tbuckley/cabot-search huggingface dataset:
Abstract 2216: SUMOylated CPAP contributes to NF-kB activation in cancer cells
Authors: Shu-Ting Yang, Liang-Yi Hung
Journal: Cancer Research (2012)

Abstract Nuclear factor kappa-B (NF-κB) is a transcription factor which involves in hepatocellular carcinoma (HCC). The development of therapeutic drugs to specifically target NF-κB signaling pathway is imperative to achieve. Centrosomal and P4.1-associated protein (CPAP) is a novel co-activator of NF-κB. The effects of CPAP on NF-κB activation pathway were determined by over-expression and knockdown approaches. CPAP increased the expression of NF-κB target genes by enhancing the transcriptional activaty of NF-κB. Through recruiting more IkappaB kinase beta (IKKα) to the inactivated NF-κB complex, CPAP augmented the phosphorylation of inhibitor of NF-κB (IαBβ) and NF-κB. Chromatin immunoprecipitation assay further showed that CPAP is recruited to IL-8 and ICAM-1 promoter under TNF-α treatment. CPAP was covalently modified by SUMO-1 (small ubiquitin-related modifier-1) protein at the C-terminal region. SUMO-deficient CPAP mutants lost the co-activator activity on NF-κB activation pathway and failed to enter the nucleus upon TNF-α treatment. By immunohistochemistry (IHC) analysis, CPAP was detected in the nucleus of HBV-associated HCC. Activation of NF-κB was synergically augmented by CPAP overexpression in HBx-expressing Hep3B (Hep3BX) and HepG2 (HepG2X) cells lines. SUMOylation of CPAP could modulate the activity of NF-κB, and CPAP may serve as a target for therapeutic purpose in HBV-associated HCC. 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 2216. doi:1538-7445.AM2012-2216
Cardiac Rhythm after the Mustard Operation for Complete Transposition of the Great Arteries
Authors: Celia J. Flinn, Grace S. Wolff, Macdonald Dick, Robert M. Campbell, Gordon Borkat, Alfonso Casta, Alan Hordof, Thomas J. Hougen, Rae-Ellen Kavey, John Kugler, Jerome Liebman, Joel Greenhouse, Paul Hees
Journal: New England Journal of Medicine (1984)

The Mustard operation corrects the effects of congenital transposition of the great arteries by creating an intraarterial baffle to direct pulmonary venous blood to the tricuspid orifice and systemic venous blood to the mitral orifice. To identify the long-term effects of this procedure, we followed 372 patients with complete transposition of the great arteries who survived the Mustard operation for at least three months. The mean follow-up period was 4.5 years (range, 0.4 to 15.9); the mean age at operation was 2.0 years. Mean resting heart rates were consistently lower than those for age-matched normal children. Seventy-six per cent of the patients had sinus rhythm during the year of operation--a figure that decreased to 57 per cent by the end of the eighth postoperative year. Twenty-five patients died during the follow-up period, nine suddenly. Life-table analysis revealed a cumulative survival rate of 91 per cent for 11 years and 71 per cent for 15 years after the operation. No strong risk factor for sudden unexpected death identified. This study demonstrates that extended survival among patients with transposition can be expected after the Mustard operation. However, over time there is a decreasing prevalence of normal sinus rhythm in survivors, as well as a small risk of sudden death.
Continuation pharmacotherapy of borderline personality disorder with haloperidol and phenelzine
Authors: J R Cornelius, P H Soloff, J M Perel, R F Ulrich
Journal: American Journal of Psychiatry (1993)

The aim of this study was to assess the effectiveness of low-dose neuroleptic medication and monoamine oxidase inhibitor (MAOI) antidepressant medication in continuation pharmacotherapy of patients with borderline personality disorder.The authors conducted a double-blind, placebo-controlled study comparing continuation therapy with a neuroleptic (up to 6 mg/day of haloperidol), an MAOI antidepressant (up to 90 mg/day of phenelzine), and placebo in 14 men and 40 women with borderline personality disorder. Continuation medication trials lasted 16 weeks, following 5 weeks of acute therapy.Continuing haloperidol demonstrated efficacy only for the treatment of irritability. Higher levels of depression, hypersomnia, and leaden paralysis were noted in the patients who received haloperidol than in those who received phenelzine and those who received placebo. The dropout rate during the first 8 weeks of the continuation study was significantly higher for the patients receiving haloperidol (64%) than for those receiving placebo (28%). Continued phenelzine demonstrated only modest efficacy for the treatment of depression and irritability. An activating effect of phenelzine was shown on measures of excitement and reactivity.No evidence of efficacy was found for continuation therapy with haloperidol in the treatment of borderline personality disorder other than in the treatment of irritability. Little evidence of efficacy was found for continuation therapy with phenelzine for borderline personality disorder other than modest improvements in irritability and depressive symptoms. There is currently no clear pharmacological treatment of choice for the continuation therapy of borderline personality disorder.
AB0336 Sexual Disturbances in Patients with Rheumatoid Arthritis and It's Relation with Disease Activity
Authors: A. Palomino, G. Saavedra-Martinez, L. Villarreal, V. Giraldo, D. Gomez, J. Bello-Gualtero, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Sexuality is an important dimension of personality and human body, therefore any involvement in this area should be considered as important. Sexual disturbances in rheumatoid arthritis (RA) patients are poorly described in literature. <h3>Objectives</h3> The aim of this study was to describe sexual disturbances using CIE-10 classification in a population with RA and a possible correlation with disease activity. <h3>Methods</h3> A descriptive cross-sectional study was performed in a specialized clinic dedicated to care patients with RA. 349 patients were included in the study, which were seen by the area of psychology, which information was collected through semi-structured interviews and non-probability sampling. Descriptive epidemiology was applied for continuous variables, using measures of central tendency and dispersion for categorical and qualitative variables by averages and percentages. By means of Pearson9s statistics it was analyzed bi-variated correlations. <h3>Results</h3> The total sample of patients was 349, 279 (79.9%) were women and 70 (20.0%) were men, average DAS28-2.46. Average age is 58.1 years. 146 (52.3%) of women reported no sexual activity, while 133 (47.6%) report sexual activity. Concerning women with sexual activity, 27 (18.4%) reported satisfactory sexual activity, 33 (22.6%) reported no-satisfactory sexual activity, 25 (18.3%) reported lack or loss of sexual desire, 53 (36.3%) reported dyspareunia, and 4 (2.9%) orgasmic dysfunction. On the other hand 18 (25.7%) of men reported no sexual activity, while 54 (70.2%) report sexual activity. Concerning men with sexual activity, 6 (11.1%) reported premature ejaculation, 8 (14.8%) reported satisfactory sexual activity, 5 (12.8%) reported no-satisfactory sexual activity, 5 (9.2%) reported lack or loss of sexual desire, 7 (12.9%) orgasmic dysfunction, 4 (7.4%) reported dyspareunia. It was not established a correlation between level of sexual activity and disease activity using DAS28. <h3>Conclusions</h3> According to these findings almost a half of men and women have a high percentage of sexual disturbances in relation to RA affecting their quality of life; on the other hand higher DAS28 is not correlated with fewer level of sexual activity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5391
Abstract A47: Metastatic development of prostate cancer and multidrug resistance
Authors: Pei-Wen Hsiao, Chin-Hsien Tsai, Yu-Chih Yang, Ming-Ting Lee, Mong-Hsun Tsai
Journal: Cancer Research (2011)

Abstract Signaling pathway of androgen receptor plays a central role in the prostate cancer progression. Accordingly, approaches and molecular mechanisms to ablate the androgen receptor function in prostate cancer have been actively studied to improve the disease treatment. However, the disease inevitably develops resistance to all forms of hormonal therapies. To further understand metastatic prostate cancer, we established orthotopic xenograft model using various human cell lines expressing Luc2 reporter by lentivirus-mediated infection. Growth of these orthotopic xenografts develops a wide spectrum of spontaneous metastases in vivo, from which we also obtained cells from more aggressive and metastasized tumors. Indeed, cancer cells isolated from larger primary tumors and metastatic tumors are more invasive than those isolated from smaller primary tumors. Genome-wide RNA expression (transcriptomes) in cancer cells from metastases against primary large and small tumors were compared to reveal the difference between the different cancer stages. Real-time RT-PCR confirmation and Ingenuity Pathways Analysis (IPA) software analysis reveal activation of NFkB pathways and P-glycoprotein, so-called multidrug resistance-associated proteins in metastasis. Our study established useful cells and indicates a potential molecular basis of the drug resistance along the in vivo development of human prostate cancer. Supported by Academia Sinica, Career Development Award. 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 A47.
Abstract LB-160: Dual application of TLR5 agonist in cancer treatment: A single agent combines supporting care and antitumor activities
Authors: Lyudmila Burdelya, Anatoly Gleiberman, Ilya Gitlin, Semra Aygun-Sunar, Youcef Rustum, Andrei V. Gudkov
Journal: Cancer Research (2011)

Abstract We have previously shown the strong radioprotective properties of TLR5 agonist flagellin in both mouse and non-human primate models (Burdelya et al., 2008, Science 320: 226–230). A pharmacologically optimized flagellin derivative, Protectan CBLB502, is currently at an advanced stage of development as a prospective radiation antidote for biodefense applications. By testing CBLB502 in combination with radiation treatment of experimental mouse tumors in vivo, we demonstrated that its tissue protection properties are limited to normal tissues with no tumor protection detected in any of numerous mouse tumor models. For example, injections of CBLB502 significantly reduced the severity of mucositis and dermatitis associated with local fractioned irradiation of the head and neck area of mice with syngeneic orthotopically grown head and neck carcinoma with no reduction of antitumor effect of experimental radiotherapy. On the contrary, use of CBLB502 led to enhanced tumor suppression by radiation and produced a detectable tumor suppressive effect even without irradiation. Similar results were obtained in s.c. grown syngeneic colon Wart tumors in rats. In this model, administration of CBLB502 reduced the severity of irinotecan-induced diarrhea, but did not interfere with the anti-tumor effect of the drug. Moreover, use of CBLB502 as a single agent had a pronounced antitumor effect in the majority of Wart tumor-carrying rats. Comparison of the effect of CBLB502 on in vivo growth of isogenic pairs of tumor cell lines differing in their TLR5 status showed that the antitumor effect of the TLR5 agonist is TLR5 dependent and is associated with tumor infiltration by immunocytes, presumably attracted following activation of TLR5 signaling in the tumor cells. Remarkably, CBLB502 caused an immunotherapeutic effect in TLR5-negative tumors growing as experimental metastases in the liver which was found to be the primary target of TLR5 agonist. The liver responds to CBLB502 injection by massive and rapid activation of NF-kB in all hepatocytes. This results in dramatic changes in the content of secreted factors, attraction of immunocytes and a strong reversible increase in liver resistance to a variety of toxic agents. Based on these results, we project clinical applications of CBLB502 as a bi-functional therapeutic agent with supporting care (protection of normal tissues from radio- and chemotherapy side effects) and immunotherapeutic activities. 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 LB-160. doi:10.1158/1538-7445.AM2011-LB-160
Early Progression of Disease in HIV-Infected Infants with Thymus Dysfunction
Authors: Athena P. Kourtis, Christian Ibegbu, Andre J. Nahmias, Francis K. Lee, W. Scott Clark, Mary K. Sawyer, Steven Nesheim
Journal: New England Journal of Medicine (1996)

Infants with congenital thymic deficiency (the DiGeorge syndrome) have immunodeficiency and a characteristic pattern of low CD4+ and CD8+ T-lymphocyte counts and low CD5+ B-lymphocyte counts. Because the thymus is essential for the generation of CD4+ cells, we sought evidence of thymus dysfunction in infants infected perinatally with the human immunodeficiency virus (HIV).
Effects of Prolonged Thyrocalcitonin Administration on Paget's Disease of Bone
Authors: John G. Haddad, Stanley J. Birge, Louis V. Avioli
Journal: New England Journal of Medicine (1970)

Three patients with an extensive and severe form of Paget's disease of bone were given porcine thyrocalcitonin every 12 hours for one month or longer. Striking reduction of alkaline phosphatase was observed in three subjects, and decreased hydroxyprolinuria in two. A 16 per cent decrease in cardiac output was measured after 17 weeks of hormone administration to one patient. Evidence of decreased bone turnover persisted for four to five weeks after withdrawal of the hormone from two subjects. Neither tetany nor rebound hypercalcemia occurred. The well tolerated suppressive effects observed suggest a role for thyrocalcitonin in the management of this disorder.
Abstract 3858: Synergistic antitumor effects of combination therapy with S-1 and HER2 targeting agents in gastric cancer with HER2 amplification
Authors: Junko Tanizaki, Isamu Okamoto, Ken Takezawa, Sayaka Tsukioka, Junji Uchida, Mamoru Kiniwa, Masahiro Fukuoka, Kazuhiko Nakagawa
Journal: Cancer Research (2010)

Abstract HER2 amplification is observed in 20-30% of gastric cancer and it has been correlated to poor outcomes and more aggressive disease. Combination therapies with HER2 targeting agents and cytotoxic agents are considered a therapeutic option for patients with HER2 amplified gastric cancer. We now investigated the effects of the combination treatment with S-1(or 5-fluorouracil (5FU)) and either lapatinib or trastuzumab on the growth of gastric cancer cells with or without HER2 amplification in vitro and in vivo. The combination of 5FU and either lapatinib or trastuzumab showed a synergistic antiproliferative effect in HER2 amplified gastric cancer cells. Combined treatment with 5FU and lapatinib or trastuzumab induced synergistic increases in the number of apoptotic cells and in the activity of caspase-3 in HER2 amplified cells, wheareas, such synergistic antiproliferative effect nor the enhancement of apoptosis was observed in cells without HER2 amplification. Thymidylate synthase (TS) is an important target enzyme for 5FU, with a reduced level of TS expression having been associated with a higher rate of response to 5FU-based chemotherapy. To elucidate the molecular mechanism of the synergistic effect by the combination of 5FU and lapatinib or trastuzumab, we examined the effects of lapatinib or trastuzumab on the expression and activity of TS in gastric cancer cells. Both lapatinib and trastuzumab induced down-regulation of TS expression and inhibition of TS activity in HER2 amplified cells, whereas neither lapatinib nor trastuzumab has such effects on TS expression and activity in cells without HER2 amplification. Similar to the effects of lapatinib or trastuzumab, TS depletion by siRNA resulted in the enhancement of 5FU-induced apoptosis, suggesting that TS down-regulation attributes, at least in part, to the synergistic proapoptotic interaction with 5FU. Furthermore, the combination of oral fluoropyrimidine S-1 and lapatinib or trastuzumab synergistically inhibited the growth of gastric cancer cell xenografts with HER2 amplification. Our results thus suggest that the combination of S-1 and lapatinib or trastuzumab has synergistic antitumor effects in HER2 amplified gastric cancer cells and that effect is likely attributable to the down-regulation of TS expression and inhibition of TS activity by lapatinib or trastuzumab. In conclusion, these observations provide a basis for clinical evaluation of combination chemotherapy with S-1 and HER2 targeting agents, lapatinib or trastuzumab, in gastric cancer patients with HER2 amplification. 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 3858.
Evaluation of lapatinib (Lap) plus capecitabine (Cap) in patients with brain metastases (BM) from HER2+ breast cancer (BC) enrolled in the Lapatinib Expanded Access Program (LEAP) and French Authorisation Temporaire d'Utilisation (ATU)
Authors: F. Boccardo, B. Kaufman, J. Baselga, V. Dieras, J. Link, M. A. Casey, A. Fittipaldo, C. Oliva, D. Zembryki, S. D. Rubin
Journal: Journal of Clinical Oncology (2008)

1094 Background: Lap has single agent activity against BM in patients (pts) with HER2+ (ErbB2+) BC. Lap + Cap increases response rate, time to progression, and progression-free survival when compared with Cap alone in pts with refractory HER2+ BC. An exploratory analysis of the latter study (EGF100151) showed fewer pts on Lap + Cap developed BM at first relapse compared with Cap alone. The LEAP and ATU were designed to provide access to Lap before commercial availability and were initiated after EGF100151 enrollment was halted. Eligibility requirements for these programs were similar to EGF100151, i.e., pts had disease progression following prior taxane, anthracycline, and trastuzumab therapy. Although data were not formally collected via case report forms, we surveyed LEAP and ATU sites to ascertain the percent of pts with progressive BM at entry and response to Lap + Cap. Methods: LEAP/ATU sites that enrolled 15 or more pts were queried to provide data via worksheets or narratives regarding progressive BM upon entry, presence of tumor-related neurological signs and symptoms (NSS), steroid use, prior Cap exposure, and improvements in NSS and CNS response. Results: 58 sites (48 LEAP and 10 ATU sites) were surveyed. 138 of 1189 (12%) pts presented with progressive BM at entry. Unconfirmed CNS response to Lap + Cap in the 138 pts were as follows: complete response (CR) 3 (2%), partial response (PR) 22 (16%), stable disease (SD) 65 (47%), progressive disease (PD) 19 (14%), unknown 29 (21%). 42% of pts with progressive BM at entry received Cap before LEAP or ATU; 36% of pts with CR or PR in the CNS received prior Cap. Investigators reported improvement in NSS in 25% of pts with BM. Conclusions: Exploratory data from the LEAP and ATU programs have clear limitations, however, they suggest that Lap + Cap provides clinical benefit to pts with progressive BM from HER2+ BC. Prospective studies evaluating lap + chemotherapy in this pt population are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline Exelixis, GlaxoSmithKline, Novartis, Pfizer GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Abstract 3580: Pre-diagnostic alcohol consumption and breast cancer recurrence and survival in postmenopausal women
Authors: Jenny C. Chang-Claude
Journal: Cancer Research (2012)

Abstract Introduction: Alcohol consumption has been consistently associated with breast cancer risk. However, studies on its association with breast cancer survival produced inconsistent results. Methods: We assessed the association of alcohol consumption (in four categories &amp;lt;0.5 g/d, 0.5 to &amp;lt;6.0 g/d, 6.0 to &amp;lt;12.0 g/d, α12.0 g/d, and continuous) with survival and recurrence in a prospective cohort study in Germany of 2,706 postmenopausal breast cancer patients aged 50-74 years after excluding those with previous cancer and/or missing information on alcohol intake. Patients were diagnosed between 2001 and 2005 and vital status, causes of death, and recurrences were verified through the end of 2009. Delayed-entry Cox proportional hazards models were stratified by age at diagnosis and study centre and adjusted for other prognostic factors. Fractional polynomials were used to assess the true dose-response relation for alcohol consumption. Results: Women were enrolled in the study a median time of 105 days after diagnosis. Median follow-up times from recruitment until death/censoring or recurrence/censoring were 5.5 years and 5.6 years, respectively. Overall, 326 deaths occurred, 239 (73.3%) due to breast cancer. Further causes of death were other cancers (n=41, 12.6%), cardiovascular disease (n=22, 6.7%), and other causes (n=24, 7.4%). Of the 2,199 patients with stage I to IIIa disease and available data on recurrence status, 250 had a breast cancer recurrence. Alcohol consumption ≤ 12 g/day compared to &amp;lt; 0.5 g/day was linearly associated with a statistically significantly higher breast cancer mortality (HR, 1.71; 95% CI, 1.12 to 2.62; P for trend = 0.03). Results were no longer statistically significant when restricted to Stage I-IIIa patients (HR, 1.28; 95% CI, 0.75 to 2.20). There was no effect modification by body mass index, hormone replacement therapy use, and estrogen receptor status. Alcohol consumption ≤ 12 g/day was not associated with overall mortality (HR, 1.27; 95% CI, 0.90 to 1.80) and mortality due to other causes (HR, 0.73; 95% CI, 0.38 to 1.42). Also, no association with breast cancer recurrence was found (HR, 1.05; 95% CI, 0.71 to 1.56). Conclusion: Consumption of more than 12 g alcohol (equivalent to one alcoholic drink) per day is associated with increased breast cancer mortality but not with breast cancer recurrence. 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 3580. doi:1538-7445.AM2012-3580