tbuckley/cabot-search huggingface dataset:
Abstract 4249: NGR-TNF, a novel direct-acting vascular targeting agent, does not induce “cytokine-rebound” recruitment of pro-angiogenic bone-marrow derived cells
Authors: Paola Di Matteo, Christina Hackl, Christopher Jedeszko, Barbara Valentinis, Claudio Bordignon, Catia Traversari, Robert S. Kerbel, Gian-Paolo Rizzardi
Journal: Cancer Research (2011)

Abstract NGR-TNF, presently in advanced clinical development, is a direct-acting vascular targeting agent coupling the CNGRCG peptide (NGR), homing to angiogenic blood vessels, and tumour necrosis factor alpha (TNF). In order to further elucidate the mechanism of action, we investigated whether NGR-TNF mobilizes bone-marrow derived cells (BMDCs) and growth factors. Herein, treatment with either certain chemotherapy drugs at maximum tolerated dose (e.g. paclitaxel, cyclophosphamide, 5-FU), vascular-disrupting agents (VDAs; e.g. fosbretabulin, Oxi4503), or local irradiation can rapidly induce mobilization and subsequent tumor homing of proangiogenic BMDCs, such as circulating endothelial progenitor cells (CEPs), CD11b/Tie-2-expressing monocytes (TEMs), CD11b+Gr1+ neutrophils and myeloid-derived suppressor cells (MDSCs), and CD11b+F4/80+ macrophages. Increase in several growth factors and chemokines, such as SDF-1, G-CSF as well as osteopontin, contribute to the mobilization of BMDCs that colonize the tumour site and induce angiogenesis and rapid tumor regrowth. Lewis lung carcinoma (LLC) cells were subcutaneously implanted into immunocompetent C57BL/6J mice or into GFP+ bone marrow-chimeric mice, obtained by transplanting into lethally irradiated C57BL/6J mice bone marrow cells from UBI-GFP/BL6 donors. Blood was obtained 4 or 24 hours after treatment with either NGR-TNF, VDA, an anti-VEGFR2/flk-1 antibody or saline, by either cardiac puncture or retro-orbital sinus bleeding. Using flow cytometry (LSRII), CEPs were defined as CD45-/CD13+/flk-1+/CD117+/7AAD-, TEMs as CD45+/CD11b+/Tie2+/flk-1+ and MDSCs as CD45+/CD11b+/Gr1+ cells. Levels of circulating growth factors were assessed by ELISAs. When administrated at low doses (optimal biological dose), comparable to doses being used in clinical trials, NGR-TNF causes a decrease of tumor blood vessels density and induces apoptosis of tumor cells and tumor endothelial cells in vivo. It is worth noting that, unlike the above-mentioned treatments, NGR-TNF fails to mobilize or recruit to the tumor site different subtypes of pro-angiogenic BMDCs nor induces growth factors. Therefore, low doses of NGR-TNF exert an antitumor activity without inducing reactive a pro-angiogenic host response, which is likely an important feature for preventing/overcoming resistance and for designing combination therapeutic strategies. 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 4249. doi:10.1158/1538-7445.AM2011-4249
The Risk of Recurrent Deep Venous Thrombosis among Heterozygous Carriers of Both Factor V Leiden and the G20210A Prothrombin Mutation
Authors: Valerio De Stefano, Ida Martinelli, Pier Mannuccio Mannucci, Katia Paciaroni, Patrizia Chiusolo, Ida Casorelli, Elena Rossi, Giuseppe Leone
Journal: New England Journal of Medicine (1999)

Point mutations in the factor V gene (factor V Leiden) and the prothrombin gene (the substitution of A for G at position 20210) are the most common causes of inherited thrombophilia. Whether or not factor V Leiden increases the risk of recurrent deep venous thrombosis is controversial, and there is no information on the risk of recurrence among carriers of both mutations.
Abstract 1175: Persistent upregulation of U6 small RNA in the serum of breast cancer patients
Authors: Hitesh Appaiah, Chirayu Goswami, Lida Mina, Sunil Badve, George Sledge, Yunlong Liu, Harikrishna Nakshatri
Journal: Cancer Research (2011)

Abstract Serum microRNAs have the potential to be valuable biomarkers of cancer. This investigation addresses two issues that impact their utility: a) appropriate normalization controls and b) whether their altered levels persist in patients who are clinically free of disease. Sera from 40 age-matched healthy women and 39 breast cancer patients without clinical disease at the time of serum collection were analyzed for microRNAs let-7f, miR-16, miR-21, and miR-155 using quantitative real-time PCR. U6 and 5S, which are transcribed by RNA polymerase III (RNAP-III), and the small nucleolar RNA44 (SNORD44), were also analyzed for normalization. Sera from additional 14 healthy and 15 patients with overt metastasis were examined for U6, miR-16, and miR-195 levels. SNORD44 and miR-16 did not vary significantly in the sera of patients and healthy volunteers and thus served as normalization controls. Unexpectedly, we observed upregulation of U6 (2.4 fold, p=0.001) and 5S RNAs (1.7-fold, p=0.02) but not any of the other microRNAs analyzed in the sera of patients without active disease. U6 level was significantly elevated in the sera of patients with overt metastasis compared to healthy women. Elevated serum U6 levels in patients who are clinically cancer-free suggest persistently altered systemic RNAP-III activity in cancer patients and that cancer cells may not be the only primary source of serum U6. Additionally, U6 and 5S, to some extent, are of limited value for normalization. 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 1175. doi:10.1158/1538-7445.AM2011-1175
Abstract 5072: Human tumor derived Oncoprint® platform predicts molecular mechanism of sensitivity and resistance to Fragmin in pancreatic cancer.
Authors: Mallikarjun Sundaram, Saravanan Thiyagarajan, Muthu Dhandapani, Nilesh Brijwani, Arun Prasath, Allen Thayakumar, Ameer Kamal, Padhma Radhakrishnan, Biswanath Majumder, Baraneedharan Ulaganathan, Pradip K. Majumder
Journal: Cancer Research (2013)

Abstract One of the formidable challenges in cancer therapeutics is developing and validating a highly effective preclinical testing platform. However, existing in vitro and in vivo testing platforms show limited success. In this context, we have developed Oncoprint®, a novel clinically relevant preclinical platform demonstrated to have very high correlation to clinical outcome for chemotherapeutics as well as targeted drugs in multiple solid and hematological cancers (with overall sensitivity of 88% and specificity of 90% in more than 500 patients). Oncoprint® is a rapid reproducible ex-vivo tumor explant system, developed to mimic native tumor microenvironment. By including autologous paracrine growth factors, cancer specific customized matrix support, autologous immune environment along with other growth promoting conditions, significant improvements were observed in viability, proliferation of tumors including retention of tumor/stroma, cancer phenotypes, integrity at micro-architecture level and maintenance of functional signaling network. Using this platform we assessed the anti-tumor efficacy of Fragmin (a low molecular weight heparin-LMWH) alone as well as in combination with various Standard-Of-Care drugs (SOCs) and compared the outcome with efficacy derived from the use of SOCs alone in twenty patient derived pancreatic tumors. Clinical trial data indicates that Fragmin when administered in patients with advanced pancreatic cancer decreased levels of circulating-tissue factor antigen and attenuated induction of cellular invasion in their blood. Oncoprint data indicates that Fragmin has potent anti-angiogenic activity as a single agent (in ∼ 77% tumor samples) and enhanced anti-proliferative and apoptotic effect in combination with SOC (Cisplatin and Gemcitabine) compared to SOC alone in ∼ 30% of these pancreatic tumors. . Our study has been powered to include 75-100 patient derived refractory pancreatic tumors for further evaluation. Detailed molecular profiling studies are underway to understand the mechanism of action of this drug to delineate the biology behind response in the responder sub-population. Citation Format: Mallikarjun Sundaram, Saravanan Thiyagarajan, Muthu Dhandapani, Nilesh Brijwani, Arun Prasath, Allen Thayakumar, Ameer Kamal, Padhma Radhakrishnan, Biswanath Majumder, Baraneedharan Ulaganathan, Pradip K. Majumder. Human tumor derived Oncoprint® platform predicts molecular mechanism of sensitivity and resistance to Fragmin in pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5072. doi:10.1158/1538-7445.AM2013-5072
Allergic Reaction to Penicillin
Authors: Eugene M. Holden
Journal: New England Journal of Medicine (1947)

EXTRACTS prepared from various species of the dermatophytes show potent antigenic properties. Jadassohn,1 using the Schultz-Dale technic, proved that pathogenic fungi contained not only species-specific antigens but also an antigenic fraction common to all species. Clinically, dermatologists have long been cognizant of explosive reactions from fungus toxins, manifested by generalized "ids" and by bullous eruptions. Therefore, it seemed probable that patients being treated with penicillin would exhibit allergic reactions, either to a common hyphomycetic allergen or to a specific penicillin allergen.Reactions to penicillin are clinically infrequent, but do occur. A recent case focused attention on this subject and prompted . . .
Incidental Localization of Baker's Cyst With Tc-99m Human Immunoglobulin
Authors: GÜLSEREN ARAS, ÖZLEM KÜÇÜK, AYFER SOYLU, ERKAN İBİS, ASIM AKIN
Journal: Clinical Nuclear Medicine (1998)

Behçets' syndrome is a multisystem disorder, with popliteal cysts previously described. A Baker's cyst was incidentally detected with Tc-99m HIG imaging in a 31-year-old woman with Behçet's syndrome.
Abstract 969: Revising and updating NCI's best practices for biospecimen resources
Authors: Jimmie Vaught, Nicole Lockhart, Rihab Yassin, Kimberly Myers, Mark David Lim, Ian Fore, Sherilyn Sawyer, Helen Moore, Carolyn Compton
Journal: Cancer Research (2010)

Abstract In 2007 the NCI Office of Biorepositories and Biospecimen Research (OBBR) published the NCI Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/practices/). The Best Practices were originally published following a public comment period on the Federal Register and internal review by several National Institutes of Health offices. The Best Practices do not comprise detailed laboratory procedures and are intended to be adapted, as appropriate, based on the mission and scientific needs of individual biospecimen resources. The Best Practices were developed to address the heterogeneity and the generally unknown or uneven quality of biospecimens used for research, which can lead to unreliable and irreproducible results. In addition to these technical and operational issues, many ethical, legal and policy guidelines and concerns must be addressed when conducting research involving the use of biospecimens from patients and other research participants. The revised version of the Best Practices is intended to respond to comments received from the biospecimen resource community over the past 2 years, and provide more current and detailed recommendations related to biospecimen and data quality. Major revisions include the addition of new sections on biospecimen resource management and operations and conflicts of interest, and expansion of recommendations related to custodianship and informed consent based on the consensus findings of the 2007 NCI-hosted Workshop on Custodianship and Ownership Issues in Biospecimen Research, addition of current references throughout the document, and harmonization with current Federal guidance documents and recommendations from international biospecimen organizations. The revised Best Practices will be launched using an interactive Web format, to provide a mechanism for more frequent updates and encourage feedback from the community. The Best Practices will continue to evolve as the field of biospecimen biology advances; novel scientific, technological, and clinical practices develop; and new ethical and legal policies and regulations emerge. Results from biospecimen research initiatives will inform future versions of the Best Practices as the community moves toward the development of evidence-based standard operating procedures that are both specimen type specific and analysis platform specific. The NCI is committed to maintaining current and scientifically accurate best practices for biospecimen resources and will continue to solicit input from stakeholders in the cancer research community. 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 969.
Abstract 2894: Co-regulatory relationship between estrogen receptor alpha and the mTOR/S6K1 signaling pathways
Authors: Marina K. Holz, D. Myriam Maruani, Fannie Seligman, Tirtza Spiegel, Emily Harris, Avielle Shachter, Faygel Beren
Journal: Cancer Research (2011)

Abstract ERα mediates the proliferative effects of estrogen and represents an important clinical target in treatment of breast cancer. Tamoxifen is an anti-estrogen that has become the standard agent for the treatment of ER-positive breast cancer, where it acts as an antagonist. However, resistance to tamoxifen, and other endocrine or anti-estrogen therapies develops in many cases. One mechanism by which resistance develops is through phosphorylation of ERα, allowing it to act in estrogen-independent manner. Phosphorylation of Ser118 and Ser167 is important for transcriptional activity of ERα. The regulation of these sites is complex, involving inputs from the mTOR and MAPK signaling pathways. Importantly, ERα phosphorylation correlates with resistance to tamoxifen, and is a prognostic marker for disease progression and survival. Thus, the mechanism of these phosphorylation events, as well as the identity of the kinases responsible may have important clinical consequences. In this study we demonstrate that the mTOR/S6K1 pathway controls activation of ERα by phopshorylating it on these two critical residues. Chromosomal region 17q23 containing the RPS6KB1 gene is frequently amplified in breast cancer cells, and S6K1 is overexpressed in about 30% of cases. Overexpression of S6K1 correlates with increased rapamycin sensitivity. The role of S6K1 in disease development and progression is supported by the observation that S6K1 overexpression is associated with poor prognosis in breast cancer patients. However, the reason for high-level amplification of the RPS6KB1 gene specifically in breast cancer, and not other cancer types is not well understood. In this study, we demonstrate that in response to estrogen activation, ERα activates expression of S6K1 by upregulating transcription of the RPS6KB1 gene. Increased levels of S6K1 promote further phosphorylation and activation of ERα, creating a positive feed-forward loop. We hypothesize that this relationship promotes breast cancer cell growth, thus providing a selective advantage to S6K1- and ERα-overexpressing cells. 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 2894. doi:10.1158/1538-7445.AM2011-2894
Regulation of Adhesion Molecules during Human Endotoxemia
Authors: BERND JILMA, ANDREW BLANN, THOMAS PERNERSTORFER, PETRA STOHLAWETZ, HANS-GEORG EICHLER, BARBARA VONDROVEC, JEAN AMIRAL, VOLKER RICHTER, OSWALD F. WAGNER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Gram-negative septic shock is mediated in part by endotoxin (lipopolysaccharide; LPS), and animal models have shown that blockade of even single adhesion molecules considerably improves survival. Thus interference with the adhesion cascade may provide a useful therapeutic approach in human sepsis. Young healthy men (n = 30) each received a bolus of 4 ng/kg LPS intravenously to study the effects of endotoxemia on adhesion processes in humans and to identify potential targets for pharmacologic intervention. One third of subjects received pretreatment with 1,000 mg aspirin and 1,000 mg paracetamol to study potential antiinflammatory effects of aspirin or effects of antipyresis. Circulating neutrophils dropped by − 80% at 67 min after LPS, monocytes by − 96% at 90 min, and lymphocytes by − 85% at 240 min. l-selectin expression decreased, particularly on monocytes. Circulating (c)E-selectin levels increased by 820%, von Willebrand factor-Ag (vWF), soluble thrombomodulin, circulating (c)P-selectin, circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular cell adhesion molecule-1 (cVCAM-1) by a mean of 65 to 98% (p < 0.001 for all), but cL-selectin by only 15%. Urinary excretion of soluble adhesion molecules was negligible. Aspirin had no influence on the LPS-induced changes of adhesion parameters, but paracetamol blunted the relative increase in vWF while having no effects on the other parameters measured. The consistent, profound, and early upregulation of cE-selectin during endotoxemia indicates that cE-selectin may be a better surrogate marker to monitor the activation status of endothelial cells in systemic inflammation than the other markers measured. Although aspirin did not have any antiinflammatory effects in this model, paracetamol lowered the relative increase in vWF.
SP0148 Using Mindfulness and Emotion-Focussed Approaches to Support Patients
Authors: H. A. Zangi
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Rheumatic diseases are associated with increased risk of psychological distress, anxiety and depressed mood. Negative emotional states, such as sorrow, worry, irritability and fatigue are common. Recent studies have shown that acknowledgement and expression of these distressing emotions are an essential part of adjustment to chronic diseases. In recent years a range of newer approaches categorised as mindfulness- and acceptance-based therapies have been applied in the treatment of the mental distress that may accompany chronic diseases. The core aspect in these approaches is training in open-hearted moment-to-moment awareness of internal experiences, such as thoughts, emotions and sensations without judging or wishing things to be otherwise. These experiences are seen as a part of being human, rather than a sign of pathology, weaknesses or limitations. It is believed that experiencing the present moment with an attitude of openness, curiosity and acceptance can effectively counter the effect of stressors, whereas excessive orientation towards the past or future can be related to feelings of depression and anxiety. The basic methods in mindfulness training are different awareness exercises with the breath as an anchor, body scan, mindful movement through yoga exercises and awareness in daily activities. Reflections on own experiences are promoted through group discussions. The most frequently applied approach is the mindfulness-based stress reduction program (MBSR). Another approach is acceptance and commitment therapy (ACT), in which mindfulness-based exercises are combined with values-based action. A third approach is the Norwegian vitality training program (VTP) that combines mindfulness training with various creative exercises and expressive writing. These approaches have been applied to people with a wide range of chronic somatic conditions, including chronic pain, fibromyalgia and inflammatory arthritis. Although the evidence is still limited, existing studies have shown that mindfulness-based training has the potential to alleviate emotional distress and promote well being in terms of reduced anxiety, depression and fatigue, and increased self-efficacy in people with fibromyalgia and inflammatory arthritis. The effects on pain are less conclusive. During the presentation, participants will have the opportunity to experience a short awareness exercise. <h3>Disclosure of Interest</h3> None Declared
TCT-113 Validating and updating a mortality risk prediction score after percutaneous coronary intervention in Brazil
Authors: Lucas Lodi-Junqueira, José Luiz P da Silva, Guilherme Rafael S Athayde, Lorena R. Ferreira, Júlio C. Borges, Thalles O. Gomes, Humberto L. Gonçalves, Bruno R. Nascimento, Enrico A. Colosimo, Pedro A. Lemos, Antônio L. Ribeiro
Journal: Journal of the American College of Cardiology (2014)
Endoscopic detorsion for sigmoid volvulus using unsedated water-immersion colonoscopy
Authors: S. Sugimoto, T. Mizukami, T. Ito, Y. Tsunoda, S. Imamura, T. Tamura, S. Nagakubo, Y. Morohoshi, Y. Koike, Y. Fujita, H. Komatsu
Journal: Endoscopy (2013)

We report a simple method of endoscopic detorsion for sigmoid volvulus using unsedated water-immersion colonoscopy, which we currently use in the majority of our cases.