tbuckley/cabot-search huggingface dataset:
Feasibility and phase I trial of tandutinib in patients with recurrent glioblastoma
Authors: J. G. Supko, S. A. Grossman, D. M. Peereboom, S. Chowdhary, G. J. Lesser, L. B. Nabors, T. Mikkelsen, S. Desideri, T. T. Batchelor
Journal: Journal of Clinical Oncology (2009)

2039 Background: Platelet-derived growth factor signaling is important in gliomagenesis and PDGFR-β is expressed on &gt;90% of endothelial cells in glioblastoma specimens. Methods: We report the results of a feasibility and phase I study of tandutinib (MLN518), an orally bioavailable, quinazoline-based inhibitor of type III receptor tyrosine kinases including PDGFR-β, FLT-3, and c-Kit, in patients with recurrent glioblastoma (GBM) conducted in the New Approaches to Brain Tumor Therapy (NABTT) consortium. Results: A feasibility study was conducted in 6 recurrent GBM patients in whom resection was clinically indicated. These patients received tandutinib 500-mg BID for 7 days prior to resection. In these patients, the drug was measured in tumor tissue and plasma samples obtained shortly before and after the resection by LC/MS. The mean ± SD concentration of tandutinib in tumor tissue was 7.2 ± 3.2 μg/mL and the mean ratio of its concentration in brain tumor-to-plasma was 9.6 ± 7.7. A phase I study was conducted in 19 patients to determine the MTD in this recurrent GBM population with sequential assessment of the following dose levels: 500-, 600-, and 700-mg BID. Four patients were replaced due to early withdrawal unrelated to toxicity. Dose limiting toxicities were observed in 1/6 patients at 500-mg BID (grade 3 phosphorous, grade 3 fatigue, grade 3 somnolence in 1 patient); 1/6 patients at 600-mg BID (grade 3 phosphorous); 2/3 patients at 700-mg BID (grade 3 fatigue, grade 3 weakness). 600-mg BID was declared the MTD and a phase II study has been initiated at this dose level. Conclusions: The mean brain tumor tissue-to-plasma ratio of tandutinib in GBM patients receiving 500-mg BID exceeded the estimated threshold ratio of 0.33 that was considered as being necessary to achieve local cytotoxic concentrations in brain tumors. The MTD of tandutinib in the recurrent GBM population is 600-mg BID. A phase II trial has been initiated at this dose level. [Table: see text]
Imatinib for the treatment of aggressive fibromatosis (desmoid tumors) failing local treatment. A phase II trial of the French Sarcoma Group
Authors: N. Penel, A. Le Cesne, B. Bui, M. Tubiana-Hulin, C. Guillemet, D. Cupissol, P. Berthaud, C. Mahier, D. Pérol, J. Blay
Journal: Journal of Clinical Oncology (2006)

9516 Background: Background: Aggressive fibromatosis/desmoid tumors (AF/DT) are rare tumors with loco regional spreading. Few options are available when local treatments have failed. Although cytotoxic agents, hormonal treatment have been reported to induced responses and tumor control in some patients, only few prospective phase II trials have been reported in the literature. Recently, antitumor activity of imatinib in AF/DT was reported. We report a phase II trial of imatinib in AF/DT after failure of local treatment options. Methods: Pts ≥ 18 years with advanced AF/DT from all sites in whom neither surgery nor radiotherapy was possible were eligible. The principal inclusion criterias were: disease not amenable to surgery and/or radiation with curative intent, systemic pre-treatments allowed and presence of a measurable lesion with evidence of progression. Imatinib was given at the dose of 400 mg/d and increased to 800 mg/d if progression. Primary endpoint was the rate of progression free at 3 months. A two stages Simon‘s optimal design was used with p 0 =10%, p 1 =30%, α=0.05 and 90% power. 18 pts were scheduled to be recruited in the first stage for a total of 35 evaluable pts. Results: Between 09/2004 and 10/2005, 40 pts were included in 15 centers. The median age was 40 years (range 20–72) with 26% males. Primary sites were extra abdominal, mesenteric, abdominal wall in 79, 15, and 6% respectively. 15% patients had not been operated previously and 17% undergone radiotherapy. Prior systemic treatments were: NSAID, hormonal therapy or chemotherapy in 34, 46 and 23%, respectively. Median treatment duration was 4 months (range 0–12). No G4 toxicity was reported. Toxicities (G1–3) were notified for 30 pts including asthenias (70%), nauseas (53%), diarrheas, oedema (40%). G3 toxicities were abdominal pain (10%), rash, nausea, vomiting and asthenia (7%). At 3 months, 22 pts (55%) were evaluable with 1 CR, 17 SD and 4PD. As of December 2005, 7 of the 40 pts had progressed. After progression, dose was stopped in 2 pts and increased to 800mg in 5 pts with 2 tumor control following dose-escalation. Conclusions: Imatinib induces prolonged disease stabilization in the majority of evaluable patients with AF/DT in whom no local treatment option was available. [Table: see text]
Foreigh body aspiration by a 31 years old female patient, mimics diaphragmatic hernia
Authors: Styliani Sarantoulaki, Maria Mouzouraki, Emmanouil Ntaoukakis
Journal: European Respiratory Journal (2012)

Introduction: We present a case of food aspiration by a 31 years old female patient, masquerading as diaphragmatic hernia.  Aims and Objectives: Our aim is to show that food aspiration is a life threatening condition and it can easily escape detection.  Methods: A 31 years old female presented at the emergency department with shortness of breath. Her past history was unremarkable. The chest X-ray demonstrated total collapse of the left lung and herniation of the stomach and large intestine into the left pleural cavity. Chest CT- scan demonstrated the presence of stomach and large bowel in the left chest suggesting a posterolateral diaphragmatic hernia. The patient was subjected to an posterolateral thoracotomy. To our surprise there was only local eventration of the left hemidiaphragm. Atelectasis of the left lung persisted despite ventilation with high pressures.The patient subjected in intraoperative flexible bronchoscopy and there was presented a large quantity of mucus surrounding a soft mass adhered at the wall of the bronchus. Rigid bronchoscopy was performed the following day and a piece of meat was extracted.  Results: Atelectasis soon dissapeard and the patient had normal breath again, after the extraction of the food mass.  Conclusion: Foreigh body aspiration is unusual in adults, except those who are debilitated or have neuropsychiatric disorders. The doctors must be suspicious about this condition even in young healthy patients and bronchoscopy must be used as diagnosting and therapeutic step, before the patient subject a thoracotomy.
Vitamin D: a novel therapeutic approach for keloid, an in vitro analysis
Authors: G.Y. Zhang, T. Cheng, Q. Luan, T. Liao, C.L. Nie, X. Zheng, X.G. Xie, W.Y. Gao
Journal: British Journal of Dermatology (2010)

Background Vitamin D and its metabolites play an important role in calcium homeostasis, bone remodelling, hormone secretion, cell proliferation and differentiation. Recent studies also suggest a beneficial role of vitamin D in slowing the progression of tissue fibrosis. However, their effects on dermal fibrosis and keloids are unknown. Objectives To investigate the effect of 1,25-dihydroxyvitamin D3 (1,25D) in the pathogenesis of tissue fibrosis by keloid fibroblasts (KFs). Methods KFs were cultured and exposed to different concentrations of 1,25D in the presence or absence of transforming growth factor (TGF)-β1. KF phenotypes and protein production were analysed by real-time reverse transcriptase-polymerase chain reaction, Western blot, immunofluorescence and multiplex enzyme-linked immunosorbent assay techniques. Collagen synthesis was evaluated by measuring 3H-proline incorporation. The effect of 1,25D on cell proliferation and viability was evaluated by Formazan assay, proliferating cell nuclear antigen expression and the colorimetric conversion of 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide. Results We confirmed the presence of vitamin D receptors (VDRs) in cultured keloid fibroblasts. Fibroblasts transfected with a vitamin D response element reporter construct and exposed to the active vitamin D metabolite 1,25D showed increased promoter activity indicating VDR functionality in these cells. Incubation of KFs with 1,25D suppressed TGF-β1-induced collagen type I, fibronectin and α-smooth muscle actin expression. 1,25D also modulated plasminogen activator inhibitor-1 and matrix metalloproteinase-9 expression induced by TGF-β1. Interestingly, 1,25D induced hepatocyte growth factor mRNA expression and protein secretion in keloid fibroblasts. Conclusions This study highlights key mechanistic pathways through which vitamin D decreases fibrosis, and provides a rationale for studies to test vitamin D supplementation as a preventive and/or early treatment strategy for keloid and related fibrotic disorders.
Effects of Breastfeeding on Obesity and Intelligence
Authors: Lisa G. Smithers, Michael S. Kramer, John W. Lynch
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
Primary mediastinal B-cell lymphoma with sclerosis: an aggressive tumor with distinctive clinical and pathologic features.
Authors: M Lazzarino, E Orlandi, M Paulli, E Boveri, E Morra, E Brusamolino, S Kindl, R Rosso, C Astori, M C Buonanno
Journal: Journal of Clinical Oncology (1993)

To evaluate the clinical features of presentation, the morphologic and immunohistochemical pattern, the modality of spread, and the response to current treatments of patients with primary mediastinal B-cell lymphoma, a recently documented subtype of non-Hodgkin's lymphoma (NHL).Thirty consecutive patients (14 males, 16 females; median age, 26 years) with primary mediastinal B-cell lymphoma with sclerosis were studied.The clinical aspects were largely homogeneous: 93% presented with chest symptoms of a rapidly enlarging mass of the anterior mediastinum; the tumor was bulky in 73%, and superior vena cava syndrome (SVCS) was present in 57%. Also, patients without SVCS symptoms showed subclinical venacaval compression at computed tomographic (CT) scan, for a total incidence of caval obstruction of 80%. Intrathoracic extension to adjacent organs was seen in 47% of patients. Despite its invasive behavior, only four patients showed extrathoracic spread at diagnosis. In 23 cases, the tumor presented with morphologic features that resembled follicular center-cell lymphomas. In seven, the neoplastic population was composed mainly of centrocyte-like cells with abundant clear cytoplasm not referable to any known B-cell lymphoma subtype. All cases showed huge sclerosis. Of 29 patients assessable for response, 16 (55%) achieved a complete response (CR): five of 14 (36%) treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 11 of 15 (73%) treated with methotrexate plus leucovarin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) or etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) (P = .047). We could identify no clinical, biologic, or histopathologic features significantly correlated with response. After chemotherapy, 14 of 16 remitters received consolidation radiotherapy to the mediastinum. At 3 years, the actuarial survival rate is 38% for all cases and 72% for remitters. None of the 13 patients who did not achieve CR responded to salvage treatments.This study shows that primary mediastinal B-cell lymphoma with sclerosis is a distinctive subtype of NHL with unique clinicopathologic aspects and aggressive behavior. Prompt recognition and aggressive treatment may provide long survival in a good proportion of cases. However, a subset of patients is extremely refractory to first- and second-line treatment. Conventional prognostic factors seem inadequate to identify these very-poor-risk cases.
Is It Better to Be Rich or Relaxed? Sociobiology Meets Bone Marrow Transplant
Authors: Lucie M. Turcotte, Michael R. Verneris
Journal: Clinical Cancer Research (2015)

Low socioeconomic status in hematopoietic cell transplant recipients is associated with increased treatment-related mortality and relapse, resulting in reduced survival. No biologic mechanism has been identified for these associations. The stress-related gene expression profile, termed the "conserved transcriptional response to adversity," may be a predictor of these negative outcomes.
Abstract 16269: Targeted Deletion of Thioredoxin-Interacting Protein (Txnip) Enhances Anaerobic Metabolism and Mitochondrial Thioredoxin Activity and Protects the Heart from Ischemia Reperfusion Injury
Authors: Jun Yoshioka, William A Chutkow, Jie Yan, Rong Tian, Jae Bum Kim, Christine E Seidman, J G Seidman, Richard T Lee
Journal: Circulation (2010)

Thioredoxin-Interacting Protein (Txnip) is a regulator of metabolism and an inhibitor of the antioxidant thioredoxin, but little is known about roles of Txnip in the myocardium. We previously showe...
An international survey of current pulmonary arterial hypertension (PAH) management
Authors: Ioana Preston, Barbara Hinzmann, Nicholas Bawden, Henning Tiede
Journal: European Respiratory Journal (2012)

Background:  The therapeutic approach to PAH is evolving, multiple classes of agents are available and physicians from expert centres and the community treat PAH.   Objectives:  To compare therapeutic management of PAH between countries and explore physicians9 attitudes towards PAH-specific therapies.   Methods:  Quantitative online survey conducted in 5 European countries, the US, and Canada during 2010. Physicians involved in PAH treatment decisions with experience in managing PAH for ≥2 years completed a perceptual questionnaire. Retrospective clinical records from last 5 patients (pts) seen by each physician were analysed.   Results:  472 physicians (43% cardiologists, 29% pulmonologists, 20% rheumatologists, and 8% internists), 62% based in pulmonary hypertension centres, entered data for 2360 pts. Among those, 51% had idiopathic PAH and 42% had PAH associated with other conditions; 38% had significant physical limitation (NYHA functional class III/IV) at diagnosis. US pts were more likely to be diagnosed in the community (40%) than pts in Europe (6%) and Canada (28%). Globally, 73% were on PAH-specific therapy, with PDE-5 inhibitors, endothelin receptor antagonists, and prostacyclins used in 57%, 54%, and 26%, respectively. Of pts treated, 29% were on combination therapies; highest usage was in the US (36%) and lowest in Italy (17%). For 95% of pts, their physicians were satisfied to some degree with the current treatment regimen. Main reasons for satisfaction included symptom control or improvement and stable disease condition.   Conclusions:  This multinational survey highlights significant differences in PAH management between countries and illustrates physicians9 perceptions of treating this condition.
Statistical controversies in clinical research: assessing pathologic complete response as a trial-level surrogate end point for early-stage breast cancer
Authors: E.L. Korn, M.C. Sachs, L.M. McShane
Journal: Annals of Oncology (2015)

A trial-level surrogate end point for a randomized clinical trial may allow assessment of the relative benefits of the treatment to be performed at an earlier time point and potentially with a smaller sample size. However, determining whether an end point is a reliable trial-level surrogate based on results of previous trials is not straightforward. The question of trial-level surrogacy is easily confused with the question of individual-level surrogacy, and this confusion can lead to controversy. A recent example concerns the evaluation of pathologic complete response (pCR) as a surrogate for event-free survival (EFS) and overall survival (OS) in early-stage breast cancer.The differences between individual-level surrogacy (i.e. for patients receiving a specific treatment, the surrogate end point predicts the definitive end point) and trial-level surrogacy (the results of the trial for the surrogate end point predict the results of the trial for the definitive end point) are discussed. Trial-level data used in two previous meta-analyses evaluating pCR as a trial-level surrogate for EFS and OS were re-analyzed using methods that appropriately account for the variability in pCR rates as well as the variability in the hazard ratios for EFS and OS.There is no evidence that pCR is a trial-level surrogate for EFS or OS, nor is there evidence that pCR could be used reliably to screen out nonpromising agents from further drug development.At present, neoadjuvant RCTs should continue to follow patients to observe EFS and OS to assess clinical benefit, and they should be designed with sufficient sample size to reliably assess EFS. However, one cannot rule out the possibility that future meta-analyses involving more trials and in which the patient population or class of treatments is restricted could suggest the validity of pCR as a trial-level surrogate for EFS or OS in some focused settings.
Extension of in vivo half-life of biologically active molecules by XTEN protein polymers
Authors: Vladimir N. Podust, Sibu Balan, Bee-Cheng Sim, Michael P. Coyle, Ulrich Ernst, Robert T. Peters, Volker Schellenberger
Journal: Journal of Controlled Release (2015)

XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted.
The prevalence and descriptive epidemiology of atopic dermatitis in Singapore school children
Authors: Y-K. Tay, K-H. Kong, L. Khoo, C-L. Goh, Y-C. Giam
Journal: British Journal of Dermatology (2002)

Atopic dermatitis is a common disease that appears to be increasing in frequency during recent decades. Most of the studies are based on the Western population, and there are few data in the Asian population.To determine the prevalence and descriptive epidemiology of atopic dermatitis among school children in the general community in Singapore.This is a questionnaire study of 12 323 students done over a 1-year period, comprising 7 year olds (4605), 12 year olds (3940) and 16 year olds (3778) from 19 primary and 17 secondary schools randomly selected in Singapore. All children had a complete cutaneous examination. The diagnosis of atopic dermatitis was based on the U.K. Working Party diagnostic criteria. The questionnaire was translated into Chinese and both the English and Chinese versions were issued simultaneously to the students.The 1-year period prevalence of atopic dermatitis was 20.8%. Atopic dermatitis was present in 22.7% of 7 year olds, 17.9% of 12 year olds and 21.5% of 16 year olds. The overall sex ratio was equal. There were slightly more boys with atopic dermatitis among the younger children (6 and 12 year olds, 1.18 : 1 and 1.19 : 1, respectively) but more girls were affected (1.57 : 1) among the 16 year olds. Atopic dermatitis was more common among the Chinese (21.6%) and Malays (19.8%) compared with the Indians (16%) and other races (14%). The onset of the disease occurred before the age of 10 years in 49.5% of the 16 year olds. "Pure" atopic dermatitis without concomitant respiratory allergies was noted in 788 respondents (30.7%); 1775 (69.3%) suffered from a "mixed" type, with 34.3% having allergic rhinitis, 9.5% having asthma and 25.5% having both asthma and allergic rhinitis. More boys had atopic dermatitis and concomitant respiratory allergies whereas more girls were affected with "pure" atopic dermatitis alone (1.4 : 1). At least one first-degree family member with atopy was noted in 1435 children (56%): atopic dermatitis (70%), asthma (62%) and allergic rhinitis (68%). Among siblings with one parent with atopic dermatitis, 37% had either a father or a mother with atopic dermatitis. Common aggravating factors reported included exercise, heat and sweating, grass intolerance, thick clothing and stress. Pityriasis alba was noted in 25% of the study population, keratosis pilaris in 13% and ichthyosis vulgaris in 8%. Most respondents had mild to moderate atopic dermatitis that could be controlled with a fairly simple regimen of moisturizers, topical steroids, antihistamines and antibiotics.The high prevalence of atopic dermatitis in Singapore is similar to that observed in developed countries, suggesting that environmental factors may be important in determining the expression of the disease.