tbuckley/cabot-search huggingface dataset:
Quantitative Evaluation of Aldo–keto Reductase Expression in Hepatocellular Carcinoma (HCC) Cell Lines
Authors: Lei Yang, Ju Zhang, Shenyan Zhang, Weiwei Dong, Xiaomin Lou, Siqi Liu
Journal: Genomics Proteomics & Bioinformatics (2013)

The involvement of aldo-keto reductases (AKRs) in tumorigenesis is widely reported, but their roles in the pathological process are not generally recognized due to inconsistent measurements of their expression. To overcome this problem, we simultaneously employed real-time PCR to examine gene expression and multiple reaction monitoring (MRM) of mass spectrometry (MS) to examine the protein expression of AKRs in five different hepatic cell lines. These include one relatively normal hepatic cell line, L-02, and four hepatocellular carcinoma (HCC) cell lines, HepG2, HuH7, BEL7402 and SMMC7721. The results of real-time PCR showed that expression of genes encoding the AKR1C family members rather than AKR1A and AKR1B was associated with tumor, and most of genes encoding AKRs were highly expressed in HuH7. Similar observations were obtained through MRM. Different from HuH7, the protein abundance of AKR1A and AKR1B was relatively consistent among the other four hepatic cell lines, while protein expression of AKR1C varied significantly compared to L-02. Therefore, we conclude that the abundant distribution of AKR1C proteins is likely to be associated with liver tumorigenesis, and the AKR expression status in HuH7 is completely different from other liver cancer cell lines. This study, for the first time, provided both overall and quantitative information regarding the expression of AKRs at both mRNA and protein levels in hepatic cell lines. Our observations put the previous use of AKRs as a biomarker into question since it is only consistent with our data from HuH7. Furthermore, the data presented herein demonstrated that quantitative evaluation and comparisons within a protein family at both mRNA and protein levels were feasible using current techniques.
Pharmaceutical Sponsorship, CME, and the Prurient Desires of Registrants-Reply
Authors: Arthur M. Osteen
Journal: JAMA (1991)

<h3>In Reply.</h3> —The ACCME guidelines for commercial support of CME and the AMA guidelines for physician relationships with industry apply regardless of whether a CME activity is designated AMA PRA category 1, AMA PRA category 2, or whether there is no designation whatsoever, meaning that a physician determines individually whether the activity meets an educational need. If an accredited sponsor finds that it cannot sponsor a pharmaceutical company-related activity for AMA PRA category 1 credit, it must also find that it cannot sponsor that activity for AMA PRA category 2 credit. In that circumstance, the pharmaceutical company has a choice of changing the activity to meet a prospective sponsor's concerns or of providing the activity without accredited sponsorship. The hope is, certainly, that pharmaceutical firms will find ways of participating in CME that meet the guidelines. Many firms have, in fact, indicated that this is their intention. If pharmaceutical firms
Abstract 3786: Activation of KLF4 by 3,3′-Diindolylmethane contributes to the cell differentiation and grow inhibition of pancreatic cancer cells
Authors: Daoyan Wei, Keping Xie
Journal: Cancer Research (2010)

Abstract 3,3′-Diindolylmethane (DIM), the major bioactive metabolite of the phytochemical indole-3-carbinol present in cruciferous vegetables, is a promising cancer preventative and anti-tumor agent for various tumor types, including pancreatic cancer. However the underlying molecular mechanisms by which DIM exerts its antitumor activity remain poorly understood. Our previous studies indicate that KLF4 has a tumor suppressive function in pancreatic cancer by up-regulation of p27 expression and induction of cell cycle arrest, which has also been suggested to be the mechanistic action of DIM in pancreatic cancer cells. However, whether KLF4 is involved in DIM's antitumor activity and if so, what are the underlying molecular mechanisms in pancreatic cancer have not been defined. In the present study, we found that DIM treatment dose dependently induced the expressions of KLF4 and its downstream target gene p27 and p21 in several, and cytokeratin 19 in Panc-28 and PANC-1 pancreatic cancer cells. Consistently, induction of KLF4 expression correlated with significant inhibition of cell cycle progression and cell growth as determined by Flow cytometry and MTT assay, while knockdown or conditional knockout of KLF4 expression significantly reduced the sensitivity of pancreatic cancer cells to DIM treatment determined by IC50 assay. These results indicate that KLF4 plays a critical role in mediating the antitumor activity of DIM in pancreatic cancer cells. To further investigate the molecular mechanism underlying DIM's induction of KLF4 expression, KLF4 promoter deletion mutation analysis identified a DIM responsible region (from nucleotide −780 to −346) in the KLF4 promoter, within which a candidate Egr-1 cis-acting element was found by computer-based motive analysis. Functionally, significant induction of Egr-1 protein expression was observed as early as 1 hr after DIM treatment in time-course experiments, which was prior to the induced expression of KLF4 in FG cells. Consistently, forced or knocking down Egr-1 expression increased or reduced the response of BxPC3 cells to DIM treatment, which was correlated with increased or decreased KLF4 expression. In addition, chromatin immunoprecipitation assay showed that Egr-1 protein physically interacted with and DIM treatment increased the binding of Egr-1 to the DIM responsive region of KLF4 promoter in FG cells in vivo. Collectively, our results suggest that Egr-1/KLF4 signaling pathways play an important role in DIM's antitumor activity in pancreatic cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3786.
Nifedipine and Ureteral Colic
Authors: SAMI VISKIN
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 July 1986Nifedipine and Ureteral ColicSAMI VISKIN, M.D., ISSAC KAVER, M.D., ALEXANDER GREENSTEIN, M.D., AVI HASSNER, M.D.SAMI VISKIN, M.D.Search for more papers by this author, ISSAC KAVER, M.D.Search for more papers by this author, ALEXANDER GREENSTEIN, M.D.Search for more papers by this author, AVI HASSNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-1-142_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: After a report on the in-vitro effects of nifedipine on ureteral muscle (1) and an anecdotal report in your journal of its successful clinical use (2), we started a prospective clinical trial to test the therapeutic value of nifedipine in the treatment of ureteral colic.So far, nine consecutive patients with definite evidence of urolithiasis and a clinical picture of ureteral colic have been studied. Informed consent was obtained from all patients, and the protocol was approved by the Ethical Committee of Tel Aviv Medical Center. Therapy consisted of a single dose of nifedipine, 10 or 20...References1. SAKANASHI M, KATO T, and MIYAMOTO Y. Comparison of the effects of nifedipine on ureter and coronary artery isolated from the dog. Arzneimittelforsch. 1985;35:584-7. MedlineGoogle Scholar2. CAROL W. Nifedipine and ureteral colic [Letter]. Ann Intern Med. 1985;102:864. LinkGoogle Scholar3. KEELE K. Pain complaint threshold in relation to pain of cardiac infarction. Br Med J. 1968;1:670-3. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SAMI VISKIN, M.D.; ISSAC KAVER, M.D.; ALEXANDER GREENSTEIN, M.D.; AVI HASSNER, M.D.Affiliations: Ichilov Hospital 64239 Tel Aviv Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNifedipine and Methylprednisolone in Facilitating Ureteral Stone Passage: A Randomized, Double-Blind, Placebo-Controlled StudyCALCIUM CHANNEL ANTAGONISTS IN THE TREATMENT OF INTERSTITIAL CYSTITISClinical and Immunological Response to Nifedipine for the Treatment of Interstitial CystitisDiclofenac sodium and spasmolytic drugs in the treatment of ureteral colic: A comparative studyNifedipine and Ureteral ColicLYNE COPPENS, M.D., FRANÇOIS LUSTMAN, M.D. 1 July 1986Volume 105, Issue 1Page: 142-142KeywordsClinical trial reportingMuscles ePublished: 1 December 2008 Issue Published: 1 July 1986 PDF downloadLoading ...
The Interaction of Alpha-Thalassemia and Homozygous Sickle-Cell Disease
Authors: Douglas R. Higgs, Beverley E. Aldridge, Janette Lamb, John B. Clegg, David J. Weatherall, Richard J. Hayes, Yvonne Grandison, Yvonne Lowrie, Karlene P. Mason, Beryl E. Serjeant, Graham R. Serjeant
Journal: New England Journal of Medicine (1982)

Patients with homozygous sickle-cell disease may be homozygous for alpha-thalassemia 2 (alpha-/alpha-), may be heterozygous for alpha-thalassemia 2 (alpha-/alpha alpha), or may have a normal alpha-globin-gene complement (alpha alpha/alpha alpha). We compared the clinical and hematologic features of 44 patients who had sickle-cell disease and homozygous alpha-thalassemia 2 with those of controls with the two hematologic conditions. The patients with homozygous alpha-thalassemia 2 had significantly higher red-cell counts and levels of hemoglobin and hemoglobin A2, as well as significantly lower hemoglobin F, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, reticulocyte counts, irreversibly-sickled cell counts, and serum total bilirubin levels, than those with a normal alpha-globin-gene complement. Heterozygotes (alpha-/alpha alpha) had intermediate values. In the group with homozygous alpha-thalassemia 2, fewer patients had episodes of acute chest syndrome and chronic leg ulceration and more patients had splenomegaly, as compared with patients in other two subgroups. These data confirm previous suggestions that alpha-thalassemia inhibits in vivo sickling in homozygous sickle-cell disease and may be an important genetic determinant of its hematologic severity.
Nearly a third of US doctors won't see new patients with Medicaid insurance
Authors: J. H. Tanne
Journal: BMJ (2012)

Many of the 16 million extra US citizens who will become eligible for health insurance under the Medicaid programme from January 2014 are expected to have trouble finding a doctor.

Many US doctors are reluctant to take patients with Medicaid insurance because of the scheme’s low proportion of reimbursement paid to doctors, and a study published in the August issue of Health Affairs has found that 31% of doctors would not be prepared to accept any new patients under Medicaid.1

Medicaid currently covers about 60 million people, including many poor people, disabled people, pregnant women, and people in long term care. President Barack Obama’s Affordable Care Act, passed in March 2010, expanded eligibility to at least 16 million more people, predominantly those on low incomes but above the …
Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases
Authors: R L Wilder
Journal: Annals of the Rheumatic Diseases (2002)

A substantial and persuasive body of data now exists that supports the view that integrin alpha V beta 3 plays a critical part in activated macrophage dependent inflammation, osteoclast development, migration, and bone resorption, and inflammatory angiogenesis. All of these processes play an important part in the pathogenesis of rheumatoid arthritis (RA) and related arthropathies. Animal arthritis model data further support these concepts and also suggest that therapeutic antagonism of integrin alpha V beta 3 is worthy of further investigation in RA and related arthropathies. To this end, Vitaxin, also known as MEDI-522, has been developed. Vitaxin is a humanised monoclonal IgG<sub>1</sub> antibody that specifically binds a conformational epitope formed by both the integrin alpha V and beta 3 subunits. It blocks the interaction of alpha V beta 3 with various ligands such as osteopontin and vitronectin. Clinical trials with Vitaxin in patients with RA are in progress.
Abstract 2327: Structural and kinetic characterization of crizotinib with wild-type and mutant anaplastic lymphoma kinase
Authors: Michele A. McTigue, Sergei L. Timofeevski, Wei Liu, Ya-Li Deng, Tami Marrone, Jean Cui, Alexei Brooun
Journal: Cancer Research (2011)

Abstract Dysregulation of Anaplastic Lymphoma Kinase (ALK), primarily through gene translocations, has been shown to be involved in a variety of cancers. Crizotinib, an orally available small molecule inhibitor of the ALK tyrosine kinase has demonstrated marked efficacy in clinical trials of NSCLC patients harboring the EML4-ALK oncogenic gene rearrangement. Mutation of some residues within the ALK kinase domain have been reported to confer acquired or de novo resistance to crizotinib. To understand the binding of crizotinib to ALK and the mechanism of resistance of specific mutations we generated and kinetically characterized wild-type (WT) and mutant ALK kinase domains (KD). Additionally, ALK KD crystal structures were determined of the WT nonphosphorylated apoenzyme and complexes with crizotinib bound to WT and a L1196M gatekeeper mutation. No large protein conformational changes are necessary for crizotinib to bind to unliganded ALK. The interactions which crizotinib makes with ALK are similar to its binding to c-Met with the exception of notable differences in the position of the activation loop between ALK and c-Met. Mutation of the L1196 gatekeeper residue to methionine results in a ∼8-fold increase in catalytic efficiency of phosphorylation of an activation loop peptide and also more rapid enzyme auto-phosphorylation. In addition, inhibition of L1196M ALK by crizotinib was reduced ∼9-fold, compared to wild-type enzyme, from Ki determinations. The crystal structures show that L1196 or M1196 make direct contact with crizotinib. The diminished activity of crizotinib against L1196M ALK is therefore likely due to both higher intrinsic kinase activity and a subtle change in the ALK-crizotinib binding interactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2327. doi:10.1158/1538-7445.AM2011-2327
Abstract 3638: Detecting prostate cancer in <i>BRCA1</i> and <i>BRCA2</i> mutation carriers: A role for EN2
Authors: Emma Killick, Richard Morgan, Francesca Launchbury, Nicola Annels, Elizabeth Bancroft, Elizabeth Page, Elena Castro, Zsofia Kote-Jarai, Rosalind Eeles, Hardev Pandha
Journal: Cancer Research (2012)

Abstract EN2 is part of the HOX gene family and plays a role in foetal development. More recently a potential oncogenic role for the protein has been postulated and its utility as a cancer biomarker has been explored in prostate cancer (PrCa) and breast cancer. Carriers of mutations in the BRCA1 and BRCA2 genes have an increased risk of PrCa (1.8-fold and 5-fold respectively) and their tumours tend to be more aggressive and advanced than sporadic cases. Currently there is no national screening program for BRCA mutation carriers in the UK, and the IMPACT study was set up to evaluate PSA screening in this particular group. Here we analyse the efficacy of the urinary EN2 protein and auto-antibody against EN2 in serum and urine as markers of early cancer detection within this higher risk group. Urine and serum were taken from the IMPACT screening study which enrolled individuals aged between 40 and 69 who were unaffected by PrCa at time of enrolment into the study (n= 418). All participants were from families harbouring a BRCA1 or BRCA2 mutation and were either BRCA mutation carriers themselves or controls with a negative predictive BRCA genetic test. They underwent annual PSA test with a PSA of &amp;gt; 3.0 ng/ml triggering a diagnostic biopsy. Annual urine and serum samples were collected from this cohort. EN2 protein was measured in the urine using an ELISA; (positive = &amp;gt; 42.5ng/ml). The autoantibody was measured in serum and urine; (positive = measurement of 2 standard deviations above the mean value when measured in a cohort of healthy volunteers). Using detection of EN2 protein in urine alone our initial results demonstrated the test had a sensitivity of 71.4% and a specificity of 75.4% when discriminating between those with a positive biopsy and those with a negative biopsy; the ROC AUC was 0.767. The difference in EN2 level between those diagnosed with cancer and those who were not was significant (p = &amp;lt;0.001). EN2 antibody measured in serum was less sensitive but more specific that the urinary protein (33.3% and 83.6% respectively), when combined with urinary protein the sensitivity is 85.7% with a specificity of 63.3% and ROC AUC 0.745. Further samples are in the process of being analysed and data and results of these will be presented. In addition a new assay to measure urinary antibody is currently under development and results from this test will be also shown. EN2 protein and auto-antibody measurement warrants further investigation as a PrCa biomarker in this higher risk group with genetic predisposition to PrCa. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3638. doi:1538-7445.AM2012-3638
Prevalence, Incidence and Correlates of HHV-8/KSHV Infection and Kaposi's Sarcoma in Renal and Liver Transplant Recipients
Authors: M. Andreoni, D. Goletti, P. Pezzotti, A. Pozzetto, P. Monini, L. Sarmati, F. Farchi, G. Tisone, A. Piazza, F. Pisani, M. Angelico, P. Leone, F. Citterio, B. Ensoli, G. Rezza
Journal: Journal of Infection (2001)
Abstract 1752: Consequences of high Chromosome Instability (CIN) in SGO1(Shugoshin1) CIN model mice.
Authors: Hiroshi Y. Yamada, Yuting Zhang, Wei Dai, Chinthalapally V. Rao
Journal: Cancer Research (2013)

Abstract Abstract Mitotic errors have been suspected to be a cause of aneuploidy, rapid accumulation of mutations, and tumorigenesis. In addition, recent cell biological studies demonstrated that mitotic errors can result in DNA damage, which would also aid accumulation of mutations then carcinogenesis. However, no observations in vivo have been provided to support the cell biological observations to date. Previously we developed two strains of high Chromosome Instability (CIN) model mice, which show an increase in mitotic errors due to haploinsufficiency in chromosome cohesion system component Sgo1 or mitotic spindle checkpoint component BubR1. The pathways affected by these mutations are suggested to play a role in aging and carcinogenesis in human. Consistently, compared with wild type, both mice strains showed a significant risk for tumor development in colon with chemical carcinogenesis assays. In this study, we used these CIN mice to test whether (i) spontaneous carcinogenesis occurs in the mice, (ii) spontaneous DNA damage occurs in the mice, (iii) whether associated marker expressions are altered, and (iv) if so, whether it is affected by the age. In 12 month old (middle-age) SGO1 and BUBR1 mice, we observed an increase in spontaneous epithelial cancers, although the carcinogenic effect is not aggressive (p&amp;lt;0.05 in SGO1). In histologically normal-looking liver tissue in the mice, increased signals of DNA damage marker pohspho-gamma-H2AX and p53 were observed (4∼5-fold higher in CIN mice), along with altered expressions of p16INK4A and Bcl2 (2∼6-fold higher in CIN mice), providing the first evidence for DNA damage in vivo with mutations that increase mitotic errors. In 4 month old (younger adult) SGO1 mice, significantly (p&amp;lt;0.05) higher percentage of p-H2AX signal in comparison with wild type was also observed. The results demonstrate that mitotic error and CIN-causing mutation can cause higher DNA damage in the tissue-level, indicating that an additional path to carcinogenesis is at work in vivo. Marker analysis in the CIN model mice would indicate molecular consequences of this type of mutation and would lead to the discovery of novel cancer prevention drug targets. Citation Format: Hiroshi Y. Yamada, Yuting Zhang, Wei Dai, Chinthalapally V. Rao. Consequences of high Chromosome Instability (CIN) in SGO1(Shugoshin1) CIN model mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1752. doi:10.1158/1538-7445.AM2013-1752
Cardiovascular Mortality Risk in Chronic Kidney Disease
Authors: Michael G. Shlipak, Linda F. Fried, Mary Cushman, Teri A. Manolio, Do Peterson, Catherine Stehman-Breen, Anthony Bleyer, Anne Newman, David Siscovick, Bruce Psaty
Journal: JAMA (2005)

Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown.To compare traditional and novel risk factors as predictors of cardiovascular mortality.A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years.Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2.Among the participants, 1249 (22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P = .05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95% confidence interval, 0.71-0.78; P for difference = .15).Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.