tbuckley/cabot-search huggingface dataset:
Abstract 1552: Cigarette smoke induces TNF-α secretion from macrophages through a pathway consisting of PPARγ, MUC1, ERK and JNK.
Authors: Xiuling Xu, Mabel T. Padilla, Alexandria Wells, Kwang Chul Kim, yong Lin
Journal: Cancer Research (2013)

Abstract The glycoprotein Mucin 1 (MUC1 in human and Muc1 in animals) is expressed in the lung and has been shown to be associated with lung carcinogenesis. Recently we have found that cigarette smoke (CS) significantly increased MUC1 expression in mouse lung macrophages and that MUC1 is required for CS-induced tumor necrosis factor-alpha (TNF-α) secretion from macrophages. Because CS potently elicits chronic pulmonary inflammation that is important for the development of lung cancer, we investigated the cell signaling pathways for CS-induced MUC1 expression and MUC1-mediated TNF-α secretion in macrophages using an in vitro model. The results showed that: CS extract (CSE) strongly induced MUC1 expression at both the mRNA and protein levels; Suppression of PPARγ effectively blocked CSE-induced MUC1 expression in THP1 cells, suggesting CSE induces MUC1 expression through PPARγ-mediated transcription; The induction of TNF-α expression was effectively blocked when ERK and JNK were blocked, suggesting these pathways are involved in CSE-induced TNF-α expression in macrophages; Knockdown of MUC1 significantly suppressed CSE-induced ERK and JNK activation; and Suppression of PPARγ that effectively blocked CSE-induced MUC1 expression also inhibited CSE-induced TNF-α secretion from macrophages. Thus, our results suggest a possible involvement of a signaling pathway consisting of PPARγ, MUC1 and ERK/JNK for CSE-induced TNF-α secretion from macrophages that may contribute to inflammation-associated lung cancer development. Note: This work is supported by the NIH/NIEHS grant 1R01ES017328. Citation Format: Xiuling Xu, Mabel T. Padilla, Alexandria Wells, Kwang Chul Kim, yong Lin. Cigarette smoke induces TNF-α secretion from macrophages through a pathway consisting of PPARγ, MUC1, ERK and JNK. [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 1552. doi:10.1158/1538-7445.AM2013-1552
A multi-institutional study of radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma: 84 subjects out of over 5,000 population
Authors: Y. Niibe, K. Hayakawa, K. Michimoto, M. Kenjo, T. Kazumoto, M. Takayama, C. Yamauchi, M. Kataoka, K. Suzuki, M. Oguchi
Journal: Journal of Clinical Oncology (2006)

5052 Background: Most patient who had any recurrent sites of cancer, have been considered to be last-stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence cases. Furthermore, patients who had only one recurrent region, even radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than pelvis is para-aortic lymph node. Furthermore, improvement of diagnostic imaging enables us to detect more frequently isolated para-aortic lymph node recurrence. Thus, we conducted the current study. Methods: Between 1994 and 2003, over 5000 uterine cervical carcinoma patients treated with curative intended treatments at sixteen Japanese major hospitals. Out of them, 84 patients developed para-arotic lymph node recurrence as the only site of initial tumor progression. Seventy-four patitents had squamous cell carcinoma and 5 had adenosquamous cell carcinoma and 5 had adenocarcinoma. These patients were treated with external beam radiation therapy prescribing 1.7–2.0 Gy per fraction, 5 fractions per week and median total dose was 50 Gy (25–60 Gy). Thirty-two patients received adjuvant systemic chemotherapy. Results: Median follow-up time of all patients was 20 months (2–92 months). Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by patients with or without chemotherapy, 3-year overall survival rate of patients with chemotherapy group was 37.7% and those without group was 56.7% (p = 0.69). Moreover, stratified by symptom sign, 3-year overall survival rate of symptom positive group was 27.6% and those of negative group was 56.1% (p = 0.018). Three-year overall survival rates of the total dose ≥ 51Gy and that of ≤ 50 Gy were 58.0% and 42.8%, respectively (p = 0.07). AS for morbidity, no patients received G3 or greater late toxicity (CTCAE ver. 3.0). Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have significant impact on overall survival. Furthermore, no symptom group and over 51Gy irradiation group could achieve better prognosis. No significant financial relationships to disclose.
Abstract 772: Rap2b, a novel p53 downstream target, promotes cell survival after DNA damage.
Authors: Yunlong He, Mangmang Li, Wendy Dubois, Alexander Kovalchuk, Xiaolin Wu, Jing Huang
Journal: Cancer Research (2013)

Abstract The tumor suppressor p53 is a critical regulator of apoptosis and cell survival. It evokes both pro-survival and pro-apoptosis programs upon DNA damage. However, the mechanisms underlying this cell fate decision are largely unclear. To identify p53 targets in a global and unbiased manner, we performed gene expression microarray and ChIP-chip assays using mouse embryonic fibroblasts (MEFs) and mouse embryonic stem (mES) cells. I treated MEFs and mES cells with adriamycin, a DNA damage agent, for 8 hours. Comparing to the untreated cells (negative controls), I obtained common genes that were dramatically induced both in MEFs and mES cells. Subsequently, we further analyzed these genes and obtained a list of 90 common genes. Then, I compared these 90 genes with published p53 targets in human cell lines U2OS and HCT116, and found 10 genes (Alox5, Eda2r, Btg2, Mdm2, Adrb2, Cdkn1a, Tnfrsf10b, Rap2b, Ddit4, Bbc3) that are conserved p53 targets between mouse and human. Most of these genes have been well studied except for Rap2b. Both mouse and human Rap2b share the same amino acid residue sequence, which indicating Rap2b might have important conserved functions both in human and in mouse. Using conventional chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay, I identified one p53 binding motif in Rap2b promoter region. After DNA damage, p53 binds to the promoter of Rap2b and activates its transcription. The reduction of Rap2b levels by small interference RNA increases the apoptosis of cells under the damaged condition, suggesting that Rap2b helps cell survive upon DNA damage. This pro-survival role of Rap2b is very similar to the function of another well-known p53 target, Mdm2. Bioinformatic analysis revealed that Rap2b is over-expressed in many types of tumors, consistent with its pro-survival function. Anchorage independent growth assay showed that Rap2b only has weak transformation activity, suggesting that it is not a typical oncogene. Importantly, Rap2b activates RalGDS-Ral survival pathway after DNA damage. Therefore, our results identified a novel player, Rap2b, in the pro-survival program conducted by p53 and revealed a connection between the p53 signaling and the RalGDS-Ral cell survival pathway. Future studies will focus on investigating whether the inhibition of Rap2b may increase the apoptosis of tumor cells. Citation Format: Yunlong He, Mangmang Li, Wendy Dubois, Alexander Kovalchuk, Xiaolin Wu, Jing Huang. Rap2b, a novel p53 downstream target, promotes cell survival after DNA damage. [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 772. doi:10.1158/1538-7445.AM2013-772
Prevention of Myocardial Damage in Acute Myocardial Ischemia by Early Treatment with Intravenous Streptokinase
Authors: Gideon Koren, Avraham T. Weiss, Yonathan Hasin, David Appelbaum, Sima Welber, Yoseph Rozenman, Chaim Lotan, Morris Mosseri, Dan Sapoznikov, Myron H. Luria, Mervyn S. Gotsman
Journal: New England Journal of Medicine (1985)

We evaluated the effectiveness of early intravenous administration of 750,000 units of streptokinase in 53 patients with acute myocardial ischemia treated by a mobile-care unit at home (9 patients) or in the hospital (44 patients). Treatment was begun an average (+/- S.D.) of 1.7 +/- 0.8 hours from the onset of pain. Non-Q-wave infarctions developed subsequently in eight patients, whereas all the others had typical Q-wave infarct patterns. In 81 per cent of the patients the infarct-related artery was patent at angiography performed four to nine days after admission. Vessel patency was independent of the time of treatment, but residual left ventricular function was time dependent. Patients treated less than 1.5 hours after the onset of pain had a significantly higher ejection fraction (56 +/- 15 vs. 47 +/- 14 per cent; P less than 0.05) and infarct-related regional ejection fraction (51 +/- 19 vs. 34 +/- 20 per cent; P less than 0.01) and a lower QRS score (5.6 +/- 4.9 vs. 8.6 +/- 5.5; P less than 0.01) than patients receiving treatment between 1.5 and 4 hours after the onset of pain. Patients treated earlier by the mobile-care unit also had better-preserved left ventricular function than patients treated in the hospital. We conclude that thrombolytic therapy with streptokinase is most effective if given within the first 1.5 hours after the onset of symptoms of acute myocardial infarction.
Severe Hypertension with Papilledema Simulating Brain Tumor
Authors: Robert Sterling Palmer, Albert F. Nyssens, James C. White
Journal: New England Journal of Medicine (1948)

ESSENTIAL hypertension is a very common condition, and expanding intracranial lesions are common enough so that coexistence of the two may be anticipated. The symptoms (impairment of vision, headache, nausea, vomiting, convulsions, stupor, unconsciousness and coma), physical findings (papilledema and localizing signs) and spinal-fluid alterations (increased pressure and elevated protein) may occur both in severe hypertension and in brain tumor. Increased intracranial pressure associated with a slowly expanding intracranial lesion is not accompanied by a significant increase in the blood pressure. The presence of an acutely expanding intracranial lesion (from trauma or hemorrhage), which may cause an elevation of the . . .
PDQ is NOT a Guideline
Authors: H. McIntosh
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article PDQ is NOT a Guideline Get access Hugh McIntosh Hugh McIntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 14, 19 July 1995, Page 1045, https://doi.org/10.1093/jnci/87.14.1045 Published: 19 July 1995
AB0881 Quality of life determines sick leave in ankylosing spondylitis
Authors: F. Santos, A.F. Mourao, E. Vieira-Sousa, J. Costa, H. Santos, A. Barcelos, V. Tavares, J.E. Fonseca, S. Rabiais, J. Felix, J.C. Branco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing Spondylitis (AS), adversely affect patients in terms of pain, function, and quality of life. AS have a significant influence on individual employment status and work-related productivity, in addition to the significant burden on patients, their families and to society. <h3>Objectives</h3> Our aim was to estimate the influence of socio-demographic and clinical characteristics and perceived quality of life on sick leave in working age AS patients. <h3>Methods</h3> A total of 369 AS patients recruited from 10 rheumatology centers, were investigated. Socio-demographic (age, gender, profession), clinical characteristics [disease duration, disease activity (BASDAI), physical function (BASFI), metrological repercussion (BASMI) and chest expansion] and Quality of Life (QoL) repercussion (SF-36, EQ-5D) data was registered. The non-parametric Mann-Whitney-Wilcoxon and the Fisher test were used to verify demographic and clinical differences between patients groups with and without sick leave. Logistic regression models were used to explain the variability of sick leave. <h3>Results</h3> Among the 316 with professional status available, 88 (23.9%) were retired and 218 were working (53,2%). Of these, 2.7% declared having had sick leave in the year preceding the survey. Lower mean of SF-36 (p=0.002) and EQ-5D (p=0.001) values were seen in patients reporting sick leave. No statistically relevant association was observed between sick leave and any of the socio-demographic and clinical variables. Controlling for age and gender, it was estimated a reduction of 9% in the probability of having sick leave days for each 1% increment in SF-36 total score. <h3>Conclusions</h3> Qol seems to be the major determinant of sick leave. All aspects influencing QoL must be considered regarding AS therapy. <h3>Disclosure of Interest</h3> None Declared
Endoscopic submucosal dissection of gastric lesions using the “yo-yo technique”
Authors: F. Baldaque-Silva, F. Vilas-Boas, M. Velosa, G. Macedo
Journal: Endoscopy (2012)

One of the main difficulties during endoscopic submucosal dissection (ESD) is the mobilization of the partially resected lesion in order to improve access to the lesion edges and the dissection plane. In the current study, the feasibility and safety of a new “yo-yo technique” to facilitate ESD procedures were evaluated. A total of 17 consecutive patients with gastric lesions were included. A standard hemoclip and snare were used to pull and push the lesion margins in order to increase the access to the lesion edges and to the submucosal space. All lesions were resected en bloc, without perforation or significant bleeding requiring blood transfusion, and all patients were discharged within 7 days. Resected specimens and lesions were 24 – 58 mm (mean 36 mm) and 18 – 45 mm (mean 25 mm) in size, respectively. The “yo-yo technique” is feasible, easy, and safe, and allows the lesion to be pulled and pushed during the ESD procedure. Further use of this technique may lead to the expansion of its indications to other gastrointestinal regions.
505 EXTENDED PEGYLATED INTERFERON ALFA-2A THERAPY IN CHINESE PATIENTS WITH HBEAG-NEGATIVE CHRONIC HEPATITIS B: A SINGLE-CENTER, PROSPECTIVE, RANDOMIZED OPEN-LABELLED STUDY
Authors: X.P. Chen, X.F. Chen, J. Huang, W.L. Chen, R. Chen, X.J. Ma, X.D. Luo
Journal: Journal of Hepatology (2012)
AB0189 Polymorphisms in genes involved in the metotrexate action mechanism. are they associated with response/toxicity of the drug?
Authors: P. Moya, J. Salazar, A. Altés, H. Corominas, C. Diaz-Torne, I. Castellví, C. Geli, M. E. Córica, E. del Rio, J. M. de Llobet, M. Baiget
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease of unknown etiology. Methotrexate (MTX) is the first-line treatment option for newly diagnosed RA patients. However, only 50–70% of the patients will respond to MTX therapy and up to one third will discontinue treatment because of toxicity. <h3>Objectives</h3> Studying SNPs (single nucleotide polymorphisms) described in the literature for its possible role as biomarkers of response and / or toxicity to MTX, in Spanish patients diagnosed with rheumatoid arthritis. <h3>Methods</h3> We analyzed 27 TagSNPs in 5 candidate genes (<i>DHFR</i>, <i>TYMS</i>, <i>MTHFR</i>, <i>ATI</i>C and <i>CCND1)</i> involved in the action mechanism of MTX. We studied its association with the therapy-related efficacy and toxicity. One hundred and twenty-four adult patients with RA treated with MTX monotherapy were studied. TagSNPs within these genes were selected using bioinformatic tools and were genotyped using a 48.48 dynamic array on the BioMark system. Toxicity was measured as the time interval that MTX was administered. Efficacy was assessed using the DAS-28 EULAR response criteria. <h3>Results</h3> Clinical data of the patients are shown in Table 1. The univariate analyses showed significant association with toxicity in the dominant model with two TagSNPs in the <i>ATIC</i> gene: rs10197559 (P=0.05) and rs16853826 (P=0.04). Two TagSNPs in the <i>MTHFR</i> gene showed significant association with response in the dominant model: rs11121832 (P=0.02) and rs17421511 (P=0.02). <h3>Conclusions</h3> Polymorphisms in the <i>ATIC</i> and <i>MTHFR</i> genes may be considered as putative pharmacogenetic markers in RA patients treated with MTX on monotherapy. <h3>References</h3> Kinder AJ, Hassell AB, Brand J, Brownfield A, Grove M, Shadforth MF. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology 2005;44:61–6 Wessels JA, van der Kooij SM, le Cessie S, Kievit W, Barerra P, Allaart CF, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoidarthritis. Pharmacogenetics Collaborative Research Group. Arthritis Rheum 2007; 56: 1765–75 <h3>Acknowledgements</h3> Societat Catalana de Reumatologia. <h3>Disclosure of Interest</h3> None Declared
Contralateral Cortical Diaschisis in a Patient With Cerebellar Astrocytoma After Radiation Therapy
Authors: A B Newberg, A Alavi, J Alavi
Journal: Clinical Nuclear Medicine (2000)

Contralateral cerebellar diaschisis, hypometabolism in the cerebellum contralateral to a cortical lesion, is a well described phenomenon in patients with stroke and brain tumor. However, few reports exist of patients with cerebellar lesions with the finding of contralateral cortical hypometabolism. The authors present a case of a patient with a right cerebellar astrocytoma after surgical resection and radiation therapy in which fluorine-18 fluorodeoxyglucose positron emission tomographic imaging, performed to rule out recurrent tumor, revealed global hypometabolism in the left cerebral cortex. The concept of contralateral cortical diaschisis and possible mechanisms and clinical implications are reviewed.
Treatment of Advanced Soft Tissue Sarcoma: Conventional Agents and Promising New Drugs
Authors: Andrew Wagner
Journal: Journal of the National Comprehensive Cancer Network (2007)

Effective treatment of advanced soft tissue sarcomas remains challenging, despite more than 30 years of clinical trials with conventional chemotherapy. Although some agents display modest efficacy against soft tissue sarcomas, modifications in the doses and combinations of therapies have not consistently led to significant improvements in response rates or concomitant increase in overall survival. Novel therapies designed to inhibit defined molecular alterations, as exemplified by the use of imatinib in gastrointestinal stromal tumors, have revolutionized the approach to the treatment of sarcomas. As more underlying genetic mechanisms are uncovered, new agents designed to target these lesions will lead to more specific, less toxic, and more effective therapies.
Abstract 250: The critical requirement of ATM function in PTEN null cell lines
Authors: Nuala McCabe, Steven M. Walker, Caroline Greenan, Katarina Wikstrom, Estelle McLean, Thomas Delaney, Michelle McCarthy, Iain James, Timothy Harrison, Paul Mullan, Paul Harkin, Richard Kennedy
Journal: Cancer Research (2011)

Abstract Introduction: The tumour suppressor PTEN is frequently lost in multiple cancer types, loss of PTEN function has been linked to activation of the AKT signalling pathway. The regulation of the AKT signalling has long been attributed as the key tumour suppressing function of PTEN. However, it has recently been demonstrated that PTEN null cells demonstrate genomic instability and require base excision repair (BER) for survival. One of the critical functions of BER is the repair of oxidative DNA damage; we postulated that PTEN might have a role in the maintenance of this form of damage. Additionally, we investigated which molecular pathways were involved in the response of this form of DNA damage in PTEN null cells. Results: Using isogenic cell lines we found an increased in baseline ROS levels according to PTEN status. Specifically the increase in ROS levels was correlated to an increase in the levels of double strand breaks as measured by levels of activated γH2AX, formation of γH2AX foci and activation of the DNA damage response kinase ATM. Furthermore, inhibition of ATM function both via siRNA knockdown and small molecule inhibition in PTEN null cells resulted in cell cycle arrest followed by apoptosis. Strikingly this dependence on ATM activity was independent of AKT activity, suggesting that the oxidative DNA damage was the result of a loss in PTEN function independent of its role in the regulation of the AKT activation. Conclusions: These observations suggest that PTEN may play a role in the maintenance of the repair of ROS DNA damage; furthermore it maybe postulated that inhibition of ATM maybe a suitable therapeutic intervention for PTEN null tumours. 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 250. doi:10.1158/1538-7445.AM2011-250
Response to biological treatment and subsequent risk of coronary events in rheumatoid arthritis
Authors: Lotta Ljung, Solbritt Rantapää-Dahlqvist, Lennart T H Jacobsson, Johan Askling
Journal: Annals of the Rheumatic Diseases (2016)

Whether the increased risk of comorbidities, such as cardiovascular disease, in rheumatoid arthritis (RA) can be reverted by particular antirheumatic therapies, or response to these, is unclear but of critical clinical importance. We wanted to investigate whether response to tumour necrosis factor inhibitors (TNFi) translates into a reduced risk for acute coronary syndrome (ACS).A cohort of patients with RA initiating a first TNFi 2001-2012 was identified in the Swedish Biologics Register. The association between European League Against Rheumatism (EULAR) response after 3-8 months of treatment (assessed using the first, the best and the measurement closest to 5 months, respectively), and the risk of incident ACS during the subsequent year was analysed in Cox regression models. Adjustments included cardiovascular risk factors, joint surgery, RA duration, education and work disability.During 6592 person-years among TNFi initiators (n=6864, mean age 55 years, 77% women), 47 ACS occurred. The adjusted HRs (95% CI), which were similar to the crude HRs, of the 1-year risk of ACS among EULAR good responders compared with non-responders were 0.5 (0.2 to 1.4), 0.4 (0.2 to 0.9) and 0.5 (0.2 to 1.2), for the first, the best and the evaluation closest to 5 months, respectively. EULAR moderate responders had equal risk to that of EULAR non-responders, who, compared with the general population referents (n=34 229), had a more than twice the risk of ACS. For good responders, there was no statistically significant difference in risk versus the general population.Optimised RA disease control has the potential to revert otherwise increased risks for ACS in RA.