tbuckley/cabot-search huggingface dataset:
Epidemiology of S pneumoniae Infection in Hematology Patients in Ile de France: Serotypes Covered by the Polysaccharide 23-Valent (PS23) and the Heltavalent Conjugate Vaccine.
Authors: Karima Debbache, Emmanuelle Varon, Yosr Hicheri, Patrick Legrand, Jean-Luc Donay, Patricia Ribaud, Catherine Cordonnier
Journal: Blood (2007)
Abstract B59: Black raspberries inhibit pancreatic carcinogenesis by suppressing Raf/MEK/ERK/STAT3 signaling pathways and promoting apoptosis
Authors: Pan Pan, Chad W. Skaer, Hsin-Tzu Wang, Susan Tsai, Kiyoko Oshima, Yi-Wen Huang, Li-Shu Wang
Journal: Cancer Research (2016)

Abstract Background: Despite improved understanding of the pathophysiology of pancreatic ductal adenocarcinoma (PDAC) in the past two decades, PDAC has an extremely low 5-year survival rate (7%). However, diets rich in fruits and vegetables have been reported to reduce the risk of cancer development. We previously demonstrated that black raspberries (BRBs) have chemopreventive effects in human colorectal cancer patients and mouse models of colorectal cancer. Our current study aimed to investigate the potential effects of BRBs against PDAC in mice. Methods: Mice that carry a constitutively activated KrasLSL.G12D/+ oncogene and loss-of-function Trp53LSL.R172H/+ tumor-suppressor gene in the pancreas (KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre) spontaneously develop PDAC that recapitulates the human PDAC. Four-week-old KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre mice were given a control diet or a control diet supplemented with 5% BRBs. In addition, luciferase-transfected human Panc-1 (Panc-1-Luc) cells were orthotopically injected into the pancreas of nonobese, diabetic, severe combined immunodeficient (NOD.SCID) mice. Four weeks after the inoculation of Panc-1-Luc cells, the NOD.SCID mice were given a control diet or a control diet supplemented with 5% BRBs for 6 weeks. Gross tumor volume of orthotopic pancreatic tumors was measured. Results: The 4-week-old KrasLSL.G12D/+-Trp53LSL.R172H/+-Pdx-1-Cre mice developed pancreatic intraepithelial neoplasia (PanIN) lesions, which are the precancerous lesions of PDAC, and they were fed control or 5% BRB diet. Kaplan-Meier survival analysis showed that 5% BRBs significantly prolonged the survival of those PDAC mice with a median survival of 189 days versus 154 days for the mice fed the control diet. Molecular studies suggested that 5% BRBs suppress the Raf/MEK/ERK/STAT3 pathway, which is the downstream of Kras activation, and inhibit cancer cell proliferation in pancreatic tumor tissues. In addition, 5% BRBs significantly decreased the gross tumor volume of orthotopic tumors produced by injecting Panc-1-Luc cells into the pancreas. Orthotopic pancreatic tumors in BRB-treated NOD.SCID mice had a higher rate of apoptosis than tumors from mice fed the control diet. Conclusions: These results support the hypothesis that BRBs have the clinical potential to delay pancreatic cancer progression by suppressing cancer cell proliferation and/or promoting apoptosis. Citation Format: Pan Pan, Chad W. Skaer, Hsin-Tzu Wang, Susan Tsai, Kiyoko Oshima, Yi-Wen Huang, Li-Shu Wang.{Authors}. Black raspberries inhibit pancreatic carcinogenesis by suppressing Raf/MEK/ERK/STAT3 signaling pathways and promoting apoptosis. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B59.
Activity of imatinib mesylate in desmoid tumors: Interim analysis of a Sarcoma Alliance for Research thru Collaboration (SARC) phase II trial
Authors: L. H. Baker, K. Wathen, R. Chugh, D. Thomas, P. F. Thall, R. G. Maki, B. L. Samuels, P. A. Meyers, D. A. Priebat, R. S. Benjamin
Journal: Journal of Clinical Oncology (2004)

9013 Background: Desmoid tumors (aggressive fibromatosis) are rare clonal neoplastic proliferations of connective tissues. Although classified as benign, local aggressiveness can lead to significant impairment. Standard treatment involves wide surgical resection and/or radiation therapy. In cases of unresectable or recurrent disease, tamoxifen, chemotherapy, and NSAIDs have been used with varying success. We and others have previously reported desmoid tumors expressing c-kit, PDGFRα, and/or PDGFR. We reported two patients with extraabdominal desmoid tumors treated with the selective tyrosine kinase inhibitor imatinib (Gleevec) with significant shrinkage. SARC, in association with the Connective Tissue Oncology Society, initiated a prospective phase II trial in patients with desmoid tumors, or one of nine sarcoma subtypes. Here, we report specifically on patients with desmoid tumors. Methods: Patients ≥ 10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg BID (BSA≥1.5m2), 200 mg BID (BSA=1.0–1.49m2), or 100 mg BID (BSA<1.0m2). Response outcomes at two and four months were collected. Rules for early termination within each disease type were based on a hierarchical Bayesian probability model accounting for correlation of the responses of the 10 disease types. Tissue specimens were analyzed by immunohistochemistry for expression of c-kit, PDGFRα, PDGFRß, AKT, PTEN, FKHR, and beta catenin. Tumor DNA was analyzed for PDGFRα exon 18 and APC mutations by allelic discrimination PCR. Results:26 patients with desmoid tumors have been enrolled with 22 currently evaluable. Two and four month progression-free survival rates of patients are 91% (20/22) and 78% (14/18), respectively. We have found polymorphisms/mutations of PDGFRα exon 18.Conclusions: Imatinib appears to be a promising agent in the management of unresectable or difficult to resect desmoid tumors. We postulate that responsiveness is a function of alteration of that gene or other downstream effectors. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
FGFR3 Associates with and Tyrosine-Phosphorylates p90RSK2, Leading to RSK2 Activation That Mediates Hematopoietic Transformation
Authors: Sumin Kang, Shannon Elf, Shaozhong Dong, Taro Hitosugi, Ailan Guo, Hong Ruan, Sagar Lonial, Hanna Khoury, Ifor Williams, Gerard Karsenty, André Hanauer, Ting-Lei Gu, Jing Chen
Journal: Blood (2008)
Elevated serum levels of Sialyl Lewis X (sLeX) and inflammatory cytokines in patients with nonmetastatic breast cancer.
Authors: J. M. Reuben, B. Arun, B. Lee, M. Galland, E. N. Cohen, S. Tin, M. Nadeem, K. Tang, M. T. Yang, A. M. Gutierrez-Barrera, I. Kiyokawa, T. Miura, V. Valero, N. T. Ueno, M. Cristofanilli
Journal: Journal of Clinical Oncology (2011)

e11061 Background: Sialyl Lewis X (sLeX), a carbohydrate antigen on tumor cells and ligand for E-selectin, mediates tethering and rolling along vascular endothelium. sLeX on tumor cells is purported to correlate with metastasis and poor prognosis. Inflammatory cytokines promote tumorigenesis and modulate metastasis. We assessed serum levels of sLeX and cytokines in patients (pts) with ductal carcinoma in situ (DCIS/stage 0), early invasive breast cancer (EBC/stages I/IIA) and locally advanced breast cancer (LABC/stages IIB/IIIA-C). Methods: Sera from 183 pts [26 DCIS, 83 EBC, 74 LABC including 23 pts with inflammatory breast cancer (IBC)] and 43 healthy donors (HD) were assessed for sLeX by CSLEX immunoassay (Nittobo Medical, Japan) and cytokines by Milliplex kits (Millipore Corp, Billerica, MA). The Kruskal-Wallis and Mann-Whitney tests determined differences in cytokine levels between patient groups and healthy donors (HD). Spearman’s Rank Correlation test determined relationship between sLeX and cytokines. Results: Compared with the sLeX level of HD (1.57 U/mL), those of DCIS (2.305 U/mL), EBC (2.830 U/mL), or LABC (3.300 U/mL) are significantly higher (all P < 0.05). sLeX levels increased with stage of disease (DCIS < EBC < LABC), and LABC is more likely than EBC to have a sLeX level above the mean ± 2SD of HD (χ2=4.8, P=0.03). IBC and non-IBC had similar sLeX levels. DCIS, EBC, or LABC pts have significantly higher median levels of cytokines [interleukin (IL)-1β, IL-1RA, IL-2, IL-6, IL-8, and IL-10; all P values < 0.05] than HD; whereas EBC and LABC pts had similar median levels. Moreover, there were positive correlations between serum levels of sLeX and inflammatory cytokines IL-1RA, IL-2, IL-6, and IL-8. Conclusions: Serum sLeX levels increase from premalignant conditions to invasive disease and appears to increase with stage of disease suggesting a potential role as a tumor marker with application for early detection. Moreover, our preliminary data support a role for inflammatory cytokines in upregulating serum sLeX to promote tumor progression. Additional analyses will be performed to determine the prognostic value of serum sLeX and the role of inflammatory cytokines in primary breast cancer.
Patterns of Management and Adherence to Venous Thromboembolism (VTE) Treatment Guidelines In a National Prospective Cohort Study of VTE Management In the Canadian Outpatient Setting: Recovery Study
Authors: Susan R Kahn, Sam Schulman, Josée Martineau, John A Stewart, Anne McLeod, Carla Strulovitch, Mark Blostein, Jacques-Philippe Faucher, Greg Gamble, Wendy Gordon, Peter K. Kagoma, Marie-José Miron, David Laverdière, Melaku Game, Allan Mills
Journal: Blood (2010)
Authors' reply: New metrics to monitor progress towards global HIV targets: using the estimated number of undiagnosed HIV-infected individuals as denominator
Authors: Anastasia Pharris, Chantal Quinten, Teymur Noori, Andrew J Amato-Gauci, Ard van Sighem
Journal: Eurosurveillance (2016)

Preview this article: Authors' reply: New metrics to monitor progress towards global HIV targets: using the estimated number of undiagnosed HIV-infected individuals as denominator, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/21/50/eurosurv-21-30428-6-1.gif
Therapy Related Myelodysplastic Syndrome and Acute Myeloid Leukaemia (tMDS/tAML) in Patients Treated with Purine Analogues (PA) for Lymphoproliferative Disorders (LPD); An Association with Alkylator Combination, Dose and Previous Alkylator Therapy.
Authors: Pallavi Kalkur, Stella J Bowcock, Anand Sharma, Evangelia Dimitriadou, Ghulam J Mufti, Saad M.B. Rassam
Journal: Blood (2009)
Abstract 17371: Benefits and Risks of Catheter Ablation of Atrial Fibrillation in Elderly Patients (75 Years or Older)
Authors: Koonlawee Nademanee, Montawatt Amnueypol, Francis Lee, Mark Schwab
Journal: Circulation (2011)

Published reports of atrial fibrillation (AF) treatment by catheter ablation (CA) included typically relatively young healthy individuals, but long-term outcomes of CA in elderly patients (PTs) remain unclear. We thus carried out the following study aiming to determine: 1) Safety and efficacy of CA in elderly PTs in maintaining sinus rhythm; 2) Risks of discontinuation of anti-coagulation in patients who remained in sinus rhythm (SR) after the ablation. Methods: We evaluated 302 elderly AF PTs (&gt; 75 years old); 246 PTs (mean age = 80) underwent CA guided by complex fractionated atrial electrogram (CFAE); 85 were paroxysmal AF, 46 persistent AF and 115 long-lasting AF. The remaining 56 patients (mean age = 79) declined the procedure. The clinical end points were SR, stroke, death and major bleeding. Warfarin was discontinued if sinus rhythm was maintained or AF burden &lt; 5% with no AF episodes was &gt; 12 hours. Results: After a mean follow-up of 3 + 6 years including multiple ablations, 196 Patients (79 %) remained in SR. The annual death rate was 4% vs. 10% in PTs who stayed in SR vs. those remained in AF after ablations respectively (p &lt; 0.001); interestingly, the annual death rate was also at 11% in patients who declined ablation. We were able to discontinue warfarin in 164 patients (70%) who had a stroke rate only 1.08 per 100 person -year compared to 2.62 per 100 person-year in patients who continued to have AF and stayed on coumadin (p &lt;0.01). Patients with CHADS score &gt; 2, who stayed in SR and stopped warfarin, had a stroke rate of 2 per 100 person-year compared to 0.98 for those with CHADS score 1. Major complications were groin bleeding (n= 9 [4%]), 2 patients had stroke (1 intracranial hemorrhage leading to death at home) and 2 patients had hemopericardium. Conclusions: Our data suggest that elderly PTs with AF benefit from AF substrate ablation which is safe and effective in maintain SR. Warfarin could be safely discontinued after SR is maintained post ablation. Our data suggest that SR after CA is associated with lower mortality and stroke risks.
A Nonselective Cation Permeabilization Pathway (Pcat) of Human Red Blood Cells (RBCs) Activated by Ca2+ and by Isotonic Dehydration.
Authors: Robert M. Bookchin, Teresa Tiffert, Adaeze Muoma, Lynn Macdonald, Zipora Etzion, Virgilio L. Lew
Journal: Blood (2004)
Inequalities in access to biological treatments for psoriasis: results from the Italian Psocare registry
Authors: L. Naldi, S. Cazzaniga, M. Di Mercurio, E. Grossi, A. Addis
Journal: British Journal of Dermatology (2016)

Limited evidence is available on the impact of socioeconomic factors on drug prescriptions for psoriasis. To investigate factors influencing prescription of conventional vs. biological treatment for patients with psoriasis, based on the Italian Psocare registry, with a special focus on socioeconomic factors. This was a cross‐sectional study evaluating the baseline data of patients included in the Psocare registry. All of the consecutive adult patients with a diagnosis of chronic plaque psoriasis or psoriatic arthritis who were prescribed a systemic treatment for psoriasis at participating centres were included in this study. Univariate and multivariate analyses of the baseline factors associated with a biologics prescription were performed. From September 2005 to September 2009, 12 838 patients were identified. A multivariate analysis revealed that, among other factors, completing a level of education higher than lower secondary school and being employed as a manager or a professional were independent factors associated with a biologics prescription at entry in the registry. Additional analyses on the association between these two variables and a severe psoriasis condition [Psoriasis Area Severity Index (PASI) score > 20] revealed a significantly increasing trend of severe disease towards lower educational attainment, while unemployed patients were more likely to have a more severe condition compared with the other categories of workers. We documented inequalities of drug prescriptions for psoriasis in Italy, with a trend towards a higher frequency of prescription for more expensive biologics in higher socioeconomic sectors of the population.
Abstract 2615: Dual ErbB blockade with KTN3379 and cetuximab yields enhanced antitumor activity by inhibiting parallel signaling pathways in SCCHN
Authors: Diego Alvarado, Scott B. Seibel, Gwenda F. Ligon, Jay S. Lillquist, Andrew Pierce, Richard Gedrich, Theresa M. LaVallee
Journal: Cancer Research (2015)

Abstract The receptor tyrosine kinase ErbB3/HER3 has been implicated as an oncogenic driver in pre-clinical models of solid tumors, and is the target of several monoclonal antibodies currently in clinical development. In squamous cell carcinoma of the head and neck (SCCHN), ErbB3 activation is regulated by its ligand neuregulin (NRG). Studies, including our own, have reported high NRG expression in a significant subset of SCCHN, providing a scientific rationale for the use of ErbB3 targeted therapies in this disease setting. Here we show that KTN3379, a potent human ErbB3 monoclonal antibody with a dual mechanism of action, demonstrates significant monotherapy activity in NRG expressing xenograft models of SCCHN and enhances cetuximab anti-tumor activity. Using a panel of SCCHN cell lines, we demonstrate that KTN3379 inhibits PI3K/AKT signaling whereas cetuximab chiefly suppresses the ERK pathway, providing an explanation for the increased anti-tumor activity of combining both drugs. Our data also suggest that ErbB3 and EGFR act independently of one another at the receptor level. Interestingly, mRNA analysis of 303 SCCHN human tumor samples shows a strong correlation between NRG expression and the EGFR ligands Amphiregulin (AREG) and TGFα. Moreover, KTN3379 activity correlates with expression of ErbB3, its ligand NRG, and both of these EGFR ligands. Overall, our data support evaluation of the combination of KTN3379 and cetuximab in SCCHN. Citation Format: Diego Alvarado, Scott B. Seibel, Gwenda F. Ligon, Jay S. Lillquist, Andrew Pierce, Richard Gedrich, Theresa M. LaVallee. Dual ErbB blockade with KTN3379 and cetuximab yields enhanced antitumor activity by inhibiting parallel signaling pathways in SCCHN. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2615. doi:10.1158/1538-7445.AM2015-2615
364. Neurological Correction of Mucopolysaccharidosis IIIB Mice by Haematopoietic Stem Cell Gene Therapy
Authors: Stuart M. Ellison, Rebecca Holley, Daniel Fil, John Mc Dermott, Nisha Senthivel, Alex Langford-Smith, Fiona Wilkinson, Simon Jones, Rob Wynn, Shih-hsin Kan, Patti Dickson, Brian Bigger
Journal: Molecular Therapy (2016)

Mucopolysaccharidosis Type IIIB (MPSIIIB) is a paediatric, autosomal recessive Lysosomal Storage Disease (LSD) caused by deficiency of α-N-acetylglucosaminidase (NAGLU), an enzyme in the heparan sulfate (HS) degradation pathway. Absence of NAGLU leads to the accumulation of partially degraded HS glycosaminoglycan in cell lysosomes, giving rise to cellular dysfunction with devastating clinical consequences. Individuals affected by this fatal disease exhibit severe central nervous system degeneration with progressive cognitive impairment and behavioural problems, alongside more attenuated somatic symptoms. There are currently no effective treatments available. Enzyme replacement therapy with recombinant NAGLU enzyme is ineffective for MPSIIIB since enzyme cannot cross the blood brain barrier (BBB) to where it is needed. Modified recombinant NAGLU enzymes that utilise the insulin growth factor II (IGFII) peptide to facilitate improved uptake across the BBB are currently in development. Haematopoietic stem cell gene therapy (HSCGT) is a promising therapeutic strategy that can circumvent the BBB via monocyte trafficking and engraftment in the brain, allowing delivery of enzyme by cross correction. We have developed a novel stem cell gene therapy approach to investigate the therapeutic potential of HSCGT for MPSIIIB. We designed two lentiviral vectors expressing therapeutic enzyme; the first vector expressing codon optimised NAGLU, and the second expressing a NAGLU.IGFII fusion to aid cellular uptake, both driven by the myeloid specific promoter CD11b and compared these in autologous MPSIIIB transplants against a normal WT bone marrow transplant. Here we present for the first time neurological correction of MPSIIIB mice by HSCGT. We observed correction of the MPSIIIB behavioural phenotype in treated mice to wild-type levels with normalisation of path length, average speed, frequency entering the centre and duration of speed >100mm/s in open field tests. In addition, we observed a significant correction of astrogliosis and lysosomal compartment size in the brains of CD11b. NAGLU LV treated mice with an accompanied normalisation of inflammatory cytokines TNFα, IL1B and IL1RN. Furthermore, NAGLU enzyme activity was substantially increased in the brain. Interestingly, WT transplant alone was able to mediate a partial brain correction, although levels of inflammation and lysosomal storage remain high.
Abstract 5463: Role of the endothelin axis in astrocyte and endothelial cell mediated chemoprotection of cancer cells
Authors: Mark S. Kim, Hyun Jin Choi, Ho-Jeong Lee, Junqin He, Qiuyu We, Robert R. Langley, Sin-Jin Kim, Isaiah J. Fidler
Journal: Cancer Research (2015)

Abstract Background. Recent evidence suggests that astrocytes protect cancer cells from chemotherapy by stimulating the upregulation of anti-apoptotic genes in cancer cells. We investigated the possibility that activation of the endothelin axis orchestrates survival gene expression and chemoprotection in MDA-MB-231 breast cancer cells and H226 lung cancer cells. Methods. Cancer cells, murine astrocytes, and murine fibroblasts were cultured in isolation and expression of endothelin (ET) peptides and ET receptors (ETAR and ETBR) was compared with expression on cancer cells and astrocytes (or cancer cells and fibroblasts) that were co-incubated for 48 hours. Type-specific endothelin receptor antagonists were used to evaluate the contribution of ETAR and ETBR to astrocyte-induced activation of the protein kinase B (AKT)/mitogen-activated protein kinase (MAPK) signal transduction pathways, anti-apoptotic gene expression, and chemoprotection of cancer cells. We also investigated the chemoprotective potential of brain endothelial cells and microglial cells. Results. Gap junction signaling between astrocytes and MDA-MB-231 cancer cells stimulates upregulation of interleukin 6 (IL-6) and IL-8 expression in cancer cells, which increases ET-1 production from astrocytes and ET receptor expression on cancer cells. ET-1 signals for activation of AKT/MAPK and upregulation of survival proteins that protect cancer cells from taxol. Brain endothelial cell-mediated chemoprotection of cancer cells also involves endothelin signaling. Dual antagonism of ETAR and ETBR is required to abolish astrocyte- and endothelial cell-mediated chemoprotection. Conclusions. Bidirectional signaling between astrocytes and cancer cells involves upregulation and activation of the endothelin axis, which protects cancer cells from cytotoxicity induced by chemotherapeutic drugs. Citation Format: Mark S. Kim, Hyun Jin Choi, Ho-Jeong Lee, Junqin He, Qiuyu We, Robert R. Langley, Sin-Jin Kim, Isaiah J. Fidler. Role of the endothelin axis in astrocyte and endothelial cell mediated chemoprotection of cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5463. doi:10.1158/1538-7445.AM2015-5463
Results of a Phase 2 Trial of HGS-ETR1 (Agonistic Human Monoclonal Antibody to TRAIL Receptor 1) in Subjects with Relapsed/Refractory Non-Hodgkin’s Lymphoma (NHL).
Authors: Anas Younes, Julie M. Vose, Andrew D. Zelenetz, Mitchell R. Smith, Howard Burris, Stephen Ansell, Jerry Klein, Elizabeth Kumm, Myron Czuczman
Journal: Blood (2005)