tbuckley/cabot-search huggingface dataset:
A meta-analysis of anticoagulants as cancer treatment: Impact on survival and bleeding complications
Authors: N. M. Kuderer, A. A. Khorana, G. H. Lyman, C. W. Francis
Journal: Journal of Clinical Oncology (2007)

9071 Background: There is substantial laboratory evidence that anticoagulants, in particular the low-molecular-weight heparins (LMWH), exert an antitumor effect, while clinical trials have reported conflicting results. This study represents the first comprehensive systematic review and meta-analysis of the evidence from randomized controlled trials (RCTs) evaluating specifically the impact of anticoagulants on survival and safety in cancer patients without venous thromboembolism (VTE). Methods: An exhaustive systematic literature review of RCTs was performed without language restrictions, including a comprehensive search of electronic databases through May 2006 with subsequent weekly updates to the end of 2006 (Medline, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, DARE, and major conference proceedings) and relevant article references. Two reviewers extracted the data independently. Primary study outcomes were 1-year overall mortality and all bleeding complications. Major and fatal bleeding complications were secondary outcomes. The meta- analysis was performed utilizing the Mantel-Haenszel method. Results: All identified 11 RCTs were performed in solid tumor patients. Anticoagulation significantly decreased overall mortality across all studies with a relative risk (RR) of 0.905 (95%CI: 0.847–0.967; p=0.003). The survival improvement appears not to be due to the prevention of fatal VTE. All bleeding complications (RR=2.309; 95%CI: 1.928–2.764; p&lt;0.0001) and major bleeding events (RR=2.598; 95%CI; 1.936–3.488; p&lt;0.0001) occurred more frequently with anticoagulation. The relative risk for mortality was 0.877 (95%CI: 0.789–0.975; p=0.015) with LMWH, compared to warfarin (RR=0.942; 95%CI: 0.854–1.040; p=0.239). Warfarin resulted in higher rates for all and major bleeding complications compared to LMWH (p&lt;0.0001, respectively). Conclusions: Anticoagulants significantly improved overall survival in cancer patients while increasing the risk of bleeding complications. Despite these encouraging findings, given limitations of available data and the potential for life-threatening complications, the use of anticoagulants as antineoplastic therapy cannot be recommended until additional RCTs confirm these results. No significant financial relationships to disclose.
Recombinant adenovirus-p53 combined with chemotherapy in treatment of locally advanced cervical cancer (a phase II study).
Authors: Jian Zhou, Fumin LIU, Jie Xiao
Journal: Journal of Clinical Oncology (2013)

5525 Background: To evaluate the efficacy and safety of recombinant adenovirus-p53 (rAd-p53) combined with chemotherapy in treatment of locally advanced cervical cancer. Methods: Forty patients with stage IIb2 IV locally advanced cervical cancer were randomly divided into 2 groups: 20 patients receiving gene plus chemotherapy (PCG) and 20 receiving sole chemotherapy (CG). The patients in PCG were given one course of PVB (cisplatin + vincristine + pingyangmycin) and 5 times intratumoral injections of rAd-p53 at a dose of 2 x 10 12 viral particles once per 3 days. The CG patients received a sole course of PVB. The study patients were followed up for at least one year. The VEGF, p53, Bax, and p21 protein expression in pre- and post-treatment tumor tissues were examined by immunohistochemistry. Results: The response was evaluated at 3 months after treatments. The response rates (CR + PR) were 95% and 75% for the PCG and CG patients, respectively. P53 proteins were strongly expressed in the tumor tissues from both groups. There were no significant changes in expression level of the p53 protein in the tumor tissue from pre- and post-treatment. However, the VEGF, Bax, and p21 protein expressions significantly increased in PCG after treatment. The overall one-year survive rates were 90% and 65%, respectively. A mild to medium grade of fever was found in 90% of the PCG patients. No serious of adverse events relative to rAd-p53 were observed. Conclusions: Combined the rAd-p53 gene with chemotherapy is an effective treatment for the patients with advanced cervical cancer. The rAd-p53 gene therapy is a safe treatment.
Application of a Lifestyle-Based Tool to Estimate Premature Cardiovascular Disease Events in Young Adults
Authors: Holly C. Gooding, Hongyan Ning, Matthew W. Gillman, Christina Shay, Norrina Allen, David C. Goff, Donald Lloyd-Jones, Stephanie Chiuve
Journal: JAMA Internal Medicine (2017)

Few tools exist for assessing the risk for early atherosclerotic cardiovascular disease (ASCVD) events in young adults.
The Role of Peg-Interferon (P-IFN) in Salvaging Patients with Chronic Myeloid Leukemia Chronic Phase (LMC-CP) in Molecular Resistant (MolRes) to Second- Generation Tyrosine Kinase Inhibitors (TKIs)
Authors: Manuel Ayala, Antonieta Chavez, Jacqueline Domínguez
Journal: Blood (2016)
Gene expression profiling of microdissected stroma from normal and malignant ovary identifies a role for CTGF in ovarian tumor progression.
Authors: Goli Samimi, Tomas Bonome, Mike Radonovich, Cindy Pise-Masison, John Brady, Sue Ghosh, Shu-wing Ng, Samuel Mok, Michael Birrer
Journal: Clinical Cancer Research (2007)

A75  It is estimated that in 2007 there will be approximately 22,430 new cases and 15,280 deaths due to ovarian cancer in the US. This high fatality rate is due in part to late diagnosis of advanced-stage disease which has already spread beyond the ovary. A majority of ovarian tumors arise from the surface epithelium of the ovary. While cell signaling between ovarian surface epithelial cells and their supporting stromal cells is required to maintain normal function of the ovary, the signaling events between ovarian tumor epithelial cells and their surrounding stromal cells remain unclear. The aim of this study was to investigate alterations in gene expression that occur in tumor-derived versus normal stromal cells. We analyzed gene expression of 51 laser-capture microdissected tumor and 10 normal stromal samples by Affymetrix microarrays. BRB-ArrayTools software (NCI) was used to analyze the data. Unsupervised hierarchical clustering analysis clearly distinguished tumor-associated stroma from normal ovarian stroma. Supervised class comparison analysis identified 2,703 probe sets (p
Efficacy and tolerance of treatments received beyond progression in men with metastatic hormone-naive prostate cancer treated with androgen deprivation therapy (ADT) with or without docetaxel in the GETUG-AFU 15 phase III trial.
Authors: Pernelle Lavaud, Gwenaelle Gravis, Clemence Legoupil, Florence Joly, Stephane Oudard, Franck Priou, Loic Mourey, Michel Soulie, Igor Latorzeff, Remy Delva, Ivan Krakowski, Brigitte Laguerre, Christine Theodore, Jean Marc Ferrero, Philippe Beuzeboc, Muriel Habibian, Stephanie Foulon, Jean Marie Boher, Gabrielle Tergemina-Clain, Karim Fizazi
Journal: Journal of Clinical Oncology (2016)

5080 Background: Since 2015, docetaxel chemotherapy, combined with ADT, is considered the standard of care in fit men with metastatic hormone-naive prostate cancer (m-HNPC), based on data from three phase III trials (GETUG-AFU 15, CHAARTED, and STAMPEDE). No data are currently available regarding the treatments used beyond progression after upfront ADT and docetaxel. Methods: We retrospectively collected data from patients (pts) participating in the GETUG-AFU 15 phase III trial concerning treatments received beyond progression for castration-resistant disease (CRPC) in both arms (ADT and ADT + docetaxel) including treatment efficacy (measured by a PSA decline > 50%, physician assessment of clinical benefit, and time to events), and toxicity (NCI-CTC grading). Results: Data concerning 164 pts are currently available. The treatments most frequently used and their efficacy are detailed in the Table. Toxicity was mild, with only rare grade 3-4 events (16% with first treatments and 13% with second treatments used for CRPC) and no treatment-related death. Conclusions: In this retrospective analysis, anticancer activity was suggested with androgen receptor axis-targeted agents in patients with metastatic prostate cancer treated upfront with ADT + docetaxel. Rather limited activity was observed following a docetaxel rechallenge in this setting. Treatment used for CRPC (n = 164 pts) PSA response (ADT vs ADT+D) Symptomatic response (ADT vs ADT+D) Median PFS Months (95%CI) (ADT vs ADT+D) First treatment for CRPC Docetaxel (n = 66) 15/47 (32%) vs 2/12 (17%) 11/32 (34%) vs 3/9 (33%) 6.8 (4.8-9) vs 4.1 (2.9-8.2) Bicalutamide (n = 56) 7/26 (27%) vs 3/24 (13%) 0/11 (0%) vs 3/19 (16%) 7.8 (4.1-14.4) vs 7.7 (2.8-8.9) Abiraterone or Enzalutamide (n = 12) 2/2 vs 6/10 Second treatment for CRPC Docetaxel (n = 34) 10/18 (56%) vs 2/13 (15%) 4/12 (33%) vs 3/9 (33%) 4.3 (2.5-8.6) vs 3.5 (1.4-6.8) Abiraterone or Enzalutamide (n = 32) 6/16 (38%) vs 7/10 (70%) 4/8 vs 2/9 7 (1.6-9.5) vs 9 (4.6-24) Mitoxantrone (n = 8) 0/8 vs 0/5 Carbo-VP16 (n = 8) 3/7 vs 1/1
Dementia prevention, intervention, and care
Authors: Gill Livingston, Andrew Sommerlad, Vasiliki Orgeta, Sergi G Costafreda, Jonathan Huntley, David Ames, Clive Ballard, Sube Banerjee, Alistair Burns, Jiska Cohen-Mansfield, Claudia Cooper, Nick Fox, Laura N Gitlin, Robert Howard, Helen C Kales, Eric B Larson, Karen Ritchie, Kenneth Rockwood, Elizabeth L Sampson, Quincy Samus, Lon S Schneider, Geir Selbæk, Linda Teri, Naaheed Mukadam
Journal: The Lancet (2017)
Novel Class of Direct Thrombin Inhibitors Prevent Thrombosis By Inhibiting Fibrinogen Cleavage While Preserving Platelet Function
Authors: Mohan Sivaraja, Sivan Sizikov, Nichole Sandoval, Kenneth Lin, Lev Igoudin, Subhadra Dash, Chengpei Xu, Daniel Clemens, Angels Estiarte, Timothy Shiau, Kevin Short, David Williams, Anirban Datta, David Kita
Journal: Blood (2016)
PTH-055 Vitamin b12 deficiency is common in children with ulcerative colitis as well as crohn’s disease
Authors: S Ibbs, R Muhammed
Journal: Gut (2017)

Introduction  Patients with Crohn’s Disease (CD) who frequently have ileal involvement are at increased risk of vitamin B12 deficiency. Vitamin B12 deficiency in patients with ulcerative colitis (UC) is not widely reported. The aim of our project is to assess the prevalence of vitamin B12 deficiency in patients with Crohn’s Disease and Ulcerative colitis and to identify risk factors associated with it.  Method  As part of routine care, patients attending Inflammatory Bowel Disease (IBD) service at Birmingham Children’s Hospital undergo vitamin B12 assessment at least once a year. We included all patients with CD and UC diagnosed who had vitamin B12 measured between 2010–2015. Retrospective review of patient notes and laboratory results were done. Patients with serum vitamin B12 values  Results  In total 244 patients (157 with CD and 87 with UC) were included. 45/157 (29%) patients with CD had low vitamin B12 levels. 28/87 (32%) patients with UC had low vitamin B12 levels. In patients with Crohn’s disease, disease not being in remission was associated with vitamin B12 deficiency ( p  Conclusion  Prevalence of Vitamin B12 deficiency is high in patients with Crohn’s Disease and Ulcerative colitis. Vitamin B12 levels need to be checked in all patients with IBD rather than testing based on presence of risk factors.  Disclosure of Interest  None Declared
Abstract 5235: Affecting activity of the linear ubiquitin chain assembly complex (LUBAC) with stapled alpha-helical peptides
Authors: Amanda L. Whiting, Francisco Aguilar-Alonso, Joseph J. Mitala, Federico Bernal
Journal: Cancer Research (2017)

Abstract The linear ubiquitin chain assembly complex (LUBAC) is the only E3 ubiquitin ligase known to generate linear polyubiquitin chains in vitro. LUBAC is composed of three proteins - HOIL-1L, HOIP and SHARPIN - of which the interaction between HOIL-1L and HOIP has been shown to be critical for LUBAC assembly and function. This interaction occurs between the ubiquitin-like (UBL) domain of HOIL-1L and the ubiquitin-associated (UBA) domain of HOIP. One known substrate of LUBAC is the regulatory subunit NEMO (NF kappa B essential modulator), part of the IKK complex, which results in activation of NF-κB. We hypothesize that disruption of the HOIL-1L-HOIP interaction would prevent LUBAC ubiquitylation activity and result in down-regulated activation of NF-κB. We have synthesized a family of small inhibitor peptides designed to mimic aspects of the bent alpha-helical interacting interface of HOIP-UBA. Here we demonstrate how single amino acid substitutions and hydrocarbon stapling can affect overall peptide shape and helicity, and correlate that structural information to peptide binding affinity, ability to affect LUBAC complex formation and resulting effect on LUBAC ubiquitylation activity in vitro. These findings continue to validate inhibition of LUBAC via interference with the HOIL-1L-HOIP interaction as a potential target to affect NF-κB signaling. Compounds which affect LUBAC activity have potential use in LUBAC-dependent NF-κB activation in the activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), the DLBCL subtype that is most resistant to current therapies. Citation Format: Amanda L. Whiting, Francisco Aguilar-Alonso, Joseph J. Mitala, Federico Bernal. Affecting activity of the linear ubiquitin chain assembly complex (LUBAC) with stapled alpha-helical peptides [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5235. doi:10.1158/1538-7445.AM2017-5235
Molecular classification of tumour cells in a patient with intravascular large B‐cell lymphoma
Authors: W.M. Bauer, M.C. Aichelburg, J. Griss, C. Skrabs, I. Simonitsch‐Klupp, A.I. Schiefer, H. Kittler, U. Jäger, M. Zeyda, R. Knobler, G. Stingl
Journal: British Journal of Dermatology (2017)

Intravascular large B‐cell lymphoma (IVLBCL) is a rare type of extranodal LBCL. It is characterized by the proliferation of tumour cells exclusively intraluminally in small blood vessels of different organs. The clinical manifestation depends on the type of organ affected; additionally, a haemophagocytic syndrome can be observed in some patients. The aim was to further understand the nosology of this lymphoma as, due to its rarity and in spite of detailed immunohistochemical investigations, its exact nosology is only incompletely understood. We used microarray‐based analysis of gene expression of tumour cells isolated from a patient with primary manifestation of the lymphoma in the skin and compared it with various other diffuse LBCLs (DLBCLs) as well as a previously published DLBCL classifier. In unsupervised analyses, the tumour cells clustered together with non‐germinal centre B‐cell (non‐GCB) DLBCL samples but were clearly distinct from GCB‐DLBCL. Analogous to non‐GCB DLBCL, molecular cell‐of‐origin classification revealed similarity to bone‐marrow derived plasma cells. The IVLBCL of this patient showed molecular similarity to non‐GCB DLBCL. Due to the prognostic and increasingly also therapeutic relevance of molecular subtyping in DLBCL, this method, in addition to immunohistochemistry, should also be considered for the diagnosis of IVLBCL in the future.
Persons with chronic widespread pain experience excess mortality: longitudinal results from UK Biobank and meta-analysis
Authors: Gary J Macfarlane, Maxwell S Barnish, Gareth T Jones
Journal: Annals of the Rheumatic Diseases (2017)

It is uncertain whether persons with chronic widespread pain (CWP) experience premature mortality. Using the largest study conducted, we determine whether such a relationship exists, estimate its magnitude and establish what factors mediate any relationship.UK Biobank, a cohort study of 0.5 million people aged 40-69 years, recruited throughout Great Britain in 2006-2010. Participants reporting 'pain all over the body' for >3 months were compared with persons without chronic pain. Information on death (with cause) was available until mid-2015. We incorporated these results in a meta-analysis with other published reports to calculate a pooled estimate of excess risk.7130 participants reported CWP and they experienced excess mortality (mortality risk ratio 2.43, 95%CI 2.17 to 2.72). Specific causes of death in excess were cancer (1.73adjusted age and sex, 95% CI 1.46 to 2.05), cardiovascular (3.24adjusted age and sex, 95% CI 2.55 to 4.11), respiratory (5.66adjusted age and sex, 95% CI 4.00 to 8.03) and other disease-related causes (4.04adjusted age and sex, 95% CI 3.05 to 5.34). Excess risk was substantially reduced after adjustment for low levels of physical activity, high body mass index, poor quality diet and smoking. In meta-analysis, all studies showed significant excess all-cause (combined estimate 1.59 (95% CI 1.05 to 2.42)), cardiovascular and cancer mortality.Evidence is now clear that persons with CWP experience excess mortality. UK Biobank results considerably reduce uncertainty around the magnitude of excess risk and are consistent with the excess being explained by adverse lifestyle factors, which could be targeted in the management of such patients.
Recommendation on Design, Execution, and Reporting of Animal Atherosclerosis Studies: A Scientific Statement From the American Heart Association
Authors: Alan Daugherty, Alan R. Tall, Mat J.A.P. Daemen, Erling Falk, Edward A. Fisher, Guillermo García-Cardeña, Aldons J. Lusis, A. Phillip Owens, Michael E. Rosenfeld, Renu Virmani
Journal: Circulation Research (2017)

Animal studies are a foundation for defining mechanisms of atherosclerosis and potential targets of drugs to prevent lesion development or reverse the disease. In the current literature, it is common to see contradictions of outcomes in animal studies from different research groups, leading to the paucity of extrapolations of experimental findings into understanding the human disease. The purpose of this statement is to provide guidelines for development and execution of experimental design and interpretation in animal studies. Recommendations include the following: (1) animal model selection, with commentary on the fidelity of mimicking facets of the human disease; (2) experimental design and its impact on the interpretation of data; and (3) standard methods to enhance accuracy of measurements and characterization of atherosclerotic lesions.
Breast cancer and neuroblastoma models for the in vivo study of stem cell like cancer cells in immune competent mice
Authors: Joerg A. Krueger, Charles D. Kaplan, Yunping Luo, He Zhou, Rong Xiang, Ralph A. Reisfeld
Journal: Cancer Research (2006)

1018   The cancer stem cell hypothesis suggests that malignant clones in a tumor are maintained by a rare fraction of cells with stem cell properties. Such stem cell like cancer cells (SCLCC) have recently been described in solid tumors such as breast carcinoma and various brain tumors. One of the key features of such SCLCCs is their ability to repopulate entire tumors in vivo. Primarily human cancer stem cells have been isolated thus far and in vivo experiments rely on the use of immuno-compromised SCID/NOD mice. Here we demonstrate that a SCLCC population can be identified in the murine 4T1 breast cancer and NXS2 neuroblastoma cell lines and may serve as a model to study SCLCCs in immuno-competent syngeneic mouse models. To identify potential cancer stem cells murine 4T1 breast carcinoma and NXS2 neuroblastoma cells were stained with Hoechst dye 33342. We clearly distinguished in both cell lines a low staining Side Population (SP), a compartment which has been shown to be enriched for stem cells, of 2% and 0.2% respectively. Specificity of the SP population was confirmed by co-incubation with the Ca++ Blocker Verapamil, which suppressed it in both cell lines. Phenotyping showed that 4T1 SP cells have a Sca-1high c-kit- CD45- phenotype and NXS2 SP cells a Sca-1high CD24high c-kit- CD45- GD2high phenotype. RT-PCR further revealed upregulation of the ABCG2 transporter and TGF-beta in SP cells. Since stem cells were shown to be resistant to various chemotherapeutic drugs, 4T1 cells were tested for chemoresistance against cisplatin and doxorubicin. Non-sorted as well as sorted cells from the SP compartment showed higher proliferation rates and lower numbers of apoptotic cells than non-SP cells. SP cells also revealed a significant decrease in intracellular doxorubicin compared to the non-SP compartment. Because stem cells have the ability to re-populate entire cell populations, sorted SP, non-SP and 4T1 cells were cultured in vitro and the degree of repopulation was determined under normal culturing conditions at different time points. Whereas both SP and non-SP sorted cells could repopulate parts of the other compartment, which suggests a certain heterogeneity in these populations, the percentages of repopulated cells was significantly higher in SP than non-SP sorted cells. Importantly, tumorogenicity was determined by orthotopical injection of sorted SP and non SP cells in Balb/c mice. Disease occurred in 7/8 mice of the SP injected mice but only in 2/8 of non-SP injected animals, with one of the two tumors being barely palpable. Furthermore, single cell suspensions of SP-induced tumors revealed an increased amount of cells in the SP compartment when compared to the non-SP tumor. These data suggest that the SP compartments in 4T1 and NXS2 cells are enriched in cells with stem cell properties and could serve as a model system for the study of SCLCCs in immune competent mice.
Comparison of positron emission tomography scanning and sentinel node biopsy in the detection of inguinal node metastases in patients with anal cancer
Authors: E. Milanesi, M. Mistrangelo, E. Pelosi, M. Bello, Isabella Castellano, Paola Cassoni, Umberto Ricardi, F. Munoz, P. Racca, V. Contu, G. Beltramo, L. Ciuffreda, Mario Morino, Antonio Mussa
Journal: Annals of Oncology (2009)