tbuckley/cabot-search huggingface dataset:
Abstract 4662: Framework for clinical evaluation of chemopreventive agents: Defining criteria for future assessment
Authors: Naomi Walsh, David S. Alberts, Powel Brown, Paul Limburg, Mark Sherman, Eva Szabo
Journal: Cancer Research (2015)

Abstract Background Although a number of cancer chemopreventive agents have now been evaluated in phase II and phase III clinical trials that assess their efficacy and tolerability in both high risk and general populations, few have shown clear efficacy and uptake of approved agents has been disappointingly low. Therefore, chemopreventive agents should undergo rigorous screening prior to clinical trial evaluation in order to improve the selection of suitable agents for testing in large, expensive multi-center phase III trials. The aim of this study is to develop a descriptive method for prioritizing candidate agents for further development. Methods This framework was developed through a systematic literature review of Pubmed/Medline, Embase and The Cochrane Library. A semi-quantitative assessment focusing on efficacy and toxicity/tolerability was established based on expert input. Data from clinical trials, cancer epidemiological, observational and preclinical studies, including in vivo and in vitro basic research, was used to retrospectively evaluate the clinical application and effectiveness of cancer chemopreventive agents. Two chemopreventive agents with either a positive (aromatase inhibitors (AIs) for breast cancer) or negative (selenium for lung cancer) phase III clinical trial outcome were subsequently evaluated to determine the usefulness of the framework. Results Chemopreventive agents must reduce or reverse the process of carcinogenesis in normal or pre-malignant tissue with minimal toxicity. Evaluation of efficacy included data from preclinical and animal models, epidemiological studies, and clinical trials (both early phase trials in the organ of interest as well as secondary endpoints from other relevant studies). Agent suitability evaluation included assessment of toxicities, tolerability, and agent specific attributes (PK/PD, bioavailability, dosing, etc.). Examination of selenium and AI historical data in these categories revealed strong concordance with phase III outcomes. The detailed descriptive evaluation of the agents will be presented. Conclusion This framework provides a descriptive paradigm for cancer chemopreventive agent evaluation through systematic and rigorous interrogation. Thorough, standardized evaluation of all available preclinical, epidemiological, and clinical data should be strongly encouraged to better inform the investments required for clinical trials. Citation Format: Naomi Walsh, David S. Alberts, Powel Brown, Paul Limburg, Mark Sherman, Eva Szabo. Framework for clinical evaluation of chemopreventive agents: Defining criteria for future assessment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4662. doi:10.1158/1538-7445.AM2015-4662
Abstract 3073: The Impact of Baseline Mitral Regurgitation on 1-Year Clinical Outcomes in Patients Undergoing Cardiac Resynchronization Therapy
Authors: Kenji Ando, Yoshimitsu Soga, Shinichi shirai, Koyu Sakai, Masahiko Goya, Masashi Iwabuchi, Hiroyoshi Yokoi, Hitoshi Yasumoto, Hideyuki Nosaka, Masakiyo Nobuyoshi
Journal: Circulation (2007)

Background: The impact of mitral regurgitation (MR) on long-term clinical outcomes in patients (pts) undergoing cardiac resynchronization therapy (CRT) is not well established. Methods: We investigated 110 pts received CRT (age 71+/−10years, NYHA class 3.1+/−0.5, LVEF 26+/−7%, LVEDD 61+/−7mm, pre QRS duration 178+/−29ms) and divided into two groups, 40 pts with baseline MR grade 0 –1 (less MR group) and 70 pts with baseline MR grade 2– 4 (severe MR group). 1-year clinical data were obtained. Results: Baseline clinical and echocardiographic characteristics were similar between two groups without baseline MR grade (0.9+/−0.3 in less MR group vs.2.2+/−0.5 in severe MR group, p&lt;0.0001). At 1-year follow up, NYHA functional class was significantly better in less MR group than severe MR group (1.9+/−0.8 vs.2.4+/−0.6, p=0.0004). Event free survival rate from heart failure hospitalization (HFH) was significantly higher in less MR group compared to severe MR group (93% vs.75% at 1 year, Log-rank p=0.037) and event free survival rate from combined death and HFH was also significantly higher in less MR group (87% vs.69% at 1 year, Log-rank p=0.039). Conclusion: Pts with severe baseline MR had worse clinical outcomes even if received CRT compared to less MR pts.
Delusions in newly admitted residents of nursing homes
Authors: Richard K. Morriss, Barry W. Rovner, Marshal F. Folstein, Pearl S. German
Journal: American Journal of Psychiatry (1990)

Two psychiatrists, using standardized clinical examinations, found that 21% of 125 patients newly admitted to nursing homes had delusions. The psychiatric disorders associated with these delusions are described. Delusional patients were more behaviorally disturbed before admission than nondelusional patients. These behavior problems were often the reason for admission, and they persisted after admission. Nursing home staff members infrequently identified and often inappropriately treated delusional patients. Since delusions are an important potentially treatable cause of behavior problems in nursing home residents, the authors suggest ways to improve the recognition and management of delusions.
Abstract 875: Risk factors for hepatocellular carcinoma (HCC) by race/ ethnicity in the United States
Authors: Oxana V. Makarova-Rusher, Sean F. Altekruse, Timothy S. McNeel, Barry I. Graubard, Austin G. Duffy, Susanna V. Ulahannan, Tim F. Greten, Katherine A. McGlynn
Journal: Cancer Research (2015)

Abstract Background: Primary liver cancer is the sixth most common cancer worldwide, with HCC representing the majority of the cases. In the U.S., HCC rates are higher among Hispanics, Asians and blacks than among whites. Whether the higher risks are due to different distributions of risk factors is not clear. Thus, we conducted an analysis of HCC risk factors by race/ethnicity in the SEER-Medicare database for the years 2000-2009. Methods: HCC cases (n = 8,116), identified by ICD-O morphology codes 8170-8175, were compared to a 5% random sample of cancer-free persons in the SEER areas (n = 313,525). Risk factors examined included type II diabetes (DM II), obesity, hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol-related disorders. Multivariate logistic regression analyses, which adjusted for age, location, gender, income and date of diagnosis as well as the other risk factors were used to compare risk factors by racial/ethnic group. Results: Risk factors by race/ethnicity Risk factorWhiteBlackAsiansHispanicsN 6,120N 668N 971N 357%OR (95% CI)%OR (95% CI)%OR (95% CI)%OR (95% CI)Obesity6.31.06 (0.9-1.2)5.51.0 (0.7-1.5)0.70.2 (0.1-0.8)7.81.2 (0.7-1.9)DM II44.52.9 (2.8-3.1)41.81.3 (1.1-1.6)38.11.8 (1.5-2.1)54.62.0 (1.5-2.7)HBV1.83.8 (2.6-5.7)3.61.6 (0.7-3.7)17.717.1 (11.8-25.0)2.01.4 (0.2-11.1)HCV16.819.7 (17.1-22.6)34.036.8 (28.0-48.6)31.121.4 (15.4-29.9)22.716.0 (9.2-28.1)Alcohol cirrhosis11.44.7 (3.7-5.8)7.64.5 (2.4-8.5)4.03.8 (1.3-11.7)17.13.3 (1.7-6.8)Alcohol NOS13.12.7 (2.2-2.9)13.21.6 (1.1-2.4)3.72.0 (1.0-4.1)14.81.6 (0.8-3.0)Cirrhosis NOS33.345.5 (41.2-50.4)24.117.9 (12.3-25.9)36.836.9 (26.2-52.0)44.827.6 (18.9-40.3) NOS not otherwise specified. Conclusion: Major HCC risk factor profile is differ across race/ethnical groups. While diabetes is most common risk factor overall, it is most prevalent in Hispanics. HCC related to HCV is more common in blacks and Asians, and to HBV in Asians. Citation Format: Oxana V. Makarova-Rusher, Sean F. Altekruse, Timothy S. McNeel, Barry I. Graubard, Austin G. Duffy, Susanna V. Ulahannan, Tim F. Greten, Katherine A. McGlynn. Risk factors for hepatocellular carcinoma (HCC) by race/ ethnicity in the United States. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 875. doi:10.1158/1538-7445.AM2015-875
P0813 : All oral therapy (Sofosbuvir–Ribavirin) combination in severe HCV-mixed cryoglobulinemia vasculitis, the vascuvaldic study
Authors: D. Saadoun, V. Thibault, G. Pialoux, L. Elkrief, M. Mallet, L. Musset, D. Bazin Kara, C. Cazorla, S. Pol, P. Cacoub
Journal: Journal of Hepatology (2015)
Abstract 17901: Mechanisms of Increased Arrhythmic Risk Associated With Exposure to Urban Air Pollution
Authors: Gopal Sivagangabalan, Danna Spears, Stephane Masse, Bruce Urch, Robert D Brook, Frances Silverman, Diane R Gold, Karl Z Lukic, Mary Speck, Marjan Kusha, Talha Farid, Kwaku Poku, Evelyn Shi, John Floras, Kumaraswamy Nanthakumar
Journal: Circulation (2010)

Introduction:  An association has been observed between elevated levels of air pollution and the occurrence of cardiac arrhythmia. However, the mechanism by which air pollution results in arrhythmia has not been defined.   Hypothesis:  We tested the hypothesis that exposure to concentrated ambient fine particles (CAP) and/or ozone (O 3 ) would increase dispersion of repolarization, a known risk factor for arrhythmogenesis, by modulation of the autonomic nervous system.   Methods:  Twenty five volunteers (18–50 years of age) each had four 2-hr exposures including: 150 μg/m 3  CAP; 120 ppb O 3 ; CAP+O 3 ; and filtered air (FA). Continuous 12-lead ECG recording was analyzed to determine exposure-induced changes (Δ=5-min epochs at end-start) in spatial dispersion of repolarization assessed by the corrected T-peak to T-end (cTp-e) interval and QT dispersion (QTd). Spectral analysis of heart rate variability (HRV) was used to identify changes in autonomic tone, with the high frequency (HF) component indicating parasympathetic heart rate modulation and the low frequency (LF) to HF ratio (LF/HF) indicating the balance between sympathetic-parasympathetic tone.   Results:  The ΔcTp-e increased significantly for the CAP+O 3  (0.17±0.03, p 3  — FA) as a control exposure (0.11±0.04, p=0.013). Spatial dispersion of repolarization was further verified by a significant increase in ΔQTd for CAP+O 3  compared to FA (5.7±1.4, p=0.0002). When the LF/HF ratio of HRV (sympathetic-parasympathetic balance) was included as a covariate in a mixed model analysis the effect estimate was positive for both ΔcTp-e (p=0.002) and Δ QTd (p=0.038), indicating a relative increase in sympathetic tone was associated with increasing spatial dispersion of repolarization. When the HF component was included as a covariate with ΔcTp-e, the effect estimate for HF was negative (p=0.016), thus indicating a reduction in parasympathetic heart rate modulation is associated with increasing ΔcTp-e.   Conclusions:  In conclusion, dispersion of cardiac repolarization was most affected by CAP+O 3  and is partly mediated by increased sympathetic tone and withdrawal of parasympathetic heart rate modulation.
Permanence of paper puts authors on best behaviour
Authors: M. Longmore
Journal: BMJ (1995)

EDITOR,--I am nervous, elated, and keyed up with all my faculties a-tingle because I am writing a letter to the BMJ. Because my thoughts may be set for eternity in print, I am on my best behaviour. I shall check my spelling, my facts, and my references, and I shall agonise over construction. Like herpes, letters to the editor are forever. Once the presses roll, that is it. And …
Fully human antimesothelin antibody drug conjugate demonstrates antitumor effects in human lung cancer models.
Authors: Sarah Pogue, Xingjie Chen, Svetlana Alexander, Rozanne Lee, Jyothsna Kuchipudi, Chetana Rao, David King, Meghan Greenbaum, Bing Chen, Tim Chen, Sanjeev Gangwar, Pina Cardarelli, Jonathan Terrett
Journal: Clinical Cancer Research (2008)

A13   Mesothelin is a GPI anchored glycoprotein present on normal mesothelial cells lining pleural, pericardial and peritoneal body cavities. It is expressed as a 69kDa precursor polypeptide that is proteolytically processed into a shed 31kDa component, Megakaryocyte Potentiating Factor, and a 40kDa membrane bound component. Detection of the 40kDa portion of Mesothelin by IHC has demonstrated that Mesothelin is over-expressed in several human malignancies including all mesotheliomas, > 85% of papillary serous ovarian cancers, and in approximately 50% of pancreatic and lung cancers. The restricted normal expression and high expression in cancer makes Mesothelin an attractive target for cancer immunotherapy. In this study, we report the generation of fully human monoclonal antibodies to Mesothelin. These antibodies internalize on cell binding as shown by HumZAP and immunofluorescence assays; enabling the development of an antibody-drug-conjugate mechanism of action. The anti Mesothelin antibodies were conjugated to DNA alkylating agents and tested in  in vivo  xenograft model of lung cancer (H226 cells.) A single dose of 0.3μm/kg of antibody caused complete regressions in this model. No toxicities were observed at this dose level. Furthermore, an antibody drug conjugate using a rat anti mouse specific Mesothelin antibody also showed no overt toxicities at these dose levels. These studies support the development of a fully human anti-Mesothelin antibody drug conjugate as therapy for the treatment of Mesothelin expressing cancers.
Placebos used not to be used in studies
Authors: F D. Hart
Journal: BMJ (1995)

EDITOR,--I qualified in medicine before the second world war, when clinical trials were not the common events that they later became in hospital practice. In the prewar and early postwar years we used to ask patients to give us signed permission to add or substitute new drugs in their treatment without informing them; there was no placebo.1

In the early days of corticosterone treatment for rheumatic disorders in 1949 …
Abstract 18777: Right Ventricular Outflow Tract Strain is Reduced in Tetralogy of Fallot Compared to Valvar Pulmonary Stenosis Patients; Regional RV Function Defined by Strain Cardiac Magnetic Resonance Imaging
Authors: Shafkat Anwar, Matthew A Harris, Kevin K Whitehead, Marc S Keller, Mark A Fogel, Laura M Mercer-Rosa
Journal: Circulation (2013)

Introduction: The right ventricular outflow tract (RVOT) patch after Tetralogy of Fallot (ToF) surgery may contribute to ventricular dysfunction, but the specific effects on RV function are not clear. We aimed to investigate RV function in patients with ToF and RVOT patch by comparing to patients with valvar pulmonary stenosis (vPS) after balloon valvuloplasty (no RVOT patch). Methods: We conducted a retrospective review of 33 CMR studies of ToF and vPS patients with similar pulmonary regurgitation (PR) Table 1. Feature tracking strain (FTS) analysis of balanced steady state free precession (SSFP) cines was performed on the RV in apical 4-chamber (4ch), RVOT sagittal &amp; mid-RV short axis views (TomTec 2D Cardiac Performance Analysis, v1.0), Figure 1. Unpaired t-tests were applied for comparison of means between groups. Results: Lagrangian longitudinal strain (LS) at the RVOT was significantly lower in ToF compared to vPS (mean -14.1% vs -18.2%, unpaired t-test p = 0.03), Table 1. Analysis of regional S within the same group showed a trend towards lower RVOT strain compared to 4ch LS in ToF (p = 0.052). There were no significant inter-group differences in strain from the 4ch or mid-RV short axis views, with normal 4ch LS in both groups. Conclusion: In a population with preserved EF, RVOT strain is significantly lower in ToF patients with a transannular patch compared to vPS patients with similar amount &amp; duration of PR. Low RVOT LS appears to be a regional phenomenon, with strain in the 4ch and mid-RV similar between groups. Further investigation is warranted in a larger sample. FTS analysis is a promising technique to evaluate regional RV mechanics in this population.
Transforming Growth Factor-β1 (TGF-β1) Induces Thrombopoietin From Bone Marrow Stromal Cells, Which Stimulates the Expression of TGF-β Receptor on Megakaryocytes and, in Turn, Renders Them Susceptible to Suppression by TGF-β Itself With High Specificity
Authors: Sumio Sakamaki, Yasuo Hirayama, Takuya Matsunaga, Hiroyuki Kuroda, Toshiro Kusakabe, Takehide Akiyama, Yuichi Konuma, Katsunori Sasaki, Naoki Tsuji, Tetsuro Okamoto, Masayoshi Kobune, Katsuhisa Kogawa, Junji Kato, Rishu Takimoto, Ryuzo Koyama, Yoshiro Niitsu
Journal: Blood (1999)
Conserving Blood in Preparation for Elective Surgery
Authors: A Baraka, T Juma, S K Asfar, H Al-Sayer
Journal: Journal of the Royal Society of Medicine (1991)

A prospective study was carried out for a period of 6 months (September 1987 to 28 February 1988) to evaluate the possible misuse of blood transfusion service in the department of surgery, Amiri Teaching Hospital, Kuwait. There was a monthly wastage of 45 +/- 13 units of blood. Five hundred and eleven units of blood were crossmatched but never transfused. The time taken by the blood bank technicians in crossmatching blood which was never used amounted to 54.4% of the normal working hours. An annual loss of about US$25000.00 was calculated to have occurred.
VEGF targeting increases the cystostatic effect of docetaxel on prostate and breast tumor cells: A new interpretation of the therapeutic effect.
Authors: Cecile Ortholan, Jerome Durivault, Andhira Viera, Gilles Pages
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2496 

Bevacizumab is a VEGF targeted humanized monoclonal antibody preventing tumor neoangiogenesis. Several studies demonstrated the benefit of bevacizumab combined with taxane, a class of microtubule stabilizing agents. As VEGF signaling pathway has been described as a survival pathway for tumor cells, we hypothesized that bevacizumab could also directly targets tumor cells.We studied the effect of docetaxel (a taxane class drug) and bevacizumab on two tumor cell lines with metastatic potential: MDA 231 (breast cancer) and PC3 (prostate cancer). Cell growth was evaluated using automatic cell counter. VEGF and VEGF receptor (VEGF-R) promoter activity was determined using luciferase reporter assays; mRNA levels were evaluated using quantitative real time PCR. Intracellular and extracellular concentrations of growth factors were measured by ELISA assay; intracellular and membrane expression of VEGF-R was determined by western blot. Bevacizumab alone has no significant effect on cell growth, but increases the cytostatic activity of docetaxel. To explore this finding, we studied the action of docetaxel on VEGF signaling pathway. Docetaxel induces a dose dependent activation of the VEGF and VEGF-R promoters, and increases both VEGF and VEGF-R mRNA levels. However, extracellular amounts of VEGF and membrane VEGF-R expression are reduced by docetaxel whereas cytoplasmic amounts of both VEGF and VEGF-R increased. The inhibitory effect of docetaxel on the expression of VEGF-R at the plasma membrane is further increased by bevacizumab VEGF trap. Extracellular quantity of others growth factors, such as EGF and PDGF are also diminished by docetaxel treatment. The combination of bevacizumab plus docetaxel strongly locks the VEGF pathway. VEGF was described to maintain the expression of its receptors at the plasma membrane. Thus, any down regulation of external VEGF amounts would also alter normal VEGF-R expression. Here we demonstrated that docetaxel, by its highly documented action on microtubule, prevents normal secretion of a lot of growth/pro survival factors including VEGF, EGF and PDGF. Hence, trapping VEGF by bevacizumab suppress a growth/pro survival pathway increasing the cytostatic effect of docetaxel. These results described for the first time that inhibitors of VEGF target the endothelial cells participating in tumor neoangiogenesis but also tumor cells themselves. This mechanism could explain why the combination of bevacizumab and taxane is strongly efficient on patients and increases clinical outcome.
Abstract 2828: Application of New Task Force Criteria for Diagnosis of Arrhythmogenic Right Ventricular Dysplasia
Authors: Moniek G Cox, Jasper J van der Smagt, Maartje Noorman, Ans C Wiesfeld, J Peter van Tintelen, Douwe E Atsma, Paul G Volders, Arthur A Wilde, Richard N Hauer
Journal: Circulation (2009)
Extracellular matrix components modulate radiosensitization of transformed keratinocytes by EGFR inhibition
Authors: Qing Ren, Ulrich Rodeck, Csaba Kari, Tung O. Chan, Adam Dicker
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2777 

Inhibition of the EGFR has been reported to sensitize malignant epithelial cells including squamous cell carcinoma of the skin to the deleterious effects of ionizing radiation. In this study we ask the question whether interaction with components of the extracellular matrix affects radiosensitization of transformed keratinocytes by EGFR blockade. To this end, we used HaCaT cells seeded in the presence and absence of the EGFR inhibitor IRESSA (ZD1839) onto 96-well plates coated with either 0.9% agarose for forced suspension culture or various extracellular matrix components including collagen I, IV, fibronectin, laminin I and Poly-D-Lysine for 2h prior to exposure of various doses of ionizing radiation (0-10 Gy). Effects of these treatments on cellular metabolism were determined 3 days after radiation using MTT assays. Consistent with previous reports, we observed that ZD1839 inhibited MTT conversion in HaCaT cells either alone or in combination with radiation. All types of extracellular matrices tested supported high levels of cellular metabolism in comparison with forced suspension culture. Furthermore, attachment to either collagen I, IV or fibronectin markedly alleviated the reduction in cellular metabolism by EGFR blockade and radiation. By contrast, cells seeded on laminin I, poly-D-lysine or tissue culture-treated plastic surface did not protect against radiosensitization by EGFR blockade. In the same experimental setting, we also found that attachment to collagen I, IV, fibronectin and laminin I demonstrated elevated levels of constitutive and EGF-induced MEK/MAPK activation and insulin-induced PI3K/AKT activation as compared to tissue culture-treated plastic surface and poly-D-lysine. Additional signaling pathways jointly controlled by EGFR activation and matrix engagement and instrumental in radioprotection are currently under investigation. Collectively, these observations suggest that the extracellular matrix surrounding tumor cells in vivo may offer protection against EGFR blockade and ionizing radiation.
HIV-associated psychosis: a study of 20 cases. San Diego HIV Neurobehavioral Research Center Group
Authors: D D Sewell, D V Jeste, J H Atkinson, R K Heaton, J R Hesselink, C Wiley, L Thal, J L Chandler, I Grant
Journal: American Journal of Psychiatry (1994)

Psychosis is an uncommon but serious complication of infection with HIV. This article presents the results of a study of HIV-infected individuals with psychosis.The authors evaluated 20 HIV-infected men who had noniatrogenic new-onset psychosis without delirium, current substance abuse, or previous psychotic episodes. Clinical, neuropsychological, CSF, magnetic resonance imaging, and neuropathologic assessments were made. A comparison group consisting of 20 nonpsychotic HIV-infected men matched to the psychotic subjects with respect to age, race, years of education, and Centers for Disease Control HIV stage was also evaluated.The psychotic patients differed from the nonpsychotic comparison subjects in having significantly higher rates of past stimulant and sedative/hypnotic abuse or dependence and, at follow-up, a significantly higher rate of mortality. They also showed a trend toward greater global neuropsychological impairment.New-onset psychosis may be, at least in part, a manifestation of an HIV-associated encephalopathy.