tbuckley/cabot-search huggingface dataset:
Knockdown of Abl interactor 1 expression impairs invadopodia formation, tumor angiogenesis, and markedly slows tumor growth of breast cancer cells.
Authors: C Li, X Sun, WC Gilmore, E Cobos, Y Tao, Z Dai
Journal: Cancer Research (2009)

Abstract Abstract #2054 Background: Abl interactor 1 (Abi1) is a key regulator of actin polymerization/depolymerization. Previous studies have revealed that Abi1 interacts with Wiskott–Aldrich syndrome protein (Wasp) family proteins, and regulates the nucleation promoting activity of Wasp proteins. In addition to Wasp family proteins, Abi1 also binds to a variety of other signaling molecules, including those involved in the signal transductions of small GTP-binding protein Rac and PI3 kinase. The ability to interact with diverse signaling pathways places Abi1 at a central position in the signaling network that regulates cell motility and proliferation. The involvement of Abi1 in the development of abnormal cytoskeletal functions of cancer cells has recently been reported. It remains unclear, however, how Abi1 exerts its effects in tumor cells and whether it contributes to tumor progression in vivo.&amp;#x2028; Material and Methods: The short hairpin RNA (shRNA)-mediated gene silencing was used, in conjunction with murine tumor xenograft models, to examine the effects of Abi1 knockdown on cytoskeleton remodeling, cell migration, invasion, as well as tumor growth and angiogenesis of MDA-MB231 breast cancer cells.&amp;#x2028; Results: We report here a novel function for Abi1 in the regulation of invadopodia formation as well as in the tumor angiogenesis and invasion of breast cancer cells, possibly through the modulation of Src and matrix metalloproteinase 9 (MMP-9) activities. Abi1 co-localizes with invadopodia, the specialized adhesive/invasive structures believed to control the invasion of tumor cells, in MDA-MB231 breast cancer cells. Epigenetic silencing of the Abi1 gene by shRNA in MDA-MB231 cells impaired the formation of invadopodia and decreased the activity of c-Src and MMP-9. The decreased invadopodia formation and MMP-9 activity correlated with a reduction in the ability of these cells to degrade extracellular matrix (ECM). Remarkably, the knockdown of Abi1 expression inhibited tumor invasion and angiogenesis and markedly slowed tumor growth in xenograft mouse models. Taken together, these results indicate that the Abi1 signaling plays a critical role in breast cancer progression and suggest that this pathway may serve as a therapeutic target for the treatment of human breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2054.
Pulmonary deposition and clearance of glass fiber in rat lungs after long-term inhalation.
Authors: I Tanaka, T Oyabu, S Ishimatsu, H Hori, T Higashi, H Yamato
Journal: Environmental Health Perspectives (1994)

In this study Wistar male rats were exposed to glass fiber obtained by the disintegration of a binderless glass fiber filter, for 6 hr/day, 5 days/week for 12 months. The mass median aerodynamic diameter (MMAD) of the fiber, determined with an Andersen sampler, was 2.6 microns. The count median diameter and length of the fibers measured by scanning electron microscopy (SEM) were 0.51 and 5.5 microns, respectively. The daily average exposure fiber concentration was 2.2 +/- 0.6 mg/m3. Some rats were sacrificed 24 hr after removal from the exposure chamber following the 12 months' exposure. Others were sacrificed 12 months after the end of exposure. The wet organ weights were recorded at the time of death and the silicon content of the lungs was determined by absorption spectrophotometry. After 12 months' exposure, the amount of glass fiber retained in the rat lungs was 1.49 mg, and after 12 months' clearance it was 0.61 mg. The biological half-life in a single exponential model was to be 8.7 months, much longer than the predicted value of 1.5 months obtained in a previous experiment in which rats were exposed for 4 weeks to the same glass fiber.
O9.03 * BRAIN TUMORS IN SWEDEN: DATA FROM A POPULATION BASED REGISTRY 1999-2012
Authors: T. Asklund, A. Malmstrom, M. Bergqvist, O. Bjor, R. Henriksson
Journal: Neuro-Oncology (2014)

BACKGROUND: The annual incidence of adult patients diagnosed with a high grade glioma (WHO grade III-IV) is approximately 400 in Sweden. The corresponding figures for low grade glioma and meningioma is 100 and 400, respectively, in a population of 9,6 million. Although clinical trials have provided us with significant amounts of data, they are confined by varying degrees of selection and publication bias. We here report on the Swedish brain tumor registry, which since the registry was launched in 1999 has provided us with data not only on histopathological diagnoses, but also on important aspects of surgical and medical management of these patients. The purpose is mainly quality assurance, but also as a resource for research. METHODS: A high registration compliance is mandatory, when claiming that a registry is truly population based. Indeed, three of the Swedish healthcare regions, constituting 40 % of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to the SNOMED/WHO classification, symptoms, performance status, pre- and post operative radiology, tumor size and localization, extent of surgery and the occurrence of possible post-operative complications. In 2009 the registry was supplemented with a one year follow-up form, including detailed data of postoperative treatment, such as radiotherapy and/or chemotherapy, possible other treatment strategies, complications and toxicity, the occurrence of possible reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse. RESULTS: Surgical radicality has increased as well as the use of early postoperative radiology. Survival of patients with high grade glioma has increased, especially in the age group 60-69, where the median survival has almost doubled since the registry was launched. A more active treatment attitude could contribute to these figures. At the same time waiting times for the pathological report has increased. Geographical differences do exist for many of the variables. DISCUSSION: Population based registration is an extremely valuable tool when evaluating and comparing the care of patients. Today, much effort is focused on patient reported outcome measures (PROM) and patient reported experience measures (PREM). They are probably more sensitive than conventional methods to assess improvements in medical care. Because of rapid disease progression causing short survival and/or the propensity to affect cognitive functions the patient group has considerable difficulties to make their voice heard in the society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.
Salvage therapy following failure or relapse after FCR chemo-immunotherapy as initial treatment for chronic lymphocytic leukemia (CLL)
Authors: M. J. Keating, W. Wierda, S. O'Brien, C. Tam, S. Lerner, H. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7009 Background: CLL treatment evolved from single agents to combination chemotherapy to chemo-immunotherapy e.g. fludarabine and rituximab (FR) or with cyclophosphamide (FCR). Reports usually describe initial response, time-to-treatment failure (TTF), and survival. Follow-up of relapsed/failed patients (pts) is rarely reported. This report summarizes our experience with such pts after FCR. Methods: 300 pts initially treated with FCR were analyzed. 15 pts failed, 6 died in remission, six developed Richter's transformation (RT) or another malignancy (14) or relapsed (77). Ten have not required therapy. Results: 67 pts received first salvage therapy (S1) with a variety of regimens. The median age was 59 years and 70% were male. Most pts were Rai stage III - IV (56%). Median TTF after initial FCR was 31 months. Initial FCR responses were CR (36 pts), NPR (10 pts), PR (14 pts), and failure (7 pts). Following S1 therapy, CR was obtained in 17%, NPR (8%) and PR (14%). Initial FCR response of CR or NPR, Rai stage, and β2-microglobulin significantly predicted S1 response. The initial TTF did not predict salvage response. OR rate for FCR-based regimen alone or with alemtuzumab (A) or lumilixamab was 62%, rituximab (R) regimens (31%) and A + R (6/9, 67%). Median survival after S1 therapy was 30 months (28 deaths) and was significantly longer for CR/NPR pts (46 months) than PR/Fail (10 months) P&lt;.001. Duration of initial FCR response, β2-microglobulin level and Rai stage predicted survival (P&lt;.01) but the S1 regimens did not. 9/13 pts who eventually received an allogeneic transplant (allo SCT) are still alive (8 in CR). Conclusions: The results of salvage therapy following FCR initial treatment are unsatisfactory. Patients who failed to obtain a CR or NPR to FCR or S1 therapy should be considered for allo SCT. No significant financial relationships to disclose.
PREVALENCIA DE LA INFECCIÓN POR HELICOBACTER PYLORI EN PACIENTES MARROQUÍES CON ENDOSCOPIA SUPERIOR NORMAL
Authors: S Oussama, M Tahiri, F Benali, F Haddad, W Hliwa, A Bellabah, W Badre
Journal: Endoscopy (2014)

Introducción: La infección con Helicobacter pylori es el principal factor de riesgo para el cáncer gástrico, que se encuentra en el 80%, la acción de las bacterias a través del efecto mutagénico de la inflamación crónica (daño oxidativo sobre el ADN celular) y, especialmente, por gastritis atrófica y metaplasia intestinal causadas por el agente patógeno.
AB0492 The Influence of Therapy on CD4+Cd25highfoxp3+ T Regulatory Cells in Systemic Lupus Erythematosus Patients: A Prospective Study
Authors: K. Tselios, A. Sarantopoulos, I. Gkougkourelas, A.-M. Georgiadou, P. Klonizakis, A. Kalogeridis, E. Vlachaki, P. Boura
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> T regulatory cells (Tregs) are inversely correlated to disease activity in systemic lupus erythematosus (SLE). However, little is known concerning the influence of immunosuppressive agents on Tregs and their kinetics, which was the objective of this study. <h3>Methods</h3> Thirty five lupus patients (29 females, 6 males, mean age 42.4±12.8 years, mean disease duration 97.5±16.2 months), in whom a dose increase of current drugs or administration of a new drug was required, were included. Tregs (CD4+CD25<sup>high</sup>FOXP3+) were prospectively assessed by flow cytometry every month for intravenous (iv) and quarterly for oral regimens. Clinical assessment was made with SLE Disease Activity Index (SLEDAI). Statistical analysis was performed with Student9s t-test or Mann-Whitney U test; <i>p</i>&lt;0.05 was considered significant. <h3>Results</h3> In total, 44 cases of SLE relapse were treated with iv cyclophosphamide (n=10), iv methylprednisolone (n=7), iv immunoglobulins (IVIGs, n=5), oral methylprednisolone (n=8), oral methylprednisolone and azathioprine (n=8) and hydroxychloroquine (n=6). Cyclophosphamide, iv methylprednisolone and IVIGs resulted in a significant increase of Tregs (4.2±1.6 to 10.1±5.7 cells/mm<sup>3</sup>, 2.9±1.3 to 10.6±4.8 cells/mm<sup>3</sup> and 5.6±2.7 to 15.2±6.3 cells/mm<sup>3</sup> respectively, <i>p</i>&lt;0.05). Oral methylprednisolone, alone or combined to azathioprine, led to significant Tregs increment (7.4±2.5 to 11.8±3.8 cells/mm<sup>3</sup> and 5.1±2.4 to 9.4±3.6 cells/mm<sup>3</sup> respectively, <i>p</i>&lt;0.05). Likewise, hydroxychloroquine resulted in significant Tregs increase (8.2±2.4 to 12.8±2.7 cells/mm<sup>3</sup>, <i>p</i>&lt;0.05). Time to Tregs recovery was significantly shorter with iv methylprednisolone and IVIGs, compared to cyclophosphamide (1.4±0.5, 1.6±0.9 and 4±1.5 months respectively, <i>p</i>&lt;0.05). <h3>Conclusions</h3> Tregs increment during SLE remission is independent of the therapeutic regimen used and probably represents an epiphenomenon. Time to Tregs restoration was significantly shorter in patients treated with iv methylprednisolone and IVIGs, compared to cyclophosphamide pulse therapy. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3810
Pulmonary vascular response to nitroprusside in dogs.
Authors: E D Sivak, B A Gray, H T McCurdy, A K Phillips
Journal: Circulation Research (1979)

Although the effects of nitroprusside (NP) on myocardial function have been studied extensively, the effects of this vasodilator on the pulmonary vasculature have received less attention.In closed-chest anesthetized dogs, we used indicator dilution measurements of pulmonary blood volume (PBV), along -with measurements of pulmonary artery (Ppa) and left atrial (Pla) pressures, to address this problem in three experimental protocols.In protocol I, NP at 10-30 ftg/kg per min in volumeexpanded dogs reduced Ppa by 20% and Pla by 44% but produced no consistent change in PBV.In protocol II, NP at 1.8-5.4pg/kg per min accompanied by autologous blood transfusion, sufficient to return Pla to the control level, resulted in no change in Ppa, but an increase in PBV from 8.8 to 9.9 ml/ kg (P < 0.05).In protocol m, NP at 2-6 fig/kg per min was compared to decreased venous return produced by partial occlusion of the inferior vena cava (TVC).With IVC occlusion adjusted to yield Pla equal to that during NP infusion, there was no difference in Ppa, but PBV was greater during NP infusion (10.5 ml/kg), compared to IVC occlusion (7.6 ml/kg, P < 0.05).In some experiments NP produced an increase in PBV when Pla and Ppa were reduced.In protocols II and m, NP decreased pulmonary vascular resistance by 40-50% (P < 0.05) at equal levels of Ppa.We conclude that NP shifts the pressure-volume curve of the pulmonary vasculature so that greater volume and flow are accommodated at the same pressure and, under some conditions, may produce a paradoxical increase in PBV while reducing pulmonary vascular pressure.
A1.75 Angiogenic T cells and derived microparticles disturbances in rheumatoid arthritis patients
Authors: Javier Rodríguez-Carrio, Patricia López, Mercedes Alperi-López, Sara Alonso-Castro, Francisco J Ballina-García, Ana Suárez
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Underlying mechanisms behind increased cardiovascular (CV) risk in Rheumatoid Arthritis (RA) remain unknown, but chronic inflammation and disease activity are supposed to play an important role. The Angiogenic T cells (Tang) are a recently described T-cell subset with potential function in endothelial repair, similar to Endothelial Progenitor Cells (EPC). Thus, Tang disturbances could play a role in impairing endothelial repair. The main aim of this study was to analyse the Tang and EPC populations in RA patients according to disease-specific markers and traditional CV risk factors. Since microparticles have emerged as a new tool to study endothelial damage and CV risk, we also have studied Tang-derived MP in RA. <h3>Material and Methods</h3> Tang (CD3+ CD31+ CD184+) and EPC (CD34+ VEGFR2+ CD133+) populations were quantified by flow cytometry in peripheral blood samples from 103 RA and 18 healthy controls (HC). DAS28 score was used for measuring disease activity. IFNa serum levels were measured by Cytometric Bead Array. Clinical and immunological data and traditional CV risk factors were obtained by reviewing clinical records. Tang-derived microparticles (Tang-MP) were analysed from platelet-poor plasma samples based on their CD3 and CD31 expression. <h3>Results</h3> Both Tang and EPC were strongly depleted in RA patients (p &lt; 0.001 and p &lt; 0.0001). Tang were positively correlated with EPC and negatively with traditional CV risk factors in HC but not in patients. In RA, reduced Tang numbers were associated with disease activity (r = -0.519, p &lt; 0.0001), autoantibodies positivity (ANA: p = 0.003, RF: p = 0.006, aCCP: p = 0.003) and IFNa serum levels (r = -0.321, p = 0.001), regardless of disease duration. EPC-Tang correlation was partially recovered in those patients under remission (DAS28 &lt;2.6; r = 0.474, p = 0.013). Multivariate regression analysis adjusted by traditional CV risk factors confirmed that only disease-specific factors and smoking were significant predictors of Tang frequency in RA. Interestingly, patients with previous CV events exhibited strongly reduced Tang numbers (p = 0.004) and higher IFNa levels (p = 0.019). Additionally, Tang-MP were increased in patients (p = 0.003) and positively correlated with DAS28 (r = 0.293, p = 0.006). In contrast, in HC a negative correlation between Tang frequency and Tang-MP was found (r = -0.502, p = 0.034). Methotrexate treatment seem to increase Tang frecuency (p = 0.020) as well as to reduce Tang-MP counts (p = 0.048). <h3>Conclusions</h3> Tang and EPC depletion could have a role in determining the increased CV risk in RA. Disease-specific factors, autoantibodies and IFNa serum levels could account for this effect. Probably, disease-activity factors are injuring Tang subpopulation, leading to higher numbers of Tang-MP and thus, leading to a Tang failure.
AB0062 IL-6'S Role in Hypertrofic Left Ventricul in Patient with Rheumatoid Arthritis
Authors: E. Rapushi, T. Backa (Cico), A. Doko (Banushi), A. Zoto, E. Ktona, Z. Ylli, A. Mitre
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid Arthritis (RA) is an inflammatory and systemic disease. Cardiac involvement during the course of the disease is increase with the RA disease activity. All the cytokines that are involved in arthritic lesions also play an important role in extra-arthritic lesions. Interleukin-6 (IL-6) is a pleiotropic cytokine responsible for many different processes including the regulation of cell growth, apoptosis, differentiation, and survival in various cell types and organs, including the heart. Increased left ventricular mass is defined as Left Ventricular Hypertrophy (LVH). Assessment of LV mass could be done with echocardiography. LHV is an independent prognostic factor of cardiovascular morbidity and mortality. <h3>Objectives</h3> Assessment of IL-6 role in LVH in patient with rheumatoid arthritis. <h3>Methods</h3> We included in the study 24 patient (16 female, 8 male) diagnosed with RA but did not safer from Arterial Hypertension. All patient were assessed for weight and height. We measured the plasmatic level of RF, CRP, anti-CCP, IL-6 and also assessed the disease activity according to DAS 28. All patient underwent echocardiography 2D color Doppler to assess LV mass index. <h3>Results</h3> The group included in the study serial percentage of RF results 27±5.4UI/mL (&lt;20.0 UI/mL); CRP serial level resulted 9.7±5.0 mg/dl (&lt;5.0mg/dl); anti-CCP IgG resulted positive &gt;500 UI/mL (0.1 – 25 UI/mL) in 19 patient (79.2%), negative &lt;7.0 UI/mL (0.1 – 25 UI/mL) in 5 pacient (20.8%); plasmatic percentage e IL-6 resulted increased 25±6.5 pg/mL (&lt;4.0 pg/mL). Disease activity measured according to DAS 28 in the group that we included in the study resulted &gt;5.3. Mass index of LV measured with echocardiography 2D color Doppler resulted female 121±6.8g/m<sup>2</sup> (43-95g/m<sup>2</sup>) and for men 143±7.5g/m<sup>2</sup> (49-115g/m<sup>2</sup>). The value of CRP/IL-6 in the group included in the study resulted 0.36±0.5. The date gives us a correlation between plasmatic level of IL-6 with RF, anti-CCP, CRP and disease activity assessed according to DAS 28 (p&lt;0.05). Increase plasmatic level of IL-6 correlate with increase mass index of the LV in women and men (P&lt;0.01). Patients which has increase ratio PCR/IL-6 ≥0.36 have an increase mass index of LV. <h3>Conclusions</h3> IL-6 play an important role in the activity of RA. Patient with increase plasmatic level of IL-6 and increase ratio CRP/IL-6 should undergo periodic echocardiography for the assessment of LV mass index. IL-6 is a risk factor for the development of LVH, which makes it a prognostic factor for the assessment of cardiac involvement in patient with RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4203
A Triple Combination Tailored Therapy (Folfiri-Cetuximab) for Safe Dose Intensification: A Multicenter Phase II Proof-Of-Concept Study.
Authors: O. Capitain, J.P. Metges, M. Boisdron-Celle, A. Adenis, J.L. Raoul, T. Lecomte, Y. Lam, R. Faroux, C. Masliah, A.L. Poirier, V. Berger, A. Morel, E. Gamelin
Journal: Annals of Oncology (2014)
Diffusion restriction as a predictor of response in recurrent glioblastoma patients receiving bevacizumab.
Authors: J. Wu, M. R. Gilbert, J. F. De Groot, W. A. Yung, V. K. Puduvalli
Journal: Journal of Clinical Oncology (2010)

2024 Background: Bevacizumab (BEV) improves outcome in a subset of patients with recurrent glioblastoma (GBM). Identification of this subset would improve patient selection for BEV therapy. The observation that BEV treatment induces diffusion weighted imaging (DWI) changes in some patients led to this study evaluating the relationship of DWI and apparent diffusion coefficient (ADC) to clinical outcome in recurrent GBM patients receiving BEV. Methods: We reviewed clinical data and brain MRIs of 262 adults with recurrent GBM treated with BEV. Patients with relevant imaging studies (MRI with DWI and ADC) at pretreatment baseline and at least 1 follow-up were categorized based on presence of DWI hyperintensity (DWI-HI) at baseline. Each group was subdivided based on the presence or absence of low ADC signal. The overall survival (OS) and progression free survival (PFS) rates were analyzed using the Kaplan Meier method and the log rank test. Results: Of 191 evaluable patients, 107 had new or increased DWI-HI after BEV. Patients with low ADC (n = 46) had a statistically significant improvement over those without low ADC (n = 61) in PFS (median 249 vs. 130 days; p = 0.0024; HR = 0.5) and OS (median 425 vs. 232 days; p < 0.0001; HR = 0.34). Of 60 patients with baseline DWI-HI which increased after BEV, patients with low ADC (n = 25) had better PFS and OS compared with those who did not (n = 35) (median PFS 218 vs. 97days; p = 0.0035, HR = 0.4; median OS 382 vs. 205 days; p = 0.0002; HR = 0.27). 47 patients developed DWI-HI after BEV; those with low ADC showed statistically significant improvement in OS but not PFS. Conclusions: Patients with a diffusion restricted (“ischemic”) MRI phenotype which appears or increases upon BEV treatment have improved PFS and OS compared with those without such changes, indicating a potential for using DWI to predict clinical outcome with BEV treatment in patients with recurrent GBM. A prospective study is being developed to better characterize the implications of these results. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Genentech, Merck, Novartis, Pfizer, Schering-Plough IMEDEX, Merck, Novartis, Schering-Plough Celgene, Genentech, Lilly, MGI Pharma, Novartis, Pfizer, Schering-Plough
Adverse Effects of Early Dexamethasone Treatment in Extremely-Low-Birth-Weight Infants
Authors: Ann R. Stark, Waldemar A. Carlo, Jon E. Tyson, Lu-Ann Papile, Linda L. Wright, Seetha Shankaran, Edward F. Donovan, William Oh, Charles R. Bauer, Shampa Saha, W. Kenneth Poole, Barbara J. Stoll, Avroy A. Fanaroff, Richard A. Ehrenkranz, Sheldon B. Korones, David K. Stevenson
Journal: New England Journal of Medicine (2001)

Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known.