tbuckley/cabot-search huggingface dataset:
Abstract LB-365: Unfolded protein response regulator BIP/HSPA5 as a chemoresistance biomarker and molecular target in acute lymphoblastic leukemia
Authors: Fatih M. Uckun, Sanjive Qazi, Amanda Garner, Hong Ma, Zahide Ozer, Jason Pitt, Kim Janda
Journal: Cancer Research (2011)

Abstract BIP/HSPA5, also known as glucose regulated protein (GRP) 78, is an endoplasmic reticulum (ER)-resident multifunctional molecular chaperone that represents a pivotal component of the pro-survival arm of the unfolded protein response (UPR) signaling pathway. We performed a comprehensive meta-analysis of 17 datasets and 668 leukemia/lymphoma cases using the Oncomine Clinical Research Database. 7 of 10 contrasts for high-grade B-lineage lymphoid malignancies exhibited signigficant up-regulation of BIP/HSPA5, including B-lineage acute lymphoblastic leukemia (ALL) (2-fold, P=5.9×10–10). Notably, the gene expression profiles of primary leukemia cells in matched-pair leukemic specimens obtained from 27 B-lineage ALL patients both at the time of initial diagnosis and at the time of relapse were extracted from the NCBI Gene Expression Omnibus (GSE18497) revealed a significant 1.4-fold up-regulation of the BIP8/HSPA5 gene in relapse clones (P=0.0016). Likewise, anti-BIP/HSPA5 Western blot analysis of whole cell lysates from primary leukemic cells from relapsed and newly diagnosed B-lineage ALL patients revealed higher levels of BIP/HSPA5 protein in relapse specimens. Confocal microscopy revealed abundant expression of BIP/HSPA5 protein in the plasma membrane of chemotherapy-resistant ALL cells. Pep42, a cyclic 13-mer cell-penetrating peptide that was identified by screening a pool of cyclic peptide phage display libraries using whole-cell panning against human melanoma cells, was found to not only specifically bind to surface expressed BIP/HSPA5 but also enter BIP/HSPA5+ cells by receptor-mediated endocytosis. We examined the ability of a doxorubicin conjugate of Pep42 (PEP-DOX) containing a cathepsin B-cleavable linker to target and induce apoptosis in surface BIP/HSPA5+ chemotherapy-resistant B-lineage ALL cells. By using a quantitative flow cytometric apoptosis assay, we documented that within 48 hours of treatment with 0.1–1.0 μM PEP-DOX (but not unconjugated drug-free Pep42, which was included as a control) apoptosis is induced in ≥99.9% of surface BIP/HSPA5+ ALL cells. As PEP-DOX specifically targets surface expressed BIP/HSPA5, 100-fold molar excess of drug-free Pep42 was able to compete with PEP-DOX for surface BIP/HSPA5 binding sites and thereby prevent PEP-DOX-induced apoptosis. Excess recombinant EGF, that was included as a negative control, did not affect PEP-DOX- induced apoptosis. The identification of the BIP/HSPA5 as a chemoresistance biomarker and molecular target for B-lineage ALL may lead to new anti-leukemic treatment strategies for relapsed disease that are much needed. 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 LB-365. doi:10.1158/1538-7445.AM2011-LB-365
P41 * IDENTIFICATION OF GLIOMA SPECIFIC APTAMER TARGETS
Authors: M. Arora, J. Alder, C. Lawrence, C. Davis, T. Dawson, G. Hall, L. Shaw
Journal: Neuro-Oncology (2014)

INTRODUCTION: Aptamers are in vitro generated DNA and RNA sequences which are randomly created as a library, with multiple permutations and combinations. These are then exposed to the target structure against which we want an aptamer ‘selected’ using Sequential Enumeration of Ligands by Exponential enrichment (SELEX). METHOD: Commercially available glioma and glial cell lines and in-house generated primary glioma cultures were used. Modified aptamers based on published sequences against glioma cell lines and newly generated sequences were used in the project to identify their binding targets. Cy3 or biotin- conjugated aptamers were incubated with live glioma cell cultures and imaged using confocal or light microscopy.To determine the target ligand, aptamers were then reacted with glial cell lysate and subjected to precipitation using streptavidin agarose beads and SDS polyacrylamide electrophoresis. Proteins were analysed by mass spectroscopy. RESULTS: Known and unknown aptamer protein ligands were co-precipitated. Ku70, Ku80 were precipitated along with nucleolin and related proteins. CONCLUSION: The aptamer has shown preferential binding to glioma cells and could act as a delivery system for therapeutic payloads. The aptamer targets Ku70 and Ku80, which are known to be over expressed in other forms of cancer but their role in gliomagenesis has not been fully elucidated. Other novel proteins have also been identified. Thus the aptamer co-precipitation technique has identified potential glioma biomarkers that may be of clinical significance.
FRI0061 Cervical Dysplasia and Cervical Cancer in Women with Rheumatoid Arthritis: Table 1.
Authors: H. Wadström, T. Frisell, J. Askling
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Immunosuppression is a key factor in the progression from HPV-infection to invasive cervical cancer. Cervical screening programmes aim to detect cervical lesions before they develop into malignancies, non-adherence to these programmes is a major risk factor for cervical cancer. Some reports have found a higher risk of cervical neoplasia in patients with rheumatoid arthritis (RA) compared to the general population. <h3>Objectives</h3> The objective was to examine screening patterns and the risk of cervical neoplasia in women with RA as compared to the general population. <h3>Methods</h3> Through register-linkages, we assembled a cohort of female biologics-naïve patients with RA (n=36,883), and a general population comparator cohort (matched 1:10). Patients with two non-primary care outpatient visits with an RA ICD code were included, at least one of the visits had to be at a rheumatology or internal medicine department. The second visit served as the index date. Incidences for these outcomes 1999 through 2012 were compared using Cox regression, adjusted for age, level of education, previous cervical screening, co-morbidities, marital status, and total days spent in hospital during last 5 yrs. Outcomes were first cytology screening with a normal outcome, first ever Cervical Intraepithelial Neoplasia (CIN) grade I-II, first ever CIN III, and first ever invasive cervical cancer during follow-up. <h3>Results</h3> Cox regression yielded higher rates of cytology screening, CIN I-II, and CIN III in the RA cohort than in the general population cohort. There was no difference in invasive cervical cancer between the groups (Table 1). Hazard ratios were not significantly altered by adjusting for age, level of education, previous cervical screening, co-morbidities, marital status, and total days spent in hospital during last 5 yrs. <h3>Conclusions</h3> This study demonstrated that screening patterns were largely similar between the cohorts, although there was a statistically significant 10% higher rate of screening among RA patients in the fully adjusted model. We further found a moderate (30-50%) increase in the observed risk of CIN I-II and of CIN III in biologics-naïve patients with RA compared to the general population, but no difference in risk of invasive cervical cancer. <h3>Disclosure of Interest</h3> None declared
Initial Chemotherapy for Asymptomatic Brain Metastasis of Non-Small Cell Lung Cancer
Authors: K. Sekihara, Y. Hosomi, Y. Nakahara, M. Yomota, Y. Okuma, Y. Takagi, M. Shibuya, T. Okamura
Journal: Annals of Oncology (2013)

Background: The optimal treatment for non-small cell lung cancer (NSCLC) in patients with asymptomatic brain metastasis is still controversial and whole-brain radiotherapy (WBRT) may reduce performance status. This study aimed to analyze the outcome for systemic chemotherapy in NSCLC patients with asymptomatic brain metastases.Patients and methods: We retrospectively reviewed the medical records of NSCLC patients with asymptomatic brain metastasis between April 2007 and March 2012.Results: From the database, 143 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between April 2007 and March 2012. 73 patients were identified to have brain metastasis without associated symptoms. For the initial therapy, 44 patients received systemic chemotherapy, 14 and 15 patients underwent WBRT and stereotactic radiosurgery (SRS), respectively. Among 44 patients who treated with initial chemotherapy, median age was 66 years (38-77), Male/Female: 18/26, Adenocarcinoma / Squamous cell carcinoma / not otherwise specified: 36/3/5, EGFR mutation positive/ negative: 10 / 34.Seventeen of 44 patients received WBRT and 13 patients received SRS in the clinical process. The median overall survival is 13 months.Discussion: This study suggested a potential role of systemic chemotherapy instead of WBRT as an initial treatment of NSCLC patients with asymptomatic brain metastases. Background: The optimal treatment for non-small cell lung cancer (NSCLC) in patients with asymptomatic brain metastasis is still controversial and whole-brain radiotherapy (WBRT) may reduce performance status. This study aimed to analyze the outcome for systemic chemotherapy in NSCLC patients with asymptomatic brain metastases. Patients and methods: We retrospectively reviewed the medical records of NSCLC patients with asymptomatic brain metastasis between April 2007 and March 2012. Results: From the database, 143 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between April 2007 and March 2012. 73 patients were identified to have brain metastasis without associated symptoms. For the initial therapy, 44 patients received systemic chemotherapy, 14 and 15 patients underwent WBRT and stereotactic radiosurgery (SRS), respectively. Among 44 patients who treated with initial chemotherapy, median age was 66 years (38-77), Male/Female: 18/26, Adenocarcinoma / Squamous cell carcinoma / not otherwise specified: 36/3/5, EGFR mutation positive/ negative: 10 / 34.Seventeen of 44 patients received WBRT and 13 patients received SRS in the clinical process. The median overall survival is 13 months. Discussion: This study suggested a potential role of systemic chemotherapy instead of WBRT as an initial treatment of NSCLC patients with asymptomatic brain metastases.
Abstract 5225: Quantification of circulating tumor cell aggregates in breast cancer patient blood using an enrichment-free detection method
Authors: Edward H. Cho, Devin Sok, Dena Marrinucci, Madelyn Luttgen, Anand Kolatkar, Craig Yoshioka, Marco Wendel, Michael A. Matrone, Daniel Lazar, Xing Yang, Michael Malchiodi, Rachelle Lamy, Melissa Torrey, Kelly Bethel, Peter Kuhn
Journal: Cancer Research (2011)

Abstract Circulating tumor cells (CTCs) have been implicated as a potential population of cells that may seed metastasis in cancer patients. In order to characterize and understand this population of cells, an enrichment-free immunofluorescence detection method was developed by our lab. This method take whole patient blood and classifies cells based on cytokeratin (CTCs) and CD45 (WBCs) antibody staining. Using this CTC detection method, a population of cells residing in tumor cell aggregates was observed in blood draws from Stage IV breast cancer patients. It was previously observed in ex vivo mouse experiments that homotypic aggregate formation of tumor cells may increase metastatic efficiency (Glinsky, et al., Cancer Research, 2003). In this work, we seek to determine if a significant proportion of CTCs reside in homotypic aggregates in patient blood by enumerating CTC aggregates from the blood draws of 23 Stage IV breast cancer patients and 16 healthy donor patients. Preliminary analysis measuring associations of CTCs with other nucleated cells found in patient blood draws revealed that ∼43% of cytokeratin-positive (CK+) cells found in breast cancer patient samples localize with either other CK+ or white blood cells (WBCs) versus 14% in healthy donor patient samples. Furthermore, ∼19% of WBCs were found to be associated with either CK+ or other WBCs in breast cancer patient samples versus ∼7% in healthy donor patient samples. Pathological review confirming CK+ cells as CTCs revealed that of the CTCs detected in patient blood after pathological review, ∼2% of CTCs were found as homotypic aggregates versus ∼0.07% in healthy donor samples (p=0.0005). Four breast cancer patients were found to have no CTC aggregates. Two breast cancer patients had significantly higher than average CTC aggregate percentages (∼6% and ∼7%). Patients will continue to be monitored to measure any differences in disease outcome of patients with high incidence of CTC aggregates versus patients with low incidence of CTC aggregates and healthy donors. 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 5225. doi:10.1158/1538-7445.AM2011-5225
Abstract P3-08-06: Triple Negative Breast Cancer and BRCA Status: Implications for Genetic Counseling
Authors: R Haque, M Alvarado, SA Ahmed, JM Shi, JWL Chung, CC Avila, CX Zheng, GE Tiller
Journal: Cancer Research (2012)

Abstract BACKGROUND: Controversy exists whether women newly diagnosed with triple negative breast cancer (TNBC) should be referred to genetic counseling as they may be more likely to be BRCA carriers. However, prior studies included small numbers of carriers and their results have had limited influence on practice guidelines. The objective of this study was to determine the association of breast cancer molecular subtype and BRCA status in a large group of medically insured women. METHODS: We examined a cohort of 2,105 women with breast cancer history tested for BRCA mutations in a large California health plan from 1997–2011. BRCA test results were recorded in the health plan's clinical genetics registry. Of the 2,105 breast cancer patients, 249 were BRCA mutation carriers (143 BRCA1 carriers, and 106 BRCA2 carriers). We conducted data linkages of all patients with the health plan's NCI-SEER affiliated tumor registry and identified ER, PR, and HER2. HER2 status was also captured from pathology reports using natural language processing. ER, PR, and HER2 status were assessed by immunohistochemical or FISH techniques. Patients were classified into four main biologic subtypes: triple negative (ER−/PR−/HER2−); luminal A (ER+ and/or PR+/HER2−); luminal B (ER+ and/or PR+/HER2+); and HER2-enriched (HER2+/ER−). We examined the association between molecular subtypes (collapsed into TNBC vs. non TNBC categories) and BRCA1/2 mutation status using contingency table analyses. P-values (two-sided) were estimated using chi-square analysis. Multivariable logistic regression was used to estimated adjusted odds ratios (OR) and 95% confidence intervals. RESULTS: TNBC subtype was strongly associated with BRCA status (P &amp;lt; 0.0001). Women with TNBC tumors were five-fold more likely to be BRCA carriers than women who had non-TNBC breast tumors (OR = 5.6, 95% CI: 4.1–7.5). Specifically, the association of TNBC with BRCA1 was more robust (OR = 12.2, 95% CI: 8.3–17.9). Adjusting for age and stage of breast cancer diagnosis and race/ethnicity did not materially modify the association between TNBC and BRCA1 status. TNBC was not associated with BRCA2 status (OR = 1.6, 95% CI: 0.9–2.7). CONCLUSION: TNBC was strongly associated with BRCA1 status, but not with BRCA2 status. Statistically significant numbers of patients with BRCA mutations have a TNBC profile. These patients should therefore be referred to clinical genetics for further evaluation and possible testing. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-06.
609 LPS INDUCES AN UNEXPECTED ENDOPLASMIC RETICULUM UNFOLDED PROTEIN RESPONSE (UPRER) IN IMMUNE CELLS FROM PATIENTS WITH CIRRHOSIS
Authors: L. Ouchia, E. Weiss, M. Fasseu, L. Elkrief, P.-E. Rautou, M. Hurtado-Nedelec, D. Valla, D. Lebrec, R. Moreau
Journal: Journal of Hepatology (2013)
Labeled Erythrocyte Scintigraphy for Splenic Hemangioma: A False-Negative Study
Authors: KAM W. CHAN
Journal: Clinical Nuclear Medicine (1998)

Labeled erythrocyte scintigraphy has been used to diagnose hemangioma with high specificity. The author reports a case in which labeled erythrocyte scintigraphy failed to demonstrate a splenic hemangioma.
A Familial Deficiency of the Phagocytosis-Enhancing Activity of Serum Related to a Dysfunction of the Fifth Component of Complement (C5)
Authors: Michael E. Miller, Ulf R. Nilsson
Journal: New England Journal of Medicine (1970)

A patient, previously described, was found to have increased susceptibility to bacterial infections related to a deficiency of serum enhancement of in vitro phagocytosis. The same deficiency affected the patient's mother and 15 other relatives. The deficiency was shown to involve a dysfunction of the fifth component of complement (C5) by the fact that the phagocytosis-enhancing activity of the mother's serum was restored to normal by the addition of highly purified C5. Also, serum from mice with a genetic deficiency of C5 indicated poor enhancement of phagocytosis, and the addition of highly purified C5 to the Co-deficient mouse serum restored phagocytosis-enhancing activity. Finally, the addition of C5-deficient mouse serum to the mother's serum failed to improve the phagocytosis-enhancing effect of the maternal serum, whereas the addition of small amounts of normal mouse serum did. In view of the patient's clinical susceptibility to primarily gram-negative bacteria, the in vitro dysfunction of C5 may be related to impaired in vivo inactivation of such organisms.
DETECTION OF METASTASIS OF HUMAN COLON TUMOR XENOGRAFTS ON NUDE MICE USING RADIOLABELED MONOCLONAL ANTIBODY (Mab) FRAGMENTS.
Authors: J G Sharp, S S Joshi, S L Mann, M A Tempero, D A Crouse, R A Stratbucker, M A Quaife
Journal: Clinical Nuclear Medicine (1987)

Sharp, J G; Joshi, S S; Mann, S L; Tempero, M A; Crouse, D A; Stratbucker, R A; Quaife, M A Author Information
Stat Bite Prevalence of Cancer, 1982-1987
Authors: L. Kessler
Journal: JNCI Journal of the National Cancer Institute (1991)

Stat Bite Prevalence of Cancer, 1982–1987 Get access Larry Kessler, Sc.D. Larry Kessler, Sc.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 3, 6 February 1991, Page 165, https://doi.org/10.1093/jnci/83.3.165 Published: 06 February 1991
Internet-Only Publication
Authors: Edward W. Campion, Kent R. Anderson, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2001)

is on our Web site but does not appear in the print version.The Journal' s first Web-only Image in Clinical Medicine, "A Hair-on-End Skull," 1 can be found at http://www.nejm.org.We plan to release about one Image in Clinical Medicine per month as a featured, Web-only publication.This Web-only feature is free and available to all visitors to the site.The Internet offers journals an opportunity to publish additional articles and other features without having to expand the size of their printed editions.For example, some of our articles already include supplementary material available only on the Web.Such supplementary material is carefully selected on the basis of its importance to the printed article and its relevance to readers.In recent years we have received many Images in Clinical Medicine that are acceptable for publication, but the space for them in the printed Journal is limited.We have decided to publish some of these Images only on the Web.
AB1010 Comparing Digital Tomogram and Ultrasound in Established Rheumatoid Arhritis: Table 1
Authors: R. Laxminarayan, K. Kulkarni, N.V. Kolhe
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Digital tomosynthesis (DT), relatively a new tool, is superior to convetional radiography (CR) in detecting erosions<sup>1</sup>. High resolution ultrasound (HRUS) is an established tool in the evaluation of rheumatoid arthritis (RA). DT is significantly cheaper and quicker compared to MRI and HRUS, and does not need intravenous contrast administration. <h3>Objectives</h3> To compare the DT and HRUS in the detection of erosions in wrists and hands in estalished RA. To compare the benefits of DT and HRUS in the evaluation of hands and wrists in RA. <h3>Methods</h3> 13 estalished RA patients underwent both DT and HRUS evaluation of hands on the same day. HRUS was performed and DT images were read by the same experienced musculoskeletal radiologist. Wrists and hands were scanned on DT and van der Heijde Modified Sharp Score<sup>2</sup> was used for image interpretation. Wrists, index finger MCP joint (MCP2), PIP joint (PIP2) and middle finger MCP joint (MCP3), PIP joint (PIP3) were scanned on HRUS. These images were interpreted using German US7 score<sup>3</sup>. Non parametric tests were used to analyse the data using the software SPSSv.21. Mann-Whitney test was used to compare the erosion scoring between the two modalities. <h3>Results</h3> See Table 1. HRUS was unable to pick up any erosion at wrist but DT detected 18 erosions in 8 joints. Detection of erosions was statistically significant on DT (p 0.007). At MCP and PIP joints numerically HRUS detected more erosions, but this was not statistically significant. We also found that strength of DT was in identifying joint space narrowing and ability to grade the severity of erosions. Whereas HRUS gave additional informations such as synovitis and activity of erosions. <h3>Conclusions</h3> 1. DT is superior to HRUS in detecting erosions in a larger joint like wrist compared to smaller joints like MCP/PIP where HRUS seems superior. 2. DT and HRUS have their own strengths and short comings. Combining both modalities would give greater understanding of disease burden in RA. 3. Both modalities are cheaper and less time intensive compared to Magnetic Resonance Imaging (MRI) with gadolinium contrast. 4. A study to compare all three modalities to will help to understand the clinical utility and the most useful imaging technique/s. <h3>References</h3> Canella C et al. Use of Tomosynthesis for Erosion Evaluation in Rheumatoid Arthritic Hands and Wrists. Radiology 2011; 258(1): 199-205 van der Heijde D et al. How to read radiograph according to the Sharp/van der Heijde method. J Rheumatol 1999; 26: 743-5 Backhaus M et al. Evaluation of a Novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arhritis Rheum 2009; 61(9): 1194-201 <h3>Acknowledgements</h3> Patients who took part in the study and radiographers performing the DT. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1314