tbuckley/cabot-search huggingface dataset:
CPG 7909, a TLR9 agonist, added to first line taxane/platinum for advanced non-small cell lung cancer, a randomized, controlled phase II study
Authors: G. Leichman, D. Gravenor, D. Woytowitz, J. Mezger, G. Albert, T. Schmalbach, M. Al-Adhami, C. Manegold
Journal: Journal of Clinical Oncology (2005)

7039 Background: First line treatment for stage IIIb/IV NSCLC continues to be a combination of a taxane + platinum with partial responses expected in only 20 - 30% of patients. Multiple pre-clinical models have shown that tumor response and survival after chemotherapies are significantly improved by the addition of CPG 7909. This new synthetic oligodeoxynucleotide acts through dendritic cells by targeting the Toll-like Receptor 9 with subsequent immunomodulatory effects. Human dose ranging, safety and biologic responses to weekly S.C. doses of CPG 7909 have been established in earlier trials. Methods: This phase II trial randomized and treated 112 patients in 23 centers. Naïve patients with NSCLC were randomized 2:1 and received 4 - 6 three-week cycles of a standard regimen of taxane and platinum plus CPG 7909 [C + CPG 7909] on weeks 2 and 3 of each cycle or [C] alone. Each dose of CPG 7909 was 0.20 mg/kg given S.C. The primary endpoint of objective response was assessed at cycles 2, 4 and 6 using RECIST criteria. A post-hoc independent radiological review [IRR] was conducted on coded and blinded scans. Secondary efficacy analyses are being completed, and include clinical benefit, time to and duration of response, and survival. Biomarker responses to CPG 7909 will be compared for responders vs non-responders in the two arms. Results: Data for an ITT response analysis are available on 83 patients from the planned protocol (57 vs 26). Baseline demographics are balanced except for more stage IV patients in the C + CPG 7909 group. Administration of CPG 7909 did not complicate standard cycles of [C]. ORR was 23% vs 40% for the [C] vs [C+CPG 7909] arms, and is supported by the retrospective IRR data. Kaplan-Meier curves show a trend to improved PFS and survival in [C + CPG 7909] compared to [C]. A complete analysis including follow up survival will be presented on the 83 planned patients plus 28 patients more recently enrolled in a protocol amendment. Conclusions: A well tolerated regimen of weekly CPG 7909 added to a taxane/platinum regimen for first line treatment of NSCLC appears to improve objective response, and pivotal studies are warranted to document clinical benefit of this new modality. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Coley Pharmaceutical Group Coley Pharmaceutical Group
Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies
Authors: Mark D. Minden, Donna E. Hogge, Scott J. Weir, Jim Kasper, Debra A. Webster, Lavonne Patton, Yulia Jitkova, Rose Hurren, Marcela Gronda, Carolyn A. Goard, Lian G. Rajewski, John L. Haslam, Kathleen E. Heppert, Kevin Schorno, Hong Chang, Joseph M. Brandwein, Vikas Gupta, Andre C. Schuh, Suzanne Trudel, Karen W. L. Yee, Gregory A. Reed, Aaron D. Schimmer
Journal: American Journal of Hematology (2013)

The antimycotic ciclopirox olamine is an intracellular iron chelator that has anticancer activity in vitro and in vivo. We developed an oral formulation of ciclopirox olamine and conducted the first-in-human phase I study of this drug in patients with relapsed or refractory hematologic malignancies (Trial registration ID: NCT00990587). Patients were treated with 5-80 mg/m² oral ciclopirox olamine once daily for five days in 21-day treatment cycles. Pharmacokinetic and pharmacodynamic companion studies were performed in a subset of patients. Following definition of the half-life of ciclopirox olamine, an additional cohort was enrolled and treated with 80 mg/m² ciclopirox olamine four times daily. Adverse events and clinical response were monitored throughout the trial. Twenty-three patients received study treatment. Ciclopirox was rapidly absorbed and cleared with a short half-life. Plasma concentrations of an inactive ciclopirox glucuronide metabolite were greater than those of ciclopirox. Repression of survivin expression was observed in peripheral blood cells isolated from patients treated once daily with ciclopirox olamine at doses greater than 10 mg/m², demonstrating biological activity of the drug. Dose-limiting gastrointestinal toxicities were observed in patients receiving 80 mg/m² four times daily, and no dose limiting toxicity was observed at 40 mg/m² once daily. Hematologic improvement was observed in two patients. Once-daily dosing of oral ciclopirox olamine was well tolerated in patients with relapsed or refractory hematologic malignancies, and further optimization of dosing regimens is warranted in this patient population.
Abstract 9939: Insulin Receptor Substrate-2 Genetic Variants Interact with Plasma Monounsaturated and n-3 PUFA Fatty Acid Levels to Influence Insulin Resistance: From the LIPGENE Study
Authors: Pablo Perez-Martinez, Javier Delgado-Lista, Antonio Garcia-Rios, Hanne L Gulseth, Ellen E Blaak, Beata Kieć-Wilk, Olfa Helal, Julie A Lovegrove, Ulf Riserus, Helen M Roche, Jose Lopez-Miranda
Journal: Circulation (2011)

Background: The insulin receptor substrate-2 (IRS-2) is a major insulin signalling molecule. IRS-2 regulates body weight control and glucose homeostasis. Several IRS-2 polymorphic sites have been studied for their potential use as risk markers for obesity and type 2 diabetes mellitus. Fatty acids are key metabolic regulators which may interact with genetic factors and influence glucose metabolism. Objective: To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in subjects with metabolic syndrome (MetS). Design: Intravenous glucose tolerance tests (IVGTT) and HOMA indices were used to estimate insulin sensitivity (insulin sensitivity index, HOMA-IR), insulin secretion (first phase insulin secretion (AIRg), disposition index, HOMA-B) and glucose effectiveness. Plasma fatty acid composition and three IRS-2 single nucleotide polymorphisms (SNPs) were also determined in a cross-sectional analysis of 452 subjects with MetS participating in the LIPGENE dietary intervention cohort ( NCT00429195 ). Results: The rs2289046 SNP interacted with plasma monounsaturated (MUFA) and omega-3 polyunsaturated fatty acids (n-3 PUFA) levels which were significantly associated with insulin resistance. Among subjects with the lowest level of MUFA (below the median) the A/A genotype was associated with lower glucose effectiveness (P&lt;0.03), higher fasting insulin concentrations (P&lt;0.02) and higher HOMA-IR (P&lt;0.03) compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR. Whereas, individuals carrying the G allele and with the highest level of n-3 PUFA (above the median) showed lower fasting insulin (P&lt;0.01) and HOMA-IR (P&lt;0.02) compared with A/A subjects. Conclusions: The rs2289046 polymorphism at the IRS-2 gene locus may influence insulin resistance and glucose effectiveness by interacting with plasma fatty acid composition in subjects with the MetS. Further studies are needed to confirm whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.
European Concern Over BSE Transmission
Authors: X Bosch
Journal: JAMA (2001)

BARCELONA—Panic over the transmission of bovine spongiform encephalopathy (BSE) to humans who may unknowingly eat infected beef has spread across Europe after Spain and Germany reported their first indigenous cases in December 2000. France, where the zoonotic disease is now endemic, experienced a renewed outbreak in October. The Spanish meat industry was severely affected within days of the announcement that two cases of BSE had been discovered in cattle in the country’s northwestern region of Galicia. There was a drop of about 50% in beef sales and prices within Spain, and six countries ordered an immediate embargo on import of Spanish cattle. (In early January, one more beef animal in Galicia and two more from the Castilla-Leon region were confirmed positive for BSE, making a total of five BSE cases in Spain at JAMA press time.)
A Single-centre Early Phase Randomised Controlled Three-arm Trial of Open, Robotic, and Laparoscopic Radical Cystectomy (CORAL)
Authors: Muhammad Shamim Khan, Christine Gan, Kamran Ahmed, Ahmad Fahim Ismail, Jane Watkins, Jennifer A. Summers, Janet L. Peacock, Peter Rimington, Prokar Dasgupta
Journal: European Urology (2015)
Clinical Significance of Dek Overexpression in Oral Squamous Cell Carcinoma
Authors: K. Oh, H. Yoon, J. Kim, S. Hong, J. Lee, S. Hong
Journal: Annals of Oncology (2014)

ABSTRACT   Aim: Human DEK gene on chromosome 6p encodes a 43kD nuclear phospoprotein that was originally identified as part of a fusion protein found in a subset of acute myeloid leukemia carrying a t(6;9) translocation. According to several in vitro studies, DEK overexpression may play a role in tumor development through suppressing cellular senescence, apoptosis, and differentiation, which result in promoting cell growth and survival. Although DEK upregulation has been described in a number of human malignancies and was significantly associated with high histologic grade, lymph node metastasis and/or advanced clinical stage, no previous report has evaluated the expression of DEK protein and its clinical significance in oral squamous cell carcinoma (OSCC). Our aims were to determine DEK expression in tissue samples of normal oral mucosa and OSCC by immunohistochemistry, to analyze the correlation between DEK expression and clinicopathologic parameters, and to evaluate the value of DEK as a predictive marker for clinical outcome in OSCC.  Methods: Ten normal oral mucosa samples and 60 OSCC samples were studied by immunohistochemistry. The immunostaining for DEK was scored as 0 (no or  50% positive cells). Cases with a score ≥ 2 were defined as high expression. Correlation between DEK expression and clinicopathological parameters were analyzed by k2 test and Fisher's exact tests. The survival rates were calculated using the Kaplan-Meier method and analyzed using the log-rank test. P   Results: High expression of DEK protein (score ≥ 2) was found in 68.3% of OSCC cases. Statistical analysis revealed that DEK overexpression in OSCC was positively correlated with high histologic grade (p = 0.001), lymph node metastasis (p = 0.003), and advanced clinical stage (p = 0.039). In the Kaplan-Meier survival analysis, DEK overexpression was significantly associated with decreased overall survival in patients with OSCC (p = 0.019).  Conclusions: We demonstrated the clinical significance of DEK overexpression in OSCC tissue samples. DEK overexpression correlated with worse clinical outcome of patients with OSCC. Therefore, our results suggest that DEK overexpression may be a reliable marker to predict the clinical outcome in OSCC.  Disclosure: All authors have declared no conflicts of interest.
Flaws in Patient Safety Measures
Authors: Jordan B. Glaser, Dina Wong, Rabih Maroun
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
An Introduction to Neurology.
Authors: C. Judson Herrick
Journal: JAMA (1927)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The risks of having children in later life
Authors: Z. Stein
Journal: BMJ (2000)

General practice p 1708 

When is the best time in life to be a mother? Or a father? These questions have been raised in the past, but the answers have left uncertainties. To address some of these issues, Andersen et al, in their paper on maternal age and fetal loss in this issue of the BMJ , have used a large set of data from the Danish Epidemiology Science Centre to good effect (p 1708).1 Their findings are largely confirmatory: older age strongly increases a woman's chances of at least three untoward outcomes—namely, stillbirth, miscarriage, and ectopic pregnancy. Prospective parents concerned about their age might hope for answers to other questions as well.

Over the past 50 years or so, options for controlling or enhancing fertility have grown. These changes began with the introduction of oral contraception and have continued with the legalisation of induced abortion and the development of ever more sophisticated techniques of in vitro fertilisation and advances in obstetrics that ensure safe deliveries. Older women especially benefit from all of these; each has had an impact on the age at which women bear children.

For instance, the Danish tables show trends in the rates of induced abortions over the period 1978-92. On one side of the reproductive age span, these occur proportionately most frequently during the teens, when the greatest social disadvantage is associated with childbearing. On the other side, the greatest number of induced …
New cancer journal to seek strategies for developing countries
Authors: Ganapati Mudur
Journal: BMJ (2000)

Asian doctors have launched a quarterly medical journal intended to focus on cancer prevention and treatment strategies in developing countries.

The Austral-Asian Journal of Cancer , released in India last week, will address cancer issues relevant to developing countries that are not always adequately discussed in current cancer journals, oncologists associated with the journal said.

Developing countries are expected to account for two thirds of an estimated 15 million new annual cancer cases by 2015, but they have to make do with just 5% of global resources for cancer control.

“The journal should stimulate a search for …
Adjuvant Chemotherapy and Immunotherapy for Colorectal Cancer: Preliminary Communication
Authors: J Bancewicz, K C Caiman, S G Macpherson, C S McArdle, J G McVie, M Soukop
Journal: Journal of the Royal Society of Medicine (1980)

Following surgical resection of Dukes’ B or C colorectal cancers 72 patients have been randomly allocated to receive: 5-fluorouracil; or 5-fluorouracil and levamisole; or no treatment. Adjuvant treatment was continued for one year. 66 patients remain evaluable for up to 24 months. Preliminary results show no significant differences in survival or recurrence rates. Two patients receiving 5-fluorouracil and levamisole developed severe, but reversible, neutropenia. Other side effects were uncommon.
Science, medicine, and the future: Behaviour and genes
Authors: P. McGuffin, N. Martin
Journal: BMJ (1999)

New discoveries in genetics seem to hit the headlines almost daily, and probably the most eyecatching and controversial are those dealing with human behaviour. Thus, there has been popular media interest in reports of genes conferring susceptibility to psychiatric diseases and a whole range of “genes for” traits such as aggression, intelligence, and neuroticism. The scope for sensationalism and oversimplification is great. Here, we outline some of the basic concepts and lines of evidence from quantitative genetics indicating that genes do have important influences in determining human behaviour but that this nearly always involves an interplay with the environment. We then look at ways in which molecular methods are being used to locate and identify genes and how such approaches may impact on clinical practice.

We tend to resemble our parents, siblings, and other close relatives not just in the way we look but in the way we behave. However, the types, patterns, and causes of familial behavioural traits are extremely varied. They range from rare single gene disorders, such as Huntington's disease, that present with dramatic changes in behaviour in adult life, to commoner but more genetically complex disorders, such as schizophrenia and manic depression, through to normal variation in traits that are usually measured quantitatively, such as personality or intelligence.1 They can also include characteristics such as political or religious persuasion and career choice.

One of the basic pitfalls in studying the genetics of behaviour (or indeed any other type of trait) is to assume that familiality necessarily implies genetic transmission or that strong evidence of familial clustering implies single gene effects. Geneticists have long been aware that mendelian inheritance can be simulated by other mechanisms.2 To illustrate this, McGuffin and Huckle studied the educational histories of the families of a cohort of medical students: they …
Sailboats Racing on the Delaware
Authors: M Therese Southgate
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Effectiveness of Integrated Care on Pediatric Behavioral Health
Authors: David J. Kolko
Journal: JAMA Pediatrics (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Signal Transduction in Lung Cells
Journal: Thorax (1993)

Part 1 General concepts: molecular diversity and functional correlates in transmembrane signalling by G proteins, Lutz Birnbaumer et al regulation of G protein-linked receptors - analysis from the genome to the cell membrane, Craig C. Malbon and John R. Hadcock G proteins in pulmonary and cardiovascular signal transduction systems, Vsevolod A. Tkachuk et al small GTPases, Burton F. Dickey and Jeffrey B. Rubins phosphoinositides and intracellular calcium, Frank S. Menniti et al protein-tyrosine kinases, Timothy O'Hare et al protein tyrosine phosphatases - a multigene family of diverse structure and function, Deborah E. Cool purinergic signal transduction - extracellular ATP and adenosine as agonists for receptor-mediated signalling, George R. Dubyak. Part 2 Epithelial cells: epithelial cells Na+ and Cl- channels, Sadis Matalon et al protein phosphorylation and dephosphorylation systems in alveolar epithelial cells, David Warburton et al growth factors and pulmonary epithelia, Rita M. Ryan and Jacob N. Finkelstein expression and regulation of chemotactic cytokine genes by nonimmune pulmonary cells, Steven L. Kunkel et al cellular and biochemical mechanisms of airway epithelial mucin release, K. Chul Kim dysregulation of cellular genes by latent viral genes, Lois J. Geist and Gary W. Hunninghake. Part 3 Smooth muscle cells: role of calcium in the regulation of smooth muscle tone, Katheleen G. Morgan the role of myosin phosphorylation in smooth muscle and macrophage signalling, Primal de Lanerolle et al growth factors and signal transduction in smooth muscle systems, Morley D. Hollenberg. Part 4 Endothelial cells: ionic currents in the membranes of cultured endothelial cells, P. Bregestovski et al receptor-dependent regulation of [Ca2+] and phospholipase C in vascular endothelial cells, Pavel Avdonin et al secretion profiles of vasoactive amine-induced leukocyte chemoattractants - evidence for endothelial cell heterogeneity, Dennis J. Beer and Harrison W. Farber high-altitude pulmonary hypertension and signal transduction in the cardiovascular system, A.A. Aldashev. Part 5 Cells of the immune system: alveolar macrophage growth-factor signalling systems, James C. Bonner and Arnold R. Brody the role of the GTPase superfamily in T-lymphocyte signal transduction, Thomas C. Ryan and William W. Cruikshank mechanisms of mast cell signalling, Stephen I. Wasserman et al beta-adrenergic receptors on alveolar macrophages and lymphocytes - studies with cells from asthmatics, Sergey A. Rudchenko et al.