tbuckley/cabot-search huggingface dataset:
Abstract 4553: Novel bispecific 111In-labeled immunoconjugates (bsICs) for imaging HER2/HER3 heterodimerization in breast cancer
Authors: Razumienko J. Eva, Raymond M. Reilly
Journal: Cancer Research (2010)

Abstract Objective: Our objective was to construct novel bsICs capable of binding HER2 and HER3 labeled with 111In for imaging HER2-HER3 heterodimerization in breast cancer (BC) possibly through higher avidity for dimeric vs. monomeric complexes. Methods: bsICs were composed of trastuzumab Fab recognizing HER2 linked to a 7.5 kDa HER3-binding peptide of heregulin-β1 (pHRG). Fab were produced by digestion of trastuzumab IgG with papain. Fab were modified with Sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC) or related analogues with polyethyleneglycol (PEG) spacers (SM-PEG12-NHS and SM-PEG24-NHS) to introduce maleimide groups for cross-linking to pHRG thiolated with Traut's reagent. bsICs were derivatized with diethylenetriaminepentaacetic acid (DTPA) for labeling with 111In. The ability to independently bind HER2 or HER3 was determined in competition assays using 111In-bsICs on cells expressing HER2, HER3 or both receptors competed with a 25-fold excess of Fab, pHRG or combined ligands. Results: Conjugation of Fab to pHRG was confirmed by SDS-PAGE, Western blot and size-exclusion HPLC. bsICs were labeled with 111In to a radiochemical purity of 98.9 ± 0.2% (specific activity 375 ± 14 MBq/mg). Insertion of a PEG spacer between Fab and pHRG was required for displacement of binding of 111In-bsICs to HER3 but not HER2. For 111In-bsICs with the longest spacer (PEG24), the binding to SKBR-3 cells (HER2+/HER3+) was reduced to 32.7 ± 0.7%, 85.9 ± 1.0% or 30.4 ± 1.6%, respectively by Fab, pHRG or both ligands. The binding to SKOV-3 cells (HER2+/HER3-) was reduced to 16.7 ± 0.8%, 88.8 ± 5.3% or 13.4 ± 0.1% by Fab, pHRG or both ligands. The binding to MDA-MB-468 cells (HER2-/HER3+) was reduced to 98.5 ± 1.5%, 68.8 ± 0.3% or 64.8 ± 4.5% by Fab, pHRG or both ligands. Less efficient competition for HER3 was observed for the PEG12 spacer and no competition for 111In-bsICs without a spacer. Conclusion: 111In-bsICs composed of trastuzumab Fab and pHRG bound specifically to HER2 and HER3 when an appropriate length PEG spacer was inserted between these two binding moieies. These 111In-bsICs may be useful for imaging HER2-HER3 heterodimerization in BC. Supported by the Ontario Institute of Cancer Research (1 mm Challenge) and the Canadian Breast Cancer Foundation (Ontario Branch). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4553.
THU0311 Transdermal Diclofenac Patch and Glucocorticoid Injection over Trochanteric Bursa on Greater Trochanter Pain Syndrome Management: A Comparative Prospective Study Based on Usual Clinical Practice
Authors: C.A. Guillen Astete, A. Boteanu, N. García Montes, M. Llop Vilatella
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recently, trasndermal diclofenac patch has been introduced into the medical practice with relative success in the management of sport injuries. Our experience of its use in the greater trochanteric pain syndrome is positive however there is no study comparing its therapeutic benefits with steroids and anesthetics injection. <h3>Objectives</h3> Purpose of present study is to assess the results of management of greater trochanteric pain syndrome with transdermal diclofenac patch compared with steroids and anesthetics injection. <h3>Methods</h3> We conducted a prospective observational study based on usual clinical practice at our hospital urgency and emergency department. Patients with greater trochanteric pain syndrome were indentified. Only were included patients treated with steroid injections (most of them also with mepivacaine 2%) or a 140 mg transdermal diclofenac patch. Patients were contacted once clinical assessment concluded to concert an interview seven days after. Clinical and epidemiological data were collected. Therapeutic success was determined by the subjective opinion of self being of each patient (dichotomous variable) and measure using a analogical visual scale (continuous variable). This protocol was aproved by the local ethics committee. <h3>Results</h3> Thirteen patients treated with transdermal diclofenac bid for at least three days (Group I) and 37 patients treated with a local injection of 40mg of triamcinolone and 1 or 2 cc of mepivacaine 2% (Group II) were included. Specific orocedure technic was not available in the records of 33 patients who underwent locally injected. Average age was 66 SD 6 in group I and 69 SD 8 years old in group II (p&gt;0.05). Female proportion was 76.9% in group I and 78.3% in group II (p&gt;0.05). Terapeutical success was achive according to patient opinion in 4 patients in group I and 11 in group II (30.7% and 29.7% respectively, p&gt;0.05). symptoms reduction measured by in analogic visual scale was 35.6 SD 18.8% in group I and La 40.5 SD 21.1% in group II (p=0.056). Considering only male patients such reduction was 78.4 SD 22.1% and 44.4 SD 27.4%, respectively (p&lt;0.01) <h3>Conclusions</h3> Our results point that transdermal diclofenac and local injections of steroids are equivalent therapies in the management of greater trochanteric pain síndrome. Although our results are preliminary, they open an interesting use of diclofenac patches, for instance, in patients in whom there are contraindications for infiltrations. The fact that men benefit more than women by this therapy could be explained by the characteristics of the male pelvis in terms of fat distribution and the penetration capacity of the patch. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4983
Abstract 941: Targeting androgen receptor in estrogen receptor-negative breast cancer
Authors: Min Ni, Yiwen Chen, Shannon T. Bailey, Yuuki Imai, X. Shirley Liu, Myles Brown
Journal: Cancer Research (2011)

Abstract Estrogen receptor (ER)-negative breast cancers account for 25-30% of all breast cancer cases and generally have a poor prognosis and little benefit from current endocrine therapy. Androgen receptor (AR) is expressed in 60-70% of human breast tumors independent of the ER status. Interestingly, while androgens inhibit the growth of ER+/AR+ breast cancer cells, they stimulate the growth of those that are ER-/AR+. However, the mechanism by which androgens and AR function to regulate breast cancer growth remains largely unknown. Analysis of gene expression microarray datasets from human breast tumors reveals enriched expression of AR in the ER- breast tumors that over-express HER2. Genome-wide analysis of the AR binding sites and androgen-regulated gene expression profiles in ER-/HER2+ breast cancer cells identified that AR mediates activation of oncogenic Wnt and HER2 signaling pathways through direct transcriptional up-regulation of WNT7B and HER3 in an androgen-dependent manner. Importantly, we demonstrate that FOXA1 and beta-catenin act as AR coactivators in inducing HER3, leading to the enforced HER2/HER3 signaling. Pharmacological inhibition of AR, Wnt or HER2 pathways impairs HER3 activation and androgen-stimulated tumor cell growth. While HER3 is receiving increased attention as a therapeutic target in HER2+ breast cancer, our study suggests that AR regulation may be yet another way to target HER3 in ER-/HER2+ tumors. Collectively, these findings not only highlight a previously unappreciated role of AR in breast cancer, but also reveals the mechanistic basis for targeting AR as a novel therapeutic opportunity for patients with invasive ER-/HER2+ breast tumors. 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 941. doi:10.1158/1538-7445.AM2011-941
Recombinant AAV-Mediated Delivery of a Tet-Inducible Reporter Gene to the Rat Retina
Authors: L.H. McGee Sanftner, K.G. Rendahl, D. Quiroz, M. Coyne, M. Ladner, W.C. Manning, J.G. Flannery
Journal: Molecular Therapy (2001)

Viral delivery of neurotrophins or other therapeutic genes is an attractive option for treating retinal degeneration. Regulated expression of these genes in the retina is needed to aid in dose delivery and to promote safety. To evaluate whether tetracycline (tet)-inducible transgenes encapsidated in recombinant adeno-associated viruses (rAAV) can provide controlled gene expression in vitro and in the rat retina, two viruses were constructed: a silencer/activator vector and an inducible doxycycline (dox)-responsive GFP vector. Combinations of these two viruses were subretinally injected into wild-type rats and dox was orally administered through the drinking water. Retinal GFP expression was monitored in vivo with a noninvasive fluorescence imaging method. Eyes were also examined by histology, Western analysis, and electroretinography. Subretinal injection of rAAV efficiently delivers inducible genes to both photoreceptors and retinal pigment epithelial cells. GFP expression was initially observed 1 week postinduction, and GFP protein was undetectable after removal of dox. In uninduced animals, GFP expression was negligible. The dox dosage was varied in vivo and showed a correlation to the level of GFP expression. Thus, transduction of retinal cells with tet-inducible vectors allows for tight regulation of gene expression. Viral delivery of neurotrophins or other therapeutic genes is an attractive option for treating retinal degeneration. Regulated expression of these genes in the retina is needed to aid in dose delivery and to promote safety. To evaluate whether tetracycline (tet)-inducible transgenes encapsidated in recombinant adeno-associated viruses (rAAV) can provide controlled gene expression in vitro and in the rat retina, two viruses were constructed: a silencer/activator vector and an inducible doxycycline (dox)-responsive GFP vector. Combinations of these two viruses were subretinally injected into wild-type rats and dox was orally administered through the drinking water. Retinal GFP expression was monitored in vivo with a noninvasive fluorescence imaging method. Eyes were also examined by histology, Western analysis, and electroretinography. Subretinal injection of rAAV efficiently delivers inducible genes to both photoreceptors and retinal pigment epithelial cells. GFP expression was initially observed 1 week postinduction, and GFP protein was undetectable after removal of dox. In uninduced animals, GFP expression was negligible. The dox dosage was varied in vivo and showed a correlation to the level of GFP expression. Thus, transduction of retinal cells with tet-inducible vectors allows for tight regulation of gene expression.
Abstract 1842: Familial demonstration of the involvement of E-cadherine germ-line mutation in inherited invasive lobular breast carcinomas
Authors: Xie Zeming, Xie Zeming, Nancy Uhrhammer, Yves Jean Bignon
Journal: Cancer Research (2010)

Abstract Introduction Germline mutations of the CDH1 (epithelial cadherin, OMIM 192090) gene have been extensively studied in hereditary diffuse gastric cancer (HDGC) families. Carriers of CDH1 germline mutations have a cumulative gastric cancer risk of 40-67% for men and 63-83% for women. Putative associated risk of lobular breast cancer(LBC) has also been documented in some HDGC families. Here we report a 86 members family, with a deleterious CDH1 germline mutation identified in 3 LBC affected members on 2 successive generations, 2 of them being bilateral LBC cases. It is noteworthy that no DGC was observed in this family. Subjects and Methods The family is of Caucasian origin, with 5 women affected by breast cancers. The proband is a female diagnosed with ILBC at the age of 60, her daughter was diagnosed with bilateral ILBC at the age of 42, one of her sisters died of breast cancer diagnosed at the age of 53, histological type was unknown. Two of her cousins were also diagnosed with breast cancer at the age of 63 and 54 respectively (one is a bilateral ILBC, another unknown). There is no confirmed diffused gastric cancer diagnosis in the history of this family. The affected members, their offspring, and siblings were recruited for genetic consultation. Two independent blood samples were tested after signing informed consent for each family member. Complete screening of CDH1, BRCA1 and BRCA2 genes was performed on 7 cases by sequencing exons and intron-exon boundaries. Results No BRCA1 and BRCA2 mutations were found in the family. A CDH1 Q95X germ-line mutation was found in all the 3 living women with invasive lobular breast cancers (2 of them developed bilateral ILBCs) and a 71-year-old healthy male member (one of the brothers of the proband). The mutation is also present in an obligatory carrier woman who developed a pancreatic cancer at the age of 56. Gastrointestinal endoscopy was recommended for indicative living individuals during genetic consultations, when they harbored the CDH1 mutations. No suspected gastric lesion was found. Conclusion Our report demonstrates the first clear example of the involvement of a deleterious E-cadherine germ-line mutation in inherited invasive lobular breast carcinoma. Screening for CDH1 mutation should be considered in families with multiple ILBC cases, even in the absence of DGC cases; ILBC risk should be considered for female carriers during consultations; prophylactic gastrectomy may not be regularly recommended in CDH1 mutations carriers without family histories of DGC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1842.
Abstract A20: Tumor selective delivery of chemotherapeutics via branched peptides
Authors: Chiara Falciani, Jlenia Brunetti, Barbara Lelli, Luisa Lozzi, Alessandro Pini, Niccolò Ravenni, Lapo Bencini, Stefano Menichetti, Renato Moretti, Luisa Bracci
Journal: Clinical Cancer Research (2010)

Abstract Oligo-branched peptides, containing the sequence of the human regulatory peptide neurotensin (NT), have been used as specific tumor targeting agents, able to selectively and specifically deliver effector units for cell imaging or killing, to tumor cells that over-express NT receptors. Tetra-branched peptides containing neurotensin (NT) sequence are described here as selective targeting agents for human colon, pancreas and prostate cancer. Fluorophore-conjugated peptides were used to measure tumor versus healthy tissue binding in human surgical samples, resulting in validation of neurotensin receptors as highly promising tumor-biomarkers. Drug-armed branched peptides were synthesized with different conjugation methods, resulting in uncleavable adducts or drug-releasing molecules. Human cell lines from colon (HT-29), pancreas (PANC-1) or prostate (PC-3) carcinoma were challenged with branched NT conjugated with 6-mercaptopurin, combretastain A-4, monastrol and 5-fluoro-deoxyuridine. Results indicated that branched NT conjugated with combretastain A-4 and 5-fluoro-deoxyuridine are the most active agents on HT-29 (EC50 1.1e-007 M) and PANC-1 (EC50 5.0e-007 M) respectively. Tetra-branched NT armed with 5-FdU was used for in vivo experiments in HT-29-xenografted mice and produced a 50% reduction in tumor growth with respect to animals treated with the free drug. An unrelated branched peptide carrying the same drug was completely ineffective. In vitro and in vivo results indicated that branched peptides are valuable tools for tumor selective targeting. The results reported in this presentation tell that branched-armed peptides are very promising pharmacodelivery options. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A20
The Liver in Ferrous Sulfate Poisoning
Authors: Michael A. Luongo, S. Stefan Bjornson
Journal: New England Journal of Medicine (1954)

CASES of toxicity from ferrous sulfate have been reported sporadically for two centuries. Revival of interest in acute iron poisoning stems back, however, to the report of Forbes1 in 1947, which included a description of clinical symptoms, pathological findings and an experimental study demonstrating the toxicity of large doses of iron compound. Since that time, many reports of both fatal and nonfatal poisoning have appeared, nearly all of which followed the accidental ingestion of ferrous sulfate tablets by children. In addition interest in the role of iron and its compounds and metabolites in human siderosis, hemosiderosis and cirrhosis of the . . .
Carbon monoxide and hospital admissions for congestive heart failure: evidence of an increased effect at low temperatures.
Authors: R D Morris, E N Naumova
Journal: Environmental Health Perspectives (1998)

The combined effects of carbon monoxide and low temperature on daily variation in hospital admissions for congestive heart failure (CHF) were examined for a 4-year period in Chicago, Illinois. Medicare hospital admissions for CHF were analyzed as a function of the maximum hourly temperature, maximum hourly levels of carbon monoxide (CO), and other criteria pollutants in Chicago for each day of the 4-year period (1986-1989). The regression analyses for the time series were conducted using single and multipollutant models with interaction terms and adjustments for weather, weekly cycles, seasonal effects, and secular trend. The data were also grouped into three temperature ranges, <40 degrees, 40 degrees-75 degrees, and >75 degrees F, and the relationship between CO and CHF admissions was evaluated for each range. For the 4-year time series, the CO level was positively associated with hospital admissions for CHF in the single pollutant and multipollutant models after adjustment for seasonal effects and weather pattern. The relative risks of hospital admissions for CHF in Chicago associated with the 75th percentile of exposure to CO in the high, medium, and low temperature ranges were 1.02 [95% confidence interval (CI), 0.95-1.10], 1.09 (CI, 1.04-1.14), and 1.15 (CI, 1.09-1.22), respectively. In these data, the effect of CO on hospital admissions for CHF was temperature dependent, with the magnitude of the effect increasing with decreasing temperature. This synergy may help to explain the association between ambient CO and CHF admissions demonstrated in other studies.
635 NATURAL COURSE OF EXTRAHEPATIC, NONMALIGNANT AND PARTIAL PORTAL VEIN THROMBOSIS IN PATIENTS WITH CIRRHOSIS
Authors: A. Luca, S. Caruso, G. Marrone, G. Mamone, F. Crinó, G. Vizzini, L. Maruzzelli, R. Miraglia
Journal: Journal of Hepatology (2012)
The Effect of Race on Access and Outcome in Transplantation
Authors: Bertram L. Kasiske, John F. Neylan, Robert R. Riggio, Gabriel M. Danovitch, Lawrence Kahana, Steven R. Alexander, Martin G. White
Journal: New England Journal of Medicine (1991)

THE American Society of Transplant Physicians directed its Patient Care and Education Committee to examine the issue of racial inequality in transplantation. The committee, made up of physicians involved in clinical transplantation, used both published data and personal experience to develop a consensus on the issues and problems related to race in transplantation. This report summarizes the conclusions reached by the committee and outlines the specific recommendations made to the society. Prevalence and Incidence of End-Stage Renal Disease among Minorities To examine the issue of racial inequality in kidney transplantation, it is important to know the incidence and prevalence of . . .
Abstract 2800: IL-5 induced migration of HT1376 cells via ERK1/2-mediated MMP-9 expression by inducing activation of NF-κB .
Authors: Eo-jin Lee, Se-Jung Lee, Sung-Kwon Moon
Journal: Cancer Research (2013)

Abstract Interleukin-5 (IL-5) plays an important role in the growth and differentiation of human B cells and eosinophils. However, little is known about the effect of IL-5 on cancer cells. In this study, we investigated the molecular mechanism involved in the IL-5-induced migration of bladder cancer HT1376 cells. Our results indicated that IL-5 significantly enhanced migration and MMP-9 expression in HT1376 cells. We also found that IL-5 induces transcriptional activation of the binding of NF-kB and AP-1, which are two important nuclear transcription factors that are linked to MMP-9 expression in HT1376 cells. In subsequent experiments, we found activation of ERK1/2 in IL-5-treated HT1376 cells. To examine the involvement of the ERK1/2 signaling pathway on IL-5-induced cell responses, we pretreated HT1376 cells with the ERK1/2 inhibitor U0126 followed by IL-5 treatment. The results showed that U0126 treatment inhibited migration of IL-5-treated HT1376 cells. Moreover, IL-5-stimulated MMP-9 expression was suppressed by the addition of U0126. Inhibition of ERK1/2 function consistently rescued transcriptional activity of NF-kB, without altering AP-1 activation, in IL-5-treated cells. Finally, inhibition of IL-5 specific receptor IL-5R alpha by small interfering RNA (siRNA) suppressed migration, ERK1/2 activation, MMP-9 expression and binding activation of NF-kB in IL-5-treated HT1376 cells. The results of the present study indicate that the IL-5/IL-5R alpha dyad induced cell migration through ERK1/2-mediated expression of MMP-9 by binding activation of NF-kB in bladder cancer cells. In conclusion, these novel findings indicate that binding of IL-5 to IL-5R alpha plays a critical role in MMP-9 expression, which might be involved in the migration of bladder cancer. Citation Format: Eo-jin Lee, Se-Jung Lee, Sung-Kwon Moon. IL-5 induced migration of HT1376 cells via ERK1/2-mediated MMP-9 expression by inducing activation of NF-κB . [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 2800. doi:10.1158/1538-7445.AM2013-2800
Prediction of the Need for Intensive Care in Patients Who Come to Emergency Departments with Acute Chest Pain
Authors: Lee Goldman, E. Francis Cook, Paula A. Johnson, Donald A. Brand, Gregory W. Rouan, Thomas H. Lee
Journal: New England Journal of Medicine (1996)

Patients who come to the emergency department with chest pain are a heterogeneous group. Some have ischemic heart disease that may lead to serious complications, whereas others have minor disorders. We performed a study to identify clinical factors that predict which patients will have complications requiring intensive care.