tbuckley/cabot-search huggingface dataset:
A1.21 Inhibitory potential of specific acpas in two mouse subspecies genetically separated about one million years ago
Authors: C Grimm, B Marklein, M Jenning, U Harre, Z Konthur, H Lehrach, GR Burmester, K Skriner
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objective</h3> Monoclonal Anti-citrullinated protein autoantibodies ACPA target different proteins and their role in RA is still largely unknown. We analysed the susceptibility of PWD Musmusculusmusculus subspecies, separated from Musmusculusdomesticus about one million years ago to collagen antibody-induced arthritis (CAIA) and the role of ACPA antibodies in the CAIA model of arthritis. <h3>Methods</h3> CAIA was induced by administration of collagen antibodies followed by lipopolysaccharide injection. Two genetically distinct mouse strains, representatives of the subspecies <i>Mus musculus domesticus</i> and <i>Mus musculus musculus</i> were analysed for the development of clinical and histological signs of arthritis upon CAIA treatment. ACPA antibodies were tested by adding it to the CAIA cocktail. Autoantigenic profile was generated using protein macroarrays. <h3>Results</h3> The wild-derived mouse strain PWD/Ph was highly susceptible to CAIA induced arthritis, whereas the classical laboratory strain C57BL/6J was resistant. Mice carrying chromosomes 5 or 12 from PWD on a B6 background display a B6-like phenotype in the CAIA model as well as the F1 hybrids (B6xPWD and PWDxB6) implicating the presence of dominant resistance modifiers in the C57BL/6J genetic background. The two mouse strains differ highly in their autoantigenic profile. Injecting specific monoclonal ACPAs reactive with the citrullintated H1 and H4 were able to block the CAIA induced arthritis. This inhibition can be explained in part by a Toll 9 dependent inhibition of osteoclasts. Moreover TLR2 activation via P.gingivalis LPS and lipomannan treated animals show a 80% reduction of arthritis score compared to E. coli LPS in a C57BL/6J CAIA model. Anti-collagen specific antibodies are increased in both strains B6 and PWD when arthritis is induced. Commercial CCP2 ELISA detected ACPA in animals regardless of the treatment. Using the arginine and citrulline containing peptides as control shows that this response is directed to the arginine containing peptide. <h3>Conclusions</h3> The <i>Mus musculus musculus&nbsp;</i>derived mouse strain PWD/Ph is highly susceptible to arthritis development in the CAIA model. TLR2 activation blocks CAIA and specific ACPAs are able to block Osteoclast activation via TLR 9 activation and these monoclonal antibodies may be used as therapeutic antibodies in the future that protect from RA development.
Chiari–Frommel Syndrome in a Patient with Primary Adrenocortical Insufficiency
Authors: Samuel Refetoff, Marshall B. Block, Edward N. Ehrlich, Henry G. Friesen
Journal: New England Journal of Medicine (1972)

Abstract For fourteen months post partum a 31-yearold woman had amenorrhea, galactorrhea, hyperpigmentation, and loss of sexual hair. A diagnosis of primary adrenocortical insufficiency was supported by low serum and urinary cortisol, high serum ACTH, circulating adrenal antibodies, aldosterone deficiency, failure to respond to exogenous ACTH, and a normal sella turcica, growth hormone, thyrotropin, and luteinizing and follicle-stimulating hormones. Base-line human prolactin levels were slightly but consistently elevated to 26 to 29 ng per milliliter. Replacement with 37.5 mg of cortisone acetate per day resulted within three weeks in spontaneous resumption of regular menstrual cycles, disappearance of galactorrhea, weight gain and regression of pigmentary changes. Serum ACTH returned to normal, and prolactin levels decreased to 10 to 11 ng per milliliter. Thus, glucocorticoid deficiency due to primary adrenocortical insufficiency can produce persistent prolactin elevation with galactorrhea in the hormona...
Natural killer cell activity and MMPI scores of a cohort of college students
Authors: J S Heisel, S E Locke, L J Kraus, R M Williams
Journal: American Journal of Psychiatry (1986)

Natural killer (NK) cells are important in immune function and appear, in part, to be regulated by the CNS. The authors compared NK cell activity and MMPI scores of 111 healthy college students and found weak but statistically significant correlations between NK values and psychopathology for 10 of 12 scales. Students with the highest NK values had a "healthier" MMPI profile than those with the lowest. Students with high MMPI scores (T greater than 70) had NK values below the sample median. These findings support theories of interaction between mental state and immune status, but the mechanisms and direction of interaction remain largely unexplored.
The Natural History of Community-Acquired Hepatitis C in the United States
Authors: Miriam J. Alter, Harold S. Margolis, Krzysztof Krawczynski, Franklyn N. Judson, Allene Mares, W.James Alexander, Pin Ya Hu, Joan K. Miller, Michael A. Gerber, Richard E. Sampliner, Emory L. Meeks, Michael J. Beach
Journal: New England Journal of Medicine (1992)

Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C.
CONFOCAL IMAGING OF PACLITAXEL INDUCED VASCULAR RESPONSE AFTER APPLICATION OF A NOVEL DRUG-COATED BALLOON
Authors: Tobias Koppara, Qi Cheng, Michael Joner, Kazuyuki Yahagi, Oscar Sanchez, Hiroyoshi Mori, Julia Feygin, Frank Kolodgie, Renu Virmani
Journal: Journal of the American College of Cardiology (2015)
Abstract P6-05-04: Expression of the Androgen Receptor in triple negative tumors and its modulation by receptor tyrosine kinases and downstream pathways
Authors: D Cuenca, JC Montero, JC Morales, A Prat, A Pandiella, A Ocana
Journal: Cancer Research (2012)

Abstract Background: Androgen receptor (AR) plays a central role in some tumor types like prostate cancer. Its expression and function in breast cancer is relatively unknown. Studies have linked tyrosine kinase (TK) receptors and their intracellular signaling pathways with AR status. In the present work we study the presence of AR in breast cancer human samples and how TKs can control its expression. Methods: Tumor samples from patients were used to assess the expression of AR by western-blot. Membrane and intracellular kinases were evaluated using phosphoprotein arrays. Cell lines representative of all breast cancer subtypes were used to assess the expression of the AR and other signaling proteins using western-blot and phosphoprotein arrays. Proliferation studies with several kinase inhibitors were measured by MTT assays. We also interrogated publicly available gene expression microarray data sets with annotated clinical-pathological data. Results: Across all the intrinsic subtypes of breast cancer, the expression of AR gene was found highly expressed in HER2-enriched and Luminal tumors and lowly expressed in Basal-like and/or triple-negative (TN) tumors. In TN tumors, PDGFRβ and EGFR were found highly activated, together with AKT and Erk1/2. A positive correlation was observed between activation of EGFR and PDGFRβ and the expression of AR. In vitro, AR protein expression varied across cell lines and was found more expressed in MCF7 (Luminal) and HS578T (TN), BT549 (TN), HCC70 (TN) and no expressed in HBL100 (TN) and MDA-MB231 (TN). Administration of the antiandrogen bicalutamide produced an anti-proliferative effect that was increased by association of an Erk1/2 inhibitor. Inhibition of the PI3K-mTOR pathway in BT549 and HS578T reduced the expression of AR but did not augment the action of bicalutamide. In TN tumors, AR gene and protein was found more expressed in older compared to younger patients. Conclusions: In breast cancer, AR is expressed and is controlled by receptor TKs through the PI3K-mTOR pathway. An increased anti-proliferative effect is observed with the combination of bicalutamide and Erk1/2 inhibitors. AR expression correlates with age at diagnosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-04.
Abstract 5292: MicroRNA signatures predictive of response to chemotherapy in mCRC.
Authors: Sonia Molina-Pinelo, Amancio Carnero, Fernando Rivera, Purificacion Estevez-Garcia, Jose M. Bozada, Maria L. Limon, Javier Gomez, Maria D. Pastor, Rocio Suarez, Luis G. Paz-Ares, Fernando de la Portilla, Andres Carranza, Isabel Sevilla, Luis Vicioso, Rocio Garcia Carbonero
Journal: Cancer Research (2013)

Abstract MicroRNAs (miRNAs) are post-transcriptional regulators involved in numerous biological and pathological processes including colorectal cancer (CRC). From a clinical perspective, several studies have identified groups of miRNAs with potential utility for early diagnosis or prognostic stratification of CRC patients. However, very few have evaluated the potential ability of miRNA to predict response to selected chemotherapy regimens. The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). We examined tumor expression levels of 667 miRNAs in the training cohort by TaqMan Low Density Arrays (TLDA). In training cohort (N=39), we identified a miRNA molecular signature with significant association in relevant clinical endpoints (objective response, progression-free and overall survival). In validation cohort (N=39), we validated significantly higher expression levels of miR-107, and miR99a* according to objective response to fluoropyrimidine-based regimens. These results support a substantial role for miRNAs in determining drug response, and highlight their potential value as biomarkers for personalized treatment strategies and as a novel class of therapeutic targets. Citation Format: Sonia Molina-Pinelo, Amancio Carnero, Fernando Rivera, Purificacion Estevez-Garcia, Jose M. Bozada, Maria L. Limon, Javier Gomez, Maria D. Pastor, Rocio Suarez, Luis G. Paz-Ares, Fernando de la Portilla, Andres Carranza, Isabel Sevilla, Luis Vicioso, Rocio Garcia Carbonero. MicroRNA signatures predictive of response to chemotherapy in mCRC. [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 5292. doi:10.1158/1538-7445.AM2013-5292
Legislation Regulating Quality Control For Pap Smears
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Legislation Regulating Quality Control For Pap Smears Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 18, 16 November 1988, Pages 1435–1437, https://doi.org/10.1093/jnci/80.18.1435 Published: 16 November 1988
DISECCIÓN ENDOSCÓPICA SUBMUCOSA DE NEOPLASIA GÁSTRICA SOBRE ANASTOMOSIS GASTROENTÉRICA EN ESTÓMAGO REMANENTE. A PROPÓSITO DE 2 CASOS
Authors: A Herreros De Tejada, M Hernández, JL Calleja, C González, I Salas, P Matallanos, E Blázquez, L Abreu
Journal: Endoscopy (2014)

Introducción: La disección submucosa endoscópica (DSE) se ha utilizado con éxito en el tratamiento de cáncer gástrico precoz en estómago con gastrectomía previa. Sin embargo, esta situación determina una mayor dificultad técnica y un mayor riesgo de perforación, particularmente en localización anastomótica
Abstract 4446: A novel nanoparticle drug delivery system: The anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes
Authors: Dongmei Sun, Xiaoyin Zhuang, William Grizzle, Donald Miller, Huang-Ge Zhang
Journal: Cancer Research (2011)

Abstract Monocyte-derived myeloid cells play vital roles in inflammation related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes and the improvement of curcumin bioavailability is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a LPS induced septic shock mouse model and mouse breast tumor model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation related diseases without significant side effects due to innocent bystander or off target effects. 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 4446. doi:10.1158/1538-7445.AM2011-4446
Abstract 367: Engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell-uptake selection
Authors: Zeyu Xiao, Etgar Levy-Nissenbaum, Wataru Aizu, Robert Langer, Omid Farokhzad
Journal: Cancer Research (2011)

Abstract There has been a substantial interest in the development of targeted nanoparticles (NPs) that provide increased efficacy and lower toxicity for cancer therapy. One of the major obstacles has been the paucity of optimal targeting ligands that can discriminate between the expression of antigens on cancer cells and normal cells, and subsequently deliver a therapeutic payload into the cancer cells. Using prostate cancer (PCa) as a model disease, we have addressed the difficulty by developing a “cell-uptake selection” strategy to isolate PCa-specific internalizing 2′-O-methyl RNA aptamers (Apts). Twelve cycles of selection and counter-selection were done to obtain a panel of PCa-specific internalizing Apts, with little or no internalization into non-prostate and normal prostate cells. After Apt characterization, size minimization, improvement of nuclease stabilization, and conjugation of the Apts with fluorescently-labeled polymeric NPs, the NP-Apt bioconjugates exhibit PCa specificity and enhancement in cellular uptake when compared to non-targeted NPs lacking the internalizing Apts. Furthermore, when docetaxel (Dtxl), a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP-Apt, a significant improvement in cytotoxicity was achieved in targeted PCa cells. Further application of this Apt by conjugating with gold nanorods demostrated remarkable anti-tumor efficacy in vivo. To our knowledge, this is the first report of designing selection to enrich cancer cell-specific internalizing aptamers rather than highest affinity aptamers in previously reported selection process. A similar cell-uptake selection strategy may be used for developing specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including drugs and siRNAs, into cells. 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 367. doi:10.1158/1538-7445.AM2011-367
Adrenal Masses of Varied Etiology
Authors: Punit Sharma, Harmandeep Singh, Varun Singh Dhull, Sudhir Suman KC, Abhishek Kumar, Chandrasekhar Bal, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2013)

A wide spectrum of benign and malignant diseases can present as an adrenal mass. Combined PET-CT is useful for evaluation of adrenocortical and adrenomedullary masses. F-FDG has been extensively used as PET radiotracer for this purpose. F-FDOPA PET, Ga-DOTA peptide (Ga-DOTANOC/TATE) PET, and C-HED PET have also been used for imaging of adrenal medullary lesions, whereas C-MTO PET has been used for adrenocortical imaging. We provide a review of imaging characteristics of adrenal gland pathologies on PET-CT using different tracers.
Abstract LB-406: A genetic variant near the PMAIP1/Noxa gene is associated with increased bleomycin sensitivity and cancer risk
Authors: Jian Gu, Yuanqing Ye, Margaret Spitz, Jie Lin, Lambertus A. Kiemeney, Jingliang Xing, Michelle AT Hildebrandt, Waun Ki Hong, Christopher I. Amos, Xfeng Wu
Journal: Cancer Research (2010)

Abstract Background: Mutagen sensitivity, a measurement of chromatid breaks induced by various mutagens in short-term cultures of peripheral blood lymphocytes, is an established risk factor for a number of cancers and is highly heritable. The purpose of this study is to identify genetic predictors of mutagen sensitivity. Methods: We conducted a multi-stage genome wide association study (GWAS). The primary scan analyzed 539,437 autosomal SNPs in 673 healthy individuals, followed by validations in two independent sets of 575 and 259 healthy individuals, respectively. Results: One SNP, rs8093763, on chromosome 18q21showed consistent association with bleomycin sensitivity (combined P = 2.64×10-8). We observed consistently lower bleomycin-induced chromotid breaks for genotypes containing wild type allele compared with the homozygous variant genotype in the discovery set (0.71 vs. 0.90, P=3.77×10-5), in replication phase one (0.61 vs. 0.84, P=7.00×10-5), and in replication phase two (0.65 vs. 0.68, P=0.44). This SNP is approximately 64 kb from the PMAIP1/Noxa gene, which is a radiation- and bleomycin-inducible gene and exhibits significantly higher expression in bleomycin-sensitive lymphoblastoid cell lines than insensitive cell lines upon bleomycin treatment. This SNP also appeared to increase the risk of lung cancer and bladder cancer in two large case control studies. Conclusions: We identified a biologically plausible genetic variation on 18q21 near PMAIP1/Noxa gene that is associated with bleomycin sensitivity. The homozygous variant genotype exhibited higher bleomycin sensitivity and increased risks of lung cancer and bladder cancer. 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 LB-406.
No Way Out
Authors: Toby Reynolds
Journal: BMJ (2007)

African Americans made up 12% of the population of the United States in the 1950s but only 2% of the medical workforce. That this proportion is now a somewhat more representative 6% may have been helped a little by a change in Hollywood medical stereotypes, the first step in which was Joseph Mankiewicz's shocking and provocative No Way Out , starring Sydney Poitier in his first credited screen appearance.

When the film was released, segregation had only recently been abolished in the army and would remain legal in schools for another four years …
Phase II trial of extended dose anti-CTLA-4 antibody ipilimumab (formerly MDX-010) with a multi-peptide vaccine for resected stages IIIC and IV melanoma
Authors: J. S. Weber, S. Targan, R. Scotland, J. Snively, M. Garcia, M. Yellin, S. Fischkoff, G. Nichol
Journal: Journal of Clinical Oncology (2006)

2510 Background: Ipilimumab is a human anti-CTLA-4 antibody shown to have clinical activity in melanoma and renal cancer that is associated with inflammatory-type adverse events termed immune breakthrough events (IBEs). Methods: 25 patients with resected stages IIIC/IV melanoma received MART-1/gp100/tyrosinase peptides with adjuvant Montanide ISA 51 12 times injected subcutaneously with Ipilimumab at 3 mg/kg intravenously every eight weeks for 12 months. The primary endpoints were toxicity and the achievement of a 40% rate of tolerable IBEs, and 20% or less rate of intolerable adverse events. Immune responses measured by ELISPOT and peptide-tetramer assays, and time to relapse were also assessed. The three melanoma peptides differed from wild type by one amino acid modification to increase HLA binding, and were administered at 1000 mcg/dose each. Results: Median age was 55, with 13 men and 12 women. 15 patients had stage IV, and 10 had stage IIIC resected disease. Thus far, 12/25 (48%) patients had grades 2–3 IBEs; 5 (20%) were dose limiting; 7 had GI toxicity, of which 2 were dose limiting; four had skin toxicity, of which 2 were dose limiting; one patient had hypopituitarism, which was also dose limiting. No patient with dose limiting toxicity required hospitalization and all returned to baseline status with the use of systemic steroids. Serologic assays of IBD-related microbial and auto-antibodies showed that seven of eight patients tested had increases in ANCA IgG or I2 IgA, and 5/8 had increases in ASCA IgA. Four of 25 patients have relapsed with a median of 10 months of follow-up. Two were again rendered NED surgically. The two remaining patients were treated with biochemotherapy, with one CR and one PR. All 25 patients are alive, one with disease. No patient with grade 2–3 IBEs has relapsed. ELISPOT assays showed that 10/11 patients tested responded in fresh PBMC to MART-1 and gp100. Conclusions: These data suggest that IBEs are associated with clinical benefit in patients with resected high-risk melanoma receiving Ipilimumab at 3 mg/kg with a peptide vaccine, and support testing the current regimen in a larger randomized trial. [Table: see text]