tbuckley/cabot-search huggingface dataset:
DAT‐positive <i>Plasmodium ovale</i> malaria presenting in a child with sickle cell anemia
Authors: Nicholas S. Whipple, Jason R. Schwartz, Kerri A. Nottage
Journal: American Journal of Hematology (2017)

A 5-year-old Nigerian boy with sickle cell anemia (SCA) presented two weeks after arrival in the United States with fever, lethargy, and altered mental status. Examination revealed hypotension, hypoxia, pallor, and hepatosplenomegaly. Laboratory investigation showed white blood cell count, 36.1 × 109/L; hemoglobin, 3.1 g/dL; platelets, 102 × 109/L; lactate dehydrogenase, 3837 units/L (> 5 × ULN); total bilirubin, 2.8 mg/dL; and direct antiglobulin test (DAT) positive for anti-IgG and anti-C3. Chest X-ray revealed cardiomegaly and a focal infiltrate. He received broad-spectrum antibiotics for treatment of presumed sepsis and acute chest syndrome, transfusion of red blood cells (RBC), and milrinone for high-output cardiac failure. Despite a positive DAT, there were no characteristic features of autoimmune hemolysis on peripheral blood smear; however, close examination revealed trophozoites and gametocytes of Plasmodium species (Image 1, Panel A and B, respectively) with a parasite load of 0.9%. Plasmodium ovale was confirmed by RT-PCR. The patient was successfully treated with quinidine and doxycycline followed by primaquine for eradication of hypnozoites. Patients with SCA have an increased risk of life-threatening anemia and death from malaria infection; prompt initiation of therapy improves outcomes. Malarial infection (most commonly Plasmodium falciparum) can induce DAT-positive hemolytic anemia and further exacerbate RBC destruction through several potential mechanisms, including host antibody recognition of parasite antigens coating RBCs and non-specific production of antibodies through malarial-mediated B-cell immunostimulation.1 Peripheral smear examination is critical in patients with SCA presenting with hemolytic anemia, especially those arriving from malaria-endemic countries, even when a common diagnosis (eg, sepsis, splenic sequestration, autoimmune hemolytic anemia) appears plausible. Peripheral blood smear demonstrating trophozoite (Panel A) and gametocyte (Panel B) of Plasmodium ovale in a patient with sickle cell anemia. Nothing to report.
Inhibition of phosphodiesterase 4 (PDE4) reduces dermal fibrosis by interfering with the release of interleukin-6 from M2 macrophages
Authors: Christiane Maier, Andreas Ramming, Christina Bergmann, Rita Weinkam, Nicolai Kittan, Georg Schett, Jörg H W Distler, Christian Beyer
Journal: Annals of the Rheumatic Diseases (2017)

To investigate the disease-modifying effects of phosphodiesterase 4 (PDE4) inhibition in preclinical models of systemic sclerosis (SSc).We studied the effects of PDE4 inhibition in a prevention and a treatment model of bleomycin-induced skin fibrosis, in the topoisomerase mouse model as well as in a model of sclerodermatous chronic graft-versus-host disease. To better understand the mode of action of PDE4 blockade in preclinical models of SSc, we investigated fibrosis-relevant mediators in fibroblasts and macrophages from healthy individuals and patients suffering from diffuse-cutaneous SSc on blockade of PDE4.Specific inhibition of PDE4 by rolipram and apremilast had potent antifibrotic effects in bleomycin-induced skin fibrosis models, in the topoisomerase I mouse model and in murine sclerodermatous chronic graft-versus-host disease. Fibroblasts were not the direct targets of the antifibrotic effects of PDE4 blockade. Reduced leucocyte infiltration in lesional skin on PDE4 blockade suggested an immune-mediated mechanism. Further analysis revealed that PDE4 inhibition decreased the differentiation of M2 macrophages and the release of several profibrotic cytokines, resulting in reduced fibroblast activation and collagen release. Within these profibrotic mediators, interleukin-6 appeared to play a central role.PDE4 inhibition reduces inflammatory cell activity and the release of profibrotic cytokines from M2 macrophages, leading to decreased fibroblast activation and collagen release. Importantly, apremilast is already approved for the treatment of psoriasis and psoriatic arthritis. Therefore, PDE4 inhibitors might be further developed as potential antifibrotic therapies for patients with SSc. Our findings suggest that particularly patients with inflammation-driven fibrosis might benefit from PDE4 blockade.
Factors Associated with Clinical Outcomes of 483 Allogeneic Peripheral Blood Stem Cell Transplants (PBSCT) in Brazil.
Authors: Afonso C. Vigorito, Francisco J.P. Aranha, Gislaine B. Oliveira, Kátia A.B. Eid, Fernanda M. Lodi, Wellington M. Azevedo, Vergílio Colturato, Mair P. De Souza, José C. Barros, Henrique Bittencourt, Lúcia M.R. Silla, Silvia R. Brandalise, Érica R. Pontes, Angelo Maiolino, Márcio Nucci, Milton A. Ruiz, Maria A. Zanichelli, Cármino A. De Souza
Journal: Blood (2004)
<i>Ex Vivo</i> Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy
Authors: Ellie Karekla, Wen-Jing Liao, Barry Sharp, John Pugh, Helen Reid, John Le Quesne, David Moore, Catrin Pritchard, Marion MacFarlane, James Howard Pringle
Journal: Cancer Research (2017)

To improve treatment outcomes in non-small cell lung cancer (NSCLC), preclinical models that can better predict individual patient response to novel therapies are urgently needed. Using freshly resected tumor tissue, we describe an optimized ex vivo explant culture model that enables concurrent evaluation of NSCLC response to therapy while maintaining the tumor microenvironment. We found that approximately 70% of primary NSCLC specimens were amenable to explant culture with tissue integrity intact for up to 72 hours. Variations in cisplatin sensitivity were noted with approximately 50% of cases responding ex vivo Notably, explant responses to cisplatin correlated significantly with patient survival (P = 0.006) irrespective of tumor stage. In explant tissue, cisplatin-resistant tumors excluded platinum ions from tumor areas in contrast to cisplatin-sensitive tumors. Intact TP53 did not predict cisplatin sensitivity, but a positive correlation was observed between cisplatin sensitivity and TP53 mutation status (P = 0.003). Treatment of NSCLC explants with the targeted agent TRAIL revealed differential sensitivity with the majority of tumors resistant to single-agent or cisplatin combination therapy. Overall, our results validated a rapid, reproducible, and low-cost platform for assessing drug responses in patient tumors ex vivo, thereby enabling preclinical testing of novel drugs and helping stratify patients using biomarker evaluation. Cancer Res; 77(8); 2029-39. ©2017 AACR.
ATIM-33. PROTEIN MICROARRAY ANALYSIS OF GLIOBLASTOMA PATIENT SERA BEFORE AND AFTER DENDRITIC CELL VACCINATION
Authors: Alexander Tucker, Richard Everson
Journal: Neuro-Oncology (2016)

Immunotherapy with dendritic cell (DC) vaccination for the treatment of glioblastoma (GBM), appears to correlate with prolonged survival in some, but not all patients treated. While some patients exhibit increased T-cell infiltration after DC vaccination, antibody responses have been under explored as an alternative hypothesis as to why there is heterogeneity in survival outcomes. To investigate this, we used a microarray with 9,000 full-length human proteins to obtain autoantibody profiles of sera from two patients (Patient A and B) with GBM before and after DC vaccination. Aside from a large difference in patient survival (67 months vs 10 months), the tumors appeared similar by standard molecular pathologic analysis (both tumors have unmethylated MGMT promotors and similar Ki-67 indices, although Patient B’s tumor showed positive expression of EGFRvIII while this was not observed in Patient A). There was an increase in the signal intensity to more protein targets after vaccination in Patient A than B (3,843 vs 709) and only one antibody was significantly elevated in both patients. This antibody is directed against a protein encoded by the BCL2-associated athanogene 5 variant 2 (BAG 5v2), believed to have anti-apoptotic functions. Upregulation of BAG 5v2 gene expression has been implicated in other solid malignancies of the body such as prostate, breast, colon, and pancreatic cancers. This findings suggests that BAG 5v2 could be a novel cancer biomarker/therapeutic target, but is being validated by expanding the project to include 11 more patients. Comprehensive analysis of antitumor antibody responses generated by DC vaccination may allow us to predict which patients will benefit from treatment, monitor response or progression and perhaps learn more about the biological mechanism by which DC vaccination works.
Checkmate 205 Update with Minimum 12-Month Follow up: A Phase 2 Study of Nivolumab in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma
Authors: John M. Timmerman, Andreas Engert, Anas Younes, Armando Santoro, Philippe Armand, Michelle A Fanale, Graham P. Collins, Voravit Ratanatharathorn, John Kuruvilla, Jonathon B. Cohen, Kerry J Savage, Marek Trneny, Jan Paul De Boer, Margaret A. Shipp, Scott J Rodig, Kazunobu Kato, Anne Sumbul, Stephen Ansell
Journal: Blood (2016)
Molecular Genetic Profiling in Chronic Myelomonocytic Leukemia with Low Risk Cytogenetic Features
Authors: Laura Palomo, Blanca Xicoy, Montse Arnan, Marta Cabezon, Rosa Coll, Vera Ademà, Francisco Fuster, Javier Grau, María José Jiménez, Helena Pomares, Sílvia Marcé, Maria Pilar Armengol, Mar Mallo, Fuensanta Millá, Evarist Feliu, Francesc Sole, Lurdes Zamora
Journal: Blood (2015)
MNGO-11. REPORT FROM THE MENINGIOMA CONSORTIUM: CONFIRMATION OF A MENINGIOMA RISK LOCUS AT 10p12
Authors: Elizabeth Claus, Lisa Calvocoressi, Joellen Schildkraut, Kyle Walsh, Helen Hansen, Ivan Smirnov, Lucie McCoy, Lingeng Lu, Xiaomai Ma, Melissa Bondy, Margaret Wrensch, Joseph Wiemels
Journal: Neuro-Oncology (2016)

OS at 10 years, with 71.7% for female and 33.3% for male (p<0.01).Multivariate analysis adjusting for gender, year of diagnosis, treatment regimens showed worse OS in advanced age group 75+ (HR 3.120, 95% CI 1.020-10.744,p=0.046, using age group 18-44 as reference).However, there was no association of statistical significance with OS for the delivery of RT (HR 1.767, 95% CI 0.636-4.772,p=0.27) or surgery such as STR (HR 2.670, 95% CI 0.680-8.915,p=0.15).Adult patients with malignant meningioma were predominantly female, which was associated with improved OS compared to male gender.Long-term OS was optimal, and there was no clear evidence of RT or surgery affecting survival outcome.Given the potential selection bias and lack of detailed information on chemotherapy and RT dose in SEER database, further study is needed to validate our findings.
Randomized PII Trial Comparing CDDP/TS1 With CDDP/DTX With Concurrent Radiotherapy in Locally Advanced NSCLC (TORG1018)
Authors: Haruhiro Saito, Hiroshi Tanaka, Tsuneo Shimokawa, Hiroaki Okamoto, Kazuhiko Yamada, Kaoru Kubota, Kazuma Kishi, Yuichi Takiguchi, Yukio Hosomi, Terufumi Kato, Koshiro Watanabe
Journal: Annals of Oncology (2016)
QLIF-05. PATIENT PREFERENCES FOR GLIOBLASTOMA MULTIFORME: A DISCRETE CHOICE EXPERIMENT
Authors: Joanna MacEwan, Jason Doctor, Suepattra May, Patrick Bonnet, Ningqi Hou, Mahlet Tebeka, Darius Lakdawalla
Journal: Neuro-Oncology (2016)

Glioblastoma multiforme (GBM) is the most common and aggressive cancer of the central nervous system. Despite prior advances in diagnosis and treatment, the prognosis for GBM patients remains poor. Novel therapies might help preserve neurological function and maintain patients’ independence, but could raise the risk of treatment-related side effects. These patients may have unique preferences for health outcomes. We assessed how GBM patients weigh the benefits of increased survival from novel therapy against the associated risk of side effects. Using a discrete choice experiment survey, GBM patients completed a web-enabled choice-format conjoint survey that presented a series of 8 choice questions each comparing two hypothetical treatment scenarios across four different attributes: expected survival, functional ability (symptom relief and patient’s ability to perform daily tasks), risk of side effects, and monthly out-of-pocket cost. Quality of life was measured using the EQ-5D and a self-reported assessment of health visual analogue scale from 0 to 100. Patient preferences and valuations for each attribute were estimated using logistic regression. All respondents provided online informed consent. Among the patients (n=27) 63% had been diagnosed with GBM within the previous year and 85% were undergoing their 1st round of treatment. Lower risk of side effects and improved functional ability did not significantly increase the patients’ treatment choice, but each additional month of survival increased the probability of choosing a treatment (p<0.001). The patients valued increased survival above improvements in functional ability and reduced side effects. In our study, GBM patients valued increases in survival significantly more than reducing the risk of side effects or increasing functional ability. Poor prognosis and short life expectancy may account for patients with GBM placing higher value on therapies that can help delay disease delay progression and extend survival, despite their risk of side effects.
LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-Mediated H3K4me2 demethylation
Authors: Yan-wen Liu, Rui Xia, Kai Lu, Min Xie, Fen Yang, Ming Sun, Wei De, Cailian Wang, Guozhong Ji
Journal: Molecular Cancer (2017)

Although the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human gastric cancers development. Our previous studies suggest that HOTAIR contributes to gastric cancer development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we investigated the characteristic of the LncRNA FEZF1-AS1 in gastric cancer. QRT-PCR was used to detect the expression of FEZF1-AS1 in gastric cancer tissues and cells. MTT assays, clonogenic survival assays and nude mouse xenograft model were used to examine the tumorigenesis function of FEZF1-AS1 in vitro and in vivo. Bioinformatics analysis were used to select downstream target genes of FEZF1-AS1. Cell cycle analysis, ChIP, RIP,RNA Pulldown assays were examined to dissect molecular mechanisms. In this study, we reported that FEZF1-AS1, a 2564 bp RNA, was overexpressed in gastric cancer, and upregulated FEZF1-AS1 expression indicated larger tumor size and higher clinical stage; additional higher expression of FEZF1-AS1 predicted poor prognosis. Further experiments revealed that knockdown FEZF1-AS1 significantly inhibited gastric cancer cells proliferation by inducing G1 arrest and apoptosis, whereas endogenous expression FEZF1-AS1 promoted cell growth. Additionally, RIP assay and RNA-pulldown assay evidenced that FEZF1-AS1 could epigenetically repress the expression of P21 via binding with LSD1, the first discovered demethylase. ChIP assays demonstrated that LSD1 could directly bind to the promoter of P21, inducing H3K4me2 demethylation. In summary, these data demonstrated that FEZF1-AS1 could act as an "oncogene" for gastric cancer partly through suppressing P21 expression; FEZF1-AS1 may be served as a candidate prognostic biomarker and target for new therapies of gastric cancer patients.
Expression of myelomonocytic antigens is associated with unfavourable clinicoprognostic factors in B-cell chronic lymphocytic leukaemia
Authors: Antonio Pinto, L. Del Vecchio, A. Carbone, M. Roncadin, R. Volpe, D. Serraino, S. Monfardini, A. Colombatti, V. Zagonel
Journal: Annals of Oncology (1991)
Very-Low-Density Lipoprotein–Associated Apolipoproteins Predict Cardiovascular Events and Are Lowered by Inhibition of APOC-III
Authors: Raimund Pechlaner, Sotirios Tsimikas, Xiaoke Yin, Peter Willeit, Ferheen Baig, Peter Santer, Friedrich Oberhollenzer, Georg Egger, Joseph L. Witztum, Veronica J. Alexander, Johann Willeit, Stefan Kiechl, Manuel Mayr
Journal: Journal of the American College of Cardiology (2017)

Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD.This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level understanding of the correlations of apolipoproteins with the plasma lipidome and proteome.Associations of 13 apolipoproteins, 135 lipid species, and 211 other plasma proteins with incident CVD (91 events), defined as stroke, myocardial infarction, or sudden cardiac death, were assessed prospectively over a 10-year period in the Bruneck Study (N = 688) using multiple-reaction monitoring mass spectrometry. Changes in apolipoprotein and lipid levels following treatment with volanesorsen, a second-generation antisense drug targeting apoC-III, were determined in 2 human intervention trials, one of which was randomized.The apolipoproteins most significantly associated with incident CVD were apoC-II (hazard ratio per 1 SD [HR/SD]: 1.40; 95% confidence interval [CI]: 1.17 to 1.67), apoC-III (HR/SD: 1.38; 95% CI: 1.17 to 1.63), and apoE (HR/SD: 1.31; 95% CI: 1.13 to 1.52). Associations were independent of high-density lipoprotein (HDL) and non-HDL cholesterol, and extended to stroke and myocardial infarction. Lipidomic and proteomic profiles implicated these 3 very-low-density lipoprotein (VLDL)-associated apolipoproteins in de novo lipogenesis, glucose metabolism, complement activation, blood coagulation, and inflammation. Notably, apoC-II/apoC-III/apoE correlated with a pattern of lipid species previously linked to CVD risk. ApoC-III inhibition by volanesorsen reduced plasma levels of apoC-II, apoC-III, triacylglycerols, and diacylglycerols, and increased apoA-I, apoA-II, and apoM (all p < 0.05 vs. placebo) without affecting apoB-100 (p = 0.73).The strong associations of VLDL-associated apolipoproteins with incident CVD in the general community support the concept of targeting triacylglycerol-rich lipoproteins to reduce risk of CVD.
Prognostic Impact of Blood Count Recovery Based Complete Remission Prior to Allogeneic Transplantation in Patients with Acute Leukemia
Authors: Moussab Damlaj, Ghazi Samer, Giamal Edin Mohamed Gmati, Walid Mashaqbeh, Mohsen Al Zahrani, Khadega Ahmed Abuelgasim, Mushtaq Rather, Hend Salama, Ahmed Askar, Ayman Hejazi
Journal: Blood (2016)
Dynamics of Improvement in Health-Related Quality of Life (HRQoL) with Long-Term Eltrombopag Treatment in Adults with Chronic Immune Thrombocytopenia (ITP) in EXTEND.
Authors: Kelly M Grotzinger, James B Bussel, Mansoor N Saleh, Christine Bieri, Yuliya Orlova, Andres Brainsky
Journal: Blood (2012)
A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC)
Authors: G. Curigliano, S. Loibl, V. Müller, X. Pivot, A. Wardley, D. Cameron
Journal: Annals of Oncology (2016)
RARE-42. LEPTOMENINGEAL DISSEMINATION IN MALIGNANT GLIOMA: A CASE SERIES
Authors: Christina Amidei, Martin Nicholas, Roberto Sica, Sunhee Kim, Jean Arzbaecher, Gayatry Mohapatra
Journal: Neuro-Oncology (2016)

Symptomatic leptomeningeal dissemination (LMD) is uncommon in patients with malignant glioma (MG), occurring in less than 5% of patients. We report a case series of 11 patients over 18 months at a single institution. Demographic, radiologic, and treatment data from the medical record are reported, and molecular characteristics of the primary tumor identified where available. Demographic and clinical features were strikingly variable. Time from initial diagnosis to LM diagnosis varied from synchronous to 30 years. Time to LM development from initial diagnosis was significantly longer for those whose tumors were initially low grade. There was no predilection for tumor location and all but the two patients (both diagnosed synchronously) received radiation and chemotherapy following initial surgery. Patients who received treatment for LM lived longer than those who did not, but the small sample size and additional variables (e.g. KPS and IDH mutation status) precluded a statistical assessment. There was a positive correlation between KPS at LM diagnosis and survival (r = 0.726027). However, relationships between the data were highly variable across the group, likely confounding results. For example, two of 4 patients who chose no treatment (one with a KPS of 90%) had IDH1 mutations but poor survival, suggesting a complex relationship between this prognostic variable and survival in LM. We are using cancer genomics in an attempt to identify molecular signatures associated with LM. Whole exome sequencing and gene expression profiling from available tissue samples is ongoing and results will be reported. Though limited in size (n=11), this represents the largest contemporaneous series of LM in patients with MG.
Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy
Authors: Ira M. Jacobson, Mary K. Washington, Maria Buti, Alexander Thompson, Nezam Afdhal, Robert Flisiak, Ulus Salih Akarca, Konstantin G. Tchernev, John F. Flaherty, Raul Aguilar Schall, Robert P. Myers, G. Mani Subramanian, John G. McHutchison, Zobair Younossi, Patrick Marcellin, Keyur Patel
Journal: Clinical Gastroenterology and Hepatology (2017)
Human Multipotent Mesenchymal Stromal Cells (MSC) Exhibit Broad Spectrum Antimicrobial Effector Functions Mediated by Indoleamine 2,3-Dioxygenase (IDO).
Authors: Roland Meisel, Kathrin Heseler, Doreen Wendholt, Huelya Buelle, Claudia Woite, Silke Stuhlsatz, Wilfried Schwippert, Dagmar Dilloo, Walter Daeubener
Journal: Blood (2007)
Evaluation of IL-10 polymorphisms in high-risk melanoma patients receiving adjuvant interferon
Authors: H. Gogas, Y. Metaxas, A. Polyzos, M. Mantzourani, A. Antoniadis, C. Floudas, G. Fountzilas, D. Pectasides, D. Tsoutsos, M. Spyropoulou-Vlachou
Journal: Journal of Clinical Oncology (2009)

9049 Background: Attempts to identify patients who benefit from adjuvant treatment of interferon alfa-2b (IFN) have been disappointing. Interleukin-10 polymorphisms have been implicated with the prognosis of patients with advanced melanoma and associated with response to biochemotherapy. Several polymorphisms have been found within the IL-10 gene. We evaluated three IL-10 Single Nucleotide Polymorphisms (SNPs) in high-risk melanoma patients enrolled in a study of two regimens of high-dose IFN and compared the distribution of SNPs found in healthy controls. Methods: We genotyped DNA from peripheral blood of 280 stage IIb, IIc and III melanoma patients and 288 healthy controls for 592 C/A, 819 C/T and 1082 G/A with PCR and pyrosequencing technology (Biotage, Uppsala, Sweden). Results: At a median follow up of 56.3 months (95% CI 47.4–63.7), 147 patients have recurred and 94 have died. The median DFS was 53 months and the median OS 86 months. There were no statistically significant differences in the incidence of IL-10 polymorphisms between the melanoma patients and healthy controls. The incidence of these polymorphisms is presented in table . RFS and OS did not differ significantly between the alleles of these polymorphisms (p=0.88 and p=0.55 for 592 C/A, p=0.84 and p=0.68 for 819 C/T and p=0.26 and p=0.30 for 1082 G/A respectively). Conclusions: No SNP studied was correlated with improved RFS and OS in this high-risk group of melanoma patients. [Table: see text] [Table: see text]