bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linked outbreaks and control of porcine reproductive and respiratory syndrome and postweaning multisystemic wasting syndrome in a pig farm in Poland
Authors: Stadejek T. , Podgorska K. , Porowski M. , Jabłoński A. , Pejsak Z. 
Published: September 2011

In a newly established farrow‐to‐finish farm (porcine reproductive and respiratory virus [PRRSV]‐free, porcine circovirus type 2 [PCV‐2]‐infected), reproductive failure was seen seven months after population. The conception rate dropped from 89 to 51 per cent, and the abortion rate increased from 0.5 to 11 per cent. The following month, characteristic lesions of postweaning multisystemic wasting syndrome (PMWS) and elevated mortality were observed in weaned pigs. Laboratory examinations confirmed reproductive failure due to PRRSV and PMWS associated with apparent activation of the PCV‐2 circulating in the farm. The herd was closed for replacement and a number of measures to improve hygiene, environmental conditions and feeding were applied. The abortion rate returned to preoutbreak levels four months after the beginning of the PRRS outbreak and the conception rate returned to normal four months later. Slower improvement was observed regarding the PMWS outbreak, with PMWS‐related losses disappearing nine months after the detection of PMWS. Analysis of seroconversion profiles to PCV‐2 and PRRSV during the outbreak and after its control indicated that while PRRSV was eliminated from sows and weaners by the control measures, the time of PCV‐2 infection was unchanged and occurred at seven weeks of age during the PMWS outbreak as well as after its elimination. However, the elimination of PMWS from the herd coincided with increased levels of maternally derived antibodies to PCV‐2 in one‐ to five‐week‐old pigs and faster serological responses to infection with PCV‐2.
THE TOPOLOGY AND ANALYSIS OF THE HANNA NEUMANN CONJECTURE
Authors: MINEYEV IGOR 
Published: September 2011

The statement of the Hanna Neumann Conjecture (HNC) is purely algebraic: for a free group Γ and any nontrivial finitely generated subgroups A and B of Γ, [Formula: see text]The goal of this paper is to systematically develop machinery that would allow for generalizations of HNC and to exhibit their relations with topology and analysis. On the topological side we define immersions of complexes, leafages, systems of complexes, flowers, gardens, and atomic decompositions of graphs and surfaces. The analytic part involves working with the classical Murray–von Neumann (!) dimension of Hilbert modules.This also gives an approach to the Strengthened Hanna Neumann Conjecture (SHNC) and to its generalizations. We present three faces of it named, respectively, the square approach, the diagonal approach, and the arrangement approach. Each of the three comes from the notion of a system, and each leads to questions beyond graphs and free groups. Partial results, sufficient conditions, and generalizations of the statement of SHNC are presented.
Toll-like Receptor 9 Agonist IMO Cooperates with Cetuximab in K-Ras Mutant Colorectal and Pancreatic Cancers
Authors: Rosa Roberta , Melisi Davide , Damiano Vincenzo , Bianco Roberto , Garofalo Sonia , Gelardi Teresa , Agrawal Sudhir , Di Nicolantonio Federica , Scarpa Aldo , Bardelli Alberto , Tortora Giampaolo 
Published: September 2011

Abstract
Purpose: K-Ras somatic mutations are a strong predictive biomarker for resistance to epidermal growth factor receptor (EGFR) inhibitors in patients with colorectal and pancreatic cancer. We previously showed that the novel Toll-like receptor 9 (TLR9) agonist immunomodulatory oligonucleotide (IMO) has a strong in vivo activity in colorectal cancer models by interfering with EGFR-related signaling and synergizing with the anti-EGFR monoclonal antibody cetuximab.
Experimental Design: In the present study, we investigated, both in vitro and in vivo, the antitumor effect of IMO alone or in combination with cetuximab in subcutaneous colon and orthotopic pancreatic cancer models harboring K-Ras mutations and resistance to EGFR inhibitors.
Results: We showed that IMO was able to significantly restore the sensitivity of K-Ras mutant cancer cells to cetuximab, producing a marked inhibition of cell survival and a complete suppression of mitogen—activated protein kinase phosphorylation, when used in combination with cetuximab. IMO interfered with EGFR-dependent signaling, modulating the functional interaction between TLR9 and EGFR. In vivo, IMO plus cetuximab combination caused a potent and long-lasting cooperative antitumor activity in LS174T colorectal cancer and in orthotopic AsPC1 pancreatic cancer. The capability of IMO to restore cetuximab sensitivity was further confirmed by using K-Ras mutant colorectal cancer cell models obtained through homologous recombination technology.
Conclusions: We showed that IMO markedly inhibits growth of K-Ras mutant colon and pancreatic cancers in vitro and in nude mice and cooperates with cetuximab via multiple mechanisms of action. Therefore, we propose IMO plus cetuximab as a therapeutic strategy for K-Ras wild-type as well for K-Ras mutant, cetuximab-resistant colorectal and pancreatic cancers. Clin Cancer Res; 17(20); 6531–41. ©2011 AACR.
A 5-MicroRNA Signature for Lung Squamous Cell Carcinoma Diagnosis and hsa-miR-31 for Prognosis
Authors: Tan Xiaogang , Qin Wenyan , Zhang Liang , Hang Jie , Li Baozhong , Zhang Cuiyan , Wan Junting , Zhou Fang , Shao Kang , Sun Yimin , Wu Jianping , Zhang Xun , Qiu Bin , Li Ning , Shi Susheng , Feng Xiaoli , Zhao Shouhua , Wang Zhen , Zhao Xiaohong , Chen Zhaoli , Mitchelson Keith , Cheng Jing , Guo Yong , He Jie 
Published: September 2011

AbstractPurpose: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients.Experimental Design: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I–III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined.Results: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan–Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan–Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2.Conclusions: Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31. Clin Cancer Res; 17(21); 6802–11. ©2011 AACR.
The Reconstruction of Transcriptional Networks Reveals Critical Genes with Implications for Clinical Outcome of Multiple Myeloma
Authors: Agnelli Luca , Forcato Mattia , Ferrari Francesco , Tuana Giacomo , Todoerti Katia , Walker Brian A. , Morgan Gareth J. , Lombardi Luigia , Bicciato Silvio , Neri Antonino 
Published: September 2011

Abstract
Purpose: The combined use of microarray technologies and bioinformatics analysis has improved our understanding of biological complexity of multiple myeloma (MM). In contrast, the application of the same technology in the attempt to predict clinical outcome has been less successful with the identification of heterogeneous molecular signatures. Herein, we have reconstructed gene regulatory networks in a panel of 1,883 samples from MM patients derived from publicly available gene expression sets, to allow the identification of robust and reproducible signatures associated with poor prognosis across independent data sets.
Experimental Design: Gene regulatory networks were reconstructed by using Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and microarray data from seven MM data sets. Critical analysis of network components was applied to identify genes playing an essential role in transcriptional networks, which are conserved between data sets.
Results: Network critical analysis revealed that (i) CCND1 and CCND2 were the most critical genes; (ii) CCND2, AIF1, and BLNK had the largest number of connections shared among the data sets; (iii) robust gene signatures with prognostic power were derived from the most critical transcripts and from shared primary neighbors of the most connected nodes. Specifically, a critical-gene model, comprising FAM53B, KIF21B, WHSC1, and TMPO, and a neighbor-gene model, comprising BLNK shared neighbors CSGALNACT1 and SLC7A7, predicted survival in all data sets with follow-up information.
Conclusions: The reconstruction of gene regulatory networks in a large panel of MM tumors defined robust and reproducible signatures with prognostic importance, and may lead to identify novel molecular mechanisms central to MM biology. Clin Cancer Res; 17(23); 7402–12. ©2011 AACR.
A Phase I Trial of Liposomal Doxorubicin, Bevacizumab, and Temsirolimus in Patients with Advanced Gynecologic and Breast Malignancies
Authors: Moroney John W. , Schlumbrecht Matthew P. , Helgason Thorunn , Coleman Robert L. , Moulder Stacy , Naing Aung , Bodurka Diane C. , Janku Filip , Hong David S. , Kurzrock Razelle 
Published: September 2011

Abstract
Purpose: Liposomal doxorubicin (D) and bevacizumab (A) are active single agents in gynecologic and breast malignancies which share a resistance mechanism: upregulation of hypoxia inducible factor (HIF-1α). We, therefore, added temsirolimus (T), which inhibits HIF-1α, to D and A (DAT). Trial objectives were assessment of safety, preliminary efficacy, and identification of biological response correlates.
Patients and Methods: Cycle length was 21 days, with IV D, A, and T on day 1; T on days 8 and 15 (3+3 dose-escalation design with expansion cohorts). Mutational assays for PIK3CA, BRAF, KRAS, and immunhistochemistry for PTEN loss were conducted.
Results: This article details 74 patients with gynecologic and breast malignancies who received at least one dose of drug on study. Median patient age: 52 (27–79); prior regimens: 4 (1–11). Responses: 1 (1.4%) complete response (CR), 14 (18.9%) partial responses (PR), and 13 (17.6%) with stable disease (SD) ≥ 6 months (total = 37.9%). The most common grade 1 toxicities were fatigue (27%) and anemia (20.2%). Notable grade 3/4 toxicities: thrombocytopenia (9.5%), mucositis (6.7%), and bowel perforation (2.7%). PIK3CA mutations or PTEN loss were identified in 25 of 59 (42.3%) of tested patients. Among these, nine (36%) achieved CR/PR and four (16%) had SD ≥ 6 months (CR+PR+SD ≥ 6 months = 52%).
Conclusions: DAT is well tolerated with manageable side effects. Responses observed warrant further evaluation. Mutational analyses were notable for a high percentage of responders with phosphoinositide-3-kinase pathway aberrations. Clin Cancer Res; 17(21); 6840–6. ©2011 AACR.
The Prognostic Significance of Various 13q14 Deletions in Chronic Lymphocytic Leukemia
Authors: Ouillette Peter , Collins Roxane , Shakhan Sajid , Li Jinghui , Li Cheng , Shedden Kerby , Malek Sami N. 
Published: September 2011

Abstract
Purpose: To further our understanding of the biology and prognostic significance of various chromosomal 13q14 deletions in chronic lymphocytic leukemia (CLL).
Experimental Design: We analyzed data from SNP 6.0 arrays to define the anatomy of various 13q14 deletions in a cohort of 255 CLL patients and have correlated two subsets of 13q14 deletions (type I exclusive of RB1 and type II inclusive of RB1) with patient survival. Furthermore, we measured the expression of the 13q14-resident microRNAs by quantitative PCR (Q-PCR) in 242 CLL patients and subsequently assessed their prognostic significance. We sequenced all coding exons of RB1 in patients with monoallelic RB1 deletion and have sequenced the 13q14-resident miR locus in all patients.
Results: Large 13q14 (type II) deletions were detected in approximately 20% of all CLL patients and were associated with shortened survival. A strong association between 13q14 type II deletions and elevated genomic complexity, as measured through CLL-FISH or SNP 6.0 array profiling, was identified, suggesting that these lesions may contribute to CLL disease evolution through genomic destabilization. Sequence and copy number analysis of the RB1 gene identified a small CLL subset that is RB1 null. Finally, neither the expression levels of the 13q14-resident microRNAs nor the degree of 13q14 deletion, as measured through SNP 6.0 array-based copy number analysis, had significant prognostic importance.
Conclusions: Our data suggest that the clinical course of CLL is accelerated in patients with large (type II) 13q14 deletions that span the RB1 gene, therefore justifying routine identification of 13q14 subtypes in CLL management. Clin Cancer Res; 17(21); 6778–90. ©2011 AACR.
Species D Adenoviruses as Oncolytics against B-cell Cancers
Authors: Chen Christopher Y. , Senac Julien S. , Weaver Eric A. , May Shannon M. , Jelinek Diane F. , Greipp Philip , Witzig Thomas , Barry Michael A. 
Published: September 2011

Abstract
Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we “mined” the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers.
Experimental Design: Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers for their ability to infect, replicate in, and kill these cells. Select viruses were also tested against B-cell cancer xenografts in immunodeficient mice.
Results: Species D adenoviruses mediated most robust killing against a range of B-cell cancer cell lines, against primary patient marginal zone lymphoma cells, and against primary patient CD138+ myeloma cells in vitro. When injected into xenografts in vivo, single treatment with select species D viruses Ad26 and Ad45 delayed lymphoma growth.
Conclusions: Relatively unstudied species D adenoviruses have a unique ability to infect and replicate in B-cell cancers as compared with other adenovirus species. These data suggest these viruses have unique biology in B cells and support translation of novel species D adenoviruses as oncolytics against B-cell cancers. Clin Cancer Res; 17(21); 6712–22. ©2011 AACR.
Lysophosphatidic Acid–Induced p21Waf1 Expression Mediates the Cytostatic Response of Breast and Ovarian Cancer Cells to TGFβ
Authors: Wu Jinhua , Mukherjee Abir , Lebman Deborah A. , Fang Xianjun 
Published: September 2011

Abstract
Lysophosphatidic acid (LPA) is a multifunctional intercellular phospholipid mediator present in blood and other biological fluids. In cancer cells, LPA stimulates expression or activity of inflammatory cytokines, angiogenic factors, matrix metalloproteinases, and other oncogenic proteins. In this study, we showed that LPA upregulated expression of the cyclin-dependent kinase inhibitor p21Waf1 in TGFβ-sensitive breast and ovarian cancer cells, but not in TGFβ-resistant ones. We examined the possibility that LPA-induced p21 might contribute to the cytostatic response to TGFβ. In serum-free conditions, TGFβ alone induced p21 expression weakly in TGFβ-sensitive cells. Serum or serum-borne LPA cooperated with TGFβ to elicit the maximal p21 induction. LPA stimulated p21 via LPA1 and LPA2 receptors and Erk-dependent activation of the CCAAT/enhancer binding protein beta transcription factor independent of p53. Loss or gain of p21 expression led to a shift between TGFβ-sensitive and -resistant phenotypes in breast and ovarian cancer cells, indicating that p21 is a key determinant of the growth inhibitory activity of TGFβ. Our results reveal a novel cross-talk between LPA and TGFβ that underlies TGFβ-sensitive and -resistant phenotypes of breast and ovarian cancer cells. Mol Cancer Res; 9(11); 1562–70. ©2011 AACR.
Hunting for the Causes of Meningioma—Obesity Is a Suspect
Authors: Rajaraman Preetha 
Published: September 2011

AbstractIn this issue of the journal, Michaud and colleagues report a 48% increased risk of meningioma in obese individuals compared with individuals with a normal body mass index (BMI). This large prospective cohort study adds weight to the suggested link between BMI and meningioma, thus contributing to the growing number of cancer sites likely associated with body fatness. Although the exact mechanisms underlying the BMI–meningioma link are unclear, possible mediators include hormonal factors, immunologic response, and levels of insulin or insulin-like growth factors, each of which has been implicated by various levels of evidence in meningioma risk. Understanding the relationships between body fatness, height, and hormonal and immunologic factors could provide important clues to the etiology of meningioma and may have implications for the early detection and prevention of these tumors. Cancer Prev Res; 4(9); 1353–5. ©2011 AACR.
Brush-based Cytology Screening in the Tonsils and Cervix: There Is a Difference!
Authors: Lingen Mark W. 
Published: September 2011

Abstract
This perspective on the report by Fakhry and colleagues in this issue of the journal (beginning on page 1378) examines the diagnostic accuracy of a “Pap-test equivalent” for screening for human papillomavirus (HPV)-associated cancers in the tonsils. HPV infection is strongly associated with cancer development in the oropharynx (tonsils and base of tongue) and cervix; the data discussed here underscore the differences in screening for cervical versus oropharyngeal malignancies and discuss some of the challenges and limitations associated with screening for tonsillar premalignancy and early cancers. Cancer Prev Res; 4(9); 1350–2. ©2011 AACR.
Personalizing CA125 Levels for Ovarian Cancer Screening
Authors: Dorigo Oliver , Berek Jonathan S. 
Published: September 2011

Abstract
Screening trials for the early detection of ovarian cancer in the general population and in patients at a high risk for this disease have so far failed to show a reduction of ovarian cancer–specific mortality. Current screening modalities include pelvic examinations, transvaginal ultrasounds, and cancer antigen 125 (CA125) serum marker levels, which are associated with a high false-positive rate. The last decade has witnessed significant modifications in the interpretation of serum CA125 that extend beyond a static CA125 cutoff point. The Risk of Ovarian Cancer Algorithm (ROCA) incorporates changes of CA125 levels over time and an individual's age-specific risk. Ongoing screening trials have incorporated ROCA, but it is still unclear whether the algorithm will increase the sensitivity and specificity of early ovarian cancer diagnosis. A very recent study analyzed baseline CA125 serum marker levels from high-risk patients included in ovarian cancer screening trials conducted by the Cancer Genetics Network and the Gynecologic Oncology Group. The findings show that the distribution of CA125 serum marker levels in this population is significantly affected by various demographic and clinical factors, in particular menopausal status and oral contraceptive use in premenopausal patients. The data suggest that CA125 cutoff points might have to be stratified for subgroups of patients to reduce false-positive results. These intriguing observations will need to be validated in future screening trials for ovarian cancer. Cancer Prev Res; 4(9); 1356–9. ©2011 AACR.
HPV-associated Oropharyngeal Cancers—Are They Preventable?
Authors: Kreimer Aimée R. , Chaturvedi Anil K. 
Published: September 2011

Abstract
It is not known whether a human papillomavirus (HPV)-induced oropharyngeal precancerous lesion could be identified by screening with a pap test equivalent or whether one even exists. In this issue of the journal (beginning on page 1378), Fakhry and colleagues report their results showing that cytologic evaluation of the oropharynx, although useful in detecting invasive oropharyngeal cancers, may have limited utility as a screening modality for detecting precancer. These findings argue against the potential for secondary prevention of HPV-associated oropharyngeal cancers through screening for and preventing the progression of precancer and highlight the opportunity for primary prevention through prophylactic HPV vaccination, if proven efficacious and cost-effective. Cancer Prev Res; 4(9); 1346–9. ©2011 AACR.
Predicting Adherence to Tamoxifen for Breast Cancer Adjuvant Therapy and Prevention
Authors: Lin Jennifer H. , Zhang Shumin M. , Manson JoAnn E. 
Published: September 2011

Abstract
Treatment with the selective estrogen receptor modulator (SERM) tamoxifen for 5 years has produced dramatic breast cancer–related benefits in (a) the adjuvant setting, with 30% to 50% reductions in recurrence, contralateral disease, and mortality and (b) the prevention setting of healthy high-risk women, where tamoxifen reduces the risk of invasive and noninvasive breast cancer by 50%. Despite these striking data, adherence to tamoxifen is low, and low adherence is associated with poor survival. Although toxicity is a major predictor of poor adherence after starting therapy, pretreatment (baseline) predictors of poor tamoxifen adherence have been minimally studied. The adherence–survival link underscores the critical need to identify early predictors of poor adherence, and recent work is beginning to address this need. A major baseline predictor of poor adherence to prevention is current smoking, which is interestingly absent from studies of adherence to adjuvant therapy. Other important prevention adherence factors include breast cancer risk, extremes of age, non-white ethnicity, low socioeconomic status, and alcohol use. The strongest adjuvant therapy predictors are age (especially very young), ethnicity, and socioeconomic status. Future studies involving prospective systematic evaluation of these and other potential predictors in endocrine chemoprevention (e.g., other SERMs and aromatase inhibitors) are critical, as is the development of effective/targeted interventions to improve adherence and thus treatment outcomes in at-risk women. Cancer Prev Res; 4(9); 1360–5. ©2011 AACR.