tbuckley/cabot-search huggingface dataset:
Research Advances and Resource Constraints
Authors: David R. Perry, David R. Challoner, Robert J. Oberst
Journal: New England Journal of Medicine (1981)

Public investment in health research is concentrated disproportionately in a limited number of United States medical schools: about 75 per cent of federal health-research expenditures occur in the "Top 40" institutions. The heavy resource demands of advanced research, coupled with constrained public investment in the foreseeable future, will cause a gradual shift of resources toward the already research-rich schools. The various implications of this shift in resources for different categories of medical schools are described under different assumptions for the future: growth, a steady state, and decline. These developments underscore a public-policy dilemma. The further concentration of health-research resources in centers of excellence, which is justifiable in terms of maximizing the potential scientific return on the public's investment, is apt to prove disruptive to medical education in many schools in the middle and lower strata of funded research activity.
"Death" Cigarettes Offer Truth in Advertising
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article “Death” Cigarettes Offer Truth in Advertising Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 10, 20 May 1992, Page 755, https://doi.org/10.1093/jnci/84.10.755 Published: 20 May 1992
SIMVASTATIN INHIBITS HUMAN ATRIAL FIBROBLAST PROLIFERATION THROUGH CELL-CYCLE REGULATING CYCLINS BY MEVALONIC ACID-DEPENDENT PATHWAY
Authors: Farhan Rizvi, Alessandra DeFranco, Ramail Siddiqui, Alisher Holmuhamedov, Larisa Emelyanova, Gracious Ross, Ekhson Holmuhamedov, Paul Werner, A. Jamil Tajik, Arshad Jahangir
Journal: Journal of the American College of Cardiology (2016)
Comparative effect of tibolone and its metabolites on sulfatase activity in normal and cancerous breast tissues.
Authors: JR Pasqualini, GS Chetrite, J Cortes-Prieto
Journal: Cancer Research (2009)

Abstract Abstract #3035 Background: Tibolone (Org OD-14, active substance of Livial®) is a synthetic steroid with a 19-nor-testosterone derivative structure. This compound has weak estrogenic, progestagenic, and androgenic properties and is used to prevent climacteric symptoms and postmenopausal bone loss. Tibolone is extensively metabolized in 3a- and 3ß-hydroxy-derivatives and their 4-en isomer. Previous studies in this laboratory demonstrated that tibolone and its metabolites are anti-sulfatase agents in the hormone-dependent breast cancer cells: MCF-7 and T-47D, while the present study explores their effect on estrone-sulfatase activity in normal and cancerous breast tissues.&amp;#x2028; Materials and Methods: : Two regions of the mammary tissue from each post-menopausal patient with breast cancer (n=8) were selected : the tumoral tissue and a distant zone which was considered as normal. Slices of tumoral or normal breast tissues (25-95 mg) were incubated in buffer (20 mM Tris-HCl, pH 7.2) with physiological concentrations of [3H]-estrone sulfate (E1S) (5x10-9M) alone or in the presence of tibolone or its metabolites (5x10-5 or 5x10-7M) during 14h at 37°C. E1S, estrone and estradiol were characterized by thin layer chromatography and quantified using the corresponding standard.&amp;#x2028; Results: In breast cancer tissues the sulfatase activity was twice as high as in normal breast tissue. At concentrations of 5x10-7 and 5x10-5M tibolone inhibits sulfatase activity in breast cancer tissue by 25 and 33% respectively. Using the same concentrations for the 3a-hydroxy these were 32 and 57%, for the 3ß-hydroxy 22 and 32%, and for 4-en derivatives 0 and 48% respectively. In the normal tissues the values were: for tibolone, 3 and 20%, for the 3a-hydroxy, 16 and 29 %, for the 3ß-hydroxy, 13 and 25%, and for the 4-en derivative 0 and 22% respectively. In these experiments, it was observed that estrone does not convert to estradiol.&amp;#x2028; Conclusion: The present data indicates that the estrone sulfatase activity is higher in breast cancer tissue and that the inhibitory effects of tibolone and its metabolites are significantly higher in this tissue than in the normal breast. It is suggested that the present results can open new possibilities in the knowledge of the mechanism of action of tibolone and its metabolites in normal and cancerous breast. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3035.
Abstract 832: Effects of beta-cryptoxanthin on cigarette smoke-induced lung oxidative damage, inflammation and activation of NF-kappa B and AP-1
Authors: Chun Liu, Roderick T. Bronson, Robert M. Russell, Xiang-Dong Wang
Journal: Cancer Research (2011)

Abstract In epidemiologic studies, high intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of beta-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which beta-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of beta-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of pro-inflammatory cytokine [tumor necrosis factor alpha (TNF-alpha)] and transcription factors [nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2′-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets. Thirty six male ferrets were assigned to cigarette smoke exposure or to no exposure and to no dose, low-dose, or high-dose beta-cryptoxanthin supplementation (2 × 3 factorial design) for 3 months. Beta-cryptoxanthin supplementation dose-dependently increased plasma and lung beta-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung beta-cryptoxanthin levels. Beta-cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. Beta-cryptoxanthin also substantially reduced smoke-elevated TNF-alpha levels in alveolar, bronchial, bronchiolar and airway serous/mucous gland epithelial cells and in lung macrophages. Moreover, beta-cryptoxanthin decreased smoke-induced activation of NF-kappa B and expression of AP-1 and 8-OHdG. The beneficial effects of beta-cryptoxanthin were stronger for high-dose beta-cryptoxanthin than for low-dose beta-cryptoxanthin. Data from this study indicate that beta-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs. Beta-cryptoxanthin may prevent lung carcinogenesis through its inhibitive effects on lung inflammation and oxidative DNA damage. 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 832. doi:10.1158/1538-7445.AM2011-832
AB0830 Role of anti-IFI16 antibodies and NT-PROBNP as candidate biomarkers in systemic sclerosis
Authors: P.L. Meroni, C. Chighizola, T. Schioppo, C. Artusi, V. Caneparo, M. Gariglio, R. Gualtierotti, C. Lubatti, F. Ingegnoli, S. Zeni, M. Borghi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune condition characterized by polymorphic clinical presentations, high morbidity and mortality. It would be therefore valuable to identify biomarkers for diagnosis, prediction of organ involvement and disease subset. <h3>Objectives</h3> Aim of this study was to retrospectively assess the role of serum anti-IFI16 antibodies and NT-proBNP levels as candidate biomarkers in a cohort of scleroderma patients. <h3>Methods</h3> 100 SSc patients (49 with diffuse disease) were enrolled in this study; patients with PAH and renal insufficiency were excluded from NT-proBNP analysis. We investigated the relationship between the two candidate biomarkers and several scleroderma clinical manifestations (severe interstitial lung disease, cardiac involvement, digital ulcers, calcinosis, arthritis) and variables (age, disease duration, BP, Hb, mRSS, ESR, DLCO). Serum anti-IFI16 antibodies were detected by a home-made semi-quantitative ELISA, NT-proBNP levels were measured by the Roche immunoassay. Statistical analysis was performed using STATA 11. <h3>Results</h3> NT-proBNP was significantly increased in patients with heart involvement compared to those without (p=0.0003, 95%CI 57-232). A cut-off value of 130pg/mL gave a specificity of 70% and a sensibility of 74% to predict cardiac involvement (area under ROC curve 0.746; 95%CI 0.63-0.86), with a predictive negative value of 85%. Moreover, NT-proBNP levels&gt;130pg/mL were strong predictors of heart involvement (OR 7). Not surprisingly, NT-proBNP levels were negatively correlated with LVEF (r=-0.266; p=0.002). Conversely, there was no association between anti-IFI16 antibodies and cardiac involvement (p=0.505). No other association was reported between the two candidate biomarkers and clinical manifestations of SSc. There was no significant difference between disease subsets in NT-proBNP levels (p=0.12) and anti-IFI16 antibodies titers (p=0.71). We report a significant association between NT-proBNP and age (r=0.315; p=0.003), disease duration (r=0.287; p=0.008), ESR (p=0.0086) and DLCO (r=-0.356; p=0.001) while anti-IFI16 antibodies were not significantly associated with any of the clinical variables. <h3>Conclusions</h3> Given the high negative predictive value, NT-proBNP may be a useful tool to identify scleroderma heart disease. SSc related cardiac involvement still heralds a poor prognosis, with 1% of annual mortality attributable to cardiac disease. Future studies are warranted to establish its role as surrogate biomarker. <h3>Disclosure of Interest</h3> None Declared
Abstract 245: Phenotypically diverse cancer cell subpopulations in a luminal-like breast cancer xenograft model are associated with different signaling pathways.
Authors: Nirma Skrbo, Kristin Andersen, Alexandr Kristian, Linn Antberg, Geir Olav Hjortland, Olav Egenbråten, Peter James, Gunhild Mari Mælandsmo, Therese Sørlie
Journal: Cancer Research (2013)

Abstract High degree of intratumor cellular diversity represent a major challenge when attempting to cure cancer. The presence of tumor cell subpopulations with enhanced in vivo tumorigenic capacity (tumor initiating cells, TICs), and high resistance to conventional cancer therapy, compared with the “bulk” tumor cell populations, has for the last decade been the focus of many breast cancer research groups. The cellular heterogeneity of an orthotopic luminal-like breast cancer xenograft model was investigated using IHC, flow cytometry, whole genome expression profiling and mass spectrometry-based proteomics combined with in vivo tumorigenicity and targeted therapy assays. Epithelial cell adhesion molecule, EpCAM, highly specific for the human tumor epithelial cells, was used to separate human tumor cells from the mouse stromal compartment. Further flow analysis of the EpCAM positive tumor cell population revealed diverse expression of several cell surface markers, including CD24 and SSEA-4 (stage specific embryonic antigen 4). SSEA-4-/CD24-, SSEA-4+/CD24- and SSEA-4-/CD24+ populations were capable of initiating tumors in NOD SCID mice while SSEA-4+/CD24+ cells were non-tumorigenic. Tumors resulting from the SSEA-4+/CD24- subpopulation did not express CD24, while tumors arising from the SSEA-4-/CD24- and SSEA-4-/CD24+ populations, contained all four subpopulations. As measured by whole genome expression analysis and mass spectrometry-based proteomics, the molecular differences were most pronounced between tumorigenic subpopulations and the non-tumorigenic subpopulation. While the mRNA expression data revealed a high degree of similarity among the four subpopulations, the proteomics data suggested that several signaling pathways might have distinct and different activity across the populations. The effects of targeted therapy against ER and WNT signaling on heterogeneity and tumorigenicity have been evaluated by in vivo experiments. Citation Format: Nirma Skrbo, Kristin Andersen, Alexandr Kristian, Linn Antberg, Geir Olav Hjortland, Olav Egenbråten, Peter James, Gunhild Mari Mælandsmo, Therese Sørlie. Phenotypically diverse cancer cell subpopulations in a luminal-like breast cancer xenograft model are associated with different signaling pathways. [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 245. doi:10.1158/1538-7445.AM2013-245
Development of an Epstein–Barr virus type 2 (EBV-2)-associated hepatic B cell non-Hodgkin's lymphoma in an HIV-1-infected patient following a change in the EBV dominant type
Authors: M Buisson, P Morand, M Peoc'h, O Bouchard, M-J Bourgeat, J-M Seigneurin
Journal: Leukemia (1999)
Sequential High-Dose Combination Chemotherapy With Granulocyte Colony-Stimulating Factor and Peripheral Blood Progenitor Cells in Patients With Solid Tumors: Intensification Limited by Nonhematologic Toxic Effects
Authors: S. LEYVRAZ, N. KETTERER, P. VUICHARD, V. VON FLIEDNER, F. LEJEUNE, P. SCHNEIDER, J.-P. GROB, F. BACHMANN
Journal: JNCI Journal of the National Cancer Institute (1993)
Autocrine Growth of Murine Lymphoma Cells
Authors: E. F. Hays, S. Kitada, C. H. Uittenbogaart, J. R. Reeve
Journal: JNCI Journal of the National Cancer Institute (1988)

By using an assay system in which small numbers of murine T lymphoma cells are stimulated to grow in serum-free medium, we have continued and expanded our previous studies of an autocrine growth factor that we call leukemia-derived growth factor (LDGF). We show that a T lymphoma cell line of immature phenotype, adapted to growth in serum-free medium, produces and responds to LDGF. LDGF activity is distinct from activities of 10 highly purified or recombinant hematopoietic growth factors including IL-1 and IL-2. However, growth-stimulating activity for the murine lymphoma cells is provided by a partially purified human LDGF.
Case 8-1999
Authors: Paul E. Farmer, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 28-year-old man was admitted to the hospital because of gram-negative sepsis.The patient had been in excellent health until three weeks earlier, when malaise developed. Ten days before admission, he attended a wedding. The next day he had fatigue, anorexia, and malaise, which waxed and waned. Four days before admission, his temperature rose to 40.6°C, with rigors, sweats, and difficulty concentrating. Two days later, the patient had a severe occipital headache.One day before admission, the patient came to the emergency department at this hospital. The temperature was 38.7°C, the pulse was 120, and the respirations . . .
Head and neck cancer (HNC), depression, and genetic polymorphism
Authors: J. Gilbert, K. Haman, W. G. Yarbrough, M. S. Dietrich, C. H. Chung, A. J. Cmelak, M. Pham, N. Muldowney, R. D. Blakely, B. A. Murphy
Journal: Journal of Clinical Oncology (2008)

6017 Background: The prevalence of depression in the cancer population exceeds that of the general population, with HNC patients having among the highest rates. Whereas genetic polymorphism (short/S allele vs. long/L allele) in the serotonin transporter (5 HTTLPR) gene is associated with depression in a general population, this relationship has not been evaluated in cancer patients. We evaluated the prevalence of psychiatric disorders in HNC patients and correlated depression with the presence of the S allele. Methods: Depressive Disorders (DD) were measured using the Structured Clinical Interview for DSM-IV (SCID). PBMCs were isolated from whole blood and PCR was used to amplify the region containing the polymorphism (S vs. L) of the 5 HTTLPR. Genotypes (L/L, L/S, S/S) were also determined. Results: 84 HNC pts were evaluated, median 6 months post CCR. Prevalence of DD was: 8 (10%) pre-cancer only, 20 (24%) post cancer only, and 9 (11%) pre and post-cancer. Blood was available from 34 pts for genotyping. The prevalence of the 5-HTTLPR S allele in HNC pts was higher than population norms (HNC∼53%, Popn ∼40%). When HNC pts were analyzed for depression, the S allele was associated with both MDD (p=0.044, OR=6.50) and general depressive diagnoses (p=0.017, OR=9.00). Conclusion: Depression is common in HNC pts in the setting of CCR. One potential contributing factor may be a higher rate of the 5HTTLPR S allele. The impact of the S allele in HNC is substantially higher than the impact seen for the S allele with depression but may reflect our relatively small sample size. The rate of new onset depression associated with CCR suggests a strong interactive effect of treatment on depression. Elevated cytokines levels are associated both with depression and with CCR. Ongoing studies seek to explore the mechanistic basis of the relationship between the 5HTTLPR and depression risk, focusing on the impact of the S allele on generation or response to cytokine production with CCR. Genotype: Depressive Disorder No Yes Total SS 3 8 11 LS 4 10 14 LL 7 2 9 Total 14 20 34 No significant financial relationships to disclose.
Abstract 4188: Whole transcriptome analyses of platinum-resistant ovarian cancer cells
Authors: David F. Miller, Yunlong Lui, Pearlly Yan, Benjamin Rodriguez, Hai Lin, Shokhi Goel, Edra Jani, Anurag Bhattrai, Kevin Koekesh, Cong Guo, Tim H-M Huang, Kenneth P. Nephew
Journal: Cancer Research (2012)

Abstract Women with advanced stage ovarian cancer have a five-year survival rate of less than 25%. Although most patients respond to platinum-based chemotherapy, relapses are common, leading to platinum-resistant ovarian cancer, which is uniformly fatal. Similar to other malignancies, ovarian cancer progression is associated with transcriptional deregulation and such changes contribute to ovarian cancer progression and development of resistance to chemotherapy. In an effort to better understand the causes of acquired platinum resistance in ovarian cancer, we performed whole transcriptome analysis of platinum sensitive and resistant ovarian cancer cell lines. We used RNA-sequencing to identify candidate genes and pathways that contribute to platinum-resistant ovarian cancer. We detected altered mRNA expression of transcription factors (DMRT3, DMRT1, GATA1, EMX2, LHX1, SRY, SOX9, FOXL2, LHX9) and signaling pathway genes (RXFP2, AR, WT1, FGF9, RSPO1, TUSC3, NROB1, WNT4). Additionally, significant up regulation (&amp;gt;20 fold increase) of the long non-coding RNAs (lncRNAs) HOTAIR and HOTTIP, which direct polycomb group and trithorax complexes to HOX promoters, was detected. We observed elevated HoxA gene expression (&amp;gt; 100 fold in some cases) associated with increased HOTTIP lncRNA expression in the platinum resistant cells. Altered expression of genes associated with DNA methylation (DNMT1, DNMT3A, DNMT3B, DNMT3L MECP2, MBD3L1, MBD6, MBD2, MBD3L2, MBD5, MBD1, MBD3, MBD4) was also observed. Furthermore, the splicing patterns of BRCA1 and BRCA2 genes in platinum resistant cells were altered, resulting in splice variants lacking functional coding regions. Altered BRCA1 and BRCA2 splicing patterns were correlated with reduced expression levels for numerous splicing factors (A2BP1, PTBP1, RBM9, SFRS3, ARID3A, ARID3B, SF1). DNA methylation analysis indicated epigenetic derepression consistent with increased expression for gonad developmental genes (HOTAIR, HOTTIP, HOXA genes). Our data suggest that genes associated ovarian development and differentiation contribute to the development of platinum resistant ovarian cancer. We are currently conducting integrated data and bioinformatics analyses to further investigate changes found in platinum resistance. 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 4188. doi:1538-7445.AM2012-4188
Aortojejunal Fistula in Non-Hodgkin’s Lymphoma
Authors: YVONNE Y. HO
Journal: Clinical Nuclear Medicine (2002)

From Radclin Medical Imaging, Cabrini Hospital, Malvern, Australia Received for publication July 17, 2001. Revision accepted October 17, 2001. Reprint requests: Yvonne Ho, Department of Diagnostic Imaging, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. E-mail: [email protected]
Recovery of Cardiac Function in Cardiomyopathy Caused by Titin Truncation
Authors: Leanne E. Felkin, Roddy Walsh, James S. Ware, Magdi H. Yacoub, Emma J. Birks, Paul J. R. Barton, Stuart A. Cook
Journal: JAMA Cardiology (2016)

Recovery of Cardiac Function in Cardiomyopathy Caused by Titin TruncationDilated cardiomyopathy (DCM) is a frequent cause of heart failure and a common indication for heart transplantation.Dilated cardiomyopathy has a strong genetic basis, and the most common disease-causing mutations are variants that truncate the sarcomeric protein titin (TTN-truncating variants [TTNtvs] are prevalent in 25% 1 of familial DCM cases and 13% 2 of idiopathic DCM cases).The prognosis of DCM is poor, but functional recovery from end-stage failure has been reported following both optimal medical therapy 3 and left ventricular assist device (LVAD) support, 4,5 although the determinants of successful recovery are unknown.It has been proposed that recovery from genetic cardiomyopathy may not be expected because the underlying cause is irre-versible, whereas recovery may be more likely when DCM is caused by reversible, nongenetic factors (eg, myocarditis). 6 To address this directly, we sequenced TTN in patients with end-stage DCM who either recovered or did not recover following LVAD support.