bluuebunny/crossref_metadata_2025_split huggingface dataset:
The History of Tumor Virology
Authors: Javier Ronald T. , Butel Janet S. 
Published: October 2008

Abstract
In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses—EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses—human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi's sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century. [Cancer Res 2008;68(19):7693–706]
Therapeutic IMC-C225 Antibody Inhibits Breast Cancer Cell Invasiveness via Vav2-Dependent Activation of RhoA GTPase
Authors: Molli Poonam R. , Adam Liana , Kumar Rakesh 
Published: October 2008

Abstract
Purpose: Abnormalities in the expression and signaling pathways downstream of epidermal growth factor receptor (EGFR) contribute to progression, invasion, and maintenance of the malignant phenotype in human cancers. Accordingly, biological agents, such as the EGFR-blocking antibody IMC-C225 have promising anticancer potential and are currently in various stages of clinical development. Because use of IMC-C225 is limited, at present, only for treatment of cancer with high EGFR expression, the goal of the present study was to determine the effect of IMC-C225 on the invasiveness of breast cancer cells with high and low levels of EGFR expression.
Experimental Design: The effect of IMC-C225 on invasion was studied using breast cancer cell lines with high and low levels of EGFR expression.
Results: The addition of EGF led to progressive stress fiber dissolution. In contrast, cells treated with IMC-C225 showed reduced invasiveness and increased stress-fiber formation. Interestingly, IMC-C225 pretreatment was accompanied by EGFR phosphorylation, as detected using an anti–phosphorylated tyrosine antibody (PY99), which correlated with phosphorylation of Vav2 guanine nucleotide exchange factor and activation of RhoA GTPase irrespective of EGFR level, and Vav2 interacted with EGFR only in IMC-C225–treated cells. The underlying mechanism involved an enhanced interaction between β1 integrins and EGFR upon IMC-C225 treatment.
Conclusion: Here, we defined a new mechanism for IMC-C225 that cross-links integrins with EGFR, leading to activation of RhoA and inhibition of breast cancer cell invasion irrespective of the level of EGFR in the cells, thus providing a rationale for using IMC-C225 in the metastatic setting independent of the levels of EGFR.
A Phase I-II Study of Combined Blockade of the ErbB Receptor Network with Trastuzumab and Gefitinib in Patients with HER2 (ErbB2)-Overexpressing Metastatic Breast Cancer
Authors: Arteaga Carlos L. , O'Neill Anne , Moulder Stacy L. , Pins Michael , Sparano Joseph A. , Sledge George W. , Davidson Nancy E. 
Published: October 2008

Abstract
Purpose: To determine the safety, and efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in combination with trastuzumab in patients with metastatic HER2-positive metastatic breast cancer.
Experimental Design: Patients with HER2-overexpressing breast cancer were treated with trastuzumab 2 mg/kg/week and gefitinib 250 to 500 mg/day. The primary end point of the study was to increase the proportion progression-free from 50% to 65% at 6 months in chemotherapy-naive patients and from 50% to 70% at 3 months in patients previously treated with chemotherapy in the metastatic setting.
Results: In the phase I study, all patients treated with gefitinib 500 mg/day developed grade 3 diarrhea. The phase II study was conducted using trastuzumab and gefitinib 250 mg/day. One patient achieved a complete response, 2 had a partial response, and 6 had stable disease for an overall response rate of 9% and a clinical benefit rate of 28% (9 of 32). Median time to progression (TTP) was 3 months (95% confidence interval, 2.3-4.1) in patients with no prior systemic therapy in the metastatic setting (n = 23). In patients treated with prior systemic therapy (n = 9), the median TTP of 5.3 months (95% confidence interval, 2.8-8.1). Overall median survival was 27 months. TTP was similar in EGFR-positive compared with EGFR-negative patients.
Conclusions: Gefitinib 250 mg/day was the maximal dose that can be safely administered with weekly trastuzumab. Interim analysis of the efficacy suggested that the combination was unlikely to result in clinical benefit compared with trastuzumab alone. These results do not support the use of this combination in patients with HER2-positive breast cancer.
Single Nucleotide Polymorphisms, Apoptosis, and the Development of Severe Late Adverse Effects After Radiotherapy
Authors: Azria David , Ozsahin Mahmut , Kramar Andrew , Peters Sheila , Atencio David P. , Crompton Nigel E.A. , Mornex Françoise , Pèlegrin André , Dubois Jean-Bernard , Mirimanoff René-Olivier , Rosenstein Barry S. 
Published: October 2008

Abstract
Purpose: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, ≥3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation.
Experimental Design: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18).
Results: Overall, 13 and 21 patients were found to possess a total of &lt;4 and ≥4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had ≥4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had ≥4 SNPs (P &lt; 0.001).
Conclusions: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.
BKM1740, an Acyl-Tyrosine Bisphosphonate Amide Derivative, Inhibits the Bone Metastatic Growth of Human Prostate Cancer Cells by Inducing Apoptosis
Authors: Seo Seong Il , Gera Lajos , Zhau Haiyen E. , Qian Wei Ping , Iqbal Shareen , Johnson Nicole A. , Zhang Shumin , Zayzafoon Majd , Stewart John , Wang Ruoxiang , Chung Leland W.K. , Wu Daqing 
Published: October 2008

Abstract
Purpose: Survivin overexpression has been associated with an unfavorable outcome in human PCa; however, its role in metastasis remains elusive. We aim to (a) evaluate the clinical implications of survivin expression in PCa bone metastasis; (b) determine in vivo efficacy of BKM1740, a small-molecule compound, against PCa skeletal growth and survival; and (c) investigate molecular mechanism by which BKM1740 augments apoptosis in bone metastatic PCa cells.
Experimental Design: Survivin expression was analyzed in PCa specimens and experimental models. Bone metastatic C4-2 and ARCaPM cell lines were used to evaluate the in vitro effects of BKM1740 and molecular mechanism for the induction of apoptosis. C4-2 cells were grown intratibially in athymic nude mice to evaluate the in vivo efficacy of BKM1740. Tumor growth in mouse bone was assessed by serum prostate-specific antigen and radiography and confirmed by immunohistochemical analyses.
Results: Survivin expression is positively associated with clinical PCa bone metastasis. BKM1740 induced apoptosis in PCa cells by repressing survivin. Mice with established C4-2 tumors in tibia showed a marked decrease in serum prostate-specific antigen and much improved bone architecture radiographically after treatment with BKM1740. Immunohistochemical assays of mouse tumor samples confirmed that the in vivo effects were mediated by inhibition of survivin and induction of apoptosis.
Conclusions: Survivin expression is associated with PCa bone metastasis. BKM1740 treatment specifically inhibited survivin and induced apoptosis in vitro and was efficacious in retarding PCa skeletal growth in a mouse model. BKM1740 is a promising small-molecule compound that could be used to treat PCa bone metastasis.
Estimation of Daytime Net Radiation from Shortwave Radiation Measurements and Meteorological Observations
Authors: Wang Kaicun , Liang Shunlin 
Published: October 2008

Abstract
Changes in surface net radiation Rn control the earth’s climate, the hydrological cycle, and plant photosynthesis. However, Rn is not readily available. This study develops a method to estimate surface daytime Rn from solar shortwave radiation measurements as well as conventional meteorological observations (or satellite retrievals) including daily minimum temperature, daily temperature range, and relative humidity, and vegetation indices from satellite data. Measurements collected at 22 U.S. and 2 Tibetan Plateau, China, sites from 2000 to 2006 are used to develop and validate the method. Land cover types include desert, semidesert, croplands, grasslands, and forest. Site elevations range from 98 to 4700 m. The results show that the method estimates Rn under clear and cloudy conditions accurately over a range of land cover types, elevations, and climates without requiring local calibration. The results show that the method estimates Rn accurately. The bias varies from −7.8 to 9.7 W m−2 (±3% in relative value) for different sites, and the root-mean-square error ranges from 12.8 to 21 W m−2 (from +5% to +9% in relative value) for different sites, with an average of 16.9 W m−2 (+6% relative) for all sites. The correlation coefficient for all sites is about 0.99. The correlation coefficient between the measured and predicted annual anomaly (year average subtracted from multiyear average) in daytime Rn is as high as 0.91, demonstrating that the method accurately estimates long-term variation in Rn.
Theoretical Studies of Convectively Forced Mesoscale Flows in Three Dimensions. Part I: Uniform Basic-State Flow
Authors: Han Ji-Young , Baik Jong-Jin 
Published: October 2008

Abstract
Convectively forced mesoscale flows in three dimensions are theoretically investigated by examining the transient response of a stably stratified atmosphere to convective heating. Solutions for the equations governing small-amplitude perturbations in a uniform basic-state wind with specified convective heating are analytically obtained using the Green function method. In the surface pulse heating case, it is explicitly shown that the vertical displacement at the center of the 3D steady heating decreases as fast as t−1 for large t. Hence, unlike in two dimensions, the steady state is approached in three dimensions. In the finite-depth steady heating case, the perturbation vertical velocity field in the stationary mode shows a main updraft region extending over the heating layer and V-shaped upward and downward motions above and below the heating layer. Including the third dimension results in a stronger updraft at an early stage, a weaker compensating downward motion, and a weaker stationary gravity wave field in a quasi-steady state than in the case of two dimensions. An examination of flow response fields for various vertical structures of convective heating indicates that stationary gravity waves above the main updraft region become strong in intensity as the height of the maximum convective heating increases. In response to the transient heating, a main updraft region extending over the heating layer no longer appears at a dissipation stage of deep convection. Instead, alternating regions of upward and downward motion with an upstream phase tilt appear.
Sea Ice in the Canadian Arctic Archipelago: Modeling the Past (1950–2004) and the Future (2041–60)
Authors: Sou Tessa , Flato Gregory 
Published: October 2008

Abstract
Considering the recent losses observed in Arctic sea ice and the anticipated future warming due to anthropogenic greenhouse gas emissions, sea ice retreat in the Canadian Arctic Archipelago (CAA) is expected and indeed is already being observed. As most global climate models do not resolve the CAA region, a fine-resolution ice–ocean regional model is developed and used to make a projection of future changes in the CAA sea ice. Results from a historical run (1950–2004) are used to evaluate the model. The model does well in representing observed sea ice spatial and seasonal variability, but tends to underestimate summertime ice cover. The model results for the future (2041–60) show little change in wintertime ice concentrations from the past, but summertime ice concentrations decrease by 45%. The ice thickness is projected to decrease by 17% in the winter and by 36% in summer. Based on this study, a completely ice-free CAA is unlikely by the year 2050, but the simulated ice retreat suggests that the region could support some commercial shipping.
Mechanisms for the Interannual Variability of SST in the East Pacific Warm Pool
Authors: Karnauskas Kristopher B. , Busalacchi Antonio J. 
Published: October 2008

Abstract
In comparison with the western and equatorial Pacific Ocean, relatively little is known about the east Pacific warm pool (EPWP). Observations indicate that the interannual variability of sea surface temperature (SST) in the EPWP is highly correlated (0.95) with the El Niño–Southern Oscillation (ENSO). In this paper, an ocean general circulation model (OGCM) of the tropical Pacific Ocean and various atmospheric and oceanic observations are used to diagnose the physical processes governing the interannual variability of SST in the EPWP. Atmospheric forcings for the OGCM are derived purely from satellite observations between 1988 and 2004.
Shortwave heating is identified as playing a dominant role in the interannual SST tendency of the EPWP. The high correlation between SST in the EPWP and eastern equatorial Pacific is therefore explained not by ocean processes, but by an atmospheric link. ENSO-driven equatorial SST anomalies modify the distribution of the overlying atmospheric vertical motions and therefore cloud cover and ultimately shortwave heating. During an El Niño event, for example, the ITCZ is equatorward displaced from its normal position over the EPWP, resulting in anomalously large shortwave heating over the EPWP. Analysis of poleward ocean heat transport and coastal Kelvin waves confirms that oceanic processes are not sufficient to explain the interannual variability of the EPWP.
Improved Turbulent Air–Sea Flux Bulk Parameters for Controlling the Response of the Ocean Mixed Layer: A Sequential Data Assimilation Approach
Authors: Skachko Sergey , Brankart Jean-Michel , Castruccio Frédéric , Brasseur Pierre , Verron Jacques 
Published: October 2008

Abstract
Bulk formulations parameterizing turbulent air–sea fluxes remain among the main sources of error in present-day ocean models. The objective of this study is to investigate the possibility of estimating the turbulent bulk exchange coefficients using sequential data assimilation. It is expected that existing ocean assimilation systems can use this method to improve the air–sea fluxes and produce more realistic forecasts of the thermohaline characteristics of the mixed layer. The method involves augmenting the control vector of the assimilation scheme using the model parameters that are to be controlled. The focus of this research is on estimating two bulk coefficients that drive the sensible heat flux, the latent heat flux, and the evaporation flux of a global ocean model, by assimilating temperature and salinity profiles using horizontal and temporal samplings similar to those to be provided by the Argo float system. The results of twin experiments show that the method is able to correctly estimate the large-scale variations in the bulk parameters, leading to a significant improvement in the atmospheric forcing applied to the ocean model.
An Analysis of the Large-Scale Climate Anomalies Associated with the Snowstorms Affecting China in January 2008
Authors: Wen Min , Yang Song , Kumar Arun , Zhang Peiqun 
Published: October 2008

Abstract
Extraordinarily frequent and long-lasting snowstorms affected China in January 2008, causing above-normal precipitation, below-normal temperature, and severe icing conditions over central–southern China. These snowstorms were closely linked to the change in the Middle East jet stream (MEJS), which intensified and shifted southeastward. The change in MEJS was accompanied by southeastward shifts of the ridge and the trough over Europe and western Asia. The intensified MEJS also strengthened the trough embedded in the southern branch of the subtropical westerlies over the southern Tibetan Plateau, enhancing the water vapor transport from western Asia and the Bay of Bengal to China. In the meantime, the subtropical western Pacific high (SWPH) was stronger and its ridgeline was farther north than normal. The anomalous high slowed down the eastward propagation of weather systems to the Pacific and favored convergence of water vapor over central–southern China. The MEJS is usually strong when the Arctic Oscillation (AO) is positive and the SWPH is farther north than normal in La Niña winters. Compared to the SWPH and the Niño-3.4 sea surface temperature (SST), the MEJS and the AO exert stronger influences on the temperature and the precipitation over central–southern China, despite the fact that these possible impacting factors are not completely independent from each other. Although the La Niña event might contribute to the climate anomalies through its relation with the SWPH in January 2008, an analysis of historical events indicates that La Niña conditions alone can hardly cause severe and persistent snow conditions over central–southern China. In addition, compared to the Niño-3.4 SST and the SWPH, the conditions of December MEJS and AO exhibit stronger precursory signals of the variability of January temperature over central–southern China.
Trochlear Contact Pressures after Straight Anteriorization of the Tibial Tuberosity
Authors: Rue John-Paul H. , Colton Anne , Zare Stephanie M. , Shewman Elizabeth , Farr Jack , Bernard R. Bach , Cole Brian J. 
Published: October 2008

Background Anteromedialization of the tibial tuberosity has been shown to decrease mean total contact pressures of the lateral trochlea and to shift contact pressures to the medial trochlea. Hypothesis Modifying the anteromedialization osteotomy to a straight anteriorization osteotomy of the tibial tuberosity can decrease trochlear contact pressures without a resultant medial shift of forces to the medial trochlear contact area. Study Design Controlled laboratory study. Methods Ten cadavers were tested before and after straight anteriorization tibial tuberosity osteotomy by loading the extensor mechanism with 89.1 and 178.2 N at 0°, 30°, 60°, and 90° of flexion following a validated patellofemoral joint loading protocol. Contact pressures were measured with electroresistive pressure sensors placed directly on the trochlea. Results The mean trochlear contact pressures after osteotomy decreased significantly ( P < .05) for loads of 89.1 and 178.2 N at both 30° (23% and 20%, respectively) and 60° (18.7% and 31.9%, respectively) of knee flexion. The peak contact pressures decreased significantly ( P < .05) for loads of 89.1 and 178.2 N at 30° (24.3% and 27.0%, respectively) and 60° (31.9% and 24.5%, respectively) and for loads of 89.1 N at 90° (13.4%) of knee flexion. Conclusion The authors demonstrated significantly decreased trochlear contact forces after straight anteriorization osteotomy of the tibial tuberosity, without a significant resultant medial shift of the center of force. Clinical Relevance Straight anteriorization of the tibial tuberosity may be a useful adjunct for patients with medial articular defects of the patellar or trochlea in whom anteromedialization would be otherwise contraindicated.
Cyclical Loading of Coracoclavicular Ligament Reconstructions
Authors: Lee Steven J. , Keefer Eric P. , McHugh Malachy P. , Kremenic Ian J. , Orishimo Karl F. , Ben-Avi Simon , Nicholas Stephen J. 
Published: October 2008

Background Reconstruction for injuries to the acromioclavicular joint remains controversial. Hypothesis A coracoclavicular ligament reconstruction with a semitendinosus tendon would have superior performance to the classic coracoacromial ligament transfer with or without augmentation. Study Design Controlled laboratory study. Methods Five cadaveric shoulders were used to reconstruct the coracoclavicular ligaments with 3 methods: coracoacromial ligament transfer without augmentation, coracoacromial ligament transfer augmented with No. 5 Ethibond suture, and a semitendinosus tendon. Each reconstruction was cyclically loaded at 40 N to 80 N for 2500 cycles, then from 40 N to 210 N for 2500 cycles, followed by loading to failure. The number of cycles to 50% and 100% loss of acromioclavicular joint reduction were recorded. Results During the 40 N to 80 N-loading cycle, the coracoacromial transfer without augmentation failed (15 ± 16 cycles). The augmented coracoacromial ligament transfer and the semitendinosus reconstruction did not fail ( P = .008). During the 40 N to 210 N-loading cycle, the augmented coracoacromial ligament transfer failed (207 ± 399 cycles). The semitendinosus reconstruction survived through both loading cycles ( P < .01). Conclusion Coracoclavicular ligament reconstruction with a semitendinosus graft is a biomechanically superior construct in a cyclically loaded setting to a coracoacromial ligament transfer augmented with a No. 5 Ethibond suture. Clinical Relevance The semitendinosus graft is a strong, biologic option for reconstruction of the coracoclavicular ligaments.