tbuckley/cabot-search huggingface dataset:
TRAIL and Noxa Are Selectively Upregulated in Prostate Cancer Cells Downstream of the RIG-I/MAVS Signaling Pathway by Nonreplicating Sendai Virus Particles
Authors: Taeko Matsushima-Miyagi, Koji Hatano, Motonari Nomura, Liu Li-Wen, Tomoyuki Nishikawa, Kotaro Saga, Takashi Shimbo, Yasufumi Kaneda
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The treatment of cancer with oncolytic viruses primarily depends on the selective viral replication in cancer cells. However, a replication-incompetent hemagglutinating virus of Japan (HVJ; Sendai virus) envelope (HVJ-E) suppresses the growth of human cancer cells as effectively as replication-competent live HVJ without producing toxic effects in nonmalignant cells. Here, we analyze the molecular mechanism of the oncolytic activity of HVJ-E. Experimental Design: The molecules responsible for HVJ-E–induced cancer cell death were elucidated in prostate cancer cell lines, and the effect of HVJ-E on orthotopic prostate cancers was evaluated in nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Results: The liposome-mediated transfer of viral RNA genome fragments from HVJ-E suppressed the viability of prostate cancer cells but not the viability of the noncancerous prostate epithelium. Knockdown experiments using siRNAs showed that the cancer cell–selective killing induced by HVJ-E was mediated by retinoic acid–inducible gene I (RIG-I) and mitochondrial antiviral signaling protein (MAVS). Downstream of the RIG-I/MAVS pathway, both TNF-related apoptosis-inducing ligand (TRAIL) and Noxa were upregulated by HVJ-E in the castration-resistant prostate cancer cell line PC3 but not in the noncancerous prostate epithelial cell line PNT2. TRAIL siRNA but not Noxa siRNA significantly inhibited HVJ-E–induced cell death in PC3 cells. However, Noxa siRNA effectively suppressed HVJ-E–induced cell death in DU145 cells, another castration-resistant prostate cancer cell line, in which Noxa but not TRAIL was upregulated by HVJ-E. Furthermore, the orthotopic prostate cancers were dramatically eradicated in immunodeficient mice injected with HVJ-E. Conclusion: The RIG-I/MAVS signaling pathway represents an attractive target for cancer therapy. Clin Cancer Res; 18(22); 6271–83. ©2012 AACR.
Frequency of α‐thalassemia in Greece
Authors: E. Kanavakis, S. Tzotzos, A. Liapaki, A. Metaxotou‐Mavromati, C. Kattamis
Journal: American Journal of Hematology (1986)

Abstract Using hematological and gene mapping techniques, a cord blood survey was carried out to estimate the frequency of α‐thalassemia in the Greek population. Out of 227 newborns studied, 16 (7.05%) were found by gene mapping to be α‐thalassemia 2 heterozygotes (‐α/αα), and of these only two had increased levels of hemoglobin Bart's in the cord blood (1.2 and 2.0%). Similarly, one heterozygote for the common Mediterranean α‐thalassemia 1 haplotype (–/αα) and one for the 20.5‐kb deletion type (‐α) 20.5 /αα) were found, showing increased levels of Bart's of 4.8 and 6.6%, respectively. Four (1.76%) heterozygotes for the triple α gene arrangement (ααα/αα) were found. One individual with a level of Bart's in the cord blood of 8% was found to be a double heterozygote for α‐thalassemia 2 and a dysfunctional α gene arrangement (‐α/‐(α)?). These results give an overall incidence for α‐thalassemia in the Greek population of 8.4%.
New opportunities for respiratory research in Europe: FP7
Authors: W. MacNee, G. Viegi, N. Kamel
Journal: European Respiratory Journal (2007)

he mission of the European Respiratory Society (ERS) is to promote respiratory health in Europe in order to alleviate suffering from respiratory disease.This is accomplished by promoting basic epidemiological and clinical respiratory research, collecting and disseminating scientific information, organising congresses and conferences, producing scientific publications, supporting training and continuous education in respiratory medicine, and collaborating with organisations that represent patients.
Trends in Emergency Medicaid Expenditures for Recent and Undocumented Immigrants
Authors: C. Annette DuBard, Mark W. Massing
Journal: JAMA (2007)

Undocumented immigrants and legal immigrants who have been in the United States less than 5 years are excluded from Medicaid eligibility, with the exception of limited coverage for emergency conditions (Emergency Medicaid). New immigrant population growth has been rapid in recent years, but little is known about use of health services by this group or the conditions for which Emergency Medicaid coverage has been applied.To describe Emergency Medicaid use by recent and undocumented immigrants including patient characteristics, diagnoses, and recent spending trends in North Carolina, a state with a rapidly increasing population of undocumented immigrants.Descriptive analysis of North Carolina Medicaid administrative data for all claims reimbursed under Emergency Medicaid eligibility criteria 2001 through 2004 in North Carolina, a state with high immigration from Mexico and Latin America. Patients are recent and undocumented immigrants who meet categorical and income criteria for Medicaid coverage, but are excluded from full coverage due to legal status.Patient characteristics, hospitalizations, diagnoses, and Medicaid spending for emergency care.A total of 48,391 individuals received services reimbursed under Emergency Medicaid during the 4-year period of this study. The patient population was 99% undocumented, 93% Hispanic, 95% female, and 89% in the 18- to 40-year age group. Total spending increased by 28% from 2001 through 2004, with more rapid spending increases among elderly (98%) and disabled (82%) patients. In 2004, childbirth and complications of pregnancy accounted for 82% of spending and 91% of hospitalizations. Injury, renal failure, gastrointestinal disease, and cardiovascular conditions were also prevalent.Childbirth and complications of pregnancy account for the majority of Emergency Medicaid spending for undocumented immigrants in North Carolina. Spending for elderly and disabled patients, however, is increasing at a faster rate. Among nonpregnant immigrants, injuries, other acute emergencies, and severe complications of chronic disease are major contributors to Emergency Medicaid use.
Say What? The Activity of the Polyamine Biosynthesis Inhibitor Difluoromethylornithine in Chemoprevention Is a Result of Reduced Thymidine Pools?
Authors: Robert A. Casero
Journal: Cancer Discovery (2013)

Abstract Summary: In this issue of Cancer Discovery, Witherspoon and colleagues use an unbiased metabolite profiling approach to study the effects of polyamine depletion by 2-difluoromethylornithine in colon cancer cells. Their surprising findings indicate that it is a decrease in thymidine pools resulting from altered tetrahydrofolate availability rather than decreases in polyamines that produces cytostasis. Cancer Discov; 3(9); 975–7. ©2013 AACR. See related article by Witherspoon et al., p. 1072
Advanced Skeletal Imaging Redefines the Management of Plasma Cell Disorders
Authors: Morie A. Gertz
Journal: Journal of Clinical Oncology (2015)

In this issue of Journal of Clinical Oncology, Dimopoulos and thought leaders in the field of myeloma, representing the International Myeloma Working Group, provide evidence-based, consensus recommendations on the use of magnetic resonance imaging (MRI) in a number of plasma cell disorders.Their recommendations are practice changing. 1When new techniques are introduced for patient evaluation, they often add expense for patients but do not affect management.These recommendations affect therapeutic decision making for patients with plasma cell disorders and represent an update of earlier International Myeloma Working Group recommendations. 2 The paper focuses on the use of MRI.However, data on the use of positron emission tomography (PET) combined with computed tomography (CT) is also applicable to decision making in patients with plasma cell disorders.This consensus publication focuses on whole-body MRI.The recommended substitution of MRI of the axial skeleton for when whole-body MRI is not available results in a failure to recognize almost 50% of skeletal lesions in myeloma. 3 The use of PET/CT, which provides a full-body scan, becomes an alternative for many.The sensitivity and specificity of FDG PET for detecting lesions in myeloma is 96%, and the specificity is 77%; it is particularly useful for the assessment of extramedullary disease. 4 In a meta-analysis of 18 studies comprising 800 patients with myeloma, FDG PET detected osteolytic lesions with a sensitivity of 80% to 90% and a specificity of 80% to 100%.A higher number of lesions were revealed with PET/CT than with MRI.Unlike MRI, however, PET/CT is not sensitive to diffuse bone marrow infiltration, which is well detected by MRI.PET/CT can distinguish old from new fractures based on uptake.MRI should, however, be preferred when the vertebral bodies are suspected to be involved and the risk of vertebral fracture is to be assessed. 5 No conclusions can be drawn on the superiority of one technique over the other in the imaging of patients with plasma cell disorders, but it appears both have a role.A comparison of the sensitivity of wholebody MRI versus traditional skeletal radiography was conducted in 171 patients with plasma cell dyscrasias. 6 In the group of patients who were evaluated by whole-body CT, 23% had lesions that were not detected with plain radiography.In the second group, whole-body MRI revealed lesions in 16% of patients that were not detected by skeletal radiographs.All lesions detected by skeletal radiography were also detected by whole-body MRI and whole-body CT, each was superior to standard radiography.
Serial Monitoring of Circulating Tumor Cells Predicts Outcome of Induction Biochemotherapy plus Maintenance Biotherapy for Metastatic Melanoma
Authors: Kazuo Koyanagi, Steven J. O'Day, Peter Boasberg, Michael B. Atkins, He-Jing Wang, Rene Gonzalez, Karl Lewis, John A. Thompson, Clay M. Anderson, Jose Lutzky, Thomas T. Amatruda, Evan Hersh, Jon Richards, Jeffrey S. Weber, Dave S.B. Hoon
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT). Experimental Design: Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome. Results: The number of positive CTC biomarkers decreased overall during induction BCT (P &amp;lt; 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P &amp;lt; 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95% confidence interval, 4.78-33.4; P &amp;lt; 0.0001) and overall survival (risk ratio, 6.11; 95% confidence interval, 2.37-15.7; P = 0.0005). Conclusion: Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma. Clin Cancer Res; 16(8); 2402–8. ©2010 AACR.
Vandetanib Plus Pemetrexed for the Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer: A Randomized, Double-Blind Phase III Trial
Authors: Richard H. de Boer, Óscar Arrieta, Chih-Hsin Yang, Maya Gottfried, Valorie Chan, Johann Raats, Filippo de Marinis, Raymond P. Abratt, Jürgen Wolf, Fiona H. Blackhall, Peter Langmuir, Tsveta Milenkova, Jessica Read, Johan F. Vansteenkiste
Journal: Journal of Clinical Oncology (2011)

Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This randomized, placebo-controlled phase III study assessed the efficacy of vandetanib plus pemetrexed as second-line therapy in advanced non-small-cell lung cancer.Patients (N = 534) were randomly assigned to receive vandetanib 100 mg/d plus pemetrexed 500 mg/m(2) every 21 days (n = 256) or placebo plus pemetrexed (n = 278). Progression-free survival (PFS) was the primary end point; overall survival, objective response rate, disease control rate, time to deterioration of symptoms, and safety were secondary assessments.There was no significant difference in PFS between treatment arms (hazard ratio [HR], 0.86; 97.58% CI, 0.69 to 1.06; P = .108). Overall survival was also not significantly different (HR, 0.86; 97.54% CI, 0.65 to 1.13; P = .219). Statistically significant improvements in objective response rate (19% v 8%; P < .001) and time to deterioration of symptoms (HR, 0.71; P = .0052; median, 18.1 weeks for vandetanib and 12.1 weeks for placebo) were observed in patients receiving vandetanib. Adding vandetanib to pemetrexed increased the incidence of some adverse events, including rash, diarrhea, and hypertension, while showing a reduced incidence of nausea, vomiting, anemia, fatigue, and asthenia with no reduction in the dose intensity of pemetrexed.This study did not meet the primary end point of statistically significant PFS prolongation with vandetanib plus pemetrexed versus placebo plus pemetrexed. The vandetanib combination showed a significantly higher objective response rate and a significant delay in the time to worsening of lung cancer symptoms versus the placebo arm as well as an acceptable safety profile in this patient population.
Pharmacology and Therapeutics of Bronchodilators
Authors: Mario Cazzola, Clive P. Page, Luigino Calzetta, M. Gabriella Matera
Journal: Pharmacological Reviews (2012)

Bronchodilators are central in the treatment of of airways disorders. They are the mainstay of the current management of chronic obstructive pulmonary disease (COPD) and are critical in the symptomatic management of asthma, although controversies around the use of these drugs remain. Bronchodilators work through their direct relaxation effect on airway smooth muscle cells. at present, three major classes of bronchodilators, β<sub>2</sub>-adrenoceptor (AR) agonists, muscarinic receptor antagonists, and xanthines are available and can be used individually or in combination. The use of the inhaled route is currently preferred to minimize systemic effects. Fast- and short-acting agents are best used for rescue of symptoms, whereas long-acting agents are best used for maintenance therapy. It has proven difficult to discover novel classes of bronchodilator drugs, although potential new targets are emerging. Consequently, the logical approach has been to improve the existing bronchodilators, although several novel broncholytic classes are under development. An important step in simplifying asthma and COPD management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence. Several once-daily β<sub>2</sub>-AR agonists or ultra-long-acting β<sub>2</sub>-AR-agonists (LABAs), such as indacaterol, olodaterol, and vilanterol, are already in the market or under development for the treatment of COPD and asthma, but current recommendations suggest the use of LABAs only in combination with an inhaled corticosteroid. In addition, some new potentially long-acting antimuscarinic agents, such as glycopyrronium bromide (NVA-237), aclidinium bromide, and umeclidinium bromide (GSK573719), are under development, as well as combinations of several classes of long-acting bronchodilator drugs, in an attempt to simplify treatment regimens as much as possible. This review will describe the pharmacology and therapeutics of old, new, and emerging classes of bronchodilator.
What Should the Optimal Timing Be for Amifostine Administration Relative to Radiation and Chemotherapy?
Authors: Ritsuko Komaki
Journal: Journal of Clinical Oncology (2005)

Thank you, Dr Belvedere for your letter regarding our recently published article on randomized phase II trial comparing two schedules of single agent gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC) and impaired Karnofsky Performance Status (KPS Ͻ 70).Patients were randomly assigned to receive gemcitabine 1000 mg/m 2 on days 1, 8, and 15 of each 28 days cycle or gemcitabine 1,500 mg/m 2 on days 1 and 8 of each 21 days cycle both for up to six cycles. 1 In this trial we have concluded that there was no difference on the symptom improvement and the KPS between the two gemcitabine regimens.We take the opportunity to focus again on the difficulties of a randomized trial in impaired performance status patients with NSCLC.Although many patients with advanced NSCLC have a performance status (PS) of more than 1, historically, clinical trials have largely excluded these patients.Furthermore the clinical benefit of palliative chemotherapy has been difficult to evaluate in this population because of the short survival. 2-4 The attrition rate in our trial was high due to the short survival, despite the entry criterion of a life expectancy of more than 4 weeks, nevertheless 63% patients completed quality of life (QoL) assessment.Some patients were not keen to fill in QoL forms, some staff were unwilling to burden them with QoL assessments, and the missing data make for the difficulties outlined in the letter of Dr Belvedere.We agree that interpretation in terms of disease-related symptoms on PS should be cautious.However as both treatment arms were balanced for prognostic factors and number of cycles of treatment given, a comparison is not unreasonable.There is now some evidence that PS 2 patients can benefit from chemotherapy in terms of symptom palliation and possible survival. 5-9Nevertheless we agree with Dr Belvedere that prospective randomized trials are required to focus attention on patients with advanced NSCLC and impaired PS, our trial could be regarded as an initial attempt in this direction.
Rituximab in psoriatic arthritis: an exploratory evaluation
Authors: Esther Jimenez-Boj, Tanja A Stamm, Martina Sadlonova, Jozef Rovensky, Helena Raffayová, Burkhard Leeb, Klaus Peter Machold, Winfried B Graninger, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2012)

Background/objective Current therapies for psoriatic arthritis (PsA) comprise synthetic drugs and tumour necrosis factor inhibitors. In contrast, other biologicals including rituximab (RTX) are available for treating rheumatoid arthritis (RA). RTX is effective in autoantibody positive RA patients, although some efficacy has been reported in seronegative individuals. RTX has not yet been assessed in PsA. Therefore, an open label study of RTX in PsA was performed. Patients and methods Nine patients with PsA and 14 with RA received RTX at 1000 mg twice within 14 days and were evaluated over 6 months. Results A PsA response criteria response was attained in 56% of patients. DAS28 improved from 6.2 to 4.9 (medians) in PsA and 6.4 to 5.2 in RA, and Health Assessment Questionnaire from 1.5 to 1.0 and from 2.1 to 1.4, respectively (all p≤0.05). Disease Activity index for PSoriatic Arthritis changed from 52.0 to 32.5 (p&lt;0.05); C reactive protein and Psoriasis Area and Severity Index did not change significantly. RTX was tolerated well. Conclusions In this exploratory open study, RTX exhibited significant efficacy in PsA patients with long-standing disease. Thus, RTX may have efficacy in PsA warranting a randomised controlled clinical trial.
Announcement: HDL biology: new insights in metabolism, function and translation: to be published in July, 2014
Authors: L. Calabresi, J.-R. Nofer, G. D. Norata
Journal: Cardiovascular Research (2014)

Cardiovascular Research publishes Spotlight review issues devoted to a specific research topic. These issues contain a number of expert reviews, which can be complemented with original research papers on this topic. All papers are subjected to the normal peer review process (an editorial decision is usually made within 22 days of receipt of any manuscript).

A Spotlight issue on ‘HDL biology: new insights in …
Electrolyte Changes in Heart Tissue and Coronary Arterial and Venous Plasma Following Coronary Occlusion
Authors: JOHN R. CUMMINGS
Journal: Circulation Research (1960)

When coronary sinus and arterial plasma samples obtained during a period of ventricular tachycardia 8 to 11 hours after coronary ligation were analyzed for electrolyte concentrations, it was found that there was an increase in K and Mg and a decrease in Ca and Na. By comparison, when blood samples were taken from sham dogs 8 to 11 hours after the ligatures had simply been placed under the artery, no significant change in plasma cation concentrations over control values was observed. Infarcted ventricular tissue, as compared with noninfarcted tissue, contained an average of 5.1 mEq./100 Gm. wet weight more Na, 4.0 mEq./100 Gm. wet weight less K, and 1.12 mEq./100 Gm. wet weight less Mg.
High-Dose Chemotherapy with Hematopoietic Stem-Cell Rescue for Multiple Myeloma
Authors: J. Anthony Child, Gareth J. Morgan, Faith E. Davies, Roger G. Owen, Susan E. Bell, Kim Hawkins, Julia Brown, Mark T. Drayson, Peter J. Selby
Journal: New England Journal of Medicine (2003)

High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer. In multiple myeloma, first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments, but evidence that this translates into improved survival is limited.
Prefrontal Contributions to Visual Selective Attention
Authors: Ryan F. Squire, Behrad Noudoost, Robert J. Schafer, Tirin Moore
Journal: Annual Review of Neuroscience (2013)

The faculty of attention endows us with the capacity to process important sensory information selectively while disregarding information that is potentially distracting. Much of our understanding of the neural circuitry underlying this fundamental cognitive function comes from neurophysiological studies within the visual modality. Past evidence suggests that a principal function of the prefrontal cortex (PFC) is selective attention and that this function involves the modulation of sensory signals within posterior cortices. In this review, we discuss recent progress in identifying the specific prefrontal circuits controlling visual attention and its neural correlates within the primate visual system. In addition, we examine the persisting challenge of precisely defining how behavior should be affected when attentional function is lost.