tbuckley/cabot-search huggingface dataset:
Chemoprevention with erlotinib and celecoxib in advanced premalignant lesions of the head and neck: Results of a phase I study.
Authors: N. F. Saba, S. Muller, A. Y. Chen, W. Grist, K. Gibson, S. Nannapaneni, C. S. Yang, F. R. Khuri, Z. G. Chen, D. M. Shin
Journal: Journal of Clinical Oncology (2010)

5535 Background: Epidermal growth factor receptor (EGFR) inhibitors and cyclooxygenase 2 (COX-2) inhibitors synergistically inhibit tumorigenesis in head and neck squamous cell carcinoma (HNSCC). We present the results of a phase I study with the combination of erlotinib and celecoxib in advanced premalignant lesions. Methods: Between October 24, 2006 and December 1, 2009, 34 subjects with pathologic dysplasia, moderate (MD) or severe dysplasia (SD), and carcinoma in situ (CIS) were screened. Fifteen subjects were enrolled, 3 of whom withdrew consent. A total of 11 subjects received therapy. A biopsy of lesions, and cytobrush of normal mucosa were performed at baseline and 3, 6 and 12 months. Erlotinib was escalated following a standard 3+3 design at 50 mg, 75 mg, and 100 mg PO daily and celecoxib was fixed at 400 mg twice daily, for 6 months. Results: Three subjects were enrolled on cohort 1 with no dose limiting toxicities (DLT) observed, allowing escalation to cohort 2. One patient had a grade 3 rash and cohort 2 was expanded to 6 subjects. As a second subject had grade 3 rash, the maximum administered dose (MAD) of erlotinib was deemed at 75 mg. An additional 3 subjects will be enrolled on cohort 1 which will be counted towards the efficacy analysis of the phase II component. Responses for 7 evaluable subjects using the last documented histologic response at 3, 6 or 12 months were noted. At baseline, 3/7 (43%) had MD and 4/7 had SD (57%). 3/7 achieved a complete remission (CR 42%), 2/7 a partial remission (PR 29%), and 2/7 progressive disease (PD 29%) with an overall response rate RR of 71%. The pharmacokinetics (oral clearance and half life) of erlotinib, were comparable to previously reported studies with erlotinib alone. Biomarker analysis suggested a correlation between EGFR and p-ERK modulation and histologic response (p=0.019 and p=0.006 for EGFR and p-ERK respectively). No correlation was observed with COX-2 (p=0.43). Conclusions: In this phase I study, the MAD of erlotinib is 75 mg. Preliminary data reveal an overall RR of 71%. Further biomarker analysis is underway and the phase II study is planned. No significant financial relationships to disclose.
Phase 1 MMRC Trial of Selinexor, Carfilzomib (CFZ), and Dexamethasone (DEX) in Relapsed and Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Andrzej Jakubowiak, Jagoda Jasielec, Cara A. Rosenbaum, Jeffrey A Zonder, Craig E. Cole, Ajai Chari, Jennifer Nam, Leonor A Stephens, Kathryn McDonnell, Rebecca Uribe, Shaun Rosebeck, Tami Rashal, Hagop Youssoufian, Sarah Henry, Sharon Shacham, Michael Kauffman, Todd Zimmerman, Theodore Karrison
Journal: Blood (2015)
Induction chemotherapy followed by concomitant chemoradiotherapy in locally advanced rectal carcinoma.
Authors: Inas Ibraheim Abdel Halim, Wael El-Sadda, Mostafa El Ebrashy, Waleed El Nahas
Journal: Journal of Clinical Oncology (2014)

e14546 Background: Locally advanced rectal cancer (LARC) represents a major therapeutic challenge. Preoperative chemoradiation has recently been approved as the new standard of care in the management of LARC. Capecitabine is an oral fluoropyrimidine converted to active 5-FU into the tumor. Induction chemotherapy XELOX followed by pelvic RT plus capecitabine achieved high rates of pathologic complete response. The aim of the study is to evaluate the efficacy, safety and response rate of induction chemotherapy with XELOX followed by chemoradiotherapy and its impact on progression free survival and overall survival. Methods: Between September 2011 and September2013; 40 patients (25 males and 15 females) with LARC (T3–T4/N±) were enrolled in the study, all patients received oxaliplatin 130 mg/m2 D1 plus capecitabine 1000 mg/m2 twice daily for 14 days, repeated every 21 days for 3 cycles then patients received oral capecitabine 825 mg/m2 twice daily on radiotherapy days. Radiation therapy was administered in 1.8 Gy/fraction, 5 days per week, with a total dose of 45 Gy, followed by surgery. The average time between the neoadjuvant chemoradiation and the surgery was 6–8 weeks. Results: All patients received 3 cycles of induction chemotherapy and concomitant chemoradiothrapy. A pathologic complete response (pCR) was achieved in 10 patients (25 %), overall tumors and nodal downstaging occurred in 24 patients (60%) including 20% pT0N0 with sphincter preservation in 40% of patients, and there was no response in 6 patients (15%). Eighteen patients (45%) had an abdominoperineal resection and 22 patients (55%) had a low anterior resection, No grade 4 toxicity were detected. The most common grade 3 toxicity was diarrhea (15%), while G2 toxicities was represented as; stomatitis (10%), radiodermatitis (10%) hand and foot syndrome (10%) and peripheral neuropathy (5%). Conclusions: Induction chemotherapy (XELOX) followed by concomitant CRT before surgery showed high pCR rate without increasing adverse events or surgical complications.
On the &lt;italic&gt;In Vitro&lt;/italic&gt; and &lt;italic&gt;In Vivo&lt;/italic&gt; Protein-binding of &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide and Related Compounds
Authors: John H. Weisburger, Preston H. Grantham, Harold P. Morris, Elizabeth K. Weisburger
Journal: JNCI Journal of the National Cancer Institute (1961)

Data are presented on the distribution of radioactivity after one intraperitoneal injection of C14-labeled N-2-fluorenylacetamide (2-FAA) into rats as a function of dose, from 10 to 0.01 mg/100 g, and of time, from 6 hours to 32 days. The urinary metabolites were qualitatively and quantitatively similar at all time intervals and dosages. The activity in blood, liver, and soluble and insoluble liver proteins decreased with decreasing doses, but not directly proportionally. The isotope in blood and liver, highest at 6 hours, dropped more rapidly in liver than in blood. Maximal labeling of the liver proteins occurred at 1 day. Hydrolysis of the labeled proteins by acid, alkali, or enzymes rendered 50 to 60 percent of the activity extractable into organic solvents. Details of the solvent partition and chromatographic experiments performed on the hydrolysate are presented. Amounts of 0.3 and 0.7 percent of the activity in the labeled protein were due to 2-FAA and 2-fluorenamine, respectively. The balance consisted of at least 6 more polar materials. Thus, with 2-FAA more than one metabolite and protein are involved in the labeling of tissues. Homogenization of rat liver with labeled 2-FAA or hydroxylated metabolites under various conditions gave negligible binding. However, the aminofluorenols studied led to considerable “protein-bound” activity by homogenization or by the mixture of soluble proteins with a solution of the compound. This artifact-binding took place to a larger extent with the ortho-aminofluorenols than with 7-amino-2-fluorenol. In contrast to the binding in vivo, no radioactivity was rendered extractable into organic solvents after hydrolysis of the proteins labeled in vitro. Artifact-binding seems to play only a limited role under conditions in vivo.
A phase II, multicenter study of the EZH2 inhibitor tazemetostat in adult subjects with INI1-negative tumors or relapsed/refractory synovial sarcoma.
Authors: Mark Agulnik, Nizar M. Tannir, Joseph Gerald Pressey, Mrinal M. Gounder, Gregory Michael Cote, Maria Roche, Susan Doleman, Stephen J Blakemore, Alicia Clawson, Scott Daigle, Jeanie Tang, Peter T.C. Ho, George D. Demetri
Journal: Journal of Clinical Oncology (2016)

TPS11071 Background: Tazemetostat is a potent and selective inhibitor of the histone methyltransferase enhancer of zeste-homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2). EZH2 is responsible for trimethylation of lysine 27 on histone H3, which results in chromatin remodelling and repressed transcription. Aberrant EZH2 activity has been implicated as an oncogenic driver in non-Hodgkin lymphoma and other malignancies. The SWI/SNF complex also remodels chromatin, activates transcription and acts in opposition to PRC2. Oncogenesis from mutation and/or loss of the SWI/SNF subunit INI1 in cancers such as malignant rhabdoid tumor (MRT) or SMARCA4 loss in ovarian "small cell carcinoma, hypercalcemic type" is associated with anticancer activity of EZH2 inhibition in preclinical models. This has translated into objective responses of promising durability in subjects (subjs) whose solid tumors exhibited either INI1 or SMARCA4 loss in the tazemetostat phase I adult study. Methods: This is a phase II, multi-center, open-label, single arm study of tazemetostat (800 mg dosed orally twice daily) in subjs whose tumors harbor mutation and/or loss of INI1 or SMARCA4. Subjs ≥ 16 years of age who have measurable disease enroll into 1 of 3 cohorts: Cohort 1 -INI1 or SMARCA4 negative rhabdoid tumors (MRT, atypical teratoid rhabdoid tumor, rhabdoid tumor of the kidney, MRT of ovary), Cohort 2 - relapsed/refractory synovial sarcoma, and Cohort 3 -other INI1 negative tumors including epithelioid sarcoma, renal medullary carcinoma, myoepithelial carcinoma, and others. Each cohort will enroll up to 30 subjs using a 2-stage Green-Dahlberg design. Tumor response is evaluated every 8 weeks using RANO or RECIST 1.1. Primary endpoints include overall response rate (ORR) (Cohorts 1 and 3) and progression-free survival (PFS) at Week 16 (Cohort 2). Secondary endpoints include ORR (Cohort 2), PFS and overall survival, duration of response, safety/tolerability, population PK and biomarkers of response. The first subj was dosed in December 2015 in the US with additional sites to be opened in Canada, the EU and Australia (NCT02601950). Clinical trial information: NCT02601950.
Inflammatory Pseudotumor of Lung: A Case Report
Authors: K Nishigauchi, H Nakamura, H Nakamura, K Yamakawa, T Matsumoto, T Nakanishi, H Nakano, T Nagasawa
Journal: JAMA (1963)

A case of inflammatory pseudotumor of the lung is reported. A 24-year-old male was referred for further examination of an abnormal shadow on chest radiography performed during a mass survey. Medical imaging data, including CT study, led to a diagnosis of benign tumor of the right lung. After right middle lobectomy, the lesion was diagnosed as inflammatory pseudotumor on the basis of histopathological study.
Platinum-based therapy and oral cyclophosphamide as salvage therapy in heavily pretreated metastatic castrate resistant prostate cancer (mCRPC) patients with poor performance status and bulky/LN/visceral disease.
Authors: Evangelos Bournakis, Eftychia Kafantari, Efthimios Kostouros, Revekka Gyftaki, Aristotelis Bamias, Meletios A. Dimopoulos, Eleni Efstathiou
Journal: Journal of Clinical Oncology (2014)

e16096 Background: platinum based therapy is a potentially valid choice for heavily pretreated mCRPC patients (pts) whose disease progresses with anaplastic features. Methods: This is a retrospective analysis of heavily pretreated symptomatic mCRPC pts with progressive mCRPC, treated with weekly cisplatin 25mg/m2 or carboplatin 1.5 AUC iv and oral cyclophosphamide 50mg bid for 3/4weeks in 28day cycles. Pt performance status (PS ECOG) pretreatment and best response were monitored as well as symptoms, adverse events, PSA, LDH, ALP and imaging. Weekly or biweekly CBC, chemistry and physical examination were performed Results: since May 2010, 29 pts initiated the regimen and 27/29 were evaluable. Median age is 76 yrs (range 61-90), PS ECOG 3 (range 1-4). Twenty-One/29 experienced “explosive” disease progression prior to treatment, 28/29 had > 20 bone mets, 23/29 lymph node mets and 12/29 visceral mets (1 brain mets) while 14/29 had bone marrow infiltration 71% of which had CBC findings (anemia-thrombopenia). All pts but one had received at least one prior chemotherapy regimen -docetaxel or cabazitaxel-median 2 chemotherapy lines (range 1-4) and 17/29 (58.6%) had also received one of the novel androgen signaling inhibitors (abiraterone acetate, orteronel, enzalutamide), median 1 (range 1-3). Pts had received prior to 1st line chemotherapy, 2-5 lines of hormonal treatment. Eighteen/27 (67%) evaluable pts experienced ECOG PS benefit, 18/27 (67%) had imaging response and 18/27 (67%) had >50% PSA decline. Main Grade 3 adverse event (AE) was anemia. Most common grade 2 AE was thrombopenia. Median therapy duration was 5.5 months (range 1.5-7.5) with 8 discontinuing upon progression and 2 due to attending physician’s decision. Among 9 non responders, 6/6 were only bone metastatic and 1 received the regimen in 2ndline after docetaxel. Conclusions: Platinum based therapy plus oral cyclophosphamide is a tolerable and promising regimen for heavily pretreated poor PS mCRPC pts with anaplastic disease behavior as opposed to best supportive care. Hematologic safety is the main concern. Further evaluation is warranted.
Respiratory decline is integral to disease progression in Huntington's disease
Authors: Una Jones, Monica Busse, Stephanie Enright, Anne E. Rosser
Journal: European Respiratory Journal (2016)

Huntington's disease is an autosomal inherited monogenetic condition in which the mutation is an expansion of the cytosine-adenine-guanine (CAG) repeat sequence at the N-terminal end of the huntingtin gene [1]. More than 40 repeats are associated with neuronal dysfunction and death, predominantly within the striatum resulting in a triad of movement, behaviour and cognitive impairment; other symptoms include weight loss, sleep disturbance and respiratory dysfunction, which may or may not be of primary neurological origin [1–3]. Death occurs 15–30 years after onset of symptoms [1], usually due to pneumonia [4], yet it is not known whether respiratory dysfunction is a feature of late stage disease or whether it appears earlier in the disease evolution. Previous research suggests that dysregulation within the respiratory centre results in irregular breathing patterns [5, 6]; decreased respiratory muscle strength and lung volumes have also been identified [7] which, alongside swallow dysfunction [4], could precipitate respiratory failure. Huntington's disease is a complex long-term condition and contributing factors such as swallow dysfunction, posture, physical inactivity and reduced exercise capacity have not yet been investigated in relation to respiratory function. We conducted a cross-sectional study aiming to characterise respiratory function across all stages of disease and explore primary and secondary contributors to respiratory decline. Given one previous report of respiratory weakness in Huntington's disease, we performed a follow-on study to assess the feasibility of home-based inspiratory muscle training in Huntington's disease. Respiratory function in Huntington's disease should be monitored from middle stage to preclude respiratory failure <http://ow.ly/YXTt300mIQw>
Update in Critical Care 2015
Authors: Martin Dres, Jordi Mancebo, Gerard F. Curley
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

This review documents important progress made in 2015 in the field of critical care. Significant advances in 2015 included further evidence for early implementation of low tidal volume ventilation as well as new insights into the role of open lung biopsy, diaphragmatic dysfunction, and a potential mechanism for ventilator-induced fibroproliferation. New therapies, including a novel low-flow extracorporeal CO2 removal technique and mesenchymal stem cell-derived microparticles, have also been studied. Several studies examining the role of improved diagnosis and prevention of ventilator-associated pneumonia also showed relevant results. This review examines articles published in the American Journal of Respiratory and Critical Care Medicine and other major journals that have made significant advances in the field of critical care in 2015.
Dissecting Clinical Heterogeneity in Neurofibromatosis Type 1
Authors: Courtney L. Monroe, Sonika Dahiya, David H. Gutmann
Journal: Annual Review of Pathology Mechanisms of Disease (2017)

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder in which affected children and adults are predisposed to the development of benign and malignant nervous system tumors. Caused by a germline mutation in the NF1 tumor suppressor gene, individuals with NF1 are prone to optic gliomas, malignant gliomas, neurofibromas, and malignant peripheral nerve sheath tumors, as well as behavioral, cognitive, motor, bone, cardiac, and pigmentary abnormalities. Although NF1 is a classic monogenic syndrome, the clinical features of the disorder and their impact on patient morbidity are variable, even within individuals who bear the same germline NF1 gene mutation. As such, NF1 affords unique opportunities to define the factors that contribute to disease heterogeneity and to develop therapies personalized to a given individual (precision medicine). This review highlights the clinical features of NF1 and the use of genetically engineered mouse models to define the molecular and cellular pathogenesis of NF1-associated nervous system tumors.
&lt;emph type="ital"&gt;Madonna and Child&lt;/emph&gt;
Authors: Janet M. Torpy
Journal: JAMA (2010)

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
Présence endémique de Salmonella enterica de sérotype Cerro au sud de l'Italie
Authors: C Mammina, L Cannova, S CarfiPavia, A Nastasi
Journal: Eurosurveillance (2000)

L’etude moleculaire de souches de salmonelles isolees entre 1997 et 1999 en Italie du Sud, menee par le Centre des Pathogenes Enteriques d’Italie du Sud, a montre une frequence importante de Salmonella enterica serotype Cerro, un serotype extremement rare chez l’homme, avec une majorite de ribotype rt2. Les auteurs emettent l’hypothese d’une dissemination de ce serotype a l’est de la Sicile et recommandent une surveillance prudente de ce serotype.
Guideline for obtaining valid consent for gastrointestinal endoscopy procedures
Authors: Simon M Everett, Helen Griffiths, U Nandasoma, Katie Ayres, Graham Bell, Mike Cohen, Siwan Thomas-Gibson, Mike Thomson, Kevin M T Naylor
Journal: Gut (2016)

Much has changed since the last guideline of 2008, both in endoscopy and in the practice of obtaining informed consent, and it is vital that all endoscopists who are responsible for performing invasive and increasingly risky procedures are aware of the requirements for obtaining valid consent. This guideline is restricted to GI endoscopy but we cover elective and acute or emergency procedures. Few clinical trials have been carried out in relation to informed consent but most areas are informed by guidance from the General Medical Counsel (GMC) and/or are enshrined in legislation. Following an iterative voting process a series of recommendations have been drawn up that cover the majority of situations that will be encountered by endoscopists. This is not exhaustive and where doubt exists we have described where legal advice is likely to be required. This document relates to the law and endoscopy practice in the UK—where there is variation between the four devolved countries this is pointed out and endoscopists must be aware of the law where they practice. The recommendations are divided into consent for patients with and without capacity and we provide sections on provision of information and the consent process for patients in a variety of situations. This guideline is intended for use by all practitioners who request or perform GI endoscopy, or are involved in the pathway of such patients. If followed, we hope this document will enhance the experience of patients attending for endoscopy in UK units.
Biophysics and physiology of cardiac calcium channels
Authors: C. W. Balke, W. C. Rose, B. O'rourke, R. Mejia-Alvarez, P. Backx, E. Marban
Journal: Circulation (1993)

Two types of calcium channels are present in heart cells; the two types, L and T, can be clearly distinguished on the basis of their biophysical and pharmacological properties. The physiological role of L-type Ca 2+  channels is clear and includes mediation of processes that are vital to the function of normal cardiac cells, such as electrical conduction and excitation-contraction coupling. The physiological role of T-channels is not known, although potential involvement in pacemaker activity can he hypothesized on the basis of their biophysical properties. The testing of these predictions is the subject of intense research interest at present
Have general hospitals become chronic care institutions for the mentally ill?
Authors: S A Salit, L R Marcos
Journal: American Journal of Psychiatry (1991)

Dramatic increases in lengths of stay for general hospital psychiatric patients in New York City in recent years have raised speculation that general hospitals are assuming a large responsibility for care of the chronically mentally ill. This study examines changes in utilization patterns and patient characteristics to assess whether such a trend is occurring.The authors obtained discharge abstract data for all New York City general hospital adult psychiatric patients in 1985 and 1988 as well as utilization data from the public general hospital system for 1977-1989. Three measures of chronicity were chosen: hospital stays longer than 60 days, discharges to long-term care, and three or more admissions per year. Data on psychiatric diagnoses and comorbid diagnoses for chronically ill patients were also reviewed.The mean length of stay of psychiatric patients in general hospitals has increased substantially in recent years and nearly tripled in the public hospitals during 1977-1989. Between 1985 and 1988, citywide increases were due largely to a growing proportion of patients with very long stays. Patients with stays longer than 60 days accounted for 35% of all inpatient days in 1988, compared with 27% in 1985. Patients with chronic illness accounted for half of all days in 1988, compared with 38% in 1985.Although many factors have contributed to these trends, the leading cause has been reimbursement policies favoring short-term inpatient care. Improving accountability for community treatment programs will be the key to redirecting funding priorities and creating more appropriate alternatives for the chronically mentally ill.