tbuckley/cabot-search huggingface dataset:
Abstract 2516: SL01, an oral gemcitabine prodrug as a potent anticancer drug
Authors: Wenbao Li, Hua Yuan, Xianjun Qu
Journal: Cancer Research (2014)

Abstract SL01,dodecyl-3-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)pyrazine-2-carboxylate, is a gemcitabine prodrug synthesized by introducing the moiety of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine ring of gemcitabine. Our goal is to investigate the efficacy and the safety of this oral prodrug as a potent oral anticancer agent, which may supplant the use of gemcitabine in clinic. The evaluation was accomplished by determining its inhibition of the growth of several tumors with gemcitabine administrated by injection as a control, and also by exploring its pharmacokinetics and its safety. In vivo, SL01 could effectively inhibit the growth of NCI-H460 human non-small cell lung cancer, MCF-7 human breast cancer, BxPC-3 human pancreatic cancer, ES-2 human bladder cancer, HepG2 human hepatocellular carcinoma cells and HCT-116 human colon adenocarcinoma cells in xenografts nude mice without loss their body weight significantly. After three weeks oral administration at the dosage of 30 umol/kg, the inhibition rates were 58.0%, 66.5%, 41.5%, 77.1%, 41.5% and 63.1%, respectively. Molecular analysis indicated that the high efficacy of SL01 was associated with its ability in inducing apoptosis, as evidenced by increase of TUNEL staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase in tumor tissues. Pharmacokinetics studies indicated that SL01 exhibited a longer mean retention time and half-life than that of gemcitabine after oral administration in rat, further analysis showed that the bioavailability of SL01 was 22.1%, which indicating that the introduction of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl moiety to gemcitabine could improve its bioavailability and reduce its first-pass metabolism. The metabolism analysis suggested that SL01 could transform into gemcitabine by hydrolyzing and then releasing into blood to keep the relatively long steady-state concentrations. Toxicity studies indicated that the LD50 was &amp;gt;1.4 g/kg for its acute toxicity, and the tolerated dosage was 45 mg/kg for 4 weeks evaluation in rat. Based on these results, SL01 is proposed as a potent oral anticancer agent, which may supplant the use of gemcitabine in clinic. Acknowledgment: This project was supported by the Ministry of Science and Technology of China (2010ZX09401-302-2-07and 2011ZX09102-001-03). Citation Format: Wenbao Li, Hua Yuan, Xianjun Qu. SL01, an oral gemcitabine prodrug as a potent anticancer drug. [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 2516. doi:10.1158/1538-7445.AM2014-2516
Abstract 18787: Hypertension Treatment and Control Rates in United States Adults by Risk Group
Authors: Kunal N Karmali, Hongyan Ning, Donald M Lloyd-Jones
Journal: Circulation (2014)

Introduction: Ten-year cardiovascular disease (CVD) risk and absolute benefit from antihypertensive therapy vary at any given BP based on associated risk factor levels. Thus, implications of treatment and control rates at a particular BP vary substantially in different risk groups. Objectives: We examined the prevalence, treatment, and control of hypertension (HTN) by risk group in US adults without prevalent CVD. Methods: We used data from the National Health and Nutrition Examination Survey 2005 to 2010 for adults age 40-79 years without prevalent CVD (n=4,066). We estimated 10-year risk for an atherosclerotic CVD (ASCVD) event using the ACC/AHA 2013 Pooled Cohort risk equations. We examined HTN treatment and control rates according to current guidelines in middle-aged (40-59 years) and older (60-79 years) adults with: 10-year ASCVD risk &lt;7.5% (no diabetes/kidney disease); 10-year ASCVD risk ≥7.5% (no diabetes/kidney disease); and either diabetes or kidney disease. Results: The proportion of adults with treatment-eligible HTN was 39.3% for those with 10-year ASCVD risk &lt;7.5%, 32.2% for those with 10-year ASCVD risk ≥7.5%, and 28.4% for those with either diabetes or kidney disease (see Table 1). Treatment rates across the risk groups varied from 51.5% to 79.0% for middle-aged adults and 81.8% to 90.2% for older adults. HTN control rates were highest (87.7%) in older adults with 10-year ASCVD risk &lt;7.5% but were lowest (29.3%) in middle-aged individuals with 10-year ASCVD risk ≥7.5%. Conclusions: US HTN guidelines, based solely on BP thresholds, identify a higher proportion of low-risk adults and a lower proportion of high-risk adults as being eligible for treatment. Control rates remain suboptimal in high-risk individuals, particularly middle-aged adults. Future guidelines should consider pre-treatment risk stratification to identify those at increased pretreatment ASCVD risk who would benefit most from more intensive therapy.
Abstract P233: Plasma essential fatty acids and type 2 diabetes risk: the Hoorn Study
Authors: Marjan Alssema, Mieke Cabout, Giel Nijpels, Coen D Stehouwer, Peter L Zock, Ingeborg A Brouwer, Amany K Elshorbagy, Helga Refsum, Jacqueline M Dekker
Journal: Circulation (2014)

Background: A high consumption of the polyunsaturated fatty acids linoleic acid (LA) and alpha-linolenic acid (ALA) instead of saturated fatty acids is known to reduce CHD risk, but data on the relation between LA and ALA intake and Type 2 Diabetes Mellitus (T2DM) risk are limited and inconsistent. Plasma levels of LA and ALA provide a relatively accurate reflection of the intake over several weeks or months, because of the essential nature of these fatty acids. Objective: To investigate the association of the percentage of LA and ALA in plasma lipids with fasting plasma glucose (FPG), post-load glucose (PLG) and glycated hemoglobin (HbA1c) as markers of T2DM risk. Methods: The study population included 667 Dutch men and women, aged 50-75 years from the population-based Hoorn Study. Baseline data for the current study were collected between 2000 and 2001, with follow-up in 2008. Linear regression models were used in cross-sectional and prospective analyses. Results: In cross-sectional analyses, plasma LA (per %) was significantly and inversely associated with FPG ( B = -0.022 [-0.044, 0.000]) and PLG ( B = -0.096 [-0.155, -0.036]), but not with HbA1c ( B = 0.000 [-0.014, 0.014]), after adjustment for age, gender, total energy intake, BMI, waist-to-hip ratio, physical activity, fiber, dietary saturated fat intake, alcohol intake and education level. In prospective analyses, plasma LA was not significantly associated with FPG, PLG or HbA1c after adjustments for baseline glucose. In addition, no significant associations were found between plasma ALA and markers of T2DM risk in cross-sectional or prospective analyses. Conclusion: Plasma LA, but not ALA, was inversely associated with fasting and post-load glucose levels in cross-sectional, but not in prospective analyses. Further studies are needed to elucidate the exact role of plasma LA and ALA levels and dietary polyunsaturated fatty acids in glucose metabolism.
The Biology and Clinical Management of Bladder Cancer.
Authors: Edward Holmes Cooper, Robert Edward Duncan Williams
Journal: Annals of Internal Medicine (1976)

This comprehensive monograph owes its inception to an academic study of cell populations in carcinoma of the bladder begun by the editors several yea-rs ago.The subject matter has since been greatly ex- panded, largely as the result of an international meeting on bladder cancer held in Leeds in 1971.With the assistance of several well-known contributors firom Europe and *the U.S.A. the book covers a wide range of
Doctor testifies to China s reuse of prisoners organs
Authors: R. Dobson
Journal: BMJ (2001)

A Chinese doctor described to a US government subcommittee last month how, when he had lived in the People's Republic of China, he had removed body parts from executed prisoners to provide material for transplantation to wealthy patients.

Dr Wang Guoqi, a 38 year old doctor with advanced degrees in surgery and human tissue studies, was a former specialist in the burns victims unit at the Paramilitary Police Tianjin General Brigade Hospital in Tianjin. He testified to the US subcommittee on International Relations and Human Rights at a hearing last month.

The committee's chairman, Republican representative Ileana Ros-Lehtinen of Miami, said that Dr Guoqi's testimony showed that China had “found a lucrative industry in the field of organ transplantation, which not only yields great financial rewards, but provides the regime with a powerful tool to coerce and intimidate the population into submission.”

Dr Guoqi told the committee: “My …
Heterogeneity of clinical response during placebo treatment
Authors: F M Quitkin, J G Rabkin, J W Stewart, P J McGrath, W Harrison, D C Ross, E Tricamo, J Fleiss, J Markowitz, D F Klein
Journal: American Journal of Psychiatry (1991)

The authors attempted to identify different patterns of improvement among patients receiving placebo during clinical trials. It was hypothesized that patients who improved abruptly would differ from patients whose improvement was gradual in that they would tend to improve earlier and would tend to have less persistent improvement.The subjects were 144 patients who met the DSM-III criteria for depressive illness and were randomly assigned to placebo medication in four double-blind antidepressant drug trials. All studies lasted 6 weeks. Mood change was rated each week on a 7-point scale; a rating of 1 or 2 was considered an indication of improvement. Improvement was judged to be abrupt if the first score of 1 or 2 was immediately preceded by a score of 4 or worse, and it was classified as gradual if the first score of 1 or 2 was preceded by a score of 3 in at least 1 week. Improvement was considered persistent if a score of 1 or 2 was not followed by a score of 3 or worse in any subsequent week.Of the 144 patients, 72 showed clinical improvement during at least one weekly visit; 33 improved abruptly and 39 improved gradually. The abrupt improvements occurred significantly earlier in the trial and were less likely to persist than the gradual improvements regardless of when they occurred.These data suggest that among patients receiving placebo abrupt improvements are a form of placebo response and gradual responses may be the result of spontaneous remission. These preliminary observations require validation.
Pitfalls of patch testing with dental materials
Authors: C. Schuster, R. Mofarrah, W. Aberer, B. Kränke
Journal: British Journal of Dermatology (2011)

Funding sources: none. Conflicts of interest: W.A. and B.K. have been invited speakers for Almirall Hermal (Reinbek, Germany). Madam, Diagnosis of intraoral contact allergy is a diagnostic challenge. Clinical manifestations include subjective burning or pain of the oral mucosa, as well as objective conditions such as lichenoid reactions and stomatitis.1 Burning or painful sensations of the oral cavity in the absence of mucosal lesions define the burning mouth syndrome (BMS).2 The role of contact allergy to oral allergens is controversial. Some studies have suggested that allergic factors are involved in patients with BMS, while others seem to contradict these results.3–5 We report a potential diagnostic pitfall in evaluation of intraoral contact allergy by patch testing. A 74‐year‐old nonatopic woman reported a 2‐year history of intermittent burning pain of her mouth and tongue. Intraoral symptoms had started after 5 years of wearing a removable complete denture. Clinical investigation of her oral mucosa showed no visible lesions. Physical and laboratory investigations by her general practitioner had not shown any pathological results. The only dental care product she was using was the one kind of toothpaste that she had used for several years.
Drug-Eluting Stents and In-Stent Restenosis—Reply
Authors: Adnan Kastrati, Albert Schömig
Journal: JAMA (2005)

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
Abstract P238: Evaluation of Low-Density Lipoprotein Cholesterol as a Confounder for Adverse Events
Authors: Shia T Kent, Emily B Levitan, Hong Zhao, Angelika Manthripragada, Monika M Safford, Jeffrey R Curtis, Paul Muntner
Journal: Circulation (2015)

Several new lipid-lowering drugs may soon be available for secondary prevention of coronary heart disease (CHD). Claims data will likely be used for pharmacovigilance of these drugs. However, claims data frequently do not have laboratory results, such as low-density lipoprotein cholesterol (LDL-C). In order to determine whether LDL-C is an uncontrolled confounder in claims-based pharmacovigilance studies, we examined associations between LDL-C and incident cancer, serious hospitalized infection, dementia, and diabetes. These outcomes were chosen due to their possible associations with statin use and low LDL-C. LDL-C was measured at baseline (2003-2007) among participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Analyses were restricted to 3,043 participants ≥ 65 years of age with a history of CHD or risk equivalents (stroke/carotid disease, peripheral artery disease, abdominal aortic aneurysm and diabetes) and Medicare fee-for-service coverage. Sensitivity analyses were performed (1) with LDL-C as a continuous variable, (2) among participants with a history of CHD or (3) among participants with a history of CHD or risk equivalents taking statins. Outcomes were identified through 2011 using validated claims-based algorithms. Multivariable models indicated LDL-C did not have any significant associations with any of the outcomes under study (Table). However, some hazard ratios indicated non-significant differences in the incidence of safety outcomes by LDL-C level. For example, compared to participants with LDL-C < 70 mg/dL, the hazard ratio (95% CI) for incident dementia during follow-up was 1.30 (0.85, 1.98), 1.41 (0.92, 2.18), and 1.29 (0.79, 2.10) for participants with LDL-C of 100 - 129, 130 - 159, and ≥ 160 mg/dL, respectively. Sensitivity analyses had similar results. This study suggests that LDL-C is not likely to be a major confounder in pharmacovigilance studies of lipid-lowering drugs with outcomes of cancer, serious hospitalized infection, dementia, or diabetes.

   ![][1]  [1]: /embed/graphic-1.gif
Abstract 2640: RN927C, a potent site-specific Trop-2 antibody-drug-conjugate (ADC) for treatment of solid tumors
Authors: Shu-Hui Liu, Pavel Strop, Thomas-Toan Tran, Magdalena Dorywalska, Katherine Delaria, Wei-Hsien Ho, Russell Dushin, Jaume Pons, Arvind Rajpal, Dave Shelton
Journal: Cancer Research (2014)

Abstract Human trophoblast cell surface antigen-2 (Trop-2), also known as TACSTD2, EGP-1, GA733-1 and MS1, is expressed on a variety of human carcinomas and its expression is often associated with poor prognosis of the diseases. Trop-2 is frequently detected in many tumor types at high levels, however, it is also present on the epithelium of a number of normal tissues. A comprehensively designed Trop-2-targeting ADC, balancing both efficacy and toxicity, is necessary to achieve clinical utility. We developed a site-specific cleavable Trop-2-ADC (RN927C) using a novel transglutaminase-mediated enzymatic conjugation method and a proprietary MTI (microtubule inhibitor) linker-payload. Our site-specific conjugation technology enables a precise drug-loading ratio of two and thus a better control of desired potency. Robust in vitro cytotoxicity of RN927C was observed selectively on multiple Trop-2 expressing tumor cell lines, with IC50 generally in the sub-nM range. Upon binding to surface Trop-2, RN927C internalized quickly and trafficked to the lysosomal compartment, as visualized by the co-localization of RN927C with lysosomal marker LAMP-2. As expected for a MTI-containing ADC, RN927C readily induced mitotic arrest of treated cells in vitro and in vivo, followed by subsequent cell death. The in vivo efficacy of RN927C was tested in multiple tumor models including pancreatic, NSCLC, and ovarian cell line and patient-derived xenograft models. Single dose administration of RN927C at 1.5 mg/kg was generally sufficient to induce sustained regression of Trop-2 expressing tumors and showed superior efficacy over standard treatment with paclitaxol or Gemcitabine. Furthermore, addition of RN927C to Gemcitiabine greatly enhanced its in vivo efficacy. RN927C was well-tolerated in non-human primates upon repeat dosing at 6mg/kg q2w, with non-severe toxicity observed primarily in skin and oral mucosa, consistent with Trop-2 expression in these epithelial tissues. Importantly, only minimal off-target hematological toxicity was observed in monkeys. Based on the combined efficacy and safety results, RN927C is expected to have a favorable therapeutic index and clinical development is currently underway. Citation Format: Shu-Hui Liu, Pavel Strop, Thomas-Toan Tran, Magdalena Dorywalska, Katherine Delaria, Wei-Hsien Ho, Russell Dushin, Jaume Pons, Arvind Rajpal, Dave Shelton. RN927C, a potent site-specific Trop-2 antibody-drug-conjugate (ADC) for treatment of solid tumors. [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 2640. doi:10.1158/1538-7445.AM2014-2640
Plasma antitrypsin levels during growth of a rat fibrosarcoma.
Authors: M. J. Waldvogel, L. H. Schmitt
Journal: Cancer Research (1950)

Summary  1.Antitrypsin levels and white blood counts at various stages in the growth of a rat fibrosarcoma are reported. There is an elevation of both during the period of most rapid growth.  2.Upon regression and after surgical removal of the tumor, the antitrypsin and white blood count decrease.  3.Control animals and those in which the implant does not take give essentially the same results, with no significant increase in either antitrypsin or white blood count.  4.Serosanguinous fluid accumulating in cysts in regressing tumors contains some antitrypsin but no white cells.
The pharmacology of nitroxyl (HNO) and its therapeutic potential: Not just the janus face of NO11This review is dedicated to the career of Prof. Herbert T. Nagasawa, a pioneer in the field of HNO chemistry, biochemistry and pharmacology.
Authors: Nazareno Paolocci, Matthew I. Jackson, Brenda E. Lopez, Katrina Miranda, Carlo G. Tocchetti, David A. Wink, Adrian J. Hobbs, Jon M. Fukuto
Journal: Pharmacology & Therapeutics (2006)
Abstract 2775: The effect of Plasma C-Reactive Protein on Neointimal Plaque Volume at 9 Month Follow-Up After Implantation of Sirolimus Eluting Stent (SES) and Paclitaxel-Eluting Stent (PES). Intravascular Ultrasound Study
Authors: Jung-Sun Kim, Byung Ho Lee, Jae-Deok Kim, Hyun-Soo Kim, Sungha Park, Sang-Hak Lee, Young-Guk Ko, Donghoon Choi, Yangsoo Jang, Namsik Chung
Journal: Circulation (2007)

Background : The aim of this study is to identify the association of hsCRP with neointimal plaque volume at 9 month follow-up IVUS after implantation of Sirolimus eluting stent (SES) and Paclitaxel-eluting stent (PES). Methods: A total of 127 patients (M:F = 78:49, age 62 ± 8 years), who underwent the elective coronary stenting for a de-novo lesion were prospectively enrolled and randomized according to type of stents (64 SES, 63PES). Infarct-related lesions within 7 days were excluded. Among them, hsCRP was serially measured in 104 patients (50 SES and 54 PES) at baseline, 48 hr after and 9 month follow-up after coronary stenting. IVUS was simultaneously performed at initial, after coronary stenting and 9 month follow-up. Neointimal volume index (neotintimal volume/stent length) at 9 month follow-up was obtained using INDEC system. Result : Baseline clinical, angiographic and IVUS parameters after stenting of both groups showed no significant differences. hsCRP was significantly increased at 48 hrs after coronary stenting but there was no significant difference between two groups (baseline: 2.9 ± 8.7 vs. 3.6 ± 7.6 mg/L, 48 hr: 10.7 ± 21.3 vs. 13.0 ± 15.3 mg/L, 9 month: 1.0 ± 1.6 vs. 1.2 ± 1.8 mg/L). At 9 month follow-up, SES showed a significantly lower neointimal volume index (0.22 ± 0.41 vs. 1.0 ± 0.9 mm 2 , p &lt; 0.001) and lower tendency of in-stent restenosis [1 (2.2 %) vs. 6 (12.5 %), p = 0.111] than PES. Neointimal plaque volume at 9 month was significantly correlated with hsCRP at 48 hr (r= 0.426, p = 0.004) and increase of hsCRP between baseline and 48 hr (r = 0.512, p &lt; 0.001). Also, higher increase of hsCRP between baseline and 48 hr (β = 0.469, p = 0.006) and PES (β = - 0.345, p = 0.024) were independently associated with increased neointimal volume index at 9 month follow-up after adjusting the clinical and angiographic parameters. Conclcusion: Increase of hsCRP at 48 hr after coronary stenting was significantly associated with neointimal volume in drug eluting stent (DES) era. Thus, control of acute inflammation after implantation of DES, especially PES might be beneficial for reducing neointimal plaque volume.
879. Morphologic and Immunohistochemical Evaluation of Dopaminergic Regions of Pahenu2 Mouse Brains Following Adminstration of rAAV-mPAH-WPRE Vector
Authors: Jennifer E. Embury, Catherine E. Charron, Philip J. Laipis
Journal: Molecular Therapy (2004)

Phenylketonuria (PKU) is one of the most common single gene disorders in man. The metabolic defect arises from a deficiency of phenylalanine hydroxylase (PAH). There is a resultant hyperphenylalanemia with subsequent impairment in cognitive abilities, executive functions and motor coordination; these functions are associated with various dopaminergic tracts.
Abstract 17051: Cardiac Rehabilitation: Characteristics of Those Who Drop Out After Initiating a Program
Authors: Billie-Jean Martin, Trina Hauer, Leslie D Austford, Merill L Knudtson, Ross Arena, D A Meldrum, Sandeep Aggarwal, James A Stone
Journal: Circulation (2013)

Background: Cardiac Rehabilitation (CR) is an efficacious, evidence based treatment for reducing mortality and hospitalization in subjects with coronary artery disease (CAD). Many appropriate patie...
A retrospective analysis of the long-term effect of splenectomy on late infections, graft-versus-host disease, relapse, and survival after allogeneic marrow transplantation for chronic myelogenous leukemia
Authors: P Kalhs, I Schwarzinger, G Anderson, M Mori, RA Clift, R Storb, CD Buckner, FR Appelbaum, JA Hansen, KM Sullivan
Journal: Blood (1995)