bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavonoids and the Risk of Renal Cell Carcinoma
Authors: Bosetti Cristina , Rossi Marta , McLaughlin Joseph K. , Negri Eva , Talamini Renato , Lagiou Pagona , Montella Maurizio , Ramazzotti Valerio , Franceschi Silvia , LaVecchia Carlo 
Published: January 2007

AbstractIntake of flavonoids has been inversely related to the risk of various common neoplasms, but limited data exist on renal cell carcinoma (RCC). We used data from a case-control study conducted between 1994 and 2002 in four Italian areas to study the relation between major flavonoid classes and RCC. The study included 767 cases with incident, histologically confirmed RCC and 1,534 hospital controls admitted for acute, nonneoplastic conditions and matched with cases by study center, sex, and quinquennia of age. We applied published data on food and beverage content of six major classes of flavonoids to dietary information collected through a validated food frequency questionnaire. After adjustment for major recognized confounding factors and total energy intake, the odds ratios for subjects in the highest versus the lowest quintile of intake were 0.80 [95% confidence interval (95% CI), 0.58-1.11] for total flavonoids, 0.76 (95% CI, 0.56-1.03) for isoflavones, 0.94 (95% CI, 0.60-1.47) for anthocyanidins, 0.77 (95% CI, 0.56-1.06) for flavan-3-ols, 0.90 (95% CI, 0.67-1.21) for flavanones, 0.68 (95% CI, 0.50-0.93) for flavones, and 0.69 (95% CI, 0.50-0.95) for flavonols. Allowance for vegetable and fruit consumption only partly explained these inverse relations. Thus, flavonoids, and particularly flavones and flavonols, may account, at least in part, for the favorable role of plant foods on RCC. (Cancer Epidemiol Biomarkers Prev 2007;16(1):98–101)
Adenovirus type 5 E1A gene therapy for ovarian clear cell carcinoma: a potential treatment strategy
Authors: Itamochi Hiroaki , Kigawa Junzo , Kanamori Yasunobu , Oishi Tetsuro , Bartholomeusz Chandra , Nahta Rita , Esteva Francisco J. , Sneige Nour , Terakawa Naoki , Ueno Naoto T. 
Published: January 2007

Abstract
Resistance of ovarian clear cell carcinoma (CCC) to platinum-based chemotherapy is associated with poor prognosis, and an effective treatment for advanced disease is urgently needed. HER2/neu is up-regulated more often in CCC than in other histologic types of epithelial ovarian cancer. The purpose of this study was to assess possible treatment for ovarian CCC with the anti-HER2 antibody trastuzumab or human adenovirus type 5 E1A. We treated 10 CCC cell lines with trastuzumab or E1A and assessed cell viability, proliferation, and colony formation and the expression of HER2 and wild-type p53 proteins and molecules downstream of those signaling pathways. HER2 protein was detected at various levels in all 10 cell lines by Western blotting and in 5 CCC cell lines by immunohistochemical staining; HER2 gene amplification was detected (by fluorescence in situ hybridization) in only one cell line (RMG-I). Trastuzumab did not inhibit proliferation in any of the four CCC cell lines tested (RMG-I, SKOV-2, OVTOKO, and OVSAYO). However, transfection with E1A (as compared with control vectors) reduced colony formation in all 10 CCC cell lines regardless of HER2 expression level. Infection of RMG-I and SMOV-2 cells with an adenoviral vector encoding E1A led to significant (P &lt; 0.05) suppression of proliferation and enhancement of cell death; this effect required stabilization of p53 (but not p73) protein and was associated with the up-regulation of Bax and the cleavage of caspase-9. Other mechanisms, such as p53-independent apoptosis, may also be involved in E1A-mediated cell death in CCC. Finally, treatment with E1A prolonged survival in a CCC xenograft model (P &lt; 0.001). E1A gene therapy, because of its ability to stabilize wild-type p53, is worth exploring as a treatment modality for women with ovarian CCC, which typically expresses wild-type p53. [Mol Cancer Ther 2007;6(1):227–35]
Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells
Authors: Kamada Masayuki , So Alan , Muramaki Mototsugu , Rocchi Palma , Beraldi Eliana , Gleave Martin 
Published: January 2007

AbstractHeat shock protein 27 (Hsp27) is a cytoprotective chaperone that is phosphoactivated during cell stress that prevents aggregation and/or regulate activity and degradation of certain client proteins. Recent evidence suggests that Hsp27 may be involved in tumor progression and the development of treatment resistance in various tumors, including bladder cancer. The purpose of this study was to examine, both in vitro and in vivo, the effects of overexpression of Hsp27 and, correspondingly, the down-regulation of Hsp27 using small interfering (si) RNA and OGX-427, a second-generation antisense oligonucleotide targeting Hsp27. Hsp27 overexpression increased UMUC-3 cell growth and resistance to paclitaxel. Both OGX-427 and Hsp27 siRNA decreased Hsp27 protein and mRNA levels by &gt;90% in a dose- and sequence-specific manner in human bladder cancer UMUC-3 cells. OGX-427 or Hsp27 siRNA treatment induced apoptosis and enhanced sensitivity to paclitaxel in UMUC-3 cells. In vivo, OGX-427 significantly inhibited tumor growth in mice, enhanced sensitivity to paclitaxel, and induced significantly higher levels of apoptosis compared with xenografts treated with control oligonucleotides. Collectively, these findings suggest that Hsp27 knockdown with OGX-427 and combined therapy with paclitaxel could be a novel strategy to inhibit the progression of bladder cancer. [Mol Cancer Ther 2007;6(1):299–308]
Deficiency of Niemann-Pick C1 Like 1 Prevents Atherosclerosis in ApoE−/−Mice
Authors: Davis Harry R. , Hoos Lizbeth M. , Tetzloff Glen , Maguire Maureen , Zhu Li-ji , Graziano Michael P. , Altmann Scott W. 
Published: January 2007

Objective—The objective of this study was to determine whether the deficiency of Niemann-Pick C1 Like 1 (Npc1l1) prevents atherosclerosis in apoE null mice.Methods and Results—Npc1l1−/−/apoE null−/−mice were generated and found to have a significant reduction in cholesterol absorption (−77%) compared with wild-type or apoE−/−mice. Npc1l1/apoE−/−mice were fed a chow or Western diet for 24 weeks, then lipoprotein, hepatic, and biliary cholesterol, and atherosclerosis development was compared with apoE−/−, Npc1l1−/−, wild-type, and ezetimibe-treated apoE−/−mice. Chylomicron remnant/ VLDL cholesterol levels were reduced 80% to 90% in both chow and Western diet-fed Npc1l1/apoE−/−mice relative to apoE−/−mice. Male Npc1l1−/−and Npc1l1/apoE−/−mice were completely resistant to diet induced hypercholesterolemia, and both male and female mice were completely resistant to increases in hepatic and biliary cholesterol levels. Atherosclerosis was reduced 99% in aortic lesion surface area, 94% to 97% in innominate artery intimal lesion area, and >90% in aortic root lesion area in both male and female Npc1l1/apoE−/−mice relative to apoE−/−mice.Conclusions—Lack of Npc1l1, the molecular target of the cholesterol absorption inhibitor ezetimibe, in apoE−/−mice results in a significant reduction in cholesterol absorption and plasma cholesterol levels, and causes a nearly complete protection from the development of atherosclerosis, under both cholesterol-fed and non-cholesterol-fed conditions.
Soft Tissue Tendon Graft Fixation in Serially Dilated or Extraction-Drilled Tibial Tunnels
Authors: Dunkin Brad S. , Nyland John , Duffee Andrew R. , Brunelli Jeffrey A. , Burden Robert , Caborn David 
Published: January 2007

Background Tibial tunnel preparation may contribute to improved soft tissue graft fixation. Hypothesis Step dilation produces greater tunnel wall bone volume than does extraction drilling and increases fixation strength. Bioabsorbable interference screw divergence decreases fixation strength, regardless of tunnel preparation method. Study Design Controlled laboratory study. Methods Twenty porcine tibias were divided into 2 groups of 10 with matching mean apparent bone mineral density. One group received 9-mm-diameter extraction-drilled tunnels, and the other group received 7-mm-diameter extraction-drilled tunnels followed by step dilation to 9 mm. High-resolution quantitative computerized tomography scans and voxel analysis techniques determined tunnel wall bone volume fraction. Screws secured 8.5-mm-diameter porcine grafts in the tunnels. Repeat scans were used to determine screw divergence. Cyclic loading was performed in a servohydraulic device before load to failure testing. Results The step dilation group had greater tunnel wall bone volume/total volume than did the extraction drilled group; however, a significant increase in fixation strength was not detected. Specimens with screw divergence angles less than 15° had superior fixation and insertion torques compared with specimens with angles 15° or more. Screw divergence correlated more strongly with fixation strength than did mean apparent bone mineral density or screw insertion torque. Conclusion Step dilation increased tunnel wall bone volume/total volume, but fixation strength did not improve. Screw divergence ≥15° decreases graft-bone tunnel fixation whether or not step dilation is performed. Clinical Relevance Screw alignment plays a greater role in anterior cruciate ligament graft fixation than does extraction drilling or step dilation tunnel preparation methods in healthy bone.
Ankle Sprain Injuries and Risk Factors in Amateur Soccer Players during a 2-Year Period
Authors: Kofotolis Nikolaos D. , Kellis Eleftherios , Vlachopoulos Symeon P. 
Published: January 2007

Background Although ankle sprains are common in soccer, the role of various risk factors in amateur soccer players is unclear. Purpose To identify the incidence of ankle sprain injuries, associated time loss of participation, and risk factors during two consecutive seasons in amateur players. Study Design Descriptive epidemiology study. Methods Of 336 athletes enrolled in the study, 312 male amateur soccer players were observed during a 2-year period. Ankle sprain injury incidents, participation time loss, injury mechanisms, ankle region injured, and other risk factors were recorded in games and practice sessions using questionnaires. Results During the study 208 ankle injuries were recorded, of which 139 were ankle sprains. These led to 975 sessions lost (on average, 7 lost sessions per injury). Most incidents (80.6%) were contact injuries, occurring mostly in defenders. Injury rates were equal between games and practice, while 61.1% of injuries were observed toward the end of each half of the game (P < .05). The injury incidence rate was higher during the first 2 months of the season as opposed to the last month (P < .05). Multinomial logistic regression showed that previous ankle sprain (P < .05) is a significant predictor of ankle sprain injury. Conclusion Ankle sprain injuries in amateur soccer players are primarily contact injuries, occurring mainly in defenders and during both games and practice. It appears that more injuries occur in players with previous ankle injury. Injury rates are higher toward the end of a game and chiefly occur during the first 2 months of the season.
Forefoot Loading during 3 Athletic Tasks
Authors: Queen Robin M. , Haynes Benjamin B. , Hardaker W. Mack , Garrett William E. 
Published: January 2007

Background Due to the popularity of soccer and the high incidence of injury among soccer players, it is valuable to know the effects of tasks like side cuts, crossover cuts, and forward acceleration on the foot. Purpose To determine the differences in forefoot loading during three different athletic tasks. Study Design Descriptive laboratory study. Methods Thirty-six subjects (17 women and 19 men) were tested. Subjects ran a slalom-style agility course 5 times while plantar pressure data was collected at 100 Hz. Plantar pressure was recorded under both feet; however, a right-foot contact was used in the analysis of the side-cut task, a left-foot plant was used in the analysis of the crossover cut, and an average of the 3 steps of acceleration were used in the analysis. The peak pressure, contact area, and contact time for the entire foot were compared between the 3 tasks. The force and the force-time integral were obtained during 5 trials for each of the 3 tasks. The foot was divided into 8 masked regions, which were used to determine the loading patterns specifically in the forefoot. Each variable was analyzed using a 1 × 3 analysis of variance to determine differences between the three movement tasks in the forefoot region (a = .05). Results Significant differences in peak pressure, contact area, and contact time existed between the movement tasks when examining the entire foot. In addition, significant differences in the force-time integral and peak pressure in the forefoot existed between the movement tasks. The force-time integral was highest during the side cut in the medial forefoot, hallux, and the lesser toes, while the force-time integral was highest during the crossover cut in the middle forefoot and the lateral forefoot. Similarly, the peak pressure was highest during the side cut in the medial forefoot, hallux, and the lesser toes, while peak pressure was highest in the middle forefoot during the acceleration task and highest in the lateral forefoot during the crossover-cutting task. Conclusions The results of this study demonstrated that the crossover cut places an increased load on the lateral portion of the forefoot, while the side-cut task places an increased load on the medial portion of the forefoot and the acceleration task places increased load on the middle forefoot. Clinical Relevance The differences in loading patterns based on athletic task are important for understanding potential injury mechanisms. In addition, this information could be important for defining a return to play protocol for athletes who have had specific injuries.
Bone Morphogenetic Proteins-Signaling Plays a Role in Tendon-to-Bone Healing
Authors: Ma C. Benjamin , Kawamura Sumito , Deng Xiang-Hua , Ying Ling , Schneidkraut Jason , Hays Peyton , Rodeo Scott A. 
Published: January 2007

Background Successful anterior cruciate ligament reconstruction requires secure healing between tendon and bone. Hypothesis Bone morphogenetic protein-signaling plays an important role in tendon-to-bone healing. rhBMP-2, a powerful osteoinductive agent, can improve tendon-bone interdigitation. Study Design Controlled laboratory study. Methods The study was designed in 2 phases: Phase I consisted of a dose-response study where 21 New Zealand White rabbits underwent bilateral anterior cruciate ligament reconstructions. Rabbits received either rhBMP-2 (11.5, 50, or 115 µg) or noggin (10, 15, 30, or 100 ng) (a potent bone morphogenetic proteins inhibitor) delivered in an injectable calcium phosphate matrix. Animals were sacrificed at 2 weeks and histomorphometric analyses were performed. In phase II, 60 rabbits underwent bilateral anterior cruciate ligament reconstructions and were assigned to 3 groups rhBMP-2 (115 µg), noggin (30 ng) in a calcium phosphate carrier, and calcium phosphate carrier alone. Animals were sacrificed at 2, 4, and 8 weeks and histomorphometric and biomechanical analyses were performed. Results rhBMP-2 treatment led to a significant increase in the width of new bone formation at the tendon-bone interface in a dose-dependent fashion (0.24-0.35 mm vs 0.13-0.16 mm in controls). All dosages of noggin inhibited new bone formation (0.06-0.1 mm vs 0.15-0.16 mm in controls); however, there was no dose-dependent effect in the concentrations studied. In the phase II study, rhBMP-2 resulted in a significant increase in new bone formation (81%, 89%, and 113%) at increasing time periods compared with controls. Tunnel diameters in the rhBMP-2 group were significantly smaller (15%-45%) than in the carrier group. The negative effect of noggin was not sustained, as new bone formation increased with time. The rhBMP-2 group demonstrated significantly increased stiffness at 8 weeks, while there was no significant difference in ultimate tensile load when compared with the other 2 groups. Conclusion rhBMP-2 demonstrated a strong, positive dose-dependent effect on osteointegration at the tendon-bone junction. In contrast, noggin decreased osteointegration. No tunnel widening was detected with rhBMP-2 using the calcium phosphate carrier. Clinical Relevance Further studies are needed to investigate the potential clinical application of enhancing healing and decreasing recovery time using bone morphogenetic proteins in soft tissue ligament reconstruction.
TLR ligands differentially affect uptake and presentation of cellular antigens
Authors: Weck Markus Michael , Grünebach Frank , Werth Daniela , Sinzger Christian , Bringmann Anita , Brossart Peter 
Published: January 2007

Abstract
Dendritic cells (DCs) have the unique ability to efficiently present T-cell epitopes from exogenous antigens on MHC class I molecules, a process called cross-presentation. In our study we demonstrate that stimulation of monocyte-derived DCs with Toll-like receptor (TLR) ligands differentially affects the uptake and cross-presentation of cellular antigens. Activation of DCs with TLR3 or TLR4 but not with TLR2 or TLR7/8 ligands inhibited phagocytosis of apoptotic tumor cells and resulted in a reduced cross-presentation of pp65-derived T-cell epitopes on MHC class I molecules upon engulfment of cytomegalovirus (CMV)–infected fibroblasts. These results have an important impact on the understanding of the interactions between the immune system and pathogens and the development of vaccination strategies to treat malignant diseases.
MEK1/2 inhibitors sensitize Bcr/Abl+ human leukemia cells to the dual Abl/Src inhibitor BMS-354/825
Authors: Nguyen Tri K. , Rahmani Mohamed , Harada Hisashi , Dent Paul , Grant Steven 
Published: January 2007

Abstract
Interactions between MEK1/2 inhibitors and the dual Abl/Src kinase inhibitor dasatinib (BMS-354825) were examined in chronic myeloid leukemia (CML) cell lines and primary specimens. Cotreatment of K562 or LAMA cells with subtoxic or marginally toxic concentrations of PD184352 (or U0126) and dasatinib synergistically potentiated mitochondrial damage, caspase activation, and apoptosis. Similar interactions were observed in CD34+ cells from one CML patient–derived but not in a normal human CD34+ bone marrow cell specimen. These interactions were associated with multiple perturbations in survival signaling pathways, including inactivation of Bcr/Abl, STAT5, and ERK1/2; down-regulation of Bcl-xL and Mcl-1; and dephosphorylation/activation of Bim. They were also associated with BAX/BAK conformational change, mitochondrial dysfunction, and caspase activation. Bim knockdown by shRNA suppressed BAX and BAK conformational change and protected cells from dasatinib/PD184352 lethality. Conversely, K562 cells ectopically expressing Mcl-1 or Bcl-xL were significantly less susceptible to dasatinib/PD184352 toxicity. Notably, the dasatinib/PD184352 regimen was active against leukemic cells exhibiting various forms of imatinib mesylate resistance, including Bcr/Abl overexpression, Lyn activation, and several Bcr/Abl kinase domain mutations (eg, E255K, M351T), but not T315I. Together, these findings suggest that strategies combining dasatanib with MEK1/2 inhibitors warrant further investigation in Bcr/Abl+ malignancies, particularly in the setting of imatinib mesylate–resistant disease.
Reciprocal regulation of human natural killer cells and macrophages associated with distinct immune synapses
Authors: Nedvetzki Shlomo , Sowinski Stefanie , Eagle Robert A. , Harris James , Vély Frédéric , Pende Daniela , Trowsdale John , Vivier Eric , Gordon Siamon , Davis Daniel M. 
Published: January 2007

AbstractNatural killer (NK) cells directly lyse tumor or viral-infected cells but also an important role for NK cell cytotoxicity in regulating the extent of immune responses is emerging. Here, we show that autologous human macrophages activated NK cell proliferation and cytokine secretion, increased expression of activating receptors, and primed NK cell cytotoxicity against susceptible target cells. Ligation of NK cell 2B4, and not NKp30 (known to be important for DC-mediated NK cell activation), is critical for this macrophage-mediated NK cell activation. Reciprocally, however, NK cells regulated macrophage activity by directly killing macrophages stimulated by high doses of LPS. Cytolysis was triggered by NKG2D recognition of stress-inducible class I major histocompatibility complex (MHC)–like ligands on macrophages: high doses of LPS induced transcription and surface expression of ULBP1, ULBP2, and ULBP3 and surface expression of constitutively transcribed MICA. Thus, these data suggest a new function for NK cell cytotoxicity in eliminating overstimulated macrophages. Additionally, these interactions define, for the first time, 2 distinct activating NK cell synapses: lytic and nonlytic. Triggering NK cell proliferation and cytokine secretion, but not cytolysis, specifically associated with synaptic accumulation of macrophage F-actin and NK cell 2B4, while macrophages were killed when NK cell F-actin and macrophage ICAM-1 accumulated around a central cluster of NK cell NKG2D/DAP10.
Genomewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells
Authors: Tissing Wim J. E. , den Boer Monique L. , Meijerink Jules P. P. , Menezes Renee X. , Swagemakers Sigrid , van der Spek Peter J. , Sallan Stephen E. , Armstrong Scott A. , Pieters Rob 
Published: January 2007

AbstractGlucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours of prednisolone exposure in leukemic cells of 13 children as compared with nonexposed cells. Following 3 hours of exposure no significant changes in gene expression could be identified. Following 8 hours of exposure, 51 genes were differentially expressed (P < .001 and false discovery rate < 10%) with 39 genes being up-regulated (median, 2.4-fold) and 12 genes were down-regulated (median, 1.7-fold). Twenty-one of those genes have not been identified before to be transcriptionally regulated by prednisolone. Two of the 3 most highly up-regulated genes were tumor suppressor genes, that is, thioredoxin-interacting protein (TXNIP; 3.7-fold) and zinc finger and BTB domain containing 16 (ZBTB16; 8.8-fold). About 50% of the differentially expressed genes were functionally categorized in 3 major routes, namely MAPK pathways (9 genes), NF-κB signaling (11 genes), and carbohydrate metabolism (5 genes). Biologic characterization of these genes and pathways might elucidate the action of glucocorticoids in ALL cells, possibly suggesting causes of glucocorticoid resistance and new potential targets for therapy.