bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybridization between the threatened herbBoltonia decurrens(Asteraceae) and its widespread congener,B. asteroides
Authors: DeWoody Jennifer , Nason John D. , Smith Marian 
Published: March 2011

Boltonia decurrens (Torr. & A. Gray) A. Wood is a federally threatened herb endemic to the Illinois River floodplain, and currently restricted to fewer than 25 populations. We tested for hybridization between this species and a widespread congener, Boltonia asteroides (L.) L’Hér., at two sites where they are known to occur in sympatry, by comparing morphological and genetic diversity with an allopatric population of each species. Morphological analyses identified significant differentiation between species. Discriminant classification analysis of the morphological data assigned most individuals to one or the other of the two parental species with high probability (>0.95), with only four plants having an intermediate probability of assignment (<0.90) indicative of hybrid origin. Similarly, likelihood-based methods based on genetic marker data (allozymes) failed to detect the presence of F1hybrids in either sympatric population and revealed only low frequencies of F2and backcross progeny. These findings demonstrate that combining morphological and genetic data increases the likelihood of detecting low-scale introgression between closely related species. Even with this combined approach, the low rate of recombination between these species together with their limited sympatry indicate that hybridization does not pose an immediate threat to the genetic integrity of B. decurrens.
Hybridization among foundation tree species influences the structure of associated understory plant communities
Authors: Lamit L. J. , Wojtowicz T. , Kovacs Z. , Wooley S. C. , Zinkgraf M. , Whitham T. G. , Lindroth R. L. , Gehring C. A. 
Published: March 2011

Understanding how genetic identity influences community structure is a major focus in evolutionary ecology, yet few studies examine interactions among organisms in the same trophic level within this context. In a common garden containing trees from a hybrid system (Populus fremontii S. Wats. × Populus angustifolia James), we tested the hypothesis that the structure of establishing understory plant communities is influenced by genetic differences among trees and explored foliar condensed tannins (CTs) and photosynthetically active radiation (PAR) as mechanisms. Several findings support our hypothesis: (i) Understory biomass and cover increase along the genetic gradient from P. angustifolia to P. fremontii. (ii) Along the same hybridization gradient, species richness decreases and species composition shifts. (iii) Populus foliar CT concentrations and PAR decrease from P. angustifolia to P. fremontii. (iv) Understory species richness increases with foliar CTs; however, biomass, cover, and composition show no relationship with CTs, and no understory variables correlate with PAR. (v) Structural equation modeling suggests that foliar CTs are a primary mechanism linking overstory tree genetics with understory richness. Using an experimental system dominated by naturally colonizing exotic species, this study demonstrates that a genetic gradient created by tree hybridization can influence understory plants.
Tree spatial pattern within the forest–tundra ecotone: a comparison of sites across CanadaThis article is a contribution to the series Tree recruitment, growth, and distribution at the circumpolar forest–tundra transition.
Authors: Harper Karen A. , Danby Ryan K. , De Fields Danielle L. , Lewis Keith P. , Trant Andrew J. , Starzomski Brian M. , Savidge Rodney , Hermanutz Luise 
Published: March 2011

Although many studies have focused on factors influencing treeline advance with climate change, less consideration has been given to potential changes in tree spatial pattern across the forest–tundra ecotone. We investigated trends in spatial pattern across the forest–tundra ecotone and geographical variation in the Yukon, Manitoba, and Labrador, Canada. Tree cover was measured in contiguous quadrats along transects up to 100 m long located in Forest, Ecotone, and Tundra sections across the forest–tundra transition. Spatial patterns were analyzed using new local variance to estimate patch size and wavelet analysis to determine the scale and amount of aggregation. Compared with the Forest, tree cover in the Ecotone was less aggregated at most sites, with fewer smaller patches of trees. We found evidence that shorter trees may be clumped at some sites, perhaps due to shelter from the wind, and we found little support for regular spacing that would indicate competition. With climate change, trees in the Ecotone will likely become more aggregated as patches enlarge and new patches establish. However, results were site-specific, varying with aspect and the presence of krummholz (stunted trees); therefore, strategies for adaptation of communities to climate change in Canada’s subarctic forest would need to reflect these differences.
Effects of manganese addition on carbon release from forest floor horizons
Authors: Trum Florence , Titeux Hugues , Cornelis Jean-Thomas , Delvaux Bruno 
Published: March 2011

Lignin concentration in organic residues largely controls their decomposition. Mn2+ may well play a key role in ligninolysis because it is a cofactor of manganese peroxidase, an enzyme of the lignin-degrading system. This study aims to investigate the effects of Mn2+ addition on forest floor horizon decomposition during laboratory incubation. Therefore, we sampled two distinct forest floors from European beech ( Fagus sylvatica L.) stands: a mor and a moder. Lignin and Mn concentrations in forest floor upper layer were significantly larger in moder than in mor. Three horizons from each forest floor were separately incubated with or without Mn2+ addition (250 mg Mn·kg dry matter–1) and the release of both CO2 and dissolved organic C was measured. The dissolved organic C release was not impacted by the Mn2+ addition, while a clear increase in CO2 release from specific horizons was observed. Our data suggest that the impact of the Mn2+ addition depends on (i) the forest floor type and on (ii) the organic matter decomposition stage.
Factors affecting northern white-cedar (Thuja occidentalis) seedling establishment and early growth in mixedwood stands
Authors: Larouche Catherine , Ruel Jean-Claude , Lussier Jean-Martin 
Published: March 2011

Regeneration of northern white-cedar ( Thuja occidentalis L.) is often deficient after harvesting in mixedwood stands growing on mesic sites even where browsing pressure is low. We compared the effectiveness of silviculture treatments on early regeneration of white-cedar after single-tree selection cutting (25% of basal area removed), shelterwood seed cut (50% of basal area removed), and group selection cutting (gaps of 625 m2) in three yellow birch ( Betula alleghaniensis Britt.) – softwood uneven-aged stands in Quebec, Canada. Three years after harvesting, the combination of factors that maximized abundance of white-cedar seedlings was single-tree selection cutting with artificial seeding on exposed mineral seedbeds (68.8% of plots with the presence of white-cedar). Early growth of planted white-cedar seedlings (40 cm tall) and biomass production were proportional to light availability, i.e., best under group selection cutting (mean height increment = 14.8 cm/year, mean root collar diameter increment = 3.0 mm/year). Browsing pressure has regional impacts depending on herbivore occupancy of the area. Our study was conducted near the northern limit of white-tailed deer ( Odocoileus virginianus (Zimmerman, 1780)), and deer were locally absent, while snowshoe hare ( Lepus americanus Erxleben, 1777) did not have a consistent effect on seedling abundance and early survival, limiting height growth only during the first year following planting.
New Strategies in Metastatic Prostate Cancer: Targeting the Androgen Receptor Signaling Pathway
Authors: Attard Gerhardt , Richards Juliet , de Bono Johann S. 
Published: March 2011

Abstract
Recent data report that abiraterone acetate, a specific inhibitor of CYP17 that is key to androgen and estrogen synthesis, improves survival in metastatic castration-resistant prostate cancer (CRPC), confirming the continued dependency of CRPC on the androgen receptor (AR) signaling pathway. MDV3100 is a novel antagonist of AR that is also in phase III clinical trials. In addition, several other agents targeting the AR axis are undergoing evaluation in early clinical studies. CRPC patients progress on these therapies with an increasing prostate specific antigen (PSA), suggesting that repeated therapeutic interventions targeting the AR signaling axis could induce secondary responses and achieve prolonged clinical benefit for a subgroup of patients. These exciting results are good news for patients but introduce a number of treatment paradigm dilemmas for physicians. Clinical studies evaluating the ideal sequence of administration of these new agents, best timing for initiation, combination strategies, discontinuation beyond progression and after commencement of subsequent therapies, and coordination with other treatments have not been done. Predictive biomarkers could allow patient selection for a specific treatment, but in their absence, most physicians will rely on a trial of treatment with a preferred agent and substitute for an alternative therapy on objective progression. Current data suggest that the response rate to drugs targeting the AR ligand-binding domain decreases with each treatment, but we hypothesize that a significant proportion of CRPC remains dependent on the AR axis and, therefore, novel strategies for disrupting AR signaling merit evaluation. Clin Cancer Res; 17(7); 1649–57. ©2011 AACR.
Direct Effects of Type I Interferons on Cells of the Immune System
Authors: Hervas-Stubbs Sandra , Perez-Gracia Jose Luis , Rouzaut Ana , Sanmamed Miguel F. , Le Bon Agnes , Melero Ignacio 
Published: March 2011

AbstractType I interferons (IFN-I) are well-known inducers of tumor cell apoptosis and antiangiogenesis via signaling through a common receptor interferon alpha receptor (IFNAR). IFNAR induces the Janus activated kinase–signal transducer and activation of transcription (JAK-STAT) pathway in most cells, along with other biochemical pathways that may differentially operate, depending on the responding cell subset, and jointly control a large collection of genes. IFNs-I were found to systemically activate natural killer (NK) cell activity. Recently, mouse experiments have shown that IFNs-I directly activate other cells of the immune system, such as antigen-presenting dendritic cells (DC) and CD4 and CD8 T cells. Signaling through the IFNAR in T cells is critical for the acquisition of effector functions. Cross-talk between IFNAR and the pathways turned on by other surface lymphocyte receptors has been described. Importantly, IFNs-I also increase antigen presentation of the tumor cells to be recognized by T lymphocytes. These IFN-driven immunostimulatory pathways offer opportunities to devise combinatorial immunotherapy strategies. Clin Cancer Res; 17(9); 2619–27. ©2011 AACR.
Tumor-Infiltrating Macrophages Are Associated with Metastasis Suppression in High-Grade Osteosarcoma: A Rationale for Treatment with Macrophage Activating Agents
Authors: Buddingh Emilie P. , Kuijjer Marieke L. , Duim Ronald A.J. , Bürger Horst , Agelopoulos Konstantin , Myklebost Ola , Serra Massimo , Mertens Fredrik , Hogendoorn Pancras C.W. , Lankester Arjan C. , Cleton-Jansen Anne-Marie 
Published: March 2011

AbstractPurpose: High-grade osteosarcoma is a malignant primary bone tumor with a peak incidence in adolescence. Overall survival (OS) of patients with resectable metastatic disease is approximately 20%. The exact mechanisms of development of metastases in osteosarcoma remain unclear. Most studies focus on tumor cells, but it is increasingly evident that stroma plays an important role in tumorigenesis and metastasis. We investigated the development of metastasis by studying tumor cells and their stromal context.Experimental Design: To identify gene signatures playing a role in metastasis, we carried out genome-wide gene expression profiling on prechemotherapy biopsies of patients who did (n = 34) and patients who did not (n = 19) develop metastases within 5 years. Immunohistochemistry (IHC) was performed on pretreatment biopsies from 2 additional cohorts (n = 63 and n = 16) and corresponding postchemotherapy resections and metastases.Results: A total of 118/132 differentially expressed genes were upregulated in patients without metastases. Remarkably, almost half of these upregulated genes had immunological functions, particularly related to macrophages. Macrophage-associated genes were expressed by infiltrating cells and not by osteosarcoma cells. Tumor-associated macrophages (TAM) were quantified with IHC and associated with significantly better overall survival (OS) in the additional patient cohorts. Osteosarcoma samples contained both M1- (CD14/HLA-DRα positive) and M2-type TAMs (CD14/CD163 positive and association with angiogenesis).Conclusions: In contrast to most other tumor types, TAMs are associated with reduced metastasis and improved survival in high-grade osteosarcoma. This study provides a biological rationale for the adjuvant treatment of high-grade osteosarcoma patients with macrophage activating agents, such as muramyl tripeptide. Clin Cancer Res; 17(8); 2110–9. ©2011 AACR.
CDDO-Imidazolide Induces DNA Damage, G2/M Arrest and Apoptosis in BRCA1-Mutated Breast Cancer Cells
Authors: Kim Eun-Hee , Deng Chu-Xia , Sporn Michael B. , Liby Karen T. 
Published: March 2011

Abstract
Breast cancer-associated gene 1 (BRCA1) protein plays important roles in DNA damage and repair, homologous recombination, cell-cycle regulation, and apoptosis. The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Imidazolide, CDDO-Im) is a promising anticancer and chemopreventive agent with potent antiproliferative and apoptotic activities against a wide variety of cancer types. However, the mechanisms responsible for the selective apoptotic effects of CDDO-Im in cancer cells remain elusive. In the present work, CDDO-Im induced G2/M arrest and apoptosis in BRCA1-mutated mammary tumor cell lines. Prior to the induction of apoptosis, CDDO-Im induced DNA damage and the phosphorylation of H2AX followed by activation of the DNA damage response. Moreover, CDDO-Im also induced the generation of reactive oxygen species (ROS), which is associated with the induction of DNA damage, in both mouse and human tumor cells containing a BRCA1 mutation. The inhibition of ROS generation by uric acid prevented the induction of DNA damage by CDDO-Im. Furthermore, treatment with CDDO-Im did not induce ROS in nonmalignant MCF-10A breast epithelial cells or in E18–14C-27 breast cancer cells with wild-type BRCA1 genes and was not cytotoxic to normal mouse 3T3 fibroblasts, highlighting a selective therapeutic potential of CDDO-Im for BRCA1-associated breast cancer cells. Altogether, our results show that CDDO-Im induces ROS and subsequent DNA damage, thereby facilitating the activation of the DNA damage checkpoint, G2/M arrest, and finally apoptosis in BRCA1-mutated cancer cells. The particular relevance of these findings to the chemoprevention of cancer is discussed. Cancer Prev Res; 4(3); 425–34. ©2011 AACR.
Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Specimens
Authors: Cramer Daniel W. , Bast Robert C. , Berg Christine D. , Diamandis Eleftherios P. , Godwin Andrew K. , Hartge Patricia , Lokshin Anna E. , Lu Karen H. , McIntosh Martin W. , Mor Gil , Patriotis Christos , Pinsky Paul F. , Thornquist Mark D. , Scholler Nathalie , Skates Steven J. , Sluss Patrick M. , Srivastava Sudhir , Ward David C. , Zhang Zhen , Zhu Claire S. , Urban Nicole 
Published: March 2011

Abstract
Establishing a cancer screening biomarker's intended performance requires “phase III” specimens obtained in asymptomatic individuals before clinical diagnosis rather than “phase II” specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network or Ovarian Cancer Specialized Program of Research Excellence sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within 6 months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study. Cancer Prev Res; 4(3); 365–74. ©2011 AACR.
Phase 0 Clinical Chemoprevention Trial of the Akt Inhibitor SR13668
Authors: Reid Joel M. , Walden Chad A. , Qin Rui , Ziegler Katie L. Allen , Haslam John L. , Rajewski Roger A. , Warndahl Roger , Fitting Cindy L. , Boring Daniel , Szabo Eva , Crowell James , Perloff Marjorie , Jong Ling , Bauer Brent A. , Mandrekar Sumithra J. , Ames Matthew M. , Limburg Paul J. 
Published: March 2011

AbstractSR13668, an orally active Akt pathway inhibitor, has demonstrated cancer chemopreventive potential in preclinical studies. To accelerate the clinical development of this promising agent, we designed and conducted the first-ever phase 0 chemoprevention trial to evaluate and compare the effects of food and formulation on SR13668 bioavailability. Healthy adult volunteers were randomly assigned to receive a single, 38-mg oral dose of SR13668 in one of five different formulations, with or without food. On the basis of existing animal data, SR13668 in a PEG400/Labrasol oral solution was defined as the reference formulation. Blood samples were obtained pre- and post-agent administration for pharmacokinetic analyses. Area under the plasma concentration–time curve (AUC0–∞) was defined as the primary endpoint. Data were analyzed and compared using established statistical methods for phase 0 trials with a limited sample size. Participants (n = 20) were rapidly accrued over a 5-month period. Complete pharmacokinetic data were available for 18 randomized participants. AUC0–∞ values were highest in the fed state (range = 122–439 ng/mL × hours) and were statistically significantly different across formulations (P = 0.007), with Solutol HS15 providing the highest bioavailability. SR13668 time to peak plasma concentration (3 hours; range, 2–6 hours) and half-life were (11.2 ± 3.1 hours) were not formulation-dependent. Using a novel, highly efficient study design, we rapidly identified a lead formulation of SR13668 for further clinical testing. Our findings support application of the phase 0 trial paradigm to accelerate chemoprevention agent development. Cancer Prev Res; 4(3); 347–53. ©2011 AACR.
Preventive Effects of (−)-Epigallocatechin Gallate on Diethylnitrosamine-Induced Liver Tumorigenesis in Obese and Diabetic C57BL/KsJ-db/db Mice
Authors: Shimizu Masahito , Sakai Hiroyasu , Shirakami Yohei , Yasuda Yoichi , Kubota Masaya , Terakura Daishi , Baba Atsushi , Ohno Tomohiko , Hara Yukihiko , Tanaka Takuji , Moriwaki Hisataka 
Published: March 2011

Abstract
Obesity and related metabolic abnormalities, including insulin resistance and a state of chronic inflammation, increase the risk of hepatocellular carcinoma. Abnormal activation of the insulin-like growth factor (IGF)/ IGF-1 receptor (IGF-1R) axis is also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of (−)-epigallocatechin gallate (EGCG), a major biologically active component of green tea, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were given tap water containing 40 ppm DEN for 2 weeks and then they received drinking water containing 0.1% EGCG for 34 weeks. At sacrifice, drinking water with EGCG significantly inhibited the development of liver cell adenomas in comparison with the control EGCG-untreated group. EGCG inhibited the phosphorylation of the IGF-1R, ERK (extracellular signal-regulated kinase), Akt, GSK-3β (glycogen synthase kinase-3β), Stat3, and JNK (c-Jun NH2-terminal kinase) proteins in the livers of experimental mice. The serum levels of insulin, IGF-1, IGF-2, free fatty acid, and TNF-α were all decreased by drinking EGCG, which also decreased the expression of TNF-α, interleukin (IL)-6, IL-1β, and IL-18 mRNAs in the livers. In addition, EGCG improved liver steatosis and activated the AMP-activated kinase protein in the liver. These findings suggest that EGCG prevents obesity-related liver tumorigenesis by inhibiting the IGF/IGF-1R axis, improving hyperinsulinemia, and attenuating chronic inflammation. EGCG, therefore, may be useful in the chemoprevention of liver tumorigenesis in obese individuals. Cancer Prev Res; 4(3); 396–403. ©2011 AACR.
Phase 0 Trials: Expediting the Development of Chemoprevention Agents
Authors: Kummar Shivaani , Doroshow James H. 
Published: March 2011

Abstract
Phase 0 trials are first-in-human clinical trials performed under the Exploratory IND [investigational new drug] Guidance of the U.S. Food and Drug Administration. Unlike traditional phase I trials, these studies have no therapeutic or diagnostic intent but instead aim to provide only pharmacokinetic and/or pharmacodynamic data to inform the next step in developing an agent. We discuss the role that such trials, including one reported by Reid and colleagues (beginning on page 347 in this issue of the journal), can play in expanding the number of drugs that are evaluated for chemoprevention while compressing the drug-development timeline. Cancer Prev Res; 4(3); 288–92. ©2011 AACR.
Inflammatory Talk: Linking Obesity, NF-κB, and Aromatase
Authors: Hursting Stephen D. 
Published: March 2011

Abstract
Obesity is associated with increased risk and worsened prognosis for postmenopausal breast cancer, but the underlying mechanisms remain unclear. Elegant work reported by Subbaramaiah and colleagues in this issue of the journal (beginning on page 329) adds important insights, particularly into the connections between obesity, inflammation, and aromatase via cross-talk among adipocytes, macrophages, and epithelial cells. This work provides several new molecular targets and strategies to test in model systems for preventing or controlling obesity-related breast cancer and provides a framework for studying the linkages among the complex mechanistic pathways underlying the obesity-cancer relationship. Cancer Prev Res; 4(3); 285–7. ©2011 AACR.