tbuckley/cabot-search huggingface dataset:
Phase IIb clinical trial of selenium in prostate cancer patients on active surveillance
Authors: M. Stratton, A. M. Algotar, J. Ranger-Moore, E. Slate, P. Hsu, S. P. Stratton, P. A. Thompson, F. R. Ahmann
Journal: Journal of Clinical Oncology (2008)

5060 Background: The Nutritional Prevention of Cancer Trial demonstrated a 52% lower incidence of prostate cancer in its selenium (Se) arm. Consequently, this trial was designed to assess if Se supplementation would reduce the progression of prostate cancer in subjects on active surveillance for their disease. Methods: A Phase 2b randomized, double-blind placebo-controlled clinical trial was conducted in men with localized prostate cancer who had elected to forego therapy for active surveillance. Subjects <85 years of age with biopsy proven non- metastatic prostate cancer, prostate specific antigen (PSA) levels <50ng/ml, Gleason score <8, no other treatment for prostate cancer, and life expectancy ≥3 years were recruited. A total of 140 men were randomized to placebo (n=46), 200μg/day (n=47) or 800μg/day (n=47) Se p.o. (as selenized yeast) and followed every 3 months for up to 5 years. The primary endpoint was PSA velocity, a surrogate marker of prostate cancer progression. Serum levels of PSA and Se were determined at baseline and at 3-month intervals thereafter. Variance-stabilizing transformation ln(PSA+1) was carried out and PSA velocity (slope of ln(PSA+1)) was estimated using mixed effects regression models. Results: Following adjustment for age, body mass index, serum selenium levels, pack-years of smoking at baseline, duration on study, race, PSA analysis method, and Gleason score; percent changes in PSA velocity (90% CI) for 200 μg/day and 800 μg/day treatment groups vs. placebo were -2.85% (-7.19, 1.70) and -0.70% (-5.16, 3.98), respectively. Estimated mean PSA velocities and PSA doubling times for placebo, 200 μg/day and 800 μg/day treatment groups were 0.09, 0.07, and 0.09 ng/mL/yr; and 4.92, 5.86 and 5.34 years, respectively. Upon secondary analyses, PSA velocity was statistically significantly higher in smokers (vs. non-smokers) (percent change in PSA velocity and 90% CI: 0.09 (0.03, 0.14)). Conclusions: Selenium supplementation did not significantly affect PSA velocity in subjects with non-aggressive disease. Longitudinal analyses also suggest that active surveillance was an appropriate choice for these subjects. Cigarette smoking may influence prostate cancer progression and needs further investigation. This work was supported by PHS CA079080 and CA023074. No significant financial relationships to disclose.
Abstract 17529: Prehypertension and Hypertension Are Associated With Non-Alcoholic Fatty Liver Disease Independent of Traditional Cardiovascular Disease Risk Factors
Authors: Ehimen Aneni, Shozab Siddiq Ali, Ebenezer Oni, Sameer Shaharyar, Michael Blaha, Seth Martin, Arthur Agatston, Roger Blumenthal, Raquel Conceicao, Jose Carvalho, Romeu S Meneghelo, Theodore Feldman, Raul Santos, Khurram Nasir
Journal: Circulation (2013)

Introduction: Earlier studies have demonstrated a relationship between hypertension and non-alcoholic fatty liver disease (NAFLD). However, little is known about the relationship between prehyperte...
Highly Electronegative LDL is Elevated in Patients With Acute Myocardial Infarction and Triggers Platelet Activation and Aggregation.
Authors: 詹華蓁(Hua-Chen Chan), 柯良胤, 朱志生, 李安生(An-Sheng Lee), 沈明毅(Ming-Yi Shen), Cruz MAC, 詹秀娟, Cheng KH, Lai WT, Yen JH, Sawamura T, Sheu SHS, 陳珠璜(Chu-Huang Chen)
Journal: Circulation (2012)
Therapeutic outcome in prognostic subgroups of de-novo acute myeloid leukemia (AML) and the role of the age factor. A study in 1834 patients of 16 to 84 years
Authors: T. Buchner, W. E. Berdel, C. Schoch, T. Haferlach, A. Reichle, P. Staib, M. C. Sauerland, B. Woermann, W. Hiddemann
Journal: Journal of Clinical Oncology (2005)

6552 Background: While 2/3 of pts with AML are 60 yrs of age or older their outcome is constantly inferior to that in younger pts. This difference is poorly understood and not explained by different incidences in prognostic factors. Though favorable karyotypes were less frequent (7% vs 23%) and unfavorable karyotypes more frequent (20% vs 10%) in older pts (Blood 2001;98:1312), MLL duplication was unfrequent overall (<5%) (Leukemia 2000;14:796), morphologic dysplasia did not prove as an independent factor (JCO 2003;21:256), and MDR1 did not predict for long- term outcome (Blood 1999;94:1086). No age relation was shown for FLT3, EVI1 or BAALC expression. Methods: We evaluated 1834 pts with de-novo AML including 750 pts of 60+ yrs and 1084 younger pts both concurrently treated in two consecutive trials. Chemotherapy was TAD-HAM (HAM, high-dose araC/ mitox) or HAM-HAM for induction, TAD for consolidation and reduced TAD for maintenance (JCO 2003;21:4496) randomly compared with intensified consolidation. Results: 72% of younger and 60% of older pts went into complete remission (p<0.001). By multivariate analysis we identified favorable and unfavorable karyotype, age, LDH and day 16 marrow blasts as independent factors predicting OAS, remission duration and RFS, while the treatment modifications did not reach significance. Favorable karyotypes were less frequent in the older pts (7% vs 14%) and unfavorable karyotypes more frequent (24% vs 20%) than in younger pts (p<0.001), being the only differences to the advantage of the younger group. The probability of ongoing remission at 4 years in the two age groups and the various prognostic subgroups are listed below. Similar differences as in remission duration were found in overall and relapse-free survival. Conclusions: Older age AML is a particular disease of unfavorable biology equally affecting the outcome across all prognostic subgroups defined so far. No significant financial relationships to disclose.
Abstract 2806: Percutaneous Intervention Leads to a Reduction in “Minimum” Microvascular Resistance
Authors: Lucy J Blows, Divaka Perera, Peter D O’Kane, Rainer Zbinden, Ardeth A Evans, Alison R Child, Simon R Redwood
Journal: Circulation (2006)

Background: Microvascular resistance has previously been believed to be constant and minimal with pharmacological induction of hyperaemia by IV adenosine infused at 140μg/kg/ min. Mathematical derivation of indices commonly used to evaluate coronary physiology is based on this assumption. The index of minimum microvascular resistance (IMR) has been shown to examine the microvasculature independently of epicardial stenosis severity using thermodilution.

Methods and Results: Comprehensive physiological assessment pre and post intervention using the pressure wire was made in 17 patients with single and multi-vessel disease undergoing elective revascularisation (hyperaemia induced with adenosine 140μg/kg/ min via femoral vein). Mean (SD) baseline FFR was 0.63 (0.14) and collateral flow index was 0.13 (0.08). Post intervention the IMR fell significantly (baseline 26.29 (13.36), post intervention 15.92 (8.66), p = 0.01). A rise in IMR above baseline was observed in only 1 patient following intervention. No correlation between FFR or CFI and change in resistance was found. In 3 patients minimum IMR was recorded following intervention to a second vessel, prior to treatment of the target artery.

Conclusions: Minimum microvascular resistance is not achieved pharmacologically and additional hyperaemia is seen following intervention. In part this is likely to be due to increased distal pressure following relief of the epicardial obstruction, however, the hyperaemic response following intervention to a non-target vessel suggests that additional global mechanisms are at play.



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Abstract 4281: Does Preoperative Aortic Insufficiency Affect Outcome Following Aortic Valve Sparing Surgery?
Authors: Laurent de Kerchove, Munir Boodhwani, David Glineur, Philippe Noirhomme, Gebrine El Khoury
Journal: Circulation (2008)

Aortic valve (AV) sparing surgery is an attractive option for the treatment of aortic root pathology. However, presence of significant preoperative aortic insufficiency (AI) or the need for cusp repair has been associated with poorer outcome. We analyze the influence of preoperative AI severity and the need for cusp repair on the early and mid-term outcomes of AV sparing surgery. From 1996 to 2007, 134 consecutive patients underwent elective AV sparing surgery. (mean age − 52±16 years; 84% male). Significant preoperative AI (3+ or 4+) was present in 83 patients (62%) and 46 (34%) had a bicuspid valve. Root repair was performed with either the reimplantation (67%) or remodeling technique (33%). A systematic approach was used for intraoperative valve assessment and cusp repair was performed in 74 patients (55%). Clinical and echocardiographic follow-up was complete in 100% and 96% respectively at a mean follow-up time of 57 months (range: 12–147 months). Kaplan-Meier curves, log rank test, and Cox regression analyses were used. Hospital mortality was 0.7%. AV cusp repair was required in 53% of patients without significant AI and in 57% with significant AI (p=0.9). Cusp repair was required more frequently in bicuspid versus tricuspid valves (89% vs. 38%, p = 0.005). Overall survival at 5 and 8 years was 94±5% and 86±10% respectively. Freedom from recurrent AI (&gt;2+) was similar with or without significant preoperative AI (90±10% vs. 86±10% at 5 years, p=0.5) and with or without cusp repair (87±11% vs. 89±10%, p=0.6; Figure 1). Freedom from AV reoperation at 5 years was similar with or without significant preoperative AI (94±6% vs. 89±8%, p=0.5) and with and without cusp repair (90±9% vs. 91±8%, p=0.8). With a systematic approach to valve assessment and cusp repair, AV sparing surgery for aortic root pathology has an acceptable early and mid-term outcome, irrespective of preoperative AI or need for cusp repair. Cusp repair is not predicted by presence of preoperative AI but is more frequent in bicuspid valves. Preoperative AI should not be considered a contra-indication for valve sparing surgery.
Abstract 4993: Time from Symptom Onset to Hospital Presentation in Women with Myocardial Infarction: A Temporal Analysis from the CRUSADE and NCDR ACTION Registry
Authors: Deborah B Diercks, Michael Kontos, Andra Blomkalns, Anita Chen, Kelly Owen, Chadwick Miller, Stephen Wiviott, Eric D Peterson
Journal: Circulation (2008)

Background: In 2002 the National Heart Lung and Blood institute initiated The Heart Truth program, an education program focused on women age 40 – 60 years old with the aim of increasing women’s awareness of their risk of heart disease. In addition, the Go Red for Women campaign was introduced by the American Heart Association in 2004 to increase awareness of cardiovascular disease. The dramatic increase in the awareness of heart disease from 2000 to 2006 in women has been attributed in part to these programs. We assessed whether there was a reduction in the time from symptom onset to hospital presentation in women who had a myocardial infarction over a similar time period.

Methods: The study population comprised 206,430 patients from 661 sites who presented with a non ST elevation myocardial infarction (NSTEMI) in the CRUSADE QI Registry from January 1, 2002 to December 31, 2006 and the NCDR ACTION Registry from January 1, 2007 to December 31, 2007. Patients were excluded if they were transfer-in patients (43,236), were missing symptom onset time or had extreme symptom onset times (37,700) or lacked documented sex (333).

Results: Of the 125,161 eligible patients, the study cohort comprised 50,162 women, predominantly Caucasian (78.7%) with a median age of 74 years (IQR 61,83). Of these women 36.4% had diabetes, 76.4% had hypertension, 27.8% prior myocardial infarction, and 27.7% had a prior coronary revascularization.. In women the median time from symptom onset to presentation was similar from 2002 through 2007 (p-value trend=0.8366). The overall median time to presentation in women was 3.0 hrs (IQR 1.4, 7.6) and in men 2.8 hrs (IQR 1.3, 7.2) p<0.001.

Conclusion: Despite significant national efforts to improve awareness of cardiovascular disease and time to presentation in women with chest pain, we noted no improvement in time from symptom onset to hospital presentation from 2002 to 2007 in a large sample of women with NSTEMI included in the CRUSADE and ACTION NCDR national registries.



![Table][1]  [1]: pending:yes
Effect of thoracocentesis on respiratory muscle strength in patients with unilateral pleural effusion
Authors: Stylianos Michaelides, Olga Vartzioti, George Bablekos, George Goulas, Ageliki Lazaratou, George Ionas, Eftychia Kourtelesi
Journal: European Respiratory Journal (2011)

It has been known that patients with pleural effusion may display a temporary reduction in arterial oxygenation soon after removal of pleural fluid, a fact that is in discrepancy with the relief of breathlessness after evacuation of effusions. We investigated changes in respiratory muscle strength before and after removal of several quantities of pleural fluid in patients with relatively large unilateral pleural effusions. We studied 49 patients (36 male & 13 female) aged 61±7.3 yrs. (mean±SD) with large unilateral pleural effusions of varying causes. Patients were selected on the basis of CT-scan not to have significant parenchymal lesions that would possibly interfere with lung physiologic properties (e.g. tuberculous effusions, neoplastic from extrathoracic primary site, hypoproteinemic effusions etc.) All patients were tested with an electronic mouth pressure meter, both before and 30 minutes after completion of thoracocentesis.The quantity of fluid removed was recorded for each patient and ranged from 0.38 to 1.41 L, with a mean value of 0.82±0.25 L (mean±SD). Maximal Respiratory Pressures were recorded 3 times and highest values were selected for statistical comparison (paired t-test).Maximal Inspiratory Pressure before removal of fluid (MIPb) was -74±12 cmH2O while after (MIPa) was -88±13 cmH2O (p<0.01). Maximal Expiratory Pressure before (MEPb) was 104±15 cmH2O while after removal of fluid (MEPa) was 121±17 cmH2O (p<0.01).We can conclude that removal of pleural fluid is accompanied by an improvement in respiratory muscle maximal pressures that may partly explain the relief of breathlessness after thoracocentesis.
Renographic Demonstration of Desmoid Tumor-Ureteral Fistula
Authors: David U. Kim, Garland McQuinn, Eugene Lin, Marie Lee
Journal: Clinical Nuclear Medicine (2015)

A 20-year-old woman with Gardner syndrome and intra-abdominal desmoid tumors presented with increasing abdominal pain. CT demonstrated a new area of central hypodensity in a presumed desmoid tumor, compressing the left ureter. Findings were suspicious for abscess or fistula to the ureter. Subsequent 99mTc-MAG3 renogram demonstrated persistent extraureteral radiotracer activity in the region of the tumor, confirming a desmoid tumor-ureteral fistula. Desmoid tumors are benign but locally aggressive fibrous neoplasms that can be sporadic or associated with familial adenomatous polyposis syndromes, specifically Gardner syndrome. Fistula formation to the ureter has been reported infrequently.
Initial Change Of Iron Metabolic Flux Prior To Differentiation Of Erythroid Progenitors After Epoetin Beta Pegol (C.E.R.A.) Treatment
Authors: Yusuke Sasaki, Mariko Noguchi-Sasaki, Yukari Matsuo, Junko Fukumura, Fumi Sato-Inomata, Keigo Yorozu, Yasushi Shimonaka
Journal: Blood (2013)
Cortactin is required for podosome formation downstream of activated Src kinase
Authors: Laura C. Kelley, Amanda Gatesman Ammer, Scott A. Weed
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1818 

Podosomes are actin-rich adhesive structures found in transformed cells that are implicated in cancer cell invasion and metastasis. Cortactin is an Arp2/3 activating and actin-binding protein initially identified as a major substrate in v-Src transformed cells, and is a core podosome component. Cortactin has recently been implicated in podosome formation and function in smooth muscle cells. However, a complete understanding of cortactin’s role in podosome formation during Src-induced transformation has not been reported. To determine the role of cortactin in podosome formation in response to Src transformation, we introduced a GFP-tagged temperature sensitive mutant of v-Src (tsLa29-GFP) into Src-deficient (SYF) fibroblasts. The optimum timing for podosome formation when cells expressing tsLa-29-GFP were switched from the non-permissive temperature (41°C) to the permissive temperature (35°C) was 2 h as determined by confocal fluoresence microscopy and rhodamine phalloidin labeling. Inhibition of cortactin expression by siRNA substantially diminished the ability of tsLA29-GFP to induce podosome formation at the permissive temperature. Pretreatment of SYF cells expressing tsLA29-GFP for 1 h with the Src/Abl small molecule inhibitor AZD0530 also ablated podosome formation at the permissive temperature. Collectively, these findings indicate that cortactin is required for Src-mediated podosome formation and that downregulation of Src activity correlates with inhibited podosome formation. We are currently investigating the role of Src-mediated cortactin phosphorylation in podosome assembly, extracellular matrix degradation and invasion.
Abstract 12891: Mitral Valve Analysis Adding a Virtual Semi-Transparent Annulus Plane for Improved Visualization of Prolapsing Segments
Authors: Karl-Andreas Dumont, Jørn Skaarud Karlsen, Stig Urheim
Journal: Circulation (2014)

Introduction: Three-dimensional echocardiography has improved the preoperative evaluation of mitral valve disease. Though, better tools to quantify the amount of prolapsing tissue is warranted. A novel 3D holographic display (Setred AS, Oslo, Norway) offer a 3-dimensional echocardiographic presentation without the need for stereo glasses. We have developed a semi-transparent annulus plane presentation that may better quantitate the prolapsing tissue. Hypothesis: We assessed the hypothesis that it is feasible to create a semi-automatic, semi-transparent annulus plane visualized on the holographic display, demonstrating the prolapsed segment that crosses the virtual mitral valve plane. Methods: Eight patients with degenerative mitral valve disease were analysed. Three-dimensional transthoracic echocardiography was obtained from an apical view and data was converted to the holographic display for further analysis. Findings were compared with visual inspection during surgery. A semi-automated tool was used to detect the annulus; placement of annulus points was done by clicking out points at small rotation intervals around a rotation center point while rotating around the long axis. After a full rotation, the plane was triangulated using a delaunay triangulation process and the annulus plane was visualized as a semi transparent blue surface. The dataset could then be shown from surgeons view in order to see where the valve crosses the visualized valve plane. Results: A total of 48 segments were analysed. We were able to obtain an annulus plane in all and by adding the annulus mitral valve plane, the prolapsing segments could be reproduced in all cases. Figure 1 shows representative recordings (surgeons view) demonstrating a P2 prolapse in the upper panel and a large A2 prolapse in the lower panel. Conclusion: In conclusion, the presentation of a semi-transparent annulus plane was feasible and the findings correlated well with that observed during surgery.
Human B-cell isotype switching origins of IgE
Authors: Timothy J. Looney, Ji-Yeun Lee, Krishna M. Roskin, Ramona A. Hoh, Jasmine King, Jacob Glanville, Yi Liu, Tho D. Pham, Cornelia L. Dekker, Mark M. Davis, Scott D. Boyd
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 14300: Modeling Human Myofibrillar Desmin-Related Cardiomyopathy With Induced Pluripotent Stem Cells
Authors: Pattraranee Limphong, Huali Zhang, Paul Cheng, Michael Riedel, Elisabeth Christians, Qiang Liu, Graydon Taylor, Josh Arnold, Kathy Ivey, Bruce Conklin, Dennis Winge, Deepak Srivastava, Ivor Benjamin
Journal: Circulation (2011)

Chronic conditions such as heart failure and Alzheimer’s are characterized by protein misfolding states for which the underlying mechanism(s) and effective therapies remain poorly defined and elusi...
Transfer of ex vivo expanded T lymphocytes after activation with dendritomas prolonged survival of mice challenged with C1498 tumor cells.
Authors: Jinhua Li, Leigh W. Theofanous, Hilary S. Bouton-Verville, Kelly E. Burgin, Susan M. Jakubchak, Thomas E. Wagner, Yanzhang Wei
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5576 

Adoptive T cell transfer after ex vivo expansion represents an attractive cancer immunotherapy. Majority of the studies so far have been focusing on the expansion of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging results. Recently, we have developed a unique tumor immune response activator, dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and early clinical trials have shown that dendritomas are able to activate tumor specific immune responses. In this study, we hypothesized that naive T cells can be primed with dendritomas and expanded ex vivo in hope to develop an adoptive transfer therapy for patients who do not have solid tumors, such as leukemia. T cells were isolated and purified from either spleen or lymph node of mice. The cells were then incubated with dendritomas made from syngeneic DCs and tumor cells and expanded ex vivo using Dynabeads Mouse CD3/CD28 T cell expander for several weeks. Tumor bearing mice receiving ex vivo expanded T cells survived significantly longer than control mice. Furthermore, the depletion of regulator T cells enhanced the survival of mice received the adoptive transfer therapy.
Regulation of FAK by Ras in brain metastases of breast cancer cells
Authors: Yanhua Zheng, Zhimin Lu
Journal: Cancer Research (2007)

3034   Brain metastases from breast cancer are common and cause significant morbidity and mortality. The underlying mechanism is still largely unknown. We found that brain metastastic breast cancer cells have a higher Ras activity corresponding to a reduced FAK phosphorylation level than their parental breast cancer cells. Dephosphorylation and inhibition of FAK is dependent on Ras activity and mediated by Cdc42 but not other Ras downstream signaling molecules, such as Raf, PI-3K, Ral, and Rac. Furthermore, overexpression of the wild-type tyrosine phosphatase PTP-PEST, but not its catalytic domain mutant, dephosphorylates FAK. Expression of FAKY397F mutant or FRNK in Ras transformed cells enhanced cell migration and invasion. These results strongly suggest that dephosphorylation and inhibition of FAK resulting from PTP-PEST, which is downstream from activation of Ras and Cdc42, contribute to brain metastases of breast cancer cells.