bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility Trial of Letrozole in Combination With Bevacizumab in Patients With Metastatic Breast Cancer
Authors: Traina Tiffany A. , Rugo Hope S. , Caravelli James F. , Patil Sujata , Yeh Benjamin , Melisko Michele E. , Park John W. , Geneus Stephanie , Paulson Matthew , Grothusen Jill , Seidman Andrew D. , Fornier Monica , Lake Diana , Dang Chau , Robson Mark , Theodoulou Maria , Flombaum Carlos D. , Norton Larry , Hudis Clifford A. , Dickler Maura N. 
Published: October 2009

PurposePreclinical models suggest that the use of anti–vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor–positive metastatic breast cancer (MBC).MethodsPatients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease.ResultsForty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease ≥ 24 weeks was noted in 67%. Median PFS was 17.1 months.ConclusionCombination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).
American Society of Clinical Oncology 2009 Clinical Evidence Review on Radiofrequency Ablation of Hepatic Metastases From Colorectal Cancer
Authors: Wong Sandra L. , Mangu Pamela B. , Choti Michael A. , Crocenzi Todd S. , Dodd Gerald D. , Dorfman Gary S. , Eng Cathy , Fong Yuman , Giusti Andrew F. , Lu David , Marsland Thomas A. , Michelson Rob , Poston Graeme J. , Schrag Deborah , Seidenfeld Jerome , Benson Al B. 
Published: October 2009

PurposeTo review the evidence about the efficacy and utility of radiofrequency ablation (RFA) for hepatic metastases from colorectal cancer (CRHM).MethodsThe American Society of Clinical Oncology (ASCO) convened a panel to conduct and analyze a comprehensive systematic review of the RFA literature from Medline and the Cochrane Collaboration Library.ResultsBecause data were considered insufficient to form the basis of a practice guideline, ASCO has instead published a clinical evidence review. The evidence is from single-arm, retrospective, and prospective trials. No randomized controlled trials have been included. The following three clinical issues were considered by the panel: the efficacy of surgical hepatic resection versus RFA for resectable tumors; the utility of RFA for unresectable tumors; and RFA approaches (open, laparoscopic, or percutaneous). Evidence suggests that hepatic resection improves overall survival (OS), particularly for patients with resectable tumors without extrahepatic disease. Careful patient and tumor selection is discussed at length in the literature. RFA investigators report a wide variability in the 5-year survival rate (14% to 55%) and local tumor recurrence rate (3.6% to 60%). The reported mortality rate was low (0% to 2%), and the major complications rate was commonly reported to be between 6% and 9%. RFA is currently performed with all three approaches.ConclusionThere is a compelling need for more research to determine the efficacy and utility of RFA to increase local recurrence-free, progression-free, and disease-free survival as well as OS for patients with CRHM. Clinical trials have established that hepatic resection can improve OS for patients with resectable CRHM.
Adaptation and failure of pancreatic β cells in murine models with different degrees of metabolic syndrome
Authors: Medina-Gomez Gema , Yetukuri Laxman , Velagapudi Vidya , Campbell Mark , Blount Margaret , Jimenez-Linan Mercedes , Ros Manuel , Orešič Matej , Vidal-Puig Antonio 
Published: October 2009

SUMMARY
The events that contribute to the expansion of β-cell mass and enhanced β-cell function in insulin-resistant states have not been elucidated fully. Recently, we showed that β-cell adaptation failed dramatically in adult, insulin-resistant POKO mice, which contrasts with the appropriate expansion of β cells in their ob/ob littermates. Thus, we hypothesised that characterisation of the islets in these mouse models at an early age should provide a unique opportunity to: (1) identify mechanisms involved in sensing insulin resistance at the level of the β cells, (2) identify molecular effectors that contribute to increasing β-cell mass and function, and (3) distinguish primary events from secondary events that are more likely to be present at more advanced stages of diabetes. Our results define the POKO mouse as a model of early lipotoxicity. At 4 weeks of age, it manifests with inappropriate β-cell function and defects in proliferation markers. Other well-recognised pathogenic effectors that were observed previously in 16-week-old mice, such as increased reactive oxygen species (ROS), macrophage infiltration and endoplasmic reticulum (ER) stress, are also present in both young POKO and young ob/ob mice, indicating the lack of predictive power with regards to the severity of β-cell failure. Of interest, the relatively preserved lipidomic profile in islets from young POKO mice contrasted with the large changes in lipid composition and the differences in the chain length of triacylglycerols in the serum, liver, muscle and adipose tissue in adult POKO mice. Later lipotoxic insults in adult β cells contribute to the failure of the POKO β cell. Our results indicate that the rapid development of insulin resistance and β-cell failure in POKO mice makes this model a useful tool to study early molecular events leading to insulin resistance and β-cell failure. Furthermore, comparisons with ob/ob mice might reveal important adaptive mechanisms in β cells with either therapeutic or diagnostic potential.
Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells
Authors: Kim Woo-Kyun , Meliton Vicente , Tetradis Sotirios , Weinmaster Gerry , Hahn Theodore J , Carlson Marc , Nelson Stanley F , Parhami Farhad 
Published: October 2009

Abstract
We previously reported that specific oxysterols stimulate osteogenic differentiation of pluripotent bone marrow stromal cells (MSCs) through activation of hedgehog (Hh) signaling and may serve as potential future therapies for intervention in osteopenia and osteoporosis. In this study we report that the osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic oxysterols did not. Similar observations were made when M2 cells were treated with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine blocked 20S-induced Notch target gene expression. 20S did not induce Notch target genes in Smo−/− mouse embryonic fibroblasts, further confirming the role of Hh signaling in 20S-induced expression of Notch target genes. Despite the inability of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in MSC responses to 20S. Moreover, 20S-induced Notch target gene expression was independent of canonical Notch signaling because neither 20S nor Shh induced CBF1 luciferase reporter activity or NICD protein accumulation in the nucleus, which are hallmarks of canonical Notch signaling activation. Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1. © 2010 American Society for Bone and Mineral Research
Persistent secondary hyperparathyroidism and vertebral fractures in kidney transplantation: Role of calcium-sensing receptor polymorphisms and vitamin D deficiency
Authors: Giannini Sandro , Sella Stefania , Silva Netto Fatima , Cattelan Catia , Dalle Carbonare Luca , Lazzarin Roberta , Marchini Francesco , Rigotti Paolo , Marcocci Claudio , Cetani Filomena , Pardi Elena , D'Angelo Angela , Realdi Giuseppe , Bonfante Luciana 
Published: October 2009

Abstract
Bone morbidity remains a major problem even after successful renal transplantation. We investigated the role of calcium-sensing receptor (CaSR) polymorphisms and 25-hydroxyvitamin D levels on the persistence of secondary hyperparathyroidism (SHPT) and their relationships with vertebral fractures (VFx) in 125 renal allograft recipients transplanted 44 ± 23 months before. All patients underwent evaluation of the main biochemical parameters of calcium metabolism as well as vertebral and femoral bone density. In 87 patients, CaSR polymorphisms (A986S, R990G, and Q1011E) also were assessed. X-ray images of the lateral spine were obtained in 102 subjects to perform vertebral morphometry. High parathyroid hormone (PTH) and 25-hydroxyvitamin D lower than 80 nmol/L were found in 54% and 97% of patients, respectively, with 40% of these showing vitamin D levels lower than 30 nmol/L. VFx were detected in 57% of the subjects. After multiple adjustments, 25-hydroxyvitamin D, age, and hemodialysis duration, but not CaSR polymorphisms, were found to be significant predictors of high PTH, whereas age and time since transplant were positively related with lower 25-hydroxyvitamin D values. PTH and time since transplant were significantly associated with VFx. Patients with two or more VFx showed serum PTH levels 50% higher than patients without fractures. We therefore conclude that persistent SHPT is a very common feature after renal transplantation and that, unlike CaSR polymorphisms, low 25-hydroxyvitamin D is involved in its pathogenesis. High PTH levels, in turn, are associated with an increased VFx risk, which confirms the need for strategies aimed at lowering serum PTH in this setting as well. © 2010 American Society for Bone and Mineral Research.
The pivotal role of the alternative NF-κB pathway in maintenance of basal bone homeostasis and osteoclastogenesis
Authors: Soysa Niroshani S , Alles Neil , Weih Debra , Lovas Agnes , Mian Anower Hussain , Shimokawa Hitoyata , Yasuda Hisataka , Weih Falk , Jimi Eijiro , Ohya Keiichi , Aoki Kazuhiro 
Published: October 2009

Abstract
The alternative NF-κB pathway consists predominantly of NF-κB-inducing kinase (NIK), IκB kinase α (IKKα), p100/p52, and RelB. The hallmark of the alternative NF-κB signaling is the processing of p100 into p52 through NIK, thus allowing the binding of p52 and RelB. The physiologic relevance of alternative NF-κB activation in bone biology, however, is not well understood. To elucidate the role of the alternative pathway in bone homeostasis, we first analyzed alymphoplasic (aly/aly) mice, which have a defective NIK and are unable to process p100, resulting in the absence of p52. We observed increased bone mineral density (BMD) and bone volume, indicating an osteopetrotic phenotype. These mice also have a significant defect in RANKL-induced osteoclastogenesis in vitro and in vivo. NF-κB DNA-binding assays revealed reduced activity of RelA, RelB, and p50 and no binding activity of p52 in aly/aly osteoclast nuclear extracts after RANKL stimulation. To determine the role of p100 itself without the influence of a concomitant lack of p52, we used p100−/− mice, which specifically lack the p100 inhibitor but still express p52. p100−/− mice have an osteopenic phenotype owing to the increased osteoclast and decreased osteoblast numbers that was rescued by the deletion of one allele of the relB gene. Deletion of both allele of relB resulted in a significantly increased bone mass owing to decreased osteoclast activity and increased osteoblast numbers compared with wild-type (WT) controls, revealing a hitherto unknown role for RelB in bone formation. Our data suggest a pivotal role of the alternative NF-κB pathway, especially of the inhibitory role of p100, in both basal and stimulated osteoclastogenesis and the importance of RelB in both bone formation and resorption. © 2010 American Society for Bone and Mineral Research
Shape variations and anisotropic growth of multiply twinned nanoparticles
Authors: Hofmeister Herbert 
Published: October 2009

Abstract
Cyclic multiple twins as nanoobjects that display nearly regular polyhedron shape variety together with strongly anisotropic shape variations due to growth processes are reviewed with regard to their unique shape evolution based on the specific formation modes as well as on the particular structure of twin-related subunits. The review includes (i) the shape variations due to growth by stacking of tetrahedral subunits, (ii) the role of growth conditions in the shape evolution of multiply twinned nanoparticles, and (iii) the modes of twin-based anisotropic growth including branching growth and unidirectional growth. The particular structures are introduced making use of electron microscopy structural characterization of multiply twinned metal nanoparticles as well as some non-metal examples, and instructive models of the various configurations.
Structural and chemical characterization of nanostructured III – V compound semiconductors by analytical TEM
Authors: Schneider Reinhard 
Published: October 2009

Abstract
The paper reports structural and microchemical investigations of low-dimensional semiconducting materials by combined imaging and spectroscopical techniques of transmission electron microscopy (TEM). The materials systems under investigation comprise graded (Al,Ga)As layers, (In,Ga)As quantum wires in V-grooved (001)InP, and (In,Ga)As quantum dots in GaAs. In order to elucidate structural peculiarities of these objects conventional and high-resolution TEM (CTEM/HRTEM) were performed, whereas information about the chemical composition and element distribution was obtained through electron energy loss spectroscopy (EELS), energy-filtered TEM (EFTEM), and energy-dispersive X-ray spectroscopy (EDXS). Particularly, the application possibilities of EFTEM are here demonstrated for revealing the local element content at high lateral resolution in a semi-quantitative manner.
Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies
Authors: Qvigstad E , Voldner N , Godang K , Henriksen T , Bollerslev J 
Published: October 2009

ObjectiveTo monitor β-cell function and insulin sensitivity longitudinally in a large cohort of pregnant women to elucidate mechanisms that influence glycemic control in pregnancy.Design and methodsFive hundred and fifty-three pregnant Scandinavian women underwent 75 g oral glucose tolerance test (OGTT) at weeks 14–16 and 30–32. Insulin sensitivity (Matsuda index) and β-cell function (ratio of AUCinsulin to AUCglucose, AUCins/glc) were calculated from 520 complete tests, and subsequently β-cell function was adjusted for insulin sensitivity, rendering an oral disposition index (DIo).ResultsEleven women (2.1%) had gestational diabetes mellitus (GDM1) at weeks 14–16, and 49 (9.4%) at weeks 30–32 (GDM2), which is higher than that previously reported in this region. In the subdivision of OGTT, more overweight (body mass index>25) was found in glucose-intolerant groups (glucose-tolerant women (normal glucose tolerance, NGT) 38 versus GDM2 women 58 and GDM1 women 82%, P<0.005). In early pregnancy, insulin sensitivity was lowest in GDM1, intermediate in GDM2, and highest in NGT. In late pregnancy, insulin sensitivity decreased in all groups, most in gestational diabetes. β-cell function demonstrated minor shifts during pregnancy, but when adjusted for decreasing insulin sensitivity, DIo levels fell by 40% (P<0.001). DIo was significantly attenuated relative to glucose intolerance (GDM1 25% and GDM2 53%) during pregnancy. In overweight women, DIo levels were lower throughout pregnancy (P<0.001 versus normal weight women), this reduction was significant (P<0.01) in both NGT (21–25%) and GDM2 subjects (26–49%).Conclusionβ-cell function adjusted for insulin sensitivity (DIo) deteriorated during pregnancy in both glucose-tolerant and glucose-intolerant women. The failure to compensate the decrease in insulin sensitivity was accentuated in overweight women.
Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age
Authors: Bueno Ana Carolina , Espiñeira Aniette R , Fernandes-Rosa Fábio L , de Souza Roberto Molina , de Castro Margaret , Moreira Ayrton Custódio , Bettiol Heloísa , Barbieri Marco Antonio , Antonini Sonir R 
Published: October 2009

ObjectiveTo assess whether the −11391G>A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life.DesignCase–control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date.MethodsADIPOQ −11391G>A genotype–phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8–10 years (catch-down growth), and at 23–25 years of age (cardiometabolic profile).ResultsThe −11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16–16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23–25 years, the −11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7±6.2 versus GA: 12.2±6.5 versus AA: 14.2±6.8 μg/ml; P<0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P<0.001) at 23–25 years.ConclusionsThe −11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.
Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome
Authors: Diamanti-Kandarakis Evanthia , Christakou Charikleia D , Kandaraki Eleni , Economou Frangiskos N 
Published: October 2009

AbstractPolycystic ovary syndrome (PCOS) is now recognized to be the most common endocrinopathy in women of reproductive age with a prevalence of 6.6–6.8%. PCOS, a syndrome of unknown etiology, was initially regarded as a reproductive disorder. However, in the last 15 years the role of insulin resistance (IR) has been identified as a significant contributor to the pathogenesis of PCOS, and the metabolic and cardiovascular sequelae of the syndrome have been increasingly appreciated. The coexistence and interaction of reproductive and cardiometabolic abnormalities in the context of PCOS have created a need for a modified therapeutic management of affected women.Insulin sensitizers, particularly metformin, have been introduced as a pharmaceutical option targeting not only IR, but several other aspects of the syndrome, including reproductive abnormalities. The landscape of the multifaceted actions of metformin evolves to broaden the therapeutic implications of this old drug in a new fashion for patients with PCOS. Most recently, the spectrum of metformin's targets has been expanded, and molecular studies have explored the tissue-specific mechanisms of metformin in the liver, the muscle, the endothelium, and the ovary. The use of metformin in pregnant women with PCOS comprises another scarcely explored, but promising area of research. This review attempts to cover the spectrum of metformin's cellular actions in different tissues and to summarize the current literature regarding the potential medical value of this medication in PCOS. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits not only in cardiometabolic aspects but also in reproductive aspects of PCOS.
Serum 25(OH)D3 vitamin status of elderly Finnish women is suboptimal even after summer sunshine but is not associated with bone density or turnover
Authors: Pekkarinen Tuula , Turpeinen Ursula , Hämäläinen Esa , Löyttyniemi Eliisa , Alfthan Henrik , Välimäki Matti J 
Published: October 2009

ObjectiveConcentrations of 50 and 75 nmol/l are proposed as serum 25-hydroxyvitamin D (25(OH)D) target for older people from the view of bone health. We evaluated vitamin D status of elderly Finnish women in light of these definitions, its relationship to bone mineral density (BMD) and turnover, and improvement by summer sunshine.DesignPopulation-based study.MethodsA total of 1604 ambulatory women aged 62–79 years were studied; 66% used vitamin D supplements. Serum 25(OH)D3was measured with HPLC before and after summer, and heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I procollagen aminoterminal propeptide (PINP) were analyzed.ResultsIn spring, 60.3% of the women had 25(OH)D3≤50 nmol/l, and the target of 75 nmol/l was reached by 9.1%. For supplement users, the respective numbers were 52.1 and 11.9%. Serum 25(OH)D3did not determine BMD or bone turnover measured by serum PINP. Summer sunshine increased serum 25(OH)D3by 17.4% (P<0.0001), but in autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement users, PTH remained stable but decreased in others during summer (P=0.025).ConclusionsVitamin D status of elderly Finnish women is suboptimal if 25(OH)D3levels of 50 or 75 nmol/l are used as a threshold. It is moderately increased by supplement intake and summer sunshine. However, 25(OH)D3concentrations did not influence bone density in terms of serum PINP and bone turnover rate.