tbuckley/cabot-search huggingface dataset:
Differentiation and Carcinogenesis in Liver Cell Cultures
Authors: Carmia. Borek, Gary M. Williams
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Differentiation and Carcinogenesis in Liver Cell Cultures Get access JNCI: Journal of the National Cancer Institute, Volume 62, Issue 6, June 1979, Page 1589, https://doi.org/10.1093/jnci/62.6.1589-a Published: 01 June 1979
Additive Effects of HSV Vectors Expressing Proenkephalin, Interleukin-4, and Tumor Necrosis Factor Alpha Soluble Receptor To Treat Bone Cancer Pain
Authors: James R. Goss, Christine Fetterolf, William Goins, Darren Wolfe, Shaohua Huang, David Krisky, Joseph C. Glorioso, Marina Mata, David J. Fink
Journal: Molecular Therapy (2004)

Top of pageAbstract
Pain associated with cancer in bone is a common clinical problem that is often difficult to treat using conventional therapies. Previously we demonstrated that transduction of dorsal root ganglia (DRG) by subcutaneous inoculation of non-replicating herpes simplex virus (HSV) vectors expressing the inhibitory neurotransmitter proenkephalin (vector SHPE) or the anti-inflammatory peptides interleukin-4 (vector S4IL4) or tumor necrosis factor alpha soluble receptor (vector T0TNFSR) administered separately reduce pain-related behavior in a mouse model of bone cancer. SHPE acts through activation of inhibitory (opioid) receptors at the spinal level. S4IL4 and T0TNFSR act through reduction of the spinal inflammatory response characteristic of chronic pain. Since these vectors act through separate mechanisms we tested the hypothesis that combined therapy would be more effective than any single vector alone. Male C3H/HeJ mice were injected with 105 NTCT 2472 osteolytic sarcoma cells into the medullary space of the right femur. One week later the ipsilateral lumbar DRG were transduced by subcutaneous inoculation into the plantar surface of the foot with 20 ul containing SHPE and S4IL4 (5 × 106 pfu each) or 20 ul containing SHPE, S4IL4, and T0TNFSR (3.3 × 106 pfu each). Pain behavior was assessed 1 and 2 weeks after vector inoculation using a 4-point spontaneous ambulatory pain score (SAPS) and mechanical allodynia (MA). These results were compared to similarly treated mice that received 10 ul containing 1 × 107 pfu of each vector separately and to mice that received 1 × 107 pfu of the control vector QOZHG. Tumor-bearing mice inoculated with all three vectors together demonstrated reduced SAPS and MA compared to single vector inoculated mice. These results suggest that therapies designed to affect different physiological pathways associated with bone cancer pain may be more efficacious than single agents and demonstrate the feasibility of using HSV based gene therapy in the treatment of chronic pain.
Abstract 11889: Phase Ib Study of Icosabutate, a Novel Structurally Enhanced Fatty Acid, in Subjects With Hypercholesterolemia
Authors: Yan Qin, Jonas Hallén, Tore Skjæret, Erling Odden, David Fraser, Hilde Nyheim, Karen Cornelissen, Joseph Chiesa, Svein Olaf Hustvedt
Journal: Circulation (2014)

Introduction: Icosabutate, an orally active structurally enhanced fatty acid (SEFA), has demonstrated reductions in triglycerides (TG) and cholesterol in several rodent models of dyslipidemia and diabetes. In clinical single and multiple ascending dose studies, icosabutate was well tolerated and significantly lowered LDL-C, non-HDL-C, and TG in subjects with mixed dyslipidemia. This phase 1b study explored the lipid-lowering effects of icosabutate in subjects with hypercholesterolemia. Methods: This was a randomized, double-blind, placebo-controlled study. Subjects with hypercholesterolemia treated with a statin for at least 3 months were screened. Statins were temporarily discontinued for at least 28 days prior to dosing and for the duration of the study. To qualify for the study, subjects were required to have an LDL-C ≥ 2.5 mmol/L (97 mg/dL) at the secondary screening visit and an increase in LDL-C of at least 20 % between the primary and secondary screening. Twenty four subjects were randomized to icosabutate 600 mg once daily or matching placebo in a 3:1 fashion and treated for 28 days. Safety and pharmacodynamics were evaluated. Results are reported as placebo-adjusted median percentage change from baseline (average of visit 2-4) to 24 hours after last dose (day 29). Results: Six subjects received placebo and 18 subjects received icosabutate. Median baseline lipid values (mg/dL) placebo/ icosabutate: TC: 270 and 240; LDL-C: 174 and 166; and TG: 204 and 168. Compared to placebo, icosabutate reduced total cholesterol (17.4 %, p &lt; 0.05), LDL-C (29.3 %, p&lt;0.05), non-HDL-C (25.4 %, p&lt;0.05), and apo B (22.8 %, p&lt; 0.05). There was a non-significant increase in HDL-C. TG reductions were not statistically significant (12.6 %, ns), but both placebo and icosabutate subjects experienced large reductions from baseline (29 % versus 42 %). Conclusions: In this randomized, double-blind, placebo-controlled phase Ib study in subjects with hypercholesterolemia, icosabutate demonstrated placebo-adjusted reductions in total cholesterol, LDL-C, non-HDL-C, and apo B. TG levels were also substantially reduced, but not statistically significant in placebo-adjusted analyses.
Abstract 4390: Non-coding RNAs in EGFR therapy resistance in breast cancer
Authors: Luis D. Borrero-García, Linette Castillo-Pichardo, Roxana S. Redis, George A. Calin, Suranganie Dharmawardhane
Journal: Cancer Research (2014)

Abstract The purpose of this study is to identify novel mechanisms of resistance to epidermal growth factor receptor (EGFR) targeted therapies. The initial success of EGFR targeted therapies such as gefitinib and lapatinib has been confounded by intrinsic or acquired therapy resistance. Emerging data, including our studies, show drug-induced dysregulation of non-coding RNAs (ncRNAs) that may downregulate multiple effectors of chemoresistance by transcriptional or post-transcriptional regulation. To investigate the role of ncRNAs in regulation of EGFR therapy resistance, we created syngeneic therapy sensitive and resistant breast cancer (BC) cell lines by exposing therapy sensitive SKBR3 and BT-474 cells to different concentrations of gefitinib or lapatinib. Differentially expressed ncRNAs in resistant and sensitive cells were identified from quantitative RT-PCR analysis and their targets detected by Western blot. A long ncRNA (lncRNA) that we have named Colon Cancer Associated Transcript 2 (CCAT2) (Ling et al., Genome Res. 2013, 23:1446-61) was downregulated in EGFR/HER2 therapy resistant BC cells. The microRNA miR -221/222 was upregulated in parallel with decreased CCAT2. Increased miR-221/222 and decreased miR-200 family have been associated with cancer malignancy and epithelial to mesenchymal transition (EMT), a hallmark of therapy resistance. Accordingly, miR-200a was downregulated in EGFR therapy resistant BC cells. miR-200 family plays an important role in suppression of EMT by downregulation of zinc finger E-box binding homeobox (Zeb)1/2 and β-catenin. Zeb 1/2 are negative regulators of E-cadherin, and β-catenin is a potent pro-cancer transcriptional activator in the absence of an E-cadherin axis. Results show upregulation of Zeb1, β-catenin and its transcriptional effector c-Myc, and stem cell-like marker CD44, while E-cadherin was downregulated in the E-cadherin positive BT-474 cells. We also found downregulation of miR-221/222 targets, PTEN and APAF1, in the SKBR3 resistant variants, which is consistent with the upregulation of miR-221/222 expression. In conclusion, this data suggest that downregulation of CCAT2 and miR-200 family, and upregulation of miR-221/222 contributes to EGFR targeted therapy resistance. Therefore, targeting these ncRNAs maybe a viable alternative to overcoming therapy resistance in BC. Citation Format: Luis D. Borrero-García, Linette Castillo-Pichardo, Roxana S. Redis, George A. Calin, Suranganie Dharmawardhane. Non-coding RNAs in EGFR therapy resistance in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4390. doi:10.1158/1538-7445.AM2014-4390
Abstract 18892: Clinical and Hemodynamic Factors Influence the Risk of Pulmonary Hypertension in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights from the PARTNER I Trial and Registry
Authors: Brian R Lindman, Alan Zajarias, Hersh Maniar, Rakesh M Suri, D. Craig Miller, John Webb, Lars G Svensson, Ke Xu, Fay Lin, Shing-Chiu Wong, Vasilis Babaliaros, Vinod H Thourani, Pamela S Douglas, Scott Lim, Martin B Leon, Michael J Mack
Journal: Circulation (2014)

Introduction: Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS). Hypothesis: We hypothesized that clinical or hemodynamic factors might influence the relationship between significant PH and increased mortality. Methods: Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the PARTNER I randomized trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included. PH was defined as: none (mPAP&lt;25 mmHg), mild (25 to &lt;35), and mod/sev (≥35). Results: One year all-cause mortality was worse with increasing severity of PH: none (n=785, 18.6%), mild (n=838, 22.7%), and mod/sev (n=557, 25.0%) (p=0.01). The association between mod/sev PH (vs. no PH) and 1y mortality varied by sex and renal function (interaction p=0.03 and p=0.06, respectively). In females, mod/sev PH was associated with increased mortality (24.6% vs. 14.1%, HR 1.89, 95% CI 1.32-2.73); in males it was not (24.9% vs. 22.2%, HR 1.12, 95% CI 0.82-1.52). Additionally, mod/sev PH was associated with mortality in those with glomerular filtration rate (GFR) &lt;40 (HR 1.76, 95% CI 1.28-2.42), but not in those with GFR ≥40. In a multivariable Cox PH model of patients with mod/sev PH, oxygen dependent lung disease, cerebrovascular disease, lower GFR, and lower baseline transvalvular mean gradient were each independently associated with increased 1y mortality (p&lt;0.05 for all), whereas pulmonary artery compliance was the only hemodynamic variable associated with mortality (p=0.043) (Table). Conclusions: The relationship between mod/sev PH and increased mortality after TAVR is altered by sex and renal function. While lower pulmonary artery compliance is associated with increased mortality in patients with significant PH, clinical factors appear to be more influential in stratifying risk than hemodynamic indices.
Abstract 2295: Current Outcomes of Simultaneous Carotid Endarterectomy and Coronary Artery Bypass in North America
Authors: Sunil M Prasad, Shuang Li, Sean M O’Brien, J. S Rankin, James S Gammie, John D Puskas, David M Shahian, Edgar G Chedrawy, Malek G Massad
Journal: Circulation (2008)

OBJECTIVE: Management of patients with concomitant carotid and coronary artery disease has been controversial. Divergent strategies have been employed, including simultaneous carotid endarterectomy and coronary bypass (SCC) versus various staged procedures. While no strict comparison group is available, this study defines current outcomes of SCC, as compared qualitatively to two reference categories. METHODS: Utilizing the STS database from 2003 to 2007, patients having SCC were compared to cerebrovascular disease patients undergoing coronary bypass with prior carotid endarterectomy (Ref Gp I), and those with carotid Doppler stenosis &gt;75% and no carotid intervention (Ref Gp II). Logistic regression analysis adjusted for differences in baseline characteristics, and operative mortality (OM) and a composite of neurological complications (NC) were assessed. RESULTS: Of 747,932 patients undergoing isolated CABG with/without CEA, 108,271 (14.4 %) had cerebrovascular disease. In this group, 5,732 (5.3%) underwent SCC. The SCC group had more males and less severe coronary disease (both p&lt;0.001). After statistical adjustment for all baseline differences, SCC had clinically and statistically higher OM and NC as compared to any of the reference groups (TABLE ). CONCLUSION: Although no proper control group exists for comparison, SCC as recently performed in North America carries a high risk, as compared to any of the reference groups. Suboptimal results associated with the SCC strategy suggest a need for quality improvement and research on the optimal management of patients with simultaneous carotid and coronary disease.
Political Activity of US Physicians
Authors: Craig A Umscheid
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Observing patients: The chair sign
Authors: F. Mackay
Journal: BMJ (1998)

A 46-year-old previously healthy man presented with 1 week of headache, nausea, vomiting and dizziness. He was found to have cranial nerve deficits, his cerebrospinal fluid (CSF) demonstrated a lymphocytic pleocytosis and brain MRI suggested rhombencephalitis. Although Gram stains and cultures of his CSF did not identify a pathogen, <i>Listeria monocytogenes</i> DNA was detected by the FilmArray Meningitis/Encephalitis panel within 2 hours of performing a lumbar puncture. He was treated with ampicillin and gentamicin and had a near-complete recovery. This case highlights the importance of recognising <i>L. monocytogenes</i> infection as a cause of acute cranial nerve impairment with MRI findings suggestive of brainstem encephalitis. It also highlights the frequently atypical CSF profile and low yield of culture in <i>L. monocytogenes</i> rhombencephalitis and the value of multiplex PCR testing of CSF to rapidly identify this pathogen and permit targeted therapy.
How many pills does it take
Authors: Renate G Justin
Journal: BMJ (2003)

From BMJ USA 2002;August:462 

My guess was that this white haired, friendly lady was about 65. I did not have a chance to ask her age because as soon as I sat down opposite her she handed me a list of about 25 problems, each one neatly written out, and next to the complaint the name of the medication she was taking to cure that particular difficulty. For instance, next to sour stomach …
Abstract 3493: An <i>in-situ</i> proximity assay using biotin ligase
Authors: Zeyu (David) Jiang, Rui Hong, Mike Farrell
Journal: Cancer Research (2014)

Abstract Protein-protein interactions (PPIs) are fundamental to biological processes, from signaling pathways that modulate gene expression, cell proliferation, tumor invasion to cytoskeleton networks that maintain morphological integrity of cells and tissues. Activation of oncogenes and inactivation of tumor suppressor genes in the cell that lead to carcinogenesis are inevitably accompanied by disruption of normal or activation of aberrant PPIs, thus detection and understanding of PPIs may advance the diagnosis and treatment of cancer. Although many methods have been developed to discover and detect PPIs in vivo and ex vivo, few are applicable to in situ detection of PPIs, particularly in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Here we report a sensitive in situ PPI detection method for FFPE tissues that utilizes biotin ligase (BirA), an enzyme that covalently labels its specific peptide target substrate (BTS) with biotin. We developed BirA and BTS conjugated antibodies, each of which binds specifically to one of the interacting protein pair and whose close proximity permits BirA to biotinylate the BTS for subsequent visualization. Using both artificial system such as hapten-labeled proteins and known biological PPI models such as E-cadherin and beta-catenin and HER2/HER3 dimers in the context of FFPE tissues, we have demonstrated that the assay is both sensitive and robust. Moreover, the assay has been fully automated and is easily adaptable for detecting protein dimers, fusion proteins, or other novel binary interactions in tissue specimens. As understanding details of signaling pathways becomes increasingly important in cancer biology, in situ proximity assay may offer novel mechanistic and therapeutic insights and provide a powerful tool for cancer diagnostics. Citation Format: Zeyu (David) Jiang, Rui Hong, Mike Farrell. An in-situ proximity assay using biotin ligase. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3493. doi:10.1158/1538-7445.AM2014-3493
Description of measles D4-Hamburg outbreak in Hamburg, Germany, December 2008 to June 2009, which disproportionally affected a local Roma community
Authors: G Hegasy, K Kätzner, M Helle, A Mankertz, S Baumgarte, A Wille, G Fell
Journal: Eurosurveillance (2012)

From December 2008 to June 2009 a measles outbreak occurred in the Federal State of Hamburg, Germany. The outbreak affected 216 persons and was caused by a new measles strain termed D4-Hamburg which led to consecutive outbreaks between 2009 and 2011 in at least 12 European countries. Here, we describe epidemiological characteristics of the outbreak and evaluate the control measures taken in Hamburg. In one of the seven boroughs of Hamburg a local Roma community comprised more than 50% of the notified cases.We compared in a stratified analysis the age distribution of these cases with cases of fellow citizens who did not belong to the Roma community. The age group of infants (0-11 months) comprised 33% among the non-Roma measles cases, while in the Roma community only 4% belonged to this stratum. In the stratum of 5-17 year-olds only 8% were affected among the non-Roma cases, whereas in the Roma community 50% belonged to this age group. We discuss the influencing factors that might have led to this difference in age distribution between the two groups.
Handbook for Prescribing Medications During Pregnancy.
Authors: Richard L. Berkowitz
Journal: Annals of Internal Medicine (1981)

Now in an up-to-date Third Edition, this pocket-sized reference provides instant access to the information physicians need when prescribing drugs for obstetric patients. It catalogues over 250 drugs by generic and trade names, summarizes essential clinical facts about each drug, and gives advice regarding whether and when each drug can safely be prescribed for pregnant or lactating women. The drug profiles include indications and recommendations; special considerations in pregnancy; dosage; adverse effects; mechanism of action; and absorption and biotransformation.The authors clearly state when a drug is safe for obstetric patients, whether specific conditions affect its use, how it affects pregnant women, fetuses, and breastfeeding infants, and whether the agent is the subject of ongoing controversy. Appendices cover special substances such as vitamins and minerals, antineoplastic drugs, vaccines, and environmental agents. To help physicians locate information quickly, two indexes list drugs by trade and generic name and by drug classification.
Hypersensitivity investigation into a folate-hapten targeted cancer immunotherapy in animal models
Authors: Yingjuan Lu, Patrick Klein, Elaine Westrick, Le-Cun Xu, Hari Krishna Santhapuram, Jeffrey Nicoson, Alicia Bloomfield, Stephen Howard, Iontcho Vlahov, P. Ellis, Philip Low, Christopher Leamon
Journal: Cancer Research (2008)

2854   Cancer vaccine and immunotherapy rarely involve systemic administration of an immunogenic compound in an actively immunized host. We have developed an active immunotherapy strategy that utilizes folic acid to deliver antigenic haptens (e.g. fluorescein, dinitrophenyl) to folate receptor-positive tumors in a host pre-vaccinated against the hapten. Such folate-targeted “haptenization” of tumor cell surfaces promotes their opsonization by endogenous anti-hapten antibodies, recruitment of immune effector cells, and subsequent removal of the tumor by the immune system. Although no allergic reactions to any folate-hapten conjugates had been observed in our preclinical studies, hapten-immunized mice were observed to produce a small amount of anti-hapten IgE antibody (an allergic Th2-type response); further, the systemic administration of folate-hapten formulations containing small amounts of multi-haptenated species was found to cause hypersensitivity responses in animal models of allergy, namely active systemic anaphylaxis and passive cutaneous anaphylaxis. Using fluorescein (FITC) as the model hapten, we investigated the extent of folate-FITC allergy in multiple animal species and devised strategies to circumvent the observed allergic response. The current findings suggest that allergic reactions to folate-FITC (or a bisFITC-eda contaminated folate-FITC formulation) may be independently prevented by two distinct manipulations: (i) increasing the immunogen (e.g. KLH-FITC) dose during the immunization phase, and (ii) dosing immunized animals early (i.e. 1 week after the initial vaccine injection) with the same folate-FITC preparation. Our data demonstrate that folate-hapten can be administered without allergic reactions in a hapten-immunized host and that the manipulations described above do not alter the effectiveness of immunotherapy against folate receptor-positive cancers.
Three-year follow-up of patients with right bundle branch block and ST segment elevation in the right precordial leads
Authors: Hirotsugu Atarashi, Satoshi Ogawa, Kenichi Harumi, Tsuneaki Sugimoto, Hiroshi Inoue, Masahiro Murayama, Junji Toyama, Hirokazu Hayakawa
Journal: Journal of the American College of Cardiology (2001)
Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2
Authors: Sarah C. Coste, Robert A. Kesterson, Kurt A. Heldwein, Susan L. Stevens, Amanda D. Heard, Jacob H. Hollis, Susan E. Murray, Jennifer K. Hill, George A. Pantely, Alan R. Hohimer, Daniel C. Hatton, Tamara J. Phillips, Deborah A. Finn, Malcolm J. Low, Marvin B. Rittenberg, Peter Stenzel, Mary P. Stenzel-Poore
Journal: Nature Genetics (2000)