bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of macromycetes determined by tree species, vegetation structure, and microenvironment in tropical cloud forests in Veracruz, Mexico
Authors: Gómez-Hernández Marko , Williams-Linera Guadalupe 
Published: March 2011

Tropical montane cloud forests (TMCFs) have high levels of plant and fungal diversity. We examined whether macromycete alpha and beta diversity were associated with woody plant diversity, forest structure, or microclimate, in four TMCFs at lower (1240–1440 m) and upper altitudes (1790–1900 m) in Veracruz, Mexico. Every 2 weeks during the growing season, macromycetes were collected from ten 10 m × 10 m permanent plots per site, and air and soil temperature and humidity were measured. In total, 2059 macromycetes (509 species) and 678 woody plants (63 species) were recorded. Macromycete diversity (Shannon Index) values of the two sites located in lower forests were higher than in upper sites. Beta diversity (Jaccard index) indicated high turnover among sites and sampling times. Macromycete richness was negatively correlated with overstorey tree richness, understorey vegetation structure, and air temperature, but was positively correlated with air humidity and soil water content and altitude. Ordinations separated lower from upper altitude forest sites. Changes in composition and abundance of macromycete species with altitude were explained by precipitation, temperature, and understorey vegetation structure, while soil water content effect changes within a growing season. Results imply that understorey vegetation structure is a more important aspect for macrofungal diversity management than for woody plant diversity.
Black spruce regeneration at the treeline ecotone: synergistic impacts of climate change and caribou activityThis article is a contribution to the series Tree recruitment, growth, and distribution at the circumpolar forest–tundra transition.
Authors: Tremblay Geneviève Dufour , Boudreau Stéphane 
Published: March 2011

Tree regeneration at treeline is often inhibited by harsh climatic conditions and ecological constraints such as the presence of a continuous lichen cover. The objective of this study was to verify if recent climate warming and increased caribou (Rangifer tarandus L.) activity, which destroys the lichen cover, could act synergistically to increase black spruce (Picea mariana (Mill.) B.S.P.) regeneration. We collected cones produced in 2006–2007 to compare seed viability with data from 1989 to 1995. We conducted experimental plantations (field and controlled conditions) to determine if germination and seedling emergence were higher in disturbed environments where mineral soil was exposed. We sampled naturally established seedlings to evaluate the relationship between the year of establishment and caribou activity and to compare growth in disturbed and undisturbed environments. We found that seed viability was significantly higher in 2006–2007 compared with 1989–1995. The number of germinated seeds per cone increased by a factor >1000. Germination and seedling establishment were higher in the disturbed environment (mineral soil). Finally, although seedling establishment in areas with continuous lichen cover was rather constant over the last 50 years, 73.5% of the seedlings recorded on bare mineral soil became established in the years following high caribou activity. Our results suggest that climate warming and caribou activity are likely to act synergistically to promote black spruce regeneration at treeline.
Stable isotope tracing of fertilizer sulphur uptake by lodgepole pine: foliar responses
Authors: Sanborn P. T. , Brockley R. P. , Mayer B. 
Published: March 2011

A plot-scale fertilizer sulphur (S) stable isotope tracer study was established in 2001 in the Sub-Boreal Spruce biogeoclimatic zone in central interior British Columbia where S deficiencies are common in lodgepole pine ( Pinus contorta var. latifolia Engelm. ex S. Wats.) stands. Treatments used operationally realistic applications of 300 kg N·ha–1 as urea and 100 kg S·ha–1 as either sulphate (SO4) or elemental S (S0). δ34S values of fertilizer S differed by >9‰ from pretreatment δ34S values of total S in foliage at the two study sites (5.2‰ and 8.2‰). These differences enabled quantification of fertilizer uptake using isotopic analysis of post-treatment foliar S. Addition of K2SO4 with δ34S of +17.5‰ increased foliar δ34S by 3.5‰ and 6.6‰ at the two sites, respectively, in the year after treatment, indicating fertilizer contributions >40% to foliar total S. For a S0 fertilizer application with a δ34S value of +19.3‰, foliar δ34S increases were smaller but steadily increased, resulting in an average tracer S uptake of ~20% over three years. These results confirmed the more rapid availability of S from SO4-based fertilizers and demonstrated the feasibility of field tracer experiments using stable S isotopes at natural abundance levels.
Assessing terrestrial lichen biomass using ecoforest maps: a suitable approach to plan conservation areas for forest-dwelling caribou
Authors: Lesmerises Rémi , Ouellet Jean-Pierre , St-Laurent Martin-Hugues 
Published: March 2011

Terrestrial lichens are an important part of the winter diet of forest-dwelling caribou ( Rangifer tarandus caribou (Gmelin, 1788)), and developing forest management guidelines to support high lichen biomass could enhance both individual- and population-level health of this threatened species. Our objective was to develop an index to assess terrestrial lichen biomass available to caribou at the landscape scale using ecoforest maps based on forest characteristics (age, density, and height) and geographical variables (slope, altitude, and latitude). We sampled 439 sites within 8340 km2 of the spruce–moss domain located >100 km north of the Saguenay River (Quebec, Canada). Since they are known to support terrestrial lichen, we sampled only spruce-dominated stands older than 50 years, representing 41.8% of the study area. Using a two-step approach, we first modeled lichen occurrence and thereafter lichen biomass in sites where lichens were found. Lichen occurrence was positively correlated with latitude but negatively with stand age, height, and density. Lichen biomass was primarily a function of altitude and tree density. Using this index could prioritize conservation of areas that are most likely to contain high lichen biomass, thus favoring caribou population maintenance in logged landscapes.
Long-term effects of weed control and fertilization on the carbon and nitrogen pools of a slash and loblolly pine forest in north-central Florida
Authors: Vogel Jason G. , Suau Luis J. , Martin Timothy A. , Jokela Eric J. 
Published: March 2011

The effects of fertilization, weed control, and fertilization plus weed control on vegetation and soil C and N pools were examined for a loblolly pine ( Pinus taeda L.) and slash pine ( Pinus elliottii var. elliottii Engelm.) forest at ages 18 and 26 years (at the end of rotation). The total C accumulated in fertilized forests without weed control was 20% (slash pine) and 40% (loblolly pine) greater than in the control forests at the end of rotation. Weed control increased pine C pools at 18 years, but by the end of rotation, weed control effectively resulted in no gain in ecosystem C. When the two treatments were combined, weed control slightly subtracted from the net C benefit produced by fertilization. This result occurred because of decreased forest floor and soil C in the weed control plots. Fertilization significantly increased stem, foliage, forest floor, and soil N pools, and N retention was 63% and 103% of the applied N in the slash and loblolly pine forests, respectively. Weed control with fertilization reduced ecosystem N retention efficiency, but weed control alone did not negatively affect ecosystem N accumulation. These results suggest that the optimal treatment for increasing C accumulation and N retention in these ecosystems is fertilization without weed control.
Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib
Authors: Morris Patrick G. , Chen Carol , Steingart Richard , Fleisher Martin , Lin Nancy , Moy Beverly , Come Steven , Sugarman Steven , Abbruzzi Alyson , Lehman Robert , Patil Sujata , Dickler Maura , McArthur Heather L. , Winer Eric , Norton Larry , Hudis Clifford A. , Dang Chau T. 
Published: March 2011

Abstract
Purpose: There are no validated methods of early detection of cardiotoxicity from trastuzumab (T) following anthracycline-based chemotherapy. Currently changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Within a prospective feasibility study of dose-dense (dd) doxorubicin and cyclophosphamide (AC) → weekly paclitaxel (P) with T and lapatinib (L), we included a preplanned analysis of correlative cardiac Troponin I (cTnI) and C-reactive protein (CRP) as early biomarkers of cardiotoxicity.
Experimental Design: As previously described, patients received ddACx 4→PTL→TL. LVEF was assessed at months 0, 2, 6, 9, and 18 and cTnI and CRP measured every 2 weeks during chemotherapy then at months 6, 9, and 18. These biomarkers were correlated with changes in LVEF.
Results: Ninety-five patients enrolled. Overall, 3 (3%) patients withdrew during AC and 41 (43%) withdrew during PTL→TL, mostly due to diarrhea. Median LVEF was 68% (baseline), 69% (month 2), 65% (month 6), 65% (month 9), and 65% (month 18). The majority (67%) had a detectable cTnI during the study. The proportion of detectable cTnIs increased over time; 4% at baseline, 11% at month 2, and 50% at month 3. The timing of these detectable cTnIs preceded maximum-recorded decline in LVEF. However, overall, maximum cTnI levels did not correlate with LVEF declines. A detectable CRP was seen in 74/95 (78%) but did not correlate with LVEF declines.
Conclusion: In patients receiving ddAC→PTL, cTnIs are commonly detected. These elevations may precede changes in LVEF but, as assessed in this trial, do not predict CHF. Clin Cancer Res; 17(10); 3490–9. ©2011 AACR.
Dual Targeting of Phosphoinositide 3-Kinase and Mammalian Target of Rapamycin Using NVP-BEZ235 as a Novel Therapeutic Approach in Human Ovarian Carcinoma
Authors: Santiskulvong Chintda , Konecny Gottfried E. , Fekete Mirela , Chen Kuang-Yui Michael , Karam Amer , Mulholland David , Eng Carol , Wu Hong , Song Min , Dorigo Oliver 
Published: March 2011

AbstractPurpose: This study evaluates the effect of dual PI3K and mTOR inhibition using NVP-BEZ235 in preclinical models of ovarian cancer as a potential novel therapeutic strategy.Experimental Design: Inhibition of PI3K/Akt/mTOR signaling by NVP-BEZ235 was demonstrated by immunoblotting. The effect on cell proliferation was assessed in 18 ovarian cancer cell lines, including four pairs of syngeneic cisplatin-sensitive and cisplatin-resistant cell lines. The in vivo effects of NVP-BEZ235 on established tumor growth were evaluated using an immunocompetent, transgenic murine ovarian cancer model (LSL-K-rasG12D/+PtenloxP/loxP).Results: NVP-BEZ235 decreased cell proliferation in all ovarian cancer cell lines assayed and sensitized cisplatin-resistant cells to the cytotoxic effects of cisplatin. Cell lines with PI3K-activating mutations or Pten deletions were significantly more sensitive to the effect of NVP-BEZ235 than cell lines without these mutations (P &lt; 0.05). A statistically significant correlation was found between relative levels of p4E-BP1 and the IC50 for NVP-BEZ235. In LSL-K-rasG12D/+PtenloxP/loxP mice with established intraperitoneal tumor disease, oral administration of NVP-BEZ235 decreased pAkt, p4E-BP1 and Ki67 in tumor tissue, and resulted in significantly longer survival compared to control animals (P &lt; 0.05). NVP-BEZ235 also induced cell cycle arrest, caspase 3 activity, and reduced cell migration.Conclusions: Targeting PI3K and mTOR simultaneously using NVP-BEZ235 effectively inhibits ovarian cancer cell growth even in the presence of platinum resistance and prolongs survival of mice with intra-abdominal ovarian tumor disease. We propose that dual PI3K and mTOR inhibition using NVP-BEZ235 may be an effective novel therapeutic approach in patients with ovarian cancer. Clin Cancer Res; 17(8); 2373–84. ©2011 AACR.
Epstein-Barr Virus–Associated B-cell Lymphomas: Pathogenesis and Clinical Outcomes
Authors: Saha Abhik , Robertson Erle S. 
Published: March 2011

Abstract
Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus that establishes a life-long asymptomatic infection in immunocompetent hosts. It is also found to be frequently associated with a broad spectrum of B-cell lymphomas predominantly seen in immunodeficient patients. Despite many resemblances, these EBV-linked lymphoproliferative disorders display heterogeneity at the clinical and the molecular level. Moreover, EBV-associated lymphoproliferative diseases differ in their differential expression patterns of the EBV-encoded latent antigens, which are directly related to their interactions with the host. EBV-driven primary B-cell immortalization is linked to the cooperative functions of these latent proteins, which are critical for perturbing many important cell-signaling pathways maintaining B-cell proliferation. Additionally, it is used as a surrogate model to explore the underlying mechanisms involved in the development of B-cell neoplasms. Recent discoveries have revealed that a number of sophisticated mechanisms are exploited by EBV during cancer progression. This finding will be instrumental in the design of novel approaches for therapeutic interventions against EBV-associated B-cell lymphomas. This review limits the discussion to the biology and pathogenesis of EBV-associated B-cell lymphomas and the related clinical implications. Clin Cancer Res; 17(10); 3056–63. ©2011 AACR.
Humanized Anti-Trop-2 IgG-SN-38 Conjugate for Effective Treatment of Diverse Epithelial Cancers: Preclinical Studies in Human Cancer Xenograft Models and Monkeys
Authors: Cardillo Thomas M. , Govindan Serengulam V. , Sharkey Robert M. , Trisal Preeti , Goldenberg David M. 
Published: March 2011

Abstract
Purpose: Evaluate the efficacy of an SN-38-anti-Trop-2 antibody–drug conjugate (ADC) against several human solid tumor types, and to assess its tolerability in mice and monkeys, the latter with tissue cross-reactivity to hRS7 similar to humans.
Experimental Design: Two SN-38 derivatives, CL2-SN-38 and CL2A-SN-38, were conjugated to the anti-Trop-2–humanized antibody, hRS7. The immunoconjugates were characterized in vitro for stability, binding, and cytotoxicity. Efficacy was tested in five different human solid tumor-xenograft models that expressed Trop-2 antigen. Toxicity was assessed in mice and in Cynomolgus monkeys.
Results: The hRS7 conjugates of the two SN-38 derivatives were equivalent in drug substitution (∼6), cell binding (Kd ∼ 1.2 nmol/L), cytotoxicity (IC50 ∼ 2.2 nmol/L), and serum stability in vitro (t/½ ∼ 20 hours). Exposure of cells to the ADC demonstrated signaling pathways leading to PARP cleavage, but differences versus free SN-38 in p53 and p21 upregulation were noted. Significant antitumor effects were produced by hRS7-SN-38 at nontoxic doses in mice bearing Calu-3 (P ≤ 0.05), Capan-1 (P &lt; 0.018), BxPC-3 (P &lt; 0.005), and COLO 205 tumors (P &lt; 0.033) when compared to nontargeting control ADCs. Mice tolerated a dose of 2 × 12 mg/kg (SN-38 equivalents) with only short-lived elevations in ALT and AST liver enzyme levels. Cynomolgus monkeys infused with 2 × 0.96 mg/kg exhibited only transient decreases in blood counts, although, importantly, the values did not fall below normal ranges.
Conclusions: The anti-Trop-2 hRS7-CL2A-SN-38 ADC provides significant and specific antitumor effects against a range of human solid tumor types. It is well tolerated in monkeys, with tissue Trop-2 expression similar to humans, at clinically relevant doses, and warrants clinical investigation. Clin Cancer Res; 17(10); 3157–69. ©2011 AACR.
Therapeutic Potential and Molecular Mechanism of a Novel, Potent, Nonpeptide, Smac Mimetic SM-164 in Combination with TRAIL for Cancer Treatment
Authors: Lu Jianfeng , McEachern Donna , Sun Haiying , Bai Longchuan , Peng Yuefeng , Qiu Su , Miller Rebecca , Liao Jinhui , Yi Han , Liu Meilan , Bellail Anita , Hao Chunhai , Sun Shi-Yong , Ting Adrian T. , Wang Shaomeng 
Published: March 2011

Abstract
Smac mimetics are being developed as a new class of anticancer therapies. Because the single-agent activity of Smac mimetics is very limited, rational combinations represent a viable strategy for their clinical development. The combination of Smac mimetics with TNF-related apoptosis inducing ligand (TRAIL) may be particularly attractive because of the low toxicity of TRAIL to normal cells and the synergistic antitumor activity observed for the combination. In this study, we have investigated the combination synergy between TRAIL and a potent Smac mimetic, SM-164, in vitro and in vivo and the underlying molecular mechanism of action for the synergy. Our study shows that SM-164 is highly synergistic with TRAIL in vitro in both TRAIL-sensitive and TRAIL-resistant cancer cell lines of breast, prostate, and colon cancer. Furthermore, the combination of SM-164 with TRAIL induces rapid tumor regression in vivo in a breast cancer xenograft model in which either agent is ineffective. Our data show that X-linked IAP (XIAP) and cellular IAP 1 (cIAP1), but not cIAP2, work in concert to attenuate the activity of TRAIL; SM-164 strongly enhances TRAIL activity by concurrently targeting XIAP and cIAP1. Moreover, although RIP1 plays a minimal role in the activity of TRAIL as a single agent, it is required for the synergistic interaction between TRAIL and SM-164. This study provides a strong rationale to develop the combination of SM-164 and TRAIL as a new therapeutic strategy for the treatment of human cancer. Mol Cancer Ther; 10(5); 902–14. ©2011 AACR.
Phase IIa Clinical Trial of Curcumin for the Prevention of Colorectal Neoplasia
Authors: Carroll Robert E. , Benya Richard V. , Turgeon Danielle Kim , Vareed Shaiju , Neuman Malloree , Rodriguez Luz , Kakarala Madhuri , Carpenter Philip M. , McLaren Christine , Meyskens Frank L. , Brenner Dean E. 
Published: March 2011

AbstractCurcumin is derived from the spice tumeric and has antiinflammatory and antineoplastic effects in vitro and in animal models, including preventing aberrant crypt foci (ACF) and adenomas in murine models of colorectal carcinogenesis. Inhibiting the production of the procarcinogenic eicosanoids prostaglandin E2 (PGE2) and 5-hydroxyeicosatetraenoic acid (5-HETE) can suppress carcinogenesis in rodents. Curcumin reduces mucosal concentrations of PGE2 (via inhibition of cyclooxygenases 1 and 2) and 5-HETE (via inhibition of 5-lipoxygenase) in rats. Although preclinical data support curcumin activity in many sites, the poor bioavailability reported for this agent supports its use in the colorectum. We assessed the effects of oral curcumin (2 g or 4 g per day for 30 days) on PGE2 within ACF (primary endpoint), 5-HETE, ACF number, and proliferation in a nonrandomized, open-label clinical trial in 44 eligible smokers with eight or more ACF on screening colonoscopy. We assessed pre- and posttreatment concentrations of PGE2 and 5-HETE by liquid chromatography tandem mass spectroscopy in ACF and normal-tissue biopsies; ACF number via rectal endoscopy; proliferation by Ki-67 immunohistochemistry; and curcumin concentrations by high-performance liquid chromatography in serum and rectal mucosal samples. Forty-one subjects completed the study. Neither dose of curcumin reduced PGE2 or 5-HETE within ACF or normal mucosa or reduced Ki-67 in normal mucosa. A significant 40% reduction in ACF number occurred with the 4-g dose (P &lt; 0.005), whereas ACF were not reduced in the 2-g group. The ACF reduction in the 4-g group was associated with a significant, five-fold increase in posttreatment plasma curcumin/conjugate levels (versus pretreatment; P = 0.009). Curcumin was well tolerated at both 2 g and 4 g. Our data suggest that curcumin can decrease ACF number, and this is potentially mediated by curcumin conjugates delivered systemically. Cancer Prev Res; 4(3); 354–64. ©2011 AACR.
A Framework for Evaluating Biomarkers for Early Detection: Validation of Biomarker Panels for Ovarian Cancer
Authors: Zhu Claire S. , Pinsky Paul F. , Cramer Daniel W. , Ransohoff David F. , Hartge Patricia , Pfeiffer Ruth M. , Urban Nicole , Mor Gil , Bast Robert C. , Moore Lee E. , Lokshin Anna E. , McIntosh Martin W. , Skates Steven J. , Vitonis Allison , Zhang Zhen , Ward David C. , Symanowski James T. , Lomakin Aleksey , Fung Eric T. , Sluss Patrick M. , Scholler Nathalie , Lu Karen H. , Marrangoni Adele M. , Patriotis Christos , Srivastava Sudhir , Buys Saundra S. , Berg Christine D. 
Published: March 2011

Abstract
A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used prediagnostic samples to assess the potential of the panels for early detection. We conducted a multisite systematic evaluation of biomarker panels using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial.
Using a nested case–control design, levels of 28 biomarkers were measured laboratory-blinded in 118 serum samples obtained before cancer diagnosis and 951 serum samples from matched controls. Five predictive models, each containing 6 to 8 biomarkers, were evaluated according to a predetermined analysis plan. Three sequential analyses were conducted: blinded validation of previously established models (step 1); simultaneous split-sample discovery and validation of models (step 2); and exploratory discovery of new models (step 3). Sensitivity, specificity, sensitivity at 98% specificity, and AUC were computed for the models and CA125 alone among 67 cases diagnosed within one year of blood draw and 476 matched controls. In step 1, one model showed comparable performance to CA125, with sensitivity, specificity, and AUC at 69.2%, 96.6%, and 0.892, respectively. Remaining models had poorer performance than CA125 alone. In step 2, we observed a similar pattern. In step 3, a model derived from all 28 markers failed to show improvement over CA125.
Thus, biomarker panels discovered in diagnostic samples may not validate in prediagnostic samples; utilizing prediagnostic samples for discovery may be helpful in developing validated early detection panels. Cancer Prev Res; 4(3); 375–83. ©2011 AACR.