tbuckley/cabot-search huggingface dataset:
Abstract 1391: Breast cancer cells and the bone: A tale of treachery
Authors: Shamik Das, J. Allan Tucker, Shikha Khullar, Rajeev S. Samant, Lalita A. Shevde
Journal: Cancer Research (2012)

Abstract Under normal physiological conditions there is a dynamic equilibrium in the bone maintained by the bone forming osteoblasts and bone resorbing osteoclasts. The bone stroma provides hospitable sites for disseminating, colonization-competent breast cancer cells. The Hedgehog (Hh) pathway plays an important role in skeletogenesis. Our studies have determined that breast tumor cells have an activated Hh pathway characterized by upregulation of Hh ligands and the transcription factor GLI1. Our findings show that breast cancer cells activate Hh signaling in pre-osteoclasts and thereby upregulate osteoclastogenesis. Paracrine Hh signaling induced in osteoclasts by breast cancer cells mediates a series of events by the up-regulation of osteopontin (OPN), which in turn enhances osteoclastic activity by up-regulating the essential proteases cathepsin K and MMP9. Surprisingly, we found that breast cancer cells also activate osteoblast differentiation as an early event, by activating Hh signaling in pre-osteoblasts. This leads to the expression of RANKL and PTHrP by the osteoblasts. RANKL and PTHrP promote osteoclastogenesis while the osteoblasts are eliminated by apoptosis. Pharmacological inhibition of Hh signaling results in an overall decrease in osteoblast differentiation and osteoclastogenesis/resorptive activity. Thus our studies suggest that the breast cancer cells orchestrate a chain of events in which they directly foster osteoclastogenesis and deceptively induce osteoblasts to differentiate which in turn produce factors that promote osteoclast differentiation. A vicious cycle ensues and in the presence of increased number of metastasing breast cancer cells the balance now shifts in favor of the osteoclasts resulting in osteolysis, the final painful outcome of a majority of breast cancer patients. Thus in the light of our findings, any therapeutic approach utilizing inhibitors for the Hh pathway need to take into consideration the dual role of the pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1391. doi:1538-7445.AM2012-1391
The Threat of Infectious Diseases in Somalia
Authors: D. Gray Heppner, Alan J. Magill, Robert A. Gasser, Charles N. Oster
Journal: New England Journal of Medicine (1993)

The Four Horsemen of the Apocalypse -- War, Famine, Pestilence, and Death -- ride the arid plains of Somalia. Despite the protection offered by modern chemoprophylaxis, immunization, and preventive medicine, military personnel safeguarding food delivery in Operation Restore Hope are threatened by exotic infectious diseases rarely seen by U.S. physicians. Some require prompt treatment to prevent death (Table 1). Many other infections acquired in Somalia will appear soon after exposure, some will become evident after the troops return home, and others will remain latent unless host immunity is compromised. Physicians caring for Somalis, particularly displaced persons in refugee camps, are . . .
ED-19 * INCIDENCE AND PATTERN OF SECONDARY GLIOBLASTOMA MULTIFORME AT A TERTIARY CARE HOSPITAL IN PAKISTAN
Authors: S. Malik, S. Pervaiz, K. Khan, A. A. Jabbar
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma multiforme (GBM) continues to be one of the most common and aggressive form of primary malignancy of brain. Ninty percent of GBM develop de novo, however a minority of them progress from low grade gliomas. No data is currently available from our region to report the incidence of secondary GBM. Aim of this study was to evaluate the incidence and pattern of secondary GBM at a tertiary care hospital in Karachi, Pakistan. METHOD: Retrospective data was retrieved using hospital based cancer registry at Aga Khan University Hospital from 2009-2011. A total of 158 patients with low and high grade gliomas were identified and data was acquired for date of first diagnosis, age, site of tumor, and time of progression. RESULT: A total of 44 patients out of 158 reviewed were diagnosed as GBM. Of these 3 (6.8%) were found to be secondary GBM with initial diagnosis of gemistocytic astrocytoma (n = 1), and oligodendroglioma, grade II (n = 2). Mean age at progression was 43 years. The site of tumors were frontal (n = 1) and fronto-parietal (n = 2). Mean time to progression was found to be approximately 4 years. CONCLUSION: The incidence and pattern of secondary GBM from our region was comparable to the reported data available in literature. This is the first study providing this information from our region.
Abstract P1-15-03: Comparison of efficacy of primary prophylaxis with pegfilgrastim, filgrastrim and a biosimilar filgrastim in TAC regimen (docetaxel, doxorubicin and cyclophosphamide)
Authors: M Brito, S Esteves, R Andre, M Isidoro, A Moreira
Journal: Cancer Research (2012)

Abstract Background: Febrile neutropenia (FN) is a major toxicity of myelosupressive chemotherapy. Primary prophylactic use of granulocyte colony stimulating factors (G-CSF) is recommended in high risk FN regimens. The comparison of pegfilgrastim (Peg) and filgrastim (Fil) FN prophylactic effectiveness is still an issue of debate. Very recently Nivestim (Niv), a new biosimilar filgrastim, has also become commercially available. We aimed to compare the efficacy of the 3 mentioned types of G-CSF in the primary prophylaxis of FN. Methods: Single-center, retrospective study to evaluate the incidence of FN in women with breast cancer treated with adjuvant or neo-adjuvant TAC (FN risk ≥20%). Patients (Pt) were divided in 3 consecutive cohorts according to G-CSF primary prophylaxis (Fil, Peg and Niv) FN was defined as axillary temperature ≥38,3 °C and absolute neutrophil count &amp;lt; 500/ul. Results: We included a total of 421 women (median age 51 y, 25–76) with Stage II (56%) and Stage III (44%) breast cancer. Age and stage distribution were similar in the 3 cohorts. A single dose of Peg was administered in all 767 cycles (cy). The standard dose of Fil and Niv was 7 daily injections, only in in 13% Fil pt and 10% Niv pt &amp;lt; 7 administrations were done. The incidence of FN per patient and per cycle is presented in Table 1. In all cohorts, approximately half of NF episodes occurred in the 1st cycle (48% Fil, 59% Peg, 42% Niv). Conclusions: No differences in terms of efficacy existed between Biosimilar Niv and original biological reference Fil. Seven daily injections of Fil and Niv seem equivalent to single dose Peg. Besides efficacy, questions like cost-effectiveness and convenience of administration should be taken into account when approaching this topic. Our data showed a predominance of events in the 1st cycle (regardless of the type of G-CSF). This has been consistently described in the literature and may support the necessity to recommend other NF preventive measures in this cycle. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-03.
P1141 SUSTAINED VIROLOGICAL RESPONSE (SVR) IN HCV TREATMENT-EXPERIENCED PATIENTS AFTER TRIPLE THERAPY WITH BOCEPREVIR (BOC) PLUS PEGINTERFERON ALFA-2a/RIBAVIRIN IN A REAL-LIFE SETTING
Authors: K.H.W. Boeker, R. Link, A. Baumgarten, A. Stoehr, R. Heyne, M. Roessle, E. Schott, R. Ullrich, P. Erren, C. Herold, W. Schmidt, K.-G. Simon, M. Geissler, W. Schiffelholz, U. Alshuth, D. Hueppe, S. Mauss
Journal: Journal of Hepatology (2014)
Abstract 4073: Proteasomal degradation of JunD is required for TGF-β induced inhibition of proliferation in prostate cancer cells.
Authors: Ana C. Millena, BaoHan T. Vo, Nicole Strong, Lindsey Walker, Yang Cao, Natalya Klueva, Curt Pfarr, Shafiq Khan
Journal: Cancer Research (2013)

Abstract Transforming growth factor-β (TGF-β) inhibits proliferation of prostate epithelial cells. However, prostate cancer cells in advanced stages become resistant to TGF-β effects on proliferation. In this study, we have investigated the role of AP-1 family of transcription factors, specifically the Jun family members (c-Jun, JunB and JunD) in TGF-β1 effects on prostate cancer cell proliferation. Basal expression of individual Jun family members was determined by RT-PCR and Western blot analysis in four prostate cell lines: RWPE1, LNCaP, DU145 and PC3 cells. Jun levels were also examined in response to TGF-β1. c-Jun was expressed in all cell lines and its expression was up-regulated by TGF-β1. Levels of JunB were higher in normal cells compared to those in cancer cells and TGF-β1caused an increase in JunB levels. JunD levels were higher in all cell lines; TGF-β1 had differential effects on JunD protein levels. While it caused a significant decrease in JunD levels in RWPE-1 and DU145 cells, it did not affect JunD levels in PC3 cells. These differential effects on JunD levels correlated with differential effects of TGF-β on cell proliferation. Individual Jun family members were overexpressed in DU145 cells and effects on cell proliferation were determined. Over-expression of c-Jun and JunB decreased proliferation rate in DU145 cells; however, overexpression of JunD increased proliferation in these cells. Interestingly, cells over-expressing JunD still succumb to inhibitory effect of TGF-β1 after six to eight days of incubation. Furthermore, silencing JunD by siRNA decreased proliferation in both DU145 and PC3 cells. To determine the molecular mechanism of TGF-β-induced down-regulation of JunD, we pretreated cells over-expressing JunD with a proteosomal inhibitor, MG132. Pretreatment of MG132 blocked the degradation of JunD in in DU145 cells over-expressing JunD. In conclusion, our studies show that specific Jun family exerts differential effects on proliferation in prostate cancer cells in response to TGF-β1. While c-Jun and Jun B mediate the inhibitory effects of TGF-β1 on proliferation, JunD counteracts these effects. TGF-β1 causes inhibition in proliferation by degrading JunD via proteasomal degradation. Acknowledgements: These studies were supported by the NIH/NIMHD/RCMI grant #G12MD007590, NIH/NIMHD #5P20MD002285, and DOD grant # W8I-08-1-0077. Citation Format: Ana C. Millena, BaoHan T. Vo, Nicole Strong, Lindsey Walker, Yang Cao, Natalya Klueva, Curt Pfarr, Shafiq Khan. Proteasomal degradation of JunD is required for TGF-β induced inhibition of proliferation in prostate cancer 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 4073. doi:10.1158/1538-7445.AM2013-4073
LARGE INCREMENTAL CHANGES IN PUMP SPEED ARE REQUIRED IN ORDER TO SEE MEANINGFUL CHANGES IN INVASIVELY MEASURED HEMODYNAMICS IN PATIENTS WITH HEARTMATE II CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICES (CF-LVADS)
Authors: Carrie Eshelbrenner, Andrea Cordero-Reyes, Arvind Bhimaraj, Barry Trachtenberg, Guha Ashrith, Matthias Loebe, Guillermo Torre-Amione, Jerry Estep
Journal: Journal of the American College of Cardiology (2015)
TRATAMIENTO ENDOSCÓPICO DE LA HEMORRAGIA DIGESTIVA POR VARICES GÁSTRICAS CON CIANOACRILATO. EXPERIENCIA EN UN HOSPITAL DE TERCER NIVEL
Authors: A Rincón, JM Alcívar, R León, T López, S Sobrino, JA Caballero, JM Bozada
Journal: Endoscopy (2014)

Introducción: La hemorragia por varices gástricas (HVG) esta asociada a una morbimortalidad significativa y a un abordaje endoscópico limitado. Los tratamientos que han demostrado eficacia óptima es la inyección de adhesivos intravariceales como el 2-octil-cianoacrilato (CA).
AB0194 Scottish early rheumatoid arthritis (sera) at nhs highland - a multi centre scottish project aiming to establish a clinical database and biorepository of newly diagnosed undifferentiated arthritis (ua) and rheumatoid arthritis (ra) patients
Authors: S. Ross
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Depression and anxiety can be prevalent in newly diagnosed UA &amp; RA patients and can be related to either environmental, social or for health reasons. The SERA study has enabled an in depth investigation of 31 patients with RA/UA to find out whether symptoms of depression and anxiety are alleviated with a reduction in disease progression as illustrated by disease activity score (DAS28). It also considers how other factors such as body mass index (BMI), HAQ, smoking, age and sex may have an influence on the above <h3>Objectives</h3> To determine the relationship between anxiety, depression and DAS28 To determine the relationship between anxiety, depression, DAS28 and other influencing factors. (Influencing factors used were sex of patient, age of patient, body mass index (BMI) and smoking status at baseline) <h3>Methods</h3> Newly diagnosed UA and RA patients were asked to complete a Hospital Anxiety &amp; Depression (HAD) questionnaire and a Health Analysis Questionnaire (HAQ) at their baseline visit. They were then asked to do the same questionnaires at six months. All data was then entered on to the e-crf. <h3>Results</h3> Trend analysis of the data appears to suggest a definite link between anxiety, depression and DAS improvement. The poster will discuss this matter and the other variables that play in specific detail. <h3>Conclusions</h3> There may be a positive relationship between an improvement of a patietns DAS score and an improvement in their anxiety and depression status <h3>Acknowledgements</h3> With kind permission from Chief Investigator of SERA study Dr D. Porter, Consultant Rheumatologist <h3>Disclosure of Interest</h3> None Declared
[The Importance of Protocol Design and Data Reporting to Research on Endocrine Disruption]: Response
Authors: Wade V. Welshons, Susan C. Nagel, Frederick S. vom Saal
Journal: Environmental Health Perspectives (1998)

our experimentation could eventually be used to discredit our findings, should they happen not to agree with the original observations.It seems important that all experiments in the rapidly expanding area of endocrine disruption toxicology should be carefully designed and fully reported.The use of con- current positive and negative control groups also seems to be prudent.These needs are independent of who conducts or sponsors studies.Good science is good science.Finally, it should be noted that the only formal retrac- tion of endocrine disruption data currently encountered derived from an academic labo- ratory (15), a salutary counterbalance to the assertions that stimulated this letter (1-3).
Abstract P3-07-02: Time-trends in survival in young women with breast cancer in a SEER population-based study
Authors: FO Ademuyiwa, A Groman, C-C Hong, S Kumar, EG Levine, A Miller, CB Ambrosone
Journal: Cancer Research (2012)

Abstract Background: As mammography is not generally recommended to women under 40, it is reasonable to conclude that documented outcome improvements over time are attributable to treatment advances with screening playing a less important role. In order to determine the contribution of screening and treatment to improvements, we evaluated the odds of presenting with more advanced disease by time-period and examined the time-trends in outcome in a population-based cohort ≤50. We evaluated whether any outcomes differentials existed by ER status. Methods: Patients in SEER diagnosed with breast cancer (BC) were divided into 4 by year of diagnosis (1990–1994, 1995–1999, 2000–2004, 2005–2008). Patients were also categorized into 2 age-groups: &amp;lt;40 and 40–50 years. Odds ratios for presenting with more advanced disease over the 4 time-periods were calculated for the 2 age-groups. Multivariate analysis was done to investigate the association of survival with time-period for the 2 age-groups by ER status. Results: 110,629 patient records were included. Multivariate adjusted hazard ratio for mortality in women aged 40–50 with ER positive BC declined over time. Comparing all time periods to 1990–1994, the HR for mortality in 1995–1999 was 0.83 (0.77–0.89), 0.61 (0.57–0.65) in 2000–2004, and 0.35 (0.30–0.40) in 2005–2008 (p &amp;lt;.001). Those &amp;lt;40 years with ER positive BC also had mortality improvements over time (HR 0.86, 0.63, 0.26 for 1995–1999, 2000–2004, and 2005–2008 respectively). On the contrary, no mortality improvements were seen in women with ER negative disease. Trends in progressively worsening mortality over time were observed in this cohort. A 1.3-fold increase in the odds of presenting with stage I BC was seen in women 40–50 years comparing the 3 latter time periods with 1990–1994. Similarly, in the same age group, there was a 2.12-fold likelihood of presenting with a tumor ≤1cm in 2005–2008 versus 1990–1994. In women &amp;lt;40 years at diagnosis, the probability of presenting with stage I disease was lower in the 3 latter time periods than in 1990–1994; and a 2.84-fold higher probability of presenting with stage III/IV disease was seen in 2005–2008 compared with 1990–1994. Conclusions: Patients who are ER positive and between 40–50 years have had time-trend changes with improvements in breast cancer outcome and smaller tumors likely attributable to both screening and hormonal therapies. Patients who are &amp;lt;40 years and/or ER negative have not had improvements in breast cancer outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-02.
OUTCOMES OF IMPELLA ASSISTED PERCUTANEOUS BALLOON AORTIC VALVULOPLASTY IN VERY HIGH RISK SEVERE AORTIC STENOSIS PATIENTS
Authors: Pradeep Yadav, Marvin Eng, George Divine, Dee Dee Wang, Heidar Arjomand-Fard, Janet Wyman, Michael Isley, Jamil Borgi, Gaetano Paone, Adam Greenbaum, William O’Neill
Journal: Journal of the American College of Cardiology (2016)
Hydroxyprolinemia* an Apparently Harmless Familial Metabolic Disorder
Authors: Risto Pelkonen, Kari I. Kivirikko
Journal: New England Journal of Medicine (1970)

In a family with hydroxyprolinemia the proposita was a 31-year-old woman whose disorder was characterized by the accumulation of large amounts of free hydroxyproline in the plasma, with overflow into the urine. Biochemical studies suggested that the accumulation of free hydroxyproline in the proposita, as in the only previously reported case, was due to deficiency of hydroxyproline oxidase, the enzyme that normally converts free hydroxyproline to Δ1-pyrroline-3-hydroxy-5-carboxylic acid. Unlike the previous patient, the proposita was not mentally retarded, and did not seem to have any clinical abnormality that could have been due to the metabolic defect. Studies on 20 relatives indicated that an apparently healthy 27-year-old brother of the proposita likewise had hydroxyprolinemia, and his two-year-old daughter had slightly elevated endogenous hydroxyproline values. The pedigree was consistent with autosomal recessive inheritance.
Abstract 2175: Src homology region 2 domain-containing phosphatase-1 is a major target of sorafenib in hepatocellular carcinoma.
Authors: Wei-Tien Tai, Chung-Wai Shiau, Pei-Jer Chen, Ann-Lii Cheng, Kuen-Feng Chen
Journal: Cancer Research (2013)

Abstract Sorafenib is the only clinical approved drug in hepatocellular carcinoma (HCC). Previously, we have investigated that Signal transducer and activator of transcription 3 (STAT3) is a kinase-independent target of sorafenib (Journal of Hepatology, 2012). Here, we report that sorafenib relieves the anto-inhibited Src homology region 2 domain-containing phosphatase-1 (SHP-1) to increase its phosphatase activity and inhibit p-STAT3-related signaling. Sorafenib increases SHP-1 activity either in HCC cell-based test or purified recombinant SHP-1 protein directly. Deletion of N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 abolished the effect of sorafenib on SHP-1 and phospho-STAT3 (p-STAT3) and apoptosis in HCC, suggesting that sorafenib may affect SHP-1 by switching the transformation from auto-inhibition to the active form. The significant correlation between inhibited SHP-1 and overexpression of p-STAT3 was demonstrated in immunohistochemistry of clinical HCC samples. Novel sorafenib derivatives, SC-43 and SC-40, showed more potent effects than sorafenib on enhancing the activity of SHP-1 activity, inhibiting p-STAT3, induction apoptosis and overcoming sorafenib resistance in HCC. SC-43 showed better survival benefits than sorafenib in orthotopic HCC tumors. SHP-1 represents a major target of sorafenib in HCC. Sorafenib derivatives (SC-43 and SC-40) show better anti-HCC effects than sorafenib by targeting SHP-1. Further clinical investigations may be warranted. Citation Format: Wei-Tien Tai, Chung-Wai Shiau, Pei-Jer Chen, Ann-Lii Cheng, Kuen-Feng Chen. Src homology region 2 domain-containing phosphatase-1 is a major target of sorafenib in hepatocellular carcinoma. [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 2175. doi:10.1158/1538-7445.AM2013-2175
Abstract 5020: Genetic and epigenetic analysis of tumors in a zebrafish model of melanoma
Authors: Angelo Casa, Caitlin Bourque, Yael Zack, Yariv Houvras
Journal: Cancer Research (2012)

Abstract The activating BRAF kinase mutation V600E occurs in ∼60% of human nevi and melanomas. A transgenic strain of zebrafish expressing BRAF-V600E under the control of the mitfa promoter on a p53 mutant background develops melanomas with 100% penetrance. Previously, we showed that a transposon-based vector, MiniCoopR, allows us to program melanocytes to express a candidate gene in a specialized zebrafish strain Tg(mitfa:BRAFV600E); mitfa-/-; p53-/-. This strain lacks melanocytes, but the lineage can be rescued by MiniCoopR injection at the 1-cell stage. This genetic system allows us to create cohorts of transgenic animals that express candidate genes and assay the effects on tumor development. Previous work identified two histone methyltransferases (HMTs), SETDB1 and SUV39H1, which cooperate with BRAF-V600E to accelerate the onset and severity of melanoma development. A number of HMTs display alterations in expression level or copy number in human cancers compared to normal tissues, and we tested a panel of methyltransferases using the MiniCoopR system. We hypothesize that HMTs promote tumorigenesis by altering the epigenetic program of melanocytes. In order to explore the effects on melanocyte specification and differentiation, we overexpressed and depleted candidate HMTs in zebrafish embryos and performed in situ hybridization for lineage-specific markers, such as crestin, sox10, mitfa, dct, and tyr. HMTs that exert specific developmental phenotypes were further characterized by performing chromatin immunoprecipitation (ChIP). Our goal is to correlate the processes affected in the developing embryo with the epigenetic program to elucidate the mechanism by which HMTs influence tumorigenesis. Additionally, we are developing a strain of zebrafish Tg(mitfa:BRAFV600E); mitfa-/-; alb-/-; p53-/-; Tg(mitfa:GFP) in which melanocytes rescued with MiniCoopR express GFP. These rescued melanocytes can be programmed to express candidate HMTs and allow us to visualize melanocyte and melanoma development in vivo. The work presented here will help correlate cancer phenotypes with specific chromatin-modifying enzymes that may be the basis for new drug development and biomarker discovery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5020. doi:1538-7445.AM2012-5020