tbuckley/cabot-search huggingface dataset:
A phase I study of vorinostat in combination with bortezomib in refractory solid tumors
Authors: J. A. Ninan, H. Bailey, J. Kolesar, R. Marnocha, J. Eickhoff, J. Wright, I. Espinoza-Delgado, D. Alberti, G. Wilding, W. Schelman
Journal: Journal of Clinical Oncology (2009)

2531 Background: Vorinostat (suberoylanilide hydroxamic acid, SAHA) is an oral histone deacytlase (HDAC) inhibitor that has anti-tumor activity in hematologic malignancies and advanced solid tumors. Vorinostat has been postulated to act synergistically with bortezomib at the level of aggresome inhibition with creation of reactive oxygen species. We previously conducted a study of this combination with once-daily dosing of vorinostat with bortezomib (Step A). This study (Step B) was conducted to evaluate twice daily dosing of vorinostat during administration of bortezomib to determine safety and efficacy, pharmacokinetics, and activity this combination. Methods: This study used standard eligibility criteria except patients must have had no prior bortezomib. The treatment plan initially consisted of vorinostat given orally twice daily on days 1–14 with bortezomib IV on days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were observed at level 1, and the protocol was amended to administer vorinostat twice daily on days 1–4 and 8–11. Starting dose was vorinostat 200 mg and bortezomib 1 mg/m 2 . RECIST was used to measure response. Results: 29 pts have been enrolled; 13 men and 16 women. Tumor types include: Prostate (1), Colorectal (3), Pancreatic (6), Sarcoma (7), Biliary (1), Thymus (1), GIST (2), Mesothelioma (1), ovarian (1), Neuroendocrine (1), Lung (1), Head and Neck (1), Breast (2), and Cervical (1). Grade 3–4 toxicities possibly related to SAHA at any dose level were as follows: thrombocytopenia (5), fatigue (3), increased ALT (1), elevated INR (1), anemia, (1), hypotension (1), diarrhea (3), anorexia (1), dizziness (1), nausea/vomiting (1), and hypoalbuminemia (1). The only dose limiting toxicities included elevated ALT (1), fatigue (1). There were two deaths but neither was felt to be related to the drug. The MTD for Step B was established at vorinostat 300 mg BID and bortezomib 1.3 mg/m 2 . Conclusions: The MTD for Step B was established at vorinostat 300 mg BID and bortezomib 1.3 mg/m 2 . Subjective evidence of clinical activity has been observed in patients with refractory solid tumors. These studies were supported by NCI, UO1, CA062491, SAIC 25XS097, and 1ULRR025011. No significant financial relationships to disclose.
Life after breast cancer: understanding women's health-related quality of life and sexual functioning.
Authors: P A Ganz, J H Rowland, K Desmond, B E Meyerowitz, G E Wyatt
Journal: Journal of Clinical Oncology (1998)

To describe the health-related quality of life (HRQL), partner relationships, sexual functioning, and body image concerns of breast cancer survivors (BCS) in relation to age, menopausal status, and type of cancer treatment.A cross-sectional sample of BCS in two large metropolitan areas was invited to participate in a survey study that included the following standardized measures: the RAND 36-Item Health Survey; the Centers for Epidemiologic Studies-Depression Scale (CES-D); the Dyadic Adjustment Scale (DAS); the Breast Cancer Prevention Trial (BCPT) Symptom Checklist; the Watts Sexual Functioning Questionnaire (WSFQ); and subscales from the Cancer Rehabilitation Evaluation System (CARES).Eight hundred sixty-four BCS completed the survey. RAND Health Survey scores were as good or better than those of healthy, age-matched women, and the frequency of depression was similar to general population samples. Marital/partner adjustment was similar to normal healthy samples, and sexual functioning mirrored that of healthy, age-matched postmenopausal women. However, these BCS reported higher rates of physical symptoms (eg, joint pains, headaches, and hot flashes) than healthy women. Sexual dysfunction occurred more frequently in women who had received chemotherapy (all ages), and in younger women who were no longer menstruating. In women > or = 50 years, tamoxifen therapy was unrelated to sexual functioning.BCS report more frequent physical and menopausal symptoms than healthy women, yet report HRQL and sexual functioning comparable to that of healthy, age-matched women. Nevertheless, some survivors still experience poorer functioning, and clinicians should inquire about common symptoms to provide symptomatic management or counseling for these women.
Timing the Implantation of Implantable Cardioverter-Defibrillators in Patients With Nonischemic Cardiomyopathy⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Francis E. Marchlinski, Mariell Jessup
Journal: Journal of the American College of Cardiology (2006)
Assessing Risk of Autism Spectrum Disorder in Children After Antidepressant Use During Pregnancy
Authors: Bryan H. King
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
Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt
Authors: P Erickson, J Gao, KS Chang, T Look, E Whisenant, S Raimondi, R Lasher, J Trujillo, J Rowley, H Drabkin
Journal: Blood (1992)
Bevacizumab plus XELOX as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer
Authors: T. Gruenberger, D. Tamandl, H. Puhalla, W. Scheithauer, C. Zielinski, B. Gruenberger
Journal: Journal of Clinical Oncology (2007)

4064 Background: Patients (pts) with colorectal cancer (CRC) and liver metastases have a poor prognosis and may benefit from perioperative chemotherapy and disease resection. Bevacizumab (BEV) is proven to improve outcomes in patients with metastatic CRC; however, its impact on surgical complications and hepatic regeneration following liver resection needs to be assessed. Methods: Patients with metastatic CRC with liver metastases potentially curable by resection were eligible for this single-centre, nonrandomised phase II trial. Eligibility criteria define pts at high risk of early recurrence: synchronous liver metastases; primary non-optimally resectable disease or multiple liver metastases. Pts received BEV 5mg/kg q2 weeks plus XELOX (capecitabine 3500mg/m 2 /day days 1–7 plus oxaliplatin 85mg/m 2 day 1 of a 2-week cycle) for 6 cycles. The sixth cycle of therapy did not include BEV, resulting in 5 weeks between the last BEV dose and surgery. Therapy with BEV plus XELOX was restarted 5 weeks after surgery for another 6 cycles. Results: 54 patients have been enrolled and are evaluable having received a median of 6 cycles of BEV plus XELOX: 39 pts underwent liver resection alone, 9 pts also had primary tumor resection (2 are awaiting surgery); major liver resections were performed in 17 pts (35%). 40 pts responded (ORR 74%) and 11 had stable disease. To date, peri- and postoperative events are consistent with previous studies evaluating chemotherapy alone: there was no intra-operative increased bleeding, perioperative blood transfusions were required in only 3 pts (6 %); further surgery was necessary in a single patient. Postoperative liver function and regeneration (assessed by CT 3 months after surgery) were normal in all but one patient (prolonged liver dysfunction due to steatohepatitis). No postoperative mortality occurred and morbidity was encountered in 8 pts (17%). Mean postoperative hospital stay was 8 days (SD ± 3.8). Conclusions: These data suggest that BEV can be safely administered until 5 weeks prior to liver resection in patients with mCRC without increasing the rate of surgical or wound healing complications or severity of bleeding. They are the first to show that neoadjuvant BEV does not affect liver regeneration after resection. No significant financial relationships to disclose.
Pacemaker-induced transient asynchrony suppresses heart failure progression
Authors: Jonathan A. Kirk, Khalid Chakir, Kyoung Hwan Lee, Edward Karst, Ronald J. Holewinski, Gianluigi Pironti, Richard S. Tunin, Iraklis Pozios, Theodore P. Abraham, Pieter de Tombe, Howard A. Rockman, Jennifer E. Van Eyk, Roger Craig, Taraneh G. Farazi, David A. Kass
Journal: Science Translational Medicine (2015)

Transient asynchrony induced by an implanted pacemaker improves pathobiology of heart failure in large animals.
3D Tissue Formation of Unilocular Adipocytes in Hydrogel Microfibers
Authors: Amy Y. Hsiao, Teru Okitsu, Hiroki Teramae, Shoji Takeuchi
Journal: Advanced Healthcare Materials (2015)

Adipose tissue, an active metabolic and endocrine organ mainly composed of unilocular adipocytes, is implicated in various obesity related diseases. Developing morphologically and functionally accurate in vitro models of the adipose tissue is therefore critically important for basic biological studies, drug screening/testing, and clinical implants to advance the understanding and treatment of these diseases. However, current adipose tissue engineering technologies either cannot replicate the unilocular morphologies of mature adipocytes, or lack the ease of monitoring, handling, and scaling up required in the above mentioned applications. This paper presents the differentiation of adipose derived stem cells (ADSCs) to mature adipocytes in highly observable and highly handleable 3D fiber shaped constructs exhibiting morphologies and functions of native adipose tissues. Using the cell fiber technology, ADSCs were encapsulated in hydrogel microfibers, allowed to form into fiber shaped constructs, and differentiated to mature unilocular adipocytes. These adipocyte fibers are observed and maintained for up to 91 d, and secretion of adipose tissue‐specific factor, adiponectin, is further confirmed. The handleability of the adipocyte fibers is demonstrated by assembling the adipocyte fibers into doll shaped constructs. Such highly observable, highly handleable, and scalable characteristics of the adipocyte fibers make them suitable for biological studies, high‐throughput drug screening/testing, and clinical applications.
Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck.
Authors: D L Morton, D R Wen, L J Foshag, R Essner, A Cochran
Journal: Journal of Clinical Oncology (1993)

PURPOSE We developed intraoperative lymphatic mapping with selective lymphadenectomy (SLND) to identify micrometastatic spread of cutaneous melanoma to regional lymph nodes. This study was undertaken to assess the sensitivity and specificity of our technique in patients with clinical stage I (CS-I) melanoma of the head or neck. PATIENTS AND METHODS Seventy-two CS-I melanoma patients underwent intraoperative lymphatic mapping of primary cutaneous melanomas located on the head, neck, or upper chest/back draining to the neck. Key (sentinel) cervical lymph nodes in the regional lymphatic drainage basin were identified, selectively excised during SLND, and examined for microscopic evidence of tumor cells. If these sentinel nodes were tumor-negative, the surgery was concluded; if the sentinel nodes were tumor-positive, all nodes in the drainage basin were removed during en bloc lymphadenectomy (LND). RESULTS Intraoperative lymphatic mapping identified sentinel nodes in 90% of the regional drainage basins. Fifteen percent of these nodes were tumor-positive, indicating the need for LND. There were no false-negative sentinel nodes, and extended follow-up showed no local nodal recurrences in patients whose sentinel-node histology did not indicate the need for LND. CONCLUSION Intraoperative lymphatic mapping and SLND is a minimally invasive and highly accurate screening technique for determining which patients with CS-I head and neck melanomas have subclinical node metastases and therefore might benefit from cervical LND.
Extended phase I trial of the oral pan-Bcl-2 inhibitor AT-101 by multiple dosing schedules in patients with advanced cancers
Authors: M. N. Saleh, H. Pitot, J. Maleski, L. Leopold, A. Forero
Journal: Journal of Clinical Oncology (2009)

e14537 Background: Over-expression of Bcl-2 family proteins is common in human cancers. Initial trials of the oral, pan-Bcl-2 inhibitor AT-101 showed acute dose limiting toxicity of Gr 3–4 AST/ALT (MTD 40 mg/d) and ileus with prolonged dosing daily (QD) for 21/28 days per cycle (Saleh, NCI/EORTC, 2005; James, ASCO, 2006 and Saleh, ASCO, 2007). MTD in the QD schedule has been previously reported. In this study different dosing schedules of AT-101 were tested in adults with advanced cancers and final results for the pulse dosing schedule of twice a day for three days every other week (b.i.d. x 3d EOW) are being reported. Methods: Serial patient (pt) cohorts received AT-101 at escalating doses of 30–80 mg b.i.d. x 3d EOW. Adverse events (AEs) were graded by the NCI CTCAE v3.0. Efficacy was determined by RECIST. Results: 37 pts have been enrolled. Safety data is available on 34/37 pts. In this b.i.d. x 3d EOW dosing schedule, ileus/small bowel obstruction (SBO) occurred in 3 pts (one at each dose level of 30, 40 and 50 mg) and was the dose limiting toxicity for this schedule. Of note, the SBO that occurred at 30 mg was felt to be unrelated to study agent therefore, 30 mg b.i.d. x 3d EOW was the MTD determined for this schedule. The most common (&gt;50%) grade 1–2 AEs included: nausea, vomiting, diarrhea, fatigue and anorexia. Grade 3–4 AEs occurring in &gt; 2 pts include: nausea, abdominal pain, elevated AST (3 pts each), vomiting, fatigue, dehydration (4 pts each), hypokalemia (5 pts). Stable disease was reported in 13/37 (35%) pts. One pt with NSCLC continues on study with stable disease for 33 cycles and 2 additional pts were on study with stable disease for 18 and 9 cycles. The mean Plasma C max was 301 ng/ml (+ 477 ng/ml SD) and mean AUC for 30 mg b.i.d.x3d EOW was 1080 ng*hr/ml (+ 1990 ng/ml SD) with a median peak concentration at 4 hours post dose. Conclusions: Pulse dosing of AT-101 achieved an MTD of 30mg b.i.d. x 3d EOW and is associated with reduced toxicity than continuous daily dosing, and may be preferable in combination regimens. [Table: see text]
Inhaled budesonide induces corticosteroid-dependent gene expression in asthmatics: Validation in primary epithelial and airways smooth muscle cells
Authors: Robert Newton, Elizabeth King, Christopher Rider, Carol Gwozd, Neil Holden, Jane Eddlestone, Bruce Zuraw, Richard Leigh, Paul O'Byrne, Margaret Kelly
Journal: European Respiratory Journal (2011)

Rationale: Inhaled corticosteroids (ICS) reduce inflammatory gene expression. This is usually attributed to direct inhibition of inflammatory gene transcription by the glucocorticoid receptor. However, while corticosteroids induce anti-inflammatory gene expression in vitro , this has not been examined in asthmatic subjects taking ICS.

Methods: Bronchial biopsies from atopic asthmatics taking inhaled budesonide (2×200 μg, twice daily for 11 days) or placebo were subjected to gene expression analysis using real-time reverse transcriptase-polymerase chain reaction. mRNA expression for the corticosteroid-inducible genes; TSC22D3 (GILZ), DUSP1 (MKP-1), both anti-inflammatory effectors, and FKBP5 (FKBP51), a regulator of glucocorticoid receptor function, was assessed. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.

Results: Expression of GILZ and FKBP51 were significantly elevated in budesonide-treated subjects compared to placebo. Budesonide also increased GILZ expression in cultured epithelial and smooth muscle cells and immunostaining showed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.

Conclusions: Expression of corticosteroid-induced genes, including the anti-inflammatory gene, GILZ, is upregulated in the airways of asthmatic subjects taking medium daily doses of inhaled budesonide. The biological effects of such genes need to be considered when assessing ICS action.

Funded by AstraZeneca.
The Graying of US Physicians
Authors: Joel M. Kupfer
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
Poor countries press for extension of exemption from drug patents
Authors: Anne Gulland
Journal: BMJ (2015)

Developing countries are still waiting to hear whether they will be granted a permanent exemption from rules on intellectual property that enables them to have access to generic drugs.

No agreement was reached after two days of talks at the World Trade Organization on 15 and 16 October, and the decision on the exemption will be deferred to next month.

Since the launch of the WTO’s Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement in 1995, low income countries have been exempt from intellectual property rules on some items such as drugs. The exemption, which enables poor countries to export and produce generic drugs regardless of patent, has been granted on a time limited basis, and the current waiver is due to expire in January 2016.

The 48 countries classed as the world’s …
NIH Report Card
Authors: Bruce Schneider, David Korn
Journal: New England Journal of Medicine (2004)

discuss the position of the National Institutes of Health (NIH) with respect to clinical research.The NIH is biased toward basic science and is prejudiced by the idea that clinical research is best performed in a university setting by means of prospective trials.However, many clinical questions cannot be addressed in this way, especially when the goal is to determine which established techniques are most effective in an era of cost containment.Doctors with access to the numbers of patients needed for both retrospective and prospective studies of outcomes are frequently not based at a university.These doctors are alienated from the
Genetic Strategies to Individualize Supportive Care
Authors: Howard L. McLeod
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2765 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065551 Genetic Strategies to Individualize Supportive Care Howard L. McLeodxHoward L. McLeodSearch for articles by this author Show More Washington University School of Medicine, Siteman Cancer Center, St Louis, MO https://doi.org/10.1200/JCO.2002.20.12.2765 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Abstract 50: Adiposity is Associated with Genome-wide DNA Methylation in Adipose Tissue
Authors: Golareh Agha, Andres E Houseman, Karl T Kelsey, Charles B Eaton, Stephen L Buka, Eric B Loucks
Journal: Circulation (2014)

Background: Adiposity is a major risk factor for type 2 diabetes, dyslipidemia, and CVD, suggesting an important role for adipose tissue in development of these conditions. There is interest in epigenetic mechanisms by which genetic and environmental factors may contribute to adiposity, however studies of DNA methylation in relation to adiposity rarely focus on adipose tissue. Objective: To determine whether genome-wide DNA methylation profiles in blood and adipose tissue are associated with central fat, body fat distribution, and obesity in adulthood. Methods: Participants (aged 44-50 years) were from the New England Family Study birth cohort, born in Providence, RI . Of 400 participants assessed during 2010-2011, a representative subsample of 106 participants (68 women, 38 men) was selected for DNA methylation analyses. DNA methylation in subcutaneous adipose tissue and peripheral blood leukocytes was evaluated using the Infinium HumanMethylation450K BeadChip. Dual-energy x-ray absorptiometry scans assessed android fat mass, android:gynoid region fat ratio, and trunk:limb region fat ratio. BMI (kg/m 2 ) was directly assessed. Results: Adipose tissue DNA methylation was associated with all four measures of adiposity, after adjusting for race, sex, smoking, and accounting for multiple testing (permutation-based omnibus p-values &lt;0.001). Associations were similar in sex-specific analyses, and upon exclusion of single nucleotide polymorphisms. Investigation of top differentially-methylated genes revealed several that are biologically relevant to adiposity development, including SOD3 , AOC3 , AQP7, TIMP4, ANGPT4, and ADAMTS4 . Blood DNA methylation was not related to adiposity. Conclusion: Adipose tissue DNA methylation was associated with directly-assessed measures of central fat and body fat distribution, as well as obesity, all of which are important determinants of cardiometabolic risk. Targeting the primary affected organ may be important for elucidating the epigenetic basis of adiposity.