tbuckley/cabot-search huggingface dataset:
Abstract 507: Nitrogen oxides-derived immunotherapy: Revealing cryptic melanoma-specific immune targets
Authors: Weidong Zhu, Ashley C. Eng, Samuel Y. Olson, Diana C. Márquez-Garbán, Hermes J. Garbán
Journal: Cancer Research (2012)

Abstract Nitrogen oxides (NOx) can exert their relevant biological functions through two reversible molecular modifications: a) direct interaction with metals (nitrosation), and b) by interacting with thiols (s-nitrosylation); or irreversible modifications of aromatic amino acid residues such as tyrosine or phenylalanine (nitration). Any of these modifications have been demonstrated to affect the biological fate of the modified molecule or alter their functions. We have previously shown that these NOx-derived changes will trigger a myriad of modifications at the genetic, epigenetic and post-translational level in tumor cells resulting in a robust and effective therapeutic immune response against cancer cells. However, the molecular mechanisms and immune-related tumor targets remain elusive. Thus, we hypothesize that NOx-derived protein modifications (i.e., Tyrosine nitration) will differentially prime the immune system with otherwise subdominant antigens (cryptic) making them immune visible and triggering an effective anti-tumor immune response. We have tested this hypothesis using the well-characterized B16-C57BL/6 syngeneic and poorly immunogenic melanoma mouse model. NOx-modified and non-modified B16-F0 melanoma cell lysates were used to immunize naïve C57BL/6. Post-immunized sera was screened against SDS-PAGE resolved untreated B16-F0 lysates and human protein library micro array for differential recognition of immune cross-reactive of novel mouse and human melanoma targets by the mouse IgG fraction. Our results demonstrated the highly significant (p &amp;lt;0.0001) IgG-associated immune recognition of five cross-reactive novel melanoma targets (in relative affinity decreasing order): 1) Golgi reassembly stacking protein 1 (GORASP1), 2) ArfGAP w/GTPase domain-ankyrin repeat and PH domain 1 (AGAP1), 3) Microtubule-associated protein tau (MAPT), 4) Mitochondrial ribosomal protein L46 (MRPL46), and 5) Protocadherin beta 6 (PCDHB6). Currently, we are evaluating the significance and functional activity of the identified targets and their isolated/purified specific immune effector (IgG) counterparts. In addition, we are characterizing the potential molecular and immunological mechanisms that might lead to the use of these novel melanoma-specific immune targets as diagnostic/prognostic and/or immunotherapeutic tools. 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 507. doi:1538-7445.AM2012-507
Preexposure Prophylaxis for HIV Prevention — Polling Results
Authors: James A. Colbert
Journal: New England Journal of Medicine (2012)

In early August, we presented two cases involving persons who were potential candidates for preexposure prophylaxis (PrEP) for HIV in Clinical Decisions,1 an interactive feature designed to assess how readers would manage a clinical problem for which there may be more than one appropriate approach to the care of the patients. The two cases involved a 46-year-old man from New York City who has sex with multiple male partners and an 18-year-old, single, heterosexual woman from South Africa who has recently become sexually active. Two experts in the prevention of HIV infection presented arguments, one in favor of the use . . .
Abstract IA14: Reprogramming cell fate by mimicking natural mechanisms
Authors: Helen M. Blau
Journal: Cancer Research (2011)

Abstract We are exploiting natural mechanisms to derive mammalian cell sources for regenerative medicine: (1) by recapitulating pathways used by newts and zebrafish, (2) by mimicking biophysical cues to which adult stem cells are exposed in the body, (3) and by gaining insights into the mechanisms such as DNA demethylation by which adult cells are reprogrammed to pluripotency (iPS) in heterokaryons. These approaches provide fundamental mechanistic insights into stem cell fate determination, provide novel cell sources, and enable clinical applications of cell therapies for regenerative medicine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA14.
Dilatation instrumentale de la sténose oesophagienne au cours du syndrome de Plummer-Vinson: à propos de 38 cas
Authors: N Oumnia, M Lahcene, A Tebaibia, MA Boudjella, B Touchene
Journal: Endoscopy (2012)

le syndrome de Plummer Vinson est une entité rare. Il est caractérisé par l'existence d'une membrane semi lunaire cervicale qui entraîne une dysphagie sévère. Ce syndrome s'accompagne d'une anémie ferriprive. Le but de ce travail est de déterminer les caractéristiques cliniques des patients et d'analyser les résultats thérapeutiques en particulier les résultats de la dilatation instrumentale.
SAT0319 Role of Spirometry in Survival Prediction in Scleroderma Related Pulmonary Arterial Hypertension
Authors: K.A. Keogh, G.C. Kane
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Pulmonary Hypertension (PH) in scleroderma may be induced by interstitial lung disease, myocardial involvement or pulmonary arterial hypertension (PAH). PAH, due to progressive pulmonary vascular remodeling is the number one cause of death in patients with scleroderma. In pulmonary function testing, a reduced diffusing capacity (DLCO) is well recognized as a strong risk predictor of mortality in PAH. Whether expiratory flow analysis with spirometry associates with outcome is unclear. <h3>Objectives</h3> The objective of this study was to assess spirometry as a predictor of mortality in patients with scleroderma associated pulmonary arterial hypertension. <h3>Methods</h3> A consecutive series of patients with newly diagnosed pulmonary arterial hypertension referred to single regional referral center was reviewed. Diagnosis was based on conventional Dana Point criteria for pulmonary arterial hypertension (group 1 PH) including right heart catheterization (excluding left heart disease) and the exclusion of clinical interstitial lung disease, including negative chest imaging. Stepwise inclusion exclusion modeling was performed with mortality assessed over 5 years. <h3>Results</h3> 440 patients with PAH (218 idiopathic (iPAH), 137 associated with connective tissue disease (cPAH, predominantly limited scleroderma), 39 with portal hypertension (PoPH) and 47 other (predominantly congenital systemic-pulmonary shunts). Forced Expiratory volumes in 1 second (FEV1) was lower in cPAH (72±18%) versus iPAH 78±16% or PoPH 77±20%; p&lt;0.001). A decline in FEV1 was associated with known markers of disease severity (elevated right atrial pressure, low cardiac index, reduced 6 minute walk distance). A decline in FEV1 was associated with worse survival in cPAH but not other forms of PAH. For every 10% decline in FEV1, 5-year all-cause mortality increased 1. 27 fold (95% C.I 1.07-1.49; p=0.008). The association of FEV1 with mortality persisted after adjusting for age, sex, DLCO, pulmonary pressure and cardiac output. <h3>Conclusions</h3> In scleroderma-related PAH, spirometry provides prognostic information over conventional parameters including pulmonary hemodynamics and diffusing capacity. Whether modest reductions in FEV1 may represent sub-clinical interstitial inflammation or fibrosis, pulmonary venous involvement or concomitant airway involvement warrants further testing. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5749
IMPS-44S100B INHIBITION WITH DULOXETINE, A SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITOR, ALTERS MACROPHAGE POLARIZATION AND ABROGATES GLIOMA GROWTH IN MICE
Authors: Hang Gao, yanyan Song, Ian zhang, Larry Zhang, Behnam Badie, Hui Zhou
Journal: Neuro-Oncology (2015)

S100B, a member of the multigene family of Ca2 + -binding proteins
Abstract 1971: Small C-terminal domain phosphatase 1 stabilizes PML to regulate the progression of renal clear cell carcinoma.
Authors: Yu-Ching Lin, Li-Ting Lu, Xin-Hua Feng, Ruey-Hwa Chen
Journal: Cancer Research (2013)

Abstract The promyelocytic leukemia (PML) protein elicits pleiotropic tumor suppressive functions and is aberrantly degraded in multiple types of human cancers through poorly understood mechanisms. Previous study in our laboratory revealed that CDK1/2-mediated phosphorylation of PML Ser518 is required for targeting PML to Pin1 for prolylisomerization and subsequently to KLHL20-containing ubiquitin ligase complex for ubiquitination and proteasomal degradation. To identify the negative regulators of this PML degradation pathway, we employed a functional genomic approach to search for phosphatases that act on PML Ser518. This study identifies the small C-terminal domain phosphatase 1/2/3 (SCP1/2/3) as PML Ser518 phosphatases. Because these three phosphatases are of structural and functional similarities, we focus on the prototype of this family, SCP1. We show that SCP1 interacts with PML and reduces PML Ser518 phosphorylation levels both in vivo and in vitro. Through this dephosphorylation, SCP1 decreases Pin1-KLHL20 mediated-PML polyubiquitination and prolongs PML half life. Consequently, SCP1 increases the number of PML-nuclear bodies and elevates PML protein abundance in both normoxia and hypoxia conditions. At functional levels, SCP1 overexpression enhances multiple tumor suppressive effects, including promotion of apoptosis and inhibition of cell proliferation and migration. Importantly, all of these effects are reversed by PML knockdown. Clinically, SCP1 expression is downregulated in renal clear cell carcinoma (RCC) and this downregulation correlates with PML downregulation. Restoration of SCP1-mediated PML stabilization inhibits RCC proliferation, migration and transformation. Together, our study identifies SCP1 as a positive regulator of PML by dephosphorylation of PML Ser518 to antagonize the Pin1/KLHL20-dependent PML degradation pathway. Blockage of SCP1/PML axis is manifested in RCC and contributes to RCC progression. Citation Format: Yu-Ching Lin, Li-Ting Lu, Xin-Hua Feng, Ruey-Hwa Chen. Small C-terminal domain phosphatase 1 stabilizes PML to regulate the progression of renal clear cell 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 1971. doi:10.1158/1538-7445.AM2013-1971
Abstract 4160: miR-34a as a radio sensitizer of triple negative breast cancer.
Authors: Anjana Bhardwaj, Nivetha Ganesan, David Molkentine, Uma Raju, Isabelle Bedrosian
Journal: Cancer Research (2013)

Abstract Introduction: Triple negative breast cancer (TNBC) is known to be relatively resistant to radiation therapy resulting in a comparatively higher rates of locoregional recurrence compared with non-TNBC patients. The mechanisms behind this relative radio resistance remain unknown. The goal of this study is to investigate the role of three miRNAs namely, miR-34a, miR-21, and miR-210, which are implicated in DNA damage-repair process, in the response of TNBC cell lines to radiation therapy. Methods: Seven TNBC breast cancer cell lines were used for the study. The levels of miR-34a, miR-21 and miR-210 were evaluated by taqman- based quantitative PCR assay. These cells were exposed to 2 Gy radiation dose and colonogenic survival was assessed after about 2 weeks. Survival fraction after 2 Gy (SF2), which is the ratio of number of cell colonies formed after 2 Gy radiation vs. the number of cell colonies with out radiation, was determined. The SF2 factor is a reliable index to measure radio sensitivity, greater the SF2 factor more radio resistant the cells are. Results: The SF2 value of the TNBC cells varied from 0.31 to 0.74 with MDA-MB-468, HCC-70 being the most radio sensitive cell lines and MDA-MB-436, BT-20 being the most radio resistant cell lines. MDA-MB- 231, BT-549 and Hs 578T were found to be moderately radio resistant breast cancer lines. The oncomiR -21 expression levels in these 7 TNBC cell lines varied from 0.85 to 4.18 fold with a very poor correlation with SF2 (r2=0.08). The oncomiR 210 levels varied from 0.49 to 9.19 fold and also did not exhibit any correlation with radio resistance in TNBC cells (r2= 0.141). Whereas the tumor suppressor miR, miR-34a expression showed an inverse correlation with radio resistance (r2=0.8) in TNBC cells. The radio resistant cell line (e.g., MDA-MB-436, SF2 = 0.74) expressed significantly low levels of miR-34a (0.016 fold) relative to miR -34a levels (set as 1) in HCC 70, which was found to be a radiosensitive cell line with SF2 of 0.309. Conclusions: Our preliminary data indicates that miR 34a may play a role in the response of TNBC cells to radiotherapy. Citation Format: Anjana Bhardwaj, Nivetha Ganesan, David Molkentine, Uma Raju, Isabelle Bedrosian. miR-34a as a radio sensitizer of triple negative breast cancer. [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 4160. doi:10.1158/1538-7445.AM2013-4160
Abstract 4154: Multi-parameter molecular characterization of circulating tumor cells (CTC): Development of a CTC-endocrine therapy index (CTC-ETI)
Authors: Costanza Paoletti, Martha Brown, Maria Muñiz, James M. Rae, Dafydd G. Thomas, Daniel F. Hayes
Journal: Cancer Research (2011)

Abstract Introduction. CTC can be reproducibly and reliably enumerated using a commercially-available, automated immunomagnetic system (CellSearch®; Veridex LLC). High levels of CTC predict rapid progression in patients with metastatic breast cancer (MBC). Only ∼ 50% of patients with estrogen receptor (ER) positive MBC benefit from endocrine therapy (ET). Patients with endocrine-refractory MBC are better palliated with chemotherapy. We have developed a multi-parameter assay using CellSearch® that may identify patients with ER positive MBC who are unlikely to benefit from ET and may be better served with chemotherapy. Methods. CellSearch® has four fluorescence channels. Three of these are used to distinguish CTC from WBC (DAPI, anti-cytokeratin, anti-CD45). The 4th “empty” channel was used to measure ER, Bcl-2, HER2, and Ki67 expression with antigen-specific fluorescent-labeled antibodies. These four markers were chosen because of their associations with sensitivity (ER, Bcl-2) or resistance (HER2, Ki-67) to ET. Cultured human breast cancer cells (MCF-7: ER +, BCL-2 +, HER2 -, Ki67 +; MDA-MB-231: ER -, Bcl-2 -, HER2 -, Ki67 +; BT-474: ER +, Bcl-2 +, HER2 +, Ki67 +) were spiked into 7.5 ml human whole blood from normal donors and separated and characterized using the CXC CellSearch® kit. Results. Each cell line stained appropriately for the respective markers, with appropriate negative controls, although staining was heterogeneous, even within a single cell line. Using these preliminary data, we have developed a CTC-ETI in which scores are assigned to the individual categories consisting of cell counts coupled with the relative percent and degree of cell positivity of each marker. We predict that lower scores (low or no CTC, or CTC with high % and intensity of ER and Bcl-2; low HER2 and Ki-67) will be associated with favorable response to ET. Conclusions. CellSearch® can be used to measure the expression of 4 clinically useful and proven breast cancer biomarkers. A clinical trial is underway at U. Michigan to permit calculation of CTC-ETI in patients with MBC, which will lead to a prospective trial to determine if high CTC-ETI predicts resistance and rapid progression on ET. Supported by Veridex, LLC, Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale ™ (DFH), Associazione Sandro Pitigliani and by a studentship from FIRC (CP) 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 4154. doi:10.1158/1538-7445.AM2011-4154
Abstract C4: Inhalational chemotherapy for malignant gliomas
Authors: Thomas C. Chen, Florence H. Hofman, Heeyon Cho, Weijun Wang
Journal: Cancer Research (2011)

Abstract Perillyl alcohol (POH) is a monoterpene that has been used orally for the treatment of systemic cancer, based on its mechanism of action as a ras inhibitor and a cell cycle inhibitor. Unfortunately, it had significant gastrointestinal side effects, and was never well received as an oral anticancer agent. Recently, POH has been administered intranasally in a Phase I/II trial for the treatment of recurrent malignant gliomas in Brazil. It is well tolerated when delivered intranasally, with a 50% progression free survival (PFS) of 6 months in patients with recurrent GBM, with radiographic reduction in size in some patients. Similar efficacy compared to bevacizumab (Avastin; Genentech) was obtained in recurrent GBM patients treated with intranasal POH alone. We have recently synthesized a pharmaceutical grade of POH with &amp;gt;98% purity. Synthesized POH inhibits vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and transforming growth factor-beta 2 (TGF-B2). Cytotoxicity, as measured by colony formation assay (CFA), demonstrated a IC50 of 0.5 mM. We have since conjugated POH to a number of different pharmaceutical agents, including temozolomide (TMZ). Data on these conjugates demonstrate increased cytotoxic activity compared to individual drugs alone or in combination. TMZ-POH is much more potent than POH alone (IC50 10–30 uM), and is effective in TMZ resistant glioma cells, inhibits glioma cancer stem cells, and is not toxic to normal astrocytes. Our goal is to use our synthesized POH and TMZ-POH in upcoming Phase I/II trials for recurrent malignant gliomas. Further definition of the perillyl alcohol derivatives will lead to a pipeline of new compounds which will enable further expansion of the intranasal delivery repertoire. Animal models demonstrating efficacy of intranasal delivery of POH and TMZ-POH is currently underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C4.
802 FOLLOW-UP AFTER CESSATION OF THERAPY WITH DIRECT ACTING ANTIVIRALS IN CHRONIC HEPATITIS C PATIENTS – WHO IS AT RISK OF LATE RELAPSE?
Authors: I. Carey, H.-J. Lee, J. Calara, J. Toledo, M. Bruce, M. Horner, I. Fletcher, D. Shang, A. Barnabas, D. Joshi, K. Childs, K. Agarwal
Journal: Journal of Hepatology (2013)
Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who Are Undergoing Dialysis
Authors: William G. Goodman, Jonathan Goldin, Beatriz D. Kuizon, Chun Yoon, Barbara Gales, Donna Sider, Yan Wang, Joanie Chung, Aletha Emerick, Lloyd Greaser, Robert M. Elashoff, Isidro B. Salusky
Journal: New England Journal of Medicine (2000)

Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease.
Abstract 330: Gene expression signature characterized by PI3Kinase activation and Stathmin overexpression validates to identify aggressive disease and a potential for PI3Kinase-inhibitors in endometrial carcinomas
Authors: Elisabeth Wik, Jone Trovik, Maria B. Raeder, Monica Mannelqvist, Karen K. Mauland, Anne M. Oyan, Karl H. Kalland, Lars A. Akslen, Helga B. Salvesen
Journal: Cancer Research (2011)

Abstract Background: We have recently reported a gene expression signature defining an aggressive subgroup of endometrial cancer patients characterized by PI3Kinase activation and Stathmin overexpression, suggesting the potential for PI3Kinase inhibitors against this disease (Salvesen et al, PNAS 2009). In the present study we wanted to validate the value of these measures for PI3Kinase activation prospectively in an independent patient series. Methods: A prospectively collected, independent patient series of 158 cases of endometrial carcinoma was assessed. Real-time quantitative PCR was performed for the 29 genes in the previously defined gene signature. Stathmin expression in formalin fixed tumor specimens was assessed by immunohistochemistry (IHC). Results: A high signature score predicted shorter recurrence free (p=0.001) and disease-specific survival (p=0.002). A high score was also significantly associated with high age (p=0.04), high FIGO stage (p=0.03), non-endometrioid histology (p&amp;lt;0.001), high grade (p&amp;lt;0.001) and lymph node metastases (p=0.02). High signature score was also correlated with overexpression of Stathmin in tumor tissue (p≪0.002). Conclusion: The finding validates that previously identified markers for PI3Kinase activation identify aggressive phenotype in endometrial cancer. This further supports a potential for PI3Kinase-inhibitors in the treatment of metastatic endometrial carcinoma. We suggest that clinical trials with drugs targeting the PI3Kinase pathway involve stratification related to biomarkers, including the expression levels for this gene signature and Stathmin. 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 330. doi:10.1158/1538-7445.AM2011-330