tbuckley/cabot-search huggingface dataset:
AB0325 Comparison of Activity Score DAS28-ESR and DAS28 -CRP in Patients with Rheumatoid Arthritis
Authors: I. Ben Slama, F. Allali, S. El Kabbaj, T. Lakhdar, L. Medrare, A. Ngeuleu, H. Rkain, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To compare the disease activity score (DAS)28- ESR versus DAS28 -CRP, and to determine the factors that might influence their difference. <h3>Methods</h3> Patients with RA were included in a cross-sectional study. We have collected the demographic characteristics and the characteristics of the RA: duration of evolution, morning stiffness in minutes, functional impact of the disease assessed by the HAQ (Health Assessment Questionnaire), and current corticosteroid dose. The disease activity was assessed by the DAS28-ESR and DAS28-CRP. A simple correlation between DAS28-ESR and DAS28-CRP was performed. We considered a difference between DAS28-ESR and DAS28-CRP as significant when it is greater than or equal to 0.6 [1]. Factors influencing this difference were tested by univariate then multivariate logistic regression. <h3>Results</h3> 103 patients were included with a female predominance (87.4%). Mean age was 49.7±11.4 years. Median disease duration was 8 years [3-14]. There was a strong positive correlation between the two indexes of 0.91 (p&lt;0.001), although the DAS28-ESR value obtained was higher than that of DAS28-CRP at approximately 90% of the visits (n=93). Significantly, the difference between both indexes was higher than 0.6 in 42.7% of the visits studied (n=44). In univariate analysis the difference between DAS28-ESR and DAS28 -CRP was associated with a significant pain intensity (OR =1.069, 95% CI [1045-1094], p&lt;0.0001), a prolonged morning stiffness (OR =1.022, 95% CI [1011-1034], p&lt;0.0001), a significant functional impairment (OR =5.430, 95% CI [2738-10767], p&lt;0.0001), a high dose of steroids (OR =1.276, 95% CI [1026-10467], p=0.029). The multivariate analysis showed that factors remained significantly associated with this difference was the intensity of severe pain (OR =1.052, 95% CI [1023-1082], p&lt;0.0001) and HAQ (OR =2.502, 95% CI [1106-5656], p=0.028). <h3>Conclusions</h3> Our study shows a strong positive correlation between the DAS28-ESR and DAS28 -CRP. But DAS VS 28 would be higher than the DAS28 CRP in patients with high pain intensity and significant functional impairment. <h3>References</h3> Are the C-reactive protein values and erythrocyte sedimentation rate equivalent when estimating the 28-joint disease activity score in rheumatoid arthritis? Clin Exp Rheumatol. 2008 Sep-Oct;26(5):769-75. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5807
Abstract 1501: Tumor cells engineered to codisplay on their surface 4-1BBL and LIGHT costimulatory proteins as a novel vaccine approach for cancer immunotherapy
Authors: Rajesh K. Sharma, Esma S. Yolcu, Kutlu G. Elpek, Haval Shirwan
Journal: Cancer Research (2010)

Abstract Therapeutic vaccines based on whole tumor cells genetically modified to express various immunomodulatory molecules represent an important modality for the treatment of cancer. However, generation of genetically modified tumor cells as vaccine is not only cost, labor, and time intensive, but also has safety repercussions. As an alternative, we have recently developed the ProtEx™ technology that involves modification of the cell membrane with biotin and engineering of biotinylated cells with proteins of interest chimeric with core streptavidin. We herein tested if tumor cells can be engineered efficiently to simultaneously display on their surface two SA-chimeric costimulatory ligands, SA-4-1BBL and SA-LIGHT, and if vaccination with such engineered cells has better therapeutic efficacy than cells displaying single molecule in the TC-1 cervical cancer mouse model. The choice of 4-1BBL is due to pleiotropic immune activity of 4-1BBL to stimulate innate, adaptive immune responses as well as overcome various immune evasion mechanisms. The choice of LIGHT is due to its stimulatory effects on tumor stroma, which pose a physical barrier to the entry of effector immune cells to tumor site. Biotinylated TC-1 tumor cells codisplayed both chimeric costimulatory ligands on their surface with equal efficiency after incubation with equal molar of SA-4-1BBL and SA-LIGHT proteins. Vaccination with irradiated TC-1 tumor cells codisplaying both chimeric costimulatory ligands resulted in the generation of antigen specific T cell proliferative and killing responses, resulting in 100% efficacy in prophylactic and &amp;gt; 57% efficacy in therapeutic settings. In marked contrast, vaccination with TC-1 tumor cells displaying on their surface either of these molecules singly only delayed the tumor growth in the prophylactic setting. Vaccine efficacy was associated with effective generation of primary and memory T cell and Ab responses, enhanced CD8+ T cell infiltration into the tumor, IFN-γ production, and tumor-specific killing. In conclusion, engineering tumor cells in a rapid and effective manner to simultaneously display on their surface a collection of immunostimulatory molecules with distinct immune functions presents a novel approach with considerable potential for cancer immunotherapy. Funded in parts by NIH 2R44 AI071618-02, R43 AI074176, R41 CA121665, KLCP, the W.M. Keck Foundation, and the Commonwealth of Kentucky Research Challenge Trust Fund. 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 1501.
Whole blood FPR1 mRNA expression identifies both non-small cell and small cell lung cancer
Authors: Scott M. Morris, Anil Vachani, Harvey I. Pass, William N. Rom, Glen J. Weiss, D Kyle Hogarth, George Runger, Robert J. Penny, Kirk Ryden, Donald Richards, W Troy Shelton, David W. Mallery
Journal: Journal of Thoracic Oncology (2016)
Abstract 3962: Wnt signaling modulates the Hedgehog pathway by stabilizing GLI1 mRNA
Authors: Felicite Noubissi, Srikanta Goswami, Nicholas A. Sanek, Kazuyuki Kawakami, Toshinari Minamoto, Amy Moser, Yevgenya Grinblat, Vladimir S. Spiegelman
Journal: Cancer Research (2010)

Abstract Wnt and Hedgehog signaling pathways play central roles in embryogenesis, stem cell maintenance, and tumorigenesis. These two pathways being fundamental in the coordination of developmental transitions, have been postulated to interact, or cross-regulate at multiple levels yet the mechanisms of these interactions are not well-understood. Here, we show that Wnt signaling pathway stimulates the transcriptional output of Hedgehog signaling. We demonstrate that Wnt/β-catenin signaling induces the expression of an RNA-binding protein, CRD-BP, which, in turn, binds and stabilizes GLI1 mRNA, causing an elevation of GLI1 expression and transcriptional activity. The newly described mode of regulation of GLI1 appears to be important to several functions of Wnt, including survival and proliferation of colorectal 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 3962.
Diabetes, obesity, and survival in a large cohort of early-stage breast cancer patients.
Authors: S. H. Giordano, S. Jiralerspong, A. Lopez, L. Feng, E. S. Kim, A. M. Gonzalez-Angulo, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2010)

1503 Background: Diabetes and obesity have risen to epidemic proportions globally. Both conditions, which share overlapping etiologies, are associated with worse breast cancer (BC) outcomes in some but not all studies. To address these inconsistencies, we examined the relationship between diabetes, body mass index (BMI), and survival in a large cohort of early-stage BC patients. Methods: We retrospectively studied patients treated at M.D. Anderson from 1996-2005. For comparison, the patients were divided into diabetic (DM) and non-diabetic (ND) groups and into 3 BMI classes: normal or underweight (N, BMI < 25), overweight (Ov, BMI 25-30), and obese (Ob, BMI ≥ 30). Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier product and compared among groups via the log-rank test. Multivariate analysis was conducted via Cox proportional hazards models. Results: There were 6,106 patients. Median age was 52 (range 19-91). 93% had stage I-II disease, 7% stage III. 77% were hormone-receptor (HR) positive, 18% HER2-positive. 476 patients had DM (7.8%). Patients distributed into BMI classes as follows: N 40%, Ov 31%, Ob 29%. By chi-squared tests, diabetes was associated with increasing age, stage, and BMI; and higher BMI was associated with increasing age, stage, grade, and diabetes. At a median follow-up of 5.4 years, there were 488 recurrences and 921 deaths. RFS and OS were significantly worse in DM vs. ND patients (p < 0.001 and p < 0.001, respectively), and in the high vs. low BMI groups (p < 0.001 and p > 0.002, respectively). After adjustment for DM status, BMI, age, stage, grade, and HR status, DM patients had decreased RFS (hazard ratio [hr], 1.22; 95% CI > 0.99,1.50; p > 0.065) and OS (hr, 1.40; 1.11,1.78; p > 0.005). In the same model, Ob vs N patients had decreased RFS (hr, 1.15; 0.99,1.33; p > 0.065) and OS (hr, 1.26; 1.06,1.50; p > 0.010). Conclusions: In this large cohort of early-stage BC patients, diabetes and obesity each correlated with a significant decrease in OS, as well as a borderline significant decrease in RFS, after adjustment for DM status, BMI, age, stage, grade, and HR status. Further studies to discover the reasons for these poorer outcomes in diabetic and obese breast cancer patients are underway. No significant financial relationships to disclose.
5-Azacytidine Selectively Increases γ-Globin Synthesis in a Patient with β<sup>+</sup>Thalassemia
Authors: Timothy J. Ley, Joseph DeSimone, Nicholas P. Anagnou, George H. Keller, R. Keith Humphries, Patricla H. Turner, Neal S. Young, Paul Heller, Arthur W. Nienhuis
Journal: New England Journal of Medicine (1982)

5-Azacytidine is a cytidine analogue that is capable of activating repressed genes in tissue-culture cells and has been shown to increase hemoglobin-F production in anemic baboons. This drug was administered to a patient with severe beta-thalassemia in an attempt to stimulate hemoglobin-F production. After seven days of 5-azacytidine treatment, gamma-globin synthesis increased approximately sevenfold, temporarily normalizing the patient's unbalanced globin synthesis. Erythropoiesis became more effective, leading to a temporary increase in the absolute reticulocyte count (from 5000 to 22,000 per cubic millimeter) and in hemoglobin concentration (from 8.0 to 10.8 g per deciliter). Hypomethylation of bone-marrow DNA near both the gamma-globin and epsilon-globin genes was directly demonstrated. At the time of peak drug effect, about 7000 gamma-globin messenger RNA molecules were present per erythroid bone-marrow cell, in contrast to 10 to 15 epsilon-globin messenger RNA molecules per cell. 5-Azacytidine selectivity increases gamma-globin synthesis and therefore provides a new approach to the treatment of severe beta-thalassemia. Further studies will be required to evaluate the efficacy, risks, and long-term toxicity of 5-azacytidine (or related compounds) before this approach can be used as a therapy for patients with disorders of hemoglobin synthesis.
Abstract 885: <i>GSTM1</i> CNV and promoter SNPs are associated with REC/SPT and survival after Retinoid Acid treatment for head and neck cancer
Authors: Xuemei Zhang, Maosheng Huang, Xifeng Wu, Susan Kadlubar, Xinfeng Yu, David Caldwell, Jie Lin, Baitang Ning, Fred F. Kadlubar
Journal: Cancer Research (2010)

Abstract Purpose: This study sought to determine if copy number variant (CNV) combined with other genetic variants in the glutatione S-transferase Mu class1 (GSTM1) promoter have an important impact on recurrence and overall survival in head and neck cancer patients after retinoid acid treatment. Experimental Method: This study included 441 head and neck patients treated with retinoid acid. Among these cases, 133 experienced recurrence of disease and/or a second primary tumor, while 308 have single primary disease. TaqMan real-time PCR and direct sequencing were used to determine genetic variants in GSTM1. Recurrence and secondary primary tumor (REC/SPT) were evaluated by logistic regression modeling and overall survival was estimated by Kaplan-Meier analysis using STATA. Results: Regression analysis revealed significantly decreased REC/SPT and increased overall survival in subjects with at least 2 copies of GSTM1 (OR=0.57; 95%CI=0.35-0.95) but not in those with 1 copy of the gene. Kaplan-Meier survival analysis also revealed longer overall survival in patients with at least 2 copies of GSTM1. Allele frequency analysis showed −498 C&amp;gt;G, −426 A&amp;gt;G, −339 C&amp;gt;T polymorphisms were significantly associated with REC/SPT in head and neck cancer patients a(OR 0.12 (0.02-0.87), 0.30 (0.11-0.80) and 1.87 (1.00-3.51), respectively. Further survival analysis demonstrated that the −498G, −426G and −339C alleles significantly increased the overall survival in head and neck cancer subjects. Conclusion: These results suggest the GSTM1 CNV combined with single nucleotide polymorphisms is a better predictor of REC/SPT and overall survival of head and neck cancer after retinoic acid treatment than just measuring the presence/absence of GSTM1. 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 885.
A Patient Found Unresponsive
Authors: Zadok Sacks, Anand Vaidya, Niraj Sharma, Barbara Gottlieb
Journal: New England Journal of Medicine (2012)

An 18-year-old woman was found in an unresponsive state in a park near her college campus. When paramedics arrived, the patient was not talking or communicating but her eyes were open, with the pupils equal in size and reactive to light. She was breathing, had a palpable and rapid pulse, and was moving her arms and legs. High-flow oxygen was administered through a face mask, and the . . .
Abstract 5375: Modulation of circulating regulatory T-cells and MDSCs in high risk melanoma patients treated with neoadjuvant ipilimumab
Authors: Ahmad A. Tarhini, Howard Edington, Lisa H. Butterfield, Stergios Moschos, Hussein Tawbi, Yongli Shuai, Janice Shipe-Spotloe, Margaret Simonetta, Jonas T. Johnson, John M. Kirkwood
Journal: Cancer Research (2012)

Abstract Background: Melanoma regional lymph node and in-transit metastases (stage IIIB-C) carry a high relapse and mortality risk. Neoadjuvant ipilimumab may modulate the host suppressor immune response, enhance antitumor immunity and improve the clinical outcome. Methods: Patients with clinically palpable stage IIIB-C melanoma were treated with induction ipilimumab (10 mg/kg IV q3weeks x2doses) preoperatively and had definitive lymphadenectomy (week ≥ 6), followed by 2 maintenance doses of ipilimumab (q3 weeks). Tissue samples were obtained at baseline and at definitive surgery (after 2 doses of ipilimumab) and blood (serum/PBMC) collected at baseline, 6 weeks, then at 3, 6, 9, 12 months and/or progression. Circulating T-regulatory cells (T-regs) and myeloid derived suppressor cells (MDSC) were monitored utilizing multicolor flow cytometry comparing preoperative (6 weeks) and baseline samples. Results: Twenty nine patients (20 male, 9 female), age 40-87 (median 54) have been enrolled since February/2010 (24 cutaneous primary, 1 unknown and 4 mucosal). Five had AJCC stage IIIB (N2b, N2c) and 24 had IIIC (N3) melanoma. Ninety one cycles have been delivered (median 4). Grade 3 (worst) toxicities include diarrhea/colitis (5 patients; 17%), hepatic enzyme elevations (2; 7%), rash (2; 7%), lipase (1; 3%), all manageable. Median follow-up is 9.7 months and 18 patients (62%) continue disease free. Median PFS is 15.5 months, 95% CI = (8.1, -). The probability of 6 and 12 months PFS is 84.2% (95% CI=0.63, 0.94) and 54.1% (95% CI=0.31, 0.73) respectively. There is a significant increase in the frequency of circulating T-regs (CD4+CD25hi+ Foxp3+; p=0.023 CD4+CD25hi+CD39+; p=0.001) from baseline to 6 weeks. In parallel there is a significant decrease in circulating MDSCs: (1) monocytic: HLA-DR+/low/CD14+; p=&amp;lt;.0001 and less significantly for (2) other monocytic: lin1neg/HLA-DRneg/CD33+/CD11b+; p=0.198 and (3) lymphoid: Lin1neg/HLA-DR-/CD33+/CD11b+; p=0.338. Conclusions: Neoadjuvant ipilimumab is clinically promising and significantly downregulates MDSCs which appear to play a significant role in the clinical activity of ipilimumab. T-regs are upregulated as part of the overall CD4+ T-cell population, and functional studies of this population are ongoing. 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 5375. doi:1538-7445.AM2012-5375
Abstract 5287: Non-invasive imaging of tumor cell death using a Hsp90 ligand
Authors: Danielle Park, Anthony Don, Tania Massamiri, Amol Karwa, Beth Warner, Christine L. Hemenway, Arati D. Naik, Kah-Tiong Kuan, Pierre J. Dilda, Jason Wong, Lori Chinen, Mary Dyszlewski, Philip J. Hogg
Journal: Cancer Research (2011)

Abstract Cell death plays an integral role in physiology, including turnover of cells in the gastrointestinal tract, the menstrual cycle and the immune system. Imbalance of this process is also associated with disease. Excessive cell death is characteristic of vascular disorders, neurodegenerative diseases, myelodysplastic syndromes, ischemia/reperfusion injury and organ transplant rejection, among others. Cell death also plays a role in the treatment of disease. In cancer for example, most chemotherapeutics, radiation treatments and anti-hormonal agents act by inducing death of cancer cells. Given the prevalence of cell death in normal physiology and disease, non-invasive imaging of this process is likely to have wide application in biological research and ultimately in patient diagnosis and management. Common to apoptotic and necrotic death cell is eventual loss of plasma membrane integrity. We have developed a small, synthetic organoarsenical compound (4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid) that rapidly accumulates in the cytosol of dying cells, coincident with loss of plasma membrane integrity. The compound is retained in the cytosol predominantly by covalent reaction with the 90-kDa heat shock protein (Hsp90), the most abundant molecular chaperone of the eukaryotic cytoplasm. The organoarsenical was tagged with either optical or radioisotope reporting groups to image cell death in cultured cells and in murine tumors ex vivo and in situ. Tumor cell death in mice was non-invasively imaged by SPECT/CT using an 111In-tagged compound. This versatile compound has the advantage of chemical stability, exquisite selectivity for dying cells and versatility with respect to the reporting group. The nature and abundance of its cytosolic target, Hsp90, also bodes well for its suitability for the imaging of cell death in most experimental settings. 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 5287. doi:10.1158/1538-7445.AM2011-5287
Resistance to Thyrotropin Caused by Mutations in the Thyrotropin-Receptor Gene
Authors: Thongkum Sunthornthepvarakul, Michael E. Gottschalk, Yoshitaka Hayashi, Samuel Refetoff
Journal: New England Journal of Medicine (1995)

Hormone-resistance syndromes can be broadly defined as conditions resulting from reduced or absent end-organ responsiveness to biologically active hormones. They are caused by defects in hormone receptors or post-receptor defects.1–3 Mutations in the thyroid hormone–receptor β gene cause resistance to thyroid hormone, which is characterized by elevated serum thyroid hormone concentrations with few or no clinical and biochemical manifestations of thyroid hormone excess and, most notably, normal or slightly increased thyrotropin secretion.1 Mutations that inactivate the thyrotropin receptor or the G (guanine nucleotide–binding) protein that couples the receptor to adenylate cyclase should cause thyrotropin resistance, resulting in either hypothyroidism . . .
Kinking, thrombosis and need for re-operation in a patient with a left ventricular assist device
Authors: Rahat Muslem, Sakir Akin, Olivier Manintveld, Kadir Caliskan
Journal: Intensive Care Medicine (2016)

A 42-year-old man was re-hospitalized by acute decompensated heart failure (HF) 4 days after discharge. Physical examination revealed a continuous machinery systolic murmur at the second right intercostal space. Transthoracic echocardiogram showed a slight pericardial effusion and no signs of valve dysfunction. A CT scan showed multiple kinks in the left ventricular assist device (LVAD) outflow graft (Fig. 1). The patient underwent reoperation. At surgery, several clots around the outflow graft and mediastinum were removed, and three kinks near the excessive long outflow graft were confirmed. We performed an uneventful LVAD replacement. He was discharged the next day from ICU and 14 days later from hospital.
Immunoscintigraphy of an Inflammatory Process in Crohn's Disease With a Technetium-99m-Labeled Fragment (MN3 Fab′) and With an Intact Monoclonal Anti-granulocyte Antibody (Mab BW 250/183)
Authors: EWALD KRESNIK, HANS-JÜRGEN GALLOWITSCH, PETER MIKOSCH, MARIO MOLNAR, OLIVER UNTERWEGER, IRIS GOMEZ, PETER LIND
Journal: Clinical Nuclear Medicine (1999)

A 70-year-old man had Crohns' disease since 1989. He was hospitalized because of abdominal pain with bloody and mucous diarrhea. Enteroscopy and CT showed an inflamed, ulcerous, and edematous colon and distal ileum. Before operation, anti-granulocyte immunoscintigraphy with intact monoclonal antibody (BW 250/183) was performed. Ten days later, scintigraphy using the fragmented antibody (MN3 Fab′) was done. On the scan, the intact Tc-99m-labeled antibody (BW 250/183) detected the inflamed intestine, whereas the fragmented Tc-99m-labeled antibody (MN3 Fab′) failed to detect the infected bowel. After an ileocecal resection, the patient recovered. A histologic examination revealed a chronic erosive bowel process in Crohn's disease.