tbuckley/cabot-search huggingface dataset:
Abstract P4-08-06: Companion Diagnostic Test for Expression of β-III tubulin (ß3T) in Breast Cancer (BC) Using an Immunohistochemical (IHC) Assay in Studies of Ixabepilone (Ixa)
Authors: C Roach, V Tanna, R Welcher, C Dumontet, P Sève, O. Trifan
Journal: Cancer Research (2010)

Abstract Background: Preclinical and retrospective clinical data suggest that ≥3T is a biomarker for poor prognosis and resistance to paclitaxel in breast cancer (BC). Preclinical studies have demonstrated that Ixa has activity in ≥3T over-expressing xenograft models resistant to taxanes and Ixa has shown clinical activity in BC patients with high ≥3T mRNA levels [Horak et al., J Clin Oncol 27:15s, 2009 (suppl; abstr 3587]. Dako and BMS have developed an IHC assay for detection of ≥3T to explore the potential of ≥3T as a biomarker to select BC patients that may benefit from Ixa. A neoadjuvant BC study comparing ixa to weekly paclitaxel employs this assay to assess ≥3T expression levels in patients’ tumor samples. Here we describe the application and initial validation testing of the assay in BC tumor samples. Methods: An IHC assay employing a murine monoclonal anti-≥3T antibody (TUJ1) was developed to assess ≥3T expression in formalin-fixed paraffin-embedded tissue specimens. Banked specimens for initial testing included 233 cases of invasive BC. Results: Patterns of ≥3T staining were typically homogeneous cytoplasmic staining with normal tissue elements such as endothelial cells and nerve cells serving as internal positive controls. Staining intensity was scored as 0, 1+, 2+ or 3+ with 0 being no visible staining and 2+ being equal to that of the internal positive control. Tumors with ≥50% cells staining ≥2+ were defined as positive for ≥3T based on previous published studies. Of the 233 breast tumors, 81 (35%) were positive and 152 (65%) were negative for ≥3T expression. HER2 status was defined for 128 of these specimens, with 37 of them (29%) found to be HER2 positive. Comparison of the samples with defined HER2 status demonstrated similar patterns of ≥3T expression, with 15 (40.5%) of the HER2+ samples being positive for ≥3T and 31 (34.1%) of HER2- specimens expressing elevated levels of ≥3T. In pathologist training exercises the inter-reader and intra-reader agreement of ≥3T scoring exceeded 85%. Antigen stability has been confirmed and other assay validation efforts are ongoing. Conclusions: These findings are consistent with previously reported data on ≥3T expression in breast cancer, and support the use of this ≥3T IHC assay in studies with ixabepilone. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-06.
A Controlled Trial of Corticosteroid Injections into Facet Joints for Chronic Low Back Pain
Authors: Simon Carette, Sylvie Marcoux, René Truchon, Charlotte Grondin, Jacques Gagnon, Yves Allard, Marie Latulippe
Journal: New England Journal of Medicine (1991)

Chronic low back pain is a common problem with many treatments, few of which have been rigorously evaluated. This randomized, placebo-controlled trial was designed to evaluate the efficacy of injections of corticosteroid into facet joints to treat chronic low back pain.
Abstract 4127: Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with targeted therapies
Authors: Françoise Farace, Claire Cropet, Ellen Blanc, David Pérol, Sylvie Négrier, Bernard Escudier
Journal: Cancer Research (2011)

Abstract Background: A biomarker allowing to predict the efficacy of targeted therapies would be of great clinical value in patients with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell levels are associated with clinical outcome in mRCC patients undergoing targeted treatments. Methods: The TORAVA trial was a randomized phase II study aimed to determine the efficacy and safety of temsirolimus and bevacizumab combination (arm A) in comparison to 2 control arms, sunitinib (arm B) or bevacizumab and α-interferon (arm C). Samples were collected at baseline and day 14 for each treatment arm. CEC levels were analysed in 117 patients (pts) using the CellSearch™ (Veridex, Warren, NJ) platform. Bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell levels were measured in 10ml blood samples of 42 pts by four-color flow cytometry after progenitor cell enrichment. Relation between CEC and CD45dimCD34+VEGFR2+ progenitor cell levels and clinico-biological characteristics, response to treatment (determined by RECIST criteria after 2 cycles) and progression free survival (PFS) was examined. Results: CEC levels were significantly higher in patients without nephrectomy (p&amp;lt;0.001). A trend between the association of high CEC levels and a PS of 2 was observed (p=0.08). CEC and CD45dimCD34+VEGFR2+ progenitor cell levels at both baseline and day 14 were not correlated to response to treatment. No correlation was found between baseline or day 14 CEC values and PFS. However, pre-treatment CD45dimCD34+VEGFR2+ progenitor cell levels were significantly correlated to PFS (p=0.003). Patients with elevated pre-treatment levels of CD45dimCD34+VEGFR2+ progenitor cell had an increased risk of tumor progression. Conclusion: Our results indicate that pre-treatment CD45dimCD34+VEGFR2+ progenitor cell levels could accurately predict PFS in MRCC patients receiving targeted therapies. The association between CEC and CD45dimCD34+VEGFR2+ progenitor cell levels and overall survival will be presented. These data suggested that measurement of CD45dimCD34+VEGFR2+ progenitor cell levels before targeted therapy in mRCC patients will allow to identify at an early stage patients who will benefit most from treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4127. doi:10.1158/1538-7445.AM2011-4127
EARLY PREDICTION OF ACUTE KIDNEY INJURY AFTER ACUTE MYOCARDIAL INFARCTION BY A CLINICAL RISK SCORE
Authors: Katsuomi Iwakura, Atsunori Okamura, Yasushi Koyama, Koichi Inoue, Hiroyuki Nagai, Yuko Toyoshima, Koji Tanaka, Takafumi Oka, Mutsum Iwamoto, Kenshi Fujii
Journal: Journal of the American College of Cardiology (2016)
Gene Therapy Depends on Finding The Right Vector
Authors: David Holzman
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Gene Therapy Depends on Finding The Right Vector Get access David Holzman David Holzman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 6, 15 March 1995, Pages 406–410, https://doi.org/10.1093/jnci/87.6.406 Published: 15 March 1995
A3.14 PD-1 Signalling and Low RORC mRNA Content Influence the TREG/TH17 Balance in Human Cord Blood
Authors: Sytze de Roock, Sanne Hoeks, Arie Jan Stoppelenburg, Berent Prakken, Ismé de Kleer, Marianne Boes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> In neonates, the immune system is less responsive than in adults. Explanations for this involve differences in T helper (Th) 1 versus Th2 cell numbers and altered cytokine profiles after stimulation. We hypothesised that neonatal immune deviation may also involve FOXP3<sup>+</sup> regulatory T cells (Treg) and Th17 cells. <h3>Materials and Methods</h3> In order to investigate this, we compared CD4<sup>+</sup>CD25<sup>–</sup>CD45RO<sup>–</sup> naïve T cells from human cord blood (CB) with cells from adult peripheral blood (APB). Cells were activated in vitro by anti-CD3 in the presence of viable antigen presenting cells (APB). The induction of regulatory T cells and Th17 cells was analysed by flow cytometry. Cytokine production was measured by multiplex immunoassays and RORC mRNA content by PCR. Specific interactions between APC and T cells were blocked with monoclonal antibodies during cell culture. <h3>Results</h3> CB cells show lower numbers of Treg ex vivo than APB. However, upon activation, high percentages of functionally suppressive FOXP3<sup>+</sup> Treg are induced in CB. Replacement of viable APC by irradiated APC or anti-CD28 abrogated this effect, suggesting that live APC from CB in particular may imprint a Treg phenotype. Indeed, CB APC were able to induce high numbers of FOXP3<sup>+</sup> cells in alloreactive immune reactions with APB T cells as well. Addition of blocking antibodies against CD80, CD86 or CTLA-4 to CB cultures did not affect the number of Tregs induced. Blockade of the PD-1/PD-Ligand (PD-L)1 interaction however showed a marked decrease in FOXP3<sup>+</sup> cell numbers. CB cells showed a consistently reduced protein kinase B (PKB)/c-Akt phosphorylation upon activation. On top of that, in contrast to APB, low concentrations of APC derived pro-inflammatory cytokines were detected in CB cultures and no Th17 cells were induced. Addition of Th17 inducing cytokines reduced FOXP3<sup>+</sup> cell numbers in CB, but did not induce IL-17 production. PCR of the Th17 defining transcription factor RORC showed a significantly reduced concentration of this protein in CB. <h3>Conclusions</h3> Human cord blood cells have an increased propensity to become FOXP3<sup>+</sup> Treg as compared to APB. This effect is due to low production of inflammatory cytokines and PD-1/PD-L1 interaction. Inability to induce Th17 cells in CB could not be abrogated by Th17 inducing cytokines, but was due to reduced RORC mRNA content. This study shows mechanisms involving the human Th17/Treg induction switch that can also be important in inflammation and auto-immune disorders.
Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis
Authors: Xiaowei Wang, Yannik Gkanatsas, Jathushan Palasubramaniam, Jan David Hohmann, Yung Chih Chen, Bock Lim, Christoph E Hagemeyer, Karlheinz Peter
Journal: Theranostics (2016)

Myocardial infarction and stroke are leading causes of morbidity/mortality. The typical underlying pathology is the formation of thrombi/emboli and subsequent vessel occlusion. Systemically administered fibrinolytic drugs are the most effective pharmacological therapy. However, bleeding complications are relatively common and this risk as such limits their broader use. Furthermore, a rapid non-invasive imaging technology is not available. Thereby, many thrombotic events are missed or only diagnosed when ischemic damage has already occurred.Design and preclinical testing of a novel 'theranostic' technology for the rapid non-invasive diagnosis and effective, bleeding-free treatment of thrombosis.A newly created, innovative theranostic microbubble combines a recombinant fibrinolytic drug, an echo-enhancing microbubble and a recombinant thrombus-targeting device in form of an activated-platelet-specific single-chain antibody. After initial in vitro proof of functionality, we tested this theranostic microbubble both in ultrasound imaging and thrombolytic therapy using a mouse model of ferric-chloride-induced thrombosis in the carotid artery. We demonstrate the reliable highly sensitive detection of in vivo thrombi and the ability to monitor their size changes in real time. Furthermore, these theranostic microbubbles proofed to be as effective in thrombolysis as commercial urokinase but without the prolongation of bleeding time as seen with urokinase.We describe a novel theranostic technology enabling simultaneous diagnosis and treatment of thrombosis, as well as monitoring of success or failure of thrombolysis. This technology holds promise for major progress in rapid diagnosis and bleeding-free thrombolysis thereby potentially preventing the often devastating consequences of thrombotic disease in many patients.
Myocardial Uptake of 99mTc-HDP and Reduced Perfusion on CT in Subacute Myocardial Infarction
Authors: Emmanouil Panagiotidis, Gemma Price, Stephen Harland, Jamshed Bomanji, Irfan Kayani
Journal: Clinical Nuclear Medicine (2013)

A 65-year-old man with known bone metastases from prostate cancer and no cardiac history attended for a restaging bone scan (BS). Diffuse increased Tc-HDP activity in the heart was noted, new since a BS 3 months earlier. A restaging contrast-enhanced CT scan on the same day showed reduced myocardial perfusion in the anterior, apical, and septal walls. On direct questioning, he described an episode of severe exertional chest pain the day before. Myocardial infarction was confirmed and treated with primary percutaneous coronary intervention. New cardiac uptake on BS, raising the possibility of myocardial infarction, is a red alert for clinicians.
Leptomeningeal Carcinomatosis and Intramedullary Spinal Cord Metastases from Lung Cancer
Authors: TSUYOSHI KOMORI, DOMINIQUE DELBEKE
Journal: Clinical Nuclear Medicine (2001)

A 64-year-old man with a history of large-cell lung carcinoma and recent resection of a brain metastasis was examined because of a general decline in his ability to function. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG PET) showed metastases along the spinal cord that were confirmed with MRI. Intramedullary spinal cord metastasis occurs rarely, and the prognosis is extremely poor. Whole-body FDG PET allows the entire spinal cord to be examined noninvasively compared with magnetic resonance imaging, computed tomography, and myelography.
S5 Prevalence of latent tuberculosis infection in immigrants to the UK: findings from a multi-centre study
Authors: M. Pareek, J. P. Watson, O. M. Kon, G. Woltmann, A. Lalvani
Journal: Thorax (2010)

<h3>Background</h3> Notifications for tuberculosis (TB) in the United Kingdom (UK) increased by 30% between 1992 and 2007 with overseas-born migrants accounting for 72% of cases in 2007. Much of this increase is due to the synergy of migration from high-TB burden countries and the reactivation of pre-existing latent TB infection (LTBI). Since 2006, NICE guidance advocates screening for LTBI in all children from countries with a TB incidence &gt;40/100 000 and adults from Sub-Saharan Africa and countries with a TB incidence &gt;500/100 000. The rationale underpinning these guidelines remains unclear particularly as there are little data on the prevalence of LTBI in immigrants to the UK from regions with different TB incidence rates. <h3>Aims</h3> To quantify the prevalence of LTBI in immigrants, assess factors associated with IGRA positivity and to determine LTBI yield from current screening thresholds recommended by NICE. <h3>Methods</h3> Analysis of data prospectively obtained through IGRA testing (QuantiFERON-Gold/QuantiFERON-Gold-in-tube) of immigrants in three different centres in the UK during 2008–2010. Descriptive analyses were undertaken. Yields at different screening thresholds were calculated. Subsequent univariate and multivariate analyses were undertaken to assess independent factors associated with IGRA positivity; p&lt;0.05 considered significant. <h3>Results</h3> In total 915 immigrants were screened during the study period. Median age was 26.8 years (interquartile range 22–33), 50.6% were female and 72.5% had previously been BCG vaccinated. 48.9% and 28.5% of migrants screened originated from the Indian Subcontinent and Sub-Saharan Africa, respectively. Overall 911/915 individuals had determinate IGRA results—199 (21.7%) tested positive and 712 (77.8%) tested negative; 4 (0.4%) individuals had indeterminate results. Multivariate analysis revealed that increasing age (p&lt;0.0001) and increasing TB incidence of country of origin (p=0.0014) were independently associated with IGRA positivity. Applying current NICE guidance resulted in a yield of 76/311 (24.4%) but would miss 61.8% of the immigrant population with LTBI (Abstract S5 Table 1). <h3>Conclusions</h3> Immigrants have a high prevalence of LTBI but current NICE guidance detects only 38.2% of new entrants with LTBI. Given the high rates of reactivation of LTBI in new entrants, our findings suggest that consideration should be given to reducing the screening threshold to include those from the Indian Subcontinent (incidence 170/100 000) which would result in 67.8% of all LTBI cases being identified.
OP0067 Cluster analysis of clinical data identifies fibromyalgia subgroups
Authors: E. Docampo, G. Escaramis, R. Rabionet, J. Carbonell, J. Rivera, J. Alegre, J. Vidal, X. Estivill, A. Collado
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia (FM) is characterized by widespread pain and other symptoms, such as psychiatric and physical comorbidities. The heterogeneity of FM hinders its assessment and management. <h3>Objectives</h3> The aim of this work is to identify FM subgroups by classifying clinical data into simplified dimensions. <h3>Methods</h3> 44 variables were evaluated in 560 unrelated Spanish FM cases of Caucasian origin. All participants fulfilled 1990 ACR FM criteria and were evaluated at one of five Rheumatology Units. A partitioning analysis was performed to find groups of variables similar to each other, thus describing underlying FM dimensions. Given the mixed nature type of the variables, these were transformed into binary types (0=mild; 1=severe), and a generalization of the Gower method was applied to find similarities between variables. A score was constructed per sample and dimension based on the weights of the variables depicting the specific dimension. Kmeans clustering procedure was then applied into resulting scores to create FM subgroups. This analysis was also performed in a replication set of 950 cases. <h3>Results</h3> Variables clustered into three independent dimensions: pain and other symptoms, family and personal comorbidities and clinical scales (fig. 1). Only the two most reliable dimensions (pain and other symptoms and comorbidities) were considered for FM subgroups construction. Resulting scores classified FM samples into three subgroups: high symptomatology and comorbidities, high symptomatology but low comorbidities and low symptomatology and comorbidities. Both the variable clustering and the sample subgrouping were replicated in the second cohort. <h3>Conclusions</h3> We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. This partitioning method could be used as a useful tool in FM severity assessment and personalized treatment. <h3>Disclosure of Interest</h3> None Declared
F-18 FDG PET/CT Imaging of Bulky Myxofibrosarcoma in Chest Wall
Authors: Kimiteru Ito, Yoko Masuda-Miyata, Saho Wada, Miyako Morooka, Kunihiro Yamasawa, Masanori Hashimoto, Kazuo Kubota
Journal: Clinical Nuclear Medicine (2011)

Myxofibrosarcoma (MFS) has a spectrum of malignant fibroblastic lesions with variably myxoid stroma and pleomorphism. A 67-year-old man with a bulky mass on his chest wall was diagnosed with MFS. He underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography for detection of metastasis. FDG positron emission tomography /computed tomography showed inhomogeneous high FDG uptake (max standardized uptake value, 10.1) in the bulky tumor with no evidence of metastasis, and the tumor was successfully resected. FDG uptake seemed to be reflected by the broad spectrum of pathologic heterogeneity. And MFS should be considered when making a diagnosis of inhomogeneous FDG-avid lesions in the bulky masses of soft tissue.
THU0269 Liposomal Local Therapy as Treatment of Sicca Symptoms in Patients with Primary SjöGren´s Syndrome
Authors: B. Hofauer, M. Bas, N. Mansour, A. Knopf
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The primary Sjögren´s Syndrome (pSS) represents the most common rheumatologic disease in the head and neck area. Due to various nonspecific symptoms many different medical specialities get involved in diagnostic and therapeutic regimes of patients with pSS. Therefore a broad awareness of symptoms and therapeutic options is important. Effective management of Xerostomia, Keratoconjunctivis sicca (KCS) and Rhinitis sicca (RS) is essential in every patient to alleviate symptoms and prevent local complications. Various substitutes with different ingredients are available for topical and symptomatic therapy, but there are no generally accepted treatment suggestions due to the lack of studies proving effective relief of symptoms. <h3>Objectives</h3> Is topic therapy with liposomal agents suitable for symptomatic treatment of sicca symptoms in pSS? <h3>Methods</h3> Between October 2007 and August 2012 pSS was diagnosed in 73 patients according to the American European Consensus Group (AECG) criteria. Before and after a 2-month-period of treatment with liposomal agents for oral, nasal and ocular complaints (LipoSaliva®, LipoNasal® und Tears Again®) AECG-criteria and subjective symptoms expressed via visual analogue scales were evaluated. <h3>Results</h3> Xerostomia (92%), KCS (92%) and recurrent salivary gland swelling (40%) were the leading clinical symptoms. Mean salivary flow rate was 1,89g (Saxon-Test), mean lacrimal flow 12,7mm (Schirmer-I-Test). SS-A/-B antibodies could be detected in 47/29% of cases. An average histologic focus score of 3 could be seen (Chisholm and Mason). Extraglandular manifestations were observed in 17%, severe local complications due to ineffective treatment of sicca symptoms were diagnosed in 71%, respectively. Liposomal local therapy caused a significant reduction of Xerostomia (p=0,0001), KCS (p=0,004) and RS (p=0,004). <h3>Conclusions</h3> Local therapy with liposomal agents is effective in the symptomatic treatment of Xerostomia, KCS and RS in patients with pSS. <h3>Disclosure of Interest</h3> None Declared
Abstract 1182: Ocimum gratissimum aqueous extract induces apoptotic signalling in human osteosarcoma cells.
Authors: Chien Chung Lin
Journal: Cancer Research (2013)

Abstract Osteosarcoma (Osteosarcoma) is a kind of bone cancer. Eighty percent of this tumor will be metastatic to the lungs or liver. Therefore, these patients generally need to use chemotherapy to improve disease and increase survival possibility. Recently, it has been reported that Ocimum gratissimum (OG) aqueous extract has anti-tumor activity. In this study, we detected the effect of OG extract on human bone cancer cell growth and metastasis. The results showed that the OG extract can inhibit cell growth and induce cell apoptosis in human bone cancer cells, but no effect in normal nerve cell. Therefore, we suggest that OG extract s may have anti-cancer ability, and can provide the use in the development of new anti-cancer drugs Figure . OGE effect on the cell growth in two osteosarcoma cells. Cell growth was determined 0∼3 or 0∼5 days after subculture using the MTT assay as described in Materials and Methods. Absorbance values obtained from the cells on day 0 after subculture were taken as 100%. Citation Format: Chien Chung Lin. Ocimum gratissimum aqueous extract induces apoptotic signalling in human osteosarcoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1182. doi:10.1158/1538-7445.AM2013-1182 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.