of the time, and 13% rarely/none of the time. There was substantial variation in oncologists' attitudes toward discussing chemotherapy costs with patients: 42% did so always or most of the time, 32% sometimes did, and 26% rarely or never did. Most oncologists (80%) felt that it was important to be explicit about the impact of treatment choices on patients' finances. However, 20% maintained that costs play no role in clinical encounters, and 31% reported a high degree of discomfort in discussing costs with patients. Referral to support staff for these discussions was common. Only a few oncologists (16%) acknowledged omitting treatment options on the basis of their perceptions of patients' ability to afford treatment. Conclusion There is important heterogeneity in medical oncologists' attitudes toward discussing chemotherapy treatment costs with patients. Mismatch between physician and patient viewpoints has the potential to result in miscommunication and suboptimally informed treatment decisions.
Afferent input modulates the chronic hypercapnia-induced increase in respiratory-related central pH/CO2 chemosensitivity in the cane toad (Bufo marinus)
Authors: Gheshmy Afshan , Anari Ali , Besada Donela , Reid Stephen G. 
Published: January 2007

SUMMARYThe goal of this study was to examine the role of respiratory-related afferent input on the chronic hypercapnia (CHC)-induced increase in central respiratory-related pH/CO2 chemosensitivity in cane toads (Bufo marinus). Toads were exposed to CHC (3.5% CO2) for 10 days,following which in vitro brainstem-spinal cord preparations were used to assess central respiratory-related pH/CO2 chemosensitivity. Motor output from the vagus nerve root was used as an index of breathing(fictive breathing). Olfactory denervation (OD), prior to exposure to CHC, was used to remove the influence of CO2-sensitive olfactory chemoreceptors, which inhibit breathing. Exposure to chronic hyperoxic hypercapnia (CHH) was used to reduce the level of arterial chemoreceptor input compared with CHC alone. In vivo experiments examined the effects of CHC, CHH and OD on the acute hypercapnic ventilatory response of intact animals. In vitro, a reduction in artifical cerebral spinal fluid(aCSF) pH increased fictive breathing in preparations taken from control and CHC animals. CHC caused an increase in fictive breathing compared with controls. OD and CHH abolished the CHC-induced augmentation of fictive breathing. In vivo, CHC did not cause an augmentation of the acute hypercapnic ventilatory response. CHH reduced the in vivo acute hypercapnic ventilatory response compared with animals exposed to CHC. In vivo, OD reduced breathing frequency and increased breath amplitude in both control and CHC animals. The results suggest that afferent input from olfactory and arterial chemoreceptors, during CHC, is involved in triggering the CHC-induced increase in central respiratory-related pH/CO2chemosensitivity.
Gait characterisation and classification in horses
Authors: Robilliard Justine J. , Pfau Thilo , Wilson Alan M. 
Published: January 2007

SUMMARY
Although a large number of foot-fall sequences are possible in quadrupeds,few sequences are routinely used. The aim of this paper is to characterise, by foot-fall pattern, the gaits used by horses and develop a novel technique to classify symmetric and asymmetric gaits using one common criterion. To achieve this speed and relative foot-fall, timings of all four limbs of eight Icelandic horses were measured using accelerometers. Linear discriminant analysis (LDA) was performed to find criteria that are optimal for discriminating between the different gaits. This also allowed us to evaluate whether gaits should be considered a continuum or as discrete entities. Foot-fall timings (stance times, swing times, duty factors and stride frequencies) for walk, tolt, trot, pace, left canter, right canter, left gallop and right gallop during over-ground locomotion at a range of speeds are presented. In the gaits of walk, tolt, trot and pace, foot-fall timings were equal between left and right hindlimbs and forelimbs so these gaits can be considered as symmetrical. Differences in stance times and duty factors were observed between gaits but are unlikely to be of biological significance due to their similar magnitude and inconsistent relative trends. This implies that metabolics or peak limb forces derived from contact times are unlikely to be the principal driving factors in gait transition between walk, trot, pace,canters and gallops, although these factors may influence the use of tolt at the lower and higher speeds. Gaits did cluster in the LDA space and the running gaits (tolt, trot, pace, left and right canters and gallops) could be considered a kinematic continuum but the relative relationship with walk may be more complex. Thus, LDA analysis has enabled common criteria to be discovered to accurately classify equine gaits on the basis of foot-fall timings on a stride-by-stride basis.
Adaptive regulation of digestive performance in the genusPython
Authors: Ott Brian D. , Secor Stephen M. 
Published: January 2007

SUMMARYThe adaptive interplay between feeding habits and digestive physiology is demonstrated by the Burmese python, which in response to feeding infrequently has evolved the capacity to widely regulate gastrointestinal performance with feeding and fasting. To explore the generality of this physiological trait among pythons, we compared the postprandial responses of metabolism and both intestinal morphology and function among five members of the genus Python: P. brongersmai, P. molurus, P. regius, P. reticulatus and P. sebae. These infrequently feeding pythons inhabit Africa, southeast Asia and Indonesia and vary in body shape from short and stout (P. brongersmai) to long and slender (P. reticulatus). Following the consumption of rodent meals equaling 25% of snake body mass, metabolic rates of pythons peaked at 1.5 days at levels 9.9-to 14.5-fold of standard metabolic rates before returning to prefeeding rates by day 6-8. Specific dynamic action of these meals (317-347 kJ) did not differ among species and equaled 23-27% of the ingested energy. For each species,feeding triggered significant upregulation of intestinal nutrient transport and aminopeptidase-N activity. Concurrently, intestinal mass doubled on average for the five species, in part due to an 85% increase in mucosal thickness, itself a product of 27-59% increases in enterocyte volume. The integrative response of intestinal functional upregulation and tissue hypertrophy enables each of these five python species, regardless of body shape, to modulate intestinal performance to meet the demands of their large infrequent meals.