tbuckley/cabot-search huggingface dataset:
PWE-096 The Impact Of Surgeon Specific Outcome Data On Patient Choice
Authors: R Harris, J Mayberry
Journal: Gut (2014)

<h3>Introduction</h3> Patients have a legal right to choose their own treatment and care within the modern NHS<i><sup>1</sup>. </i>NHS England and the <i>Association of Coloproctology of Great Britain and Ireland<sup>2,</sup></i> has recently released the mortality rates for individual colorectal surgeons for patients within the first 90 days of a planned operation undertaken for bowel cancer. With these figures now publicly accessible on the Internet, Gastroenterology physicians, in collaboration with their inflammatory bowel disease (IBD) patients, could utilise the information to assist in deciding who they would choose to perform the surgery should it be required. <h3>Methods</h3> One hundred and ten consecutive IBD patients who had stable disease, and seen within the outpatient setting, completed a questionnaire about which fictional surgeon they would choose dependent on the published mortality rates and their location within the country. The options included a fictional surgeon with the lowest mortality rate who was based furthest away (Newcastle), a fictional surgeon with the highest mortality rate who was local (Leicester) and a fictional surgeon with an average mortality rate who was based in between (Nottingham). There was an additional option of the patient allowing their fictional gastroenterologist to decide for them. Similarly, ten Gastroenterology colleagues were also questioned about this surgeon-specific outcome data. <h3>Results</h3> The majority of the 110 IBD patients chose between two options. 45% chose a fictional surgeon with the lowest mortality rate based furthest away (Newcastle) and 41% opted for their fictional Gastroenterology consultant to decide for them. Of the 10 Gastroenterology colleagues questioned 50% were aware that the information was now publicly accessible, 20% were aware of where to access the information and 10% had reviewed the information online. On answering which fictional surgeon they would choose if the patient wanted their Gastroenterologist to decide for them, 40% chose the fictional surgeon with the lowest mortality rates based furthest away (Newcastle) and 20% chose the fictional surgeon with the highest mortality rates based locally (Leicester). <h3>Conclusion</h3> The Government has proposed that the NHS allows patients to make informed choices about their own care. These results demonstrate that given that choice these IBD patients would either choose a surgeon with the lowest mortality rates, even if they were not based locally, or would allow their own Gastroenterologist to decide for them. However, the majority of the Gastroenterologists surveyed had not utilised the information on surgeon-specific outcomes. The legal consequences for gastroenterologists who choose the “less than best” option are yet to be tested in court. <h3>References</h3> 2013/2014 Choice Framework, NHS England Individual surgical outcomes for England 2013, The Association of Coloproctology of Great Britain and Ireland <h3>Disclosure of Interest</h3> None Declared.
Abstract 4329: Novel HER2 targeting antibody-drug conjugates based on DNA-interacting duocarmycin and an unique linker technology with great potential in breast cancer and NSCLC.
Authors: Wim Dokter, Patrick Beusker, Gijs Verheijden, Ruud Ubink, Miranda van der Lee, Diels van den Dobbelsteen, Peter Goedings, Jacques Lemmens, Vincent de Groot, Marco Timmers
Journal: Cancer Research (2013)

Abstract We have generated cleavable linker-duocarmycin payloads that previously have been shown to be highly stable in human plasma and to cause excellent in vitro and in vivo efficacy when conjugated to antibodies directed against multiple targets in different models. In our HER2 program, we have used these linker-duocarmycin payloads to generate HER2-targeting antibody-drug conjugates (ADCS) and prepare these for FIM studies. HER2 is a validated target in breast (BC) and gastric cancer (GC) that is currently used to target trastuzumab towards HER2-positive BC and GC tumors. We have generated a set of cysteine-coupled ADCs using newly developed duocarmycins conjugated to a therapeutic HER2/neu antibody. In vitro studies with the anti-Her2 ADCs showed that compared to the naked Ab, the ADCs tested have gained a more than 100-fold potency and more than two-fold efficacy in cell killing capacity. Studies in HER2 positive and negative cell lines indicated that cytotoxicity was HER2- mediated. HER2 binding and ADCC activity was not affected by conjugation. Single dose and multiple dose xenograft studies in mice using a human HER2-positive breast cancer cell line showed dose-dependent anti-tumor activity of the ADCs in vivo. Patient-derived xenografts (PDx) using primary tumors from HER2-positive breast cancer and NSCLC patients demonstrated the ability of the ADC to induce complete remission of tumors that remained unresponsive to the naked Ab trastuzumab. Also taken into account toxicology studies in rodents and cynomolgous monkeys, we conclude that we have generated a new class of HER2-based ADCs that have great potential to become effective treatment for HER2-positive tumors, including breast cancer and NSCLC. From a series of compounds, a preclinical candidate was selected that is currently being prepared for Phase I clinical trials that will start in 2014. Citation Format: Wim Dokter, Patrick Beusker, Gijs Verheijden, Ruud Ubink, Miranda van der Lee, Diels van den Dobbelsteen, Peter Goedings, Jacques Lemmens, Vincent de Groot, Marco Timmers. Novel HER2 targeting antibody-drug conjugates based on DNA-interacting duocarmycin and an unique linker technology with great potential in breast cancer and NSCLC. [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 4329. doi:10.1158/1538-7445.AM2013-4329
Abstract 2331: Role of MMP expression in the effect of Plk4 on cell migration and invasion
Authors: Volha Brashavitskaya, Carla O. Rosario, James W. Dennis, Carol J. Swallow
Journal: Cancer Research (2011)

Abstract Plk4 is a haploinsufficient tumor suppressor in mice (Ko et al, Nature Genetics, 2005). Plk4+/− mouse embryonic fibroblasts (MEFs) spontaneously immortalize in culture and become tumorigenic by passage 15 (Rosario et al, PNAS, 2010). We investigated the secondary genetic alterations associated with tumorigenicity. Early passage (P3) Plk4+/+, P3 Plk4+/− and late passage (P15) Plk4+/− MEFs were compared by genome-wide expression array (Illumina). When differentially expressed genes were organized by biological function, increased cell proliferation and death (p=2.13E10-1.31E02, p = 2.52E07-1.14E02 respectively), and decreased cell motility (p = 3.74E07-1.27E02) in the P15 MEFs were predicted. An independent array analysis comparing tumorigenic (T) to nontumorigenic (NT) Plk4+/− MEFs showed a pattern of altered gene expression predictive of decreased motility in the T MEFs. These results suggested the hypothesis that Plk4 modulates cell motility. To directly test this hypothesis in functional assays we measured cell spreading, scratch-wound healing and transwell migration through Matrigel; in all these assays P3 Plk4+/− were inferior to P3 Plk4+/+ MEFs. We hypothesized that altered MMP expression was one mechanism for the difference observed in migration, and tested this by comparing MMP-13,-10 and -3 expression as shown in the Table. Plk4 status was associated with altered expression of MMPs; in particular, MMP-13 expression was confirmed to be significantly reduced in P3 Plk4+/− compared to P3 Plk4+/+ MEFs by RT-qPCR. Our results indicate that Plk4 regulates cell motility and invasion. One potential mechanism is through upregulation of MMP-3,-10, and -13 expression. To further elucidate the molecular mechanisms of Plk4 related carcinogenesis we will next directly determine the effect of Plk4 on MMP activity and correlate this with migration and invasion. 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 2331. doi:10.1158/1538-7445.AM2011-2331
COPD and risk of venous thromboembolism and mortality in a general population
Authors: Trond Børvik, Sigrid K. Brækkan, Kristin Enga, Henrik Schirmer, Ellen E. Brodin, Hasse Melbye, John-Bjarne Hansen
Journal: European Respiratory Journal (2015)

The relationship between chronic obstructive pulmonary disease (COPD) and risk of venous thromboembolism (VTE) has been scarcely studied in the general population. We aimed to investigate the association between COPD and risk of VTE and mortality in a population-based cohort. Spirometry was conducted in 8646 males and females, participating in the fifth (2001–02) and sixth (2007–08) surveys of the Tromsø Study. Incident VTE events during follow-up were registered from the date of inclusion to December 31, 2011. Cox-regression models with COPD stages and confounders as time varying covariates were used to calculate hazard ratios with 95% confidence intervals for VTE and all-cause mortality. During a median follow-up of 6.2 years, 215 subjects developed VTE. Subjects with COPD stage III/IV had a two-fold higher risk of secondary VTE compared to subjects with normal airflow (HR 2.05, 95% CI 1.02–4.10). COPD patients, particularly those with stage III/IV disease, with VTE had a higher mortality rate than COPD patients without VTE (50.2% versus 5.6% per year). Our findings suggest that patients with severe COPD may have increased risk of secondary VTE, and that COPD patients with VTE have a higher mortality rate than COPD patients without VTE.
SP0103 Raising Awareness - the Perspective of Eular
Authors: F. Berenbaum
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Rheumatism and musculoskeletal diseases (RMDs) include any diseases affecting joint, bone, spine, tendon, ligament or muscle. Because of this wide range of tissues involved in RMDs, these latter affect more than 120 million people throughout Europe. Acute and chronic pain, loss of mobility, disability, structural damage, impact on quality of life, on personal and professional relationships are the main concerns due to RMDs. Moreover, several RMDs are independent risk factors for cardiovascular comorbidities due to chronic inflammation and loss of physical activity participating in the metabolic syndrome. Taken together, it is obvious that these conditions are a huge problem in term of public health, by increasing the direct and indirect costs for a population. So, it is hard to understand why the awareness of RMDs among the public, politics and even the patients and their families themselves, remain quite low compared to other chronic conditions with a similar (and sometimes lower) impact on quality of life. This lecture will focus on the initiatives EULAR is developing in order to increase the awareness of RMDs at the national and international levels. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6209
Abstract 4616: Age dependent increase in Prostaglandin pathway coincides with onset of ovarian cancer in laying hens
Authors: Erfan Eilati, Lurui Pan, Janice M. Bahr, Dale Buchanan Hales
Journal: Cancer Research (2012)

Abstract The link between chronic inflammation and cancer has been recognized for many years. Cyclooxygenase (COX) (PTGS) is the rate limiting enzyme in catalyzing the conversion of arachidonic acid to prostaglandins. Two isoforms of cyclooxygenase has been identified, COX-1 and COX-2. Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecological malignancy. Ovarian cancer is mainly seen in older women when their ovaries are not reproductively functional. Hens spontaneously develop ovarian adenocarcinomas that are similar in histological appearance to human ovarian carcinomas and share similar symptoms of the disease thus the laying hen is the only accessible animal model that recapitulates human ovarian cancer. Many hypotheses about etiology of ovarian cancer have been proposed but the factors that contribute to correlation of age and ovarian cancer are unknown. The purpose of this study was to examine the expression of inflammatory factors and compare them to age. White Leghorn hens aged 12-45 months were used. The incidence of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 mRNA were extracted from ovarian tissue, preserved in RNAlater and their expression was determined using quantitative real-time PCR (qRT-PCR). Protein of both COX enzymes was isolated from ovarian tissue frozen in liquid nitrogen and were analyzed by Western blot. Ovarian tissue fixed in neutral buffered formalin was used for histology. Prostaglandin E2 amounts was measured in frozen ovarian tissues using ELISA. A significant increase in the incidence of ovarian cancer with age in laying hen was detected. The expression of both COX-1 and COX-2 protein and mRNA was remarkably increased in older hens compared to younger hens. In correlation with increased ovarian cancer incidence, expression of both COX enzymes and PGE2 concentration were elevated significantly with age. Our finding suggests that the up-regulation of COX mRNA and protein levels with age is the main contributing factor in the age associated increase in prostaglandin E2. The present study provides the first insight into the age-related changes in the expression of COX-1, COX-2 and prostaglandin E2. The results of current study demonstrated that PGE2 was elevated in ovaries of hens concomitant with age indicating its possible role in initiation and/or progression of ovarian malignancies. These finding may provide the basis for clinical trials utilizing COX specific inhibitors or dietary intervention targeting prostaglandin biosynthesis for the treatment and prevention of ovarian cancer. 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 4616. doi:1538-7445.AM2012-4616
Case 32-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Harry Acquatella, Anthony R. Mattia
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 27-year-old man was admitted to the hospital because of syncope.The patient had been in excellent health until the day of admission, when he experienced palpitations and dizziness while playing soccer and abruptly lost consciousness. He awoke after two or three minutes and was unaware of chest pain or dyspnea. He was admitted to the hospital.The patient was born in El Salvador and was raised in an agricultural area in a small house without plumbing. At the age of six years he had a severe illness with considerable loss of weight; he was given herbal . . .
Quality of colonoscopy: the real need is for universal quality measurement and common standards for certification and credentialing
Authors: G. Elta
Journal: Endoscopy (2011)

The study by Leyden and colleagues [1] has provided us with more evidence that the quality of colonoscopy is not carefully controlled. This is true throughout the world. Although common training standards would likely improve colonoscopy quality, I would argue that the most important control over quality comes at the stages of certification and/or credentialing. Those two steps determine who is allowed to perform colonoscopies. In the United States, certification by the American Board of Surgery or the gastroenterology subspecialty board of the American Board of Internal Medicine determines which trainees have successfully completed their training. Credentialing, which occurs at the local level of hospitals and ambulatory surgery centers, represents the final decision as to which providers are allowed to perform colonoscopy. Perhaps more control at the training level would work in Europe because certification and credentialing rules are different from those in the United States. However, common training standards would not address the problem of the older clinician who is no longer performing quality work. Competence should not be considered to be a static entity during training or throughout a career [2]. Continuous measurement of quality outcomes for all endoscopists, regardless of specialty or training, and the use of these quality measures for granting of endoscopic privileges is the only real solution.
Abstract 5270: Evaluation of Cell-able spheroid culture system for culturing patient derived primary tumor cells
Authors: Kesavan Nair Praveen, Nicole Streiner, Martin Vo, Kenna Anderes, Koichi Yokota, Takeshi Ikeya
Journal: Cancer Research (2012)

Abstract Tumor cell microenvironment has significant impact on growth kinetics, cell signaling and response to drug treatments. 3D models are more biologically relevant models compared to 2D models and have gained preference among researchers and drug developers. It is well recognized that primary tumor cell cultures grown in 2D monolayer quickly lose the ability to proliferate while 3D culture conditions on extracellular matrix allows for spheroid formation and proliferation. Cell-able, a novel micropatterned plate has cell adhesion areas in the well bottom where the size and shape of these areas are tightly controlled. Micro-fabrication of the well bottom enables rapid cell attachment and spheroid formation. Cell-able plates are potentially an alternative to culturing cells in 3D without extracellular matrix. We have evaluated spheroid formation, morphology, duration of viability, histopathology and expression of markers in patient-derived primary tumor cells from different tumor types when cultured on Cell-able plates compared to Cultrex extracellular matrix (ECM) coated plates. In addition we have utilized Cell-able plates to grow patient-derived tumor cells and evaluate the anti-proliferative responses to cytotoxic and targeted agents using high content imaging coupled with immunofluorescence characterization enabling subpopulation analysis within the spheroids. Our results indicate that patient-derived tumor cells from multiple indications as well as tumor cell lines can be cultured on Cell-able plates as spheroids that resemble the micro architecture of tumors and are therefore a suitable 3D model. The results of high content imaging analysis suggest that Cell-able plates could be used as a valuable tool in in vitro predictive assay models in oncology drug development. 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 5270. doi:1538-7445.AM2012-5270
Role of Epidemiology in Defining Events That Influence Transmission and Natural History of Anogenital Papillomavirus Infections
Authors: Laura Koutsky
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Role of Epidemiology in Defining Events That Influence Transmission and Natural History of Anogenital Papillomavirus Infections Get access Laura Koutsky Laura Koutsky Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 14, 17 July 1991, Pages 978–979, https://doi.org/10.1093/jnci/83.14.978 Published: 17 July 1991
Abstract 4756: Anti-melanoma-specific humoral immune responses <i>in vitro</i> in patients vaccinated with DC-rIL-2-VMO
Authors: Manijeh Berenji, Khorshed Alam, Raj Somasundaram, Marc K. Wallack
Journal: Cancer Research (2010)

Abstract Introduction: DC-rIL-2-VMO, an allogeneic cellular melanoma vaccine consisting of five melanoma cell lines, a recombinant vaccinia virus encoding for IL-2, as well as dendritic cells, has previously been shown to generate a potent cellular response in murine tumor models. We now demonstrate that this vaccine also has the capacity to generate a sustained humoral response in vitro. Methods: To detect anti-tumor antibodies in pre- and post-vaccinated melanoma patients’ sera, a mixed hemadsorption assay (MHA) was used. The binding of human antibody from diluted patients’ sera (1:05, 1:15 and 1:45) to cultured melanoma cells (Mel-2, Mel V, GLM-2 and KFM cells) was determined as indicator cells, sheep red blood cells (SRBC) coated sequentially with mouse anti-SRBC sera, goat sera against mouse sera, and mouse anti-human IgG sera to detect binding of human anti-melanoma antibodies. Results: Out of four patients evaluated with Stage IIIA-C and Stage IV resected with no evaluable disease (NED), three patients’ post-vaccination sera showed antibodies specifically binding to melanoma cell lines. Antibodies from two of the patients’ sera showed moderate to strong binding to three different melanoma cell lines (Mel 2, Mel V and GLM-2). Additionally, antibodies from patients’ sera and sera from two normal healthy donors did not show any binding to colorectal carcinoma (SW1116) cells (CRC), a negative control. Conclusions: Treatment of patients with Stage IIIA-C and Stage IV melanoma resected to be NED with DC-rIL-2-VMO induced a tumor-specific antibody response. The presence of these anti-melanoma antibodies suggests that this vaccine may be effective in slowing the progression of melanoma in some patients via cellular and humoral immune mechanisms. DC-rIL-2-VMO has been FDA-approved for Phase I trials. 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 4756.
Abstract C18: Identification of epigenetically silenced tumor suppressor genes in colorectal cancer
Authors: Ahmed Khamas, Toshiaki Ishikawa, Satoru Iida, Megumi Ishiguro, Kazuro Shimokawa, Hiroshi Mizushima, Hiroyuki Uetake, Kenichi Sugihara
Journal: Cancer Research (2011)

Abstract Background: The importance of gene inactivation by promoter CpG island hypermethylation has encouraged the unearthing of silenced tumor suppressor genes (TSGs) in various cancers. We aimed to identify and examine novel methylation silenced TSGs in colorectal cancer (CRC). Method: We employed Oligonucleotide microarray to find changes in global gene expression of five colon cancer cell lines (HCT116, RKO, Colo320, SW480, and HT29) that were analyzed before and after treatment with the demethylating agent 5-aza-2′-Deoxycitidine (5-aza-dC), expression of the responding genes was compared with microarray expression data of CRC tissue samples. Five genes (ASPP1, GADD45B, LIFR, SCARA5, and THSD1), which had a putative 5′ CpG islands in their promoter, were subjected to methylation-specific PCR (MSP) using 13 colon cell lines and 23 paired tumor and normal CRC tissues. Result: Seventy-two genes were up-regulated in demethylated cell lines and were simultaneously down-regulated in primary colorectal carcinomas, including genes that were known to be frequently hypermethylated and silenced in CRC. Among 13 colon cancer cell lines, hypermethylation was identified for three of five candidate genes, LIFR (61%), SCARA5 (15%), and THSD1 (23%). The methylation status of LIFR, SCARA5, and THSD1 was subsequently investigated in 23 colorectal tumors, hypermethylation was detected in (87%), (17%), and (9%), respectively. Data from normal colorectal mucosa demonstrated that the observed promoter hypermethylation was cancer-specific in the latter two genes. Conclusion: The use of a refined microarray screening led to the identification of two TSGs affected by hypermethylation with a cancer-specific manner in CRC. SCARA5 and THSD1 may have a role in CRC tumorigenesis. 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 C18.