tbuckley/cabot-search huggingface dataset:
Results from a pivotal phase II study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma (HL).
Authors: R. W. Chen, A. K. Gopal, S. E. Smith, S. M. Ansell, J. D. Rosenblatt, K. J. Savage, J. M. Connors, A. Engert, E. K. Larsen, D. A. Kennedy, E. L. Sievers, A. Younes
Journal: Journal of Clinical Oncology (2011)

8031 Background: CD30 expression by Reed-Sternberg cells is a defining feature of HL. Brentuximab vedotin comprises an anti-CD30 antibody conjugated by a plasma-stable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). Brentuximab vedotin selectively induces apoptotic death of CD30+ cells by binding, internalizing, and releasing MMAE. Methods: A pivotal, phase II, single-arm, multicenter study evaluated the efficacy and safety of brentuximab vedotin in patients (pts) with relapsed or refractory HL after autologous stem cell transplant (SCT). Pts received brentuximab vedotin 1.8 mg/kg q3 weeks (wks) as a 30‐minute outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Results: 102 pts were enrolled; 53% were female and median age was 31 yrs (range, 15–77 yrs). Pts had received a median of 3.5 (range 1–13) prior cancer-related systemic therapies excluding autologous SCT. 71% of pts had primary refractory disease and 42% had not responded to their most recent prior therapy. The ORR per IRF assessment was 75% (76 of 102 pts), with complete remissions (CRs) in 34% of pts (n=35). At the time of database lock (August 2010), the median duration of follow up from first dose was ~9 months (for responders). The median duration of response for pts with CR per IRF has not yet been reached (range 0.3+ to 61.4+ wks); follow up continues and 6+ months of additional data will be available for presentation. The most common (≥15%) treatment-related adverse events (AEs) of any grade were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. AEs ≥ Grade 3 occurring in ≥5% of pts were neutropenia, peripheral sensory neuropathy, thrombocytopenia, and anemia. Conclusions: With manageable AEs, single-agent brentuximab vedotin induced objective responses in 75% of pts with relapsed or refractory HL. In this heavily pretreated population, 35 of 102 pts (34%) achieved a durable CR, with more than 65% of pts remaining in CR.
SP0068 Developing Indices for SjÖGren's Syndrome
Authors: R. Seror
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Primary Sjögren9s syndrome (pSS) is characterized by a lymphocytic infiltration of exocrine glands. Involvement of salivary and lachrymal glands results in dry eye and dry mouth which are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, Clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, great efforts have been made to develop valid tools for the assessment of theses both facets. Disease specific questionnaires such as Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptom Inventory (SSI) have been proposed for evaluation of patients symptoms, whereas different composite indexes have been suggested for the assessment of systemic disease activity. Nevertheless, an international project supported by EULAR, emerged to develop consensus disease activity indexes: the EULAR Sjögren9s Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjögren9s Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. Both EULAR indexes have been developed by an international collaboration to be consensual. Both indexes have also been validated in a large independent international cohort. They both have been shown to be valid and reliable instruments. Also, the 2 scores have been shown not to correlate, suggesting that these 2 indexes assess 2 different disease components that poorly overlap, and are complementary. The sensitivity to change of both scores has been assessed, they are both able to detect change, however ESSDAI score, like other systemic score, seems to be more sensitive to change than ESSPRI and other patient scores. The next steps have been to define disease activity levels and clinically important changes for defining significant clinical improvement with the systemic score ESSDAI, and ESSPRI. This increased knowledge on the way to assess patients with primary SS, along with the emergence of new targeted therapy, aims to put a great input in the improvement of conduction of clinical trials in pSS <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6288
A Rewarding Pursuit of Certainty
Authors: Stephen G. Pauker, Richard I. Kopelman
Journal: New England Journal of Medicine (1993)

A 53-year-old, previously healthy college professor was brought to the emergency room in status epilepticus. He had no history of seizures.After giving intravenous medication to stop the seizures, I would obtain some medical and social history. Does the patient have hypertension or underlying vascular disease? Is he a drinker or a user of recreational drugs? These days we must always keep the possibility of human immunodeficiency virus (HIV) infection in mind.Three weeks earlier he had seen his physician for new bifrontal headaches that were relieved with aspirin. His physical examination was normal at that time. . . .
Targeting novel microtentacles to reduce the adhesion of circulating tumor cells to blood vessel walls.
Authors: RA Whipple-Bettes, EM Balzer, JR Yoon, EH Cho, MA Matrone, SS Martin
Journal: Cancer Research (2009)

Abstract Abstract #2044 Detached human breast tumor cell lines produce novel protrusions of the plasma membrane that promote reattachment of tumor cells to each other and extracellular matrix. We have termed these protrusions “microtentacles” due to clear mechanistic distinctions from either actin-based filopodia/invadopodia or tubulin-based cilia.&amp;#x2028; &amp;#x2028; Compelling in vivo studies show that a mechanism consistent with microtentacles is responsible for the attachment of circulating tumor cells to blood vessel walls. Human breast tumor cell lines that display a disorganized actin cortex and hallmarks of epithelial-to-mesenchymal transition produce higher frequencies and greater extension of microtentacles. Conversely, some current and proposed tumor drugs that target the cytoskeleton actually increase microtentacles. While many cancer therapies are directed against the process of cell division, it remains important to consider the effects of these drugs on the invasive characteristics of tumor cells. Our current research has determined that microtentacles are composed of coordinated filaments of vimentin and detyrosinated tubulin. Previous studies indicate that elevated levels of vimentin and detyrosinated tubulin in tumors predict poor patient outcome, although the specific mechanisms remain unclear. Time-lapse video microscopy also indicates that the rapid extension and dynamic motion of microtentacles relies on kinesin activation. Again, our results suggest that the kinesin responsible is a conventional kinesin, rather than the mitotic kinesins commonly targeted by cancer therapies. We propose that the independent roles of vimentin, detyrosinated tubulin and kinesin in tumor metastasis could result from their interdependent contributions to microtentacle formation. Since large epithelial tumor cells are often fragmented in narrow capillaries, we are targeting microtentacles to promote the fragmentation of circulating tumor cells in the capillaries of the lung. We are currently using time-lapse confocal microscopy of tumor cells circulating in intact blood vessels and whole-animal optical imaging to define therapies that reduce microtentacle-dependent adhesion of circulating breast tumor cells during metastasis.&amp;#x2028; &amp;#x2028; This image shows circulating tumor cells (red) adhering to the walls of an intact blood vessel (green). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2044.
Abstract 2134: Copy number variation in low- and high-grade breast tumors
Authors: Rachel E. Ellsworth, Heather L. Patney, Jennifer L. Kane, Jeffrey A. Hooke, Craig D. Shriver
Journal: Cancer Research (2010)

Abstract Objective Histological grade classifies breast carcinomas into low-, intermediate- and high-grade. Developmental pathways for high-grade disease remain controversial; clinical data have been used to describe both linear models, in which high-grade tumors evolve from low-grade precursors, as well as models that depict low- and high-grade carcinomas as distinct molecular diseases. Genome-wide copy number alterations were examined in low- and high-grade breast tumors to identify genetic changes associated with the etiology of low- and high-grade breast carcinomas. Methods Tumors were diagnosed and characterized by a single, dedicated breast pathologist. DNA was isolated after laser microdissection from low- (n= 53) and high-grade (n=68) tumors. Genotype data were generated using Human Mapping 250K Sty arrays (Affymetrix). Copy number alterations and LOH were detected using GenomeConsole 3.0.2 (Affymetrix). Results The most common alterations in low-grade carcinomas were gain of chromosomes 1q (75%) and 16p (58%) and loss of chromosome 16q (86%). These alterations were frequently simple and included the entire chromosomal arm. In contrast, patterns of alterations were complex in high-grade tumors, frequently with alternating gains and losses on a single chromosomal arm. In high-grade tumors, the most frequent alterations included gain of chromosome 1q (85%), 8q (84%), and loss of chromosomes 8p (54%), 14q (57%) and 17p (69%). Loss of 16q (P&amp;lt;0.0000005) and gain of 16p (P&amp;lt;0.005) occurred significantly more frequently in low- compared to high-grade tumors, while gain of 8q24 (P&amp;lt;0.000005) and 10p15-p14 (P&amp;lt;0.00005) and loss of chromosome 17p13 (P&amp;lt;0.00005) occurred significantly more frequently in high- compared to low-grade tumors. Only two samples, one low- and one high-grade, had a “flat” profile with no detectable chromosomal alterations. Conclusion Low- and high-grade breast tumors are genetically different. Gain of chromosome 1q is common in both low- and high-grade tumors, and may be an early event in tumorigenesis. Given the significantly different patterns of alterations, especially significantly higher loss of chromosome 16q in high- compared to low-grade tumors, high-grade disease may not arise from dedifferentiation of low-grade but rather represent a separate disease defined by unique genetic alterations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2134.
ET-67 * SUICIDE GENE THERAPY FOR GLIOMA USING MULTILINEAGE-DEFFERENTIATING STRESS ENDURING (MUSE) CELLS
Authors: T. Yamasaki, S. Wakao, H. Kawaji, T. Suzuki, Y. Kamio, S. Amano, T. Sameshima, N. Sakai, T. Tokuyama, M. Dezawa, H. Namba
Journal: Neuro-Oncology (2014)

INTRODUCTION: We have been investigating cell-based glioma gene therapy using various kinds of stem cells transduced with the herpes simplex virus thymidine kinase gene (HSVtk). In our previous study, we used SSEA3/CD105 double-positive multilineage-differentiating stress-enduring (Muse) cells transduced with HSVtk (Muse-tk cells) as the vehicle for HSVtk/ganciclovir (GCV) gene therapy. We demonstrated a potent in vitro tumoricidal bystander effect for various glioma cells. In the present study, we examined the in vivo bystander effect between U87 human glioma cells and human Muse-tk cells. METHODS: Muse-tk cells were obtained by lentiviral transduction of HSVtk in human Muse cells. U87 cells transduced with the luciferase gene were used for the brain tumor model, in which tumor volume could be measured using a bioluminescence imaging system (IVIS 200). Nude mice were intracranially co-implanted at Muse-tk:U87 cell ratios of 1:4, 1:8, and 1:16 (U87 cell number: 1 × 105); GCV was intraperitoneally administered (100 mg/kg/day) for 10 days. RESULTS: Luminescence intensity progressively increased in the control mice implanted with U87 alone with or without GCV treatment, and in those implanted with Muse-tk and U87 but not treated with GCV. All control mice died because of the tumor by Day 51 post tumor implantation (no difference among the control groups). In contrast, no luminescence was observed in the mice implanted with Muse-tk and U87 (Muse-tk:U87 cell ratios of 1:4 and 1:8) from Day 14 onward. Almost all mice survived longer than 100 days and no mouse died as a result of the tumor. CONCLUSIONS: There was a potent in vivo bystander effect between human glioma and Muse-tk cells. The results of the present study suggest that HSVtk/GCV gene therapy using Muse-tk is a promising treatment strategy for malignant glioma.
Epidermoid Carcinoma Primary in Bartholin's Gland
Authors: John F. Curran, Thomas V. Healey
Journal: New England Journal of Medicine (1949)

CARCINOMA of Bartholin's gland is one of the rarest malignant lesions occurring in the female genital tract, approximately 75 cases having been reported in the literature. In 1939, Simendinger,1 with a detailed résumé of 38 cases, enumerated and classified the cases since Klob's2 initial reference to the lesion in 1864. Isolated reports have subsequently appeared in the surgical literature,3 and Boughton,4 in a scholarly review of the problem in 1943, adjudged that by that time 75 cases had been listed, but that "a great number of these are published with inadequate data and may not be accepted as proved cases . . .
OP0136 Impact of morning stiffness on work performance in people with rheumatoid arthritis:
Authors: F. Buttgereit, R. Tuominen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Work disability remains a major problem for patients with rheumatoid arthritis (RA).<sup>1</sup> Early retirement from work in patients with RA is associated with morning stiffness.<sup>2</sup> However, there is little known about the impact of morning stiffness on work in those who continue in employment. <h3>Objectives</h3> Assess the impact of morning stiffness on work performance in patients with RA. <h3>Methods</h3> A survey was conducted among working age patients (18 years to state retirement age) in 11 European countries. Patients with RA for ≥6 months and RA-related morning stiffness were interviewed by telephone using a structured questionnaire, translated into the appropriate language. Findings from those in work were assessed. <h3>Results</h3> A total of 1061 patients (55 from Norway and approximately 100 from all other countries; 78% female) completed the questionnaires. Overall, 534 respondents (50%) were considered to be in work: 314 (59%) were in full time work, 129 (24%) worked part time or on reduced hours, 47 (9%) were self-employed, 24 (4%) were students and 20 (4%) combined work and retirement (semi-retired). Among these respondents, 80 (15%) had taken sick leave in the past month as a direct consequence of morning stiffness (mean 4.5 days). Morning stiffness caused a third of workers (176, 33%) to arrive late at work (mean 2.2 hours), most commonly due to taking longer to get ready (136, 77%) or problems getting dressed (67, 38%). Nearly half the working respondents (250, 47%) considered that morning stiffness adversely affected their work performance, for a mean of 8.8 hours/week. During these hours, patients reported performing at only 59% of their usual level. There were considerable differences between countries (see table). <h3>Conclusions</h3> Morning stiffness impairs work performance in patients with RA. The survey was conducted by Ipsos MORI and sponsored by an educational grant from Mundipharma International Limited <h3>References</h3> [1]Sokka et al. Arthritis Res Ther 2010;12:R42. [2]Westhoff et al. Rheumatology 2008; 47: 980–4. <h3>Disclosure of Interest</h3> F. Buttgereit Grant/Research support from: Merck Serono, Horizon Pharma, Consultant for: Merck Serono, Horizon Pharma, Mundipharma International Limited, Speakers Bureau: Mundipharma International Limited, R. Tuominen Consultant for: Mundipharma International Limited, Speakers Bureau: Mundipharma International Limited
Metastatic Renal Cell Carcinoma Avid for 82Rb but not 18F-FDG
Authors: Venkatesh L. Murthy, Richard K. J. Brown, James R. Corbett
Journal: Clinical Nuclear Medicine (2013)

Renal cell carcinoma has a variable uptake of 18F-FDG resulting in poor sensitivity and limited clinical application. There is intense interest in improved molecular imaging of this condition. We present a case of a 64-year-old man with known metastatic renal cell carcinoma found to have intense uptake of 82Rb but not 18F-FDG in multiple thoracic metastases seen on imaging performed to assess myocardial hibernation.
P2-01-25: Truncated p110 ERBB2 (CTF611) Increases Migration and Invasion of Breast Epithelial Cells by Inhibiting STAT5b Activation.
Authors: TM Ward, E Iorns, N Hoe, P Kim, S Singh, V Ernani, X Liu, A-M Jegg, M Gallas, ME Lippman, MD Pegram
Journal: Cancer Research (2011)

Abstract Background: Truncated ERBB2 receptors are present in a subset of human ERBB2+ amplified/overexpressing breast tumors, and are associated with trastuzumab resistance, metastasis, and poor clinical prognosis. However, whether truncated ERBB2 receptors are drivers of metastasis has not been well defined. In this study, we examined effects of full-length (p185) and truncated (p110) ERBB2 on the migration and invasion of human mammary epithelial cells, including HMLE and MCF10A cells. Material and Methods: Recombinant p185 and p110 ERBB2 were stably expressed in human mammary epithelial cells (HMLE) and MCF10A cells via retroviral vector. Expression of comparable levels of p185 and p110 in cells was confirmed by western blot. The phosphorylation states of downstream signaling proteins including STAT5 were assayed via phosphoproteomics and Collaborative Enzyme Enhanced Reactive (CEER™) immunoassay. The effects of the p110 constructs on cell migration and invasion were investigated by transwell assays. shRNA-encoding lentivirus was used for specific silencing of STAT5b in HMLE cells, and STAT5b silencing was confirmed at the protein level using western blot. Results and Discussion: Expression of p110 ERBB2 increased cell migration (HMLE, p = 0.04; MCF10A, p&amp;lt; 0.01) and invasion (HMLE, p= 0.03) when compared to expression of p185. Furthermore, expression of p110 in HMLE cells was associated with reduced phosphorylation of STAT5b. shRNA mediated silencing of STAT5b was sufficient to increase the migration (p &amp;lt; 0.01) and invasion of HMLE cells, phenocopying the p110 driven effects on HMLE cells. In clinical studies, loss of activated STAT5 protein correlates with breast cancer progression and is a negative predictor of survival. By analyzing publicly available gene expression datasets, we found that STAT5b mRNA expression is also significantly decreased in breast cancer compared to normal breast tissues in several studies, as well as in ERBB2 amplified vs. nonamplified samples. To our knowledge, this is the first reported perturbation of STAT signaling by truncated ERBB2 receptor, and suggests a mechanism by which truncated p110 ERBB2 (CTF611) increases migration and invasion of breast epithelial cells. This study extends the available data regarding STAT5 loss in breast cancer progression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-25.
Case 4-2011
Authors: Chadi M. El Saleeby, Brian E. Grottkau, Alison M. Friedmann, Sjirk J. Westra, Aliyah R. Sohani
Journal: New England Journal of Medicine (2011)

A 4-year-old boy was admitted to this hospital because of a 1-week history of back pain, with sleepiness, constipation, and refusal to walk. The serum calcium level was elevated. Initial radiographs and MRI studies were interpreted as normal. Diagnostic tests were performed.
OP0204-PC Multisite Peripheral Joint Pain in the Community: Prevalence and Impact in the North West Midlands, United Kingdom (UK)
Authors: A. Finney, E. L. Healey, M. Lewis, S. Ryan, K. S. Dziedzic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Current research and guidelines are often focused on single joint osteoarthritis (OA). The National Institute for Health and Clinical Excellence OA guidelines recommended that future research should consider the impact of multisite joint pain (NICE, 2008). <h3>Objectives</h3> To describe the prevalence and pattern of multisite joint pain (pain in two or more joint sites; hip, knee, hand, foot) and the impact on quality of life (QoL) and general health in a community dwelling population. <h3>Methods</h3> A cross-sectional population survey was mailed to adults aged 45 years and over (n=28,443) registered with 8 general practices in the North West Midlands, UK as part of the MOSAICS study. Participants provided information on demographic characteristics, general health, QoL and joint pain in the hand, hip, knee or foot in the last year. Participants were divided into mutually exclusive subgroups based on 16 combinations of multisite joint pain. These subgroups were collapsed into five groups based on the number of pain sites: 0,1,2,3 and 4. Linear regression analysis was used to investigate the association of multisite joint pain with general health (SF12, PCS &amp; MCS) and QoL (EQ5D) after adjusting for age, gender, BMI, and social deprivation. <h3>Results</h3> Of those mailed the survey, it was completed by 15,083 (53.0%). Average age of responders was 63.9 years (11.2 sd) and approximately half were female. 11,928 (42.0%) had joint pain, 8206 (28.8%) had multisite joint pain. Knee pain was the most prevalent single site pain (n=1492, 5.2%). Knee and hand was the most prevalent combination of 2 sites of joint pain (n=857, 3.0%) and knee, hand and foot was the most prevalent of 3 sites of joint pain (n=712, 2.5%). The prevalence of pain in all four sites was n=1953 (6.9%). After adjusting for covariates the linear regression showed a statistically significant association between multisite joint pain and the EQ5D and SF12. Each additional joint site demonstrated an increasing negative impact on QoL and general health (see table 1.) Table 1. The impact of multisite joint pain on the EQ5D and SF12 <h3>Conclusions</h3> Self-reported multisite peripheral joint pain has a significant negative impact on general health and QoL in the community. Multisite joint pain also shows a greater impact with each additional affected joint site. These findings suggest that the impact of multisite joint pain should be assessed in consultations with health care professionals. <h3>References</h3> NICE (2008) Osteoarthritis. The care and management of osteoarthritis in adults. National practice guideline no 59. London: NICE. <h3>Disclosure of Interest</h3> None Declared
Suivi à long terme de la résection endoscopique de la dysplasie de haut grade/Adénocarcinome superficiel sur endobrachyoesophage
Authors: F Caillol, E Bories, A Autret, C Pesenti, F Poizat, C Loeve, JP Ratone, J Guiramand, JR Delpero, M Giovannini
Journal: Endoscopy (2015)

La résection endoscopique (RE) est considéré comme le traitement de première intention des lésions en dysplasie de haut grade (DHG) ou adénocarcinome superficiel (ADKs) développé sur endobrachyoesophage (EBO). Peu de données existent encore sur le suivi à long terme.