tbuckley/cabot-search huggingface dataset:
Reolysin®, an unmodified Reovirus, has significant anti-tumor activity in childhood sarcomas
Authors: Wendong Ellen Zhang, E. Anders Kolb
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4331 

Reolysin® is an unmodified oncolytic reovirus which replicates selectively in ras transformed cells causing cell lysis. Activating mutations in ras or mutations in oncogenes signaling through the ras pathway may occur is as many as 80% of human tumors. Such mutations have been described in many of the common sarcomas of childhood. In the currently study, ras activation is confirmed in several Ewing’s sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma cell lines. In vitro cytotoxicity assays reveal complete cell kill at reovirus titers greater than 1 to 10 pfu for all cell lines tested. A cytopathic effect is observed by microscopy and viral replication assessed by immunoprecipitation of vrial protein in whole cell lysates. The ani-tumor effect of the reovirus is confirmed in vivo using established xenograft models of pediatric sarcomas. Initial experiments using reovirus doses of 1 × 108 pfu, 5 × 108 pfu and 5 × 109 pfu daily for 3 days per week times 2 weeks, reveal that the 5 × 109 pfu dose is well tolerated and effective in the nude mice xenograft model of osteosarcoma. The antitumor effect of the reovirus is subsequently evaluated in 4 additional independent pediatric sarcoma xenografts (Ewing’s sarcoma and rhabdomyosarcoma, respectively). In all tumor lines evaluated, the reovirus exhibits significant antitumor activity, including a complete response in a rhabdomyosarcoma line. Relosysin® demonstrates excellent anti-tumor activity in vitro and in vivo in childhood sarcoma cell lines. These promising preclinical results suggest that a clinical trial of systemic reovirus in pediatric solid tumors is warranted.
Novel tyrosine phosphorylation targets of EGF signaling and gefitinib in human cancer cells.
Authors: Yunhao Chen, Teck Yew Low, Lee Yee Choong, Rajarshi Ray, Yee Ling Tan, Weiyi Toy, Qingsong Lin, Boon Keong Ang, Chee Hong Wong, Simin Lim, Bin Li, Choy Leong Hew, Newman Siu-Kwan Sze, Brian J. Druker, Yoon Pin Lim
Journal: Clinical Cancer Research (2007)

B64   Analysis of enriched phosphotyrosyl proteins from epidermal growth factor (EGF)-induced proteome permits the identification of novel downstream substrates of the EGF receptor (EGFR). Using cICAT-based LC-MS/MS phosphoproteomics method, we identified and relatively quantified the tyrosine phosphorylation levels of 21 proteins between control and EGF-treated A431 human cervical cancer cells. Of these, Endofin, DCBLD2, and KIAA0582 were validated to be novel tyrosine-phosphorylation targets of EGF signaling and Gefitinib, a highly selective inhibitor of EGFR. In addition, EGFR activity was shown to be necessary for EGF-induced localization of Endofin, an FYVE domain-containing protein regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Although several groups have conducted phosphoproteomics of EGF signaling in recent years, our study is the first to identify and validate Endofin, DCBLD2, and KIAA0582 as part of a complex EGF phosphotyrosine signaling network. These novel data will provide new insights into the complex EGF signaling and may have implications on target-directed cancer therapeutics.
Primary Infection with Zidovudine-Resistant HIV
Authors: P. Hermans, S. Sprecher, N. Clumeck, Bernard Masquelier, Emmanuelle Lemoigne, Isabelle Pellegrin, Danielle Douard, Boris Sandler, Herve J.a. Fleury, Alejo Erice, Henry H. Balfour
Journal: New England Journal of Medicine (1993)
Ponatinib Safety and Efficacy in Japanese Patients with Philadelphia Positive Leukemia: Update of a Phase 1/2 Study
Authors: Taiichi Kyo, Arinobu Tojo, Kazuhito Yamamoto, Naoto Takahashi, Hirohisa Nakamae, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Hiromi Iwasaki, Kiyohiko Hatake, Itaru Matsumura, Noriko Usui, Kumiko Yanase, Simin Hu, Tomoki Naoe, Kazuma Ohyashiki
Journal: Blood (2014)
P0040 : Long-term cardiovascular mortality after liver transplantation: Analysis of risk factors
Authors: D. D’Avola, V. Cuervas-Mons, J. Martí, J. Ortiz de Urbina, L. Lladó, C. Jimenez, E. Otero, F. Suarez, J.M. Rodrigo, M.A. Gomez, E. Fraga, P. Lopez, T. Serrano, A. Rios, E. Fabrega, J.I. Herrero
Journal: Journal of Hepatology (2015)
A clinical note on hysterical psychosis
Authors: J O Cavenar, J L Sullivan, A A Maltbie
Journal: American Journal of Psychiatry (1979)

The authors review the concept of hysterical psychosis and its reported psychodynamics. They suggest a psychodynamic issue that apparently has not been previously reported, namely, emotions engendered by an overt sexual advance or rage and disappointment over a lack of a sexual advance. This finding can be most helpful in distinguishing a case of hysterical psychosis from an acute schizophrenic episode.
Abstract 3024: Autogenic Training to Manage Chest pain in Women with Angina and Normal Coronary Arteries.
Authors: Elizabeth A Asbury, Nasim Kanji, Edzard Ernst, Mahmoud Barbir, Peter Collins
Journal: Circulation (2007)

Background: Women with angina pectoris, a positive exercise ECG for myocardial ischaemia and angiographically smooth coronary arteries (Cardiac Syndrome X), suffer increased psychological morbidity, debilitating symptomology and a poor quality of life. Autogenic Training (AT), a hypnosis-based auto-suggestive relaxation technique improved anxiety and quality of life in patients with CHD, multiple sclerosis and breast cancer. An exploration of AT as a treatment for Syndrome X was therefore undertaken. Methods: Fifty three female Syndrome X patients (mean ± SD; 57.4 ± 8.0 yrs) were randomised to an 8-week group-based AT and symptom diary program or symptom diary only control. Weekly group AT sessions were supported by an individual home program. The Hospital Anxiety and Depression Scale (HADS) Spielberger State-Trait Anxiety Inventory (STAI) Cardiac Anxiety Questionnaire (CAQ) and the Ferrans &amp; Powers Quality of Life Index (QLI) were completed pre- and post-intervention and at 8-week follow-up. Results : Post-intervention, AT patients had reduced symptom severity (2.08 ± 1.03 vs. 1.23 ± 1.36, p=0.02) and frequency (6.11 ± 3.17 vs. 1.66 ± 2.19, p&lt;0.001) with improved severity (8.04 ± 10.08 vs. 1.66 ± 2.19, p&lt;0.001) and a trend toward reduced symptom frequency (1.95 ± 1.19 vs. 1.23 ± 1.36, p=0.063) compared to controls. Following AT, improved QLI health functioning (17.80 ± 5.74 vs. 19.41 ± 5.19, p=0.04) and CAQ fear (1.53 ± 0.61 vs. 1.35 ± 0.56, p=0.02) were found, with improvements in QLI health functioning (17.80 ± 5.74 vs. 20.09 ± 5.47, p=0.01), CAQ fear (1.53 ± 0.61 vs. 1.30 ± 0.67, p=0.002) CAQ total (1.42 ± 0.54 vs. 1.29 ± 0.475, p=0.04), STAI trait anxiety (42.95 ± 11.19 vs. 38.68 ± 11.47, p=0.01) and QLI quality of life (20.67 ± 5.37 vs. 21.9 ± 4.89, p=0.02) at follow-up. Post-monitoring changes in HADS depression (5.1 ± 3.3 vs. 4.2 ± 3.2, p=0.01), total HADS (13.95 ± 6.84 vs. 12.22 ± 5.75, p=0.02), CAQ avoidance (1.51 ± 0.92 vs. 1.24 ± 0.89, p=0.03), attention (1.33 ± 0.78 vs. 1.16 ± 0.57. p=0.05) and CAQ total (1.39 ± 0.6 vs. 1.23 ± 0.52, p=0.01) were shown in the control group. None were maintained at follow-up. Conclusion : An 8-week AT program has been shown to improve symptom severity and frequency, psychological morbidity and quality of life in women with Cardiac Syndrome X.
Phase I/II study of 2-chloro-2 '-deoxyadenosine (CdA) in combination with cyclophosphamide (CP) in patients (pts) with advanced low grade lymphoid malignancies.
Authors: Eric Van Den Neste, Lucienne Michaux, Augustin Ferrant, I Louviaux, André Delannoy, Jl. Michaux, André Bosly, Anne Sonet, Chantal Doyen, M Meyns, Marc André, P. Mineur, Nicole Straetmans
Journal: Blood (1998)
Effects of Arsenite Exposure during Fetal Development on Energy Metabolism and Susceptibility to Diet-Induced Fatty Liver Disease in Male Mice
Authors: Eric J. Ditzel, Thu Nguyen, Patricia Parker, Todd D. Camenisch
Journal: Environmental Health Perspectives (2015)

Chronic exposure to arsenicals at various life stages and across a range of exposures has been implicated in cardiometabolic and liver disease, but disease predisposition from developmental exposures remains unclear.In utero and post-weaning exposure to trivalent arsenic (AsIII) was examined on the background of a Western-style diet to determine whether AsIII exposure affects metabolic disease.Male Swiss Webster mice were exposed to 100 ppb AsIII in utero, after weaning, or both. Ad libitum access to a Western-style diet was provided after weaning, and the plasma metabolome, liver histopathology, liver enzyme activity, and gene expression were analyzed.Hepatic lipid composition and histopathology revealed that developmental AsIII exposure exacerbated Western-style diet-induced fatty liver disease. Continuous AsIII exposure increased cardiometabolic risk factors including increased body weight, insulin resistance, hyperglycemia, and plasma triglycerides. AsIII exposure produced a decrease in the intermediates of glycolysis and the TCA cycle while increasing ketones. Hepatic isocitrate dehydrogenase activity was also decreased, which confirmed disruption of the TCA cycle. Developmental AsIII exposure increased the expression of genes involved in fatty acid synthesis, lipogenesis, inflammation, and packaging of triglycerides, suggesting an increased acetyl coenzyme A (acetyl-CoA) load.In utero and continuous early-life exposure to AsIII disrupted normal metabolism and elevated the risk for fatty liver disease in mice maintained on a high-fat diet. Our findings suggest that individuals exposed to AsIII during key developmental periods and who remain exposed to AsIII on the background of a Western-style diet may be at increased risk for metabolic disease later in life.
Impact of antidiabetic agents on the survival of subjects with colorectal cancer (CRC).
Authors: T. C. Gray, E. Siegel, R. Govindarajan
Journal: Journal of Clinical Oncology (2010)

2586 Background: Metformin has anticancer effect by inhibiting mTOR pathway in CRC via TSC2 activation and by reducing circulating insulin and adiponectin. Thiazolidinediones (TZD) suppress intestinal polyp formation in APC-min mice through PPAR γ pathway. Sulfonylureas activate MAP kinase, promote cellular growth through mTOR inactivation of GSK3, and increase circulating insulin and adiponectin. The effect of antidiabetic agents on the survival of subjects with colorectal cancer was evaluated. Methods: A retrospective cohort study of male diabetics aged ≥40 was conducted from the patient data base VISN 16 comprising 10 VA hospitals. Subjects with CRC between 10/01/96 and 12/31/05 were identified using ICD 9 codes, and followed from diagnosis to death or last recorded visit. Data were analyzed for effects of diabetes treatment on OS using multivariate Cox regression with drug exposures as time-dependent covariates, and with stratification on race and age quartiles. Results: 845 deaths were observed among CRC subjects during a total follow-up of 8870.4 years. Median age (quartiles) at CRC diagnosis was 70 yrs (62–75). 19% were African-American, 65% were Caucasian, and 16% were other /unknown. The Table shows the influence of antidiabetic agents on the survival of subjects with colorectal cancer. Conclusions: Metformin and TZDs appear to have beneficial effects on OS in subjects with CRC. Insulin and sulfonylureas appear to have detrimental effect on OS. The effects of these agents on the stage and the influence of coexisting treatments of colorectal cancer need further analysis. Exposure summary and multivariate Cox-regression results Diabetes treatment >Exposure summary Adjusted HR3 (95% confidence limits) P value N (%1) Years (%2) Deaths Diet only 526 (21%) 2826.9 (32%) 198 1.00 (reference) — Insulin 730 (29%) 1983.4 (22%) 282 1.91 (1.65–2.21) <.0001 Metformin 573 (23%) 1610.0 (18%) 116 0.80 (0.66–0.98) 0.0323 Sulfonylureas 1304 (52%) 4130.7 (47%) 448 1.34 (1.17–1.54) <.0001 TZDs 401 (16%) 899.3 (10%) 63 0.63 (0.48–0.82) 0.0005 1 % of total number of 2,496 subjects on study. 2 % of total follow-up of 8870.4 years. 3 Hazard ratio of each treatment adjusting for the presence of the other treatments. No significant financial relationships to disclose.
Cholestatic hepatitis in association with celecoxib
Authors: F. Mohammed
Journal: BMJ (2002)

Editor—We appreciated the report by O'Beirne and Cairns concerning a patient with liver test dysfunction in the setting of treatment with the COX 2 inhibitor celecoxib.1 We are, however, concerned at their use of “cholestatic hepatitis” as the most appropriate description of the pattern of liver test abnormality observed. The patient they described had a maximal aspartate transaminase concentration of 1650 IU/l (reference range 10-40 IU/l), a maximal alkaline phosphatase concentration of 232 IU/l (25-115 IU/l), and peak total serum bilirubin of 123 μmol/l (5-20 μmol/l).

In broad terms, two categories of drug associated liver injury are encountered commonly, namely cholestatic and hepatocellular.2 Cholestatic injury has been defined further as occurring when the peak transaminase concentration is less than eight times the upper limit of normal, and the corresponding ALP is greater than threefold normal, whereas hepatocellular injury has been defined as being present when the peak transaminase concentration is greater than eight times the upper limit of normal and the concomitant alkaline phosphatase concentration is less than threefold normal. A mixed pattern of injury, showing features of both, may also be found.3 According to these criteria the patient of O'Beirne and Cairns had evidence of hepatocellular injury primarily, rather than a mixed pattern as the term “cholestatic hepatitis” suggests. Liver biopsy might have helped to emphasise this distinction.

The article by Maddrey et al referred to in their report was misquoted4: where the term alkaline phosphatase was used, it should have read alanine aminotransferase. In that study only 0.4% and 0.3% respectively of 6376 patients treated with celecoxib had maximal alanine aminotransferase and aspartate transaminase concentrations greater than or equal to three times the upper limit of normal. None of these transaminase elevations was greater than eight times the upper limit of normal, in contrast to that found in the patient of O'Beirne and Cairns (about 41 times upper normal limit).

Therefore, although we disagree with the view that this patient had cholestatic hepatitis on the basis of data quoted, the case does represent the first reported instance of severe hepatocellular liver dysfunction in association with celecoxib treatment.
Improvement in Vision-Related Function with Intravitreal Aflibercept
Authors: Mitsuko Yuzawa, Kyoko Fujita, Kim U. Wittrup-Jensen, Christiane Norenberg, Oliver Zeitz, Kenji Adachi, Edward C.Y. Wang, Jeffrey Heier, Peter Kaiser, Victor Chong, Jean-Francois Korobelnik
Journal: Ophthalmology (2014)
Outpatient alcohol detoxification: initial findings on 564 patients
Authors: Daniel J. Feldman, E. M. Pattison, Linda C. Sobell, T. Graham, Mark B. Sobell
Journal: American Journal of Psychiatry (1975)

The authors report on a large-scale outpatient alcohol detoxification program, presenting a clinical rationale for outpatient detoxification, describing the program method, and giving initial evaluation data on the first 564 patients. Only 47 percent of the patients required detoxification, and only 19 percent of these required inpatient care. The majority of the patients successfully completed outpatient detoxification; half of these continued in the related rehabilitation program. There were no fatalities. The authors believe the results support the utility of outpatient detoxification as a cost-effective alternative to inpatient detoxification for the majority of acute alcoholics.
Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation
Authors: Rabea Hinkel, Philipp Lange, Björn Petersen, Elena Gottlieb, Judy King Man Ng, Stefanie Finger, Jan Horstkotte, Seungmin Lee, Michael Thormann, Maike Knorr, Chiraz El-Aouni, Peter Boekstegers, Bruno Reichart, Philip Wenzel, Heiner Niemann, Christian Kupatt
Journal: Journal of the American College of Cardiology (2015)
Maturation of Responsiveness to Cardioactive Drugs
Authors: Kern Wildenthal, Jacquline R. Wakeland
Journal: Journal of Clinical Investigation (1973)

Freshly isolated hearts of fetal mice of gestational ages ranging between 12 and 22 days (term) were exposed to several concentrations of a variety of chronotropic agents. Acetylcholine (10(-4)-10(-2) M) caused marked bradycardia in all hearts, even after only 12-14 days' gestation (i.e., even before cardiac innervation had occurred), and the intensity of the response increased steadily with advancing age throughout gestation. Responsiveness to norepinephrine was present but minimal at 12-14 days, so that mean atrial rate rose by < 10% with a maximal concentration of the drug (10(-5) M); responsiveness became more marked by 15-16 days (just after the time atrial innervation is thought to begin) and still greater effects appeared just before term. Glucagon had no effect in hearts of < 17 days' gestational age, but caused tachycardia thereafter, indicating that cardiac responsiveness to glucagon differentiates later than does responsiveness to norepinephrine. Responses to theophyl-line in 12-14 day hearts exceeded those to norepinephrine, indicating that the drug can affect heart rate independently of its ability to cause release of endogenous catecholamines. In contrast, tyramine caused no response until 21-22 days, well after the time the beta-receptor has differentiated and after innervation is fairly well developed, suggesting that the drug's primary sympathomimetic effect is indirect rather than direct. Dibutyryl cyclic AMP did not cause tachycardia at any fetal age. It is concluded that maturation of responsiveness of the mouse heart to cardioactive drugs develops in specific patterns for different agents. The identification of differential patterns of maturation for various drugs may provide valuable means for characterizing the differentiation of specific receptors and for investigating possible mechanisms of action of the drugs.
Predictors of Benefit in Colorectal Cancer Treated With Cetuximab: Are We Getting "Lost in TranslationAL"? Reply
Authors: Bart Jacobs, Hubert Piessevaux, Wendy De Roock, Bart Biesmans, Jef De Schutter, Bart Claes, Sabine Tejpar
Journal: Journal of Clinical Oncology (2010)
Abstract 341: Both Beta-1 and Beta-2 Adrenergic Receptors (ARs) are Required for Pressure Overload Cardiac Hypertrophy
Authors: Mingming Zhao, Roger Wagner, Giovanni Fajardo, Takashi Urashima, Sara Farahani, Brian K Kobilka, Thomas Quertermous, Daniel Bernstein
Journal: Circulation (2007)

In isolated myocytes, hypertrophy induced by norepinephrine is mediated via β-ARs, however, in vivo, mice with deletions of both major cardiac β-ARs still develop hypertrophy with pressure overload. The mechanism by which the heart adapts to pressure overload, producing either adaptive or maladaptive remodeling is still not completely understood. To study the role of β-ARs in pressure overload hypertrophy, we performed transverse aortic constriction (TAC) in congenic mice with targeted deletions of β1, β2 and both β1 and β2-ARs and in sham controls. After 3 wks, β1−/− mice showed a 21% increase in heart weight to body weight ratio (HW/BW) vs. sham, similar to WT (HW/BW 5.02 ± 0.72 for β1−/− vs. 5.20 ± 0.92 for WT). β2−/− mice showed an exaggerated (49%) hypertrophic response (HW/BW 5.81 ± 0.53, p &lt; 0.001 vs. WT). Only when both β-ARs were ablated was hypertrophy fully attenuated: in β1β2−/− mice HW/BW increased only 8% (HW/BW 4.30 ± 0.31, p &lt; 0.01 vs. WT). Echocardiography showed that peak band gradient was not different between groups (WT 45.3 ± 4.1, β1−/− 47.2 ± 10.2, β2−/− 49.0 ± 9.7, β1β2−/− 53.2 ± 11.3 mmHg) and all groups maintained normal LV function. Morphometric analysis confirmed the absence of hypertrophy in the β1β2−/−: mean cross-sectional area for WT was 254.7 ± 34.9 vs. β1β2−/− 115.8 ± 16.7μm 2 , which was not different from sham. Gene microarray analysis detected a set of genes which were differentially expressed in β1β2−/− vs. WT, β1−/−, or β2−/−: S100 calcium binding protein A9/calgranulin B (S100a9, 4.5-fold up); Cyclin-dependent kinase inhibitor 1A/P21 (Cdkn1a, 3.8-fold up); Metallothioneins Mt1 (3-fold up) and Mt2 (2.7-fold up); FK506 binding protein 5, a glucocorticoid receptor-regulating co-chaperone and calcineurin inhibitor (3.2-fold up). In contrast, TGFβ2 was upregulated in WT, β1−/− and β2−/− but not in β1β2−/−. Differentially regulated genes were validated by SYBR QRT-PCR on the same RNA samples. Thus, β2-AR signaling may serve to limit the hypertrophic response to pressure afterload. However, both β-ARs are required for the development of a normal hypertrophic response. Ablation of both β-AR subtypes alters expression of several genes, some of which may be critical to the hypertrophic program.
Abstract P233: Generalization of Adiposity-Related Common Genetic Variants among U.S. Hispanic Women in WHI-SHARe
Authors: Lindsay Fernández-Rhodes, Mariaelisa Graff, Simin Liu, Christopher Carlson, Sylvia Wassertheil-Smoller, Marian Neuhouser, Alexander Reiner, Charles Kooperberg, Evadnie Rampersaud, JoAnn E Manson, Lewis Kuller, Barbara V Howard, Heather M Ochs-Balcom, Karen C Johnson, Mara Z Vitolins, Lara Sucheston, Keri Monda, Kari E North
Journal: Circulation (2012)

Obesity is a global health concern. Recent studies suggest there may be shared genetic predispositions to obesity phenotypes across diverse racial and ethnic groups, yet the identification of adiposity-related genetic variants among Hispanics, now the largest minority group in the United States (U.S.), remains largely unknown. We interrogated an a priori list of 58 (41 overall body mass and 17 central adiposity) index single nucleotide polymorphisms (SNPs) previously studied in samples of European descent (ED) among 3,587 U.S. Hispanic women in the Women's Health Initiative-SNP Health Association Resource (WHI-SHARe). Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) were measured using standardized protocols. Inverse normal BMI, WC, and WHR models were adjusted for age, smoking status, study center, and genetic ancestry using principal components. Additionally WC and WHR were adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of the previously described SNP, the closest available SNP was selected as a proxy (r2≥0.3 in CEU). No SNPs reached genome-wide significance in this analysis likely due to limited power. Eight BMI/weight loci (TMEM18, ETV5, SLC39A8, NUDT3/HMGA1, FAIM2, FTO, MC4R, KCTD15) and two WC/WHR loci (VEGFA, ITPR2-SSPN) were nominally significant (p&lt;0.05) at the reference SNP in the corresponding BMI and WC and/or WHR adjusted BMI models. To account for distinct linkage disequilibrium (LD) patterns in Hispanics and to more broadly assess generalization of genetic effects at each locus, we assessed the evidence for association at the 58 surrounding loci, for each SNP within 500 kb of the reference SNP. Two additional BMI/weight loci (FANCL, TFAP2B) and six WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86, MSRA, NRXN3) displayed statistically significant associations with BMI and waist measures after Bonferroni correction (p&lt;0.001 and &lt;0.003, respectively), with varying patterns of LD (r2=0.001-0.871) with the index SNP (using HapMap CEU). Sequential conditional analyses will be used to further determine if our top findings from these loci are tagging the index signal or represent novel secondary signals. In summary, we provide evidence for the generalization of ten BMI and eight central adiposity loci in Hispanic American women. This study expands the current knowledge of common adiposity-related genetic predisposition among Hispanic women in the U.S. and suggests a general relevance of ED adiposity loci to Hispanic descent individuals.