tbuckley/cabot-search huggingface dataset:
Abstract 4329: Modulation of metastatic behavior in breast cancers harboring p53 mutations
Authors: Bethanie L. Morrison, Federico Bernal
Journal: Cancer Research (2012)

Abstract The mutation of p53 generally occurs during the later stages of cancer and leads to the increased metastatic potential of triple negative (ER_/PR_/Her2_) breast cancer. The low survival rates of advanced metastatic cancer make it critical not only to understand the mechanisms underlying the functional implications of p53 mutation, but also to identify ways to regulate its impact in cancer cell physiology. We have previously described the design, synthesis, and evaluation of a stabilized α-helix of p53 (SAH-p53) capable of inhibiting the p53-HDM2 and p53-HDMX interactions in order to restore the functionality of p53. Despite having low expression of both HDM2 and HDMX and mutations in p53, SAH-p53 treatment of the triple negative breast cancer cell lines MDA-MB-231 and HS578T results in a modest decrease in proliferative activity. While mutant p53 is known to promote metastatic behavior of breast cancer cells, the propensity of triple negative breast cancer cells to migrate and invade through Matrigel in the presence of EGF was decreased by treatment with SAH-p53. The anti-proliferative and anti-migratory effects of SAH-p53 treatment are independent of each other, yet both are accompanied by an alteration in cell morphology that includes the loss of cell membrane integrity and actin cytoskeletal organization. The surface level of β1 integrin, which is typically kept constant by mutant p53, is decreased in the presence of SAH-p53, pointing to possible alterations in integrin recycling. SAH-p53 also causes a change in the localization of the adhesion protein and stem cell marker CD44. Moreover, it has been suggested that mutant p53 enhances invasive properties by interacting with and inhibiting isoforms of p63, which have been implicated in the regulation of cell adhesion. Treatment of the triple negative breast cancer cells with a stabilized α-helix of p63 showed a significant decrease in cell viability as well as an enhanced inhibition of migration when treated simultaneously with SAH-p53. Targeted therapy for triple negative breast cancer is currently very limited and patients must rely on standard chemotherapeutic regimens. These data show that the use of SAH-p53 and SAH-p63 peptides provides a novel avenue to study the molecular interactions that drive metastatic behavior originated by p53 gain-of-function mutations. 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 4329. doi:1538-7445.AM2012-4329
P605 GENE EXPRESSION AND DNA METHYLATION PROFILING OF DISTINCT ADULT HUMAN LIVER CELLS AND CULTURE-ACTIVATED HEPATIC STELLATE CELLS
Authors: A. El Taghdouini, A.L. Sørensen, M. Coll, I. Mannaerts, C.I. Øie, Å.A. Fretland, B.I. Rosøk, M. Najimi, E. Sokal, A. Luttun, B. Smedsrød, P. Sancho-Bru, P. Collas, L.A. van Grunsven
Journal: Journal of Hepatology (2014)
Abstract 2505: Neurotensin receptor antagonist, SR48692, sensitizes prostate cancer cells to radiation <i>in vitro</i> and <i>in vivo</i>
Authors: Eli V. Casarez, John O. DaSilva, Nicholas C.K. Valerie, Suresh Anaganti, Marya E. Dunlap-Brown, George P. Amorino, James M. Larner, Sarah J. Parsons, Jaroslaw Dziegielewski
Journal: Cancer Research (2011)

Abstract Prostate cancer (PCa) is one of the major causes of cancer-related deaths in men. Androgen receptor (AR) and androgen sensitivity play a crucial role in the development of the disease. Thus, androgen depletion therapy has become a cornerstone of advanced PCa treatment, with or without radiotherapy. Multiple mechanisms have been proposed for the development of hormone-refractory disease, including an increase in neuroendocrine-like (NE-like) cells, which secrete survival and growth factors for surrounding tumor cells (Deeble et al., Cancer Res 2007). Neurotensin (NT) is secreted by both NE-like and cancer cells, and stimulate proliferation of PCa cells through its interaction with neurotensin receptor 1 (NTR1) (Amorino et al., Oncogene, 2007). In this report we investigate the efficacy of a NTR1 antagonist, SR48692, as a radiosensitizer in an orthotopic PC-3M xenograft model. The role of AR/sensitivity to androgen in response to SR48692 was also investigated using LNCaP and C4-2 cell lines. The latter studies were done to test the hypothesis that AR positive cells may be refractory to the raditherapy, because we had previously shown that neuropeptides from NE-like cells resulted in Src-mediated phosphorylation of AR (DaSilva et al., Cancer Res 2009). The results of the xenograft studies indicate that mice bearing PC-3M tumors and receiving the combination treatment (drug+radiation) showed a statistically significant decrease in tumor growth over radiation or SR48962 treatments alone. SR48692 was also found to radiosensitize PCa cells in vitro, independently of their androgen receptor/androgen sensitivity status. We further demonstrate that NT stimulates accumulation of AR under conditions of reduced androgen and that this activity is blocked by SR48692/radiation co-treatment. These findings suggest that in cells expressing the AR, NT reduces the efficacy of radiation by elevating AR levels and its ensuing pro-growth and -survival signals. Blocking the actions of NT by SR48692 reduces the levels of AR protein and as a result increases cellular sensitivity to radiation. However, in cells lacking the AR, another mechanism(s) of drug action must be operative. Together, our studies suggest that in AR positive or negative PCa cells, NTR1 signaling pathway(s) are novel targets for combined SR48962/radiotherapy of PCa. 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 2505. doi:10.1158/1538-7445.AM2011-2505
Induction of Antitumor Immunity in Mice by Allo-Major Histocompatibility Complex Class I Gene Transfectant With Strong Antigen Expression
Authors: K.-i. Isobe, Y. Hasegawa, T. Iwamoto, T. Hasegawa, K. Kawashima, L.-n. Ding, I. Nakashima
Journal: JNCI Journal of the National Cancer Institute (1989)

An allo-major histocompatibility complex class I gene (H-2Kb) was transfected to murine mastocytoma P1.HTR (P815 subline) cells, after which several transfectant clones were obtained. Two clones, which expressed a low level of H-2Kb antigen, grew well and killed the syngeneic DBA/2 mice when they were inoculated ip. These mice lived longer than the mice given injections of the parental P1.HTR tumor. However, one clone, which expressed a high level of H-2Kb antigen, was rejected completely by the syngeneic DBA/2 mice and induced a generation of H-2Kb-specific cytotoxic T cells. Interestingly, the mice that had rejected the clone with high H-2Kb expression received strong anti-tumor immunity for rejection of the parental P1.HTR tumor challenged at the high dose.
A memorable patient: My room
Authors: E. H Hare
Journal: BMJ (2001)

As a not so junior junior doctor training part time in psychiatry, I have rotated through a fair number of doctors' offices. For several years when I was a clinical assistant, my personal effects had to be confined to a pair of grey plastic trays. Part share of an office is more usual.

The presence of a colleague is very inhibiting to work, particularly the dictation of letters. However, gossiping about colleagues, letting off steam about the job (not to mention my own friends and family), and occasionally even pondering the whole nature of psychiatric illness have helped keep me relatively cheerful.

Through sessions at peripheral clinics and day hospitals, you often share a room with colleagues who, like Major Major from Catch 22, are always out when you are in. Here rooms can accumulate mystery detritus: half eaten packets of biscuits, journals, clothing, bicycle pumps. Often these turn out to belong to no one, but the other occupants, like you, don't feel proprietorial enough to bin them.

Essential equipment is seating, a telephone, a pen, and a Dictaphone. The office should have space to interview patients with carers or host tutorial groups and should also provide peace and quiet to let you catch whether the hesitant, mumbling person before you is thought-disordered or deluded rather than just shy. A hook on the door, a filing cabinet, a kettle, and a green view are luxury items. One of these years, a computer might appear.

Recently, as part of my special interest sessions, I took a patient from an adjacent ward to my room to ask about his experience of electroconvulsive therapy. Perhaps not surprisingly, he was more interested in talking about antidepressants. An overdose attempt with his latest tablet had provoked acute retention of urine, and he was still encumbered with a catheter. He pointed to mugs, pens, paper hankies, the desk lamp, and calendar, all of which bore the trade names of antidepressants he had heard of. Did I recommend them, were they better than some of the older drugs that had helped him in the past?

I, of course, demurred, suggesting he discuss these concerns with his own consultant. Realising my room had been annexed as advertising space for the pharmaceutical industry, I swept the free gifts into the waste bin. The desk lamp didn't even work.

Drug companies have to be profitable. Who else is going to come up with safe and effective agents without side effects for my patients? Still, rather than give free product endorsements, I have decided to cover the walls with a heroes gallery of public figures who have spoken openly about their experience of mental illness. Any suggestions?
Abstract 2790: Establishment and characterization of human skingraft model in immunodeficient mice.
Authors: Guillaume Serin, Loïc Morgand, Marie Leblanc, Francis Bichat
Journal: Cancer Research (2013)

Abstract The humanization process of mice with various tissues named Chi-mice aimed to reproduce better the human situation and to be more predictive than conventional models. In order to evaluate new targeting therapies or adverse side effects involving skin components, pre-clinical studies need to be assayed with new molecules in adequate and validated mouse models bearing human skin. The collection of skin samples was done under ethically approved master agreements and with the signed consent of each patient. The patient's clinical history, the serology results (HIV, HBV and HCV) and tissue banking were centralized in our internal approved biological resource center. To develop such models, we used skins of different origins including foreskin, breast and abdomen that were isolated by different methods (full recovery of about 1 cm depth sample or dermatomization of the 1-2 mm epidermal/dermal layer). These samples were xenografted on immune deficient NOD-SCID mice under different conditions including matrigel grafting. After one month implantation, skingrafts were collected and observed microscopically to confirm the preservation of human organization of skin by full histology. Also, the species nature of vessels was characterized by immunochemistry to evaluate the host penetration within human skingraft and both CD-31 positive mouse and human vessels were found in the skingraft. In the context of vascular leak syndrome (VLS) induction by IL2 treatment, we have used the wet/dry ratio of skingraft to measure the induced-edema and we have measured the blue evans uptake in those injured skingraft to appreciate the epidermal vasculature leaking. Anapathological comparisons were also performed to reveal the histological modifications observed during VLS. These different characterizations performed during development of the skingraft model enabled us to obtain human skin xenografted on mice that retained the human characteristics of the primary material. The co-implantation of other human tissue (tumor) with skin in same mice which refined better the humanized model will be presented. The use of fresh skin and various tissues in drug discovery and early preclinical development of new therapies aimed at corroborating results with clinical reality. Altogether, these processes from the clinical sample collection to the in vivo drug efficacy study through ex vivo assays should help the preclinical drug selection, development and clinical positioning as well as companion biomarker identification. Citation Format: Guillaume Serin, Loïc Morgand, Marie Leblanc, Francis Bichat. Establishment and characterization of human skingraft model in immunodeficient mice. [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 2790. doi:10.1158/1538-7445.AM2013-2790
SP0080 Eular Recommendations in Imaging RA in Clinical Practice
Authors: P. G. Conaghan
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Objective To develop evidence-based recommendations on the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA). Methods A EULAR task force comprising an expert group of rheumatologists, radiologists, methodologists and experienced rheumatology practitioners from 13 countries was. Thirteen key questions on the role of imagingin RA were generated using a process of discussion and consensus. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, dual-emission x-ray absorptiometry, digital x-ray radiogrammetry, scintigraphy and positron emission tomography. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. The experts used the evidence obtained from the relevant studies to develop a set of 10 recommendations. The strength of recommendation was assessed using a visual analogue scale. Results A total of 6888 references was identified from the search process, from which 199 studies were included in the systematic review. Ten recommendations were produced encompassing the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. The strength of recommendation for each proposition varied according to both the research evidence and expert opinion. Conclusions Ten key recommendations for the role of imaging in the management of RA were developed using research-based evidence and expert opinion <h3>Disclosure of Interest</h3> None Declared
FIRST REPORT ON THE USE OF A POLYMER FREE BIOLIMUS COATED STENT IN PRIMARY ANGIOPLASTY FOR ST-ELEVATION MYOCARDIAL INFARCTION
Authors: JinHyun Lee, Dasdo Sinaga, Alyssa Sim, Fahim Jafary, Jason Loh, Julian Tan, Hee Hwa Ho, Paul Ong
Journal: Journal of the American College of Cardiology (2016)
Organ-Specific Promoting Effects of Phenobarbital Sodium and Sodium Saccharin in the Induction of Liver and Urinary Bladder Tumors in Male F344 Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: K Nakanishi, S Fukushima, A Hagiwara, S Tamano, N Ito
Journal: JNCI Journal of the National Cancer Institute (1982)

Studied were conducted to determine whether initial treatment with N-2-fluorenylacetamide (2-FAA) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) followed by treatment with either phenobarbital sodium (PB) or sodium saccharin (SS) induced or enhanced liver and/or bladder tumorigenesis. Male inbred F344 rats were given 0.05% PB and 5.0% SS in the diet for 32 weeks after 4-week administration of 0.02% 2-FAA treatment and induced hyperplastic liver nodules after BBN treatment. The SS significantly enhanced induction of bladder hyperplasias, but not papilloma after BBN treatment, and induced bladder hyperplasias after 2-FAA treatment. However, PB had no effect on the bladder and SS had no effect on the liver after either 2-FAA or BBN treatment. The data indicate that although 2-FAA and BBN have tumor-initiating effects in the liver and urinary bladder, the tumor-promoting effects of PB and SS are organ-specific. The tumor-promoting effect of PB for the liver is relatively greater than that of SS for the urinary bladder.
FRI0441 Risk factors of chloroquine maculopathy and role of plasma chloroquine and desethylchloroquine concentrations in predicting chloroquine maculopathy:
Authors: P. Chiowchanwisawakit, S. Nilganuwong, V. Srinonprasert, R. Boonprasert, W. Chandranipapongse, S. Chatsiricharoenkul, W. Katchamart, P. Pongnarin, A. Koolvisoot, E. Arromdee, N. Ruangvaravate
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate the risk factors for chloroquine maculopathy (CM), and to explore factors associated with plasma chloroquine (CQ) and desethylchloroquine (DCQ) levels. <h3>Methods</h3> Two-hundred and thirty-three rheumatoid arthritis (RA) patients who had taken CQ at least 6 months with stable CQ dosage for at least 2 months were included between March 1, 2010 and September 30, 2011 at Siriraj Hospital, Thailand. CM was diagnosed by ophthalmologist utilizing dilated ocular examination and Humphrey visual field 10-2 white protocol. Plasma CQ and DCQ levels were determined by liquid chromatography tandem mass spectrometry method. Logistic regression models were applied to explore risk factors associated with CM. <h3>Results</h3> One hundred and ninety-three patients were included with median CQ duration (range) of 50.2 (6.0 – 269.8) months and cumulative dose of 137.4 (16.4-1226.5) gm. The prevalence of CM was 13.5%. One hundred and fifty seven plasma samples were available for determining the CQ and DCQ levels. Factors associated with developing CM identified from univariate analysis were age more than 60 years old, and poor creatinine clearance (CCl) with odds ratio (OR) (95%CI) of 5.79 (2.42,13.84), and 0.98 (0.96,1.00), respectively while current daily CQ dose from 2.5 mg/kg had marginal association, p=0.06. Plasma CQ and DCQ was not associated with CM with OR of 1.00 (1.00, 1.01) and 0.99 (0.98, 1.01), respectively. In multivariate analysis, older age, CQ exposure duration &gt;5 years, and current daily dose of at least 2.5 mg/kg-IBW were the factors significantly associated with CM with OR of 5.89 (2.38, 14.57), 2.94 (1.10, 7.83), and 3.32 (1.04, 10.60), respectively while plasma CQ and DCQ showed no association with CM. With respect to plasma CQ and DCQ levels, current daily CQ dosage had the strongest positive correlation with both plasma levels as shown in the table. <h3>Conclusions</h3> Age more than 60 year-old, duration of CQ use more than 5 years and current CQ dose ≥2.5 mg/kg-IBW/day were the risk factors of CM. The plasma CQ or DCQ levels demonstrated no correlation in developing CM. The plasma levels were strongly associated with current daily dose of CQ. <h3>Funding</h3> Siriraj Research Development Fund, Faculty of Medicine Siriraj Hospital, Mahidol University. <h3>Disclosure of Interest</h3> None Declared
OP0121 Combined and specific costs for hospitalisations, drugs, and lost work days in prevalent contemporary RA: A nationwide cohort study
Authors: J. Eriksson, J. Askling, M. Neovius
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Whereas several studies have estimated various aspects of the economic burden of RA in defined cohorts of patients, few studies from the biologic era have had the possibility to simultaneously assess several cost components using nationwide data or put these costs in relation to general population comparators. <h3>Objectives</h3> To estimate the societal annual costs related to work loss, health care utilization, and drug use in contemporary prevalent RA patients. <h3>Methods</h3> RA patients ≥18y on Jan 1, 2009, were identified from the Swedish National Patient Register (requiring ≥2 visits listing RA) and the Swedish Rheumatology Quality Register, and followed until Dec 31, 2009. Sick leave and disability pension data were retrieved from the Social Insurance Office, while healthcare utilization, drug use, and mortality data were retrieved from the national and virtually complete Patient Register, Prescribed Drug Register and Causes of Death Register, respectively. Five sex-, age-, education-, and county-matched general population comparators were sampled per RA patient from the Register of the Total Population. Prevalent RA patients exposed to biologics (for these analysis defined as dispensings of etanercept or adalimumab in 2008) were evaluated in subgroup analyses. <h3>Results</h3> We identified 51,193 RA patients, alive and living in Sweden Jan 1, 2009 (mean age 64y; estimated prevalence=0.7%). The mean total costs for individuals aged 18-64y were €22,000 (median €15,000) per RA patient vs €8,000 (median €300) per matched general population comparator. Although the mean cost level differed, the distributions of the cost components in the RA patients and the general population comparators were similar. In both groups disability pension (66% vs 72% of total cost) contributed by far the most, followed by sick leave (9% vs 12%) and biologic drug use (10% in RA patients). In RA patients ≥65y the mean direct cost was €8,000 vs €3,000 (median €2,000 vs €700) in the general population comparators. Inpatient care dominated (63% vs 68%), followed by drug use (22% vs 16%) and non-primary outpatient care (15% vs 15%). In RA patients exposed to biologics the mean total cost was €31,000 and €17,000 (median €26,000 and €15,000) in the 18-64y and ≥65y age group, respectively, with biologics accounting for €10,000 in both groups. <h3>Conclusions</h3> The mean total cost in RA patients was 2-3 times higher than in matched general population comparators. With the exception of biologic drugs, the included cost components were of comparable magnitude in all RA patients as in the RA patients exposed to biologics. <h3>Disclosure of Interest</h3> None Declared
Coronary Artery Occlusion and Myocardial Infarction
Authors: IGNACIO BANZO, ALFONSO MONTERO, ISABEL URIARTE, NICOLAS VALLINA, ANA HERNÁNDEZ, CONSTANTINO GUEDE, REMEDIOS QUIRCE, JOSE MANUEL CARRIL
Journal: Clinical Nuclear Medicine (1999)

Myocardial infarction is a rare complication that can occur after blunt chest trauma. The authors describe a 30-year-old man who experienced a fatal anterolateral myocardial infarction after chest trauma in a motorcycle accident. The electrocardiogram and creatine phosphokinase-MB isoenzymes levels suggested myocardial necrosis. Tc-99m phosphate myocardial scintigraphy identified an extensive doughnut-shaped uptake over the cardiac area. An echocardiogram revealed severe left ventricular impairment. Coronary angiography confirmed complete occlusion of the proximal left anterior descending coronary artery.
British Team Pioneers PET Studies of Chemotherapy
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article British Team Pioneers PET Studies of Chemotherapy Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 4, 15 February 1995, Pages 246–247, https://doi.org/10.1093/jnci/87.4.246 Published: 15 February 1995