bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiinflammatory Effects of Aprotinin
Authors: Taylor Kenneth M. 
Published: February 2008

SUMMARYAprotinin is a serine protease inhibitor that binds to human serine proteases with various affinities. This small protein has profound effects on the systemic inflammatory response syndrome induced by cardiopulmonary bypass. The intersecting pathways of complement, cytokines, coagulation, fibrinolytic, and kinin‐kallikrein systems all converge with tremendous amplification and potentially damaging effects to the patient. Aprotinin exerts a dose‐dependent inhibition of plasmin and kallikrein activities. Activation of these entities occurs ‘early’ in their respective pathways, and inhibition by aprotinin has downstream implications such as reducing the generation of thrombin, to minimize amplification of systems involved in the systemic inflammatory response. More localized effects of aprotinin at the level of the neutrophil, endothelial cell interaction or platelet‐thrombin interaction can have significant effects in terms of minimizing the damage to organs and tissues. The antiinflammatory effects associated with aprotinin treatment, in tandem with the hemostatic action, result in beneficial outcomes for many patients.
Participation in dementia research: rates and correlates of capacity to give informed consent: Table 1
Authors: Warner J , McCarney R , Griffin M , Hill K , Fisher P 
Published: March 2008

Background:Many people participating in dementia research may lack capacity to give informed consent and the relationship between cognitive function and capacity remains unclear. Recent changes in the law reinforce the need for robust and reproducible methods of assessing capacity when recruiting people for research.Aims:To identify numbers of capacitous participants in a pragmatic randomised trial of dementia treatment; to assess characteristics associated with capacity; to describe a legally acceptable consent process for research.Methods:As part of a pragmatic randomised controlled trial of Ginkgo biloba for mild-moderate dementia, we used a consenting algorithm that met the requirements of existing case law and the exigencies of the new Mental Capacity Act. We decided who had capacity to give informed consent for participation in the trial using this algorithm and sought predictors of capacity.Results:Most participants (76%) with mild-moderate dementia in this trial were unable to give informed consent according to the legal criteria. When adjusted for confounding, the Mini Mental State examination did not predict the presence of capacity.Conclusion:Cognitive testing alone is insufficient to assess the presence of capacity. Researchers and clinicians need to be aware of the challenging processes regarding capacity assessment. We outline a procedure which we believe meets the ethical and legal requirements.
Inheritance of density, microfibril angle, and modulus of elasticity in juvenile wood ofPinus radiataat two locations in Australia
Authors: Baltunis Brian S. , Wu Harry X. , Powell Mike B. 
Published: March 2008

A total of 1640 increment cores from 343 radiata pine ( Pinus radiata D. Don) families were sampled at two second-generation progeny trials, aged 6 and 7 years, for a detailed genetic study of juvenile wood quality traits. Density, microfibril angle (MFA), and modulus of elasticity (MOE) were determined from pith to bark using SilviScan®technology. Heritability was greatest for area-weighted density at the two sites (0.63 and 0.77, respectively), and the lowest for growth traits (<0.23). Genotype by environment interaction was low for all three wood quality traits. A positive genetic correlation between density and MOE (0.43), and a highly negative, and therefore, favourable genetic correlation between MFA and MOE (–0.92) were observed, implying that improvement of multiple juvenile wood properties is possible. The genetic correlations between whole-core wood quality traits and individual-ring measurements suggest that improvement for juvenile wood properties across the entire profile of the corewood including the innermost rings can be achieved. However, density, MFA, and MOE had unfavourable genetic correlations with diameter growth suggesting that selection for increased density and MOE, and reduced MFA in the absence of selection for growth will result in a genetic loss for growth rate.
Effects of 12 years of repeated fertilization on the foliar nutrition and growth of young lodgepole pine in the central interior of British Columbia
Authors: Brockley R. P. 
Published: March 2008

The effects of different regimes and frequencies of repeated fertilization (applied periodically and yearly) on the foliar nutrition and growth of young lodgepole pine ( Pinus contorta Dougl. ex Loud. var. latifolia Engelm.) were investigated in central British Columbia. After 12 years, tree and stand growth responses indicated modest positive effects of two applications of nitrogen (N) and boron, with relatively large incremental gains to added sulphur and other nutrients (complete). Despite large increases in effective leaf area index and foliar N concentration relative to the control and periodic treatments, yearly applications of fertilizer were relatively ineffective in stimulating growth. When combined with frequent additions of other essential nutrients, annual fertilization with 50–100 kg N/ha over 12 years (825 kg N/ha in total) produced only slightly more “extra” wood than two applications of the multinutrient, complete fertilizer (400 kg N/ha in total) (19.4 m3/ha vs. 17.2 m3/ha, respectively). The most intensive fertilization treatment (1550 kg N/ha plus other nutrients over 12 years) produced shorter trees and less stand volume increment than periodic fertilization with the complete fertilizer. Treatment-induced changes in stand dynamics and growth allocation, disrupted foliar nutrient balance, and changes in soil biota and understory vegetation community structure may have negatively affected tree growth in intensively fertilized treatment plots.
Growth and foliar nutrition of juvenile western hemlock and western redcedar plantations on low- and medium-productivity sites on northern Vancouver Island: response to fertilization and planting density
Authors: Negrave R. W. , Prescott C. E. , Barker J. E. 
Published: March 2008

A factorial trial was established to examine the effects of planting density and fertilization on the growth of western redcedar ( Thuja plicata Donn ex D. Don) and western hemlock ( Tsuga heterophylla (Raf.) Sarg.) on nutrient-poor (CH) sites and nutrient-medium (HA) sites. Two levels of NPK fertilization were crossed with three levels of planting density (500, 1500, and 2500 stems/ha). Fifteen years after establishment and 10 years after the last fertilizer application, height, individual stem volume increment, stand volume, 5 year periodic annual increment (PAI), and 5 year periodic height increment were all increased by fertilization. Fertilization of CH sites increased annual stand volume increment by 753%–2552% and 122%–209% for hemlock and cedar, respectively; fertilization of HA sites increased PAI by 94%–264%. Volume growth response to fertilization was greater on HA than on CH sites. Increasing stand density reduced height growth on CH sites but not on HA sites. These results suggest that competition for nutrients can be a significant growth-limiting factor even before canopy closure occurs and that treatment of ericaceous sites may not be justified by productivity increases.
Postfire root distribution of Scots pine in relation to fire behaviour
Authors: Smirnova Evgeniya , Bergeron Yves , Brais Suzanne , Granström Anders 
Published: March 2008

Fire can potentially have a large direct impact on tree roots and, thus, contribute to reduced vitality. Tree canopy status after fire should have an impact on the postfire production of fine roots, further affecting root function. We analyzed the standing crop of live and dead roots in Pinus sylvestris L. with varying degrees of crown scorch, 1 year after fire in northern Sweden. On the burned sites, total Pinus live fine-root biomass was 74% of that at the control sites, and it was only 19% of the control for roots <2 mm, indicating an 80% reduction due to fire. Root mortality was highest for high-scorch trees, but this was probably due to greater depth of burn in the organic soil for these trees and not to higher fire intensity per se. Fine-root production was also assessed by an ingrowth experiment. This showed relatively similar fine-root production in both control trees and fire-damaged trees, indicating a high allocation to root growth for the damaged trees, to make up for lost root function. Root dynamics after fire are related to a number of factors, and direct effects are determined by the depth of burn in the organic soil layer. Indirect, long-lasting effects could be due mainly to girdling of coarse roots close to tree stems and canopy loss.
Preliminary survey of clonal variation in rooting of Allanblackia floribunda leafy stem cuttings
Authors: Atangana A. R. , Khasa D. P. 
Published: March 2008

Clonal and cutting stem morphology variations in rooting ability were simultaneously examined in Allanblackia floribunda Oliv. using leafy stem cuttings in two experiments. The hypothesis tested is that clonal variation in rooting percentage is due to variation in cutting morphology. Each of the four replicate blocks used per experiment consisted of 18 treatments from two crossed factors, diameter or length × clone, making a total of n = 216 cuttings (3 cutting lengths (3, 4, and 5 cm) or diameters (2, 3, and 4 mm) × 6 stumps (clones) × 12 cuttings, as each experimental unit consisted of 12 cuttings). The cuttings were used for rooting in nonmist propagators. No clone × cutting diameter and clone × cutting length interactions (P = 0.293 and 0.513, respectively) on rooting percentage were found at the end of the study. Highly significant and significant clonal variations in rooting percentage were noted throughout the experiments. Results from this study reject the hypothesis being tested. Finally, further work should be done on the effects of physiological status of the cuttings and clonal variation in this species.
Convergence Theorems of Fixed Points for a Finite Family of Nonexpansive Mappings in Banach Spaces
Authors: Cho Yeol J. e. , Kang Shin Min , Qin Xiaolong 
Published: February 2008

AbstractWe modify the normal Mann iterative process to have strong convergence for a finite family nonexpansive mappings in the framework of Banach spaces without any commutative assumption. Our results improve the results announced by many others.
Expression of HER2 and Estrogen Receptor α Depends upon Nuclear Localization of Y-Box Binding Protein-1 in Human Breast Cancers
Authors: Fujii Teruhiko , Kawahara Akihiko , Basaki Yuji , Hattori Satoshi , Nakashima Kazutaka , Nakano Kenji , Shirouzu Kazuo , Kohno Kimitoshi , Yanagawa Takashi , Yamana Hideaki , Nishio Kazuto , Ono Mayumi , Kuwano Michihiko , Kage Masayoshi 
Published: March 2008

Abstract
In our present study, we examined whether nuclear localization of Y-box binding protein-1 (YB-1) is associated with the expression of epidermal growth factor receptors (EGFR), hormone receptors, and other molecules affecting breast cancer prognosis. The expression of nuclear YB-1, clinicopathologic findings, and molecular markers [EGFR, HER2, estrogen receptor (ER)α, ERβ, progesterone receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), phosphorylated Akt, and major vault protein/lung resistance protein] were immunohistochemically analyzed. The association of the expression of nuclear YB-1 and the molecular markers was examined in breast cancer cell lines using microarrays, quantitative real-time PCR, and Western blot analyses. Knockdown of YB-1 with siRNA significantly reduced EGFR, HER2, and ERα expression in ERα-positive, but not ERα-negative, breast cancer cell lines. Nuclear YB-1 expression was positively correlated with HER2 (P = 0.0153) and negatively correlated with ERα (P = 0.0122) and CXCR4 (P = 0.0166) in human breast cancer clinical specimens but was not correlated with EGFR expression. Nuclear YB-1 expression was an independent prognostic factor for overall (P = 0.0139) and progression-free (P = 0.0280) survival. In conclusion, nuclear YB-1 expression might be essential for the acquisition of malignant characteristics via HER2-Akt–dependent pathways in breast cancer patients. The nuclear localization of YB-1 could be an important therapeutic target against not only multidrug resistance but also tumor growth dependent on HER2 and ERα. [Cancer Res 2008;68(5):1504–12]
CDC25A Phosphatase: a Rate-Limiting Oncogene That Determines Genomic Stability
Authors: Ray Dipankar , Kiyokawa Hiroaki 
Published: March 2008

Abstract
CDC25A is a critical regulator of cell cycle progression and checkpoint response. Overexpression of this cyclin-dependent kinase phosphatase occurs often in human cancers. Our recent genetic studies in the mouse indicate that restricting CDC25A can limit tumorigenesis induced by the HER2/neu-RAS oncogenic pathway without compromising normal cell division or viability. These findings offer a sound foundation to justify development of CDC25A inhibitors for antitumor therapy. [Cancer Res 2008;68(5):1251–3]
EpCAM and α-Fetoprotein Expression Defines Novel Prognostic Subtypes of Hepatocellular Carcinoma
Authors: Yamashita Taro , Forgues Marshonna , Wang Wei , Kim Jin Woo , Ye Qinghai , Jia Huliang , Budhu Anuradha , Zanetti Krista A. , Chen Yidong , Qin Lun-Xiu , Tang Zhao-You , Wang Xin Wei 
Published: March 2008

Abstract
The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. Recently, we have identified that a hepatic stem cell marker, epithelial cell adhesion molecule (EpCAM), may serve as an early biomarker of HCC because its expression is highly elevated in premalignant hepatic tissues and in a subset of HCC. In this study, we aimed to identify novel HCC subtypes that resemble certain stages of liver lineages by searching for EpCAM-coexpressed genes. A unique signature of EpCAM-positive HCCs was identified by cDNA microarray analysis of 40 HCC cases and validated by oligonucleotide microarray analysis of 238 independent HCC cases, which was further confirmed by immunohistochemical analysis of an additional 101 HCC cases. EpCAM-positive HCC displayed a distinct molecular signature with features of hepatic progenitor cells including the presence of known stem/progenitor markers such as cytokeratin 19, c-Kit, EpCAM, and activated Wnt-β-catenin signaling, whereas EpCAM-negative HCC displayed genes with features of mature hepatocytes. Moreover, EpCAM-positive and EpCAM-negative HCC could be further subclassified into four groups with prognostic implication by determining the level of α-fetoprotein (AFP). These four subtypes displayed distinct gene expression patterns with features resembling certain stages of hepatic lineages. Taken together, we proposed an easy classification system defined by EpCAM and AFP to reveal HCC subtypes similar to hepatic cell maturation lineages, which may enable prognostic stratification and assessment of HCC patients with adjuvant therapy and provide new insights into the potential cellular origin of HCC and its activated molecular pathways. [Cancer Res 2008;68(5):1451–61]
Macrophage Inflammatory Protein–1δ: A Novel Osteoclast Stimulating Factor Secreted by Renal Cell Carcinoma Bone Metastasis
Authors: Kominsky Scott L. , Abdelmagid Samir M. , Doucet Michele , Brady Kelly , Weber Kristy L. 
Published: March 2008

AbstractApproximately 30% of patients with renal cell carcinoma (RCC) develop bone metastasis, which is characterized by extensive osteolysis leading to severe bone pain and pathologic fracture. Although the mechanism of RCC-induced osteolysis is unknown, studies of bone metastasis have shown that tumor-induced changes in bone remodeling are likely mediated by alterations in the bone microenvironment. Here, we report the discovery of a novel osteoclast stimulatory factor secreted by RCC bone metastasis (RBM). Through microarray analysis, we found expression of the chemokine, macrophage inflammatory protein-1δ (MIP-1δ), to be increased in RBM versus patient-matched primary RCC tissues and confirmed this finding by quantitative reverse transcription-PCR (qRT-PCR) and ELISA (P &lt; 0.05). Furthermore, MIP-1δ expression in RBM tissues was significantly (P &lt; 0.001) higher than in human bone marrow, suggesting a potential alteration of the bone microenvironment. The receptors for MIP-1δ, CCR1 and CCR3, were expressed in both osteoclast precursors and mature, bone-resorbing osteoclasts as shown by qRT-PCR and Western analysis. In functional studies, MIP-1δ stimulated chemotaxis of two osteoclast precursor cell types: murine bone marrow mononuclear cells (BM-MNC) and RAW 264.7 cells. Furthermore, MIP-1δ treatment of murine calvaria caused increased bone resorption as determined by measurement of released calcium. Correspondingly, MIP-1δ significantly enhanced osteoclast formation and activity in response to RANKL in both BM-MNC and RAW 264.7 cells. Taken together, these data suggest that MIP-1δ expression is increased in RBM relative to RCC and bone marrow, and may promote RBM-induced osteolysis by stimulating the recruitment and differentiation of osteoclast precursors into mature osteoclasts. [Cancer Res 2008;68(5):1261–6]
Allogeneic Granulocyte Macrophage Colony-Stimulating Factor–Secreting Tumor Immunotherapy Alone or in Sequence with Cyclophosphamide for Metastatic Pancreatic Cancer: A Pilot Study of Safety, Feasibility, and Immune Activation
Authors: Laheru Dan , Lutz Eric , Burke James , Biedrzycki Barbara , Solt Sara , Onners Beth , Tartakovsky Irena , Nemunaitis John , Le Dung , Sugar Elizabeth , Hege Kristen , Jaffee Elizabeth 
Published: March 2008

Abstract
Purpose: The combination of chemotherapy and immunotherapy has not been examined in patients with advanced pancreatic cancer. We conducted a study of two granulocyte macrophage colony-stimulating factor–secreting pancreatic cancer cell lines (CG8020/CG2505) as immunotherapy administered alone or in sequence with cyclophosphamide in patients with advanced pancreatic cancer.
Experimental Design: This was an open-label study with two cohorts: cohort A, 30 patients administered a maximum of six doses of CG8020/CG2505 at 21-day intervals; and cohort B, 20 patients administered 250 mg/m2 of cyclophosphamide i.v. 1 day before the same immunotherapy given as in cohort A. The primary objective was to evaluate safety and duration of immunity. Secondary objectives included time to disease progression and median overall survival.
Results: The administration of CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity. Median survival values in cohort A and cohort B were 2.3 and 4.3 months, respectively. CD8+ T-cell responses to HLA class I–restricted mesothelin epitopes were identified predominantly in patients treated with cyclophosphamide + CG8020/CG2505 immunotherapy.
Conclusion: Granulocyte macrophage colony-stimulating factor–secreting pancreatic cancer cell lines CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity in patients with advanced pancreatic cancer. Also, mesothelin-specific T-cell responses were detected/enhanced in some patients treated with CG8020/CG2505 immunotherapy. In addition, cyclophosphamide-modulated immunotherapy resulted in median survival in a gemcitabine-resistant population similar to chemotherapy alone. These findings support additional investigation of cyclophosphamide with CG8020/CG2505 immunotherapy in patients with advanced pancreatic cancer.
U.S. Food and Drug Administration Approval: Panitumumab for Epidermal Growth Factor Receptor–Expressing Metastatic Colorectal Carcinoma with Progression Following Fluoropyrimidine-, Oxaliplatin-, and Irinotecan-Containing Chemotherapy Regimens
Authors: Giusti Ruthann M. , Shastri Kaushikkumar , Pilaro Anne M. , Fuchs Chana , Cordoba-Rodriguez Ruth , Koti Kallappa , Rothmann Mark , Men Angela Yuxin , Zhao Hong , Hughes Monica , Keegan Patricia , Weiss Karen D. , Pazdur Richard 
Published: March 2008

Abstract
Purpose: To describe the Food and Drug Administration review and marketing approval considerations for panitumumab (Vectibix) for the third-line treatment of patients with epidermal growth factor receptor–expressing metastatic colorectal carcinoma.
Experimental Design: Food and Drug Administration reviewed a single, open-label, multicenter trial in which 463 patients with epidermal growth factor receptor–expressing metastatic colorectal cancer who had progressed on or following treatment with a regimen containing a fluoropyrimidine, oxaliplatin, and irinotecan were randomized (1:1) to receive best supportive care (BSC) with or without panitumumab (6 mg/kg every other week) administered until disease progression or intolerable toxicity. Progression and response were confirmed by an independent review committee masked to treatment assignment. At progression, patients in the BSC-alone arm were eligible to receive panitumumab.
Results: Although median progression-free survival (PFS) was similar in both treatment arms (∼8 weeks), the mean PFS was ∼50% longer among patients receiving panitumumab than among those receiving BSC alone (96 versus 60 days, respectively) and the objective response rate in patients receiving panitumumab was 8%. However, no difference in overall survival was shown between the two study arms.
Conclusions: Panitumumab received accelerated approval based on improvement in PFS and an independently confirmed response rate of 8%, similar to that observed with other active agents at this advanced stage of disease. Confirmation of clinical benefit will be required for full approval.
Synergy of a Herpes Oncolytic Virus and Paclitaxel for Anaplastic Thyroid Cancer
Authors: Lin Shu-Fu , Gao Sizhi Paul , Price Daniel L. , Li Sen , Chou Ting-Chao , Singh Paramjeet , Huang Yu-Yao , Fong Yuman , Wong Richard J. 
Published: March 2008

Abstract
Purpose: Novel therapeutic regimens are needed to improve the dismal outcomes of patients with anaplastic thyroid cancer (ATC). Oncolytic herpes simplex virus have shown promising activity against human ATC. We studied the application of oncolytic herpes simplex virus (G207 and NV1023) in combination with currently used chemotherapeutic drugs (paclitaxel and doxorubicin) for the treatment of ATC.
Experimental Design and Results: All four agents showed dose-response cytotoxicity in vitro for the human ATC cell lines KAT4 and DRO90-1. G207, combined with paclitaxel, showed synergistic cytotoxicity. Chou-Talalay combination indices ranged from 0.56 to 0.66 for KAT4, and 0.68 to 0.74 for DRO90-1 at higher affected fractions. Paclitaxel did not enhance G207 viral entry and early gene expression or G207 viral replication. Paclitaxel combined with G207 compared with single-agent treatment or controls showed significantly increased microtubule acetylation, mitotic arrest, aberrant chromatid separation, inhibition of metaphase to anaphase progression, and apoptosis. A single i.t. injection of G207 combined with biweekly i.p. paclitaxel injections in athymic nude mice bearing KAT4 flank tumors showed significantly reduced mean tumor volume (74 ± 38 mm3) compared with G207 alone (388 ± 109 mm3), paclitaxel alone (439 ± 137 mm3), and control (520 ± 160 mm3) groups at 16 days. There was no morbidity in vivo attributable to therapy.
Conclusions: Mechanisms of paclitaxel antitumoral activity, including microtubule acetylation, mitotic block, and apoptosis, were enhanced by G207, which also has direct oncolytic effects. Combination of G207 and paclitaxel therapy is synergistic in treating ATC and holds promise for patients with this fatal disease.