bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination with Antigen-Transfected, NKT Cell Ligand–Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells
Authors: Shimizu Kanako , Mizuno Takuya , Shinga Jun , Asakura Miki , Kakimi Kazuhiro , Ishii Yasuyuki , Masuda Kenichi , Maeda Tomoji , Sugahara Hidetoshi , Sato Yusuke , Matsushita Hirokazu , Nishida Keigo , Hanada Kenichi , Dorrie Jan , Schaft Niels , Bickham Kara , Koike Hisashi , Ando Tsuyoshi , Nagai Ryozo , Fujii Shin-ichiro 
Published: October 2012

Abstract
Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with cancer patients have yet to be developed. In murine models, α-galactosylceramide (α-GalCer)–loaded, tumor antigen–expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the innate and adaptive immune systems. In the current study, we established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the natural killer T (NKT) immune cell receptor CD1d, loaded with the CD1d ligand α-GalCer and then transfected with antigen-encoding mRNA. When administered to mice or dogs, these aAVC-activated invariant NKT (iNKT) cells elicited antigen-specific T-cell responses with no adverse events. In parallel experiments, using NOD/SCID/IL-2rγcnull–immunodeficient (hDC-NOG) mouse model, we also showed that the human melanoma antigen, MART-1, expressed by mRNA transfected aAVCs can be cross-presented to antigen-specific T cells by human dendritic cells. Antigen-specific T-cell responses elicited and expanded by aAVCs were verified as functional in tumor immunity. Our results support the clinical development of aAVCs to harness innate and adaptive immunity for effective cancer immunotherapy. Cancer Res; 73(1); 62–73. ©2012 AACR.
Immune-Dependent and Independent Antitumor Activity of GM-CSF Aberrantly Expressed by Mouse and Human Colorectal Tumors
Authors: Urdinguio Rocio G. , Fernandez Agustin F. , Moncada-Pazos Angela , Huidobro Covadonga , Rodriguez Ramon M. , Ferrero Cecilia , Martinez-Camblor Pablo , Obaya Alvaro J. , Bernal Teresa , Parra-Blanco Adolfo , Rodrigo Luis , Santacana Maria , Matias-Guiu Xavier , Soldevilla Beatriz , Dominguez Gemma , Bonilla Felix , Cal Santiago , Lopez-Otin Carlos , Fraga Mario F. 
Published: October 2012

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) is a cytokine produced in the hematologic compartment that may enhance antitumor immune responses, mainly by activation of dendritic cells. Here, we show that more than one-third of human colorectal tumors exhibit aberrant DNA demethylation of the GM-CSF promoter and overexpress the cytokine. Mouse engraftment experiments with autologous and homologous colon tumors engineered to repress the ectopic secretion of GM-CSF revealed the tumor-secreted GM-CSF to have an immune-associated antitumor effect. Unexpectedly, an immune-independent antitumor effect was observed that depended on the ectopic expression of GM-CSF receptor subunits by tumors. Cancer cells expressing GM-CSF and its receptor did not develop into tumors when autografted into immunocompetent mice. Similarly, 100% of the patients with human colon tumors that overexpressed GM-CSF and its receptor subunits survived at least 5 years after diagnosis. These data suggest that expression of GM-CSF and its receptor subunits by colon tumors may be a useful marker for prognosis as well as for patient stratification in cancer immunotherapy. Cancer Res; 73(1); 395–405. ©2012 AACR.
A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease
Authors: Laderach Diego J. , Gentilini Lucas D. , Giribaldi Laura , Delgado Victor Cardenas , Nugnes Lorena , Croci Diego O. , Al Nakouzi Nader , Sacca Paula , Casas Gabriel , Mazza Osvaldo , Shipp Margaret A. , Vazquez Elba , Chauchereau Anne , Kutok Jeffery L. , Rodig Scott J. , Elola María T. , Compagno Daniel , Rabinovich Gabriel A. 
Published: October 2012

Abstract
Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the “galectin signature” of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evolution, whereas expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during prostate cancer progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in prostate cancer angiogenesis. In human prostate cancer tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in prostate cancer cells reduced tumor vascularization without altering expression of other angiogenesis-related genes. Collectively, our findings identify a dynamically regulated “galectin-specific signature” that accompanies disease evolution in prostate cancer, and they highlight a major role for Gal-1 as a tractable target for antiangiogenic therapy in advanced stages of the disease. Cancer Res; 73(1); 86–96. ©2012 AACR.
A Classification Model for BRCA2 DNA Binding Domain Missense Variants Based on Homology-Directed Repair Activity
Authors: Guidugli Lucia , Pankratz Vernon S. , Singh Namit , Thompson James , Erding Catherine A. , Engel Christoph , Schmutzler Rita , Domchek Susan , Nathanson Katherine , Radice Paolo , Singer Christian , Tonin Patricia N. , Lindor Noralane M. , Goldgar David E. , Couch Fergus J. 
Published: October 2012

Abstract
The relevance of many BRCA2 variants of uncertain significance (VUS) to breast cancer has not been determined due to limited genetic information from families carrying these alterations. Here, we classified six new variants as pathogenic or nonpathogenic by analysis of genetic information from families carrying 64 individual BRCA2 DNA binding domain (DBD) missense mutations using a multifactorial likelihood model of cancer causality. Next, we evaluated the use of a homology-directed DNA break repair (HDR) functional assay as a method for inferring the clinical relevance of VUS in the DBD of BRCA2 using 18 established nonpathogenic missense variants and all 13 established pathogenic missense mutations from the BRCA2 DBD. Compared with the known status of these variants based on the multifactorial likelihood model, the sensitivity of the HDR assay for pathogenic mutations was estimated at 100% [95% confidence interval (CI): 75.3%–100%] and specificity was estimated at 100% (95% CI: 81.5%–100%). A statistical classifier for predicting the probability of pathogenicity of BRCA2 DBD variants was developed using these functional results. When applied to 33 additional VUS, the classifier identified eight with 99% or more probability of nonpathogenicity and 18 with 99% or more probability of pathogenicity. Thus, in the absence of genetic evidence, a cell-based HDR assay can provide a probability of pathogenicity for all VUS in the BRCA2 DBD, suggesting that the assay can be used in combination with other information to determine the cancer relevance of BRCA2 VUS. Cancer Res; 73(1); 265–75. ©2012 AACR.
Dose-Dense Chemotherapy Improves Mechanisms of Antitumor Immune Response
Authors: Chang Chih-Long , Hsu Yun-Ting , Wu Chao-Chih , Lai Yan-Zen , Wang Connie , Yang Yuh-Cheng , Wu T.-C. , Hung Chien-Fu 
Published: October 2012

Abstract
Dose-dense (DD) regimens of combination chemotherapy may produce superior clinical outcomes, but the basis for these effects are not completely clear. In this study, we assessed whether a DD combinatorial regimen of low-dose cisplatin and paclitaxel produces superior immune-mediated efficacy when compared with a maximum tolerated dose (MTD) regimen in treating platinum-resistant ovarian cancer as modeled in mice. Immune responses generated by the DD regimen were identified with regard to the immune cell subset responsible for the antitumor effects observed. The DD regimen was less toxic to the immune system, reduced immunosuppression by the tumor microenvironment, and triggered recruitment of macrophages and tumor-specific CD8+ T-cell responses to tumors [as determined by interleukin (IL)-2 and IFN-γ secretion]. In this model, we found that the DD regimen exerted greater therapeutic effects than the MTD regimen, justifying its further clinical investigation. Fourteen patients with platinum-resistant relapse of ovarian cancer received DD chemotherapy consisting of weekly carboplatin (AUC2) and paclitaxel (60–80 mg/m2) as the third- or fourth-line treatment. Serum was collected over the course of treatment, and serial IFN-γ and IL-2 levels were used to determine CD8+ T-cell activation. Of the four patients with disease control, three had serum levels of IL-2 and IFN-γ associated with cytotoxic CD8+ T-cell activity. The therapeutic effect of the DD chemotherapy relied on the preservation of the immune system and the treatment-mediated promotion of tumor-specific immunity, especially the antitumor CD8+ T-cell response. Because the DD regimen controlled drug-resistant disease through a novel immune mechanism, it may offer a fine strategy for salvage treatment. Cancer Res; 73(1); 119–27. ©2012 AACR.
VEGFA-VEGFR Pathway Blockade Inhibits Tumor-Induced Regulatory T-cell Proliferation in Colorectal Cancer
Authors: Terme Magali , Pernot Simon , Marcheteau Elie , Sandoval Federico , Benhamouda Nadine , Colussi Orianne , Dubreuil Olivier , Carpentier Antoine F. , Tartour Eric , Taieb Julien 
Published: October 2012

Abstract
Multitarget antiangiogenic tyrosine kinase inhibitors (TKI) have been shown to reduce regulatory T cells (Treg) in tumor-bearing animals and patients with metastatic renal carcinomas. However, a direct role of the VEGF-A/VEGFR pathway inhibition in this phenomenon is a matter of debate and molecular mechanisms leading to Treg modulation in this setting have not been explored to date. Treg proportion, number, and proliferation were analyzed by flow cytometry in peripheral blood of patients with metastatic colorectal cancer (mCRC) treated with bevacizumab, a monoclonal antibody targeting specifically VEGF-A, and in colon cancer–bearing mice (CT26) treated with drugs targeting the VEGF/VEGFR axis. The direct impact of VEGF-A on Treg induction was assessed together with specific blockade of different isoforms of VEGFRs that may be involved. In CT26-bearing mice, anti-VEGF antibody and sunitinib treatments reduced Treg but masitinib, a TKI not targeting VEGFR, did not. Targeting VEGF-A/VEGFR axis seems sufficient to affect Treg percentages, without any changes in their function. Similarly, bevacizumab inhibited Treg accumulation in peripheral blood of patients with mCRCs. In vitro, Treg expressing VEGFR from tumor-bearing mice directly proliferated in response to VEGF-A. Anti-VEGF-A treatment decreased Treg proliferation in mice as well as in patients with mCRCs. VEGFR-2- but not VEGFR-1–specific blockade led to the same results. We identified a novel mechanism of tumor escape by which VEGF-A directly triggers Treg proliferation. This proliferation is inhibited by VEGF-A/VEGFR-2 blockade. Anti-VEGF-A therapies also have immunologic effects that may be used with a therapeutic goal in the future. Cancer Res; 73(2); 539–49. ©2012 AACR.
Retrieval Orientation and the Control of Recollection: An fMRI Study
Authors: Morcom Alexa M. , Rugg Michael D. 
Published: October 2012

Abstract
This study used event-related fMRI to examine the impact of the adoption of different retrieval orientations on the neural correlates of recollection. In each of two study–test blocks, participants encoded a mixed list of words and pictures and then performed a recognition memory task with words as the test items. In one block, the requirement was to respond positively to test items corresponding to studied words and to reject both new items and items corresponding to the studied pictures. In the other block, positive responses were made to test items corresponding to pictures, and items corresponding to words were classified along with the new items. On the basis of previous ERP findings, we predicted that in the word task, recollection-related effects would be found for target information only. This prediction was fulfilled. In both tasks, targets elicited the characteristic pattern of recollection-related activity. By contrast, nontargets elicited this pattern in the picture task, but not in the word task. Importantly, the left angular gyrus was among the regions demonstrating this dissociation of nontarget recollection effects according to retrieval orientation. The findings for the angular gyrus parallel prior findings for the “left-parietal” ERP old/new effect and add to the evidence that the effect reflects recollection-related neural activity originating in left ventral parietal cortex. Thus, the results converge with the previous ERP findings to suggest that the processing of retrieval cues can be constrained to prevent the retrieval of goal-irrelevant information.
Observational Evidence of Summer Shamal Swells along the West Coast of India*
Authors: Glejin Johnson , Kumar V. Sanil , Nair T. M. Balakrishnan , Singh Jai , Mehra Prakash 
Published: October 2012

Abstract
Wave data collected off Ratnagiri, which is on the west coast of India, in 2010 and 2011 are used to examine the presence of the summer shamal swells. This study also aims to understand variations in wave characteristics and associated modifications in wind sea propagation at Ratnagiri. Wind data collected using an autonomous weather station (AWS), along with Advanced Scatterometer (ASCAT) and NCEP data, are used to identify the presence of summer shamal winds along the west coast of the Indian subcontinent and on the Arabian Peninsula. NCEP and ASCAT data indicate the presence of summer shamal winds over the Arabian Peninsula and northwesterly winds at Ratnagiri. This study identifies the presence of swells from the northwest that originate from the summer shamal winds in the Persian Gulf and that reach Ratnagiri during 30% of the summer shamal period. AWS data show the presence of northwest winds during May and southwest winds during the strong southwest monsoon period (June–August). Another important factor identified at Ratnagiri that is associated with the summer shamal events is the direction of wind sea waves. During the onset of the southwest monsoon (May), the sea direction is in the direction of swell propagation (northwest); however, during the southwest monsoon (June–August), a major part of the wind sea direction is from the southwest. The average occurrence of summer shamal swells is approximately 22% during the southwest monsoon period. An increase in wave height is observed during June and July at Ratnagiri due to the strong summer shamal event.
Precipitation Modulation by the Saint Lawrence River Valley in Association with Transitioning Tropical Cyclones*
Authors: Milrad Shawn M. , Atallah Eyad H. , Gyakum John R. 
Published: October 2012

Abstract
The St. Lawrence River valley (SLRV) is an important orographic feature in eastern Canada that can affect surface wind patterns and contribute to locally higher amounts of precipitation. The impact of the SLRV on precipitation distributions associated with transitioning, or transitioned, tropical cyclones that approached the region is assessed. Such cases can result in heavy precipitation during the warm season, as during the transition of Hurricane Ike (2008). Thirty-eight tropical cyclones tracked within 500 km of the SLRV from 1979 to 2011. Utilizing the National Centers for Environmental Prediction (NCEP) North American Regional Reanalysis (NARR), 19 of the 38 cases (group A) had large values of ageostrophic frontogenesis within and parallel to the SLRV, in a region of northeasterly surface winds associated with pressure-driven wind channeling. Using composite and case analyses, results show that the heaviest precipitation is often located within the SLRV, regardless of the location of large-scale forcing for ascent, and is concomitant with ageostrophic frontogenesis. The suggested physical pathway for precipitation modulation in the SLRV is as follows. Valley-induced near-surface ageostrophic frontogenesis is due to pressure-driven wind channeling as a result of the along-valley pressure gradient [typically exceeding 0.4 hPa (100 km)−1] established by the approaching cyclone. Near-surface cold-air advection as a result of the northeasterly pressure-driven channeling results in a temperature inversion, similar to what is observed in cool-season wind-channeling cases. The ageostrophic frontogenesis, acting as a mesoscale ascent-focusing mechanism, helps air parcels to rise above the temperature inversion into a conditionally unstable atmosphere, which results in enhanced precipitation focused along the SLRV.
Ability to Return to Sports 5 Years After Matrix-Associated Autologous Chondrocyte Transplantation in an Average Population of Active Patients
Authors: Zak Lukas , Aldrian Silke , Wondrasch Barbara , Albrecht Christian , Marlovits Stefan 
Published: October 2012

Background: Cartilage injuries often occur during sports activities, and return to sports after cartilage surgery is an important outcome parameter for different treatment methods in the competitive as well as the recreationally active population. Hypothesis: At the time of midterm follow-up after matrix-associated autologous chondrocyte transplantation (MACT), return to recreational sports at the preinjury level will be possible. Study Design: Case series; Level of evidence, 4. Methods: Seventy patients (51 men, 19 women; age [mean ± standard deviation], 34.9 ± 8.6 y; range, 18-55 y) were clinically evaluated 5 years after MACT through subjective clinical scores such as the Knee Injury and Osteoarthritis Outcome Score (KOOS) sport and recreation subscales, the Tegner activity scale, and the Noyes sports activity rating scale. The level of sports participation was included in the investigation. Results: The results 5 years after MACT showed mean values of 60.1 for the KOOS–sport, 67.4 for the Noyes, and 3.8 for the Tegner scores, meaning that regular sports activity such as cycling or running on flat ground, as well as medium-level manual labor, is possible. We noted that 74.3% of our patients returned to at least their preinjury sports level. Conclusion: Midterm postoperative results after MACT show that in a moderately active population, participation in regular sports is possible for most patients, at least at their preinjury recreational level and intensity, and there is a good rate of return to sports.
The Effect of Medial Opening Wedge Proximal Tibial Osteotomy on Patellofemoral Contact
Authors: Javidan Pooya , Adamson Gregory J. , Miller Jennifer R. , Durand Pierre , Dawson Patrick A. , Pink Marilyn M. , Lee Thay Q. 
Published: October 2012

Background: It has been suggested that patellofemoral contact pressures and contact forces may be altered secondary to an opening wedge high tibial osteotomy, yet few data are available that quantify the effect of varying degrees of medial opening wedge osteotomy on the patellofemoral joint contact characteristics. Hypothesis: Opening wedge medial proximal tibial osteotomy will increase patellofemoral contact force and pressure. Study Design: Controlled laboratory study. Methods: Nine human cadaver knees were used. Pressure-sensitive film was placed in the suprapatellar pouch, leaving the patellar tendon and medial and lateral retinacula intact. The quadriceps tendon was attached to a materials testing machine along the axis of the femur, whereby a pulley mechanism generated 950 N of force. Patellofemoral contact characteristics were measured with pressure-sensitive film at 30°, 60°, 90°, and 120° of flexion for the native knee and after subsequent 10-mm and 15-mm medial opening wedge proximal tibial osteotomies. The film was analyzed with imaging software. Results: There was a statistically significant increase ( P < .05) in mean contact pressure at 30° and 120° between the 10-mm osteotomy and native knee and across all flexion angles between the 15-mm osteotomy and native knee. Furthermore, a significant difference was seen in peak pressures when native knees were compared with 10-mm and 15-mm opening wedge osteotomies at all flexion angles. Conclusion: There was a significant increase in patellofemoral pressures at varying degrees of knee flexion after medial opening wedge proximal tibial osteotomies of only 10 mm; a larger osteotomy resulted in a greater increase. Clinical Relevance: When performing a medial opening wedge proximal tibial osteotomy, the surgeon should consider the negative effects of increased patellofemoral peak pressure.
Some new applications of the GLPD micromorphic model of ductile fracture
Authors: Enakoutsa Koffi 
Published: October 2012

This paper presents some new applications of a model of ductile rupture of porous ductile materials proposed by Gologanu, Leblond, Perrin and Devaux (GLPD). The first application is concerned with the relationship between this model and the class of generalized standard materials. We show that the GLPD model fits in this class, provided that the porosity is not allowed to change and the hypothesis of linearized theory is adopted. The advantage of this property is that it automatically warrants the unicity of the solution for the ‘projection’ problem of the (supposedly) elastic stress predictor onto the GLPD’s yield locus. The second application leads to some exact analytical solutions of the GLPD model constitutive equations for the problems of an elastic hollow sphere in the framework of linearized theory, and viscous in large deformations. Comparisons between the numerical predictions of the GLPD model and the analytical solutions confirm the robustness of the numerical scheme used to implement this model into SYSTUS© finite element (FE) code. Thus, these exact analytical solutions can be used to validate the implementation of the GLPD model in another finite element code. In the third application, comparisons between experimental and numerical load vs. displacement curves for an axisymmetric pre-cracked specimen made of a typical stainless steel are found to yield satisfactory results.