bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Prevalence of Preinvasive Lesions Adjacent to BRCA1/2-Associated Breast Cancers
Authors: Arun Banu , Vogel Kristen J. , Lopez Adriana , Hernandez Mike , Atchley Deann , Broglio Kristine R. , Amos Christopher I. , Meric-Bernstam Funda , Kuerer Henry , Hortobagyi Gabriel N. , Albarracin Constance T. 
Published: January 2009

Abstract
Mutations in BRCA1 and BRCA2 increase a woman's lifetime risk of developing breast cancer by 43% to 84%. It was originally postulated that BRCA1/2-associated breast cancers develop more rapidly than sporadic cancers and may lack preinvasive lesions. More recent studies have found preinvasive lesions in prophylactic mastectomy specimens from mutation carriers; however, there is little information on the presence of preinvasive lesions in tissue adjacent to breast cancers. Our aim is to investigate the role of preinvasive lesions in BRCA-associated breast carcinogenesis.
We retrospectively compared BRCA1/2-associated breast cancers and sporadic breast cancers for the prevalence of preinvasive lesions [ductal carcinoma in situ (DCIS), lobular carcinoma in situ, and atypical lobular hyperplasia] in tissue adjacent to invasive breast cancers.
Pathology was reviewed for 73 BRCA1/2-associated tumors from patients with breast cancer. We selected 146 patients with mutation-negative breast cancer as age-matched controls. Among the BRCA1/2-associated breast cancers, 59% had at least one associated preinvasive lesion compared with 75% of controls. Preinvasive lesions were more prevalent in BRCA2 mutation carriers than in BRCA1 mutation carriers (70% versus 52%, respectively). The most common preinvasive lesion in both groups was DCIS; 56% of BRCA1/2-associated breast cancers and 71% of the sporadic breast cancers had adjacent intraductal disease, respectively.
Preinvasive lesions, most notably DCIS, are common in BRCA1/2-associated breast cancers. These findings suggest that BRCA1/2-associated breast cancers progress through the same intermediate steps as sporadic breast cancers, and that DCIS should be considered as a part of the BRCA1/2 tumor spectrum.
Identification of Modulated Genes by Three Classes of Chemopreventive Agents at Preneoplastic Stages in a p53-Null Mouse Mammary Tumor Model
Authors: Abba Martín C. , Hu Yuhui , Levy Carla C. , Gaddis Sally , Kittrell Frances S. , Hill Jamal , Bissonnette Reid P. , Brown Powel H. , Medina Daniel , Aldaz C. Marcelo 
Published: January 2009

Abstract
Genetically engineered mouse cancer models are among the most useful tools for testing the in vivo effectiveness of the various chemopreventive approaches. The p53-null mouse model of mammary carcinogenesis was previously characterized by us at the cellular, molecular, and pathologic levels. In a companion article, Medina et al. analyzed the efficacy of bexarotene, gefitinib, and celecoxib as chemopreventive agents in the same model. Here we report the global gene expression effects on mammary epithelium of such compounds, analyzing the data in light of their effectiveness as chemopreventive agents. SAGE was used to profile the transcriptome of p53-null mammary epithelium obtained from mice treated with each compound versus controls. This information was also compared with SAGE data from p53-null mouse mammary tumors. Gene expression changes induced by the chemopreventive treatments revealed a common core of 87 affected genes across treatments (P &lt; 0.05). The effective compounds, bexarotene and gefitinib, may exert their chemopreventive activity, at least in part, by affecting a set of 34 genes related to specific cellular pathways. The gene expression signature revealed various genes previously described to be associated with breast cancer, such as the activator protein-1 complex member Fos-like antigen 2 (Fosl2), early growth response 1 (Egr1), gelsolin (Gsn), and tumor protein translationally controlled 1 (Tpt1), among others. The concerted modulation of many of these transcripts before malignant transformation seems to be conducive to predominantly decrease cell proliferation. This study has revealed candidate key pathways that can be experimentally tested in the same model system and may constitute novel targets for future translational research.
Prevention of Tumorigenesis in p53-Null Mammary Epithelium by Rexinoid Bexarotene, Tyrosine Kinase Inhibitor Gefitinib, and Celecoxib
Authors: Medina Daniel , Kittrell Frances , Hill Jamal , Zhang Yun , Hilsenbeck Susan G. , Bissonette Reid , Brown Powel H. 
Published: January 2009

Abstract
The chemopreventive effects of three agents, rexinoid bexarotene, tyrosine kinase inhibitor gefitinib, and celecoxib, were tested on mammary tumor development arising in p53-null mammary epithelium. The rexinoid bexarotene was the most efficacious inhibitor as it reduced mammary tumor development by 75% in virgin mice and significantly delayed mean tumor development by 98 days in hormone-stimulated mice. The tyrosine kinase inhibitor gefitinib reduced mammary tumor incidence by 50% in virgin mice but did not significantly delay mean tumor latency in hormone-stimulated mice. Celecoxib did not reduce tumor incidence or mean tumor latency in either of the two models. The high doses of the rexinoid and the tyrosine kinase inhibitor did not affect the progression of tumors arising from the premalignant mammary outgrowth line, PN8a. A comparison of these agents with tamoxifen shows the superiority of tamoxifen in preventing tumor development in p53-null mammary cells. Similarly, a comparison of the results of the p53 model with other transgenic models in their response to the chemopreventive agents showed that mammary tumors arising from different oncogenic events will respond differently to the different agents.
Screening for Oral Precancer with Noninvasive Genetic Cytology
Authors: Bremmer Jantine F. , Graveland A. Peggy , Brink Arjen , Braakhuis Boudewijn J.M. , Kuik Dirk J. , Leemans C. René , Bloemena Elisabeth , van der Waal Isaäc , Brakenhoff Ruud H. 
Published: January 2009

Abstract
Oral squamous cell carcinomas develop in precancerous fields consisting of genetically altered mucosal epithelial cells. These precancerous fields may appear as clinically visible lesions, in particular, oral leukoplakia, but the large majority remains clinically undetectable. The aim of this study was to assess the potential value of a noninvasive screening approach to detect precancerous fields. As a first step, we developed a suitable assay and investigated 25 leukoplakia patients and 20 noncancer control subjects. Exfoliated cells were removed by a brush from multiple small areas of the oral mucosa, including the leukoplakia. Brushed samples were investigated for allelic imbalance (AI) at chromosomes 3p, 9p, 11q, and 17p using microsatellite markers known to show frequent alterations in oral precancer. AI was absent in all (137) of the samples of the 20 control subjects, yielding a specificity of 100%. AI was detected in exfoliated cell samples of 40% (10 of 25) of the leukoplakia lesions studied. Genetic changes were also found outside the leukoplakia lesions. Most frequent was AI at 9p (9 of 10). The noninvasive assay was validated against the biopsy results of the leukoplakia lesions yielding an estimate of sensitivity of 78% (7 of 9) and a positive predictive value of 100% (7 of 7). Altogether, these results show the feasibility of a noninvasive genetic screening approach for the detection and monitoring of oral precancer. This assay could therefore contribute to the secondary prevention of oral squamous cell carcinoma. The assay also shows promise for the detection of precancerous changes that are not macroscopically visible.
Antigen-loaded exosomes alone induce Th1-type memory through a B cell–dependent mechanism
Authors: Qazi Khaleda Rahman , Gehrmann Ulf , Domange Jordö Emilie , Karlsson Mikael C. I. , Gabrielsson Susanne 
Published: January 2009

AbstractExosomes are nanovesicles harboring proteins important for antigen presentation. We compared the potency of differently loaded exosomes, directly loaded with OVA323-339 peptide (Pep-Exo) or exosomes from OVA-pulsed DCs (OVA-Exo), for their ability to induce specific T-cell proliferation in vitro and in vivo. Both Pep-Exo and OVA-Exo elicited specific transgenic T-cell proliferation in vitro, with the Pep-Exo being more efficient. In contrast, only OVA-Exo induced specific T-cell responses in vivo highlighting the importance of indirect loading strategies in clinical applications. Coadministration of whole OVA overcame the unresponsiveness with Pep-Exo but still elicited a lower response compared with OVA-Exo. In parallel, we found that OVA-Exo not only augmented the specific T-cell response but also gave a Th1-type shift and an antibody response even in the absence of whole OVA. We detected IgG2a and interferon-γ production from splenocytes showing the capability of exosomes to provide antigen for B-cell activation. Furthermore, we found that B cells are needed for exosomal T-cell stimulation because Bruton tyrosine kinase–deficient mice showed abrogated B- and T-cell responses after OVA-Exo immunization. These findings reveal that exosomes are potent immune regulators and are relevant for the design of vaccine adjuvants and therapeutic intervention strategies to modulate immune responses.
FAS-L, IL-10, and double-negative CD4−CD8− TCR α/β+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function
Authors: Magerus-Chatinet Aude , Stolzenberg Marie-Claude , Loffredo Maria S. , Neven Bénédicte , Schaffner Catherine , Ducrot Nicolas , Arkwright Peter D. , Bader-Meunier Brigitte , Barbot José , Blanche Stéphane , Casanova Jean-Laurent , Debré Marianne , Ferster Alina , Fieschi Claire , Florkin Benoit , Galambrun Claire , Hermine Olivier , Lambotte Olivier , Solary Eric , Thomas Caroline , Le Deist Francoise , Picard Capucine , Fischer Alain , Rieux-Laucat Frédéric 
Published: January 2009

AbstractAutoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRαβ+ CD4−CD8− T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.
Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and require a novel type of cooperation with myeloid dendritic cells for maturation
Authors: Piccioli Diego , Sammicheli Chiara , Tavarini Simona , Nuti Sandra , Frigimelica Elisabetta , Manetti Andrea G.O. , Nuccitelli Annalisa , Aprea Susanna , Valentini Sara , Borgogni Erica , Wack Andreas , Valiante Nicholas M. 
Published: January 2009

AbstractDendritic cell (DC) populations play unique and essential roles in the detection of pathogens, but information on how different DC types work together is limited. In this study, 2 major DC populations of human blood, myeloid (mDCs) and plasmacytoid (pDCs), were cultured alone or together in the presence of pathogens or their products. We show that pDCs do not respond to whole bacteria when cultured alone, but mature in the presence of mDCs. Using purified stimuli, we dissect this cross-talk and demonstrate that mDCs and pDCs activate each other in response to specific induction of only one of the cell types. When stimuli for one or both populations are limited, they synergize to reach optimal activation. The cross-talk is limited to enhanced antigen presentation by the nonresponsive population with no detectable changes in the quantity and range of cytokines produced. We propose that each population can be a follower or leader in immune responses against pathogen infections, depending on their ability to respond to infectious agents. In addition, our results indicate that pDCs play a secondary role to induce immunity against human bacterial infections, which has implications for more efficient targeting of DC populations with improved vaccines and therapeutics.
Zyxin is a novel interacting partner for SIRT1
Authors: Fujita Yuki , Yamaguchi Atsushi , Hata Katsuhiko , Endo Mitsuharu , Yamaguchi Naoto , Yamashita Toshihide 
Published: January 2009

Abstract

Background
SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin family. It regulates longevity in several model organisms and is involved with cell survival, differentiation, metabolism among other processes in mammalian cells. SIRT1 modulates functions of various key targets via deacetylation. Recent studies have revealed SIRT1 protects neurons from axonal degeneration or neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and developmental defects, suggesting its critical roles in neurons and development.

Results
To identify novel binding partners for SIRT1 in the central nervous system, we performed yeast two-hybrid screening on human fetal brain cDNA library and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript were both preferentially expressed in developmental mouse brain. Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its function through deacetylation.

Conclusion
Zyxin could be a novel interacting partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and signal transduction to convey signal from the ECM (extracellular matrix) to the nucleus. Our results raise the possibility that SIRT1 regulates signal transmission from ECM to the nucleus by modulating the functions of zyxin via deacetylation.
Differential selection on gene translation efficiency between the filamentous fungus Ashbya gossypii and yeasts
Authors: Jiang Huifeng , Zhang Yue , Sun Jun , Wang Wen , Gu Zhenglong 
Published: January 2009

Abstract

Background
The filamentous fungus Ashbya gossypii grows into a multicellular mycelium that is distinct from the unicellular morphology of its closely related yeast species. It has been proposed that genes important for cell cycle regulation play central roles for such phenotypic differences. Because A. gossypii shares an almost identical set of cell cycle genes with the typical yeast Saccharomyces cerevisiae, the differences might occur at the level of orthologous gene regulation. Codon usage patterns were compared to identify orthologous genes with different gene regulation between A. gossypii and nine closely related yeast species.

Results
Here we identified 3,151 orthologous genes between A. gossypii and nine yeast species. Two groups of genes with significant differences in codon usage (gene translation efficiency) were identified between A. gossypii and yeasts. 333 genes (Group I) and 552 genes (Group II) have significantly higher translation efficiency in A. gossypii and yeasts, respectively. Functional enrichment and pathway analysis show that Group I genes are significantly enriched with cell cycle functions whereas Group II genes are biased toward metabolic functions.

Conclusion
Because translation efficiency of a gene is closely related to its functional importance, the observed functional distributions of orthologous genes with different translation efficiency might account for phenotypic differentiation between A. gossypii and yeast species. The results shed light on the mechanisms for pseudohyphal growth in pathogenic yeast species.
Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in patients with left-ventricular dysfunction: a systematic review and meta-analysis
Authors: van der Avoort Charlotte J , Filion Kristian B , Dendukuri Nandini , Brophy James M 
Published: January 2009

Abstract

Background
Studies have demonstrated that the use of implantable cardioverter defibrillators (ICDs) is effective for the primary prevention of arrhythmic events but due to imposing costs, there remains a need to identify which patients will derive the greatest benefit. Microvolt T-wave alternans (MTWA) has been proposed to assist in this stratification.

Methods
We systematically searched the literature using MEDLINE, EMBASE, Current Contents, the Cochrane Library, INAHTA, and the Web of Science to identify all primary prevention randomized controlled trials and prospective cohort studies with at least 12 months of follow-up examining MTWA as a predictor of mortality and severe arrhythmic events in patients with severe left-ventricular dysfunction. The search was limited to full-text English publications between January 1990 and May 2007. The primary outcome was a composite of mortality and severe arrhythmias. Data were synthesized using Bayesian hierarchical models.

Results
We identified no trials and 8 published cohort studies involving a total of 1,946 patients, including 332 positive, 656 negative, 84 indeterminate, and 874 non-negative (which includes both positive and indeterminate tests) MTWA test results. The risk of mortality or severe arrhythmic events was higher in patients with a positive MTWA compared to a negative test (RR = 2.7, 95% credible interval (CrI) = 1.4, 6.1). Similar results were obtained when comparing non-negative MTWA to a negative test.

Conclusion
A positive MTWA test predicts mortality or severe arrhythmic events in a population of individuals with severe left ventricular dysfunction. However, the wide credible interval suggests the clinical utility of this test remains incompletely defined, ranging from very modest to substantial. Additional high quality studies are required to better refine the role of MTWA in the decision making process for ICD implantation.
Epithelial ovarian cancer relapsing as isolated lymph node disease: natural history and clinical outcome
Authors: Legge Francesco , Petrillo Marco , Adamo Vincenzo , Pisconti Salvatore , Scambia Giovanni , Ferrandina Gabriella 
Published: January 2009

Abstract

Background
Several evidences suggested that ovarian cancer (OC) patients showing isolated lymph node recurrence (ILNR) have an indolent evolution. The aim of the study was to retrospectively review ILNR observed in our Institution over the past 11 years in order to investigate: the pattern of disease progression after the first diagnosis of ILNR, and their clinical outcome.

Methods
Between September 1995 and September 2006, 523 epithelial OC were diagnosed in our centers, and 301 of these relapsed. Cases with a diagnosis of ILNR, and at least 12 months of follow up after the diagnosis of ILNR were included. Post-relapse survival (PRS) was recorded from the date of the diagnosis of ILNR to the date of death or date last seen. Survival probabilities were estimated according to the method of Kaplan and Meier and compared by the log rank test. Cox's regression model with stepwise variable selection was used to analyse the role of clinico-pathological parameters as prognostic factors for PRS.

Results
Thirty-two cases were identified as ILNR (10.6% of the recurrences, and 6.1% of the OC population). Most of the patients continued to exhibit the same pattern of progression during follow up, with 75% of the patients free from peritoneal disease after 2 years from the diagnosis of ILNR. Median Post-Relapse Survival (PRS) was 37 months, and median Overall Survival (OS) was 109 months, with all patients surviving more than 2 years after the initial diagnosis. In multivariate analysis only Platinum-Free Interval (PFI) retained a prognostic role for PRS (p value = 0.033).

Conclusion
ILNR represents a less aggressive pattern of OC relapse which keeps progressing in the lymph nodes in a relatively high percentage of cases. On the other hand, the occurrence of peritoneal spreading after ILNR is associated with a rapidly fatal outcome.
Summary of the primer on tumor immunology and the biological therapy of cancer
Authors: Li Yufeng , Liu Shujuan , Margolin Kim , Hwu Patrick 
Published: January 2009

Abstract
The International Society for Biological Therapy of Cancer (iSBTc) is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this program includes investigators from academic, regulatory, and biopharmaceutical venues. The program goal is to enable the attendees to learn the current status and the most recent advances in biologic therapies, and to leverage this knowledge towards the improvement of cancer therapy. The 2008 immunologic primer course was held on October 30 at the 23rd Annual meeting of iSBTc in San Diego, CA. Nine internationally renowned investigators gave excellent presentations on different topics. The topics covered in this primer included: (1) cytokines in cancer immunology; (2) anti-angiogenic therapy; (3) end stage: immune killing of tumors; (4) blocking T cell checkpoints; (5) approach to identification and therapeutic exploitation of tumor antigens; (6) T regulatory cells; (7) adoptive T cell therapy; (8) immune monitoring of cancer immunotherapy; and (9) immune adjuvants. We summarized the topics in this primer for public education. The related topic slides and schedule can be accessed online http://www.isbtc.org/meetings/am08/primer08.
Determination of patient-specific internal gross tumor volumes for lung cancer using four-dimensional computed tomography
Authors: Ezhil Muthuveni , Vedam Sastry , Balter Peter , Choi Bum , Mirkovic Dragan , Starkschall George , Chang Joe Y 
Published: January 2009

Abstract

Background
To determine the optimal approach to delineating patient-specific internal gross target volumes (IGTV) from four-dimensional (4-D) computed tomography (CT) image data sets used in the planning of radiation treatment for lung cancers.

Methods
We analyzed 4D-CT image data sets of 27 consecutive patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV, defined to be the envelope of respiratory motion of the gross tumor volume in each 4D-CT data set was delineated manually using four techniques: (1) combining the gross tumor volume (GTV) contours from ten respiratory phases (IGTVAllPhases); (2) combining the GTV contours from two extreme respiratory phases (0% and 50%) (IGTV2Phases); (3) defining the GTV contour using the maximum intensity projection (MIP) (IGTVMIP); and (4) defining the GTV contour using the MIP with modification based on visual verification of contours in individual respiratory phase (IGTVMIP-Modified). Using the IGTVAllPhases as the optimum IGTV, we compared volumes, matching indices, and extent of target missing using the IGTVs based on the other three approaches.

Results
The IGTVMIP and IGTV2Phases were significantly smaller than the IGTVAllPhases (p < 0.006 for stage I and p < 0.002 for stage III). However, the values of the IGTVMIP-Modified were close to those determined from IGTVAllPhases (p = 0.08). IGTVMIP-Modified also matched the best with IGTVAllPhases.

Conclusion
IGTVMIP and IGTV2Phases underestimate IGTVs. IGTVMIP-Modified is recommended to improve IGTV delineation in lung cancer.