tbuckley/cabot-search huggingface dataset:
VERY LONG-TERM (10- TO 14-YEAR) OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION VERSUS CORONARY ARTERY BYPASS GRAFTING FOR MULTI-VESSEL CORONARY ARTERY DISEASE
Authors: Hiroki Shiomi, Kyohei Yamaji, Takeshi Morimoto, Satoshi Shizuta, Kenji Nakatsuma, Hirooki Higami, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Kenji Ando, Ryuzo Sakata, Hitoshi Okabayashi, Michiya Hanyu, Mitsuomi Shimamoto, Noboru Nishiwaki, Tatsuhiko Komiya, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2016)
Abstract 1848: Decursin derivatives with increased in vivo stability suppress androgen receptor signaling and prostate cancer cell growth: Structure-bioactivity relationship
Authors: Yong Zhang, Ahmad Shaik, Yubo Chai, Li Li, Jinhui Zhang, Wei Zhang, Chengguo Xing, Sung-Hoon Kim, Junxuan Lü, Cheng Jiang
Journal: Cancer Research (2011)

Abstract Androgen receptor (AR) signaling is crucial for the genesis and progression of prostate cancer (PCa). Targeting AR signaling remains an attractive approach for PCa chemoprevention and therapy. Our previous studies suggest that decursin, which is isolated from the Korean medicinal herb Angelica gigas Nakai, has novel anti-androgen attributes in comparison to that of AR antagonist drug bicalutamide (Casodex) and stronger anti-proliferative and pro-apoptotic activities in cell culture models. However, decursin quickly de-esterifies to decursinol in vivo, which lacks the anti-androgen and anti-proliferative activities. We report here that a novel prototype derivative (decursinol thiocarbamate, DTC) shows in vivo stability in single dose pharmacokinetic studies, with no detection of decursinol. Molecular docking with the wild type AR ligand binding domain (LBD) suggested that its AR-binding energy is inferior to DHT, but higher than decursin. Mechanistically DTC retains all the desirable properties of decursin, including inhibiting AR nuclear translocation, decreasing cellular AR protein abundance by promoting its 26S proteasomal-mediated degradation and lacking agonist activity. Dose-response comparisons showed that DTC was half as potent as decursin to inhibit AR signaling and androgen sensitive LNCaP PCa cell growth. In animal studies with mice, daily i.p. injection of DTC (2 mg per mouse) decreased AR transcriptional targets such as probasin and NKX3.1 in the mouse prostates. Chemical deposits on the surface of liver and other organs were observed suggesting poor solubility. Additional derivatives aimed to improved solubility had been synthesized and are being investigated for structure-activity relationship. Overall, the data suggest that DTC is a prototype stable decursin derivative retaining the novel AR antagonist activity for PCa chemoprevention or treatment. 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 1848. doi:10.1158/1538-7445.AM2011-1848
S25 Sleepy Snorers With "flow Limitation Syndrome": A Missed Opportunity For Cpap?
Authors: R. Yadavilli, B. Chakrabarti, S. McDougall, L. Horne, S. Emegbo, S. Craig, N. Duffy, R. Parker, J. O'Reilly
Journal: Thorax (2014)

<h3>Background</h3> The apnoea–hypopnoea index (AHI) is used to define Obstructive Sleep Apnoea Syndrome (OSAS). Some subjects however, present primarily with excessive daytime sleepiness (EDS) and loud snoring, but investigation may reveal an elevated Respiratory Disturbance Index (RDI) with most events comprising Flow limitations. Little UK based data exists regarding treatment outcomes in this group. <h3>Methodology/results</h3> 118 subjects (mean age 52 years; Epworth sleepiness scale score (ESS) 13.58 (5.30); 80% male) presented between November 2011–October 2013 to the Sleep Service with EDS as a primary symptom, loud snoring, RDI &gt;15 with AHI≤11 (Mean RDI 21.77 (9.43)); AHI 8.03(2.74); ODI 6.72 (4.49) and were treated with CPAP. At 30 day compliance review, 60% (71/118) had benefited from CPAP with mean ESS pre-CPAP 14.13 (5.12) falling to 7.70 (4.82) following CPAP. The mean BMI was found to be significantly higher in those 71 subjects benefiting from CPAP (33.20 (SD 8.13) v 30.26 (SD 7.40); p = 0.04) but no significant differences were noted in baseline Epworth score, age, gender, AHI, RDI, ODI and Pulse Transit Time (PTT). This “Flow Limitation” cohort was compared with 261 subjects (mean age 56 years; ESS 12.47(5.61); 82%Male) diagnosed with OSAS during the same time period (Mean AHI 37.11 (19.94); mean ODI 31.15 (19.74) and treated with CPAP. 76% (199/261) of the OSAS group reported benefit from CPAP; ESS fell from 13.24 (5.35) to 6.60 (4.74) following CPAP therapy. Comparing the “Flow Limitation” group with the “OSA” group, the mean BMI (32.03(7.94) v 34.70(8.65); p = 0.004) and age (51.75(12.34) v 56.20(12.18); p = 0.001) were significantly lower in the “Flow Limitation” subjects but no significant difference was noted in baseline ESS. Those deriving benefit from CPAP in the OSA group demonstrated significantly higher CPAP usage (4.45(2.24) v 3.83(2.15) hours/night; p = 0.04). <h3>Conclusion</h3> Basing treatment decisions on AHI rather than RDI may miss a proportion of patients exhibiting similar levels of EDS as those with OSAS who would otherwise have gained benefit from CPAP. Despite the observed benefit, CPAP usage appeared lower in this “Flow Limitation” cohort who appeared overall to be a younger group with a lower BMI compared to those with OSA.
Abstract 3802: PPAR gamma mediated induction of transglutaminase in aerodigestive preneoplasia in vitro
Authors: Elizabeth K. Weidman, Beverly R. Wuertz, Patrick M. Gaffney, Frank G. Ondrey
Journal: Cancer Research (2010)

Abstract Currently there are no validated biomarkers or therapies for human aerodigestive preneoplasia. There is increasing interest in the utilization of PPAR gamma mediated therapy for oral leukoplakia reversal based on preliminary clinical trial results. Transglutaminases (TGMs) are associated with squamous differentiation, and therefore might be hypothesized to be upregulated with PPAR gamma differentiation therapies. In the present study we sought to examine the feasibility of utilizing transglutaminases as a downstream readout for PPAR gamma activator treatment of oral leukoplakia. First we examined our Affymetrix database of human head and neck tumors for the presence or absence of transglutaminases 1-3 in 41 tumors compared to 13 normal oral mucosa samples. We discovered that TGM 1 and 3 were significantly upregulated in normal tissues compared to tumors (p&amp;lt;0.0001). Next, we examined whether PPAR gamma activators could activate TGM1 reporter genes in cell lines. We found that TGM1 luciferase reporters were significantly activated by ciglitazone (0-5uM) and pioglitazone (0-10 uM) in MSK leuk and HOK oral preneoplastic cell lines, as well as CA-9-22 oral cancer cells in several experiments. Next we examined pioglitazone activation of transglutaminases in these cell lines by real time PCR. We found that pioglitazone significantly activated TGM 1 and 2 in MSK leuk and CA-9-22 oral cancer cells on qRT-PCR. We conclude that the clinically relevant PPAR gamma activator, pioglitazone, can activate transglutaminases in aerodigetsive cancer cell lines and may be useful in upregulating differentiation in oral preneoplasia in clinical trials. We also conclude that transglutaminases may provide a family of proteins for PPAR gamma effects and should be included as exploratory biomarkers in leukoplakia clinical trials with PPAR gamma activators. 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 3802.
Abstract 1638: Preclinical evaluation of the PI3K inhibitor BEZ235 in nasopharyngeal carcinoma cell lines
Authors: Brigette B. Ma, Vivian WY Lui, Kakiu Ho, Cecilia PY Lau, Margaret HL Ng, Suk-Hang Cheng, Chi-Man Tsang, Sai-Wah Tsao, Michael Shi, Edwin P. Hui, Anthony TC Chan
Journal: Cancer Research (2010)

Undifferentiated nasopharyngeal carcinoma (NPC) is endemic to parts of Asia and ubiquitously associated with Epstein-Barr virus (EBV) infection. AKT is frequently activated in NPC and PIK3CA amplification can be found in 40% of NPC tissues. BEZ235 is a dual inhibitor of PI3K and mTOR, which results in inhibition of downstream effectors AKT, S6 ribosomal protein and 4EBP1. The preclinical activity of BEZ235 was evaluated in 6 NPC cell lines (Table 1). Western Blot analysis showed all 6 NPC cell lines showed basal activation of AKT and mTOR. The effect of BEZ235 on cell growth was evaluated by exposing NPC cell lines to increasing concentrations of BEZ235 (0.1nM, 0.5nM, 1nM, 10nM, 100nM, 1µM& 10µM) for up to 72 hrs followed by MTT assay. Over 80% of growth inhibition was achieved in all NPC cell lines except C666-1 (∼70% inhibition), with the respective IC50 concentrations in the nanomolar range (Table 1). Two representative cell lines (HONE1-LMP-1 and CNE-2 cells) were selected for assessing the effect of BEZ235 on AKT-mTOR signaling, apoptosis, cell cycle and synergism with chemotherapy. Treatment of HONE1-LMP-1 and CNE-2 cells with BEZ235 at 5nM and 50nM for 24-48 hours, resulted in cell cycle arrest at G1 phase, apoptosis (indicated by the induction of PARP cleavage), and moderate reduction of cyclin D1 expression. After BEZ235 treatment, the expression level of phosphorylated (p-)AKT, pS6K, p4EBP-1 and p-mTOR were reduced, but the level of p-p44/42 MAPK was increased in both HONE1-LMP-1 and CNE-2 cells. No synergistic effect on growth inhibition was observed when HONE1-LMP-1 and CNE-2 cells were treated with concomitant BEZ235 and chemotherapy (cisplatin, or paclitaxel). Our preliminary result suggests that BEZ235 has promising activity in most NPC cells, while the increase in p-p44/42 MAPK observed in some cell lines suggest the presence of compensatory MAPK activation that have been previously described with mTORC1 inhibitors in other cancer types. Further investigations are warranted.Table 1: IC50 (growth)% growth inhibition by BEZ235% cells at G1 arrest after BEZ235 (5nM) treatment for 24hrsEBV-associated NPC cell linesHK1-LMP14.1nM∼85%-HONE-1-LMP14.9nM∼75%62%C666-19.5nM∼70%-Poorly-differentiated NPC cell linesHONE-16.4nM∼85%-CNE-25.7nM∼90%58%Well-differentiated NPC cell lineHK14.7nM∼90%-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 1638.
Abstract 170: Hypermethylation of <i>DBCCR1</i> gene in acute myeloid leukemia
Authors: Aili Dai, Chen Zhao, C. Cameron Yin, Ling Chen, Xiaoping Sun, Sanat Dave, Xiaoyan Huang, Yu H. Zhang, Xin Han, M. James You
Journal: Cancer Research (2010)

Abstract DNA hypermethylation likely plays a role in the tumorigenesis and prognosis of acute myeloid leukemia (AML). To identify relevant methylated genes in AML, we have compared several expression and methylation profiles. With expression analysis, we identified that DBCCR1, TRPC6, DCC and SOX9 have decreased expression levels in the most analyzed AML cell lines. Among these candidates, DBCCR1 (deleted in bladder cancer chromosomal region candidate 1) gene at chromosome 9q33 was identified as a putative tumor suppressor gene that is frequently targeted by hypermethylation in transitional cell carcinomas of the bladder. In addition, DBCCR1 was reported frequently methylated in hematological malignancies, including diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. DBCCR1 may play an important role in the regulation of cell growth and programmed cell death. But the expression levels and methylation status of DBCCR1 in AML have not been established. In this study, we analyzed the expression pattern of DBCCR1 in AML cell lines with RT-PCR analysis. DBCCR1 mRNA expression was robust in normal bone-marrow mononucleated cells but markedly diminished in all of 9 AML cell lines. DBCCR1 was methylated in all of AML cell lines (9 of 9, 100%) and its methylation was inversely correlated with DBCCR1 mRNA expression, which was demonstrated by RT-PCR and COBRA (Combined Bisulfite Restriction Analysis) analyses. Furthermore, we also detected frequent methylation (at least 90%) of DBCCR1 in multiple primary AML samples. These findings indicate that DBCCR1 is frequently silenced by hypermethylation in AML. We are investigating the functional role of DBCCR1 in the pathogenesis of AML. In addition, the diagnostic and prognostic values of methylated DBCCR1 in AML are being pursued. In summary, putative tumor suppressor gene DBCCR1 shows significantly diminished expression in AML due to frequent hypermethylation. * Aili Dai and Chen Zhao contributed equally to the presented work. 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 170.
P5-14-18: Today's Estrogen Receptor Positive/Her-2-neu Receptor Negative Breast Cancer Patients Do Significantly Better Than Yesterday's Estrogen Receptor Positive Breast Cancer Patients.
Authors: EV Madsen, SG Elias, PD Gobardhan, Oort PM van, der Ent FW van, OE Nieweg, Olmos RA Valdés, M Smidt, Dalen T van
Journal: Cancer Research (2011)

Abstract Background: Her-2-neu receptor (Her2) positive and triple negative breast cancer patients have a poor prognosis. The majority of cancers are characterized as estrogen receptor (ER)+/Her2- and these patients may now have a better prognosis compared to before the introduction of the Her-2-neu receptor. Material and methods: Since 1997 3424 patients were treated for cT1-2N0 breast cancer in three hospitals. Determination of Her2-neu status was introduced between 1999 and 2004. Trastuzumab treatment has been given routinely since 2005. Survival was evaluated for the different groups; ER+/Her2-, ER+/Her2+, ER+/Her2 unknown (status not determined). Results: 2284 patients had ER+/Her2- tumors, 259 had ER+/Her2+ tumors and 262 had ER+/Her2 unknown tumors. Systemic treatment was given to 48.4%, 71.0% and 43.9% respectively. Estimated 5-and 10-year overall survival was 92.0% and 82.2% for ER+/Her2-, 91.6% and 70.8% ER+/Her2+ and 83.4% and 72.2% for ER+/Her2 unknown (p &amp;lt; 0.001). The outcome differences between ER+/Her-2- and ER+/Her-2 unknown tumors remained following adjustment for tumor malignancy grade, nodal status and adjuvant systemic treatment (OR 0.8: CI 0.72 — 0.88; p&amp;lt;0.001). For patients with ER+/Her2+ tumors 5 year overall survival was comparable with ER+/Her2- tumors but 10 year overall survival was comparable with ER+/Her2 unknown tumors. Discussion: Patients with ER+/Her2- tumors have a significantly better outcome than patients who were classified as ER+ before the assessment of Her-2-neu over-expression. Current prognostic models do not take this effect into account. The branching off of the survival curve for patients with ER+/Her2+ tumors can be explained by the standard use of trastuzumab during the last five years. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-18.
Abstract 988: F14512, a novel vectorized topoiserase II inhibitor, bypasses MDR1 mediated resistance.
Authors: Jean Philippe Annereau, Viviane Brel, William Riquet, Laurent Créancier, Isabelle Vandenberghe, Emmanuel Fournier, Céline Robichon, Aline Stennevin, Vanessa Offrete, Laurence Lacastaigneratte, Bruno Gomes, Anna Kruczynski, Christian Bailly, Nicolas Guilbaud
Journal: Cancer Research (2013)

Abstract F14512 is a novel polyamine-vectorized topoisomerase II inhibitor currently in phase 1/2 clinical trial in acute myeloid leukemia (AML). Since ABCB1 (also called P-glycoprotein or MDR1) has been reported to be expressed at high levels in patients with resistant leukaemia cells, and constitutes a pejorative marker of therapy, we decided to investigate whether F14512 could be exported by ABCB1 or other ABC transporters susceptible to confer drug resistance to chemotherapy, such as MRP1. In addition, we established a F14512-resistant cell line to study the mechanism of resistance to the drug. With membrane preparation enriched in functional MDR1, we found that F14512 was unable to stimulate the ATPase activity of this transporter. Using a cellular assay over expressing MDR1 transporter by recombinant transfection of MDCKII cells, F14512 was detectable, but the intracellular level was unchanged regardless of the MDR1 status or in presence of MDR1 competitors. Consistently, iterative selection of a F14512-resistant A-549 cell line with 36 cycles of F14512 at cytotoxic doses (0.5 EC50) over 9 months, led to only moderate shift of resistance (9 fold). In the resulting selected A-549 subclones, MDR1, MRP1 and ABCG2 were detectable at the basal level. The ability of F14512 to bypass MDR1 was finally assessed in a vinorelbine-resistant P388 model overexpressing high level of functional ABCB1 as indicated with the positive rhodamine export assay and cross resistance to MDR1 substrate. Moreover, F14512 displays strong antileukemic activity in MDR1-positive P388 cells in vitro and additional in vivo measurements are in progress. In conclusion, the data concur to show that the antitumor activity of the targeted cytotoxic agent F14512 is not impacted by the MDR1 status of cancer cells. MDR1 clearly does not affect the potency of F14512 and this characteristic augurs well for the ongoing development of the drug in AML patients. Citation Format: Jean Philippe Annereau, Viviane Brel, William Riquet, Laurent Créancier, Isabelle Vandenberghe, Emmanuel Fournier, Céline Robichon, Aline Stennevin, Vanessa Offrete, Laurence Lacastaigneratte, Bruno Gomes, Anna Kruczynski, Christian Bailly, Nicolas Guilbaud. F14512, a novel vectorized topoiserase II inhibitor, bypasses MDR1 mediated resistance. [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 988. doi:10.1158/1538-7445.AM2013-988
Comparison of SEER registry data to patient self-report.
Authors: R. Jagsi, P. Abrahamse, J. J. Graff, S. T. Hawley, S. J. Katz
Journal: Journal of Clinical Oncology (2010)

6003 Background: SEER data has been used to suggest underuse and racial disparities in receipt of radiation therapy (RT). Prior studies have cautioned that SEER underascertains RT, but they lacked adequate representation to assess whether underascertainment varies by important SES and clinical patient subgroups. Methods: We evaluated data from 2,260 survey respondents with nonmetastatic breast cancer, aged 20-79, diagnosed from 6/05-2/07 in Detroit and Los Angeles and reported to SEER registries (72% response rate). Survey responses regarding treatment and sociodemographic factors were merged to SEER data. We compared RT receipt as reported by patients versus SEER records. We then assessed correlates of RT underascertainment in SEER. Results: Of the 1,292 patients who reported receiving radiation, 297 (23%) were coded as not receiving RT in SEER (“underascertained”). Underascertainment was more common in patients with younger age (30% for patients < 50, 24% for 50-64, and 17% for 65 and older, p < 0.001), nonwhite minorities (36% for Latinas, 22% for blacks, 18% for whites, and 17% for others, p < 0.001), lower income (29% for earners < $20K, 24% for $20K-69.9K, and 17% for $70K p = 0.008), underinsurance (51% for uninsured at time of diagnosis, 26% for Medicaid, 18% for Medicare, and 22% for all others p < 0.001), later stage (18% for DCIS, 19% for stage I, 28% for stage II, and 34% for stage III, p < 0.001), self-reported chemotherapy receipt (31% for those who received treatment vs. 17% for those who did not, p < 0.001), and self-reported delay in initiating RT (31% of those reporting delay vs. 21% of those who did not, p = 0.001). On multivariate analysis, age (p < 0.001), race (p < 0.001), income (p < 0.001), stage (p = 0.04), insurance (p < 0.001), self-reported chemotherapy receipt (p < 0.001), and self-reported delay in initiating RT (p < 0.001) were significantly associated with underascertainment by SEER. Conclusions: Large systematic differences in underascertainment of RT across SES and clinical subgroups of patients suggests that SEER data alone are not an appropriate source for investigation of treatment disparities in breast cancer. No significant financial relationships to disclose.
AB1164 Results of the multinational e-mail survey regarding follow up of patients with localised scleroderma and raynaud’s phenomenon
Authors: I. Foeldvari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Secondary Raynaud phenomenon is an orphan disease in childhood. Currently there are no guidelines how to follow these patients and what is the most sensitive sign to differentiate between primary and secondary Raynaud's phenomenon. In this survey special issues of this diseases and follow up concepts were surveyed. <h3>Objectives</h3> To learn about the clinical practice regarding diagnosis and follow up concepts fro primary and secondary Raynaud's phenomenon <h3>Methods</h3> Members of the paediatric rheumatology e-mail board and of the juvenile scleroderma working group of the PRES were asked to fill out a survey with 3 items regarding diagnosis and follow up of primary and secondary Raynauds phenomenon. <h3>Results</h3> 28 colleagues responded to the survey with a wide spread geographic distribution. 7 questions were asked and the following responses received. The following questions were asked: 1.If you see a patients with Raynaud's-phenomenon how often you see them for follow up: 14 of the centres followed the patient every 6 months, 7 every 3 months, 2 centres every two months and other 2 for every 12 months. 2. Which findings do you find helpful to define secondary Raynauds? - you can give several choices: 23 of the centres found a positive nailfold capillaroscopy findings, 12 ANA positivity and 10 antiphospholipid positivity as an important sign for secondary Raynaud's phenomenon. 3 centres considered any sign of rheumatic disease supportive. 3. If you see a patients with secondary Raynaud's phenomenon how often you see them for follow up: 16 of the centres followed the patients every 3 months, 3 of the centres every 6 months, two of the centres every 2 months. 3 of the centres made the follow up dependent in the clinical symptoms. <h3>Conclusions</h3> The range of follow up periods differs widely between the centres. Regarding supportive sign for secondary Raynaud's a positive nailfold capillaroscopy finding appeared to be the most important sign. Prospective collection of clinical data of patients with primary and secondary Raynaud's phenomenon would help us to better understand, the most rational way to follow this patients <h3>Disclosure of Interest</h3> None Declared