bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pertuzumab in Combination with Trastuzumab Shows Significantly Enhanced Antitumor Activity in HER2-Positive Human Gastric Cancer Xenograft Models
Authors: Yamashita-Kashima Yoriko , Iijima Shigeyuki , Yorozu Keigo , Furugaki Koh , Kurasawa Mitsue , Ohta Masateru , Fujimoto-Ouchi Kaori 
Published: June 2011

Abstract
Purpose: We investigated the antitumor activity of the combination of two different humanized monoclonal human epidermal growth factor receptor (HER) 2 antibodies, pertuzumab and trastuzumab, for gastric cancer.
Experimental Design: Tumor mouse xenograft models were used to examine antitumor activity. Cell proliferation was examined using crystal violet staining. HER family proteins' expression was analyzed by ELISA and immunohistochemistry. Phosphorylated proteins and heterodimers were detected by Western blotting and in situ proximity ligation assay (PLA), respectively. Apoptosis activity was examined by caspase 3/7 activity. Antibody-dependent cellular cytotoxicity (ADCC) activity was detected by xCELLigence. Microvessel density was examined by CD31 staining.
Results: Pertuzumab in combination with trastuzumab showed significant antitumor activity compared with each monotherapy in NCI-N87, an HER2-positive human gastric cancer xenograft model. The efficacy was stronger than that of the maximum effective dose with each monotherapy. Similar antitumor activity was shown in 4-1ST, another HER2-positive gastric cancer model, but not in MKN-28, an HER2-negative model. Combining pertuzumab with trastuzumab enhanced cell growth inhibition and apoptosis activity by inhibiting EGFR-HER2 heterodimerization and the phosphorylation of these receptors and their downstream factors. This effect was also seen in HER2-HER3 signaling. Furthermore, pertuzumab in combination with trastuzumab potentiated the ADCC activity of those antibodies and reduced tumor microvessel density.
Conclusions: We showed the significantly enhanced efficacy of pertuzumab combining with trastuzumab for HER2 overexpressing gastric cancer through the potentiation of cell growth inhibition, apoptosis activity, cell killing activity by ADCC, and antiangiogenic activity. This study suggests the clinical benefit of combination therapy with pertuzumab and trastuzumab for patients with HER2-positive gastric cancers. Clin Cancer Res; 17(15); 5060–70. ©2011 AACR.
TAK1–TAB2 Signaling Contributes to Bone Destruction by Breast Carcinoma Cells
Authors: Safina Alfiya , Sotomayor Paula , Limoge Michelle , Morrison Carl , Bakin Andrei V. 
Published: June 2011

AbstractAdvanced-stage breast cancers frequently metastasize to the bones and cause bone destruction, but the underlying mechanism is not fully understood. This study presents evidence that TGF-β–activated protein kinase 1 (TAK1) signaling in tumor cells promotes bone destruction by metastatic breast carcinoma cells, controlling expression of prometastatic factors including matrix metalloproteinase (MMP) 9 and COX2. Suppression of TAK1 signaling by dominant-negative TAK1 (dn-TAK1) in breast carcinoma MDA-MB-231 cells impairs bone colonization by carcinoma cells and bone osteolysis in the intracardiac injection model. Mechanistic studies showed that inhibition of TAK1 by dn-TAK1 or siRNA blocked expression of factors implicated in bone metastasis, such as MMP-9, COX2/PTGS2, parathyroid hormone–related protein (PTHrP) and interleukin 8 (IL-8), but did not affect activation of p38MAPK by TGF-β. TAK1 signaling is mediated by TAK1-binding partners TAB1, TAB2, and TAB3. Carcinoma cells express elevated mRNA levels of TAB2 and TAB3, whereas the TAB1 expression is noticeably low. Accordingly, depletion of TAB2 by siRNA reduced expression of MMP-9 and COX2. Together, these studies show that the TAK1–TAB2-TAB3 signaling axis is critical for carcinoma-induced bone lesions, mediating expression of proinvasive and osteolytic factors. These findings identify the TAK1–TAB2 axis as a potential therapeutic target in bone metastasis. Mol Cancer Res; 9(8); 1042–53. ©2011 AACR.
High cervical spinal cord stimulation for chronic cluster headache
Authors: Wolter Tilman , Kiemen Andrea , Kaube Holger 
Published: June 2011

Background: Cluster headache (CH) is the most painful and debilitating primary headache syndrome. Conventional treatment combines acute and prophylactic drugs. Also with maximal therapy a substantial proportion of patients do not experience a meaningful prevention or pain relief. Recent case series and early trials have suggested that occipital nerve stimulation can be very effective in the management of intractable CH. Methods: Seven patients with medically intractable chronic cluster headache were implanted with high cervical epidural electrodes. After a median test phase of 10 days (range 4–19 days) an impulse generator was implanted subcutaneously. Mean follow up was 23 months (median 12 months, range 3–78 months). Results: All patients showed significant treatment effects. In all patients, improvement occurred immediately after electrode implantation. The mean attack frequency decreased, as well as the mean duration and intensity of attacks. Also, depression, anxiety, and pain-related impairment scores decreased and medication intake was markedly reduced. Conclusions: In this prospective series, high cervical spinal cord stimulation shows an effect size equal or larger than occipital nerve stimulation with immediate onset after surgery and may serve as a valuable additional treatment option of intractable cluster headache in the future.
Results of Isolated Lateral Meniscus Allograft Transplantation
Authors: Kim Chang-Wan , Kim Jong-Min , Lee Sang-Hoon , Kim Jae-Hyan , Huang Jingmin , Kim Kyung-Ah , Bin Seong-Il 
Published: June 2011

Background: Although numerous studies have reported outcomes of meniscus allograft transplantation, only a few dealt with isolated procedures or employed objective evaluation methods. Hypothesis: Isolated lateral meniscus allograft transplantation (LMAT) provides clinical improvements and favorable objective results in symptomatic lateral meniscus–deficient knees. Study Design: Case series; Level of evidence, 4. Methods: The authors collected and analyzed the results of 29 consecutive isolated LMATs with a minimum of 24 months’ follow-up. The mean age of the patients was 29.6 years (range, 18-48 years). The modified Lysholm scoring system and the Hospital for Special Surgery score were used to evaluate subjective improvements. Every patient underwent postoperative magnetic resonance imaging (MRI) or second-look arthroscopy or both as objective evaluation. The allograft extrusion and relative percentage of extrusion (RPE) was measured on final MRI. Status of the allograft was classified according to the above 3 categories into 3 grades; satisfactory, fair, or poor. Results: The average length of follow-up was 53.6 months. Symptoms and functions of the involved knee improved in 28 knees (96.6%) at the last follow-up. The average preoperative modified Lysholm score was 69.5, which increased to 89.9 postoperatively ( P < .001). The average preoperative Hospital for Special Surgery pain score was 15.3, which increased to 26.7 postoperatively ( P < .001). Postoperative MRI alone was performed in 22 knees (75.9%), second-look arthroscopy alone in 1 knee (3.4%), and both examinations in 6 knees (20.7%). The MRI scans revealed 4 gross and 5 small tears in the allograft and also provided valuable information despite magnetic susceptibility artifacts. Mean allograft extrusion was 4.0 mm and mean RPE was 45.4%. At second-look arthroscopy, 3 gross tears and a small flap tear were identified in 4 cases. According to the clinical and the objective criteria, the allografts were graded as satisfactory in 20 cases (69.0%), fair in 5 cases (17.2%), and poor in 4 cases (13.8%). Conclusion: The results of the present study showed remarkable symptomatic improvements and acceptable objective findings in short- to intermediate-term follow-up. Even in cases with favorable clinical results, MRI or second-look arthroscopy was necessary to identify the actual status of the allograft. Isolated LMAT could be an effective treatment for symptomatic, lateral meniscus–deficient knees.
Using Wii Fit to reduce fatigue among African American women with systemic lupus erythematosus: A pilot study
Authors: Yuen HK , Holthaus K , Kamen DL , Sword DO , Breland HL 
Published: June 2011

Fatigue and physical deconditioning are common, difficult to treat conditions among patients with systemic lupus erythematosus (SLE). The aim of this pilot study was to evaluate the effectiveness of a home-based exercise program using the Wii Fit system in patients with SLE. Fifteen sedentary African American women with SLE experiencing moderate to severe fatigue participated in a home exercise program using the Wii Fit 3 days a week for 30 minutes each for 10 weeks. A one-group pretest–post test design was used to evaluate the effectiveness of this program. Primary outcome measure was severity of fatigue. Secondary outcome measures were body weight, waist circumference, fatigue-related symptoms of distress, activity level, and physical fitness. At the completion of the 10-week Wii Fit exercise program, participants perceived fatigue severity as measured by the Fatigue Severity Scale to be significantly decreased ( p = 0.002), and body weight and waist circumference were significantly reduced ( p = 0.01). In addition, anxiety level, as measured by Hospital Anxiety and Depression Scale, and overall intensity of total pain experience, as measured by Short-form of the McGill Pain Questionnaire, were also significantly reduced ( p < 0.05). Findings provide preliminary evidence that the Wii Fit motivates this population to exercise, which leads to alleviation of fatigue and reduced body weight, waist circumference, anxiety level, and overall intensity of total pain experience.
The use of screws in the treatment of scapholunate instability
Authors: Cognet J. M. , Levadoux M. , Martinache X. 
Published: June 2011

Seven patients with chronic scapholunate instability (Geissler grade 2–4) were treated by percutaneous placement of screws across the scapholunate joint after arthroscopic debridement of the remnants of the scapholunate ligament. In all seven cases, the screw caused partial destruction of the lunate and/or scaphoid requiring screw removal within 6 months. We no longer perform this procedure.
The molecular pathogenesis of primary mediastinal large B-cell lymphoma
Authors: Steidl Christian , Gascoyne Randy D. 
Published: June 2011

AbstractPrimary mediastinal large B-cell lymphoma (PMBCL) is a recognized non-Hodgkin lymphoma entity with unique pathologic, clinical, and molecular characteristics distinct from those of other diffuse large B-cell lymphomas. Immunohistochemical characterization and molecular studies strongly suggest that PMBCL is of germinal center or postgerminal center origin. Pivotal gene expression profiling work defined major deregulated pathway activities that overlap with Hodgkin lymphoma and prompted a more detailed analysis of candidate genes. In particular, the nuclear factor-κB and the Janus Kinase-Signal Transducer and Activator of Transcription signaling pathways are targeted by multiple genomic hits, and constitutive activity of both pathways can be considered molecular hallmark alterations of PMBCL. Moreover, data are emerging giving unique insight into remodeling of the epigenome that affects transcriptional regulation of a multitude of genes. More recently, the tumor microenvironment of PMBCL has shifted into focus based on a number of gene perturbations altering expression of surface molecules that contribute to immune escape. These findings highlight the importance of immune privilege in the pathogenesis of PMBCL and suggest that disrupting crosstalk between the tumor cells and the microenvironment might be a rational new therapeutic target in conjunction with traditional treatment strategies.
Diagnosing tuberculosis with urine lipoarabinomannan: systematic review and meta-analysis
Authors: Minion J. , Leung E. , Talbot E. , Dheda K. , Pai M. , Menzies D. 
Published: June 2011

Lipoarabinomannan (LAM) is a potential marker of active tuberculosis (TB). We performed a systematic review and meta-analysis regarding use of urinary LAM assays for diagnosing active TB.We systematically searched for published and unpublished studies that evaluated urinary LAM for active TB diagnosis. Extracted data were pooled using bivariate random effects models and hierarchical summary receiver operating characteristic curves. Heterogeneity was explored through subgroup analysis and meta-regression. Quality was assessed according to standardised QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria.In seven studies that assessed test accuracy in microbiologically confirmed cases only, estimates of sensitivity ranged from 13% to 93%, while specificity ranged from 87% to 99%. In five studies that assessed accuracy in clinical and confirmed TB cases, sensitivity ranged from 8% to 80%, while specificity ranged from 88% to 99%. In five studies with results stratified by HIV status, sensitivity was 3–53% higher in HIV-positive than HIV-negative subgroups; sensitivity was highest with advanced immunosuppression.The LAM urinary assay has several characteristics that make it attractive for diagnosing active TB, but has suboptimal sensitivity for routine clinical use. Further studies are needed to evaluate the potential value of the LAM assay in individuals with advanced HIV or for diagnosis of paediatric TB.
Endobronchial ultrasound-guided lymph node biopsy with transbronchial needle forceps: a pilot study
Authors: Herth F.J.F. , Schuler H. , Gompelmann D. , Kahn N. , Gasparini S. , Ernst A. , Schuhmann M. , Eberhardt R. 
Published: June 2011

One limitation of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the size of the available needles, frequently yielding only cells for cytological examination. The aim of this pilot study was to evaluate the efficacy and safety of newly developed needle forceps to obtain tissue for the histological diagnosis of enlarged mediastinal lymph nodes.Patients with enlarged, positron emission tomography (PET)-positive lymph nodes were included. The transbronchial needle forceps (TBNF), a sampling instrument combining the characteristics of a needle (bevelled tip for penetrating through the bronchial wall) with forceps (two serrated jaws for grasping tissue) was used through the working channel of the EBUS-TBNA scope. Efficacy and safety was assessed.50 patients (36 males and 14 females; mean age 51 yrs) with enlarged or PET-positive lymph nodes were included in this pilot study. In 48 (96%) patients penetration of the bronchial wall was possible and in 45 patients tissue for histological diagnosis was obtained. In three patients TBNF provided inadequate material. For patients in whom the material was adequate for a histological examination, a specific diagnosis was established in 43 (86%) out of 50 patients (nonsmall cell lung cancer: n=24; small cell lung cancer: n=7; sarcoidosis: n=4; Hodgkin's lymphoma: n=4; tuberculosis: n=2; and non-Hodgkin’s lymphoma: n=2).No clinically significant procedure-related complications were encountered.This study demonstrated that EBUS-TBNF is a safe procedure and provides diagnostic histological specimens of mediastinal lymph nodes.
Preschool asthma after bronchiolitis in infancy
Authors: Koponen P. , Helminen M. , Paassilta M. , Luukkaala T. , Korppi M. 
Published: June 2011

Asthma risk is lower after wheezing associated with respiratory syncytial virus (RSV) than with non-RSV infection in infancy. RSV is the main wheezing-associated virus in infants aged <6 months. We evaluated the outcome of children hospitalised for bronchiolitis at <6 months of age, with special focus on viral aetiology and early risk factors.Out of 205 infants hospitalised for bronchiolitis at <6 months of age, 127 (62%) attended a control visit at a mean age of 6.5 yrs and the parents of an additional 39 children were interviewed by telephone. Thus, follow-up data collected by identical structured questionnaires were available from 166 (81%) children. Viral aetiology of bronchiolitis, studied on admission by antigen detection or PCR, was demonstrable in 97% of cases.Current asthma was present in 21 (12.7%) children: 8.2% in the 110 former RSV patientsversus24% in non-RSV patients (p=0.01). 45 (27%) children had ever had asthma. In adjusted analyses, atopic dermatitis, non-RSV bronchiolitis and maternal asthma were independently significant early-life risk factors for asthma.The risk of asthma was lower after RSV bronchiolitis than after bronchiolitis caused by other viruses in children hospitalised at <6 months of age.
Unrecognised ventricular dysfunction in COPD
Authors: Macchia A. , Rodriguez Moncalvo J.J. , Kleinert M. , Comignani P.D. , Gimeno G. , Arakaki D. , Laffaye N. , Fuselli J.J. , Massolin H.P. , Gambarte J. , Romero M. , Tognoni G. 
Published: June 2011

While both chronic congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) impose a substantial disease burden and share aetiological and epidemiological associations, they have largely been studied separately. The aim of our study was to assess the prevalence and the prognostic implications of the coexistence of left ventricular dysfunction in COPD patients and airway obstruction in CHF patients.We used a prospective cohort study including stable ≥60-yr-old patients with echocardiographically confirmed CHF (n=201) and stable ≥60-yr-old patients with clinically and spirometry-confirmed COPD (n=218). All CHF patients underwent routine spirometry, and all COPD patients underwent routine echocardiographic assessment and B-type natriuretic peptide (BNP) measurement. Patients were followed for 2 yrs.The prevalence of airway obstruction among CHF patients was 37.3% and the prevalence of ventricular dysfunction among COPD patients was 17%. The presence of ventricular dysfunction in patients with COPD tended to increase the risk of mortality during follow-up (hazard ratio 2.34, 95% CI 0.99–5.54; p=0.053). The presence of airway obstruction in patients with CHF did not influence survival.CHF and COPD frequently coexist, and ventricular dysfunction worsens survival in patients with COPD. Considering the high prevalence and the prognostic implications of ventricular dysfunction, routine assessment with either BNP or echocardiogram should be considered in COPD patients.
Tiotropium improves walking endurance in COPD
Authors: Bédard M-E. , Brouillard C. , Pepin V. , Provencher S. , Milot J. , Lacasse Y. , Leblanc P. , Maltais F. 
Published: June 2011

The primary objective of this study was to evaluate the effects of a 3-week treatment with tiotropium on walking capacity in chronic obstructive pulmonary disease (COPD).After familiarisation with study procedures, 36 patients were randomised to receive tiotropium 18 μg once daily or a matching placebo in a double-blind, parallel-group study. Pre- (trough) and 2-h post-dose pulmonary function was measured. An endurance shuttle walk was then completed. The same procedures were repeated after 3 weeks of treatment. Ventilatory parameters were monitored during exercise.At 3 weeks, tiotropium significantly improved walking endurance time in comparison with placebo, with a mean±sdbetween-group difference of 128±141 s (p=0.017). At 3 weeks, trough values for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were significantly improved with tiotropium in comparison with placebo. The post-dose response to tiotropium was statistically superior to placebo after the first dose and after 3 weeks of treatment for FEV1, FVC and inspiratory capacity. Ventilation and tidal volume at the end of walking were significantly improved with tiotropium.3 weeks of tiotropium resulted in a greater walking endurance in patients with COPD. Improvements in FEV1, maximal ventilation and tidal volume may contribute to this enhanced exercise capacity.
Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score
Authors: Brand Bodo , Hartmann Anja , Repsilber Dirk , Griesbeck-Zilch Bettina , Wellnitz Olga , Kühn Christa , Ponsuksili Siriluck , Meyer Heinrich HD , Schwerin Manfred 
Published: June 2011

Abstract

Background
During the past ten years many quantitative trait loci (QTL) affecting mastitis incidence and mastitis related traits like somatic cell score (SCS) were identified in cattle. However, little is known about the molecular architecture of QTL affecting mastitis susceptibility and the underlying physiological mechanisms and genes causing mastitis susceptibility. Here, a genome-wide expression analysis was conducted to analyze molecular mechanisms of mastitis susceptibility that are affected by a specific QTL for SCS on Bos taurus autosome 18 (BTA18). Thereby, some first insights were sought into the genetically determined mechanisms of mammary gland epithelial cells influencing the course of infection.

Methods
Primary bovine mammary gland epithelial cells (pbMEC) were sampled from the udder parenchyma of cows selected for high and low mastitis susceptibility by applying a marker-assisted selection strategy considering QTL and molecular marker information of a confirmed QTL for SCS in the telomeric region of BTA18. The cells were cultured and subsequently inoculated with heat-inactivated mastitis pathogens Escherichia coli and Staphylococcus aureus, respectively. After 1, 6 and 24 h, the cells were harvested and analyzed using the microarray expression chip technology to identify differences in mRNA expression profiles attributed to genetic predisposition, inoculation and cell culture.

Results
Comparative analysis of co-expression profiles clearly showed a faster and stronger response after pathogen challenge in pbMEC from less susceptible animals that inherited the favorable QTL allele 'Q' than in pbMEC from more susceptible animals that inherited the unfavorable QTL allele 'q'. Furthermore, the results highlighted RELB as a functional and positional candidate gene and related non-canonical Nf-kappaB signaling as a functional mechanism affected by the QTL. However, in both groups, inoculation resulted in up-regulation of genes associated with the Ingenuity pathways 'dendritic cell maturation' and 'acute phase response signaling', whereas cell culture affected biological processes involved in 'cellular development'.

Conclusions
The results indicate that the complex expression profiling of pathogen challenged pbMEC sampled from cows inheriting alternative QTL alleles is suitable to study genetically determined molecular mechanisms of mastitis susceptibility in mammary epithelial cells in vitro and to highlight the most likely functional pathways and candidate genes underlying the QTL effect.