tbuckley/cabot-search huggingface dataset:
ATPS-11DEXAMETHASONE INDUCES A MESENCHYMAL SHIFT IN GLIOBLASTOMA STEM CELLS
Authors: Markus Luedi, Sanjay Singh, Islam Hassan, Joy Gumin, Eric Sulman, Frederick Lang, Rivka Colen, Pascal Zinn
Journal: Neuro-Oncology (2015)

Dexamethasone is routinely administered to manage cerebral edema in glioblastoma (GBM). Its impact on molecular mechanisms driving GBM invasion is unknown. Utilizing radiogenomic strategies, we previously introduced Periostin as key mediator of GBM associated edema and cellular invasion. We observed that multiple molecular targets of Dexamethasone are significantly upregulated and overlap with Periostin correlated genes, including CEBPB. We hypothesized that Dexamethasone, by regulating Periostin correlated genes, promotes a mesenchymal program of tumor cells including Glioblastoma Stem Cells (GSCs). A panel of GSCs were profiled for Periostin correlated genes after Dexamethasone treatment, using microarray, qPCR and Western blotting. Tests for self-renewal (limiting dilution assay), differentiation (neural lineage marker analysis), invasion (Boyden chamber) and proliferation (BrdU) were performed after Dexamethasone exposure. Three independent GSC lines were used to generate orthotopic tumors and mice were then treated with Dexamethasone (intraperitoneal). Differentially expressed genes in GSC derived tumors (total RNA from cells of human origin were isolated using human specific Anti- HLA Class I ABC antibody by FACS) upon Dexamethasone exposure were evaluated with connectivity map (cmap) to screen for specific therapeutics. Cells treated with Dexamethasone showed an increased CEBPB expression, indicating a more aggressive mesenchymal gene signature. Histopathologic validation of orthotopic tumors supported this effect of Dexamethasone. Treatment with specific, FDA approved therapeutics in combination with Dexamethasone suppressed Periostin correlated gene levels and subsequently reduced this mesenchymal shift. In this preclinical study we showed that Dexamethasone promotes a molecular mesenchymal shift by elevating CEBPB expression levels in both, in vitro and in vivo. These results warrant an evaluation of Dexamethasone for managing edema in glioblastoma patients. Neutralizing side effects of Dexamethasone by adding our shortlisted drugs may improve GBM patient care.
Protein kinase C α inhibition prevents peritoneal damage in a mouse model of chronic peritoneal exposure to high-glucose dialysate
Authors: Le Wang, Michael S. Balzer, Song Rong, Jan Menne, Sibylle von Vietinghoff, Lei Dong, Faikah Gueler, Mi-Sun Jang, Gang Xu, Kai Timrott, Sergey Tkachuk, Marcus Hiss, Hermann Haller, Nelli Shushakova
Journal: Kidney International (2016)
Molecular mechanisms of interethnic differences in irinotecan disposition: Impact of variants in ABCG2
Authors: C. Balram, J. Li, Q. Y Zhou, E. H Tan, R. H. Mathijssen, R. H. van Schaik, J. Verweij, A. Sparreboom, S. D. Baker
Journal: Journal of Clinical Oncology (2005)

2018 Background: ABCG2 is an efflux transporter involved in the biliary secretion of the irinotecan metabolites SN-38 and SN-38 glucuronide (SN-38G). The ABCG2 421C>A polymorphism is associated with decreased protein expression in vitro, and may be associated with increased sensitivity to irinotecan treatment. Here, we evaluated the impact of ABCG2 variants (-19572–19569)delCTCA and 421C>A on the disposition of irinotecan. Methods: Dose-normalized irinotecan pharmacokinetic parameters and ABCG2 genotype were determined in 29 Asian and 31 Caucasian patients receiving the drug as a 1.5-h infusion. Results: ABCG2 421C>A was more common in Asians than Caucasians (allele frequency, 0.29 vs 0.11; P<.05), but ABCG2 (-19572–19569)delCTCA was not. The haplotype frequency of both wild-type alleles at the two loci (CTCA-C) was similar in Asians and Caucasians (0.42 vs 0.45), while those of delCTCA-C (0.29 vs 0.44), CTCA-A (0.25 vs 0.11), and delCTCA-A (0.04 vs 0) were ethnically dependent. Asians had a lower irinotecan area under the curve (AUC, 13 ± 5.5 vs 21 ± 6.6 μg.h/ml; P < .0001) and a higher SN-38G AUC (20 ± 11 vs 2.7 ± 1.7 μg.h/ml; P < .0001). SN-38 AUC was higher in Asians (0.53 ± 0.27 vs 0.46 ± 0.37 μg.h/ml; P = .37), as were the AUC ratios of SN-38 to irinotecan (REC, 0.044 ± 0.020 vs 0.021 ± 0.010) and SN-38G to SN-38 (REG, 54 ± 62 vs 7.5 ± 5.1; P < .0001). In 21 patients with at least one variant ABCG2 421C>A allele, the mean REC and SN-38G AUC were 42% and 74% higher, respectively, than those with the wild-type sequence (P < .05); SN-38 AUC was 44% higher in those with the variant allele (P = .08). Patients with the combined CTCA-A genotype for the two variants had an increased REC compared to the delCTCA-C genotype group (0.047 ± 0.027 vs 0.026 ± 0.015; P < .05). Conclusions: ABCG2 genotype status accounts, in part, for the observed differences in irinotecan disposition between Asian and Caucasian cancer patients. No significant financial relationships to disclose.
Six Months Evaluation Of Pathogens and Drug Resistance In Blood Cultures From Hematoogy Patients With Febrile Neutropenia. Casablanca University Hospital Experience
Authors: Benzaid Hanane, Hachmane Soukaina, Khoubila Nisrine, El Kadiou Fatima, Ouhadous Mohamed, Igala Marielle, Benbachir Mohamed, Zerouali Khalid
Journal: Blood (2013)
Effect of ipilimumab at 10 mg/kg on disease control in patients (pts) with M1c-stage melanoma in relation to baseline lactate dehydrogenase (LDH) levels
Authors: M. Smylie, S. Francis, B. Neyns, M. Maio, D. Minor, C. Verschraegen, K. Chin, R. Ibrahim, A. Hoos, D. Schadendorf
Journal: Journal of Clinical Oncology (2009)

9041 Background: Ipilimumab, a fully human, anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody, enhances antitumor immunity. Ipilimumab is clinically active in advanced melanoma, with a 1-year survival rate of ∼50% in Phase II studies (Wolchok et al. CRI-CVC annual meeting 2008. Oral presentation). Serum LDH level is an independent prognostic factor for malignant melanoma, and is strongly predictive of reduced survival in stage IV disease (Bedikian et al. J Clin Oncol. 2006;24:4738–4745.). This analysis evaluated the association between baseline LDH levels and disease control (stable or reduced measurable tumor burden) in previously treated pts with M1c-stage melanoma (metastasis to vital organs other than the lungs) who received ipilimumab in 2 recently completed Phase II studies (CA184008 and 022). Methods: Ipilimumab at 10 mg/kg was given every 3 weeks (Q3W) × 4; eligible pts could continue to receive ipilimumab Q12W beginning at Week 24. In study 022, pts were randomized to receive ipilimumab induction dosing at 0.3, 3.0, or 10 mg/kg Q3W × 4; study 008 was a single- arm trial of ipilimumab at 10 mg/kg. Disease control data were pooled from the 2 Phase II studies for pts treated with ipilimumab at 10 mg/kg and stratified by normal and elevated (&gt;1× upper normal limit [UNL]) LDH levels. Elevated LDH was not capped. Results: For 227 pts treated at 10 mg/kg, 123 had M1c-stage disease: 42 had normal LDH and 81 had LDH &gt;1 × UNL (of which 32 had LDH 2 × UNL). Among these 123 pts, 17/81 (21.0%) [95% CI 12.7–31.5] with elevated LDH levels experienced disease control, whereas 12/42 (28.6%) [95% CI 15.7–44.6] with LDH levels at or below the UNL experienced disease control. Conclusions: Our data show that ipilimumab exerts similar disease control in pts with normal and elevated LDH levels. Ipilimumab therefore appears to have clinical activity in the form of disease control in pts with a very poor prognosis, i.e., M1c-stage melanoma and elevated LDH levels. [Table: see text]
Gaze discrimination in patients with schizophrenia: preliminary report
Authors: R B Rosse, K Kendrick, R J Wyatt, A Isaac, S I Deutsch
Journal: American Journal of Psychiatry (1994)

The authors administered a gaze discrimination task to 24 patients with chronic schizophrenia and 25 subjects with no psychiatric history. Each subject was shown slides and asked, "Is the person in the slide looking directly at you?" Patients with schizophrenia were more likely than comparison subjects to perceive the person in the slide as looking at them when the person was looking away. Because there is evidence that gaze discrimination performance involves the superior temporal sulcus region of the brain and this region has been implicated in theories about the pathogenesis of schizophrenia, further study of the gaze discrimination task seems indicated.
Nab-Paclitaxel (Nab-P) Plus Gemcitabine (Gem) Vs Gem Alone for Patients (Pts) with Metastatic Pancreatic Cancer (Pc): Subgroup Analyses of the Mpact Trial Based on the Presence of Liver Metastases (Lms) and Number of Metastatic Sites
Authors: C. Weekes, F. Parnis, J. Thaler, H. Prenen, R. Letourneau, E. Raymond, A. Santoro, R. Garcia-Carbonero, J. Weis, A. Romano, D. McGovern, D. Penenberg, D.D. Von Hoff
Journal: Annals of Oncology (2014)
GPCR Signaling Mediates Tumor Metastasis via PI3Kβ
Authors: Bassem D. Khalil, Christine Hsueh, Yanyan Cao, Widian F. Abi Saab, Yarong Wang, John S. Condeelis, Anne R. Bresnick, Jonathan M. Backer
Journal: Cancer Research (2016)

Abstract Inappropriate activation of PI3K signaling has been implicated strongly in human cancer. Although studies on the role of PI3K signaling in breast tumorigenesis and progression have focused most intensively on PI3Kα, a role for PI3Kβ has begun to emerge. The PI3Kβ isoform is unique among class IA PI3K enzymes in that it is activated by both receptor tyrosine kinases and G-protein–coupled receptors (GPCR). In previous work, we identified a mutation that specifically abolishes PI3Kβ binding to Gβγ (p110526KK-DD). Expression of this mutant in p110β-silenced breast cancer cells inhibits multiple steps of the metastatic cascade in vitro and in vivo and causes a cell autonomous defect in invadopodial matrix degradation. Our results identify a novel link between GPCRs and PI3Kβ in mediating metastasis, suggesting that disruption of this link might offer a novel therapeutic target to prevent the development of metastatic disease. Cancer Res; 76(10); 2944–53. ©2016 AACR.
Abstract 12465: Dabigatran in Real World of Atrial Fibrillation: Systematic Review and Meta-analysis of Comparison Studies With Vitamin K Antagonists
Authors: João Carmo, Francisco M Costa, Jorge Ferreira, Miguel Mendes
Journal: Circulation (2015)

Background: In the clinical trial RE-LY, dabigatran showed a better efficacy/safety profile in comparison with warfarin, but clinical trials are few representative of the real world. We aim to access if dabigatran in real-world patients with atrial fibrillation (AF) showed a better profile in comparison with warfarin, through a systematic review and meta-analysis of observational studies comparing with vitamin K antagonists. Methods: PubMed, Embase and Scopus databases were searched through December 2014. We include observational studies comparing dabigatran to warfarin for non-valvular AF that reported clinical events during a follow-up for dabigatran 75mg, 110 mg or 150 mg, and warfarin. We proceeded to the extraction and analysis of data for clinical thromboembolic events, bleeding and mortality. Data were pooled by meta-analysis using a random-effects model. Results: We selected 9 studies involving a total of 291,703 patients, 85,399 treated with dabigatran and the remaining 206,304 with warfarin. The incidence of stroke was 1.71 / 100 patient-years for dabigatran and 2.44 / 100 patient years for warfarin (relative risk [RR] 0.91, 95% CI 0.66 to 1.27, p=0.58). The major bleeding rate was 3.90 / 100 patient-years for dabigatran and 3.92 / 100 patient years for warfarin (RR 0.90; 0.78 to 1.03, p=0.11). The all-cause mortality (RR 0.81, 0.75-0.88, p&lt;0.001) and intracranial hemorrhage (RR 0.45, from 0.27 to 0.76, p=0.002) were significantly lower in patients treated with dabigatran in comparison to those treated with warfarin. There were no significant differences in risk of myocardial infarction (RR 0.55; 0.29 to 1.07, p=0.08), total hemorrhage (RR 1.00; 0.57 to 1.77, p=0.99), and gastro-intestinal bleeding (RR 1.14; 0.78 to 1.69, p=0.50). Conclusions: In this combined analysis of observational studies of real world, dabigatran compared to warfarin was associated with a similar risk of stroke, myocardial infarction, major bleeding, total bleeding and gastrointestinal bleeding, and a lower risk of intracranial hemorrhage and mortality.
Effect of BCG Immunotherapy on &lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-methylurea-Induced Carcinogenesis of Guinea Pig Colon&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G L Cockerell, R W O'Donnell, W L Kriedemann, D A Amato, B W Turnbull
Journal: JNCI Journal of the National Cancer Institute (1984)

A total of 480 guinea pigs each received twice weekly intrarectal instillations of 1 mg N-nitroso-N-methylurea (NMU) during 14-35 weeks (total dose NMU, 28-70 mg) to induce colon neoplasms. At 24, 28, or 35 weeks after the start of NMU instillation, the distal colon was exposed by a ventral laparotomy and suspected neoplastic lesions were treated by one of four methods: A, intratumoral instillation of an emulsion of killed BCG cell walls attached to oil droplets; B, intratumoral instillation of a control emulsion of killed BCG cell walls in an aqueous phase rather than lipid phase; C, surgical excision of the colon lesion with formation of a ventral diverting colostomy; or D, sham operation (no treatment). All guinea pigs were allowed to recover from surgery and were then observed for a period of 1 year for the study of the effects of these treatments on NMU-induced colon neoplasms. Colon neoplasms were produced in 76% of all sham-operated control guinea pigs, and the frequency of such neoplasms was dependent on the total dose of NMU. Most neoplasms were adenocarcinomas with invasion of the bowel wall but only approximately 5% of them metastasized. Treatment with BCG failed to alter the course of NMU-induced colon carcinogenesis, as determined by the frequency of colon neoplasia, the number, the gross, or microscopic characteristics of colon neoplasms, or the rate of survival.
AB0148 Vitamin D Deficiency in Rheumatoid Arthritis, Ankylosing Spondylitis and Psoriatic Arthritis. Results of the Carma Study
Authors: A. Urruticoechea Arana, M.A. Martin Martinez, S. Castañeda, C.A.S. Piedra, C. Gonzalez Juanatey, J. Llorca, F. Diaz Gonzalez, M.A. Gonzalez-Gay
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To study the association between vitamin D levels and the clinical characteristics of patients with chronic inflammatory rheumatic diseases (CIRD). <h3>Methods</h3> Analysis of data from the baseline visit of the CARMA project (CARdiovascular in rheuMAtology); a 10-year prospective study evaluating the risk of cardiovascular events in a cohort of rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients, and a cohort of unexposed matched individuals who attended rheumatology outpatient clinics from 67 hospitals in Spain. Sociodemographic characteristics, comorbidities, and disease activity of CIRD were analyzed. Patients were defined as having vitamin D deficiency if 25-OH vitamin D levels were &lt;20 ng/ml <h3>Results</h3> 2.234 patients (775 RA, 738 AS and 721 PsA) and 677 unexposed subjects were assessed. The median [p25-p75] 25-OH vitamin D levels were: 20.4 [14.4-29.2] ng/ml in RA, 20.9 [13.1-29.0] in AS, 20.0 [14.0-28.8] in PsA and 24.8 [18.4-32.6] ng/ml in unexposed controls. Vitamin D deficiency was detected in 40.5% RA, 39.7% AS, 40.9% PsA and 26.7% unexposed cohort (p&lt;0.001). A positive association between CIRD and vitamin D deficiency was found: adjusted (adj.) OR=2.28 (95% CI=1.77-2.93) in RA, 1.94 (95% CI=1.44-2.60) in AS and 1.99 (95% CI=1.54-2.58) in PsA (p&lt;0.001). A significant association between vitamin D deficiency and anti-cyclic citrullinated peptide antibodies (ACPA) in RA and BASFI in AS was also found. However, no association between vitamin D deficiency and other disease parameters was observed. <h3>Conclusions</h3> Patients with CIRD show an increased risk of having vitamin D deficiency compared to unexposed matched individuals. ACPA and BASFI were the main factors associated with vitamin D deficiency in RA and AS, respectively <h3>Disclosure of Interest</h3> A. Urruticoechea Arana: None declared, M. A. Martin Martinez: None declared, S. Castañeda: None declared, C. A. Piedra: None declared, C. Gonzalez Juanatey: None declared, J. Llorca: None declared, F. Diaz Gonzalez: None declared, M. A. Gonzalez-Gay Grant/research support from: This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results and preparation of the manuscript has been done independently of Abbvie. Dr. González-Gay9s studies have been supported by grants from "Fondo de Investigaciones Sanitarias" PI06/0024, PS09/00748 and PI12/00060, and RD12/0009/0013 (RIER) from "Instituto de Salud Carlos III" (ISCIII) (Spain).
Different Deficiencies in the Prevention of Tumorigenic-Low-Metastatic Murine K-1735b Melanoma Cells From Producing Metastases&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S L Aukerman, J E Price, I J Fidler
Journal: JNCI Journal of the National Cancer Institute (1986)

To produce metastasis, malignant tumor cells must be able to complete a sequence of many steps that depend not only on tumor cell properties but also on ability of the tumor cells to interact effectively with host homeostatic mechanisms to avoid destruction. Therefore, it should be possible to isolate clonal populations non- or low metastatic. In a study of K-1735 clones introduced into normal syngeneic hosts, the reasons for the lack of or low ability of metastasis production did indeed differ among different clones. Some clones were identified that were low metastatic in syngeneic C3H/HeN mice because of antigenic characteristics. Others failed to give rise to metastases because they could not survive and grow once arrested in the lung parenchyma. These data suggested that the success of future studies dealing with genetic analysis of the metastatic phenotype could depend on the use of appropriate tumor cell populations.
Special issues regarding psychotherapy with the deaf
Authors: M F Hoyt, E Y Siegelman, H S Schlesinger
Journal: American Journal of Psychiatry (1981)

The authors interviewed 10 therapists and supervisors who had clinical experience in working with deaf patients. The responses centered on issues related to the necessity of visual rather than auditory communication, problems of diagnosis and assessment, therapist and patient expectations, special strengths of deaf patients, involvement of third parties, and modification of therapeutic technique. The authors emphasize that additional resources and research are necessary for clinicians to meet the needs of this large but still underserved population.
Marital Status and Incidence of Ovarian Cancer: The U. S. Third National Cancer Survey, 1969–712
Authors: Noel S. Weiss, John L. Young, Gilbert J. Roth
Journal: JNCI Journal of the National Cancer Institute (1977)

As determined in the U.S. Third National Cancer Survey, 1969–71, the incidence of ovarian cancer was 60–70% higher in women who had never married than in those who had. This relationship was present in both whites and blacks and in all age groups over 25 years. Among ovarian epithelial tumors, those for which the incidence rates between never-married and ever-married women differed most were endometrioid and clear cell tumors. The incidence of tumors of germ cell and sex cord-mesenchyme origin, however, showed no relationship to marital status.
How to Monitor Patients with Chronic Myelogenous Leukemia
Authors: Michael E O'Dwyer
Journal: Journal of the National Comprehensive Cancer Network (2003)

The introduction of imatinib has radically altered the treatment options and, perhaps, prognosis for patients with newly diagnosed chronic myelogenous leukemia (CML). However, although the majority of patients appear to benefit from this agent, it is important to recognize as early as possible the patients who experience a sub-optimal response and those who may be at risk of disease progression. This article reviews current available methods of monitoring and provides recommendations for appropriate follow up of imatinib-treated patients.
Targeted Inactivation of Murine Band 3 (AE1) Gene Produces a Hypercoagulable State Causing Widespread Thrombosis In Vivo
Authors: Hani Hassoun, Ying Wang, John Vassiliadis, Mohini Lutchman, Jiri Palek, Leo Aish, Irene S. Aish, Shih-Chun Liu, Athar H. Chishti
Journal: Blood (1998)
Lifetime perturbations of bipolar disorder [clinical conference]
Authors: D G Blazer
Journal: American Journal of Psychiatry (1996)

This woman initially presented with a question that not infrequently arises in medical practice, i.e., “Why am I taking this medicine?” In this case, ongoing use of a neuroleptic medication as she aged placed this woman at increased risk for tardive dyskinesia. Therefore, a thorough evaluation of the rationale for the mcdication’s initial prescription and its current use was in order. The first task of the psychiatrist was to ascertain, as well as
Neuroendocrine Prostate Cancer (Nepc) in Patients (Pts) with Metastatic Castration Resistant Prostate Cancer (Mcrpc) Resistant to Abiraterone (Abi) or Enzalutamide (Enz): Preliminary Results from the Su2C/Pcf/Aacr West Coast Prostate Cancer Dream Team (Wcdt)
Authors: E.J. Small, J. Youngren, J. Alumkal, C. Evans, C.J. Ryan, P. Lara, T. Beer, O. Witte, R. Baertsch, J. Stuart
Journal: Annals of Oncology (2014)
Confirmation That a Specific Haplotype of the Dopamine Transporter Gene Is Associated With Combined-Type ADHD
Authors: Philip Asherson, Keeley Brookes, Barbara Franke, Wai Chen, Michael Gill, Richard P Ebstein, Jan Buitelaar, Tobias Banaschewski, Edmund Sonuga-Barke, Jacques Eisenberg, Iris Manor, Ana Miranda, Robert D Oades, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Hans-Christoph Steinhausen, Stephen V Faraone
Journal: American Journal of Psychiatry (2007)

The primary purpose of this study was to confirm the association of a specific haplotype of the dopamine transporter gene and attention deficit hyperactivity disorder (ADHD), which could be one source of the heterogeneity seen across published studies.The authors previously reported the association of ADHD with a subgroup of chromosomes containing specific alleles of two variable-number tandem repeat polymorphisms within the 3' untranslated region and intron 8 of the dopamine transporter gene. They now report on this association in a sample of ADHD combined-type probands.The original observations were confirmed, with an overall odds ratio of 1.4 across samples.These data challenge results of meta-analyses suggesting that dopamine transporter variation does not have an effect on the risk for ADHD, and they indicate that further investigation of functional variation in the gene is required.
Some Special Views in Bone Scanning
Authors: HENRI E. SCH??TTE
Journal: Clinical Nuclear Medicine (1980)

Radionuclide bone scanning may sometimes demonstrate increased focal lesions with more or less symmetrical patterns. In the femoral neck, ribs, and axillary margins of the scapulae, these lesions may indicate pseudofractures. In the pelvis, irregular activity of the bladder may cause problems in differentiating between bladder diverticula and pelvic lesions. The routine use of imaging tables and traditional gamma camera views may lead to understating certain scintigraphic patterns and/or diagnosing these as metastatic disease. This article emphasizes the importance of certain special views in recognizing these patterns and making the proper diagnosis.