tbuckley/cabot-search huggingface dataset:
A phase 1b study of VEGFR inhibitor fruquintinib in patients with pretreated advanced colorectal cancer.
Authors: Jin Li, Junning Cao, Rui-hua Xu, Zhiyu Chen, Jian Zhang, Dongmei Ji, Sheng Dong Zhang, Fenghua Wang, Songhua Fan, Hua MU
Journal: Journal of Clinical Oncology (2014)

3548 Background: Fruquintinib is a novel oral small molecule compound selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 with potent inhibitory effects on multiple human tumor xenografts. In the first-in-human phase I study, fruquintinib demonstrated good tolerability and impressive antitumor activity (ORR=38.2% and DCR=82.4%) in patients (pts) with various heavily pre-treated solid tumors including colorectal cancer (CRC) (ASCO 2012 Abs#3038). Methods: This phase Ib study was designed to evaluate the safety, pharmacokinetics , and efficacy of two fruquintinib regimens: 4mg once daily continuously (QD) or 5mg once daily for three weeks followed with one week break (3/1 wk), as treatment for pts with advanced CRC who had failed at least two prior systemic therapies. The study consists of two stages: a two-arm 1:1 randomization stage including both QD and 3/1 wk regimens, and an expansion stage with the selected regimen. Tumor response was assessed per RECIST1.1. Results: Forty pts were enrolled in the randomization phase, with 20 pts in each QD or 3/1 wk group. Patient characteristics at baseline were similar between the two groups. The median treatment duration was 90 (7-280) days for QD regimen and 119 (14-364) days for 3/1 wk regimen. The most common treatment-related toxicities were hand-foot syndrome (HFS), hoarseness, proteinuria, hypertension and fatigue. The 3/1 wk group had less Grade 3/4 AEs than the QD group, particularly HFS (5% vs. 30%). Thirty-five pts were evaluable for response, 17 in QD and 18 in 3/1 wk. In QD group: DCR=76.2% (2 partial responses or PRs and 2 minor responses or MRs who achieved a 20-30% tumor reduction), 16-wk progression free survival (PFS)=40.0%, and 9-month survival=41.2%. In 3/1 wk group: DCR=83.3% (1 PR and 3 MRs), 16-wk PFS=65.0%, and 9-month survival=53.8%. 5mg 3/1 wk regimen was selected as the recommended regimen and additional 22 CRC pts were enrolled in the expansion stage. Conclusions: Fruquintinib administered at 5mg once daily in cycles of three weeks on and one week off was well tolerated and demonstrated encouraging preliminary clinical efficacy in pts with advanced CRC. Further clinical studies are warranted. Clinical trial information: NCT01975077.
Core-multishell nanocarriers: Transport and release of dexamethasone probed by soft X-ray spectromicroscopy
Authors: K. Yamamoto, A. Klossek, R. Flesch, T. Ohigashi, E. Fleige, F. Rancan, J. Frombach, A. Vogt, U. Blume-Peytavi, P. Schrade, S. Bachmann, R. Haag, S. Hedtrich, M. Schäfer-Korting, N. Kosugi, E. Rühl
Journal: Journal of Controlled Release (2016)
Identification of Oxidative Post-Translational Modifications on Plasma Albumin in Patients with Pulmonary Hypertension of Sickle Cell Anemia.
Authors: Elizabeth S. Klings, Adam Odhiambo, David Perlman, Hua Huang, Catherine Costello, Harrison W. Farber, Mark McComb, Martin H. Steinberg
Journal: Blood (2006)
PSMA ADC for progressive glioblastoma: Phase II Brown University Oncology Research Group Study.
Authors: Heinrich Elinzano, Nicholas Hebda, Denise Luppe, Wendy Turchetti, Kayla Rosati, William M. Sikov, Howard Safran
Journal: Journal of Clinical Oncology (2016)

2065 Background: Antiangiogenic agents targeting new blood vessel formation are approved to treat progressive glioblastoma (GBM), but limited data are available on the activity of vascular disrupting agents targeting established blood vessels in these tumors. Prostate specific membrane antigen (PSMA) is a transmembrane peptidase upregulated on endothelial cells of solid tumors including GBM, making it a potential therapeutic target. A PSMA-targeted monoclonal antibody conjugated with microtubule disrupting agent monomethyl auristatin E (MMAE) is undergoing evaluation in advanced prostate cancer (PSMA ADC, Progenics Pharmaceuticals). Unconjugated MMAE has demonstrated activity against GBM cell lines. Methods: We investigated the activity of PSMA ADC in a single arm Phase II study in progressive GBM patients following prior treatment with radiation, temozolomide and bevacizumab. 2.5 mg/kg PSMA ADC was administered intravenously every 3 weeks until disease progression, unacceptable toxicity or removal from study. Disease status was evaluated clinically and with contrast enhanced brain MRI every 3 cycles. Primary endpoint was objective response and secondary endpoints were progression-free survival (PFS), 6-month PFS and overall survival (OS). Results: 6 patients (4 males, 2 females, median age 63 years, KPS 70-90%) received PSMA ADC treatment. No objective responses were noted. 2/6 (33%) patients progressed after 1 cycle, 3/6 (50%) patients progressed after 2 cycles and 1/6 (17%) patient progressed after cycle 3. Median PFS was 6 weeks. Median OS was 2 months from study entry. Grade 3 and 4 adverse events included lymphopenia, dysphasia, syncope, neutropenia, leucopenia and fatigue. One patient had dose-limiting toxicity (sigmoid perforation possibly related to study drug) within 30 days of study treatment and off-study carboplatin resulting in death. Immunohistochemistry staining showed no PSMA expression in viable tumor samples of 2 patients and low expression (relative to that seen in prostate cancer trials) in 1. Conclusions: PSMA ADC had no demonstrable activity in these patients with progressive GBM likely due to minimal expression of the PSMA target and was associated with dose-limiting toxicity. Clinical trial information: NCT01856933.
Dasatinib (SPRYCEL®) 140 mg Once Daily (QD) vs 70 mg Twice Daily (BID) in Patients (pts) with Advanced Phase Chonic Myeloid Leukemia (ABP-CML) or Ph(+) ALL Who Are Resistant or Intolerant to Imatinib (im): Results of the CA180-035 Study.
Authors: Hagop Kantarjian, O. Ottmann, R. Pasquini, Y.T. Goh, D.W. Kim, J. VanTornout, A. Damokosh, N. Shah
Journal: Blood (2006)
Adolescents Who Attempt Suicide-Reply
Authors: David Shaffer
Journal: JAMA (1991)

In Reply.—  Drs Kaufman and Mann accurately restate the findings and reservations that appeared in our article. We would like to take issue with three points made in their letter.  They correctly state that an unpleasant intervention is not necessarily a bad one, drawing what may be an inappropriate analogy to vaccination, where an unpleasant inflammatory reaction or mild infection is expected and required for the vaccination to be effective. In the instance of suicide prevention classes, a negative response to programs is neither expected nor planned, nor, as far as we can determine, is there any a priori theory that predicts that an unpleasant reaction should serve a positive outcome. It is precisely because we do not understand why a significantly greater number of high-risk teenagers indicate that they are upset by a program and that, in their view, programs could increase the risk of suicide that we cannot
Long-Term Immunological Profile of Patients Treated with Haploidentical HSCT and TK-Cells to Study the Requirements of Memory T Cell Persistence
Authors: Giacomo Oliveira, Maria Teresa Lupo Stanghellini, Eliana Ruggiero, Nicoletta Cieri, Mattia D'Agostino, Raffaella Greco, Sara Mastaglio, Maddalena Noviello, Luca Vago, Luca Biasco, Attilio Bondanza, Alessandro Aiuti, Antonio Lambiase, Manfred Schmidt, Catia Traversari, Christof von Kalle, Fabio Ciceri, Claudio Bordignon, Chiara Bonini
Journal: Blood (2014)
NAGging Hexokinase PEPs up NLRP3
Authors: Henry Hampton, Carolyn Hutcheon, Naeha Subramanian
Journal: Cell Host & Microbe (2016)

Recognition of peptidoglycan is integral to detection of gram-positive bacterial pathogens. In a recent issue of Cell, Wolf et al. (2016) report that detection of the N-acetylglucosamine component of peptidoglycan by the glycolytic enzyme hexokinase activates the NLRP3 inflammasome, revealing an intriguing interplay between pathogen detection and metabolism.
Phase II trial of utidelone as monotherapy or in combination with capecitabine in heavily pretreated metastatic breast cancer patients
Authors: Pin Zhang, Zhongsheng Tong, Fuguo Tian, Yongsheng Wang, Junlan Yang, Weilian Li, Lijun Di, Wei Liu, Li Tang, Rongguo Qiu, Binghe Xu
Journal: Journal of Hematology & Oncology (2016)

The treatment of metastatic breast cancer (MBC) remains a great clinical challenge as drug resistance frequently develops. Alternative agents that can overcome drug resistance would offer new therapeutic options. The primary aim of this phase II study was to evaluate the efficacy and safety of utidelone as a monotherapy or in combination with capecitabine in metastatic breast cancer patients previously treated with and resistant to anthracyclines and taxanes. In two open-label, noncomparative clinical studies, patients with metastatic breast cancer who previously received anthracycline- and/or taxane-containing regimens were given (1) 25 to 35 mg/m2/day intravenously infused utidelone, once daily for 5 days, in combination with 14 days of 2000 mg/m2 capecitabine, divided in two equal daily oral doses or (2) 40 mg/m2/day intravenously infused utidelone, once daily for 5 days. These regimens were administered per each 21-day treatment cycle, and the maximum of treatment cycles allowed per protocol is 6. Objective response rate (ORR), progression-free survival (PFS), and tolerability were evaluated. In the combination study, 33 patients completed a median of 6 cycles of therapy, which was the highest cycles a trial patient could receive under the criteria of the study protocol. Efficacy was evaluated (n = 32) with an ORR of 42.4 % (FAS, 95 % CI, 26.6, 60.9) and a median PFS of 7.9 (FAS, 95 % CI, 6.1, 9.8) months. The monotherapy study (n = 63) resulted in an ORR of 28.57 % (FAS, 95 % CI, 18.4, 40.6) and a median PFS of 5.4 (FAS, 95 % CI, 2.9, 9.8) months. In both studies, common toxicities associated with utidelone administration included peripheral neuropathy, fatigue, myalgia, and arthralgia, but the toxicities were limited and manageable. Notably, very mild myelosuppression, low liver and renal toxicities, and very limited gastrointestinal toxic effect were observed, in contrast to other agents in the same class. Utidelone showed promising efficacy, tolerability, and advantageous safety profiles in the treatment of patients with advanced anthracycline/taxane-refractory metastatic breast cancer and may offer new treatment options to overcome drug resistance. CHiCTR-TRC-13004205 , registered on August 15, 2013.
Evaluation of the clinical advantage of endo-rectal balloons (ERBs) for prostate treatments.
Authors: Sarah J Barton, Julia Stratford, Douglas Brand, Catherine Thompson, Cathy Taylor, John P. Logue, James Wylie, Catherine Coyle, Alan McWilliam, Ananya Choudhury
Journal: Journal of Clinical Oncology (2016)

148 Background: The challenge of prostate and rectal motion during radiotherapy has been firmly established, both these problems are exacerbated by rectal instability. A number of different mechanical methods have been explored to see if the rectum can be stabilised. This study aimed to establish whether there is a clinical advantage in the use of ERB’s for the treatment of prostate patients, assessing inter-fractional prostate stability and dose to the rectum. Methods: This planning study was based on 10 patients with 2 sets of CT and Cone beam CT (CBCT) data with and without an ERB in situ. The ERB was a 100cc air filled RectalPro balloon. CBCT scan with and without the ERB were taken on the same day. The scans were contoured and planned using pinnacle version 9.8 with rotational arc therapy to a dose of 60Gy in 20 fractions, for an Elekta Agility treatment unit. An assumption was made that the prostate stability was directly related to the rectal stability. Based on this assumption, comparisons of the rectal position and dose on the CBCT verses the respective CBCT were made. The rectal DVH on the plans for the ERB verses no ERB were compared and a two-tailed T-test was used for statistical analysis of all comparisons. Results: Positional analysis demonstrated 12% improvement in the dice coefficient similarity score of the rectum for the ERB (P=0.0003). This only correlated to a significant improvement in the AP movement at mid prostate for the ERBs (P=0.031). The ERB position was seen to be influenced by the angle of insertion. Removal of the CBCT data from the 4 ERBs with largest deviations in insertion angle significantly reduced the inter-fractional movement seen with the ERBs. The lower rectal doses showed an improvement of around 8% for the ERB group, although for the 57Gy dose was 2.5% better with no-ERB as shown in the Table. Conclusions: There is a clinical and statistical benefit in the dose reduction for the rectal wall in the use of ERB’s for prostate radiotherapy. Although the ERB position needs to be confirmed with IGRT to remove the potential for inter-fractional positional error. [Table: see text]
Integration of Signal Transduction Inhibitors with Endocrine Therapy
Authors: Stephen R. D. Johnston, Julia Head, Sunil Pancholi, Simone Detre, Lesley-Ann Martin, Ian E. Smith, Mitch Dowsett
Journal: Clinical Cancer Research (2003)

Recent evidence suggests that common molecular adaptations occur during resistance to both tamoxifen and estrogen deprivation that use various signal transduction pathways, often involving cross-talk with a retained and functional estrogen receptor (ER) protein. There appear to be several different levels at which this cross-talk may occur, including peptide growth factor signaling via the type 1 tyrosine kinase growth factor receptor family [epidermal growth factor receptor (EGFR) and HER2], which may become up-regulated during endocrine treatment, ultimately being harnessed by cells to allow them hormone-independent growth. ER may remain involved in cell growth with ligand-independent phosphorylation and activation via different intracellular mitogen-activated protein kinases. ER may also become involved in non-nuclear estrogen-dependent signaling via interaction with the phosphatidylinositol 3′-kinase/Akt cell survival pathway or may interact with the stress-activated protein kinase/c-Jun-NH2-terminal kinase pathway. Understanding these mechanisms will permit the optimal integration of new signal transduction inhibitors (STIs) into breast cancer therapy. Preclinical approaches that have shown promise include the use of EGFR tyrosine kinase inhibitors for hormone-resistant breast cancer cells that are dependent on either EGFR or HER2 signaling. Likewise, farnesyl transferase inhibitors, mitogen-activated protein kinase inhibitors, and cell cycle inhibitors have all shown activity in experimental breast cancer models. Emerging data suggest that STIs may be more effective when given in combination with endocrine therapy either to overcome resistance or to prevent/delay emergence of the resistance phenotype. Clinical trials are in progress to determine the safety and optimal schedule for each of the various STIs, and studies of STIs in combination with aromatase inhibitors have commenced in breast cancer to see whether the therapeutic response to endocrine therapy can be enhanced further.
A Possible Role Of The Tetraspanin CD9 In Bone Marrow Retention and Engraftment Of Human CD34+ Hematopoietic Stem/Progenitor Cells
Authors: Kam Tong Leung, Karen Li, Kam Sze Kent Tsang, Kathy Yuen Yee Chan, Pak Cheung Ng, Chi Kong Li
Journal: Blood (2013)
The ACO Experiment in Infancy—Looking Back and Looking Forward
Authors: Zirui Song, Elliott S. Fisher
Journal: JAMA (2016)

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
HLA Ligandome Analysis Of Chronic Myeloid Leukemia (CML), Revealed Novel Tumor Associated Antigens For Peptide Based Immunotherapy
Authors: Juliane S. Stickel, Daniel J. Kowalewski, Mirle Schemionek, Lothar Kanz, Tim H. Brümmendorf, Helmut R. Salih, Hans-Georg Rammensee, Stefan Stevanovic
Journal: Blood (2013)
Assessing Cardiovascular Risk to Guide Hypertension Diagnosis and Treatment
Authors: Ann Marie Navar, Michael J. Pencina, Eric D. Peterson
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated the benefit of lowering systolic blood pressure (SBP) to 120 mm Hg, yet other trials, such as Heart Outcomes Prevention Evaluation–3 (HOPE-3), did not find consistent benefit. How to incorporate these results into the treatment of those with elevated SBP in the general population is not clear. <h3>Objectives</h3> To assess the representativeness of SPRINT and HOPE-3 relative to patients in the United States and to explore the cardiovascular disease (CVD) risk profiles of various populations with elevated SBP. <h3>Design, Setting, and Participants</h3> The study examined data from nonpregnant adults aged 20 to 79 years participating in the 2007-2012 National Health and Nutrition Examination Survey (NHANES) who had complete data available (n = 14 142), representing 206.9 million US adults. The study was performed from October 1, 2015, to August 2, 2016. <h3>Main Outcomes and Measures</h3> The study estimated the number and characteristics of adults with SBP of 120 mm Hg or higher, including SPRINT and HOPE-3 eligibility, and estimated who may have newly required treatment initiation or intensification if various trial or risk-based criteria were applied. <h3>Results</h3> NHANES included completed clinical evaluations from mobile examination centers on 15 974 adults aged 20 to 79 years (mean [SD] age, 45.9 [15.5] years). The study excluded 182 pregnant women and 1650 adults in whom CVD risk data were unavailable, leaving a final study population of 14 142 (50.5% women [95% CI, 49.6%-51.3%] and 49.5% men [95% CI, 48.6%-50.4%]). An estimated 53.3 million untreated and 19.8 million treated US adults have an SBP in the diagnostic and treatment gray zone (120-139 mm Hg), a small proportion of whom would have been eligible for SPRINT (5.4% untreated, 13.9% treated) or HOPE-3 (13.9% treated, 1.7% untreated). Even among those with prior CVD or high risk of CVD and elevated SBP (120-139 mm Hg), only a few would have qualified for SPRINT (27.0% and 21.9% of untreated and treated patients, respectively) or HOPE-3 (10.6% and 2.1% of untreated and treated, respectively). If blood pressure treatment recommendations were extended to adults with an SBP between 120 and 139 mm Hg, as well as prior CVD or CVD risk of 15% or higher, then 5.8 million untreated adults would be reclassified as treatment eligible; furthermore, 8.5 million treated patients would require medication intensification. <h3>Conclusions and Relevance</h3> Millions of US adults have elevated SBP and high CVD risk, most of whom would not have been eligible for SPRINT. Until more definitive evidence becomes available, clinicians should consider a management paradigm based on CVD risk in addition to blood pressure measurements.
Faces of Medicine: A Philosophical Study
Authors: Wim J. van der Steen, P. J. Thung
Journal: Annals of Internal Medicine (1988)

1. MEDICINE Illness, disease and disability plague man in every culture. But the form they take is not the same everywhere. Neither is man's reaction. Coping strategies, and the experience and knowledge backing them, depend very much on cultural setting. So medicine, the fabric of strategy and know ledge, can only be understood in the context of culture. In western society today, severe judgements are passed on medicine. Its store of knowledge and experience, and its repertory of strategies, have grown immensely during the last few decades. But it hardly alleviates dominant ailments, especially chronic diseases, diseases of old age and disturbances of social and mental functioning. We know that these ailments have come to the fore as the incidence of more primitive diseases declined in industrial societies. Infant deaths, and malnutrition and infections striking at young age, have dwindled to marginal significance in Western Europe and life expectancy at birth is twice that of some 150 years ago. Thus our new troubles are connected with past successes.
Abstract 3664: Pioglitazone Increases Plasma Adiponectin Concentration and Decreases Coronary Plaque Necrotic Core: Intravascular Ultrasound Virtual Histology Study
Authors: Daisuke Ogasawara, Junya Shite, Toshiro Shinke, Hiromasa Otake, Yusuke Tanino, Oscar L Paredes, Takahiro Sawada, Mitsuhiro Yokoyama
Journal: Circulation (2006)